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Sample records for recombinant tetravalent dengue

  1. Efficacy of a tetravalent dengue vaccine in children in Latin America.

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    Villar, Luis; Dayan, Gustavo Horacio; Arredondo-García, José Luis; Rivera, Doris Maribel; Cunha, Rivaldo; Deseda, Carmen; Reynales, Humberto; Costa, Maria Selma; Morales-Ramírez, Javier Osvaldo; Carrasquilla, Gabriel; Rey, Luis Carlos; Dietze, Reynaldo; Luz, Kleber; Rivas, Enrique; Miranda Montoya, Maria Consuelo; Cortés Supelano, Margarita; Zambrano, Betzana; Langevin, Edith; Boaz, Mark; Tornieporth, Nadia; Saville, Melanie; Noriega, Fernando

    2015-01-08

    In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development. In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection. A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur

  2. 75 FR 6211 - Prospective Grant of Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine...

    Science.gov (United States)

    2010-02-08

    ... Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1,2,3, and 4 AGENCY: National Institutes of Health, Public Health...., ``Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses''-- European Patent...

  3. Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials.

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    Sophia Gailhardou

    2016-07-01

    Full Text Available A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target

  4. In silico prediction of monovalent and chimeric tetravalent vaccines for prevention and treatment of dengue fever.

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    Vijayakumar, Subramaniyan; Ramesh, Venkatachalam; Prabhu, Srinivasan; Manogar, Palani

    2017-11-01

    Reverse vaccinology method was used to predict the monovalent peptide vaccine candidate to produce antibodies for therapeutic purpose and to predict tetravalent vaccine candidate to act as a common vaccine to cover all the fever dengue virus serotypes. Envelope (E)-proteins of DENV-1-4 serotypes were used for vaccine prediction using NCBI, Uniprot/Swissprot, Swiss-prot viewer, VaxiJen V2.0, TMHMM, BCPREDS, Propred-1, Propred and MHC Pred,. E-proteins of DENV-1-4 serotypes were identified as antigen from which T cell epitopes, through B cell epitopes, were predicted to act as peptide vaccine candidates. Each selected T cell epitope of E-protein was confirmed to act as vaccine and to induce complementary antibody against particular serotype of dengue virus. Chimeric tetravalent vaccine was formed by the conjugation of four vaccines, each from four dengue serotypes to act as a common vaccine candidate for all the four dengue serotypes. It can be justifiably concluded that the monovalent 9-mer T cell epitope for each DENV serotypes can be used to produce specific antibody agaomst dengue virus and a chimeric common tetravalent vaccine candidate to yield a comparative vaccine to cover any of the four dengue virus serotype. This vaccine is expected to act as highly immunogenic against preventing dengue fever.

  5. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

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    Govindarajan, Dhanasekaran; Guan, Liming; Meschino, Steven; Fridman, Arthur; Bagchi, Ansu; Pak, Irene; ter Meulen, Jan; Casimiro, Danilo R; Bett, Andrew J

    2016-01-01

    Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV) are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT) viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD) viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  6. Tetravalent Dengue Vaccine: A Review in the Prevention of Dengue Disease.

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    Scott, Lesley J

    2016-09-01

    Tetravalent, live-attenuated, dengue vaccine (Dengvaxia(®); CYD-TDV) is the first vaccine approved for the prevention of dengue disease caused by dengue virus (DENV) serotypes 1-4 in individuals aged 9-45 or 9-60 years living in high dengue endemic areas. This narrative review discusses the immunogenicity, protective efficacy, reactogenicity and safety of CYD-TDV in the prevention of dengue disease. In Latin American and Asian phase 3 trials in children and adolescents (n > 30,000), the recommended three-dose CYD-TDV regimen was efficacious in preventing virologically-confirmed dengue (VCD) during the period from 28 days after the last dose (month 13) to month 25, meeting the primary endpoint criteria. Protective efficacy against VCD in the respective individual trials was 60.8 and 56.5 % (primary analysis). During the 25-month active surveillance phase, CYD-TDV also provided protective efficacy against VCD, severe dengue, any grade of dengue haemorrhagic fever and VCD-related hospitalization in children aged 9 years and older. CYD-TDV was generally well tolerated, with no safety concerns identified after up to 4 years' follow-up (i.e. from post dose 1) in ongoing long-term studies. Based on evidence from the dengue clinical trial program, the WHO SAGE recommended that countries with high dengue endemicity consider introducing CYD-TDV as part of an integrated disease prevention strategy to lower disease burden. Pharmacoeconomic considerations will be pivotal to implementing dengue vaccination prevention strategies in these countries. The availability of a dengue vaccine is considered essential if the 2012 WHO global strategy targets for reducing the burden of dengue disease by 2020 are to be attained. Hence, CYD-TDV represents a major advance for the prevention of dengue disease in high dengue endemic regions.

  7. Neutralizing Antibody Response and Efficacy of Novel Recombinant Tetravalent Dengue DNA Vaccine Comprising Envelope Domain III in Mice

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    Ajit Kulkarni

    2017-03-01

    Full Text Available Background: Dengue is a global arboviral threat to humans; causing 390 million infections per year. The availability of safe and effective tetravalent dengue vaccine is a global requirement to prevent epidemics, morbidity, and mortality associated with it. Methods: Five experimental groups (6 mice per group each of 5-week-old BALB/c mice were immunized with vaccine and placebo (empty plasmid (100 µg, i.m. on days 0, 14 and 28. Among these, four groups (one group per serotype of each were subsequently challenged 3 weeks after the last boost with dengue virus (DENV serotypes 1-4 (100 LD50, 20 µl intracerebrally to determine vaccine efficacy. The fifth group of each was used as a control. The PBS immunized group was used as mock control. Serum samples were collected before and after subsequent immunizations. EDIII fusion protein expression was determined by Western blot. Total protein concentration was measured by Bradford assay. Neutralizing antibodies were assessed by TCID50-CPE inhibition assay. Statistical analysis was performed using Stata/IC 10.1 software for Windows. One-way repeated measures ANOVA and Mann-Whitney test were used for neutralizing antibody analysis and vaccine efficacy, respectively. Results: The recombinant EDIII fusion protein was expressed adequately in transfected 293T cells. Total protein concentration was almost 3 times more than the control. Vaccine candidate induced neutralizing antibodies against all four DENV serotypes with a notable increase after subsequent boosters. Vaccine efficacy was 83.3% (DENV-1, -3, -4 and 50% (DENV-2. Conclusion: Our results suggest that vaccine is immunogenic and protective; however, further studies are required to improve the immunogenicity particularly against DENV-2.

  8. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Directory of Open Access Journals (Sweden)

    Dhanasekaran Govindarajan

    Full Text Available Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  9. Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study.

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    Sirivichayakul, Chukiat; Barranco-Santana, Elizabeth A; Esquilin-Rivera, Inés; Oh, Helen M L; Raanan, Marsha; Sariol, Carlos A; Shek, Lynette P; Simasathien, Sriluck; Smith, Mary Kathryn; Velez, Ivan Dario; Wallace, Derek; Gordon, Gilad S; Stinchcomb, Dan T

    2016-05-15

    A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries. This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4. Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups. TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mailjournals.permissions@oup.com.

  10. Genetic and phenotypic characterization of manufacturing seeds for a tetravalent dengue vaccine (DENVax.

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    Claire Y-H Huang

    Full Text Available We have developed a manufacturing strategy that can improve the safety and genetic stability of recombinant live-attenuated chimeric dengue vaccine (DENVax viruses. These viruses, containing the pre-membrane (prM and envelope (E genes of dengue serotypes 1-4 in the replicative background of the attenuated dengue-2 PDK-53 vaccine virus candidate, were manufactured under cGMP.After deriving vaccine viruses from RNA-transfected Vero cells, six plaque-purified viruses for each serotype were produced. The plaque-purified strains were then analyzed to select one stock for generation of the master seed. Full genetic and phenotypic characterizations of the master virus seeds were conducted to ensure these viruses retained the previously identified attenuating determinants and phenotypes of the vaccine viruses. We also assessed vector competence of the vaccine viruses in sympatric (Thai Aedes aegypti mosquito vectors.All four serotypes of master vaccine seeds retained the previously defined safety features, including all three major genetic loci of attenuation, small plaques, temperature sensitivity in mammalian cells, reduced replication in mosquito cell cultures, and reduced neurovirulence in new-born mice. In addition, the candidate vaccine viruses demonstrated greatly reduced infection and dissemination in Aedes aegypti mosquitoes, and are not likely to be transmissible by these mosquitoes. This manufacturing strategy has successfully been used to produce the candidate tetravalent vaccine, which is currently being tested in human clinical trials in the United States, Central and South America, and Asia.

  11. Biodistribution and safety of a live attenuated tetravalent dengue vaccine in the cynomolgus monkey.

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    Ravel, Guillaume; Mantel, Nathalie; Silvano, Jeremy; Rogue, Alexandra; Guy, Bruno; Jackson, Nicholas; Burdin, Nicolas

    2017-10-13

    The first licensed dengue vaccine is a recombinant, live, attenuated, tetravalent dengue virus vaccine (CYD-TDV; Sanofi Pasteur). This study assessed the biodistribution, shedding, and toxicity of CYD-TDV in a non-human primate model as part of the nonclinical safety assessment program for the vaccine. Cynomolgus monkeys were given one subcutaneous injection of either one human dose (5log 10 CCID 50 /serotype) of CYD-TDV or saline control. Study endpoints included clinical observations, body temperature, body weight, food consumption, clinical pathology, immunogenicity, and post-mortem examinations including histopathology. Viral load, distribution, persistence, and shedding in tissues and body fluids were evaluated by quantitative reverse transcriptase polymerase chain reaction. The subcutaneous administration of CYD-TDV was well tolerated. There were no toxicological findings other than expected minor local reactions at the injection site. A transient low level of CYD-TDV viral RNA was detected in blood and the viral genome was identified primarily at the injection site and in the draining lymph nodes following immunization. These results, together with other data from repeat-dose toxicity and neurovirulence studies, confirm the absence of toxicological concern with CYD-TDV and corroborate clinical study observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Dengue, zika, chikungunya and the development of vaccines

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    Isabel N. Kantor

    2018-01-01

    Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjec...

  13. Plant-expressed Fc-fusion protein tetravalent dengue vaccine with inherent adjuvant properties.

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    Kim, Mi Young; Copland, Alastair; Nayak, Kaustuv; Chandele, Anmol; Ahmed, Muhammad S; Zhang, Qibo; Diogo, Gil R; Paul, Matthew J; Hofmann, Sven; Yang, Moon-Sik; Jang, Yong-Suk; Ma, Julian K-C; Reljic, Rajko

    2017-12-09

    Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi Pasteur Dengvaxia vaccine does not protect children under the age of nine, and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant expression to produce a humanized and highly immunogenic poly-immunoglobulin G scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor-targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralizing antibodies and evidence of cell-mediated immunity. Furthermore, these molecules were able to prime immune cells from human adenoid/tonsillar tissue ex vivo as evidenced by antigen-specific CD4 + and CD8 + T-cell proliferation, IFN-γ and antibody production. The purified polymeric fraction of dengue PIGS (D-PIGS) induced stronger immune activation than the monomeric form, suggesting a more efficient interaction with the low-affinity Fcγ receptors on antigen-presenting cells. These results show that the plant-expressed D-PIGS have the potential for translation towards a safe and easily scalable single antigen-based tetravalent dengue vaccine. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  14. In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination.

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    Stephen S Whitehead

    2017-05-01

    Full Text Available Infection caused by the four serotypes of dengue virus (DENV-1-4 is a leading cause of mosquito-borne disease. Clinically-severe dengue disease is more common when secondary dengue infection occurs following prior infection with a heterologous dengue serotype. Other flaviviruses such as yellow fever virus, Japanese encephalitis virus, and Zika virus, can also elicit antibodies which are cross-reactive to DENV. As candidate dengue vaccines become available in endemic settings and for individuals who have received other flavivirus vaccines, it is important to examine vaccine safety and immunogenicity in these flavivirus-experienced populations. We performed a randomized, controlled trial of the National Institutes of Health live attenuated tetravalent dengue vaccine candidate (TV003 in fifty-eight individuals with prior exposure to flavivirus infection or vaccine. As in prior studies of this vaccine in flavivirus-naive volunteers, flavivirus-experienced subjects received two doses of vaccine six months apart and were followed closely for clinical events, laboratory changes, viremia, and neutralizing antibody titers. TV003 was well tolerated with few adverse events other than rash, which was predominately mild. Following one dose, 87% of vaccinees had an antibody response to all four serotypes (tetravalent response, suggesting a robust immune response. In addition, 76% of vaccinees were viremic; mean peak titers ranged from 0.68–1.1 log10 PFU/mL and did not differ by serotype. The second dose of TV003 was not associated with viremia, rash, or a sustained boost in antibody titers indicating that a single dose of the vaccine is likely sufficient to prevent viral replication and thus protect against disease. In comparison to the viremia and neutralizing antibody response elicited by TV003 in flavivirus-naïve subjects from prior studies, we found that subjects who were flavivirus-exposed prior to vaccination exhibited slightly higher DENV-3 viremia

  15. The Immunodominance Change and Protection of CD4+ T-Cell Responses Elicited by an Envelope Protein Domain III-Based Tetravalent Dengue Vaccine in Mice.

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    Hsin-Wei Chen

    Full Text Available Dengue is the leading cause of mosquito-borne viral infections and no vaccine is available now. Envelope protein domain III (ED3 is the major target for the binding of dengue virus neutralizing antibodies; however, the ED3-specifc T-cell response is less well understood. To investigate the T-cell responses to four serotypes of dengue virus (DENV-1 to 4, we immunized mice using either a tetravalent ED3-based DNA or protein vaccine, or combined both as a DNA prime-protein boost strategy (prime-boost. A significant serotype-dependent IFN-γ or IL-4 response was observed in mice immunized with either the DNA or protein vaccine. The IFN-γ response was dominant to DENV-1 to 3, whereas the IL-4 response was dominant to DENV-4. Although the similar IgG titers for the four serotypes were observed in mice immunized with the tetravalent vaccines, the neutralizing antibody titers varied and followed the order of 2 = 3>1>4. Interestingly, the lower IFN-γ response to DENV-4 is attributable to the immunodominance change between two CD4+ T-cell epitopes; one T-cell epitope located at E349-363 of DENV-1 to 3 was more immunogenic than the DENV-4 epitope E313-327. Despite DENV-4 specific IFN-γ responses were suppressed by immunodominance change, either DENV-4-specific IFN-γ or neutralizing antibody responses were still recalled after DENV-4 challenge and contributed to virus clearance. Immunization with the prime-boost elicited both IFN-γ and neutralizing antibody responses and provided better protection than either DNA or protein immunization. Our findings shed light on how ED3-based tetravalent dengue vaccines sharpen host CD4 T-cell responses and contribute to protection against dengue virus.

  16. Dengue envelope-based 'four-in-one' virus-like particles produced using Pichia pastoris induce enhancement-lacking, domain III-directed tetravalent neutralising antibodies in mice.

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    Rajpoot, Ravi Kant; Shukla, Rahul; Arora, Upasana; Swaminathan, Sathyamangalam; Khanna, Navin

    2018-06-05

    Dengue is a significant public health problem worldwide, caused by four antigenically distinct mosquito-borne dengue virus (DENV) serotypes. Antibodies to any given DENV serotype which can afford protection against that serotype tend to enhance infection by other DENV serotypes, by a phenomenon termed antibody-dependent enhancement (ADE). Antibodies to the viral pre-membrane (prM) protein have been implicated in ADE. We show that co-expression of the envelope protein of all four DENV serotypes, in the yeast Pichia pastoris, leads to their co-assembly, in the absence of prM, into tetravalent mosaic VLPs (T-mVLPs), which retain the serotype-specific antigenic integrity and immunogenicity of all four types of their monomeric precursors. Following a three-dose immunisation schedule, the T-mVLPs elicited EDIII-directed antibodies in mice which could neutralise all four DENV serotypes. Importantly, anti-T-mVLP antibodies did not augment sub-lethal DENV-2 infection of dengue-sensitive AG129 mice, based on multiple parameters. The 'four-in-one' tetravalent T-mVLPs possess multiple desirable features which may potentially contribute to safety (non-viral, prM-lacking and ADE potential-lacking), immunogenicity (induction of virus-neutralising antibodies), and low cost (single tetravalent immunogen produced using P. pastoris, an expression system known for its high productivity using simple inexpensive media). These results strongly warrant further exploration of this vaccine candidate.

  17. A recombinant live attenuated tetravalent vaccine for the prevention of dengue.

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    Guy, Bruno; Noriega, Fernando; Ochiai, R Leon; L'azou, Maïna; Delore, Valentine; Skipetrova, Anna; Verdier, François; Coudeville, Laurent; Savarino, Stephen; Jackson, Nicholas

    2017-07-01

    Dengue is an important and still growing public health problem associated with substantial morbidity, as well as significant social and economic impact. The present review describes the main features and development of the first dengue vaccine (CYD-TDV, Dengvaxia®), which has been licensed by several dengue-endemic countries in Asia and Latin America for use in populations above 9 years of age. Areas covered: The review focuses on the large clinical development of CYD-TDV, which includes in particular two pivotal phase III efficacy trials conducted in Asia and Latin America and supported vaccine licensure. Based on these clinical data, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended considering introduction of the vaccine in geographic settings (national or subnational) with high burden of disease. Long-term safety follow-up studies of the efficacy trials are currently ongoing, and post-licensure studies will evaluate the vaccine effectiveness and safety in 'real-life' following vaccine introduction. Expert commentary: During vaccine development, a number of complexities were tackled, innovation pursued, and risk managed. These aspects, as well as the potential impact of CYD-TDV on public health are also discussed.

  18. Resource Use and Costs of Dengue: Analysis of Data from Phase III Efficacy Studies of a Tetravalent Dengue Vaccine.

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    El Fezzazi, Hanna; Branchu, Marie; Carrasquilla, Gabriel; Pitisuttithum, Punnee; Perroud, Ana Paula; Frago, Carina; Coudeville, Laurent

    2017-12-01

    A tetravalent dengue vaccine (CYD-TDV) has recently been approved in 12 countries in southeast Asia and Latin America for individuals aged 9-45 years or 9-60 years (age indication approvals vary by country) living in endemic areas. Data on utilization of medical and nonmedical resources as well as time lost from school and work were collected during the active phase of two phase III efficacy studies performed in 10 countries in the Asia-Pacific region and Latin America (NCT01373281; NCT01374516). We compared dengue-related resource utilization and costs among vaccinated and nonvaccinated participants. Country-specific unit costs were derived from available literature. There were 901 virologically confirmed dengue episodes among participants aged ≥ 9 years ( N = 25,826): corresponding to 373 episodes in the CYD-TDV group ( N = 17,230) and 528 episodes in the control group ( N = 8,596). Fewer episodes in the CYD-TDV group resulted in hospitalization than in the control group (7.0% versus 13.3%; P = 0.002), but both had a similar average length of stay of 4 days. Overall, a two-thirds reduction in resource consumption and missed school/work days was observed in the CYD-TDV group relative to the control group. The estimated direct and indirect cost (2014 I$) associated with dengue episodes per participant in the CYD-TDV group was 73% lower than in the control group (I$6.72 versus I$25.08); representing a saving of I$I8.36 (95% confidence interval [CI]:17.05-19.78) per participant with vaccination. This is the first study providing information on dengue costs among vaccinated individuals and direct confirmation that vaccination has the potential to reduce dengue illness costs.

  19. Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

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    Zhang Quanfu

    2011-06-01

    Full Text Available Abstract Background The incidence of dengue, an infectious disease caused by dengue virus (DENV, has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated. Results By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses. Conclusions Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.

  20. Working towards dengue as a vaccine-preventable disease: challenges and opportunities.

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    Shrivastava, Ambuj; Tripathi, Nagesh K; Dash, Paban K; Parida, Manmohan

    2017-10-01

    Dengue is an emerging viral disease that affects the human population around the globe. Recent advancements in dengue virus research have opened new avenues for the development of vaccines against dengue. The development of a vaccine against dengue is a challenging task because any of the four serotypes of dengue viruses can cause disease. The development of a dengue vaccine aims to provide balanced protection against all the serotypes. Several dengue vaccine candidates are in the developmental stages such as inactivated, live attenuated, recombinant subunit, and plasmid DNA vaccines. Area covered: The authors provide an overview of the progress made in the development of much needed dengue vaccines. The authors include their expert opinion and their perspectives for future developments. Expert opinion: Human trials of a live attenuated tetravalent chimeric vaccine have clearly demonstrated its potential as a dengue vaccine. Other vaccine candidate molecules such as DENVax, a recombinant chimeric vaccine andTetraVax, are at different stages of development at this time. The authors believe that the novel strategies for testing and improving the immune response of vaccine candidates in humans will eventually lead to the development of a successful dengue vaccine in future.

  1. Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccination.

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    Vigne, Claire; Dupuy, Martin; Richetin, Aline; Guy, Bruno; Jackson, Nicholas; Bonaparte, Matthew; Hu, Branda; Saville, Melanie; Chansinghakul, Danaya; Noriega, Fernando; Plennevaux, Eric

    2017-09-02

    Two large pivotal phase III studies demonstrated the efficacy of the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®, Sanofi Pasteur) against all dengue serotypes. Here we present an unprecedented integrated summary of the immunogenicity of CYD-TDV to identify the parameters driving the neutralizing humoral immune response and evolution over time. We summarized the immunogenicity profiles of a 3-dose schedule of CYD-TDV administered 6 months apart across 10 phase II and 6 phase III trials undertaken in dengue endemic and non-endemic countries. Dengue neutralizing antibody titers in sera were determined at centralized laboratories using the 50% plaque reduction neutralization test (PRNT 50 ) at baseline, 28 d after the third dose, and annually thereafter for up to 4 y after the third dose in some studies. CYD-TDV elicits neutralizing antibody responses against all 4 dengue serotypes; geometric mean titers (GMTs) increased from baseline to post-dose 3. GMTs were influenced by several parameters including age, baseline dengue seropositivity and region. In the 2 pivotal studies, GMTs decreased initially during the first 2 y post-dose 3 but appear to stabilize or slightly increase again in the third year. GMTs persisted 1.2-3.2-fold higher than baseline levels for up to 4 y post-dose 3 in other studies undertaken in dengue endemic countries. Our integrated analysis captures the fullness of the CYD-TDV immunogenicity profile across studies, age groups and regions; by presenting the available data in this way general trends and substantial outliers within each grouping can be easily identified. CYD-TDV elicits neutralizing antibody responses against all dengue serotypes, with differences by age and endemicity, which persist above baseline levels in endemic countries.

  2. Phase I Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults from Puerto Rico.

    Science.gov (United States)

    Diaz, Clemente; Lin, Leyi; Martinez, Luis J; Eckels, Kenneth H; Campos, Maribel; Jarman, Richard G; De La Barrera, Rafael; Lepine, Edith; Toussaint, Jean-François; Febo, Irma; Innis, Bruce L; Thomas, Stephen J; Schmidt, Alexander C

    2018-05-01

    The safety and immunogenicity of four adjuvanted formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV) were evaluated in a predominantly dengue-primed population in Puerto Rico. In this placebo-controlled, randomized, observer-blind, phase I trial, 100 healthy adults were randomized 1:1:1:1:1 to receive DPIV at Day (D)0 and D28 (1 μg per dengue virus [DENV] type 1-4 adjuvanted with either alum, AS01 E or AS03 B , or 4 μg per DENV type adjuvanted with alum) or saline placebo. Functional antibody responses were assessed using a microneutralization assay at D56, Month (M)7, and M13. All DPIV formulations were well tolerated and no safety signals were identified through M13. The M13 according-to-protocol (ATP) immunogenicity cohort included 83 participants. The ATP analysis of immunogenicity was performed only on the 78 subjects seropositive for ≥ 1 DENV type at baseline: 69 tetravalent, three trivalent, two bivalent, and four monovalent. In all DPIV groups, geometric mean antibody titers (GMTs) increased from D0 to D56 and waned modestly through M13, while remaining well above prevaccination levels. The 4 μg + alum and the AS01 E - and AS03 B -adjuvanted formulations were highly immunogenic, with M13-neutralizing antibody GMTs against all four DENV types above 1,000. M13/D0 GMT ratios were highest in the 1 μg + AS03 B group (ranging 3.2-3.7 depending on the DENV type). These results encourage continued clinical development of DPIV (ClinicalTrials.gov: NCT01702857).

  3. Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

    Science.gov (United States)

    Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

    2012-09-07

    In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Safety issues from a Phase 3 clinical trial of a live-attenuated chimeric yellow fever tetravalent dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B

    2018-02-26

    A tetravalent live-attenuated 3-dose vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (CYD, also called Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that vaccine be administered to >/ = 9 year-olds residing in highly dengue- endemic countries. When clinical trial results were assessed 2 years after the first dose, vaccine efficacy among seropositives was high, but among seronegatives efficacy was marginal. Breakthrough dengue hospitalizations of vaccinated children occurred continuously over a period of 4-5 years post 3rd dose in an age distribution suggesting these children had been vaccinated when seronegative. This surmise was validated recently when the manufacturer reported that dengue NS1 IgG antibodies were absent in sera from hospitalized vaccinated children, an observation consistent with their having received Dengvaxia when seronegative. Based upon published efficacy data and in compliance with initial published recommendations by the manufacturer and WHO the Philippine government undertook to vaccinate 800,000-plus 9 year-olds starting in April 2016. Eighteen months later, dengue hospitalizations and a deaths were reported among vaccinated children. The benefits of administering Dengvaxia predicted by the manufacturer, WHO and others derive from scoring dengue hospitalizations of vaccinated children as vaccine failures rather than as vaccine enhanced dengue disease. Recommended regimens for administration of Dengvaxia should have been structured to warn of and avoid serious adverse events.

  5. Production of recombinant dengue non-structural 1 (NS1) proteins from clinical virus isolates.

    Science.gov (United States)

    Yohan, Benediktus; Wardhani, Puspa; Aryati; Trimarsanto, Hidayat; Sasmono, R Tedjo

    2017-01-01

    Dengue is a febrile disease caused by infection of dengue virus (DENV). Early diagnosis of dengue infection is important for better management of the disease. The DENV Non-Structural Protein 1 (NS1) antigen has been routinely used for the early dengue detection. In dengue epidemic countries such as Indonesia, clinicians are increasingly relying on the NS1 detection for confirmation of dengue infection. Various NS1 diagnostic tests are commercially available, however different sensitivities and specificities were observed in various settings. This study was aimed to generate dengue NS1 recombinant protein for the development of dengue diagnostic tests. Four Indonesian DENV isolates were used as the source of the NS1 gene cloning, expression, and purification in bacterial expression system. Recombinant NS1 proteins were successfully purified and their antigenicities were assessed. Immunization of mice with recombinant proteins observed the immunogenicity of the NS1 protein. The generated recombinant proteins can be potentially used in the development of NS1 diagnostic test. With minimal modifications, this method can be used for producing NS1 recombinant proteins from isolates obtained from other geographical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Characterization of recombinant yellow fever-dengue vaccine viruses with human monoclonal antibodies targeting key conformational epitopes.

    Science.gov (United States)

    Lecouturier, Valerie; Berry, Catherine; Saulnier, Aure; Naville, Sophie; Manin, Catherine; Girerd-Chambaz, Yves; Crowe, James E; Jackson, Nicholas; Guy, Bruno

    2018-04-26

    The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in several dengue-endemic countries. Although the vaccine provides protection against dengue, the level of protection differs by serotype and warrants further investigation. We characterized the antigenic properties of each vaccine virus serotype using highly neutralizing human monoclonal antibodies (hmAbs) that bind quaternary structure-dependent epitopes. Specifically, we monitored the binding of dengue virus-1 (DENV-1; 1F4), DENV-2 (2D22) or DENV-3 (5J7) serotype-specific or DENV-1-4 cross-reactive (1C19) hmAbs to the four chimeric yellow fever-dengue vaccine viruses (CYD-1-4) included in phase III vaccine formulations using a range of biochemical and functional assays (dot blot, ELISA, surface plasmon resonance and plaque reduction neutralization assays). In addition, we used the "classic" live, attenuated DENV-2 vaccine serotype, immature CYD-2 viruses and DENV-2 virus-like particles as control antigens for anti-serotype-2 reactivity. The CYD vaccine serotypes were recognized by each hmAbs with the expected specificity, moreover, surface plasmon resonance indicated a high functional affinity interaction with the CYD serotypes. In addition, the hmAbs provided similar protection against CYD and wild-type dengue viruses in the in vitro neutralization assay. Overall, these findings demonstrate that the four CYD viruses used in clinical trials display key conformational and functional epitopes targeted by serotype-specific and/or cross-reactive neutralizing human antibodies. More specifically, we showed that CYD-2 displays serotype- specific epitopes present only on the mature virus. This indicates that the CYD-TDV has the ability to elicit antibody specificities which are similar to those induced by the wild type DENV. Future investigations will be needed to address the nature of CYD-TDV-induced responses after vaccine administration, and how these

  7. The Immunogenicity and Safety of CYD-Tetravalent Dengue Vaccine (CYD-TDV) in Children and Adolescents: A Systematic Review.

    Science.gov (United States)

    Agarwal, Raksheeth; Wahid, Mardiastuti H; Yausep, Oliver E; Angel, Sharon H; Lokeswara, Angga W

    2017-01-01

    to assess the immunogenicity and safety of CYD-tetravalent dengue vaccine (CYD-TDV) in children. comprehensive literature searches were conducted on various databases. Randomized-controlled trials on children with CYD-TDV as intervention were selected based on inclusion and exclusion criteria. Data extracted from selected trials included safety of vaccine and immunogenicity in terms of Geometric Mean Titres (GMT) of antibodies.   six clinical trials were selected based on preset criteria. GMT values were obtained using 50% Plaque Reduction Neutralization Test (PRNT) and safety was semi-quantitatively assessed based on adverse effects. Additional data processing was done to obtain a better understanding on the trends among the studies. The results showed that the groups vaccinated with CYD-TDV showed higher immunogenicity against dengue virus antigens than the control groups. Safety results were satisfactory in all trials, and most severe side effects were unrelated to the vaccine. CYD-TDV is both effective and safe for patients in endemic regions. This gives promise for further development and large-scale research on this vaccine to assess its efficacy in decreasing dengue prevalence, and its pervasive implementation in endemic countries, such as Indonesia.

  8. Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children.

    Science.gov (United States)

    Watanaveeradej, Veerachai; Simasathien, Sriluck; Mammen, Mammen P; Nisalak, Ananda; Tournay, Elodie; Kerdpanich, Phirangkul; Samakoses, Rudiwilai; Putnak, Robert J; Gibbons, Robert V; Yoon, In-Kyu; Jarman, Richard G; De La Barrera, Rafael; Moris, Philippe; Eckels, Kenneth H; Thomas, Stephen J; Innis, Bruce L

    2016-06-01

    We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1-4 waned during the 1-3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response. © The American Society of Tropical Medicine and Hygiene.

  9. DENGUE VACCINE, CHALLENGES, DEVELOPMENT AND STRATEGIES

    Directory of Open Access Journals (Sweden)

    Dewi Marbawati

    2014-08-01

    Full Text Available ABSTRAKPenyakit demam Dengue endemik di lebih dari 100 negara di dunia. Obat anti virus Dengue efektif belum ditemukan danpengendalian vektor dinilai kurang efektif, sehingga diperlukan upaya pencegahan dengan vaksinasi. Vaksin Dengue yangideal adalah murah, mencakup 4 serotipe, efektif dalam memberikan kekebalan, cukup diberikan sekali seumur hidup, aman,memberi kekebalan jangka panjang, stabil dalam penyimpanan dan stabil secara genetis (tidak bermutasi. Beberapakandidat vaksin yang telah dan sedang dikembangkan oleh para peneliti di seluruh dunia adalah tetravalent live attenuatedvaccine, vaksin Chimera (ChimeriVax, vaksin subunit dan vaksin DNA. Vaksin Dengue dipandang sebagai pendekatan yangefektif dan berkesinambungan dalam mengendalikan penyakit Dengue. Tahun 2003 telah terbentuk Pediatric DengueVaccine Initiative (PDVI, yaitu sebuah konsorsium internasional yang bergerak dalam advokasi untuk meyakinkanmasyarakat internasional akan penting dan mendesaknya vaksin Dengue. Konsorsium vaksin Dengue Indonesia saat iniberupaya mengembangkan vaksin Dengue dengan menggunakan strain virus lokal.Kata kunci: Dengue, virus, vaksinABSTRACTDengue fever is endemic in more than 100 countries in the world. The effective dengue antiviral drug has not been found yet,and vector control is considered less effective. Prevention program by vaccination is needed. An ideal dengue vaccine shouldbe inexpensive, covering four serotypes (tetravalent, effective in providing immunity, given once a lifetime, safe, stable instorage and genetically. Several vaccine candidates have been and are being developed included attenuated tetravalentvaccine, ChimeriVax, sub- unit vaccines and DNA vaccines. Dengue vaccine is seen as an effective and sustainable approachto controll Dengue infection. In 2003, Pediatric Dengue Vaccine Initiative (PDVI has been formed as an internationalconsortium involved in advocacy to convince the international community about the essence and urgency

  10. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial.

    Science.gov (United States)

    Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki S; Ismail, Hussain Imam H J Muhammad; Chotpitayasunondh, Tawee; Chua, Mary Noreen; Luong, Chan Quang; Rusmil, Kusnandi; Wirawan, Dewa Nyoman; Nallusamy, Revathy; Pitisuttithum, Punnee; Thisyakorn, Usa; Yoon, In-Kyu; van der Vliet, Diane; Langevin, Edith; Laot, Thelma; Hutagalung, Yanee; Frago, Carina; Boaz, Mark; Wartel, T Anh; Tornieporth, Nadia G; Saville, Melanie; Bouckenooghe, Alain

    2014-10-11

    An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children. We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2-14 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281. We randomly assigned 10,275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confirmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 56·5% (95% CI 43·8-66·4) efficacy. We recorded 647 serious adverse

  11. Enhancing the Immunogenicity of a Tetravalent Dengue DNA Vaccine

    Science.gov (United States)

    2016-08-01

    season’s influenza vaccine. There is no overlap with the proposed project. Title: Serological survey for Zika virus and other vector-borne pathogen...studying human immunology and pathogenesis of dengue virus infection Time Commitments: 5% 0.6 calendar months Supporting Agency: Military Infectious...attenuated dengue virus vaccine (LAV), and (3) inactivated dengue virus vaccine. Dengue fever ranks among the top infectious diseases that afflict

  12. Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Galler R.

    2005-01-01

    Full Text Available A chimeric yellow fever (YF-dengue serotype 2 (dengue 2 virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.

  13. A tetravalent dengue nanoparticle stimulates antibody production in mice

    Directory of Open Access Journals (Sweden)

    Silva Elisângela F

    2012-03-01

    Full Text Available Abstract Background Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines. Findings Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p Conclusions Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.

  14. Dengue serotype immune-interactions and their consequences for vaccine impact predictions

    Directory of Open Access Journals (Sweden)

    José Lourenço

    2016-09-01

    Full Text Available Dengue is one of the most important and wide-spread viral infections affecting human populations. The last few decades have seen a dramatic increase in the global burden of dengue, with the virus now being endemic or near-endemic in over 100 countries world-wide. A recombinant tetravalent vaccine candidate (CYD-TDV has recently completed Phase III clinical efficacy trials in South East Asia and Latin America and has been licensed for use in several countries. The trial results showed moderate-to-high efficacies in protection against clinical symptoms and hospitalisation but with so far unknown effects on transmission and infections per se. Model-based predictions about the vaccine's short- or long-term impact on the burden of dengue are therefore subject to a considerable degree of uncertainty. Furthermore, different immune interactions between dengue's serotypes have frequently been evoked by modelling studies to underlie dengue's oscillatory dynamics in disease incidence and serotype prevalence. Here we show how model assumptions regarding immune interactions in the form of antibody-dependent enhancement, temporary cross-immunity and the number of infections required to develop full immunity can significantly affect the predicted outcome of a dengue vaccination campaign. Our results thus re-emphasise the important gap in our current knowledge concerning the effects of previous exposure on subsequent dengue infections and further suggest that intervention impact studies should be critically evaluated by their underlying assumptions about serotype immune-interactions.

  15. Dengue Preventive Strategies: Third World (My World Entrepreneurs Wake Up and Please Stand Up

    Directory of Open Access Journals (Sweden)

    Deepak Gupta

    2015-12-01

    Full Text Available It has taken me almost 19 years and observing/enduring/ignoring 20 seasons of dengue fever in our country’s capital, Delhi to finally say “Enough is enough”. How many more precious lives dengue will consume before infrastructure resolves to fight back and eradicate dengue. Why the development of vaccine has been difficult for this mosquito borne disease. The good news is that the WHO has promising data accumulation in favor of live attenuated recombinant tetravalent dengue vaccine titled CYD-TDV that has taken up the arduous challenge to counter all four serotypes of dengue virus. Hopefully, by April 2016, the WHO may have their recommendations (if any about how and when to use CYD-TDV. Subsequently, the ball will be in the court of dengue-endemic nations’ regulatory authorities to take on the implementations of the WHO recommendations. Herein will lay the prerogative of dengue-endemic nations’ physician-entrepreneurs/pharmaceutical-entrepreneurs in the Third World (my world to take it upon them to ensure that although they have been slow to catch up (already 20 seasons have flown past, they should not miss the train now once the WHO publishes its recommendations in near future so that hopefully, the next season sees the dawn of hope and shifting of gears from economy-draining sluggish anti-dengue campaign to economy-driving future eradicate-dengue campaign initiating from the dengue-endemic nations across the world, including India.

  16. The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response.

    Directory of Open Access Journals (Sweden)

    Jacky Flipse

    Full Text Available Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection.

  17. The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response

    Science.gov (United States)

    Flipse, Jacky; Smit, Jolanda M.

    2015-01-01

    Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection. PMID:26065421

  18. The Complexity of a Dengue Vaccine : A Review of the Human Antibody Response

    NARCIS (Netherlands)

    Flipse, Jacky; Smit, Jolanda M.

    Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV

  19. Production of dengue virus envelope protein domain III-based antigens in tobacco chloroplasts using inducible and constitutive expression systems.

    Science.gov (United States)

    Gottschamel, Johanna; Lössl, Andreas; Ruf, Stephanie; Wang, Yanliang; Skaugen, Morten; Bock, Ralph; Clarke, Jihong Liu

    2016-07-01

    Dengue fever is a disease in many parts of the tropics and subtropics and about half the world's population is at risk of infection according to the World Health Organization. Dengue is caused by any of the four related dengue virus serotypes DEN-1, -2, -3 and -4, which are transmitted to people by Aedes aegypti mosquitoes. Currently there is only one vaccine (Dengvaxia(®)) available (limited to a few countries) on the market since 2015 after half a century's intensive efforts. Affordable and accessible vaccines against dengue are hence still urgently needed. The dengue envelop protein domain III (EDIII), which is capable of eliciting serotype-specific neutralizing antibodies, has become the focus for subunit vaccine development. To contribute to the development of an accessible and affordable dengue vaccine, in the current study we have used plant-based vaccine production systems to generate a dengue subunit vaccine candidate in tobacco. Chloroplast genome engineering was applied to express serotype-specific recombinant EDIII proteins in tobacco chloroplasts using both constitutive and ethanol-inducible expression systems. Expression of a tetravalent antigen fusion construct combining EDIII polypeptides from all four serotypes was also attempted. Transplastomic EDIII-expressing tobacco lines were obtained and homoplasmy was verified by Southern blot analysis. Northern blot analyses showed expression of EDIII antigen-encoding genes. EDIII protein accumulation levels varied for the different recombinant EDIII proteins and the different expression systems, and reached between 0.8 and 1.6 % of total cellular protein. Our study demonstrates the suitability of the chloroplast compartment as a production site for an EDIII-based vaccine candidate against dengue fever and presents a Gateway(®) plastid transformation vector for inducible transgene expression.

  20. Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

    Science.gov (United States)

    Vannice, Kirsten S; Wilder-Smith, Annelies; Barrett, Alan D T; Carrijo, Kalinka; Cavaleri, Marco; de Silva, Aravinda; Durbin, Anna P; Endy, Tim; Harris, Eva; Innis, Bruce L; Katzelnick, Leah C; Smith, Peter G; Sun, Wellington; Thomas, Stephen J; Hombach, Joachim

    2018-03-07

    Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Multiple recombinants in two dengue virus, serotype-2 isolates from patients from Oaxaca, Mexico.

    Science.gov (United States)

    Perez-Ramirez, Gerardo; Diaz-Badillo, Alvaro; Camacho-Nuez, Minerva; Cisneros, Alejandro; Munoz, Maria de Lourdes

    2009-12-15

    Dengue (DEN) is a serious cause of mortality and morbidity in the world including Mexico, where the infection is endemic. One of the states with the highest rate of dengue cases is Oaxaca. The cause of DEN is a positive-sense RNA virus, the dengue virus (DENV) that evolves rapidly increasing its variability due to the absence of a repair mechanism that leads to approximately one mutational event per genome replication; which results in enhancement of viral adaptation, including the escape from host immune responses. Additionally, recombination may play a role in driving the evolution of DENV, which may potentially affect virulence and cause host tropism changes. Recombination in DENV has not been described in Mexican strains, neither has been described the relevance in virus evolution in an endemic state such as Oaxaca where the four serotypes of DENV are circulating. To study whether there are isolates from Oaxaca having recombination, we obtained the sequence of 6 different isolates of DENV-2 Asian/American genotype from the outbreak 2005-6, one clone of the C(91)-prM-E-NS1(2400) structural genes, and 10 clones of the E gene from the isolate MEX_OAX_1656_05. Evidence of recombination was found by using different methods along with two softwares: RDP3 and GARD. The Oaxaca MEX_OAX_1656_05 and MEX_OAX_1038_05 isolates sequenced in this study were recombinant viruses that incorporate the genome sequence from the Cosmopolitan genotype. Furthermore, the clone of the E gene namely MEX_OAX_165607_05 from this study was also recombinant, incorporating genome sequence from the American genotype. This is the first report of recombination in DENV-2 in Mexico. Given such a recombinant activity new genomic combinations were produced, this could play a significant role in the DENV evolution and must be considered as a potentially important mechanism generating genetic variation in this virus with serious implications for the vaccines and drugs formulation as occurs for other

  2. Multiple recombinants in two dengue virus, serotype-2 isolates from patients from Oaxaca, Mexico

    Directory of Open Access Journals (Sweden)

    Cisneros Alejandro

    2009-12-01

    Full Text Available Abstract Background Dengue (DEN is a serious cause of mortality and morbidity in the world including Mexico, where the infection is endemic. One of the states with the highest rate of dengue cases is Oaxaca. The cause of DEN is a positive-sense RNA virus, the dengue virus (DENV that evolves rapidly increasing its variability due to the absence of a repair mechanism that leads to approximately one mutational event per genome replication; which results in enhancement of viral adaptation, including the escape from host immune responses. Additionally, recombination may play a role in driving the evolution of DENV, which may potentially affect virulence and cause host tropism changes. Recombination in DENV has not been described in Mexican strains, neither has been described the relevance in virus evolution in an endemic state such as Oaxaca where the four serotypes of DENV are circulating. Results To study whether there are isolates from Oaxaca having recombination, we obtained the sequence of 6 different isolates of DENV-2 Asian/American genotype from the outbreak 2005-6, one clone of the C(91-prM-E-NS1(2400 structural genes, and 10 clones of the E gene from the isolate MEX_OAX_1656_05. Evidence of recombination was found by using different methods along with two softwares: RDP3 and GARD. The Oaxaca MEX_OAX_1656_05 and MEX_OAX_1038_05 isolates sequenced in this study were recombinant viruses that incorporate the genome sequence from the Cosmopolitan genotype. Furthermore, the clone of the E gene namely MEX_OAX_165607_05 from this study was also recombinant, incorporating genome sequence from the American genotype. Conclusions This is the first report of recombination in DENV-2 in Mexico. Given such a recombinant activity new genomic combinations were produced, this could play a significant role in the DENV evolution and must be considered as a potentially important mechanism generating genetic variation in this virus with serious implications for

  3. An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes.

    Science.gov (United States)

    Khanam, Saima; Rajendra, Pilankatta; Khanna, Navin; Swaminathan, Sathyamangalam

    2007-02-15

    Dengue is a public health problem of global significance for which there is neither an effective antiviral therapy nor a preventive vaccine. It is a mosquito-borne viral disease, caused by dengue (DEN) viruses, which are members of the Flaviviridae family. There are four closely related serotypes, DEN-1, DEN-2, DEN-3 and DEN-4, each of which is capable of causing disease. As immunity to any one serotype can potentially sensitize an individual to severe disease during exposure to a heterologous serotype, the general consensus is that an effective vaccine should be tetravalent, that is, it must be capable of affording protection against all four serotypes. The current strategy of creating tetravalent vaccine formulations by mixing together four monovalent live attenuated vaccine viruses has revealed the phenomenon of viral interference leading to the manifestation of immune responses biased towards a single serotype. This work stems from the emergence of (i) the DEN virus envelope (E) domain III (EDIII) as the most important region of the molecule from a vaccine perspective and (ii) the adenovirus (Ad) as a promising vaccine vector platform. We describe the construction of a recombinant, replication-defective Ad (rAd) vector encoding a chimeric antigen made of in-frame linked EDIIIs of DEN virus serotypes 2 and 4. Using this rAd vector, in conjunction with a plasmid vector encoding the same chimeric bivalent antigen, in a prime-boost strategy, we show that it is possible to elicit equipotent neutralizing and T cell responses specific to both DEN serotypes 2 and 4. Our data support the hypothesis that a DEN vaccine targeting more than one serotype may be based on a single DNA-based vector to circumvent viral interference. This work lays the foundation for developing a single Ad vector encoding EDIIIs of all four DEN serotypes to evoke a balanced immune response against each one of them. Thus, this work has implications for the development of safe and effective

  4. An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes

    Directory of Open Access Journals (Sweden)

    Swaminathan Sathyamangalam

    2007-02-01

    Full Text Available Abstract Background Dengue is a public health problem of global significance for which there is neither an effective antiviral therapy nor a preventive vaccine. It is a mosquito-borne viral disease, caused by dengue (DEN viruses, which are members of the Flaviviridae family. There are four closely related serotypes, DEN-1, DEN-2, DEN-3 and DEN-4, each of which is capable of causing disease. As immunity to any one serotype can potentially sensitize an individual to severe disease during exposure to a heterologous serotype, the general consensus is that an effective vaccine should be tetravalent, that is, it must be capable of affording protection against all four serotypes. The current strategy of creating tetravalent vaccine formulations by mixing together four monovalent live attenuated vaccine viruses has revealed the phenomenon of viral interference leading to the manifestation of immune responses biased towards a single serotype. Results This work stems from the emergence of (i the DEN virus envelope (E domain III (EDIII as the most important region of the molecule from a vaccine perspective and (ii the adenovirus (Ad as a promising vaccine vector platform. We describe the construction of a recombinant, replication-defective Ad (rAd vector encoding a chimeric antigen made of in-frame linked EDIIIs of DEN virus serotypes 2 and 4. Using this rAd vector, in conjunction with a plasmid vector encoding the same chimeric bivalent antigen, in a prime-boost strategy, we show that it is possible to elicit equipotent neutralizing and T cell responses specific to both DEN serotypes 2 and 4. Conclusion Our data support the hypothesis that a DEN vaccine targeting more than one serotype may be based on a single DNA-based vector to circumvent viral interference. This work lays the foundation for developing a single Ad vector encoding EDIIIs of all four DEN serotypes to evoke a balanced immune response against each one of them. Thus, this work has

  5. [Dengue, zika, chikungunya and the development of vaccines].

    Science.gov (United States)

    Kantor, Isabel N

    2018-01-01

    Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.

  6. Dengue, zika, chikungunya and the development of vaccines

    Directory of Open Access Journals (Sweden)

    Isabel N. Kantor

    2018-01-01

    Full Text Available Dengue (DENV, zika (ZIKV and chikungunya (CHIKV, three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.

  7. Dengue human infection models to advance dengue vaccine development.

    Science.gov (United States)

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide.

    Science.gov (United States)

    Rothan, Hussin A; Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M; Rahman, Noorsaadah Abd; Yusof, Rohana

    2013-11-01

    Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.

  9. Novel vaccination approach for dengue infection based on recombinant immune complex universal platform.

    Science.gov (United States)

    Kim, Mi-Young; Reljic, Rajko; Kilbourne, Jacquelyn; Ceballos-Olvera, Ivonne; Yang, Moon-Sik; Reyes-del Valle, Jorge; Mason, Hugh S

    2015-04-08

    Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes.

    Science.gov (United States)

    Holman, David H; Wang, Danher; Raviprakash, Kanakatte; Raja, Nicholas U; Luo, Min; Zhang, Jianghui; Porter, Kevin R; Dong, John Y

    2007-02-01

    Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

  11. Sofosbuvir as treatment against dengue?

    Science.gov (United States)

    Gan, Chye Sheng; Lim, See Khai; Chee, Chin Fei; Yusof, Rohana; Heh, Choon Han

    2018-02-01

    Dengvaxia ® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC 90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in-depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue. © 2017 John Wiley & Sons A/S.

  12. Prevention and Control Strategies to Counter Dengue Virus Infection

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    Irfan A. Rather

    2017-07-01

    Full Text Available Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.

  13. Prevention and Control Strategies to Counter Dengue Virus Infection.

    Science.gov (United States)

    Rather, Irfan A; Parray, Hilal A; Lone, Jameel B; Paek, Woon K; Lim, Jeongheui; Bajpai, Vivek K; Park, Yong-Ha

    2017-01-01

    Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV) has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.

  14. Dengue vaccines: Are they safe for travelers?

    Science.gov (United States)

    Halstead, Scott B; Aguiar, Maira

    2016-01-01

    The four dengue viruses (DENV) circulate among nearly one-half of the world's population in tropical and semitropical countries imposing a huge morbidity burden on travelers. Sanofipasteur has developed a tetravalent live-attenuated vaccine, Dengvaxia, recently approved by the World Health Organization and licensed in four dengue-endemic countries. An additional two dengue vaccines, developed by the National Institute of Allergy and Infectious Diseases (NIAID), USA and Takeda, are entering phase III testing. Dengvaxia is composed of four yellow fever 17D-DENV chimeras, the NIAID vaccine contains three mutagenized DENV and one DENV2/4 chimera while the Takeda vaccine contains an attenuated DENV 2 and three DENV 2-DENV chimeras. Which of these vaccines might be useful in protecting travelers against dengue infections and disease? Dengvaxia requires three doses administered over the course of one year but in addition has safety signals suggesting that susceptible individuals should not be vaccinated. The NIAID vaccine is promising as a travel vaccine as a single dose fully protected susceptible adults against live dengue 2 virus challenge. The protective efficacy and safety of the Takeda vaccine remain to be demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Desarrollo de agentes inmunizantes contra el dengue Development of immunizing agents against dengue

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    Francisco J. López Antuñano

    2000-05-01

    vacunas eficaces contra el dengue tiene especial importancia si se toma en cuenta la magnitud del problema de la transmisión de los cuatro serotipos en el mundo. La inmunización efectiva contra el dengue contribuirá a su prevención y la relación costo-beneficio será positiva. El hecho de que el dengue endémico afecte a niños de corta edad hace necesaria su inmunización, aprovechando la oportunidad que ofrece el Programa Ampliado de Inmunización.The four serotypes of dengue flaviviruses are transmitted mainly by the Aedes aegypti mosquito, and some epidemics have been attributed to Ae. albopictus, Ae. polynesiensis, and various species of the Ae. scutellaris complex. The risk factors involved in dengue mortality and morbidity are related to the human host (genetic characteristics of infected persons; lifestyles, immune status, and health conditions of people; basic sanitation of dwellings; and water supply and to the virus (genetic variability between and among serotypes, different pathogenicities, and geographic distribution. Notwithstanding the lack of knowledge of the immunopathobiology of dengue fever, important advances have been made in terms of a protective immune response, using attenuated dengue viruses or antigens produced by means of recombinant technologies. Efforts have been made since the 1940s to develop dengue vaccines. Immunity acquired from natural infection is specific for each serotype, and as many as three different serotype infections have been reported in one individual. For this reason, a tetravalent vaccine may likely be needed. Candidate vaccines against the four serotypes have been tested in volunteers and have proven to be immunogenic and safe. Although attenuated live virus vaccines are promising, more study is needed regarding their effectiveness and safety. Currently, several studies are ongoing to develop dengue vaccines using antigens from structural proteins (particularly E glycoprotein and nonstructural proteins, with

  16. Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials.

    Science.gov (United States)

    Plennevaux, Eric; Moureau, Annick; Arredondo-García, José L; Villar, Luis; Pitisuttithum, Punnee; Tran, Ngoc H; Bonaparte, Matthew; Chansinghakul, Danaya; Coronel, Diana L; L'Azou, Maïna; Ochiai, R Leon; Toh, Myew-Ling; Noriega, Fernando; Bouckenooghe, Alain

    2018-04-03

    We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. NCT01373281 and NCT01374516.

  17. Heterologous prime-boost strategy in non-human primates combining the infective dengue virus and a recombinant protein in a formulation suitable for human use.

    Science.gov (United States)

    Valdés, Iris; Hermida, Lisset; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Martín, Jorge; Bernardo, Lídice; López, Carlos; Niebla, Olivia; Menéndez, Tamara; Romero, Yaremis; Sánchez, Jorge; Guzmán, María G; Guillén, Gerardo

    2010-05-01

    The aim of the present work was to test the concept of the heterologous prime-boost strategy combining an infective dengue virus with a recombinant chimeric protein carrying domain III of the envelope protein. Two studies in monkeys, combining recombinant protein PD5 (domain III of the envelope protein from dengue-2 virus, fused to the protein carrier P64k) and the infective dengue virus in the same immunization schedules were carried out. Humoral and cell-mediated immunity were evaluated. In the first study, monkeys received four doses of the protein PD5 and were subsequently infected with one dose of dengue virus. Antibody response measured after virus inoculation was significantly higher compared to that in non-primed monkeys and comparable to that elicited after two doses of infective virus. In a second study, monkeys were infected with one dose of the virus and subsequently boosted with one dose of the recombinant protein, reaching high levels of neutralizing antibodies, which were still detectable 14 months after the last immunization. In addition, the cellular immune response was also recalled. The results obtained in the present work support the approach of heterologous prime-boosting, in either order prime or boost, combining the chimeric protein PD5 (formulated in alum-CPS-A) and an infective dengue virus. The latter could potentially be replaced by an attenuated vaccine candidate. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. Dengue situation in Brazil by year 2000

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    Hermann G Schatzmayr

    2000-01-01

    Full Text Available Dengue virus types 1 and 2 have been isolated in Brazil by the Department of Virology, Instituto Oswaldo Cruz, in 1986 and 1990 respectively, after many decades of absence. A successful continental Aedes aegypti control program in the Americas, has been able to eradicate the vector in most countries in the 60's, but the program could not be sustained along the years. Dengue viruses were reintroduced in the American region and the infection became endemic in Brazil, like in most Central and SouthAmerican countries and in the Caribbean region, due to the weaning of the vector control programs in these countries. High demographic densities and poor housing conditions in large urban communities, made the ideal conditions for vector spreading. All four dengue types are circulating in the continent and there is a high risk of the introduction in the country of the other two dengue types in Brazil, with the development of large epidemics. After the Cuban episode in 1981, when by the first time a large epidemic of dengue hemorrhagic fever and dengue shock syndrome have been described in the Americas, both clinical presentations are observed, specially in the countries like Brazil, with circulation of more than one dengue virus type. A tetravalent potent vaccine seems to be the only possible way to control the disease in the future, besides rapid clinical and laboratory diagnosis, in order to offer supportive treatment to the more severe clinical infections.

  19. A tetravalent virus-like particle vaccine designed to display domain III of dengue envelope proteins induces multi-serotype neutralizing antibodies in mice and macaques which confer protection against antibody dependent enhancement in AG129 mice.

    Directory of Open Access Journals (Sweden)

    Viswanathan Ramasamy

    2018-01-01

    Full Text Available Dengue is one of the fastest spreading vector-borne diseases, caused by four antigenically distinct dengue viruses (DENVs. Antibodies against DENVs are responsible for both protection as well as pathogenesis. A vaccine that is safe for and efficacious in all people irrespective of their age and domicile is still an unmet need. It is becoming increasingly apparent that vaccine design must eliminate epitopes implicated in the induction of infection-enhancing antibodies.We report a Pichia pastoris-expressed dengue immunogen, DSV4, based on DENV envelope protein domain III (EDIII, which contains well-characterized serotype-specific and cross-reactive epitopes. In natural infection, <10% of the total neutralizing antibody response is EDIII-directed. Yet, this is a functionally relevant domain which interacts with the host cell surface receptor. DSV4 was designed by in-frame fusion of EDIII of all four DENV serotypes and hepatitis B surface (S antigen and co-expressed with unfused S antigen to form mosaic virus-like particles (VLPs. These VLPs displayed EDIIIs of all four DENV serotypes based on probing with a battery of serotype-specific anti-EDIII monoclonal antibodies. The DSV4 VLPs were highly immunogenic, inducing potent and durable neutralizing antibodies against all four DENV serotypes encompassing multiple genotypes, in mice and macaques. DSV4-induced murine antibodies suppressed viremia in AG129 mice and conferred protection against lethal DENV-4 virus challenge. Further, neither murine nor macaque anti-DSV4 antibodies promoted mortality or inflammatory cytokine production when passively transferred and tested in an in vivo dengue disease enhancement model of AG129 mice.Directing the immune response to a non-immunodominant but functionally relevant serotype-specific dengue epitope of the four DENV serotypes, displayed on a VLP platform, can help minimize the risk of inducing disease-enhancing antibodies while eliciting effective tetravalent

  20. 78 FR 43219 - Prospective Grant of Exclusive License: Live Attenuated Dengue Tetravalent Vaccine Containing a...

    Science.gov (United States)

    2013-07-19

    ...) E-120-2001/0, Whitehead et al., ``Development of Mutations Useful for Attenuating Dengue Viruses and..., and (3) E-139-2006/0, Whitehead et al., ``Development of Dengue Vaccine Components'', Australian... August 15, 2007, Chinese Patent Application Number 200780031489.4, filed August 15, 2007, European Patent...

  1. Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15-18 Months of Age in Mexico: A Randomized Trial.

    Science.gov (United States)

    Melo, Flor Irene Rodriguez; Morales, José Juan Renteria; De Los Santos, Abiel Homero Mascareñas; Rivas, Enrique; Vigne, Claire; Noriega, Fernando

    2017-06-01

    The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in a number of dengue endemic countries for individuals ≥9 years of age. Before the integration of any vaccine into childhood vaccination schedules, a lack of immune interference and acceptable safety when coadministered with other recommended vaccines should be demonstrated. This randomized, multi-center phase III trial was conducted in Mexico. Healthy toddlers (n = 732) received a booster dose of a licensed pentavalent combination vaccine [diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and Haemophilus influenzae type b (DTaP-IPV//Hib)] either concomitantly or sequentially, with the second dose of CYD-TDV administered as a 3-dose schedule. Antibody titers against diphtheria toxoid, tetanus toxoid and pertussis antigens were measured by enzyme-linked immunosorbent assay. Antibodies against poliovirus and dengue serotypes were measured using a plaque reduction neutralization test. Noninferiority was demonstrated for each of the DTaP-IPV//Hib antigens if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates between the 2 groups (CYD-TDV and placebo) was ≥10%. Safety of both vaccines was assessed. Noninferiority in immune response was demonstrated for all DTaP-IPV//Hib antigens. After 3 doses of CYD-TDV, no difference was observed in the immune response for CYD-TDV between groups. There were no safety concerns during the study. Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.

  2. Experimental in vitro and in vivo systems for studying the innate immune response during dengue virus infections.

    Science.gov (United States)

    Kitab, Bouchra; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

    2018-03-08

    Dengue is the most prevalent arboviral disease in humans and leads to significant morbidity and socioeconomic burden in tropical and subtropical areas. Dengue is caused by infection with any of the four closely related serotypes of dengue virus (DENV1-4) and usually manifests as a mild febrile illness, but may develop into fatal dengue hemorrhagic fever and shock syndrome. There are no specific antiviral therapies against dengue because understanding of DENV biology is limited. A tetravalent chimeric dengue vaccine, Dengvaxia, has finally been licensed for use, but its efficacy was significantly lower against DENV-2 infections and in dengue-naïve individuals. The identification of mechanisms underlying the interactions between DENV and immune responses will help to determine efficient therapeutic and preventive options. It has been well established how the innate immune system responds to DENV infection and how DENV overcomes innate antiviral defenses, however further progress in this field remains hampered by the absence of appropriate experimental dengue models. Herein, we review the available in vitro and in vivo approaches to study the innate immune responses to DENV.

  3. VAKSIN DENGUE DAN PERKEMBANGANNYA SAAT INI DAN DI MASA MENDATANG

    Directory of Open Access Journals (Sweden)

    Triwibowo Ambar Garjito

    2012-09-01

    Full Text Available Dengue virus merupakan salah satu virus anggota dari famili Flaviviridae yang sejak tahun 1956 telah dikenal dapat menimbulkan demam dengue maupun demam berdarah dengue (DBD. Penyakit yang ditularkan oleh nyamuk Aedes aegypti ini diperkirakan telah menjangkiti pada selatar 50-100 juta manusia dengan 500.000 kasus di antaranya dalam manifestasi yang ganas yang dikenal sebagai dengue haemorrhagic fever dan dengue shock syndrome dan 25.000 di antaranya berakibat fatal (meninggal. Saat ini pengembangan vaksin merupakan salah satu solusi yang diharapkan dapat menekan penyebaran penyakit tersebut. E (envelope merupakan salah satu bagian dari protein struktural virus yang sangat penting dalam pengembangan vaksin, yaitu sebagai badan yang memproduksi antibodi netralisasi untuk protein. Non-struktural protein l juga telah diketahui sebagai salah satu komponen penting dalam pengembangan vaksin oleh karena kemampuannya untuk dapat diekspresi pada permukaan sel yang diinfeksi yang dapat menjadi target untuk immune cytolisis. Ada dua pendekatan yang digunakan dalam memproduksi suatu vaksin dengue, yaitu: a. Vaksin hidup yang telah dilemahkan (live attenuated vaccine: b. Vaksin hasil rekayasa (engineered vaccine. Penelitian terhadap vaksin DENV baik rekombinan maupun non-rekombinan yang didasarkan pada uji virus telah dilakukan secara terus-menerus baik pada monyet dan manusia. Sampai saat ini telah dikembangkan sejumlah kandidat vaksin DENV yang berdasar pada tetravalent virus dengue, yaitu a. vaksin konvensional, b. vaksin dengue rekombinan berdasar pada flavivirus, c. vaksin intertypic chimeric, d. vaksin chimerivac, e. vaksin dengue rekombinan menggunakan vector non-ftavivirus dan f. vector adenovirus. Namun demikian, sampai sekarang belum ada vaksin yang siap digunakan untuk menangkal infeksi ke empat serotype virus dengue, sehingga masih diharapkan untuk pengembangan virus lebih lanjut.   Kata kunci: Aedes aegypti, dengue virus, vaksin dengue.

  4. Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.

    Science.gov (United States)

    Dorigatti, Ilaria; Aguas, Ricardo; Donnelly, Christl A; Guy, Bruno; Coudeville, Laurent; Jackson, Nicholas; Saville, Melanie; Ferguson, Neil M

    2015-07-17

    The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing the four dengue viruses on the yellow fever vaccine backbone (CYD-TDV) developed by Sanofi Pasteur. Several analyses have been published on the safety and immunogenicity of the CYD-TDV vaccine from single trials but none modelled the heterogeneity observed in the antibody responses elicited by the vaccine. We analyse the immunogenicity data collected in five phase-2 trials of the CYD-TDV vaccine. We provide a descriptive analysis of the aggregated datasets and fit the observed post-vaccination PRNT50 titres against the four dengue (DENV) serotypes using multivariate regression models. We find that the responses to CYD-TDV are principally predicted by the baseline immunological status against DENV, but the trial is also a significant predictor. We find that the CYD-TDV vaccine generates similar titres against all serotypes following the third dose, though DENV4 is immunodominant after the first dose. This study contributes to a better understanding of the immunological responses elicited by CYD-TDV. The recent availability of phase-3 data is a unique opportunity to further investigate the immunogenicity and efficacy of the CYD-TDV vaccine, especially in subjects with different levels of pre-existing immunity against DENV. Modelling multiple immunological outcomes with a single multivariate model offers advantages over traditional approaches, capturing correlations between response variables, and the statistical method adopted in this study can be applied to a variety of infections with interacting strains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Effective Protection Induced by a Monovalent DNA Vaccine against Dengue Virus (DV Serotype 1 and a Bivalent DNA Vaccine against DV1 and DV2 in Mice

    Directory of Open Access Journals (Sweden)

    Xiaoyan Zheng

    2017-05-01

    Full Text Available Dengue virus (DV is the causal pathogen of dengue fever, which is one of the most rapidly spread mosquito-borne disease worldwide and has become a severe public health problem. Currently, there is no specific treatment for dengue; thus, a vaccine would be an effective countermeasure to reduce the morbidity and mortality. Although, the chimeric Yellow fever dengue tetravalent vaccine has been approved in some countries, it is still necessary to develop safer, more effective, and less costly vaccines. In this study, a DNA vaccine candidate pVAX1-D1ME expressing the prME protein of DV1 was inoculated in BALB/c mice via intramuscular injection or electroporation, and the immunogenicity and protection were evaluated. Compared with traditional intramuscular injection, administration with 50 μg pVAX1-D1ME via electroporation with three immunizations induced persistent humoral and cellular immune responses and effectively protected mice against lethal DV1 challenge. In addition, immunization with a bivalent vaccine consisting of pVAX1-D1ME and pVAX1-D2ME via electroporation generated a balanced IgG response and neutralizing antibodies against DV1 and DV2 and could protect mice from lethal challenge with DV1 and DV2. This study sheds new light on developing a dengue tetravalent DNA vaccine.

  6. Effective Protection Induced by a Monovalent DNA Vaccine against Dengue Virus (DV) Serotype 1 and a Bivalent DNA Vaccine against DV1 and DV2 in Mice.

    Science.gov (United States)

    Zheng, Xiaoyan; Chen, Hui; Wang, Ran; Fan, Dongying; Feng, Kaihao; Gao, Na; An, Jing

    2017-01-01

    Dengue virus (DV) is the causal pathogen of dengue fever, which is one of the most rapidly spread mosquito-borne disease worldwide and has become a severe public health problem. Currently, there is no specific treatment for dengue; thus, a vaccine would be an effective countermeasure to reduce the morbidity and mortality. Although, the chimeric Yellow fever dengue tetravalent vaccine has been approved in some countries, it is still necessary to develop safer, more effective, and less costly vaccines. In this study, a DNA vaccine candidate pVAX1-D1ME expressing the prME protein of DV1 was inoculated in BALB/c mice via intramuscular injection or electroporation, and the immunogenicity and protection were evaluated. Compared with traditional intramuscular injection, administration with 50 μg pVAX1-D1ME via electroporation with three immunizations induced persistent humoral and cellular immune responses and effectively protected mice against lethal DV1 challenge. In addition, immunization with a bivalent vaccine consisting of pVAX1-D1ME and pVAX1-D2ME via electroporation generated a balanced IgG response and neutralizing antibodies against DV1 and DV2 and could protect mice from lethal challenge with DV1 and DV2. This study sheds new light on developing a dengue tetravalent DNA vaccine.

  7. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development.

    Science.gov (United States)

    Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung

    2017-01-01

    The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5-60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  8. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

    Directory of Open Access Journals (Sweden)

    Wen-Yang Tsai

    2017-07-01

    Full Text Available The four serotypes of dengue virus (DENV are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur, a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8% in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  9. Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

    Directory of Open Access Journals (Sweden)

    Monica Poggianella

    Full Text Available Dengue virus (DENV infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

  10. Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

    Science.gov (United States)

    Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

    2017-10-09

    Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance

  11. Advances in the development of vaccines for dengue fever

    Directory of Open Access Journals (Sweden)

    Simmons M

    2012-05-01

    Full Text Available Monika Simmons1, Nimfa Teneza-Mora1, Robert Putnak21Viral and Rickettsial Diseases Department, Naval Medical Research Center, 2Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, USAAbstract: Dengue fever is caused by the mosquito-borne dengue virus (DENV serotypes 1–4, and is the most common arboviral infection of humans in subtropical and tropical regions of the world. There are currently no prophylaxis or treatment options in the form of vaccines or antivirals, leaving vector control the only method of prevention. A particular challenge with DENV is that a successful vaccine has to be effective against all four serotypes without predisposing for antibody-mediated enhanced disease. In this review, we discuss the current lead vaccine candidates in clinical trials, as well as some second-generation vaccine candidates undergoing preclinical evaluation. In addition, we discuss DENV epidemiology, clinical disease and strategies used for Flavivirus antivirals in the past, the development of new DENV therapeutics, and their potential usefulness for prophylaxis and treatment.Keywords: tetravalent dengue vaccine, live attenuated vaccine, purified inactivated vaccine, DNA vaccine, antibody-dependent enhancement, antivirals

  12. Protective and immunological behavior of chimeric yellow fever dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B; Russell, Philip K

    2016-03-29

    Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen.

    Science.gov (United States)

    Alves, Rúbens Prince Dos Santos; Pereira, Lennon Ramos; Fabris, Denicar Lina Nascimento; Salvador, Felipe Scassi; Santos, Robert Andreata; Zanotto, Paolo Marinho de Andrade; Romano, Camila Malta; Amorim, Jaime Henrique; Ferreira, Luís Carlos de Souza

    2016-06-01

    Dengue fever is caused by any of the four known dengue virus serotypes (DENV1 to DENV4) that affect millions of people worldwide, causing a significant number of deaths. There are vaccines based on chimeric viruses, but they still are not in clinical use. Anti-DENV vaccine strategies based on nonstructural proteins are promising alternatives to those based on whole virus or structural proteins. The DENV nonstructural protein 5 (NS5) is the main target of anti-DENV T cell-based immune responses in humans. In this study, we purified a soluble recombinant form of DENV2 NS5 expressed in Escherichia coli at large amounts and high purity after optimization of expression conditions and purification steps. The purified DENV2 NS5 was recognized by serum from DENV1-, DENV2-, DENV3-, or DENV4-infected patients in an epitope-conformation-dependent manner. In addition, immunization of BALB/c mice with NS5 induced high levels of NS5-specific antibodies and expansion of gamma interferon- and tumor necrosis factor alpha-producing T cells. Moreover, mice immunized with purified NS5 were partially protected from lethal challenges with the DENV2 NGC strain and with a clinical isolate (JHA1). These results indicate that the recombinant NS5 protein preserves immunological determinants of the native protein and is a promising vaccine antigen capable of inducing protective immune responses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Virological confirmation of suspected dengue in a Phase 2 Latin American vaccine trial: Implications for vaccine efficacy evaluation

    Directory of Open Access Journals (Sweden)

    Mark Boaz

    2014-01-01

    Full Text Available The CYD tetravalent dengue vaccine candidate is being evaluated for protective efficacy against symptomatic dengue in Phase 3 efficacy trials. The laboratory test algorithm to confirm dengue cases was evaluated prior to Phase 3 trials. During a Phase 2 trial in Latin America a dengue epidemic occurred in the study countries. A total of 72 suspected dengue cases were reported and assessed: virological confirmation comprised qRT-PCR methods and a commercial ELISA kit for NS1 protein (Bio-Rad. The qRT-PCR included a screening assay targeting a conserved dengue region of the 3′-UTR (dengue screen assay followed by 4 individual serotype assays targeting the conserved dengue NS5 genomic region (WT dengue qRT-PCR assays. The NS1 and WT dengue qRT-PCR were endpoint assays for protocol virological confirmation (PVC. Of the 72 suspected cases, 14 were PVC. However, a unique pattern of dengue qRT-PCR results were observed in 5 suspected cases from Honduras: the dengue screen qRT-PCR assay was positive but WT dengue qRT-PCR and NS1 Ag ELISA were negative. To investigate these observations, additional molecular methods were applied: a SYBR® Green-based RT-PCR assay, sequencing assays directed at the genome regions covered by the WT dengue qRT-PCR, and a modified commercial dengue RT-PCR test (Simplexa™ Dengue, Focus Diagnostics. The exploratory data confirmed these additional cases as dengue and indicated the serotype 2 WT dengue qRT-PCR assay was unable to detect a circulating Latin American strain (DENV-2/NI/BID-V608/2006 due to a sequence variation in the isolate. The Simplexa Dengue RT-PCR test was able to detect and serotype dengue. Based on these findings an updated molecular test algorithm for the virological confirmation of dengue cases was developed and implemented in the Phase 3 efficacy trials.

  15. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

    OpenAIRE

    Kontny, U; Kurane, I; Ennis, F A

    1988-01-01

    It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexe...

  16. The Dengue Vaccine Dilemma: Balancing the Individual and Population Risks and Benefits

    OpenAIRE

    Flasche, Stefan; Jit, Mark; Rodr?guez-Barraquer, Isabel; Coudeville, Laurent; Recker, Mario; Koelle, Katia; Milne, George; Hladish, Thomas J.; Perkins, T. Alex; Cummings, Derek A. T.; Dorigatti, Ilaria; Laydon, Daniel J.; Espa?a, Guido; Kelso, Joel; Longini, Ira

    2016-01-01

    BACKGROUND: Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-na?ve vaccinees. We here report predictions from eight independent modelling ...

  17. Tetravalent one-regular graphs of order 4p2

    DEFF Research Database (Denmark)

    Feng, Yan-Quan; Kutnar, Klavdija; Marusic, Dragan

    2014-01-01

    A graph is one-regular if its automorphism group acts regularly on the set of its arcs. In this paper tetravalent one-regular graphs of order 4p2, where p is a prime, are classified.......A graph is one-regular if its automorphism group acts regularly on the set of its arcs. In this paper tetravalent one-regular graphs of order 4p2, where p is a prime, are classified....

  18. Cost-utility analysis of an adjunctive recombinant activated factor VIIa for on-demand treatment of bleeding episodes in dengue haemorrhagic fever.

    Science.gov (United States)

    Naing, Cho; Poovorawan, Yong; Mak, Joon Wah; Aung, Kyan; Kamolratankul, Pirom

    2015-06-01

    The present study aimed to assess the cost-utility analysis of using an adjunctive recombinant activated factor VIIa (rFVIIa) in children for controlling life-threatening bleeding in dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS). We constructed a decision-tree model, comparing a standard care and the use of an additional adjuvant rFVIIa for controlling life-threatening bleeding in children with DHF/DSS. Cost and utility benefit were estimated from the societal perspective. The outcome measure was cost per quality-adjusted life years (QALYs). Overall, treatment with adjuvant rFVIIa gained QALYs, but the total cost was higher. The incremental cost-utility ratio for the introduction of adjuvant rFVIIa was $4241.27 per additional QALY. Sensitivity analyses showed the utility value assigned for calculation of QALY was the most sensitive parameter. We concluded that despite high cost, there is a role for rFVIIa in the treatment of life-threatening bleeding in patients with DHF/DSS.

  19. Global Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions

    Science.gov (United States)

    2014-10-26

    disease transmission within the community before, during and after conduct of a dengue vaccine efficacy trial. Sanofi Pasteur had selected the AFRIMS...WRAIR tetravalent live-attenuated DENV vaccine and Sanofi Pasteur chimerivax candidates demonstrated safety and immunogenicity in pre-clinical testing...of the Sanofi Pasteur tetravalent Chimerivax dengue vaccine phase 11/111 efficacy trial in Kamphaeng Phet. Year 2012 and 2013: Continuation of the

  20. Cost of production of live attenuated dengue vaccines: a case study of the Instituto Butantan, Sao Paulo, Brazil.

    Science.gov (United States)

    Mahoney, R T; Francis, D P; Frazatti-Gallina, N M; Precioso, A R; Raw, I; Watler, P; Whitehead, P; Whitehead, S S

    2012-07-06

    A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. Although this study does not seek to compute the price of the final

  1. Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas

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    Alba Grifoni

    2017-10-01

    Full Text Available BackgroundDengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV. To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua.MethodsHLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a “megapool” (MP consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays.ResultsWe detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005. This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80

  2. Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

    Directory of Open Access Journals (Sweden)

    Anna P. Durbin

    2011-09-01

    Full Text Available Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

  3. Next-generation dengue vaccines: novel strategies currently under development.

    Science.gov (United States)

    Durbin, Anna P; Whitehead, Stephen S

    2011-10-01

    Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

  4. A tetravalent vaccine comprising hexon-chimeric adenoviruses elicits balanced protective immunity against human adenovirus types 3, 7, 14 and 55.

    Science.gov (United States)

    Tian, Xingui; Jiang, Zaixue; Fan, Ye; Qiu, Shuyan; Zhang, Ling; Li, Xiao; Zhou, Zhichao; Liu, Tiantian; Ma, Qiang; Lu, Xiaomei; Zhong, Baimao; Zhou, Rong

    2018-04-04

    Human adenovirus (Ad) species B contains several of the most important types associated with acute respiratory diseases, Ad3, -7, -14 and -55, which often lead to severe lower respiratory tract diseases and epidemic outbreaks. However, there is currently no Ad vaccine approved for general use. The major capsid protein, hexon, is the primary determinant recognized by neutralizing antibodies (NAbs). In this study, four recombinant Ads that have the same genome sequence as Ad3 with the exception of the hexon genes, rAd3EGFP, rAd3H7, rAd3H14 and rAd3H55, were combined as a tetravalent Ad candidate vaccine against Ad3, -7, -14 and -55. The replication efficiencies of chimeric rAd3H14, rAd3H7 and rAd3H55 were similar to that of rAd3EGFP. Recombinant rAd3EGFP, rAd3H7, rAd3H14 and rAd3H55 induced high titers of NAbs against Ad3, -7, -14 and -55, respectively, which were comparable to those induced by wild-type Ads. The mixture of the four recombinant Ads in equal proportions, rAdMix, or rAdMix inactivated by β-propiolactone, induced balanced NAb responses against Ad3, -7, -14 and -55 in mice without reciprocal immunological interference. In co-culture the four recombinant Ads replicated with a similar efficiency without reciprocal inhibition, and the progeny virions may be chimeric. Purified co-culture, rAdMix-C, also elicited balanced immune responses, suggesting a simple method for multivalent vaccine production. These results indicate the possible advantage of the four Ads as a live combined vaccine. Importantly, pre-immunization with rAdMix conferred protection against Ad3, -7, -14 or -55 challenge in mice in vivo. Thus, this research provides a novel tetravalent Ad vaccine candidate against Ad3, -7, -14 and -55. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Atomistic Simulation of Intrinsic Defects and Trivalent and Tetravalent Ion Doping in Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Ricardo D. S. Santos

    2014-01-01

    Full Text Available Atomistic simulation techniques have been employed in order to investigate key issues related to intrinsic defects and a variety of dopants from trivalent and tetravalent ions. The most favorable intrinsic defect is determined to be a scheme involving calcium and hydroxyl vacancies. It is found that trivalent ions have an energetic preference for the Ca site, while tetravalent ions can enter P sites. Charge compensation is predicted to occur basically via three schemes. In general, the charge compensation via the formation of calcium vacancies is more favorable. Trivalent dopant ions are more stable than tetravalent dopants.

  6. Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study.

    Science.gov (United States)

    Sáez-Llorens, Xavier; Tricou, Vianney; Yu, Delia; Rivera, Luis; Tuboi, Suely; Garbes, Pedro; Borkowski, Astrid; Wallace, Derek

    2017-06-01

    Dengue is the most common mosquito-borne viral disease in human beings, and vector control has not halted its spread worldwide. A dengue vaccine for individuals aged 9 years and older has been licensed, but there remains urgent medical need for a vaccine that is safe and effective against all four dengue virus serotypes (DENV-1-4) in recipients of all ages. Here, we present the preplanned interim analyses at 6 months of a tetravalent dengue vaccine candidate (TDV), which is comprised of an attenuated DENV-2 virus strain (TDV-2) and three chimeric viruses containing the premembrane and envelope protein genes of DENV-1, DENV-3, and DENV-4 genetically engineered into the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4). An ongoing phase 2, randomised, double-blind, placebo-controlled trial of a TDV is being done at three sites in dengue-endemic countries (Dominican Republic, Panama, and the Philippines) to determine its safety and immunogenicity over 48 months in healthy participants aged 2-17 years who were randomly assigned (1:2:5:1) using an interactive web response system (stratified by age) to subcutaneous TDV injection (one 0·5 mL dose containing 2·5 × 10 4 plaque-forming units [PFU] of TDV-1; 6·3 × 10 3 PFU of TDV-2; 3·2 × 10 4 PFU of TDV-3; and 4·0 × 10 5 PFU of TDV-4) in different dose schedules (two-dose regimen at 0 and 3 months, one dose at 0 months, or one dose at 0 months and a booster at 12 months) or placebo. The primary endpoint of this 6 month interim analysis was geometric mean titres (GMTs) of neutralising antibodies against DENV-1-4 in the per-protocol immunogenicity subset at 1 month, 3 months, and 6 months after the first injection. Safety was assessed as a secondary outcome as percentage of participants with serious adverse events in all participants who were injected (safety set), and solicited and unsolicited adverse events (immunogenicity subset). This trial is registered with ClinicalTrials.gov, number NCT

  7. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

    Science.gov (United States)

    Flasche, Stefan; Jit, Mark; Rodríguez-Barraquer, Isabel; Coudeville, Laurent; Recker, Mario; Koelle, Katia; Milne, George; Hladish, Thomas J; Perkins, T Alex; Cummings, Derek A T; Dorigatti, Ilaria; Laydon, Daniel J; España, Guido; Kelso, Joel; Longini, Ira; Lourenco, Jose; Pearson, Carl A B; Reiner, Robert C; Mier-Y-Terán-Romero, Luis; Vannice, Kirsten; Ferguson, Neil

    2016-11-01

    Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in

  8. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia: A Model Comparison Study.

    Directory of Open Access Journals (Sweden)

    Stefan Flasche

    2016-11-01

    Full Text Available Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9. These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%, the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34% and in high-transmission settings (SP9 ≥ 70% by 13%-25% (all simulations: 10%- 34%. These endemicity levels are representative of the

  9. Dengue Fever/Dengue Haemorrhagic Fever : Case Management

    OpenAIRE

    Nimmannitya, Suchitra

    1995-01-01

    Dengue infections caused by the four antigenically distinct dengue virus serotypes (dengue virus 1, dengue virus 2, dengue virus 3, dengue virus 4) of the family Flavivindae, are the most important arbovirus disease in man, both in terms of morbidity and mortality. The infection is transmitted from man to man by Aedes mosquitoes. Since 1956, dengue virus infection has resulted in more than 3 million hospital admissions and more than 50,000 deaths in Southeast Asia, Western Pacific countries, ...

  10. Clinical Efficacy, Safety, and Immunogenicity of a Live Attenuated Tetravalent Dengue Vaccine (CYD-TDV in Children: A Systematic Review with Meta-analysis

    Directory of Open Access Journals (Sweden)

    Moffat Malisheni

    2017-08-01

    Full Text Available BackgroundDengue hemorrhagic fever is the leading cause of hospitalization and death in children living in Asia and Latin America. There is an urgent need for an effective and safe dengue vaccine to reduce morbidity and mortality in this high-risk population given the lack of dengue specific treatment at present. This review aims to determine the efficacy, safety, and immunogenicity of CYD-TDV vaccine in children.MethodsThis is a systematic review including meta-analysis of randomized controlled clinical trial data from Embase, Medline, the Cochrane Library, Web of Science, and ClinicalTrials.gov. Studies that assessed CYD-TDV vaccine efficacy [(1 − RR*100], safety (RR, and immunogenicity (weighted mean difference in children were included in this study. Random effects model was employed to analyze patient-level data extracted from primary studies.ResultsThe overall efficacy of CYD-TDV vaccine was 54% (40–64, while serotype-specific efficacy was 77% (66–85 for DENV4, 75% (65–82 for DENV3, 50% (36–61 for DENV1, and 34% (14–49 for DENV2. 15% (−174–74 vaccine efficacy was obtained for the unknown serotype. Meta-analysis of included studies with longer follow-up time (25 months revealed that CYD-TDV vaccine significantly increased the risk of injection site reactions (RR = 1.1: 1.04–1.17; p-value = 0.001. Immunogenicity (expressed as geometric mean titers in descending order was 439.7 (331.7–547.7, 323 (247 – 398.7, 144.1 (117.9–170.2, and 105 (88.7–122.8 for DENV3, DENV2, DENV1, and DENV4, respectively.ConclusionCYD-TDV vaccine is effective and immunogenic in children overall. Reduced efficacy of CYD-TDV vaccine against DENV2 notoriously known for causing severe dengue infection and dengue outbreaks cause for serious concern. Post hoc meta-analysis of long-term follow-up data (≥25 months from children previously vaccinated with CYD-TDV vaccine is needed to make a conclusion regarding CYD-TDV vaccine

  11. Limited replication of yellow fever 17DD and 17D-Dengue recombinant viruses in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Gisela F. Trindade

    2008-06-01

    Full Text Available For the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. We have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17DD virus (YFV 17DD and recombinant yellow fever 17D viruses expressing envelope proteins of dengue virus serotypes 2 and 4 (17D-DENV-2 and 17D-DENV-4. Serum samples from rhesus monkeys inoculated with YFV 17DD and 17D-DENV chimeras by intracerebral or subcutaneous route were used to determine and compare the viremia induced by these viruses. Viral load quantification in samples from monkeys inoculated by either route with YFV 17DD virus suggested a restricted capability of the virus to replicate reaching not more than 2.0 log10 PFU mL-1 or 3.29 log10 copies mL-1. Recombinant 17D-dengue viruses were shown by plaquing and real-time PCR to be as attenuated as YF 17DD virus with the highest mean peak titer of 1.97 log10 PFU mL-1 or 3.53 log10 copies mL-1. These data serve as a comparative basis for the characterization of other 17D-based live attenuated candidate vaccines against other diseases.Uma das principais propriedades a serem estabelecidas para o desenvolvimento de vacinas seguras e atenuadas de flavivirus,é a taxa de replicação viral. Neste trabalho, aplicamos a metodologia de amplificação pela reação em cadeia da polimerase em tempo real e titulação viral por plaqueamento para determinação da replicação do vírus 17DD (FA 17DD e recombinantes, expressando proteínas do envelope de dengue sorotipos 2 e 4 (17D-DENV-2 e 17D-DENV-4. As amostras de soros de macacos inoculados por via intracerebral ou subcutânea com FA 17DD ou 17D-DENV foram usadas para determinar e comparar a viremia induzida por estes vírus. A quantificação da carga viral em amostras de macacos inoculados por ambas as vias com FA 17DD sugere restrita capacidade de replicação com

  12. Dengue encephalitis–A rare manifestation of dengue fever

    OpenAIRE

    Madi, Deepak; Achappa, Basavaprabhu; Ramapuram, John T; Chowta, Nityananda; Laxman, Mridula; Mahalingam, Soundarya

    2014-01-01

    The clinical spectrum of dengue fever ranges from asymptomatic infection to dengue shock syndrome. Dengue is classically considered a non-neurotropic virus. Neurological complications are not commonly seen in dengue. The neurological manifestations seen in dengue are encephalitis, meningitis, encephalopathy, stroke and Guillain-Barré syndrome. Dengue encephalitis is a rare disease. We report an interesting case of dengue encephalitis from Southern India. A 49-year-old gentleman presented with...

  13. Complex formation of transferrin with tetravalent plutonium and cerium

    International Nuclear Information System (INIS)

    Subramanian, M.S.; Oomen, I.K.

    1981-01-01

    Gel filtration experiments with 239 Pu labelled In Vitro bovine serum showed that the metal ion is bound to the transferrin of the serum proteins as in the case of iron labelled serum. This was confirmed by polyacrylamide gel electrophoresis. The ovotransferrin prepared from chicken egg white which was devoid of hemopexin contaminant was found to complex both tetravalent plutonium and cerium giving visible absorption peak at 365 and 435 nm respectively. The binding capacity of ovotransferrin with tetravalent plutonium and cerium, determined by spectrophotometric titration indicates that two metal ions are bound to each protein molecule as in the case of iron. The average molecular weight computed from this binding capacity measurements was found to be 71,000-75,000. The number of protons liberated for each metal ion bound was found to be three as in the case of iron. (author)

  14. Preparation of hexavalent plutonium and its determination in the presence of tetravalent plutonium; Preparation de plutonium hexavalent et dosage en presence de plutonium tetravalent

    Energy Technology Data Exchange (ETDEWEB)

    Corpel, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Corpel, J [Institut du Radium, 75 - Paris (France)

    1958-07-01

    In order to study the eventual reduction of plutonium from the VI-valent state to the IV-valent state, in sulphuric medium, under the influence of its own {alpha} radiation or of the {gamma}-rays from a cobalt-60 source, we have developed a method for preparing pure hexavalent plutonium and two methods for determining solutions containing tetravalent and hexavalent plutonium simultaneously. Hexavalent plutonium was prepared by anodic oxidation at a platinum electrode. Study of the oxidation yield as a function of various factors has made it possible to define experimental conditions giving complete oxidation. For concentrations in total plutonium greater than 1.5 x 10{sup -3} M, determination of the two valencies IV and VI was carried out by spectrophotometry at two wavelengths. For lower concentrations, the determination was done by counting, after separation of the tetravalent plutonium in the form of fluoride in the presence of a carrier. (author) [French] Afin d'etudier l'eventuelle reduction du plutonium de l'etat de valence VI a l'etat de valence IV, en milieu sulfurique sous l'influence de son propre rayonnement {alpha} ou des rayons {gamma} d'une source de cobalt-60, nous avons mis au point une methode de preparation de plutonium hexavalent pur et deux methodes de dosage des solutions contenant simultanement du plutonium tetravalent et du plutonium hexavalent. Nous avons prepare le plutonium hexavalent par oxydation anodique au contact d'une electrode de platine. L'etude de rendement de l'oxydation en fonction des divers facteurs nous a permis de definir des conditions experimentales donnant une oxydation complete. Pour des concentrations en plutonium total superieures a 1,5.10{sup -3} M, le dosage des deux valences IV et VI a ete realise par spectrophotometrie a deux longueurs d'onde. Pour des concentrations inferieures, le dosage a ete effectue par comptage apres separation du plutonium tetravalent sous la forme du fluorure en presence d'un entraineur

  15. Dengue Epidemiology

    Science.gov (United States)

    ... and dengue shock syndrome (DSS). Transmission of the Dengue Virus Dengue is transmitted between people by the ... the vectors is too infrequent to sustain transmission. Dengue is an Emerging Disease The four dengue viruses ...

  16. Current status of flavivirus vaccines.

    Science.gov (United States)

    Barrett, A D

    2001-12-01

    Although there are approximately 68 flaviviruses recognized, vaccines have been developed to control very few human flavivirus diseases. Licensed live attenuated vaccines have been developed for yellow fever (strain 17D) and Japanese encephalitis (strain SA14-14-2) viruses, and inactivated vaccines have been developed for Japanese encephalitis and tick-borne encephalitis viruses. The yellow fever live attenuated 17D vaccine is one of the most efficacious and safe vaccines developed to date and has been used to immunize more than 300 million people. A number of experimental vaccines are being developed, most notably for dengue. Candidate tetravalent live attenuated dengue vaccines are undergoing clinical trials. Other vaccines are being developed using reverse genetics, DNA vaccines, and recombinant immunogens. In addition, the yellow fever 17D vaccine has been used as a backbone to generate chimeric viruses containing the premembrane and envelope protein genes from other flaviviruses. The "Chimerivax" platform has been used to construct chimeric Japanese encephalitis and dengue viruses that are in different phases of development. Similar strategies are being used by other laboratories.

  17. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? There Is Only One True Winner.

    Science.gov (United States)

    Halstead, Scott B

    2017-07-17

    The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1. It is also possible that chimeric structure does not present the correct virion conformation permitting the development of protective neutralizing antibodies. A premonitory signal shared by the Sanofi Pasteur and the Takeda vaccines was the failure of fully immunized subhuman primates to prevent low-level viremia and/or anamnestic antibody responses to live DENV challenge. The vaccine developed by the National Institute of Allergy and Infectious Diseases (National Institutes of Health [NIH]) has met virtually all of the goals needed to demonstrate preclinical efficacy and safety for humans. Each monovalent vaccine was comprehensively studied for reactogenicity and immunogenicity in human volunteers. Protective immunity in subjects receiving tetravalent candidate vaccines was evidenced by the fact that when vaccinated subjects were given further doses of vaccine or different strains of DENV the result was "solid immunity," a nonviremic and nonanamnestic immune response. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  18. Development of a Novel Tetravalent Synthetic Peptide That Binds to Phosphatidic Acid.

    Directory of Open Access Journals (Sweden)

    Rina Ogawa

    Full Text Available We employed a multivalent peptide-library screening technique to identify a peptide motif that binds to phosphatidic acid (PA, but not to other phospholipids such as phosphatidylcholine (PC, phosphatidylethanolamine (PE, and phosphatidylserine (PS. A tetravalent peptide with the sequence motif of MARWHRHHH, designated as PAB-TP (phosphatidic acid-binding tetravalent peptide, was shown to bind as low as 1 mol% of PA in the bilayer membrane composed of PC and cholesterol. Kinetic analysis of the interaction between PAB-TP and the membranes containing 10 mol% of PA showed that PAB-TP associated with PA with a low dissociation constant of KD = 38 ± 5 nM. Coexistence of cholesterol or PE with PA in the membrane enhanced the PAB-TP binding to PA by increasing the ionization of the phosphomonoester head group as well as by changing the microenvironment of PA molecules in the membrane. Amino acid replacement analysis demonstrated that the tryptophan residue at position 4 of PAB-TP was involved in the interaction with PA. Furthermore, a series of amino acid substitutions at positions 5 to 9 of PAB-TP revealed the involvement of consecutive histidine and arginine residues in recognition of the phosphomonoester head group of PA. Our results demonstrate that the recognition of PA by PAB-TP is achieved by a combination of hydrophobic, electrostatic and hydrogen-bond interactions, and that the tetravalent structure of PAB-TP contributes to the high affinity binding to PA in the membrane. The novel PA-binding tetravalent peptide PAB-TP will provide insight into the molecular mechanism underlying the recognition of PA by PA-binding proteins that are involved in various cellular events.

  19. Analysis of Individuals from a Dengue-Endemic Region Helps Define the Footprint and Repertoire of Antibodies Targeting Dengue Virus 3 Type-Specific Epitopes.

    Science.gov (United States)

    Andrade, Daniela V; Katzelnick, Leah C; Widman, Doug G; Balmaseda, Angel; de Silva, Aravinda M; Baric, Ralph S; Harris, Eva

    2017-09-19

    The four dengue virus serotypes (DENV1 to 4) cause dengue, a major public health problem worldwide. Individuals exposed to primary DENV infections develop serotype-specific neutralizing antibodies, including strongly neutralizing antibodies targeting quaternary epitopes. To date, no studies have measured the levels and kinetics of serum antibodies directed to such epitopes among populations in regions where dengue is endemic. Here, we use a recombinant DENV4 (rDENV4/3-M14) displaying a major DENV3 type-specific quaternary epitope recognized by human monoclonal antibody 5J7 to measure the proportion, magnitude, and kinetics of DENV3 type-specific neutralizing antibody responses targeting this epitope. Primary DENV3 sera from 30 individuals in a dengue hospital-based study in Nicaragua were studied 3, 6, 12, and 18 months post-infection, alongside samples collected annually 1 to 4 years post-primary DENV3 infection from 10 individuals in a cohort study in Nicaragua. We found substantial individual variation in the proportion of DENV3 type-specific neutralizing antibody titers attributed to the 5J7 epitope (range, 0 to 100%), with the mean significantly increasing from 22.6% to 41.4% from 3 to 18 months. We extended the transplanted DENV3 5J7 epitope on the virion (rDENV4/3-M16), resulting in increased recognition in several individuals, helping define the footprint of the epitope. However, 37% and 13% of the subjects still showed little to no recognition of the 5J7 epitope at 3 and 18 months, respectively, indicating that one or more additional DENV3 type-specific epitopes exist. Overall, this study demonstrates how DENV-immune plasma from populations from areas of endemicity, when coupled with structurally guided recombinant viruses, can help characterize the epitope-specific neutralizing antibody response in natural DENV infections, with direct implications for design and evaluation of dengue vaccines. IMPORTANCE The four serotypes of dengue virus cause dengue

  20. Dengue

    Science.gov (United States)

    Dengue is an infection caused by a virus. You can get it if an infected mosquito bites you. Dengue does not spread from person to person. It ... the world. Outbreaks occur in the rainy season. Dengue is rare in the United States. Symptoms include ...

  1. Dengue and Severe Dengue

    Science.gov (United States)

    ... all regions of WHO in recent years. Dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus . This mosquito also transmits chikungunya, yellow fever and Zika infection. Dengue is widespread throughout the tropics, with ...

  2. Dengue NS1 Antigen - for Early Detection of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Amol Hartalkar

    2015-08-01

    Full Text Available Objectives: To evaluate the efficacy of NS1 antigen assay for early diagnosis of dengue virus infection in a tertiary care hospital. Methods: This cross sectional study was carried out in department of Medicine from August to December 2013. Total 100 patients with dengue fever were included. Complete blood count, alanine aminotransferase (ALT, aspartate aminotransferase (AST, Dengue NS1 antigen and IgM and IgG antibodies of dengue virus were done in all cases. Results: Of the 100 sera tested, 75% were positive for dengue virus infection based on dengue NS1 antigen, IgM antibody and IgG antibody. Dengue NS1 antigen and IgM, IgG antibody were able to detect dengue virus infection between day 1 to day 8 in 92% of samples, 86.7% of samples and 82.6% of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were IgM positive and 62% were IgG positive. Based on the dengue NS1 antigen and IgM antibody combination, 74% were positive for dengue virus infections. Sensitivity of Dengue NS1 antigen was 92.3% and specificity of 74.28% in comparison to IgM antibody. Detection rate increased to 75%, based on the antigen and IgG antibody combination. Sensitivity of dengue NS1 antigen was 90.3% and specificity of 65.8% in comparison to IgG antibody. Conclusion: Dengue NS1 antigen is a useful, sensitive and specific test for early diagnosis of dengue virus infection and it improves diagnostic efficiency in combination with antibody test. Key words: Dengue fever, NS1 antigen. Introduction: Dengue fever (DF is the most common arboviral illness in humans. Each year, an estimated 50-100 million cases of dengue fever and 500,000 cases of dengue hemorrhagic fever occur worldwide, with 30000 deaths (mainly in children. Globally 2.5-3 billion people in approximately 112 tropical and subtropical countries are at risk of dengue.of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were Ig

  3. Dynamic profiles of neutralizing antibody responses elicited in rhesus monkeys immunized with a combined tetravalent DTaP-Sabin IPV candidate vaccine.

    Science.gov (United States)

    Sun, Mingbo; Ma, Yan; Xu, Yinhua; Yang, Huijuan; Shi, Li; Che, Yanchun; Liao, Guoyang; Jiang, Shude; Zhang, Shumin; Li, Qihan

    2014-02-19

    The World Health Organization has recommended that a Sabin inactivated polio vaccine (IPV) should gradually and synchronously replace oral polio vaccines for routine immunizations because its benefits in eliminating vaccine-associated paralytic poliomyelitis have been reported in different phases of clinical trials. It is also considered important to explore new tetravalent diphtheria, tetanus, and acellular pertussis-Sabin IPV (DTaP-sIPV) candidate vaccines for possible use in developing countries. In this study, the immunogenicity of a combined tetravalent DTaP-sIPV candidate vaccine was investigated in primates by evaluating the neutralizing antibody responses it induced. The dynamic profiles of the antibody responses to each of the separate antigenic components and serotypes of Sabin IPV were determined and their corresponding geometric mean titers were similar to those generated by the tetravalent diphtheria, tetanus, and acellular pertussis-conventional IPV (DTaP-cIPV), the tetravalent diphtheria, tetanus, and acellular pertussis (DTaP), and Sabin IPV vaccines in the control groups. This implies that protective immunogenic effects are conferred by this combined tetravalent formulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Dengue-1 envelope protein domain III along with PELC and CpG oligodeoxynucleotides synergistically enhances immune responses.

    Directory of Open Access Journals (Sweden)

    Chen-Yi Chiang

    Full Text Available The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus.

  5. Dengue vaccination during pregnancy - An overview of clinical trials data.

    Science.gov (United States)

    Skipetrova, Anna; Wartel, Tram Anh; Gailhardou, Sophia

    2018-04-28

    The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in several endemic countries and contraindicated during pregnancy. Inadvertent vaccination during pregnancy may occur during clinical trials that include women of childbearing age. The potential risk associated with dengue vaccination in pregnancy remains unknown. We describe pregnancy outcomes following inadvertent dengue vaccination in pregnancy from CYD-TDV trial data. Data were collected from trials conducted as part of the CYD-TDV clinical development. Women who received CYD-TDV or placebo during the pre-specified pregnancy risk window (from 30 days before the date of their last menstrual period to end of pregnancy) were considered as exposed; pregnancies occurring in non-risk periods during the trials were considered to be non-exposed. Pregnancy losses were defined as abortion (spontaneous or unspecified), death in utero, and stillbirth. 615 pregnancies were reported from 19 CYD-TDV trials: 404 in the CYD-TDV arm, and 211 in the placebo arm. Exposure could not be determined for 7 pregnancies (5, CYD-TDV; 2, placebo). In the CYD-TDV arm, 58 pregnancies were considered as exposed. Most of these (n = 47, 81%) had healthy live births; 6 (10.3%) had pregnancy losses; 3 underwent elective termination and 2 had unknown outcome. In the placebo group, 30 pregnancies were considered exposed. Most of these (n = 25, 83%) had healthy births; 4 (13.3%) had pregnancy losses; and 1 had elective termination. Among non-exposed pregnancies, most resulted in healthy live births; 23/341 (6.7%) in the CYD-TDV group and 17/179 (9.5%) in the placebo group had pregnancy losses. Most reported pregnancy losses were in women considered high-risk for adverse pregnancy outcome, primarily due to young age. In the small dataset assessed, no evidence of increased adverse pregnancy outcomes has been identified from inadvertent immunization of women in early pregnancy with CYD-TDV compared with the control group

  6. Dengue in children.

    Science.gov (United States)

    Verhagen, Lilly M; de Groot, Ronald

    2014-11-01

    Dengue is a mosquito-borne viral disease of expanding geographical range and increasing incidence. The vast majority of dengue cases are children less than 15 years of age. Dengue causes a spectrum of illness from mild fever to severe disease with plasma leakage and shock. Infants and children with secondary heterologous dengue infections are most at risk for severe dengue disease. Laboratory diagnosis of dengue can be established within five days of disease onset by direct detection of viral components in serum. After day five, serologic diagnosis provides indirect evidence of dengue. Currently, no effective antiviral agents are available to treat dengue infection. Therefore, treatment remains supportive, with emphasis on close hematological monitoring, recognition of warning signs of severe disease and fluid-replacement therapy and/or blood transfusions when required. Development of a dengue vaccine is considered a high public health priority. A safe and efficacious dengue vaccine would also be important for travelers. This review highlights the current understanding of dengue in children, including its clinical manifestations, pathogenesis, diagnostic tests, management and prevention. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  7. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  8. DenguePredict: An Integrated Drug Repositioning Approach towards Drug Discovery for Dengue.

    Science.gov (United States)

    Wang, QuanQiu; Xu, Rong

    2015-01-01

    Dengue is a viral disease of expanding global incidence without cures. Here we present a drug repositioning system (DenguePredict) leveraging upon a unique drug treatment database and vast amounts of disease- and drug-related data. We first constructed a large-scale genetic disease network with enriched dengue genetics data curated from biomedical literature. We applied a network-based ranking algorithm to find dengue-related diseases from the disease network. We then developed a novel algorithm to prioritize FDA-approved drugs from dengue-related diseases to treat dengue. When tested in a de-novo validation setting, DenguePredict found the only two drugs tested in clinical trials for treating dengue and ranked them highly: chloroquine ranked at top 0.96% and ivermectin at top 22.75%. We showed that drugs targeting immune systems and arachidonic acid metabolism-related apoptotic pathways might represent innovative drugs to treat dengue. In summary, DenguePredict, by combining comprehensive disease- and drug-related data and novel algorithms, may greatly facilitate drug discovery for dengue.

  9. Dengue-associated kidney disease.

    Science.gov (United States)

    Lizarraga, Karlo J; Nayer, Ali

    2014-01-01

    A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue is considered a major global health threat by the World Health Organization. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. An RNA virus from the genus Flavivirus, dengue virus is transmitted by Aedes aegypti,the yellow fever mosquito. Dengue is asymptomatic in as many as one half of infected individuals. Dengue fever is an acute febrile illness accompanied by constitutional symptoms. Dengue hemorrhagic fever and dengue shock syndrome are the severe forms of dengue infection.Dengue infection has been associated with a variety of renal disorders. Acute renal failure is a potential complication of severe dengue infection and is typically associated with hypotension, rhabdomyolysis, or hemolysis. Acute renal failure complicates severe dengue infection in 2-5% of the cases and carries a high mortality rate. Proteinuria has been detected in as high as 74% of patients with severe dengue infection. Hematuria has been reported in up to 12.5% of patients. Various types of glomerulonephritis have been reported during or shortly after dengue infection in humans and mouse models of dengue infection. Mesangial proliferation and immune complex deposition are the dominant histologic features of dengue-associated glomerulonephritis. On a rare occasion, dengue infection is associated with systemic autoimmune disorders involving the kidneys. In the vast majority of cases, dengue infection and associated renal disorders are self-limited.

  10. Primary vaccination with low dose live dengue 1 virus generates a proinflammatory, multifunctional T cell response in humans.

    Directory of Open Access Journals (Sweden)

    Janet C Lindow

    Full Text Available The four dengue virus serotypes (DENV-1-DENV-4 have a large impact on global health, causing 50-100 million cases of dengue fever annually. Herein, we describe the first kinetic T cell response to a low-dose DENV-1 vaccination study (10 PFU in humans. Using flow cytometry, we found that proinflammatory cytokines, IFNγ, TNFα, and IL-2, were generated by DENV-1-specific CD4(+ cells 21 days post-DENV-1 exposure, and their production continued through the latest time-point, day 42 (p<0.0001 for all cytokines. No statistically significant changes were observed at any time-points for IL-10 (p = 0.19, a regulatory cytokine, indicating that the response to DENV-1 was primarily proinflammatory in nature. We also observed little T cell cross-reactivity to the other 3 DENV serotypes. The percentage of multifunctional T cells (T cells making ≥ 2 cytokines simultaneously increased with time post-DENV-1 exposure (p<0.0001. The presence of multifunctional T cells together with neutralizing antibody data suggest that the immune response generated to the vaccine may be protective. This work provides an initial framework for defining primary T cell responses to each DENV serotype and will enhance the evaluation of a tetravalent DENV vaccine.

  11. Randomized clinical trial of human interleukin-11 in dengue fever-associated thrombocytopenia

    International Nuclear Information System (INIS)

    Suliman, M.I.; Qayum, I.

    2014-01-01

    Objective: To assess the effectiveness of recombinant human (rh) IL-11 to increase platelets count in patients suffering from Dengue fever (DF). Study Design: Randomized double blind placebo control study. Place and Duration of Study: Farooq Hospital, Lahore, from July to October 2011. Methodology: Forty hospitalized patients suffering from Dengue fever having platelets count A 30000 per micro liter were randomly categorized into two groups, rhIL-11 (test) and distilled water (placebo) groups. The efficacy outcomes (as indicated by step up in platelets count at 48 hours) for the treatment group were compared with the outcomes for the placebo group. Results: The data revealed that the increase in platelet response with recombinant human interleukin 11, 1.5 mg subcutaneously is significantly more brisk than the placebo group. The platelets response in patients with severe thrombocytopenia was greater in the treatment group (50%) at 48 hours as compared to the placebo group (20%) (p=0.047). Response rate was slightly greater among males (6/10, 60%) than females (8/16, 50%); moreover, three-fourth (75%) female responders were in the placebo group, compared to half (50%) male responders in the treatment group. Conclusion: Results of the study suggest that treatment of severe thrombocytopenia accompanying DF with recombinant human interleukin 11 may be a useful therapeutic option. (author)

  12. Introducing dengue vaccine: Implications for diagnosis in dengue vaccinated subjects.

    Science.gov (United States)

    Alagarasu, Kalichamy

    2016-05-27

    Diagnosis of dengue virus infections is complicated by preference for different diagnostic tests in different post onset days of illness and the presence of multiple serotypes leading to secondary and tertiary infections. The sensitivity of the most commonly employed diagnostic assays such as anti dengue IgM capture (MAC) ELISA and non structural protein (NS) 1 capture ELISA are lower in secondary and subsequent infections. Introduction of dengue vaccine in endemic regions will affect the way how dengue is diagnosed in vaccinated subjects. This viewpoint article discusses implications of introduction of dengue vaccine on the diagnosis of dengue infections in vaccinated subjects and the strategies that are needed to tackle the issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. The dengue vaccine pipeline: Implications for the future of dengue control

    OpenAIRE

    Schwartz, Lauren M.; Halloran, M. Elizabeth; Durbin, Anna P.; Longini Jr., Ira M.

    2015-01-01

    Dengue has become the most rapidly expanding mosquito-borne infectious disease on the planet, surpassing malaria and infecting at least 390 million people per year. There is no effective treatment for dengue illness other than supportive care, especially for severe cases. Symptoms can be mild or life-threatening as in dengue hemorrhagic fever and dengue shock syndrome. Vector control has been only partially successful in decreasing dengue transmission. The potential use of safe and effective ...

  14. Analysis of genotype diversity and evolution of Dengue virus serotype 2 using complete genomes

    Directory of Open Access Journals (Sweden)

    Vaishali P. Waman

    2016-08-01

    Full Text Available Background Dengue is one of the most common arboviral diseases prevalent worldwide and is caused by Dengue viruses (genus Flavivirus, family Flaviviridae. There are four serotypes of Dengue Virus (DENV-1 to DENV-4, each of which is further subdivided into distinct genotypes. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 consists of six genotypes such as Asian/American, Asian I, Asian II, Cosmopolitan, American and sylvatic. Comparative genomic study was carried out to infer population structure of DENV-2 and to analyze the role of evolutionary and spatiotemporal factors in emergence of diversifying lineages. Methods Complete genome sequences of 990 strains of DENV-2 were analyzed using Bayesian-based population genetics and phylogenetic approaches to infer genetically distinct lineages. The role of spatiotemporal factors, genetic recombination and selection pressure in the evolution of DENV-2 is examined using the sequence-based bioinformatics approaches. Results DENV-2 genetic structure is complex and consists of fifteen subpopulations/lineages. The Asian/American genotype is observed to be diversified into seven lineages. The Asian I, Cosmopolitan and sylvatic genotypes were found to be subdivided into two lineages, each. The populations of American and Asian II genotypes were observed to be homogeneous. Significant evidence of episodic positive selection was observed in all the genes, except NS4A. Positive selection operational on a few codons in envelope gene confers antigenic and lineage diversity in the American strains of Asian/American genotype. Selection on codons of non-structural genes was observed to impact diversification of lineages in Asian I, cosmopolitan and sylvatic genotypes. Evidence of intra/inter-genotype recombination was obtained and the uncertainty in classification of recombinant strains was resolved using the population genetics approach. Discussion Complete genome-based analysis

  15. Dengue-associated neuromuscular complications

    OpenAIRE

    Ravindra Kumar Garg; Hardeep Singh Malhotra; Amita Jain; Kiran Preet Malhotra

    2015-01-01

    Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evo...

  16. Nonequilibrium method for estimating the first hydrolysis constant of tetravalent plutonium

    International Nuclear Information System (INIS)

    Silver, G.L.

    2010-01-01

    Six discrete formulas are used to estimate the equilibrium constant of the first hydrolysis reaction of tetravalent plutonium. They apply the pH, the oxidation number, one equilibrium constant, and fractions of two of the plutonium oxidation states. The new formulas are not restricted to the equilibrium condition. (author)

  17. Dengue viral infections

    Directory of Open Access Journals (Sweden)

    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  18. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host...

  19. Recombinant Envelope-Proteins with Mutations in the Conserved Fusion Loop Allow Specific Serological Diagnosis of Dengue-Infections.

    Directory of Open Access Journals (Sweden)

    Alexandra Rockstroh

    2015-11-01

    Full Text Available Dengue virus (DENV is a mosquito-borne flavivirus and a major international public health concern in many tropical and sub-tropical areas worldwide. DENV is divided into four major serotypes, and infection with one serotype leads to immunity against the same, but not the other serotypes. The specific diagnosis of DENV-infections via antibody-detection is problematic due to the high degree of cross-reactivity displayed by antibodies against related flaviviruses, such as West Nile virus (WNV, Yellow Fever virus (YFV or Tick-borne encephalitis virus (TBEV. Especially in areas where several flaviviruses co-circulate or in the context of vaccination e.g. against YFV or TBEV, this severely complicates diagnosis and surveillance. Most flavivirus cross-reactive antibodies are produced against the highly conserved fusion loop (FL domain in the viral envelope (E protein. We generated insect-cell derived recombinant E-proteins of the four DENV-serotypes which contain point mutations in the FL domain. By using specific mixtures of these mutant antigens, cross-reactivity against heterologous flaviviruses was strongly reduced, enabling sensitive and specific diagnosis of the DENV-infected serum samples in IgG and IgM-measurements. These results have indications for the development of serological DENV-tests with improved specificity.

  20. Hemoterapia e febre Dengue Blood banking e Dengue fever

    Directory of Open Access Journals (Sweden)

    Estácio F. Ramos

    2008-02-01

    Full Text Available Dengue is an endemic/epidemic arboviral disease with a variable symptomatic benign course, but potentially fatal. Once in an inhabited area, the disease will exist forever, with the best achievement being to keep vectors suppressed and the disease under control. Tiger mosquitoes (aedes aegypti, aedes albopictus are active breeders and urban hunters, becoming resistant to pesticides. Global warming and population growth are propelling the disease worldwide at tropical and subtropical regions, victimizing new populations. Dengue virus is very infective, and has been transmitted by needlestick, intrapartum, through blood transfusion and mucosal contact with blood. One patient got dengue while undergoing bone marrow transplantation. We address the growing dengue epidemics in Brazil, with more than half a million official cases in 2007, to estimate the risks of transfusion transmitted dengue. Calculations however were surpassed by reality: the major Blood Center in Brazil (FHSP-USP has found dengue virus in one out of each thousand blood units. In 2007, industry sold 2,6 million disposable blood bags in Brazil. Plotting data from FHSP-USP to the whole country, 2600 blood units would have been infective. Through blood components, around 5000 patients must have received dengue virus intravenously. Beatty et al. estimated to be 1:1300 the risk for dengue transmission through blood transfusion in Puerto Rico, close to what has been demonstrated in Sao Paulo. Throughout Brazil, the average risk may be lower, but the epidemics grows towards a worst scenario. Whatever the risk is, it imposes that all blood units in Brazil (and wherever dengue is endemic must be EIA tested for dengue NS1 antigen. This marker appears early after infection, and the EIA testing platform is available at all blood banks. Also, donors must report febrile states up to two weeks after donation. Morbidity from dengue virus injected in hospitalized patients is unknown, but it may lead

  1. Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses.

    Directory of Open Access Journals (Sweden)

    Stefan W Metz

    2016-10-01

    Full Text Available Dengue virus (DENV is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE, purified and adsorbed to poly (lactic-co-glycolic acid (PLGA nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.

  2. Post-dengue parkinsonism

    OpenAIRE

    Azmin, Shahrul; Sahathevan, Ramesh; Suehazlyn, Zainudin; Law, Zhe Kang; Rabani, Remli; Nafisah, Wan Yahya; Tan, Hui Jan; Norlinah, Mohamed Ibrahim

    2013-01-01

    Background Dengue is a common illness in the tropics. Equally common are neurological complications that stem from dengue infection. However, to date, parkinsonism following dengue has not been reported in medical literature. Case presentation A previously well 18-year old man developed parkinsonism, in addition to other neurological symptoms following serologically confirmed dengue fever. Alternative etiologies were excluded by way of imaging and blood investigations. Conclusions The authors...

  3. Autoimmunity in dengue pathogenesis

    Directory of Open Access Journals (Sweden)

    Shu-Wen Wan

    2013-01-01

    Full Text Available Dengue is one of the most important vector-borne viral diseases. With climate change and the convenience of travel, dengue is spreading beyond its usual tropical and subtropical boundaries. Infection with dengue virus (DENV causes diseases ranging widely in severity, from self-limited dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia, and hemorrhage are the major clinical manifestations associated with severe DENV infection, yet the mechanisms remain unclear. Besides the direct effects of the virus, immunopathogenesis is also involved in the development of dengue disease. Antibody-dependent enhancement increases the efficiency of virus infection and may suppress type I interferon-mediated antiviral responses. Aberrant activation of T cells and overproduction of soluble factors cause an increase in vascular permeability. DENV-induced autoantibodies against endothelial cells, platelets, and coagulatory molecules lead to their abnormal activation or dysfunction. Molecular mimicry between DENV proteins and host proteins may explain the cross-reactivity of DENV-induced autoantibodies. Although no licensed dengue vaccine is yet available, several vaccine candidates are under development. For the development of a safe and effective dengue vaccine, the immunopathogenic complications of dengue disease need to be considered.

  4. The unusual stability of homoleptic di- and tetravalent chromium alkyls

    NARCIS (Netherlands)

    Schulzke, C.; Enright, D.; Sugiyama, H.; LeBlanc, G.; Gambarotta, S.; Yap, G.P.A.; Thompson, L.K.; Wilson, D.R.; Duchateau, R.

    2002-01-01

    Reaction of CrCl3(THF)3 with 3 equiv of R-M [R = Me3CCH2 (a), Me3SiCH2 (b)] afforded either the previously reported tetravalent homoleptic R4Cr (1a, b) [M = MgCl] or the unprecedented divalent and tetranuclear homoleptic [R2Cr]4 (2b) [M = Li]. Both types of compounds display a remarkable chemical

  5. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  6. Dengue retinochoroiditis.

    Science.gov (United States)

    Tabbara, Khalid

    2012-01-01

    Dengue is a mosquito-borne infection caused by a flavivirus. I describe the ocular findings observed in two patients infected with dengue virus who presented with acute onset of loss of vision preceded by febrile illness, malaise, generalized fatigue headache, and maculopapular rash. Ophthalmologic evaluation in each patient revealed a normal anterior segment. Vitreous cells were noted in one patient. Ophthalmoscopy revealed multiple foci of retinochoroiditis, vasculitis, cotton-wool spots, and retinal hemorrhages. The healing of the lesion showed discrete atrophic and pigmented retinochoroiditic scars. Fluorescein angiography displayed early hypofluorescence and late hyperfluorescence suggestive of leakage. The healed scars showed late staining. The serologic testing showed elevated IgG antibodies, and one had high IgM antibodies to dengue virus. Ocular findings of dengue fever consist of multifocal areas of retinochoroiditis and may lead to loss of vision. In Saudi Arabia, dengue fever should be considered in the differential diagnosis of multifocal chorioretinal lesions and retinal vasculitis.

  7. Equilibrium method for estimating the first hydrolysis constant of tetravalent plutonium

    International Nuclear Information System (INIS)

    Silver, G.L.

    2010-01-01

    A new method for estimating the numerical value of the first hydrolysis constant of tetravalent plutonium is illustrated by examples. It uses the pH and the equilibrium fractions of two of the Pu oxidation states. They are substituted into one or more of a choice of formulas that render explicit estimates of the hydrolysis constant. (author)

  8. Could peak proteinuria determine whether patient with dengue fever develop dengue hemorrhagic/dengue shock syndrome? - A prospective cohort study

    Directory of Open Access Journals (Sweden)

    Suhail Sufi M

    2011-08-01

    Full Text Available Abstract Background Worldwide there is a need to develop simple effective predictors that can distinguish whether a patient will progress from dengue fever (DF to life threatening dengue hemorrhagic (DHF or dengue shock syndrome (DSS. We explored whether proteinuria could be used as such a marker. Methods We included patients admitted to hospital with suspected dengue fever. Starting at enrollment until discharge, each patient's daily spot urine protein creatinine ratio (UPCR was measured. We classified those with confirmed dengue infection as DF or DHF (including DSS based on WHO criteria. Peak and day of onset of proteinuria was compared between both groups. Results Compared to those with DF, patients with DHF had significantly higher median peak proteinuria levels (0.56 versus 0.08 g/day; p Conclusions Peak UPCR could potentially predict DHF in patients with dengue requiring close monitoring and treatment.

  9. Dengue in children

    NARCIS (Netherlands)

    Verhagen, L.M.; Groot, R. de

    2014-01-01

    Dengue is a mosquito-borne viral disease of expanding geographical range and increasing incidence. The vast majority of dengue cases are children less than 15 years of age. Dengue causes a spectrum of illness from mild fever to severe disease with plasma leakage and shock. Infants and children with

  10. Points for Consideration for dengue vaccine introduction - recommendations by the Dengue Vaccine Initiative.

    Science.gov (United States)

    Lim, Jacqueline Kyungah; Lee, Yong-Seok; Wilder-Smith, Annelies; Thiry, Georges; Mahoney, Richard; Yoon, In-Kyu

    2016-01-01

    Dengue is a public health problem in the tropics and subtropics. There are several vaccine candidates in clinical development. However, there may be gaps in the new vaccine introduction after vaccine licensure before it becomes available in developing countries. In anticipation of the first dengue vaccine candidate to be licensed, Dengue Vaccine Initiative (DVI) and, its predecessor, Pediatric Dengue Vaccine Initiative (PDVI) have been working on points for consideration to accelerate evidence-based dengue vaccine introduction, once a vaccine becomes available. In this paper, we review the history of PDVI and its successor, the DVI, and elaborate on the points of consideration for dengue vaccine introduction.

  11. DengueTools: innovative tools and strategies for the surveillance and control of dengue

    Directory of Open Access Journals (Sweden)

    Annelies Wilder-Smith

    2012-03-01

    Full Text Available Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of ‘Comprehensive control of Dengue fever under changing climatic conditions’. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named ‘DengueTools’ to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe in the context of globalization and climate change.The consortium comprises 12 work packages to address a set of research questions in three areas: Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring. Research area 2: Develop novel strategies to prevent dengue in children. Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change.In this paper, we report on the rationale and specific study objectives of ‘DengueTools’. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant

  12. DengueTools: innovative tools and strategies for the surveillance and control of dengue.

    Science.gov (United States)

    Wilder-Smith, Annelies; Renhorn, Karl-Erik; Tissera, Hasitha; Abu Bakar, Sazaly; Alphey, Luke; Kittayapong, Pattamaporn; Lindsay, Steve; Logan, James; Hatz, Christoph; Reiter, Paul; Rocklöv, Joacim; Byass, Peter; Louis, Valérie R; Tozan, Yesim; Massad, Eduardo; Tenorio, Antonio; Lagneau, Christophe; L'Ambert, Grégory; Brooks, David; Wegerdt, Johannah; Gubler, Duane

    2012-01-01

    Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of 'Comprehensive control of Dengue fever under changing climatic conditions'. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named 'DengueTools' to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe) in the context of globalization and climate change.The consortium comprises 12 work packages to address a set of research questions in three areas:Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring.Research area 2: Develop novel strategies to prevent dengue in children.Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change.In this paper, we report on the rationale and specific study objectives of 'DengueTools'. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant Agreement Number: 282589 Dengue Tools.

  13. Dengue fever and dengue haemorrhagic fever in adolescents and adults.

    Science.gov (United States)

    Tantawichien, Terapong

    2012-05-01

    Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients.

  14. Epidemiologi dan Diagnosis Dengue di Indonesia

    OpenAIRE

    Zilhadia, Zilhadia

    2007-01-01

    Dengue fever/DF and dengue hemorrhagic fever/DHF is a global public health problem that occured in tropical and subtropical region. Epidemic dengue occurs every years, and it continues to be a major health problem in Indonesia. Due to its asymptomatic nature, a reliable, rapid and accurate dengue diagnosis is needed. Dengue diagnosis method based on molecular dengue virus properties and it will be developed by researcher. Dengue rapid test isnewly method. This article explaine about dengue ep...

  15. Dengue en Colombia

    Directory of Open Access Journals (Sweden)

    Jorge Boshell

    1986-12-01

    Full Text Available El Gobierno Colombiano estableció una campaña que erradicó el Aedes aegypti de su territorio en atención a las recomendaciones que hizo la Oficina Sanitaria Panamericana en 1947. Esta campaña consiguió desaparecer el dengue endémico durante aproximadamente 20 años, apareciendo de nuevo en forma explosiva con la epidemia de dengue 2 en la Costa Atlántica (1971-1972, seguida de dos epidemias bien documentadas de dengue 3 (1975-1977 y dengue 1 en 1978. Se hace un resumen de las actividades que desarrolla el Laboratorio de Virología del Instituto Nacional de Salud para apoyar el diagnóstico de esta enfermedad en el país incluyendo el primer aislamiento de dengue 4 en 1982, la actividad de los virus dengue 1, 2 y 4 detectada hasta la fecha, los hallazgos clínicos y virológicos en un caso fatal de enfermedad hemorrágica asociada a infección por virus del dengue y un breve recuento de la epidemia de Tumaco en la Costa Pacífica en la cual se comprobó actividad simultánea de dengue 1 y 2. Finalmente se informa sobre el estado de infestación que tiene el país actualmente con el Aedes aegypti y sobre la actividad del virus de fiebre amarilla en focos selváticos vecinos a ciudades altamente infestadas, detectada en el mes de enero de 1987 en Colombia.

  16. DenguePredict: An Integrated Drug Repositioning Approach towards Drug Discovery for Dengue

    OpenAIRE

    Wang, QuanQiu; Xu, Rong

    2015-01-01

    Dengue is a viral disease of expanding global incidence without cures. Here we present a drug repositioning system (DenguePredict) leveraging upon a unique drug treatment database and vast amounts of disease- and drug-related data. We first constructed a large-scale genetic disease network with enriched dengue genetics data curated from biomedical literature. We applied a network-based ranking algorithm to find dengue-related diseases from the disease network. We then developed a novel algori...

  17. Dengue fever and dengue haemorrhagic fever in adolescents and adults

    OpenAIRE

    Tantawichien, Terapong

    2012-01-01

    Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a...

  18. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    Science.gov (United States)

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  19. Dengue fever

    African Journals Online (AJOL)

    symptoms and research has been limited to studies ... severity and problems with vaccination (4). History of ... Americas in 1970s reduced the spread of dengue fever. After this .... Reiter P. Yellow fever and dengue: a threat to Europe? 9.

  20. Psychosis in dengue fever

    OpenAIRE

    Suprakash Chaudhury; Biswajit Jagtap; Deepak Kumar Ghosh

    2017-01-01

    An 18-year-old male student developed abnormal behavior while undergoing treatment for dengue fever. He was ill-kempt, irritable and had auditory and visual hallucinations and vague persecutory delusions in clear sensorium with impaired insight. The psychotic episode had a temporal correlation with dengue fever. Psychiatric comorbidities of dengue fever including mania, anxiety, depression, and catatonia are mentioned in literature but the literature on the psychosis following dengue is spars...

  1. Dengue e dengue hemorrágico: aspectos do manejo na unidade de terapia intensiva Dengue and dengue hemorrhagic fever: management issues in an intensive care unit

    Directory of Open Access Journals (Sweden)

    Sunit Singhi

    2007-05-01

    Full Text Available OBJETIVOS: Descrever a epidemiologia, as características clínicas e o tratamento do dengue e das síndromes do choque associadas ao dengue. FONTES DOS DADOS: Para esta revisão de literatura, foi feita uma pesquisa no Pubmed e nos websites da Organização Mundial da Saúde (OMS e OPAS usando os termos dengue e síndrome do choque associada ao dengue. A informação foi complementada com a experiência pessoal dos autores. SÍNTESE DOS DADOS: O dengue é a mais importante doença viral transmitida por artrópodos em seres humanos. A doença se manifesta de diversas formas, variando desde uma síndrome viral não-diferenciada até febre hemorrágica e choque grave. O dengue é uma enfermidade autolimitada, não específica, caracterizada por febre, cefaléia, mialgia, e sintomas constitucionais. As formas mais graves (febre hemorrágica e síndrome do choque podem levar a um comprometimento multissistêmico e ao óbito. O diagnóstico precoce e um acompanhamento contínuo do agravamento e da resposta ao tratamento são necessários em todos os casos. A OMS recomenda uma abordagem escalonada para o manejo, adequada para as formas mais leves e para o choque precoce. Nas formas mais graves, é preciso uma abordagem agressiva de reanimação com fluidos e de suporte à falência de órgãos em pacientes em estado crítico. As pesquisas sobre as diferenças fisiopatológicas entre o choque do dengue e o choque séptico, seleção de fluidos, agentes inotrópicos e técnicas de suporte a órgãos podem beneficiar os pacientes em estado crítico. CONCLUSÕES: Não há uma terapia específica para infecções causadas pelo dengue. Um bom tratamento de suporte pode salvar vidas mas, em última análise, as iniciativas de controle do vetor e de prevenção contra picadas do mosquito podem trazer os maiores benefícios.OBJECTIVES: To describe the epidemiology, clinical features and treatment of dengue fever and dengue shock syndrome. SOURCES: To prepare

  2. Dengue: a reappraisal

    OpenAIRE

    Serufo, José Carlos; Nobre, Vandack; Rayes, Abdunnabi; Marcial, Tânia Maria; Lambertucci, José Roberto

    2000-01-01

    Os conceitos de dengue clássico, com ou sem hemorragia, e de febre hemorrágica do dengue (FHD) que, pode cursar sem fenômenos hemorrágicos, com ou sem síndrome do choque do dengue (SCD), são revistos neste artigo. As definições clássicas propostas, úteis em outros tempos, geram confusão e dificultam a tomada de decisões no momento do tratamento dos pacientes com as formas graves da doença porque deixaram de incorporar novos conceitos e avanços terapêuticos. A classificação do dengue proposta ...

  3. Relato de caso: transmissão vertical de dengue Case report: vertical dengue infection

    Directory of Open Access Journals (Sweden)

    Samara L. C. Maroun

    2008-12-01

    Full Text Available OBJETIVOS: Relatar um caso de transmissão vertical de dengue ocorrido durante epidemia de 2008 pelo vírus tipo II no Rio de Janeiro e revisar a literatura sobre transmissão vertical de dengue. DESCRIÇÃO: Relatamos um caso de transmissão vertical de dengue. Recém-nascido a termo do sexo feminino, peso de nascimento de 3.940 g, foi admitida na unidade de terapia intensiva neonatal com rash cutâneo, hipoatividade e febre no quinto dia de vida. O hemograma evidenciava plaquetopenia importante (38.000 plaquetas. A mãe apresentou quadro clínico compatível com dengue 3 dias antes do parto. Foram colhidos então IgM para dengue da mãe e do recém-nascido, realizados pelo método de ELISA, sendo positivos em ambos. Dengue tipo 2 foi detectado no recém-nascido através de reação em cadeia da polimerase. COMENTÁRIOS: Este relato enfatiza a importância do pediatra estar alerta para a possibilidade de transmissão vertical de dengue iniciando precocemente o tratamento.OBJECTIVES: To report a case of vertical dengue infection in a newborn from Rio de Janeiro, Brazil, and to review the literature concerning this problem. DESCRIPTION: We report a case of vertical dengue infection. Female neonate, birth weight 3,940 g, term, was admitted to a neonatal intensive care unit on the fifth day of life with fever and erythematous rash. Her mother had had dengue fever 3 days before delivery. Her platelet count was 38,000, dropping to 15,000. She did not have any hemorrhagic episodes, including cerebral hemorrhages. Anti-dengue antibodies (IgM were positive in the mother and infant. Dengue type 2 was detected in the infant using polymerase chain reaction. COMMENTS: This report emphasizes that pediatricians should be aware of the possibility of vertical dengue infection so that early management can be instituted.

  4. Dengue in Bali: Clinical characteristics and genetic diversity of circulating dengue viruses.

    Science.gov (United States)

    Megawati, Dewi; Masyeni, Sri; Yohan, Benediktus; Lestarini, Asri; Hayati, Rahma F; Meutiawati, Febrina; Suryana, Ketut; Widarsa, Tangking; Budiyasa, Dewa G; Budiyasa, Ngurah; Myint, Khin S A; Sasmono, R Tedjo

    2017-05-01

    A high number of dengue cases are reported annually in Bali. Despite the endemicity, limited data on dengue is available for Bali localities. Molecular surveillance study was conducted to explore the clinical and virological characteristics of dengue patients in urban Denpasar and rural Gianyar areas in Bali during the peak season in 2015. A total of 205 adult dengue-suspected patients were recruited in a prospective cross-sectional study. Demographic and clinical information were obtained, and dengue screening was performed using NS1 and IgM/IgG ELISAs. Viral RNA was subsequently extracted from patients' sera for serotyping using conventional RT-PCR and Simplexa Dengue real-time RT-PCR, followed by genotyping with sequencing method. We confirmed 161 patients as having dengue by NS1 and RT-PCR. Among 154 samples successfully serotyped, the DENV-3 was predominant, followed by DENV-1, DENV-2, and DENV-4. Serotype predominance was different between Denpasar and Gianyar. Genotyping results classify DENV-1 isolates into Genotype I and DENV-2 as Cosmopolitan Genotype. The classification grouped isolates into Genotype I and II for DENV-3 and DENV-4, respectively. Clinical parameters showed no relationship between infecting serotypes and severity. We observed the genetic diversity of circulating DENV isolates and their relatedness with historical data and importation to other countries. Our data highlights the role of this tourist destination as a potential source of dengue transmission in the region.

  5. Clinical and laboratory profile of different dengue sub types in dengue virus infection

    OpenAIRE

    Niloy Gan Chaudhuri; S. Vithyavathi; K. Sankar

    2016-01-01

    Background: Dengue infection, an arthropod-borne viral hemorrhagic fever is caused by Arbovirus of Flavivirus genus and transmitted by Aedes aegypti, Aedes albopictus. Liver involvement in dengue fever is manifested by the elevation of transaminases representing reactive hepatitis, due to direct attack of virus itself or the use of hepatotoxic drugs. The objective of the study was to investigate clinical and laboratory profile of different dengue sub type's patients admitted for dengue fever....

  6. A epidemia de dengue/dengue hemorrágico no município do Rio de Janeiro, 2001/2002 The epidemic of dengue and hemorrhagic dengue fever in the city of Rio de Janeiro, 2001/2002

    Directory of Open Access Journals (Sweden)

    Clarisse Guimarães Casali

    2004-08-01

    Full Text Available O objetivo deste estudo foi avaliar a ocorrência dos principais sinais e sintomas dos casos de dengue clássico e dengue hemorrágico na epidemia de 2001-2002 do município do Rio de Janeiro. Foram analisados os 155.242 casos notificados ao Sistema de Informações de Agravos de Notificação, desde janeiro/2001, até junho/2002; deste total, excluindo-se os ignorados, 81.327 casos foram classificados como dengue clássico e 958 como dengue hemorrágico, com um total de 54 óbitos. Avaliaram-se as variáveis referentes à sintomatologia da doença. Manifestações gerais como febre, cefaléia, prostração, mialgia, náuseas e dor retro-orbitária tiveram alta incidência tanto no dengue clássico como no dengue hemorrágico. Por outro lado, manifestações hemorrágicas e algumas de maior gravidade como choque, hemorragia digestiva, petéquias, epistaxe, dor abdominal e derrame pleural, estiveram significativamente associadas ao dengue hemorrágico. Além disso, a evolução do quadro clínico para o óbito foi 34,8 vezes maior no dengue hemorrágico que no dengue clássico (OR=34,8; IC 19,7-61,3.The following study was intended to evaluate the occurrence of typical signs and symptoms in the cases of classic dengue and hemorrhagic dengue fever, during the 2001-2002 epidemic in the city of Rio de Janeiro. The authors reviewed 155,242 cases notified to the Information System of Notification Diseases, from January/2001 to June/2002: 81,327 cases were classified as classic dengue and 958 as hemorrhagic dengue fever, with a total of 60 deaths. Common symptoms, such as fever, headache, prostration, myalgia, nausea and retro-orbital pain, had a high incidence in both classic and hemorrhagic dengue fever. On the other hand, hemorrhagic signs and other signs of severe disease, such as shock, gastrointestinal bleeding, petechiae, epistaxis, abdominal pain and pleural effusion, were strongly associated to hemorrhagic dengue fever. Besides, the occurrence

  7. Post dengue neurological complication

    Directory of Open Access Journals (Sweden)

    Hizlinda Tohid

    2015-12-01

    Full Text Available Dengue infection is highly endemic in many tropical countries including Malaysia. However, neurological complications arising from dengue infection is not common; Gullain–Barre syndrome (GBS is one of these infrequent complications. In this paper, we have reported a case in which a 39-year-old woman presented with a neurological complication of dengue infection without typical symptoms and signs of dengue fever. She had a history of acute gastroenteritis (AGE followed by an upper respiratory tract infection (URTI weeks prior to her presentation rendering GBS secondary to the post viral URTI and AGE as the most likely diagnosis. Presence of thrombocytopenia was the only clue for dengue in this case.

  8. La epidemiología del dengue y del dengue hemorrágico en Santiago de Cuba, 1997 The epidemiology of dengue and dengue hemorrhagic fever in Santiago de Cuba, 1997

    Directory of Open Access Journals (Sweden)

    Luis Valdés

    1999-07-01

    Full Text Available En 1977, Cuba informó de su primera epidemia de dengue, durante la cual se registraron más de 500 000 casos de fiebre del dengue causados por el serotipo 1 del virus. En 1981, se produjo una gran epidemia de dengue hemorrágico causada por el serotipo 2. Esa vez se notificaron 344 203 casos en total, 10 312 casos clínicos de dengue hemorrágico y 158 defunciones, de las cuales 101 correspondieron a niños. Por medio de una búsqueda activa con confirmación de laboratorio, en el municipio de Santiago de Cuba de la provincia del mismo nombre se detectó precozmente en enero de 1997 la reintroducción del dengue, específicamente del virus del tipo 2, genotipo Jamaica. En este trabajo se presentan los aspectos epidemiológicos de mayor interés referentes a esa epidemia. Se notificaron 3 012 casos confirmados por serología, 205 clasificados como fiebre hemorrágica del dengue/síndrome de choque del dengue, de los cuales 12 fallecieron (todos adultos. La infección secundaria por virus del dengue fue uno de los principales factores de riesgo en el desarrollo de dengue hemorrágico y 98% de los casos, así como 92% de los fallecidos, manifestaron una respuesta de tipo secundario. Por primera vez se observó la posibilidad de contraer dengue hemorrágico en personas con una infección secundaria de 16 a 20 años después de la primera infección. Pertenecer a la raza blanca fue otro factor de riesgo de importancia, tal como se había observado desde la epidemia de 1981. En la última epidemia se demostró que la llamada “alerta de fiebre” no es útil para la detección temprana de una epidemia. Las medidas tomadas por las autoridades sanitarias del país evitaron la extensión de la epidemia a otros municipios que estaban infestados por Aedes aegypti.A dengue epidemic that Cuba reported in 1997 registered more than 500 000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by

  9. Is drought helping or killing dengue? Investigation of spatiotemporal relationship between dengue fever and drought

    Science.gov (United States)

    Lee, Chieh-Han; Yu, Hwa-Lung

    2015-04-01

    Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

  10. Polymerization of a divalent/tetravalent metal-storing atom-mimicking dendrimer

    OpenAIRE

    Albrecht, Ken; Hirabayashi, Yuki; Otake, Masaya; Mendori, Shin; Tobari, Yuta; Azuma, Yasuo; Majima, Yutaka; Yamamoto, Kimihisa

    2016-01-01

    The phenylazomethine dendrimer (DPA) has a layer-by-layer electron density gradient that is an analog of the Bohr atom (atom mimicry). In combination with electron pair mimicry, the polymerization of this atom-mimicking dendrimer was achieved. The valency of the mimicked atom was controlled by changing the chemical structure of the dendrimer. By mimicking a divalent atom, a one-dimensional (1D) polymer was obtained, and by using a planar tetravalent atom mimic, a 2D polymer was obtained. Thes...

  11. Dengue and Calcium

    OpenAIRE

    Shivanthan, Mitrakrishnan C; Rajapakse, Senaka

    2014-01-01

    Dengue is potentially fatal unless managed appropriately. No specific treatment is available and the mainstay of treatment is fluid management with careful monitoring, organ support, and correction of metabolic derangement. Evidence with regards to the role of calcium homeostasis in dengue is limited. Low blood calcium levels have been demonstrated in dengue infection and hypocalcemia maybe more pronounced in more severe forms. The cause of hypocalcemia is likely to be multifactorial. Calcium...

  12. Controlling dengue with vaccines in Thailand.

    Directory of Open Access Journals (Sweden)

    Dennis L Chao

    Full Text Available Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes.We developed an individual-level (including both humans and mosquitoes, stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period.Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels.

  13. Controlling Dengue with Vaccines in Thailand

    Science.gov (United States)

    Chao, Dennis L.; Halstead, Scott B.; Halloran, M. Elizabeth; Longini, Ira M.

    2012-01-01

    Background Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes. Methodology/Principal Findings We developed an individual-level (including both humans and mosquitoes), stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period. Conclusions/Significance Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels. PMID:23145197

  14. Tri-phasic fever in dengue fever.

    Science.gov (United States)

    D, Pradeepa H; Rao, Sathish B; B, Ganaraj; Bhat, Gopalakrishna; M, Chakrapani

    2018-04-01

    Dengue fever is an acute febrile illness with a duration of 2-12 days. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and compared this with 26 others with fever due to a non-dengue aetiology. A tri-phasic fever pattern was seen among two-thirds of dengue fever patients, but in only one with an inflammatory disease. One-third of dengue fever patients exhibited a single peak temperature. Continuous temperature monitoring and temperature pattern analysis in clinical settings can aid in the early differentiation of dengue fever from non-dengue aetiology.

  15. Recombinant Lipoproteins as Novel Vaccines with Intrinsic Adjuvant.

    Science.gov (United States)

    Chong, Pele; Huang, Jui-Hsin; Leng, Chih-Hsiang; Liu, Shih-Jen; Chen, Hsin-Wei

    2015-01-01

    A core platform technology for high production of recombinant lipoproteins with built-in immunostimulator for novel subunit vaccine development has been established. This platform technology has the following advantages: (1) easily convert antigen into lipidated recombinant protein using a fusion sequence containing lipobox and express high level (50-150mg/L) in Escherichia coli; (2) a robust high-yield up- and downstream bioprocess for lipoprotein production is successfully developed to devoid endotoxin contamination; (3) the lipid moiety of recombinant lipoproteins, which is identical to that of bacterial lipoproteins is recognized as danger signals by the immune system (Toll-like receptor 2 agonist), so both innate and adaptive immune responses can be induced by lipoproteins; and (4) successfully demonstrate the feasibility and safety of this core platform technology in meningococcal group B subunit vaccine, dengue subunit vaccine, novel subunit vaccine against Clostridium difficile-associated diseases, and HPV-based immunotherapeutic vaccines in animal model studies. © 2015 Elsevier Inc. All rights reserved.

  16. A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice

    International Nuclear Information System (INIS)

    Valdes, Iris; Bernardo, Lidice; Gil, Lazaro; Pavon, Alekis; Lazo, Laura; Lopez, Carlos; Romero, Yaremis; Menendez, Ivon; Falcon, Viviana; Betancourt, Lazaro; Martin, Jorge; Chinea, Glay; Silva, Ricardo; Guzman, Maria G.; Guillen, Gerardo; Hermida, Lisset

    2009-01-01

    Based on the immunogenicity of domain III from the Envelope protein of dengue virus as well as the proven protective capacity of the capsid antigen, we have designed a novel domain III-capsid chimeric protein with the goal of obtaining a molecule potentially able to induce both humoral and cell-mediated immunity (CMI). After expression of the recombinant gene in Escherichia coli, the domain III moiety retained its antigenicity as evaluated with anti-dengue sera. In order to explore alternatives for modulating the immunogenicity of the protein, it was mixed with oligodeoxynucleotides in order to obtain particulated aggregates and then immunologically evaluated in mice in comparison with non-aggregated controls. Although the humoral immune response induced by both forms of the protein was equivalent, the aggregated variant resulted in a much stronger CMI as measured by in vitro IFN-γ secretion and protection experiments, mediated by CD4 + and CD8 + cells. The present work provides additional evidence in support for a crucial role of CMI in protection against dengue virus and describes a novel vaccine candidate against the disease based on a recombinant protein that can stimulate both arms of the acquired immune system.

  17. Development and characterization of a reverse genetic system for studying dengue virus serotype 3 strain variation and neutralization.

    Directory of Open Access Journals (Sweden)

    William B Messer

    Full Text Available Dengue viruses (DENV are enveloped single-stranded positive-sense RNA viruses transmitted by Aedes spp. mosquitoes. There are four genetically distinct serotypes designated DENV-1 through DENV-4, each further subdivided into distinct genotypes. The dengue scientific community has long contended that infection with one serotype confers lifelong protection against subsequent infection with the same serotype, irrespective of virus genotype. However this hypothesis is under increased scrutiny and the role of DENV genotypic variation in protection from repeated infection is less certain. As dengue vaccine trials move increasingly into field-testing, there is an urgent need to develop tools to better define the role of genotypic variation in DENV infection and immunity. To better understand genotypic variation in DENV-3 neutralization and protection, we designed and constructed a panel of isogenic, recombinant DENV-3 infectious clones, each expressing an envelope glycoprotein from a different DENV-3 genotype; Philippines 1982 (genotype I, Thailand 1995 (genotype II, Sri Lanka 1989 and Cuba 2002 (genotype III and Puerto Rico 1977 (genotype IV. We used the panel to explore how natural envelope variation influences DENV-polyclonal serum interactions. When the recombinant viruses were tested in neutralization assays using immune sera from primary DENV infections, neutralization titers varied by as much as ∼19-fold, depending on the expressed envelope glycoprotein. The observed variability in neutralization titers suggests that relatively few residue changes in the E glycoprotein may have significant effects on DENV specific humoral immunity and influence antibody mediated protection or disease enhancement in the setting of both natural infection and vaccination. These genotypic differences are also likely to be important in temporal and spatial microevolution of DENV-3 in the background of heterotypic neutralization. The recombinant and synthetic tools

  18. Dengue fever (image)

    Science.gov (United States)

    Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

  19. Manifestações mucocutâneas da dengue Mucocutaneous manifestations of dengue

    Directory of Open Access Journals (Sweden)

    Omar Lupi

    2007-08-01

    Full Text Available Dengue é doença viral sistêmica que ocorre de forma epidêmica em áreas tropicais e subtropicais da Ásia, Américas e África. O vírus da dengue pertence ao gênero Flavivirus e à família Flaviviridae (arbovírus do grupo B. Aedes aegypti é o principal vetor e verdadeiro reservatório. A febre na dengue clássica persiste por período de dois a cinco dias com cefaléia intensa, mialgia, artralgia e dor retro-orbital. Alterações cutâneas incluem diversos achados como erupção morbiliforme que pode ser pruriginosa e que gera descamação residual, algumas manifestações hemorrágicas discretas como epistaxe, petéquias e sangramento gengival. Extravasamento capilar de plasma é responsável pela hemoconcentração e trombocitopenia observadas e que caracterizam a dengue hemorrágica. Manifestações cutâneas da dengue hemorrágica incluem lesões hemorrágicas disseminadas como petéquias e equimoses, mas também instabilidade hemodinâmica com pulso filiforme, pressão arterial convergente, extremidades frias, confusão mental e choque.Dengue fever is a systemic viral disease that occurs epidemically in tropical and subtropical regions of Asia, Americas and Africa. The dengue virus belongs to the genus Flavivirus of the family Flaviviridae (group B arbovirus. Aedes aegypti is the major vector and the true reservoir for the virus. Classic dengue fever lasts for two-five days, with severe headache, intense myalgia, arthralgia and retro-orbital pain. Cutaneous alterations include several findings such as a diffuse morbilliform rash that may be pruritic and heals with desquamation, and minor bleeding phenomena such as epistaxis, petechiae, and gingival bleeding. Diffuse capillary leakage of plasma is responsible for the hemoconcentration and thrombocytopenia that characterize dengue hemorrhagic fever. Cutaneous manifestations of dengue hemorrhagic fever include many disseminated hemorrhagic lesions such as petechiae and ecchymoses, but

  20. Ensemble method for dengue prediction.

    Science.gov (United States)

    Buczak, Anna L; Baugher, Benjamin; Moniz, Linda J; Bagley, Thomas; Babin, Steven M; Guven, Erhan

    2018-01-01

    In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maximum weekly number of cases during a transmission season; 2) peak week (i.e., week in which the maximum weekly number of cases occurred); and 3) total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date. Our approach used ensemble models created by combining three disparate types of component models: 1) two-dimensional Method of Analogues models incorporating both dengue and climate data; 2) additive seasonal Holt-Winters models with and without wavelet smoothing; and 3) simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations. Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week. The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru.

  1. Ensemble method for dengue prediction.

    Directory of Open Access Journals (Sweden)

    Anna L Buczak

    Full Text Available In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico during four dengue seasons: 1 peak height (i.e., maximum weekly number of cases during a transmission season; 2 peak week (i.e., week in which the maximum weekly number of cases occurred; and 3 total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date.Our approach used ensemble models created by combining three disparate types of component models: 1 two-dimensional Method of Analogues models incorporating both dengue and climate data; 2 additive seasonal Holt-Winters models with and without wavelet smoothing; and 3 simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations.Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week.The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru.

  2. THROMBOCYTOPENIA IN DENGUE HAEMORRHAGIC FEVER

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    I Wayan Putu Sutirta-Yasa

    2013-04-01

    Full Text Available The incidence and geographical distribution of dengue has gradually increased during the past decade. Today, dengue is considered one of the most important arthropod-borne viral diseasases in humans in term of morbidity and mortality. Dengue infection   a potential life-threatening dengue hemorrhagic fever (DHF / dengue shock syndrome(DSS, characterized by thrombocytopenia and increased vascular permiability. Thrombocytopenia causes bleeding, but in   DHF patients with thrombocytopenia do not always develop bleeding manifestation. The pathogenesis of thrombocytopenia are not cleared. Multiple factors  may be involved in the machanisms leading to thrombocytopenia in DHF/DSS patients.

  3. Dengue and dengue hemorrhagic fever in the Americas: lessons and challenges.

    Science.gov (United States)

    Guzman, María G; Kouri, Gustavo

    2003-05-01

    The incidence of dengue and dengue hemorrhagic fever (DF/DHF) has increased significantly over the last decades. Yearly, an estimated 50-100 million cases of DF and about 250000-500000 cases of DHF occur worldwide. The epidemiological situation in Latin America now resembles that in Southeast Asia. Here, the main clinical, epidemiological and virological observations in the American region are presented and compared with those previously reported from Southeast Asia. During 2002, more than 30 Latin American countries reported over 1000000 DF cases. DHF occurred in 20 countries with more than 17000 DHF cases, including 225 fatalities. The co-circulation of multiple serotypes has been reported from many countries. In the Americas, DHF is observed both in children and adults; secondary infection by a different dengue virus serotype has been confirmed as an important risk factor for this severe form of the disease. However, some new risk factors such as the interval of dengue virus infections and the ethnicity and underlying chronic conditions of the patient have also been identified. The sequence of dengue virus infections and association with certain genotypes are further factors of importance. We also discuss the control and prevention strategies. In conclusion, without urgent action for the prevention and control of dengue/DHF and its vector, the current situation will worsen and, more dramatical, there is a risk of the urbanization of yellow fever.

  4. Ecg manifestations in dengue infection

    International Nuclear Information System (INIS)

    Tarique, S.; Murtaza, G.; Asif, S.; Qureshi, I.H.

    2013-01-01

    To determine the frequency of ECG changes in patients with dengue fever and dengue hemorrhagic fever. Place of study: Department of Medicine, Mayo Hospital Lahore Duration of study: September to November 201 Study design: Cross sectional analytical study Patient and methods: 116 patients with dengue infection were enrolled in the study. Their clinical presentation and examination was duly noted. Each patient had baseline and then regular monitoring of blood counts, metabolic profile and fluid status. Patients with Dengue Hemorrhagic fever underwent radiological examination in form of chest radiograph and ultrasound abdomen. ECG was carried out in all patients. Results: Out of 116 patients, 61(52.6%) suffered from Dengue Fever and 55(47.4%) had Dengue Hemorrhagic Fever. Overall 78 patients had normal ECG. Abnormal ECG findings like tachycardia, bradycardia, supraventricular tachycardia, left bundle branch block, ST depression, poor progression of R wave were noted. There was no significant relationship of ECG findings with the disease. Conclusion: ECG changes can occur in dengue infection with or without cardiac symptoms. Commonly noted findings were ST depression and bradycardia. (author)

  5. Dengue viruses in Brazil, 1986-2006 Virus del dengue en Brasil, 1986-2006

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    Rita Maria Ribeiro Nogueira

    2007-11-01

    Full Text Available A total of 4 243 049 dengue cases have been reported in Brazil between 1981 and 2006, including 5 817 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS and a total of 338 fatal cases. Although all Brazilian regions have been affected, the Northeast and Southeast regions have registered the highest number of notifications. DENV-1 and DENV-4 were isolated for the first time in the Amazon region of Brazil in 1981 and 1982. The disease became a nationwide public health problem following outbreaks of DENV-1 and DENV-2 in the state of Rio de Janeiro in 1986 and 1990, respectively. The introduction of DENV-3 in 2000, also in the state of Rio de Janeiro, led to a severe epidemic with 288 245 reported dengue cases, including 91 deaths. Virus strains that were typed during the 2002 epidemic show that DENV-3 has displaced other dengue virus serotypes and entered new areas, a finding that warrants closer evaluation. Unusual clinical symptoms, including central nervous system involvement, have been observed in dengue patients in at least three regions of the country.En Brasil se han notificado 4 243 049 casos de dengue entre 1981 y 2006, de ellos 5 817 casos de dengue hemorrágico/síndrome de choque por dengue (DH/SCD y un total de 338 casos mortales. A pesar de que la enfermedad ha afectado a todas las regiones brasileñas, el mayor número de casos se ha notificado en las regiones nororiental y suroriental. Los virus del dengue (DENV 1 y 4 se aislaron por primera vez en la región amazónica de Brasil en 1981 y 1982. La enfermedad se convirtió en un problema nacional de salud pública después de los brotes de DENV-1 y DENV-2 en el Estado de Río de Janeiro en 1986 y 1990, respectivamente. La introducción del DENV-3 en 2000, también en el Estado de Río de Janeiro, llevó a una grave epidemia con 288 245 casos notificados de dengue y 91 muertes. Las cepas del virus identificadas durante la epidemia de 2002 demostraron que el DENV-3 ha

  6. Neurological Manifestations of Dengue Infection

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    Guo-Hong Li

    2017-10-01

    Full Text Available Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS, peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

  7. Human Immune Response to Dengue Infections

    Science.gov (United States)

    1991-06-30

    had been immunized with yellow fever vaccine and later became infected with dengue 3 virus, responded best to dengue 3 antigen but also responded to...effective dengue virus subunit vaccines . We found evidence of marked T cell activation in patients with DHF. T cell activation in patients with DF was similar...Treatment and Control of Dengue Hemorrhagic Fever. World Health Organization, Geneva, Switzerland 7. Sabin AB (1952) Research on dengue during World

  8. Evaluation of Internet-based dengue query data: Google Dengue Trends.

    Directory of Open Access Journals (Sweden)

    Rebecca Tave Gluskin

    2014-02-01

    Full Text Available Dengue is a common and growing problem worldwide, with an estimated 70-140 million cases per year. Traditional, healthcare-based, government-implemented dengue surveillance is resource intensive and slow. As global Internet use has increased, novel, Internet-based disease monitoring tools have emerged. Google Dengue Trends (GDT uses near real-time search query data to create an index of dengue incidence that is a linear proxy for traditional surveillance. Studies have shown that GDT correlates highly with dengue incidence in multiple countries on a large spatial scale. This study addresses the heterogeneity of GDT at smaller spatial scales, assessing its accuracy at the state-level in Mexico and identifying factors that are associated with its accuracy. We used Pearson correlation to estimate the association between GDT and traditional dengue surveillance data for Mexico at the national level and for 17 Mexican states. Nationally, GDT captured approximately 83% of the variability in reported cases over the 9 study years. The correlation between GDT and reported cases varied from state to state, capturing anywhere from 1% of the variability in Baja California to 88% in Chiapas, with higher accuracy in states with higher dengue average annual incidence. A model including annual average maximum temperature, precipitation, and their interaction accounted for 81% of the variability in GDT accuracy between states. This climate model was the best indicator of GDT accuracy, suggesting that GDT works best in areas with intense transmission, particularly where local climate is well suited for transmission. Internet accessibility (average ∼ 36% did not appear to affect GDT accuracy. While GDT seems to be a less robust indicator of local transmission in areas of low incidence and unfavorable climate, it may indicate cases among travelers in those areas. Identifying the strengths and limitations of novel surveillance is critical for these types of data to

  9. Reviewing dengue: still a neglected tropical disease?

    Science.gov (United States)

    Horstick, Olaf; Tozan, Yesim; Wilder-Smith, Annelies

    2015-04-01

    Dengue is currently listed as a "neglected tropical disease" (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003-2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

  10. Reviewing dengue: still a neglected tropical disease?

    Directory of Open Access Journals (Sweden)

    Olaf Horstick

    2015-04-01

    Full Text Available Dengue is currently listed as a "neglected tropical disease" (NTD. But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D (2003-2013. NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a poverty related, b endemic to the tropics and subtropics, c lacking public health attention, d having poor research funding and shortcomings in R&D, e usually associated with high morbidity but low mortality, and f often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

  11. Dengue fever outbreak: a clinical management experience

    International Nuclear Information System (INIS)

    Ahmed, S.; Illyas, M.

    2008-01-01

    To determine the frequency of dengue as a cause of fever and compare the clinical and haematological characteristics of Dengue-probable and Dengue-proven cases. All patients with age above 14 years, who were either hospitalized or treated in medical outdoor clinic due to acute febrile illness, were evaluated for clinical features of Dengue Fever (DF), Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). Patients showing typical clinical features and haematological findings suggestive of Dengue fever (As per WHO criteria) were evaluated in detail for comparison of probable and confirmed cases of Dengue fever. All other cases of acute febrile illness, not showing clinical features or haematological abnormalities of Dengue fever, were excluded. The clinical and laboratory features were recorded on SPSS 11.0 programme and graded where required, for descriptive and statistical analysis. Out of 5200 patients with febrile illness, 107 (2%) presented with typical features of DF, 40/107 (37%) were Dengue-proven while 67/107 (63%) were Dengue-probable. Out of Dengue-proven cases, 38 were of DF and 2 were of DHF. Day 1 temperature ranged from 99-105 degreeC (mean 101 degree C). Chills and rigors were noticed in 86 (80%), myalgia in 67%, headache in 54%, pharyngitis in 35%, rash in 28%, and bleeding manifestations in 2% cases. Hepatomegaly in 1(0.5%), lymphadenopathy in 1 (0.5%) and splenomegaly in 12 (11.2%) cases. Leucopoenia (count 40 U/L in 57% cases. Frequency of clinically suspected dengue virus infection was 107 (2%), while confirmed dengue fever cases were 40 (0.8%) out of 5200 fever cases. Fever with chills and rigors, body aches, headache, myalgia, rash, haemorrhagic manifestations, platelet count, total leukocyte count, and ALT, are parameters to screen the cases of suspected dengue virus infection, the diagnosis cannot be confirmed unless supported by molecular studies or dengue specific IgM. (author)

  12. Profile of dengue hepatitis in children from India and its correlation with WHO dengue case classifiation

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    Neelam Mohan

    2017-06-01

    Full Text Available Objective: To study the profile of liver involvement in children with dengue fever and to compare the severity of liver involvement with World Health Organization case definition. Methods: A prospective study was carried out from October 2013 to December 2014. Serologically confirmed dengue patients were grouped into three categories according to the World Health Organization classification. Groups 1 and 2 were dengue fever without and with warning signs, respectively; Group 3 was severe dengue. Biochemical and clinical profile of hepatic involvement was studied. Results: A total of 162 children with dengue fever (M:F = 2.37 were included in the study. Median (inter quartile range age was 12 years (IQR: 0.5–18 years. Hepatitis was observed in 151 (93.2% patients. Analysis revealed that out of all liver function test parameters, total bilirubin was found to be a significant predictor of dengue category two and three and albumin and ALT levels were significant predictors for category three. Eight cases presented with ALF. Their median AST was 4 817 (range 61–26 957; median ALT was 2 386 (range 39–11 100; median INR was 2.57 (range 1.6–4.2 and their median serum bilirubin was 2.95 (range 0.6–9.0. Conclusions: Some degree of hepatitis is very common in dengue infection with rise in AST being more than ALT irrespective of the severity of dengue. Severity of hepatitis correlates well with the severity of dengue and can help in triaging of dengue patients. Of all liver function parameters, total bilirubin levels correlate best with severity of dengue infection.

  13. Climate and dengue transmission: evidence and implications.

    Science.gov (United States)

    Morin, Cory W; Comrie, Andrew C; Ernst, Kacey

    2013-01-01

    Climate influences dengue ecology by affecting vector dynamics, agent development, and mosquito/human interactions. Although these relationships are known, the impact climate change will have on transmission is unclear. Climate-driven statistical and process-based models are being used to refine our knowledge of these relationships and predict the effects of projected climate change on dengue fever occurrence, but results have been inconsistent. We sought to identify major climatic influences on dengue virus ecology and to evaluate the ability of climate-based dengue models to describe associations between climate and dengue, simulate outbreaks, and project the impacts of climate change. We reviewed the evidence for direct and indirect relationships between climate and dengue generated from laboratory studies, field studies, and statistical analyses of associations between vectors, dengue fever incidence, and climate conditions. We assessed the potential contribution of climate-driven, process-based dengue models and provide suggestions to improve their performance. Relationships between climate variables and factors that influence dengue transmission are complex. A climate variable may increase dengue transmission potential through one aspect of the system while simultaneously decreasing transmission potential through another. This complexity may at least partly explain inconsistencies in statistical associations between dengue and climate. Process-based models can account for the complex dynamics but often omit important aspects of dengue ecology, notably virus development and host-species interactions. Synthesizing and applying current knowledge of climatic effects on all aspects of dengue virus ecology will help direct future research and enable better projections of climate change effects on dengue incidence.

  14. Overview of current situation of dengue and dengue vector control

    Science.gov (United States)

    Dengue is the most important arbovirus of humans in the world. It is caused by one of four closely related virus serotypes whose primary vector is Aedes aegypti and secondarily by Ae. albopictus. A global dengue pandemic began in Southeast Asia after World War II and has intensified during the las...

  15. Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril) When Administered Concomitantly With a Tetravalent Dengue Vaccine Candidate in Healthy Toddlers at 12-13 Months of Age in Colombia and Peru: A Randomized Trial.

    Science.gov (United States)

    López, Pio; Lanata, Claudio F; Zambrano, Betzana; Cortés, Margarita; Andrade, Teresa; Amemiya, Isabel; Terrones, Cynthia; Gil, Ana I; Verastegui, Hector; Marquez, Viviana; Crevat, Denis; Jezorwski, John; Noriega, Fernando

    2016-10-01

    Dengue and yellow fever (YF) viruses are closely related members of the Flaviviridae family. Given the inherent similarities between the YF vaccine and dengue vaccine (CYD-TDV) candidate, it is possible that the latter could interfere with the response to the licensed YF vaccine when coadministered. In this randomized, observer-blind, controlled, phase III trial, conducted in Colombia and Peru, 787 toddlers were administered YF vaccine concomitantly with CYD-TDV (group 1) or placebo (group 2), followed by CYD-TDV after 6 and 12 months. YF and dengue neutralizing antibody titers were determined using a 50% plaque reduction neutralization test. Noninferiority was demonstrated if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates [(YF + CYD-TDV) - YF alone] was greater than -10%. The safety of both vaccines was also assessed. Concomitant administration of YF with either CYD-TDV or placebo yielded YF seroconversion rates of 100.0% and 99.7%, respectively. The difference in YF seroconversion rates between the 2 groups was 0.33% (95% confidence interval:0.98; 1.87), demonstrating that the immune response against YF administered concomitantly with CYD-TDV was noninferior to YF administered with placebo. After 2 injections of CYD-TDV, the percentage of participants with dengue titres ≥10 (1/dil) for the 4 dengue serotypes were 91.2%-100% for group 1 and 97.2%-100% in group 2. There were no safety concerns during the study period. Concomitant administration of YF vaccine with CYD-TDV has no relevant impact on the immunogenicity or safety profile of the YF vaccine.

  16. Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

    Science.gov (United States)

    Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

    2015-01-01

    HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

  17. Lo que usted debe saber acerca del dengue

    OpenAIRE

    Vélez, Juan David; Fundación Valle de Lili; Salazar, Juan Carlos; Rosso Suárez, Fernando

    1998-01-01

    Epidemiología del dengue/Transmisión/Presentación clínica/Síntomas en niños/Diagnostico de laboratorio/Dengue clásico/Dengue hemorrágico/Dengue hemorrágico con choque/ ¿Qué es dengue hemorrágico?/ ¿Cuál es la diferencia entre dengue hemorrágico y dengue clásico?/ ¿Qué son las plaquetas?/ ¿Qué puedo hacer para prevenir el dengue?/ ¿Cuándo debo consultar?/ ¿Cuándo se debe hacer un hemograma?/ ¿Cuándo se debe hospitalizar un paciente con dengue?

  18. Neurological manifestations of dengue viral infection

    Directory of Open Access Journals (Sweden)

    Carod-Artal FJ

    2014-10-01

    Full Text Available Francisco Javier Carod-Artal1,21Neurology Department, Raigmore hospital, Inverness, UK; 2Universitat Internacional de Catalunya (UIC, Barcelona, Spain Abstract: Dengue is the most common mosquito-borne viral infection worldwide. There is increased evidence for dengue virus neurotropism, and neurological manifestations could make part of the clinical picture of dengue virus infection in at least 0.5%–7.4% of symptomatic cases. Neurological complications have been classified into dengue virus encephalopathy, dengue virus encephalitis, immune-mediated syndromes (acute disseminated encephalomyelitis, myelitis, Guillain–Barré syndrome, neuritis brachialis, acute cerebellitis, and others, neuromuscular complications (hypokalemic paralysis, transient benign muscle dysfunction and myositis, and dengue-associated stroke. Common neuro-ophthalmic complications are maculopathy and retinal vasculopathy. Pathogenic mechanisms include systemic complications and metabolic disturbances resulting in encephalopathy, direct effect of the virus provoking encephalitis, and postinfectious immune mechanisms causing immune-mediated syndromes. Dengue viruses should be considered as a cause of neurological disorders in endemic regions. Standardized case definitions for specific neurological complications are still needed. Keywords: encephalitis, encephalopathy, dengue fever, neurological complications

  19. Coordination polymers: trapping of radionuclides and chemistry of tetravalent actinides (Th, U) carboxylates

    International Nuclear Information System (INIS)

    Falaise, Clement

    2014-01-01

    The use of nuclear energy obviously raises the question of the presence of radionuclides in the environment. Currently, their mitigation is a major issue associated with nuclear chemistry. This thesis focuses on both the trapping of radionuclides by porous solids called Metal-Organic Frameworks (MOF) and the crystal chemistry of the carboxylate of tetravalent actinides (AnIV). The academic knowledge of the reactivity of carboxylate of AnIV could help the understanding of actinides speciation in environment. We focused on the sequestration of iodine by aluminum based MOF. The functionalization (electron-donor group) of the MOF drastically enhances the iodine capture capacity. The removal of light actinides (Th and U) from aqueous solution was also investigated as well as the stability of (Al)-MOF under γ radiation. More than twenty coordination polymers based on tetravalent actinides have been synthesized and characterized by single crystal X-ray diffraction. The use of controlled hydrolysis promotes the formation of coordination polymers exhibiting polynuclear cluster ([U 4 ], [Th 6 ], [U 6 ] and [U 38 ]). In order to understand the formation of the largest cluster, the ex-situ study of the solvo-thermal synthesis of compound {U 38 } has also been investigated. (author)

  20. Comparison of real-time SYBR green dengue assay with real-time taqman RT-PCR dengue assay and the conventional nested PCR for diagnosis of primary and secondary dengue infection

    Science.gov (United States)

    Paudel, Damodar; Jarman, Richard; Limkittikul, Kriengsak; Klungthong, Chonticha; Chamnanchanunt, Supat; Nisalak, Ananda; Gibbons, Robert; Chokejindachai, Watcharee

    2011-01-01

    Background: Dengue fever and dengue hemorrhagic fever are caused by dengue virus. Dengue infection remains a burning problem of many countries. To diagnose acute dengue in the early phase we improve the low cost, rapid SYBR green real time assay and compared the sensitivity and specificity with real time Taqman® assay and conventional nested PCR assay. Aims: To develop low cost, rapid and reliable real time SYBR green diagnostic dengue assay and compare with Taqman real-time assay and conventional nested PCR (modified Lanciotti). Materials and Methods: Eight cultured virus strains were diluted in tenth dilution down to undetectable level by the PCR to optimize the primer, temperature (annealing, and extension and to detect the limit of detection of the assay. Hundred and ninety three ELISA and PCR proved dengue clinical samples were tested with real time SYBR® Green assay, real time Taqman® assay to compare the sensitivity and specificity. Results: Sensitivity and specificity of real time SYBR® green dengue assay (84% and 66%, respectively) was almost comparable to those (81% and 74%) of Taqman real time PCR dengue assay. Real time SYBR® green RT-PCR was equally sensitive in primary and secondary infection while real time Taqman was less sensitive in the secondary infection. Sensitivity of real time Taqman on DENV3 (87%) was equal to SYBR green real time PCR dengue assay. Conclusion: We developed low cost rapid diagnostic SYBR green dengue assay. Further study is needed to make duplex primer assay for the serotyping of dengue virus. PMID:22363089

  1. Alterações hematológicas em pacientes com dengue Hematological abnormalities in patients with dengue

    Directory of Open Access Journals (Sweden)

    Éveny Cristine Luna de Oliveira

    2009-12-01

    Full Text Available Dengue é uma doença negligenciada de alta morbidade e mortalidade em crianças e adultos, ocorrendo principalmente em regiões tropicais e subtropicais. O objetivo desse trabalho foi avaliar as alterações hematológicas de pacientes com quadro clínico de dengue. Foram estudados 543 prontuários de atendimentos referentes à epidemia pelo vírus tipo 3, ocorrida no ano de 2007, em Campo Grande, Mato Grosso do Sul. Houve predomínio de casos de dengue clássico (90,2%, com quadro clínico leve sem complicações. As principais alterações hematológicas observadas foram a leucopenia (68,3%, plaquetopenia (66,5%, linfocitopenia (67,2% e presença de linfócitos atípicos (67%. A febre hemorrágica do dengue apresentou plaquetopenia mais prolongada e maior número de linfócitos atípicos, as demais alterações hematológicas apresentaram evolução diária semelhante às encontradas no dengue clássico. As alterações hematológicas observadas no dengue apresentaram-se de acordo com a evolução clínica e gravidade da doença.Dengue is a neglected disease with high morbidity and mortality among children and adults that occurs mainly in tropical and subtropical regions. The objective of this study was to evaluate hematological changes in patients with clinical manifestations of dengue. Medical records relating to 543 cases of dengue virus 3 that occurred during the 2007 epidemic in Campo Grande, Mato Grosso do Sul, were studied. Cases of classic dengue predominated (90.2%, with mild clinical manifestations lacking complications. The main hematological findings were leukopenia (68.3%, thrombocytopenia (66.5%, lymphocytopenia (67.2% and atypical lymphocytes (67%. In dengue hemorrhagic fever, thrombocytopenia was more prolonged and the number of atypical lymphocytes was higher, while the other hematological abnormalities presented daily evolution similar to those in classic dengue. The hematological changes observed in dengue present according

  2. Dengue fever outbreak: a clinical management experience.

    Science.gov (United States)

    Ahmed, Shahid; Ali, Nadir; Ashraf, Shahzad; Ilyas, Mohammad; Tariq, Waheed-Uz-Zaman; Chotani, Rashid A

    2008-01-01

    To determine the frequency of dengue as a cause of fever and compare the clinical and haematological characteristics of Dengue-probable and Dengue-proven cases. An observational study. The Combined Military Hospital, Malir Cantt., Karachi, from August 2005 to December 2006. All patients with age above 14 years, who were either hospitalized or treated in medical outdoor clinic due to acute febrile illness, were evaluated for clinical features of Dengue Fever (DF), Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). Patients showing typical clinical features and haematological findings suggestive of Dengue fever (As per WHO criteria) were evaluated in detail for comparison of probable and confirmed cases of Dengue fever. All other cases of acute febrile illness, not showing clinical features or haematological abnormalities of Dengue fever, were excluded. The clinical and laboratory features were recorded on SPSS 11.0 programme and graded where required, for descriptive and statistical analysis. Out of 5200 patients with febrile illness, 107(2%) presented with typical features of DF, 40/107(37%) were Dengue-proven while 67/107(63%) were Dengue-probable. Out of Dengue-proven cases, 38 were of DF and 2 were of DHF. Day 1 temperature ranged from 99-1050C (mean 1010C). Chills and rigors were noticed in 86 (80%), myalgia in 67%, headache in 54%, pharyngitis in 35%, rash in 28%, and bleeding manifestations in 2% cases. Hepatomegaly in 1(0.5%), lymphadenopathy in 1(0.5%) and splenomegaly in 12 (11.2%) cases. Leucopoenia (count40 U/L in 57% cases. Frequency of clinically suspected dengue virus infection was 107 (2%), while confirmed dengue fever cases were 40 (0.8%) out of 5200 fever cases. Fever with chills and rigors, body aches, headache, myalgia, rash, haemorrhagic manifestations, platelet count, total leukocyte count, and ALT, are parameters to screen the cases of suspected dengue virus infection; the diagnosis cannot be confirmed unless supported by

  3. Economic Cost of Dengue in Puerto Rico

    Science.gov (United States)

    Halasa, Yara A.; Shepard, Donald S.; Zeng, Wu

    2012-01-01

    Dengue, endemic in Puerto Rico, reached a record high in 2010. To inform policy makers, we derived annual economic cost. We assessed direct and indirect costs of hospitalized and ambulatory dengue illness in 2010 dollars through surveillance data and interviews with 100 laboratory-confirmed dengue patients treated in 2008–2010. We corrected for underreporting by using setting-specific expansion factors. Work absenteeism because of a dengue episode exceeded the absenteeism for an episode of influenza or acute otitis media. From 2002 to 2010, the aggregate annual cost of dengue illness averaged $38.7 million, of which 70% was for adults (age 15+ years). Hospitalized patients accounted for 63% of the cost of dengue illness, and fatal cases represented an additional 17%. Households funded 48% of dengue illness cost, the government funded 24%, insurance funded 22%, and employers funded 7%. Including dengue surveillance and vector control activities, the overall annual cost of dengue was $46.45 million ($12.47 per capita). PMID:22556069

  4. Cells in Dengue Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Sansanee Noisakran

    2010-01-01

    Full Text Available Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS. The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease.

  5. Dengue antibodies in blood donors.

    Science.gov (United States)

    Ribas-Silva, Rejane Cristina; Eid, Andressa Ahmad

    2012-01-01

    Dengue is an urban arbovirus whose etiologic agent is a virus of the genus Flavorius with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. The Campo Mourão region in Brazil is endemic for dengue fever. OBTECTIVE: The aim of this study was to evaluate the presence of IgG and IgM antibodies specific to the four serotypes of dengue in donors of the blood donor service in the city of Campo Mourão. Epidemiological records were evaluated and 4 mL of peripheral blood from 213 blood donors were collected in tubes without anticoagulant. Serum was then obtained and immunochromatographic tests were undertaken (Imuno-Rápido Dengue IgM/IgG(TM)). Individuals involved in the study answered a social and epidemiological questionnaire on data which included age, gender and diagnosis of dengue. Only three (1.4%) of the 213 blood tests were positive for IgG anti-dengue antibodies. No donors with IgM antibody, which identifies acute infection, were identified. The results of the current analysis show that the introduction of quantitative or molecular serological methods to determine the presence of anti-dengue antibodies or the detection of the dengue virus in blood donors in endemic regions should be established so that the quality of blood transfusions is guaranteed.

  6. Proteomic Identification of Dengue Virus Binding Proteins in Aedes aegypti Mosquitoes and Aedes albopictus Cells

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Muñoz

    2013-01-01

    Full Text Available The main vector of dengue in America is the mosquito Aedes aegypti, which is infected by dengue virus (DENV through receptors of midgut epithelial cells. The envelope protein (E of dengue virus binds to receptors present on the host cells through its domain III that has been primarily recognized to bind cell receptors. In order to identify potential receptors, proteins from mosquito midgut tissue and C6/36 cells were purified by affinity using columns with the recombinant E protein domain III (rE-DIII or DENV particles bound covalently to Sepharose 4B to compare and evaluate their performance to bind proteins including putative receptors from female mosquitoes of Ae. aegypti. To determine their identity mass spectrometric analysis of purified proteins separated by polyacrylamide gel electrophoresis was performed. Our results indicate that both viral particles and rE-DIII bound proteins with the same apparent molecular weights of 57 and 67 kDa. In addition, viral particles bound high molecular weight proteins. Purified proteins identified were enolase, beta-adrenergic receptor kinase (beta-ARK, translation elongation factor EF-1 alpha/Tu, and cadherin.

  7. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.

    Directory of Open Access Journals (Sweden)

    Michael J Conway

    2016-09-01

    Full Text Available Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.

  8. Dengue: a new challenge for neurology

    Directory of Open Access Journals (Sweden)

    Marzia Puccioni-Sohler

    2012-11-01

    Full Text Available Dengue infection is a leading cause of illness and death in tropical and subtropical regions of the world. Forty percent of the world’s population currently lives in these areas. The clinical picture resulting from dengue infection can range from relatively minor to catastrophic hemorrhagic fever. Recently, reports have increased of neurological manifestations. Neuropathogenesis seems to be related to direct nervous system viral invasion, autoimmune reaction, metabolic and hemorrhagic disturbance. Neurological manifestations include encephalitis, encephalopathy, meningitis, Guillain-Barré syndrome, myelitis, acute disseminated encephalomyelitis, polyneuropathy, mononeuropathy, and cerebromeningeal hemorrhage. The development of neurological symptoms in patients with positive Immunoglobulin M (IgM dengue serology suggests a means of diagnosing the neurological complications associated with dengue. Viral antigens, specific IgM antibodies, and the intrathecal synthesis of dengue antibodies have been successfully detected in cerebrospinal fluid. However, despite diagnostic advancements, the treatment of neurological dengue is problematic. The launch of a dengue vaccine is expected to be beneficial.

  9. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

    Whitehorn, James; Rodriguez Roche, Rosmari; Guzman, Maria G

    2012-01-01

    Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage...... of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity...... of the responses highlights the variation in clinical practice and lack of an evidence base in this area and underscores the importance of prospective clinical trials to address this key question in the clinical management of patients with dengue....

  10. Clinical predictors of dengue fever co-infected with leptospirosis among patients admitted for dengue fever - a pilot study.

    Science.gov (United States)

    Suppiah, Jeyanthi; Chan, Shie-Yien; Ng, Min-Wern; Khaw, Yam-Sim; Ching, Siew-Mooi; Mat-Nor, Lailatul Akmar; Ahmad-Najimudin, Naematul Ain; Chee, Hui-Yee

    2017-06-28

    Dengue and leptospirosis infections are currently two major endemics in Malaysia. Owing to the overlapping clinical symptoms between both the diseases, frequent misdiagnosis and confusion of treatment occurs. As a solution, the present work initiated a pilot study to investigate the incidence related to co-infection of leptospirosis among dengue patients. This enables the identification of more parameters to predict the occurrence of co-infection. Two hundred sixty eight serum specimens collected from patients that were diagnosed for dengue fever were confirmed for dengue virus serotyping by real-time polymerase chain reaction. Clinical, laboratory and demographic data were extracted from the hospital database to identify patients with confirmed leptospirosis infection among the dengue patients. Thus, frequency of co-infection was calculated and association of the dataset with dengue-leptospirosis co-infection was statistically determined. The frequency of dengue co-infection with leptospirosis was 4.1%. Male has higher preponderance of developing the co-infection and end result of shock as clinical symptom is more likely present among co-infected cases. It is also noteworthy that, DENV 1 is the common dengue serotype among all cases identified as dengue-leptospirosis co-infection in this study. The increasing incidence of leptospirosis among dengue infected patients has posed the need to precisely identify the presence of co-infection for the betterment of treatment without mistakenly ruling out either one of them. Thus, anticipating the possible clinical symptoms and laboratory results of dengue-leptospirosis co-infection is essential.

  11. Acute disseminated encephalomyelitis in dengue viral infection.

    Science.gov (United States)

    Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

    2017-09-01

    Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Performance Evaluation of Commercial Dengue Diagnostic Tests for Early Detection of Dengue in Clinical Samples

    Directory of Open Access Journals (Sweden)

    Tuan Nur Akmalina Mat Jusoh

    2017-01-01

    Full Text Available The shattering rise in dengue virus infections globally has created a need for an accurate and validated rapid diagnostic test for this virus. Rapid diagnostic test (RDT and reverse transcription-polymerase chain reaction (RT-PCR diagnostic detection are useful tools for diagnosis of early dengue infection. We prospectively evaluated the diagnostic performance of nonstructural 1 (NS1 RDT and real-time RT-PCR diagnostic kits in 86 patient serum samples. Thirty-six samples were positive for dengue NS1 antigen while the remaining 50 were negative when tested with enzyme-linked immunosorbent assay (ELISA. Commercially available RDTs for NS1 detection, RTK ProDetect™, and SD Bioline showed high sensitivity of 94% and 89%, respectively, compared with ELISA. GenoAmp® Trioplex Real-Time RT-PCR and RealStar® Dengue RT-PCR tests presented a comparable kappa agreement with 0.722. The result obtained from GenoAmp® Real-Time RT-PCR Dengue test showed that 14 samples harbored dengue virus type 1 (DENV-1, 8 samples harbored DENV-2, 2 samples harbored DENV-3, and 1 sample harbored DENV-4. 1 sample had a double infection with DENV-1 and DENV-2. The NS1 RDTs and real-time RT-PCR tests were found to be a useful diagnostic for early and rapid diagnosis of acute dengue and an excellent surveillance tool in our battle against dengue.

  13. Chloroquine use improves dengue-related symptoms

    Directory of Open Access Journals (Sweden)

    Marcos Carvalho Borges

    2013-08-01

    Full Text Available Dengue is the most important arboviral disease in the world. As chloroquine, an antimalarial agent, has shown some antiviral effects, this study evaluated its effect in patients with dengue. A randomised, double-blind study was performed by administering chloroquine or placebo for three days to 129 patients with dengue-related symptoms. Of these patients, 37 were confirmed as having dengue and completed the study; in total, 19 dengue patients received chloroquine and 18 received placebo. There was no significant difference in the duration of the disease or the degree and days of fever. However, 12 patients (63% with confirmed dengue reported a substantial decrease in pain intensity and a great improvement in their ability to perform daily activities (p = 0.0004 while on the medication and the symptoms returned immediately after these patients stopped taking the medication. The same effect was not observed in patients with diseases other than dengue. Therefore, this study shows that patients with dengue treated with chloroquine had an improvement in their quality of life and were able to resume their daily activities. However, as chloroquine did not alter the duration of the disease or the intensity and days of fever, further studies are necessary to confirm the clinical effects and to assess the side effects of chloroquine in dengue patients.

  14. Dengue perinatal

    Directory of Open Access Journals (Sweden)

    Doris Martha Salgado

    2013-08-01

    Full Text Available El dengue es en la actualidad la enfermedad viral más relevante de transmisión vectorial hiperendémica en las Américas. El incremento en el número de casos se ha relacionado con la aparición de dengue durante la gestación y en el periodo neonatal. De acuerdo con la edad de gestación en la que ocurra la infección, podrían presentarse manifestaciones en el feto, como aborto, y en los pacientes a término,dengue neonatal. En este artículo se presenta una reseña de los casos reportados a nivel mundial, y especialmente en las Américas, así como aspectos fisiopatogénicos de la enfermedad.   doi: http://dx.doi.org/10.7705/biomedica.v33i0.1449

  15. Recent Advances in Dengue: Relevance to Puerto Rico

    Science.gov (United States)

    Noyd, David H.; Sharp, Tyler M.

    2015-01-01

    Dengue represents an increasingly important public health challenge in Puerto Rico, with recent epidemics in 2007, 2010, and 2012–2013. Although recent advances in dengue vaccine development offer hope for primary prevention, the role of health professionals in the diagnosis and management of dengue patients is paramount. Case definitions for dengue, dengue with warning signs, and severe dengue provide a framework to guide clinical decision-making. Furthermore, the differentiation between dengue and other acute febrile illnesses, such as leptospirosis and chikungunya, is necessary for the appropriate diagnosis and management of cases. An understanding of dengue epidemiology and surveillance in Puerto Rico provides context for clinicians in epidemic and non-epidemic periods. This review aims to improve health professionals’ ability to diagnose dengue, and as highlight the relevance of recent advances in dengue prevention and management in Puerto Rico. PMID:26061055

  16. Recent advances in understanding dengue

    Science.gov (United States)

    Yacoub, Sophie; Mongkolsapaya, Juthathip; Screaton, Gavin

    2016-01-01

    Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research. PMID:26918159

  17. Recent advances in understanding dengue.

    Science.gov (United States)

    Yacoub, Sophie; Mongkolsapaya, Juthathip; Screaton, Gavin

    2016-01-01

    Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research.

  18. Dengue viruses – an overview

    Directory of Open Access Journals (Sweden)

    Anne Tuiskunen Bäck

    2013-08-01

    Full Text Available Dengue viruses (DENVs cause the most common arthropod-borne viral disease in man with 50–100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF, and dengue shock syndrome (DSS are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence.

  19. Dengue fever: diagnosis and treatment.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2010-07-01

    Dengue fever is a common tropical infection. This acute febrile illness can be a deadly infection in cases of severe manifestation, causing dengue hemorrhagic shock. In this brief article, I will summarize and discuss the diagnosis and treatment of this disease. For diagnosis of dengue, most tropical doctors make use of presumptive diagnosis; however, the definite diagnosis should be based on immunodiagnosis or viral study. Focusing on treatment, symptomatic and supportive treatment is the main therapeutic approach. The role of antiviral drugs in the treatment of dengue fever has been limited, but is currently widely studied.

  20. Serodiagnosis of dengue infection using rapid immunochromatography test in patients with probable dengue infection.

    Science.gov (United States)

    Kidwai, Aneela Altaf; Jamal, Qaiser; Saher; Mehrunnisa; Farooqi, Faiz-ur-rehman; Saleem-Ullah

    2010-11-01

    To determine the frequency of seropositive dengue infection using rapid immunochromatographic assay in patients with probable dengue infection as per WHO criteria. A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immunochromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results.

  1. Dengue: an arthropod-borne disease of global importance.

    NARCIS (Netherlands)

    Mairuhu, A.T.; Wagenaar, J.; Brandjes, D.P.; Gorp, E. van

    2004-01-01

    Dengue viruses cause a variable spectrum of disease that ranges from an undifferentiated fever to dengue fever to the potentially fatal dengue shock syndrome. Due to the increased incidence and geographical distribution of dengue in the last 50 years, dengue is becoming increasingly recognised as

  2. Ongoing dengue epidemic - Angola, June 2013.

    Science.gov (United States)

    2013-06-21

    On April 1, 2013, the Public Health Directorate of Angola announced that six cases of dengue had been reported to the Ministry of Health of Angola (MHA). As of May 31, a total of 517 suspected dengue cases had been reported and tested for dengue with a rapid diagnostic test (RDT). A total of 313 (60.5%) specimens tested positive for dengue, including one from a patient who died. All suspected cases were reported from Luanda Province, except for two from Malanje Province. Confirmatory diagnostic testing of 49 specimens (43 RDT-positive and six RDT-negative) at the CDC Dengue Branch confirmed dengue virus (DENV) infection in 100% of the RDT-positive specimens and 50% of the RDT-negative specimens. Only DENV-1 was detected by molecular diagnostic testing. Phylogenetic analysis indicated this virus has been circulating in the region since at least 1968, strongly suggesting that dengue is endemic in Angola. Health-care professionals throughout Angola should be aware of the ongoing epidemic, the recommended practices for clinical management of dengue patients, and the need to report cases to MHA. Persons in Angola should seek medical care for acute febrile illness to reduce the risk for developing complications. Laboratory-confirmed dengue also has been reported from seven countries on four continents among persons who had recently traveled to Luanda, including 79 persons from Portugal. Angola is the third of four African countries to report a dengue outbreak in 2013. Persons returning from Africa with acute febrile illness should seek medical care, including testing for DENV infection, and suspected cases should be reported to public health authorities.

  3. Dengue fever: a Wikipedia clinical review

    OpenAIRE

    Heilman, James M; Wolff, Jacob De; Beards, Graham M; Basden, Brian J

    2014-01-01

    Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treat...

  4. Dengue, Zika y Chikungunya

    OpenAIRE

    Kantor, Isabel N

    2016-01-01

    Los responsables de la actual pandemia de Chikungunya (alfavirus), dengue y Zika (flavivirus) son virus trasmitidos por artrópodos, arbovirus. Su importancia aumentó en las Américas en los últimos 20 años. Los vectores principales son Aedes aegypti y A. albopictus. La infección por dengue provee inmunidad duradera al serotipo específico y temporaria a otros tres. La posterior infección por otro serotipo determina mayor gravedad. Existe una vacuna contra dengue registrada, Dengvaxia (Sanofi Pa...

  5. Dengue virus transovarial transmission by Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Monica Dwi Hartanti

    2016-02-01

    Full Text Available Dengue is a disease that is caused by dengue virus and transmitted to humans through the bite of infected Aedes mosquitoes, especially Aedes aegypti. The disease is hyper-endemic in Southeast Asia, where a more severe form, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS, is a major public health concern. The purpose of the present study was to find evidence of dengue virus transovarial transmision in local vectors in Jakarta. Fifteen Aedes larvae were collected in 2009 from two areas in Tebet subdistrict in South Jakarta, namely one area with the highest and one with the lowest DHF prevalence. All mosquitoes were reared inside two cages in the laboratory, eight mosquitoes in one cage and seven mosquitoes in another cage and given only sucrose solution as their food. The results showed that 20% of the mosquitoes were positive for dengue virus. Dengue virus detection with an immunohistochemical method demonstrated the occurrence of transovarial transmission in local DHF vectors in Tebet subdistrict. Transovarial dengue infection in Ae.aegypti larvae appeared to maintain or enhance epidemics. Further research is needed to investigate the relation of dengue virus transovarial transmission with DHF endemicity in Jakarta.

  6. Dengue virus transovarial transmission by Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Monica Dwi Hartanti

    2010-08-01

    Full Text Available Dengue is a disease that is caused by dengue virus and transmitted to humans through the bite of infected Aedes mosquitoes, especially Aedes aegypti. The disease is hyper-endemic in Southeast Asia, where a more severe form, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS, is a major public health concern. The purpose of the present study was to find evidence of dengue virus transovarial transmision in local vectors in Jakarta. Fifteen Aedes larvae were collected in 2009 from two areas in Tebet subdistrict in South Jakarta, namely one area with the highest and one with the lowest DHF prevalence. All mosquitoes were reared inside two cages in the laboratory, eight mosquitoes in one cage and seven mosquitoes in another cage and given only sucrose solution as their food. The results showed that 20% of the mosquitoes were positive for dengue virus. Dengue virus detection with an immunohistochemical method demonstrated the occurrence of transovarial transmission in local DHF vectors in Tebet subdistrict. Transovarial dengue infection in Ae.aegypti larvae appeared to maintain or enhance epidemics. Further research is needed to investigate the relation of dengue virus transovarial transmission with DHF endemicity in Jakarta.

  7. Appendicular perforation in dengue fever: our experience

    Directory of Open Access Journals (Sweden)

    Gunjan Desai

    2014-09-01

    Full Text Available Dengue viral infections have become one of major emerging infectious diseases in the tropics. Acute abdomen occurring in dengue viral infection is not uncommon. The spectrums of acute surgical emergencies which raise suspicion of an abdominal catastrophe in patients presenting with dengue fever include acute pancreatitis, acute acalculous cholecystitis, non-specific peritonitis and very rarely acute appendicitis. The presence of low white cell count and platelet count can raise suspicion of a diagnosis of dengue in a patient presenting with acute abdominal pain, during a dengue epidemic. We herein report three patients with dengue fever who had appendicular perforation during the course of their viral fever.

  8. Treatment of dengue fever

    Directory of Open Access Journals (Sweden)

    Rajapakse S

    2012-07-01

    Full Text Available Senaka Rajapakse,1,2 Chaturaka Rodrigo,1 Anoja Rajapakse31Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka; 2Lincoln County Hospital, United Lincolnshire NHS Trust, Lincoln, UK; 3Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Mansfield, UKAbstract: The endemic area for dengue fever extends over 60 countries, and approximately 2.5 billion people are at risk of infection. The incidence of dengue has multiplied many times over the last five decades at an alarming rate. In the endemic areas, waves of infection occur in epidemics, with thousands of individuals affected, creating a huge burden on the limited resources of a country's health care system. While the illness passes off as a simple febrile episode in many, a few have a severe illness marked by hypovolemic shock and bleeding. Iatrogenic fluid overload in the management may further complicate the picture. In this severe form dengue can be fatal. Tackling the burden of dengue is impeded by several issues, including a lack of understanding about the exact pathophysiology of the infection, inability to successfully control the vector population, lack of specific therapy against the virus, and the technical difficulties in developing a vaccine. This review provides an overview on the epidemiology, natural history, management strategies, and future directions for research on dengue, including the potential for development of a vaccine.Keywords: dengue, treatment, fluid resuscitation

  9. Roles for Endothelial Cells in Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Nadine A. Dalrymple

    2012-01-01

    Full Text Available Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease.

  10. Current management of severe dengue infection.

    Science.gov (United States)

    Lee, Tau Hong; Lee, Linda Kay; Lye, David Chien; Leo, Yee Sin

    2017-01-01

    Traditionally a disease mainly affecting the pediatric population, dengue burden has increased significantly in recent decades and adults with severe disease may become more common. There is currently no effective anti-viral agent available for the treatment of dengue and supportive care is the mainstay of management. Areas covered: We present a review of current literature on dengue severity classification systems and the management of severe dengue in adults. In particular, emphasis was placed on organ impairment in dengue and management of elderly individuals with multiple medical problems. Expert commentary: There is an urgent need to search for an effective anti-viral agent to treat infected individuals. The commercial availability of a dengue vaccine in older children has provided optimism in reducing the disease burden but long term efficacy and safety are unknown. The results from phase III trials of two new candidate vaccines are eagerly awaited.

  11. RNAi: antiviral therapy against dengue virus.

    Science.gov (United States)

    Idrees, Sobia; Ashfaq, Usman A

    2013-03-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  12. Cost of Dengue Vector Control Activities in Malaysia

    Science.gov (United States)

    Packierisamy, P. Raviwharmman; Ng, Chiu-Wan; Dahlui, Maznah; Inbaraj, Jonathan; Balan, Venugopalan K.; Halasa, Yara A.; Shepard, Donald S.

    2015-01-01

    Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them. PMID:26416116

  13. [Hepatic alterations in patients with dengue].

    Science.gov (United States)

    Larreal, Yraima; Valero, Nereida; Estévez, Jesús; Reyes, Ivette; Maldonado, Mery; Espina, Luz Marina; Arias, Julia; Meleán, Eddy; Añez, German; Atencio, Ricardo

    2005-06-01

    Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

  14. Dengue virus markers of virulence and pathogenicity

    OpenAIRE

    Rico-Hesse, Rebeca

    2009-01-01

    The increased spread of dengue fever and its more severe form, dengue hemorrhagic fever, have made the study of the mosquito-borne dengue viruses that cause these diseases a public health priority. Little is known about how or why the four different (serotypes 1–4) dengue viruses cause pathology in humans only, and there have been no animal models of disease to date. Therefore, there are no vaccines or antivirals to prevent or treat infection and mortality rates of dengue hemorrhagic fever pa...

  15. Hemophagocytic syndrome in classic dengue fever

    Directory of Open Access Journals (Sweden)

    Sayantan Ray

    2011-01-01

    Full Text Available A 24-year-old previously healthy girl presented with persistent fever, headache, and jaundice. Rapid-test anti-dengue virus IgM antibody was positive but anti-dengue IgG was nonreactive, which is suggestive of primary dengue infection. There was clinical deterioration during empiric antibiotic and symptomatic therapy. Bone marrow examination demonstrated the presence of hemophagocytosis. Diagnosis of dengue fever with virus-associated hemophagocytic syndrome was made according to the diagnostic criteria of the HLH 2004 protocol of the Histiocyte Society. The patient recovered with corticosteroid therapy. A review of literature revealed only a handful of case reports that showed the evidence that this syndrome is caused by dengue virus. Our patient is an interesting case of hemophagocytic syndrome associated with classic dengue fever and contributes an additional case to the existing literature on this topic. This case highlights the need for increased awareness even in infections not typically associated with hemophagocytic syndrome.

  16. Serodiagnosis of dengue infection using rapid immuno chromatography test in patients with probable dengue infection

    International Nuclear Information System (INIS)

    Kidwai, A.A.; Jamal, Q.; Mehrunnisa, S.; Farooqi, F.R.

    2010-01-01

    Objective: To determine the frequency of seropositive dengue infection using rapid immuno chromatographic assay in patients with probable dengue infection as per WHO criteria. Method: A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immuno chromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Result: Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Conclusion: Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results. (author)

  17. Geochemical modelling of the sorption of tetravalent radioelements

    International Nuclear Information System (INIS)

    Bond, K.A.; Tweed, C.J.

    1991-05-01

    The results of an experimental study of the sorption of a range of tetravalent radioelements, plutonium (IV), tin (IV), thorium(IV) and uranium(IV), onto clay at pH8 and pH11 have been successfully simulated using a triple layer sorption model. The model has been incorporated into HARPHRQ, a geochemical program based on PHREEQE. The model has been parameterised using data for sorption onto ferric oxyhydroxide and goethite. The effects of hydroxycarboxylic acids on the sorption process have also been investigated experimentally. It was generally observed that in the presence of 2x10 -3 M gluconate, sorption was reduced by up two orders of magnitude. The model has satisfactorily simulated these lower sorptivities, through assuming competing sorption and complexation reactions. This work, therefore, further confirms the need to take account of such organic materials in safety assessment modelling. (author)

  18. Dengue fever: a Wikipedia clinical review.

    Science.gov (United States)

    Heilman, James M; De Wolff, Jacob; Beards, Graham M; Basden, Brian J

    2014-01-01

    Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treatment of acute dengue fever is supportive, with either oral or intravenous rehydration for mild or moderate disease and use of intravenous fluids and blood transfusion for more severe cases. Along with attempts to eliminate the mosquito vector, work is ongoing to develop a vaccine and medications targeted directly at the virus.

  19. Dengue vaccines: Challenges, development, current status and prospects

    Directory of Open Access Journals (Sweden)

    A Ghosh

    2015-01-01

    Full Text Available Infection with dengue virus (DENV is the most rapidly spreading mosquito-borne viral disease in the world. The clinical spectrum of dengue, caused by any of the four serotypes of DENV, ranges from mild self-limiting dengue fever to severe dengue, in the form dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. Increased rates of hospitalization due to severe dengue, during outbreaks, result in massive economic losses and strained health services. In the absence of specific antiviral therapy, control of transmission of DENV by vector management is the sole method available for decreasing dengue-associated morbidity. Since vector control strategies alone have not been able to satisfactorily achieve reduction in viral transmission, the implementation of a safe, efficacious and cost-effective dengue vaccine as a supplementary measure is a high public health priority. However, the unique and complex immunopathology of dengue has complicated vaccine development. Dengue vaccines have also been challenged by critical issues like lack of animal models for the disease and absence of suitable markers of protective immunity. Although no licensed dengue vaccine is yet available, several vaccine candidates are under phases of development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, subunit vaccines, DNA vaccines and viral-vectored vaccines. Although some vaccine candidates have progressed from animal trials to phase II and III in humans, a number of issues regarding implementation of dengue vaccine in countries like India still need to be addressed. Despite the current limitations, collaborative effects of regulatory bodies like World Health Organization with vaccine manufacturers and policy makers, to facilitate vaccine development and standardize field trials can make a safe and efficacious dengue vaccine a reality in near future.

  20. Challenges in dengue fever in the elderly: atypical presentation and risk of severe dengue and hospital-acquired infection [corrected].

    Directory of Open Access Journals (Sweden)

    Emily K Rowe

    2014-04-01

    Full Text Available BACKGROUND/METHODS: To better understand dengue fever in the elderly, we compared clinical features, World Health Organization (WHO dengue classification and outcomes between adult (<60 and elderly (≥60 dengue patients. We explored the impact of co-morbidity and hospital-acquired infection (HAI on clinical outcomes in the elderly. All patients managed at the Communicable Disease Centre, Singapore, between 2005 and 2008 with positive dengue polymerase chain reaction (PCR or who fulfilled WHO 1997 or 2009 probable dengue criteria with positive dengue IgM were included. RESULTS: Of the 6989 cases, 295 (4.4% were elderly. PCR was positive in 29%. The elderly suffered more severe disease with more dengue haemorrhagic fever (DHF (29.2% vs. 21.4% and severe dengue (SD (20.3% vs. 14.6% (p<0.05. Classic dengue symptoms were more common in the adult group. The elderly were less likely to fulfill WHO 1997 (93.6% vs. 96.4% (p = 0.014, but not WHO 2009 probable dengue (75.3% vs. 71.5%. Time to dengue diagnosis was similar. There was no significant difference in the frequency of warning signs between the two groups, but the elderly were more likely to have hepatomegaly (p = 0.006 and malaise/lethargy (p = 0.033 while the adults had significantly more mucosal bleeding (p<0.001. Intensive care admission occurred in 15 and death in three, with no age difference. Notably, the elderly stayed in hospital longer (median 5 vs. 4 days, and suffered more pneumonia (3.8% vs. 0.7% and urinary infection (1.9% vs. 0.3% (p = 0.003. Predictors of excess length of stay were age (adjusted odds ratio [aOR] 2.01, 95% confidence interval [CI] 1.37-2.88, critical illness (aOR 5.13, 95%CI 2.59-9.75, HAI (aOR 12.06, 95%CI 7.39-19.9, Charlson score (aOR 6.9, 95%CI 2.02-22.56 and severe dengue (DHF/dengue shock syndrome/SD (aOR 2.24, 95%CI 1.83-2.74. CONCLUSION: Elderly dengue patients present atypically and are at higher risk of DHF, SD and HAI. Aside from dengue

  1. Cost of Dengue Vector Control Activities in Malaysia.

    Science.gov (United States)

    Packierisamy, P Raviwharmman; Ng, Chiu-Wan; Dahlui, Maznah; Inbaraj, Jonathan; Balan, Venugopalan K; Halasa, Yara A; Shepard, Donald S

    2015-11-01

    Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them. © The American Society of Tropical Medicine and Hygiene.

  2. Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil.

    Science.gov (United States)

    Ferraz, Fernanda Oliveira; Bomfim, Maria Rosa Quaresma; Totola, Antônio Helvécio; Ávila, Thiago Vinícius; Cisalpino, Daniel; Pessanha, José Eduardo Marques; da Glória de Souza, Danielle; Teixeira Júnior, Antônio Lúcio; Nogueira, Maurício Lacerda; Bruna-Romero, Oscar; Teixeira, Mauro Martins

    2013-09-01

    Dengue is a widely spread arboviral disease in tropical and subtropical regions of the world. Dengue fever presents clinical characteristics similar to other febrile illness. Thus laboratory diagnosis is important for adequate management of the disease. The present study was designed to evaluate the diagnostic performance of real-time PCR and serological methods for dengue in a real epidemic context. Clinical data and blood samples were collected from consecutive patients with suspected dengue who attended a primary health care unit in Belo Horizonte, Brazil. Serologic methods and real-time PCR were performed in serum samples to confirm dengue diagnosis. Among the 181 consecutive patients enrolled in this study with suspected dengue, 146 were considered positive by serological criteria (positive NS1 ELISA and/or anti-dengue IgM ELISA) and 138 were positive by real-time PCR. Clinical criteria were not sufficient for distinguishing between dengue and non-dengue febrile illness. The PCR reaction was pre-optimized using samples from patients with known viral infection. It had similar sensitivity compared to NS1 ELISA (88% and 89%, respectively). We also evaluated three commercial lateral flow immunochromatographic tests for NS1 detection (BIOEASY, BIORAD and PANBIO). All three tests showed high sensitivity (94%, 91% and 81%, respectively) for dengue diagnosis. According to our results it can be suggested that lateral flow tests for NS1 detection are the most feasible methods for early diagnosis of dengue. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Reemergence of Dengue in Southern Texas, 2013

    Science.gov (United States)

    Thomas, Dana L.; Santiago, Gilberto A.; Abeyta, Roman; Hinojosa, Steven; Torres-Velasquez, Brenda; Adam, Jessica K.; Evert, Nicole; Caraballo, Elba; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L.; Smith, Brian; Banicki, Alison; Tomashek, Kay M.; Gaul, Linda

    2016-01-01

    During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico. PMID:27191223

  4. Trends in clinical trials of dengue vaccine

    Directory of Open Access Journals (Sweden)

    Priya Marimuthu

    2016-01-01

    Full Text Available Dengue is one of the most important vector-borne disease and an increasing problem worldwide because of current globalization trends. Roughly, half the world′s population lives in dengue endemic countries, and nearly 100 million people are infected annually with dengue. India has the highest burden of the disease with 34% of the global cases. In the context of an expanding and potentially fatal infectious disease without effective prevention or specific treatment, the public health value of a protective vaccine is clear. There is no licensed dengue vaccine is available still, but several vaccines are under development. Keeping in view the rise in dengue prevalence globally, there is a need to increase clinical drug and vaccine research on dengue. This paper briefly reviews on the development and current status of dengue vaccine to provide information to policymakers, researchers, and public health experts to design and implement appropriate vaccine for prophylactic intervention.

  5. Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.

    Science.gov (United States)

    Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

    2015-01-01

    The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. © 2014 by the Society for Experimental Biology and Medicine.

  6. Dengue Fever: Causes, Complications, and Vaccine Strategies

    Directory of Open Access Journals (Sweden)

    Niyati Khetarpal

    2016-01-01

    Full Text Available Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through female Aedes mosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur’s chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals.

  7. CLINICAL AND LABORATORY PROFILE OF DENGUE FEVER

    Directory of Open Access Journals (Sweden)

    Farhan Fazal

    2015-02-01

    Full Text Available AIM: Dengue is a major health problem in many parts of India and Gulbarga (North Karnataka was previously not a known endemic area f or dengue. Infection with dengue virus can cause a spectrum of three clinical syndromes , classic dengue fever (DF , dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. The present study was undertaken to determine the disease profile of dengue virus infection in hospitalized patients. METHODS AND MATERIAL: One hundred patients admitted in Basaveshwar Teaching and General hospital with fever more than 38.5 degree Celsius and IgM dengue positive were selected. They were followed from the onset of fever to twelve days or till they are recovered according to WHO discharge criteria whichever is earlier. They underwent relevant investigations to identify specific organ dysfunction and categorize them into the spectrum of Dengue fever in accordance to W HO criteria . RESULTS: Out of 100 cases in this study 70 cases belongs to DF , 23 cases to DHF and 7 cases to DSS based on WHO criteria. All the cases had fever (100%. Other common symptoms noted were myalgia (61% , joint pain (54% , headache (66% , vomitin g (55% , pain abdomen (48% , rash (41% , hepatomegaly (20% , bleeding (21% and shock (8%. Hess test was positive in 24% patients. Low platelet count of less than 100 , 000/cu mm according to WHO criteria was present in 73% patients. Deranged liver functio n test and renal parameters were seen in 26 and 8 patients respectively . Mortality documented was 7 patients due to delayed presentation. The average duration of hospital stay was 4.65 days. CONCLUSION: Dengue fever was a more common manifestation than DHF or DSS. During aepidemic , dengue should be strongly considered on the differential diagnosis of any patient with fever. The treatment of dengue is mainly fluid management and supportive. Early recognition and management of alarm symptoms is the key to bet ter outcome

  8. Dengue hemorrágico en el niño Dengue hemorrágica na criança

    Directory of Open Access Journals (Sweden)

    Carlos Dotres Martinez

    1987-06-01

    Full Text Available Foi realizada uma revisão completa da Dengue Hemorrágica, doença infecciosa viral aguda e potencialmente, grave, transmitida por mosquito, que, em 1981, causou a morte de 158 pessoas durante uma epidemia em Cuba, sendo 101 menores de 15 anos. A Dengue, em sua forma clássica (benigna, foi primeiramente referida em 1823, porém,no ano de 1953, em Manila, Filipinas, se registrou uma nova apresentação da doença, caracterizada por manifestações hemorrágicas, choque e alta mortalidade que se denominou Febre Hemorrágica Dengue e Síndrome de Choque por Dengue (FHD/SSD. Sua patogenia é apresentada, discutindo-se também a possibilidade de repetição do fenômeno nas Américas.A thorough revision on hemorragic dengue fever is presented. Dengue, an acute mosquito-borne infectious disease has occurred in epidemic form in Cuba 1981, causing death of 158 persons. The disease in its classical form was first reported in 1823 but in 1953 a new presentation characterized by hemorrhagic manifestations, shock and a high mortality was observed in Manila, Phillipines. This form was called Hemorrhagic Dengue Fever and Dengue Shock Syndrome (HDF/DSS. Its pathogenesis can be explained by two different theories: it could be a primary infection or a hipersensibility reaction depending on a previous infection.

  9. Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study

    OpenAIRE

    Mallhi, Tauqeer Hussain; Khan, Amer Hayat; Adnan, Azreen Syazril; Sarriff, Azmi; Khan, Yusra Habib; Jummaat, Fauziah

    2015-01-01

    Background The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. Methods A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period o...

  10. Spatiotemporal dynamics and epistatic interaction sites in dengue virus type 1: a comprehensive sequence-based analysis.

    Directory of Open Access Journals (Sweden)

    Pei-Yu Chu

    Full Text Available The continuing threat of dengue fever necessitates a comprehensive characterisation of its epidemiological trends. Phylogenetic and recombination events were reconstructed based on 100 worldwide dengue virus (DENV type 1 genome sequences with an outgroup (prototypes of DENV2-4. The phylodynamic characteristics and site-specific variation were then analysed using data without the outgroup. Five genotypes (GI-GV and a ladder-like structure with short terminal branch topology were observed in this study. Apparently, the transmission of DENV1 was geographically random before gradual localising with human activity as GI-GIII in South Asia, GIV in the South Pacific, and GV in the Americas. Genotypes IV and V have recently shown higher population densities compared to older genotypes. All codon regions and all tree branches were skewed toward a negative selection, which indicated that their variation was restricted by protein function. Notably, multi-epistatic interaction sites were found in both PrM 221 and NS3 1730. Recombination events accumulated in regions E, NS3-NS4A, and particularly in region NS5. The estimated coevolution pattern also highlights the need for further study of the biological role of protein PrM 221 and NS3 1730. The recent transmission of emergent GV sublineages into Central America and Europe mandates closely monitoring of genotype interaction and succession.

  11. Social justice, climate change, and dengue.

    Science.gov (United States)

    Chang, Aileen Y; Fuller, Douglas O; Carrasquillo, Olveen; Beier, John C

    2014-06-14

    Climate change should be viewed fundamentally as an issue of global justice. Understanding the complex interplay of climatic and socioeconomic trends is imperative to protect human health and lessen the burden of diseases such as dengue fever. Dengue fever is rapidly expanding globally. Temperature, rainfall, and frequency of natural disasters, as well as non-climatic trends involving population growth and migration, urbanization, and international trade and travel, are expected to increase the prevalence of mosquito breeding sites, mosquito survival, the speed of mosquito reproduction, the speed of viral incubation, the distribution of dengue virus and its vectors, human migration patterns towards urban areas, and displacement after natural disasters. The burden of dengue disproportionately affects the poor due to increased environmental risk and decreased health care. Mobilization of social institutions is needed to improve the structural inequalities of poverty that predispose the poor to increased dengue fever infection and worse outcomes. This paper reviews the link between dengue and climatic factors as a starting point to developing a comprehensive understanding of how climate change affects dengue risk and how institutions can address the issues of social justice and dengue outbreaks that increasingly affect vulnerable urban populations. Copyright © 2014 Chang, Fuller, Carrasquillo, Beier. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

  12. Metformin Use and Severe Dengue in Diabetic Adults.

    Science.gov (United States)

    Htun, Htet Lin; Yeo, Tsin Wen; Tam, Clarence C; Pang, Junxiong; Leo, Yee Sin; Lye, David C

    2018-02-20

    Diabetes mellitus is a risk factor for severe dengue in adults, but few studies have examined the association between metformin use and disease severity in dengue. In addition to its effect on glucose control, metformin has been associated with pleiotropic properties in preclinical studies. Using a cohort of laboratory-confirmed adult (≥21 years) dengue patients with diabetes mellitus admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study involving 131 (58.7%) metformin users and 92 (41.3%) non-users. Dengue severity was categorized as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in World Health Organization (WHO) 1997 criteria and severe dengue (SD) in WHO 2009 criteria. Multivariable Poisson regression with robust error variance was used to estimate risk ratio (RR). Compared with non-use, metformin use was associated with a decreased risk of developing severe dengue (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI]: 0.37-0.98, P = 0.04). Additionally, there was an inverse dose-response relationship (aRR = 0.69, 95% CI: 0.49-0.98, P = 0.04) with dengue severity as classified by WHO 2009 criteria. Use of metformin, however, was not associated with dengue severity based on WHO 1997 criteria; and no dose-response relationship was noted. Our results suggest metformin use could attenuate disease severity in dengue-infected diabetes mellitus individuals.

  13. PATHOGENESIS OF HEMORRHAGIC DUE TO DENGUE VIRUS

    Directory of Open Access Journals (Sweden)

    Arief Suseno

    2015-01-01

    Full Text Available Dengue is a viral disease that is mediated by a mosquito, which causes morbidity and mortality. Viruses can increase vascular permeability which can lead to hemorrhagic diathesis or disseminated intravascular coagulation (DIC known as dengue hemorrhagic fever (DHF. In Indonesia, dengue hemorrhagic fever (DHF are caused by dengue virus infection which was found to be endemic accompanied by an explosion of extraordinary events that appear at various specified period. The diagnosis of dengue is determined based on the criteria of the World Health Organization (WHO, 1999, which are sudden high fever accompanied by a marked tendency to hemorrhage positive tourniquet test, petechiae, ecchymosis, purpura, mucosal hemorrhagic, hematemesis or melena and thrombocytopenia. The problem that still exists today is the mechanism of thrombocytopenia in patients with varying degrees of dengue involving levels of vWF (von Willebrand factor and prostaglandin I2 (PGI2 can not be explained. The mechanism of hemorrhagic in dengue virus infections acquired as a result of thrombocytopenia, platelet disfunction decreased coagulation factors, vasculopathy with endothelial injury and disseminated intravascular coagulation (DIC.

  14. A PATIENT DENGUE HEMORRHAGIC FEVER WITH SPASMS

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    Ulfa Kholili

    2014-09-01

    Full Text Available Indonesia is one of the countries with the high endemic of Dengue viral infection followed by Thailand, Myanmar, India and Srilanka. For more 10-15 years, Dengue Viral Infection/DHF has become a cause of patient who should be hospitalized and was the first cause of death children in south easthern Asia.1,2 Batavia was the first city of Indonesia found Dengue Viral infection which had been written in journal by David Bylon in the 1779. Encephalopathy of dengue (ED is one unusually complication of dengue viral infection which had been characterized by aberration the arrangement of nerves central (CNS. This paper want to describe of a young teenage with suffer from DHF and seizure. Beside it, pleural effusion and cerebral edema had been found. Seizure most likely due to dengue encephalopathy associated with cerebral edema and was supported by positive IgG and IgM anti dengue. Corticosteroid was given to improve cerebral edema. By good management as long as admission, she was discharged from hospital with a good condition.

  15. Transmission spectroscopy of dengue viral infection

    International Nuclear Information System (INIS)

    Firdous, S; Ahmed, M; Rehman, A; Nawaz, M; Anwar, S; Murtaza, S

    2012-01-01

    We presented the rapid diagnostic test for dengue infection based on light spectrum of human blood. The transmission spectra of dengue infected whole blood samples have been recorded in ultra violet to near infrared range (400 – 800 nm) of about 30 conformed infected patients and compared to normal blood samples. Transmission spectra of dengue infected blood illustrate a strong band from 400 – 600 nm with prominant peaks at 540 and 580 nm, where is in case of normal blood below 600 nm, total absorption has been observed. These prominent peaks from 400 – 600 nm are characteristics of cells damage and dangue virus antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) produced against dengue antigen. The presented diagnostic method is non invasive, cost effective, easy and fast screening technique for dengue infected patients

  16. Epidemic dengue and dengue hemorrhagic fever at the Texas-Mexico border: results of a household-based seroepidemiologic survey, December 2005.

    Science.gov (United States)

    Ramos, Mary M; Mohammed, Hamish; Zielinski-Gutierrez, Emily; Hayden, Mary H; Lopez, Jose Luis Robles; Fournier, Marta; Trujillo, Alfredo Rodríguez; Burton, Roy; Brunkard, Joan M; Anaya-Lopez, Luis; Banicki, Allison Abell; Morales, Pablo Kuri; Smith, Brian; Muñoz, Jorge L; Waterman, Stephen H

    2008-03-01

    A dengue-2 epidemic causing dengue hemorrhagic fever (DHF) occurred in the contiguous border cities of Matamoros, Tamaulipas (Mexico), and Brownsville, TX, in 2005. In December, we conducted a household-based epidemiologic survey to determine the incidence and seroprevalence of dengue infection among Matamoros and Brownsville residents and to identify risk factors associated with infection. Antibodies to dengue were measured in 273 individuals. The estimated incidence of recent dengue infection was 32% and 4% among Matamoros and Brownsville participants, respectively. The estimated prevalence of past dengue infection was 77% and 39% among Matamoros and Brownsville participants, respectively. The Breteau index was 28 in Matamoros and 16 in Brownsville, reflecting an abundant winter population of Aedes mosquitoes. Discarded waste tires and buckets were the two largest categories of infested containers found in both cities. Our results underscore the risk for epidemic dengue and DHF in the Texas-Mexico border region.

  17. Mediational effects of self-efficacy dimensions in the relationship between knowledge of dengue and dengue preventive behaviour with respect to control of dengue outbreaks: a structural equation model of a cross-sectional survey.

    Directory of Open Access Journals (Sweden)

    Affendi Isa

    Full Text Available Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour.We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ(2 = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963. Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours.To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy.

  18. Penentuan Serotipe Virus Dengue dan Gambaran Manifestasi Klinis serta Hematologi Rutin pada Infeksi Virus Dengue

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    Basti Andriyoko

    2012-12-01

    Full Text Available All DENV serotypes can cause a spectrum of disease from dengue fever (DF to dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. It is difficult to differentiate clinical characteristicand hematologic result for each serotype. Aim of this study were to determine dengue serotype and describe clinical manifestation of DF, DHF, DSS and routine hematologic results, i.e.haemoglobin, hematocrit, leukocyte, and thrombocyte in each serotype. This study was conducted at Dr. Hasan Sadikin Hospital Bandung from March 2010 until July 2011. Subjects were dengue patients aged >14 years with a history of fever <5 days. Blood samples were taken for serotype determination by reverse transcription polymerase chain reaction (RT-PCR followed by semi-nested PCR. Clinical manifestation data and haematologic result were obtained from medical records. This was a descriptive study. Seventy five patients were included in this study. Dengue serotype can be detected in 27 (36% samples with DENV-3 (13 were dominating followed by DENV-2 (8, DENV-4 (4, and DENV-1 (2. DHF was mainly found in DENV-3. DENV-2 gavethe highest decrease in hemoglobin, highest percentage increase in haematocrit, lowest leukocyte, and lowest thrombocyte. In conclusion, all 4 serotypes are found in RSUP Dr. Hasan Sadikin Hospital Bandung with DENV-3 domination. DHF is mainly caused by DENV-3.

  19. Current perspectives on the spread of dengue in India

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    Gupta E

    2014-12-01

    Full Text Available Ekta Gupta, Neha Ballani Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, IndiaAbstract: Dengue fever (DF and dengue hemorrhagic fever (DHF are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with DHF, mainly in Southeast Asia. Dengue in India has dramatically expanded over the last few decades, with rapidly changing epidemiology. The first major DHF outbreak in the entire nation occurred in 1996 by dengue virus serotype 2, and after a gap of almost a decade, the country faced yet another DF outbreak in the year 2003 by dengue virus serotype 3. A dramatic increase in the number and frequency of outbreaks followed, and, at present, in most of the states of India, dengue is almost endemic. At present, all the four serotypes are seen in circulation, but the predominant serotype keeps changing. Despite this trend, surveillance, reporting, and diagnosis of dengue remain largely passive in India. More active community-based epidemiological studies with intensive vector control and initiatives for dengue vaccine development should be geared up to control the spread of dengue in India. We review here the factors that may have contributed to the changing epidemiology of dengue in India.Keywords: dengue, epidemiology, India, pathogenesis, vaccine

  20. Facing dengue fever - our first experience

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    Cvjetković Dejan

    2017-01-01

    Full Text Available Introduction. Dengue fever is a mosquito-borne disease caused by dengue virus, endemic in tropical and subtropical regions, where it is mostly imported from. The most common clinical form is classic dengue fever. We presented the first dengue case microbiologically confirmed in Serbia. Case report. A 34-year-old male got classic dengue fever after arrival from Cuba. The disease occurred suddenly with fever, myalgias, skin rash, hepatosplenomegaly, cytopenia, abnormal aminotransferase and creatine kinase levels. The diagnosis was confirmed with virological diagnostic methods. Significant leukopenia and thrombocytopenia as well as elevation of serum creatine kinase activity were recorded from the very beginning of hospitalization, but were gradually normalized. The whole duration of hospitalization was accompanied by laboratory signs of liver lesion. The disease had favourable outcome. At hospital discharge, the patient was afebrile, asymptomatic, with discrete erythematous rash on torso and arms, normal hemathological values and creatine kinase level and moderately elevated alanine-aminotransferase level. Conclusion. Considering global climate changes and growing international traffic, our health care service needs to be ready for possible massive outbreaks of dengue and other tropical infectious diseases in forthcoming years.

  1. Seropositivity of Dengue Antibodies during Pregnancy

    Directory of Open Access Journals (Sweden)

    Nor Azlin Mohamed Ismail

    2014-01-01

    Full Text Available Purpose. Malaysia a dengue endemic country with dengue infections in pregnancy on the rise. The present study was aimed at determining dengue seroprevalence (IgG or IgM during pregnancy and its neonatal transmission in dengue seropositive women. Methods. Maternal with paired cord blood samples were tested for dengue antibodies (IgG and IgM using an enzyme-linked immunosorbent assay (ELISA. Maternal age, parity, occupation, ethnic group, and gestational age were recorded. Data on neonatal Apgar score and admissions to the Neonatal Intensive Care Unit (NICU were analyzed. Results. Out of 358 women recruited, about 128 (35.8% patients were seropositive. Twelve patients (3.4% had recent infections (IgM positive and another 116 women (32.4% were with past infections (IgG positive. All babies born to seropositive mothers had positive IgG paired cord blood; however, no IgM seropositivity was observed. All neonates had good Apgar scores and did not require NICU admission. Conclusion. In this study, 35.8% pregnant women were found to be dengue seropositive. However, transplacental transfer of IgG antibodies had no detrimental effect on the neonatal outcomes.

  2. Mediational Effects of Self-Efficacy Dimensions in the Relationship between Knowledge of Dengue and Dengue Preventive Behaviour with Respect to Control of Dengue Outbreaks: A Structural Equation Model of a Cross-Sectional Survey

    Science.gov (United States)

    Isa, Affendi; Loke, Yoon K.; Smith, Jane R.; Papageorgiou, Alexia; Hunter, Paul R.

    2013-01-01

    Background Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour. Methods and Findings We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ2 = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours. Conclusions To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy. PMID:24086777

  3. Dengue in Grenada El dengue en el país de Granada

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    André Panagos

    2005-04-01

    Full Text Available OBJECTIVES: Dengue fever is endemic in the country of Grenada and is grossly underreported as a source of morbidity. The goal of this study was to assess the status of dengue fever in a representative community in Grenada. METHODS: Surveys were conducted in the Mont Tout/Grand Anse Valley area in the parish of St. George's from March to June 1996. The objectives of the survey were to: (1 to assess the knowledge, attitudes, and practices (KAP of residents; (2 to determine the presence of larval and adult Aedes aegypti and their potential breeding sites; and (3 to identify the seroprevalence of specific immunoglobulin G (IgG dengue antibodies in the local population. RESULTS: Out of the 102 respondents to the KAP survey, 100 of them (98% reported never having had dengue fever. Of the 75 persons who agreed to have blood samples taken, 70 of them (93% (95% confidence interval = 85.1%-97.8% tested positive with the IgG enzyme-linked immunosorbent assay, indicating past exposure. In terms of water storage, 98 of 102 respondents (96% stored fresh water in containers. The vector survey found 57 of the 102 households (56% had Ae. aegypti larvae in water containers on their property, and 94 of 102 dwellings (92% had adult Ae. aegypti mosquitoes indoors. CONCLUSIONS: Although many people were familiar with dengue fever and mosquitoes, the 1996 survey found that their knowledge of the important relationships among mosquitoes, human behavior, and disease transmission was incomplete. Since 1996, continued education efforts have been made in the public school system and with national public health campaigns, yet little effort has been specifically targeted towards our study community. These data suggest Grenada has a need for continued community education that addresses dengue fever transmission and Ae. aegypti reduction.OBJETIVOS: La fiebre del dengue es endémica en el país caribeño de Granada y es grande su subnotificación como fuente de morbilidad. El

  4. Dengue and dengue haemorrhagic fever: Indian perspective

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    mainly in children (Halstead 2002, 2007; Chaturvedi and. Shrivastava 2004). Dengue ... of molecular epidemiology, immunopathology and vaccine development. Selected work done in ..... Only the Indian initiative in this field is presented here.

  5. Epidemiology of dengue: past, present and future prospects

    Directory of Open Access Journals (Sweden)

    Murray NE

    2013-08-01

    Full Text Available Natasha Evelyn Anne Murray,1,2 Mikkel B Quam,1 Annelies Wilder-Smith1,31Institute of Public Health, University of Heidelberg, Heidelberg, Germany; 2Population Health, Waikato District Health Board, Hamilton, New Zealand; 3Lee Kong Chian School of Medicine, Nanyang Technological University, SingaporeAbstract: Dengue is currently regarded globally as the most important mosquito-borne viral disease. A history of symptoms compatible with dengue can be traced back to the Chin Dynasty of 265–420 AD. The virus and its vectors have now become widely distributed throughout tropical and subtropical regions of the world, particularly over the last half-century. Significant geographic expansion has been coupled with rapid increases in incident cases, epidemics, and hyperendemicity, leading to the more severe forms of dengue. Transmission of dengue is now present in every World Health Organization (WHO region of the world and more than 125 countries are known to be dengue endemic. The true impact of dengue globally is difficult to ascertain due to factors such as inadequate disease surveillance, misdiagnosis, and low levels of reporting. Currently available data likely grossly underestimates the social, economic, and disease burden. Estimates of the global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. The expansion of dengue is expected to increase due to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement and also viral evolution. No vaccine or specific antiviral therapy currently exists to address the growing threat of dengue. Prompt case detection and appropriate clinical management can reduce the mortality from severe dengue. Effective vector control is the mainstay of dengue prevention and control. Surveillance and improved reporting of dengue

  6. FEVER AS INDICATOR TO SECONDARY INFECTION IN DENGUE VIRAL INFECTION

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    Soegeng Soegijanto

    2018-04-01

    Full Text Available Dengue Virus Infections are distributed in tropical and sub-tropical regions and transmitted by the mosquitoes such as Aedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome or dengue and severe dengue classified by World Health Organization. Beside it concurrent infection virus salmonella had been found some cases who showed fever more than 7 days. Concurrent infection with two agents can result in an illness having overlapping symptoms creating a diagnostic dilemma for treating physician, such as dengue fever with typhoid fever. The aim of this research is detection of dengue virus and secondary infection with Salmonella typhi in patients suspected dengue virus infection. Detection of dengue virus and Salmonella typhi using immunochromatography test such as NS1, IgG/IgM for dengue virus infection, and IgM/IgG Salmonella and blood culture. The fifty children with dengue virus infection came to Soerya hospital and 17 cases suspected dengue virus infection, five cases showed a positive NS1 on the second day of fever and one case concurrent with clinical manifestation of convulsi on the third days of fever there were five cases only showed positive. It was showed in this study that on the fourth to six day of fever in dengue virus infection accompanied by antibody IgM & IgG dengue. There were 12 cases showed the clinical manifestation of concurrent dengue viral infection and Salmonella, all of them showed a mild clinical manifestation and did not show plasma leakage and shock. In this study we found the length of stay of concurrent Dengue Virus Infection and Salmonella infection is more than 10 days. These patients were also more likely to have co-existing haemodynamic disturbances and bacterial septicaemia which would have required treatment with inotropes and antibiotics. This idea is very important to make update dengue viral management to decrease mortality in outbreak try to

  7. Peptides as Therapeutic Agents for Dengue Virus.

    Science.gov (United States)

    Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

    2017-01-01

    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

  8. Dengue

    Science.gov (United States)

    ... emerged as a worldwide problem only since the 1950s. Although dengue rarely occurs in the continental United ... OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232-4636) , TTY: 888- ...

  9. Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study.

    Science.gov (United States)

    Mallhi, Tauqeer Hussain; Khan, Amer Hayat; Adnan, Azreen Syazril; Sarriff, Azmi; Khan, Yusra Habib; Jummaat, Fauziah

    2015-09-30

    The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period of six years (2008 - 2013) was performed. Patient's demographics, clinical and laboratory findings were recorded via structured data collection form. Patients were categorized into dengue fever (DF) and dengue hemorrhagic fever (DHF). Appropriate statistical methods were used to compare these two groups in order to determine difference in clinico-laboratory characteristics and to identify independent risk factors of DHF. A total 667 dengue patients (30.69 ± 16.13 years; Male: 56.7 %) were reviewed. Typical manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting, abdominal pain and skin rash were observed in more than 40 % patients. DHF was observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath, pleural effusion and thick gall bladder were more significantly (P  40 years (OR: 4.1, P hospitalization (OR: 2.3, P = 0.037) as independent predictors of DHF. Overall mortality was 1.2 % in our study. Current study demonstrated that DF and DHF present significantly different clinico-laboratory profile. Older age, secondary infection, diabetes mellitus, lethargy, thick gallbladder and delayed hospitalization significantly predict DHF. Prior knowledge of expected clinical profile and predictors of DHF/DSS development would provide information to identify individuals at higher risk and on the other hand, give sufficient time to clinicians for reducing dengue related morbidity and mortality.

  10. An expanded dengue syndrome patient with manifestation myocarditis: case report

    Science.gov (United States)

    Arifijanto, M. V.; Luqmana, H. P.; Rusli, M.; Bramantono

    2018-03-01

    Dengue infection may manifest asymptomatic, dengue fever, dengue hemorrhagic fever, dengue shock syndrome. However, atypical manifestations in other organs have been increasingly reported and called expanded dengue syndrome. One of the cardiac complications in dengue is myocarditis. An 18-year-old woman complains of high fever since 3 days, epistaxis, chest pain, dyspnea, and vomiting. Laboratory examination obtained thrombocytopenia, hemoconcentration, NS1, IgG-IgM dengue positive, CKMB and Troponin- I increase. Electrocardiogram result ischemic anterior-posterior. Echocardiography results hyperechogenic on myocardial suspicious a myocarditis. The patient was diagnosed with acute myocarditis and dengue hemorrhagic fever. Condition improved after five days of treatment. Cardiac complications in dengue are now increasingly observed with the most common case is myocarditis. The main mechanism of dengue myocarditis is still unknown though both direct viral infection and immune mediated damage have been suggested to be the cause of myocardial damage. The low incidence of dengue myocarditis is because it’s asymptomatic and diagnosis is easily missed. Almost all cases of dengue myocarditis are self-limiting and severe myocarditis leading to dilated cardiomyopathy is extremely rare. There have been reported a patient with dengue hemorrhagic fever with manifestation myocarditis. Condition improve with supportive management.

  11. Clinical profile and outcome of Dengue fever cases.

    Science.gov (United States)

    Ratageri, Vinod H; Shepur, T A; Wari, P K; Chavan, S C; Mujahid, I B; Yergolkar, P N

    2005-08-01

    Dengue fever is on rise globally. In India, Dengue epidemics are expanding geographically, even into the rural areas. Dengue can present with varied manifestations. The mortality rate has been brought down with high index of suspicion, strict monitoring and proper fluid resuscitation. Herewith, we are presenting clinical features and outcome of Dengue cases seen in and around Hubli (North Karnataka).

  12. Dengue Infection in Children in Ratchaburi, Thailand: A Cohort Study. I. Epidemiology of Symptomatic Acute Dengue Infection in Children, 2006–2009

    Science.gov (United States)

    Sabchareon, Arunee; Sirivichayakul, Chukiat; Limkittikul, Kriengsak; Chanthavanich, Pornthep; Suvannadabba, Saravudh; Jiwariyavej, Vithaya; Dulyachai, Wut; Pengsaa, Krisana; Margolis, Harold S.; Letson, G. William

    2012-01-01

    Background There is an urgent need to field test dengue vaccines to determine their role in the control of the disease. Our aims were to study dengue epidemiology and prepare the site for a dengue vaccine efficacy trial. Methods and Findings We performed a prospective cohort study of children in primary schools in central Thailand from 2006 through 2009. We assessed the epidemiology of dengue by active fever surveillance for acute febrile illness as detected by school absenteeism and telephone contact of parents, and dengue diagnostic testing. Dengue accounted for 394 (6.74%) of the 5,842 febrile cases identified in 2882, 3104, 2717 and 2312 student person-years over the four years, respectively. Dengue incidence was 1.77% in 2006, 3.58% in 2007, 5.74% in 2008 and 3.29% in 2009. Mean dengue incidence over the 4 years was 3.6%. Dengue virus (DENV) types were determined in 333 (84.5%) of positive specimens; DENV serotype 1 (DENV-1) was the most common (43%), followed by DENV-2 (29%), DENV-3 (20%) and DENV-4 (8%). Disease severity ranged from dengue hemorrhagic fever (DHF) in 42 (10.5%) cases, dengue fever (DF) in 142 (35.5%) cases and undifferentiated fever (UF) in 210 (52.5%) cases. All four DENV serotypes were involved in all disease severity. A majority of cases had secondary DENV infection, 95% in DHF, 88.7% in DF and 81.9% in UF. Two DHF (0.5%) cases had primary DENV-3 infection. Conclusion The results illustrate the high incidence of dengue with all four DENV serotypes in primary school children, with approximately 50% of disease manifesting as mild clinical symptoms of UF, not meeting the 1997 WHO criteria for dengue. Severe disease (DHF) occurred in one tenth of cases. Data of this type are required for clinical trials to evaluate the efficacy of dengue vaccines in large scale clinical trials. PMID:22860141

  13. A Case of Dengue Maculopathy with Spontaneous Recovery

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    Fiona Oi-jing Luk

    2013-06-01

    Full Text Available Purpose: To report a case of dengue maculopathy, which resolved spontaneously without treatment. Methods: A 25-year-old female patient with good past health was admitted to a general hospital in Hong Kong with fever of unknown origin after traveling to Indonesia. Based on the clinical features and a positive real-time polymerase chain reaction for dengue virus type 1, she was diagnosed with dengue fever. The patient developed dengue maculopathy mainly affecting the vision of her left eye. Abnormalities on a multifocal electroretinogram showed bilateral involvement. Results: As there is no proven treatment for dengue maculopathy, the patient opted for observation. Her vision returned to normal within 3 weeks. Conclusion: Dengue maculopathy can cause severe visual loss and may resolve without treatment.

  14. Severe Dengue Fever Outbreak in Taiwan.

    Science.gov (United States)

    Wang, Sheng-Fan; Wang, Wen-Hung; Chang, Ko; Chen, Yen-Hsu; Tseng, Sung-Pin; Yen, Chia-Hung; Wu, Deng-Chyang; Chen, Yi-Ming Arthur

    2016-01-01

    Dengue fever (DF) is a vector-borne disease caused by dengue viruses (DENVs). Epidemic dengue occurs intermittently in Taiwan. In 2014, Taiwan experienced its largest DF outbreak. There were 15,732 DF cases reported. There were a total of 136 dengue hemorrhagic fever (DHF) cases, of which 20 resulted in death. Most DF cases were reported in southern Taiwan. A total of 15,043 (96%) cases were from Kaohsiung, a modern city in southern Taiwan. This report reviews DF epidemics in Taiwan during 2005-2014. The correlation between DF and DHF along with temperature and precipitation were conjointly examined. We conclude that most dengue epidemics in Taiwan resulted from imported DF cases. Results indicate three main factors that may have been associated with this DF outbreak in Kaohsiung: an underground pipeline explosion combined with subsequent rainfall and higher temperature. These factors may have enhanced mosquito breeding activity, facilitating DENV transmission. © The American Society of Tropical Medicine and Hygiene.

  15. Dengue in the Americas and Southeast Asia: do they differ?

    Science.gov (United States)

    Halstead, Scott B

    2006-12-01

    The populations of Southeast Asia (SE Asia) and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF), principally in children, whereas in the Americas there were 2.8 million dengue fever (DF) cases, principally in adults, and only 65,000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, -2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs.

  16. Dengue in the Americas and Southeast Asia: do they differ?

    Directory of Open Access Journals (Sweden)

    Scott B. Halstead

    2006-12-01

    Full Text Available The populations of Southeast Asia (SE Asia and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF, principally in children, whereas in the Americas there were 2.8 million dengue fever (DF cases, principally in adults, and only 65 000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, -2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs.

  17. An information value based analysis of physical and climatic factors affecting dengue fever and dengue haemorrhagic fever incidence

    Directory of Open Access Journals (Sweden)

    Tripathi Nitin

    2005-06-01

    Full Text Available Abstract Background Vector-borne diseases are the most dreaded worldwide health problems. Although many campaigns against it have been conducted, Dengue Fever (DF and Dengue Haemorrhagic Fever (DHF are still the major health problems of Thailand. The reported number of dengue incidences in 1998 for the Thailand was 129,954, of which Sukhothai province alone reported alarming number of 682. It was the second largest epidemic outbreak of dengue after 1987. Government arranges the remedial facilities as and when dengue is reported. But, the best way to control is to prevent it from happening. This will be possible only when knowledge about the relationship of DF/DHF with climatic and physio-environmental agents is discovered. This paper explores empirical relationship of climatic factors rainfall, temperature and humidity with the DF/DHF incidences using multivariate regression analysis. Also, a GIS based methodology is proposed in this paper to explore the influence of physio-environmental factors on dengue incidences. Remotely sensed data provided important data about physical environment and have been used for many vector borne diseases. Information Values (IV method was utilised to derive influence of various factors in the quantitative terms. Researchers have not applied this type of analysis for dengue earlier. Sukhothai province was selected for the case study as it had high number of dengue cases in 1998 and also due to its diverse physical setting with variety of land use/land cover types. Results Preliminary results demonstrated that physical factors derived from remotely sensed data could indicate variation in physical risk factors affecting DF/DHF. A composite analysis of these three factors with dengue incidences was carried out using multivariate regression analysis. Three empirical models ER-1, ER-2 and ER-3 were evaluated. It was found that these three factors have significant relation with DF/DHF incidences and can be related to

  18. Environmentally-driven ensemble forecasts of dengue fever

    Science.gov (United States)

    Yamana, T. K.; Shaman, J. L.

    2017-12-01

    Dengue fever is a mosquito-borne viral disease prevalent in the tropics and subtropics, with an estimated 2.5 billion people at risk of transmission. In many areas where dengue is found, disease transmission is seasonal but prone to high inter-annual variability with occasional severe epidemics. Predicting and preparing for periods of higher than average transmission remains a significant public health challenge. Recently, we developed a framework for forecasting dengue incidence using an dynamical model of disease transmission coupled with observational data of dengue cases using data-assimilation methods. Here, we investigate the use of environmental data to drive the disease transmission model. We produce retrospective forecasts of the timing and severity of dengue outbreaks, and quantify forecast predictive accuracy.

  19. Urbanização e ecologia do dengue Urbanization and dengue ecology

    Directory of Open Access Journals (Sweden)

    Pedro Luiz Tauil

    2001-01-01

    Full Text Available As mudanças demográficas ocorridas nos países subdesenvolvidos, a partir dos anos 60, geradas por intenso fluxo migratório rural-urbano, resultaram em crescimento desordenado das cidades, nas quais se destacam a carência de facilidades - em particular, de habitação e saneamento básico. Cerca de 20% da população das grandes e médias cidades estão vivendo em favelas, cortiços ou em áreas de invasão. Pela falta de abastecimento de água, há necessidade de armazená-la precariamente, tal como pela ausência de destino adequado do lixo ocorre a proliferação de criadouros potenciais do Aedes aegypti, principal mosquito vetor da dengue, ou seja, depósitos improvisados para água potável e recipientes em que a água é acumulada, constituídos principalmente por latas, plásticos e garrafas usadas. A indústria moderna, por outro lado, privilegia a produção de material descartável. O vírus do dengue tem sua propagação facilitada pela intensidade e freqüência dos meios de transporte, os quais favorecem também a disseminação dos vetores da doença. Estes são alguns dos fatores que tentam explicar o ressurgimento do dengue, a mais importante arbovirose no mundo atualmente e que acomete milhares de pessoas todos os anos.Demographic changes occurring in underdeveloped countries due to intense rural-urban migration since the 1960s have resulted in overcrowded cities with multiple deficiencies, particularly in housing and basic sanitation. Some 20% of the population in large and medium-sized cities live in slums or under similar conditions. Lack of regular water supply and public garbage collection foster the proliferation of potential breeding sites for Aedes aegypti (the main mosquito vector for dengue, including precarious reservoirs for potable water and disposable recipients which accumulate water, like used cans and plastic and glass bottles. Modern industries also produce large volumes of disposable materials. Propagation

  20. Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies

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    Leticia Barboza Rocha

    2017-10-01

    Full Text Available Dengue nonstructural protein 1 (NS1 is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2, which were used to map three NS1 epitopes. The sequence 193AVHADMGYWIESALNDT209 was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV protein. On the other hand, the sequence 25VHTWTEQYKFQPES38 was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence 127ELHNQTFLIDGPETAEC143, is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections.

  1. Changing haematological parameters in dengue viral infections

    International Nuclear Information System (INIS)

    Jamil, T.; Mehmood, K.; Mujtaba, G.; Choudhry, N.

    2012-01-01

    Background: Dengue Fever is the most common arboviral disease in the world, and presents cyclically in tropical and subtropical regions of the world. The four serotypes of dengue virus, 1, 2, 3, and 4, form an antigenic subgroup of the flaviviruses (Group B arboviruses). Transmission to humans of any of these serotypes initiates a spectrum of host responses, from in apparent to severe and sometimes lethal infections. Complete Blood count (CBC) is an important part of the diagnostic workup of patients. Comparison of various finding in CBC including peripheral smear can help the physician in better management of the patient. Material and Methods: This cross sectional study was carried out on a series of suspected patients of Dengue viral infection reporting in Ittefaq Hospital (Trust). All were investigated for serological markers of acute infection. Results Out of 341 acute cases 166 (48.7%) were confirmed by IgM against Dengue virus. IgG anti-dengue was used on 200 suspected re-infected patients. Seventy-one (39.5%) were positive and 118 (59%) were negative. Among 245 confirmed dengue fever patients 43 (17.6%) were considered having dengue hemorrhagic fever on the basis of lab and clinical findings. Raised haematocrit, Leukopenia with relative Lymphocytosis and presence atypical lymphocytes along with plasmacytoid cells was consistent finding at presentation in both the patterns of disease, i.e., Dengue Haemorrhagic fever (DHF) and Dengue fever (DF). Conclusion: Changes in relative percentage of cells appear with improvement in the symptoms and recovery from the disease. These findings indicate that in the course of the disease, there are major shifts within cellular component of blood. (author)

  2. Binuclear trivalent and tetravalent uranium halides and cyanides supported by cyclooctatetraene ligands

    International Nuclear Information System (INIS)

    Wang, Cong-Zhi; Wu, Qun-Yan; Lan, Jian-Hui; Shi, Wei-Qun; Gibson, John K.

    2017-01-01

    Although the first organoactinide chloride Cp_3UCl (Cp = η"5-C_5H_5) was synthesized more than 50 years ago, binuclear uranium halides remain very rare in organoactinide chemistry. Herein, a series of binuclear trivalent and tetravalent uranium halides and cyanides with cyclooctatetraene ligands, (COT)_2U_2X_n (COT = η"8-C_8H_8; X=F, Cl, CN; n=2, 4), have been systematically studied using scalar-relativistic density functional theory (DFT). The structures with bridging halide or cyanide ligands were predicted to be the most stable complexes of (COT)_2U_2X_n, and all the complexes show weak antiferromagnetic interactions between the uranium centers. However, for each species, there is no significant uranium-uranium bonding interaction. The bonding between the metal and the ligands shows some degree of covalent character, especially between the metal and terminal halide or cyanide ligands. The U-5f and 6d orbitals are predominantly involved in the metal-ligand bonding. All the (COT)_2U_2X_n species were predicted to be more stable compared to the mononuclear half-sandwich complexes at room temperature in the gas phase such that (COT)_2U_2X_4 might be accessible through the known (COT)_2U complex. The tetravalent derivatives (COT)_2U_2X_4 are more energetically favorable than the trivalent (COT)_2U_2X_2 analogs, which may be attributed to the greater number of strong metal-ligand bonds in the former complexes.

  3. Dengue: an update on treatment options.

    Science.gov (United States)

    Chan, Candice Y Y; Ooi, Eng Eong

    2015-01-01

    Dengue is the most important mosquito-borne viral pathogen globally, with approximately 100 million cases of acute dengue annually. Infection can result in severe, life-threatening disease. Currently, there is no effective vaccine or licensed antiviral. Management is primarily supportive with fluids. Direct antiviral therapies that reduce dengue severity could be useful although these would need to inhibit all four viral serotypes effectively. This review focuses on the interventions that currently considered the gold standard in case management as well as exploratory therapies that have been studied in clinical trials. Although antiviral drug and therapeutic antibodies for dengue remain a work in progress, these studies have produced some promising results and may have the potential to be future drugs.

  4. System Dynamics based Dengue modeling environment to simulate evolution of Dengue infection under different climate scenarios

    Science.gov (United States)

    Anwar, R.; Khan, R.; Usmani, M.; Colwell, R. R.; Jutla, A.

    2017-12-01

    Vector borne infectious diseases such as Dengue, Zika and Chikungunya remain a public health threat. An estimate of the World Health Organization (WHO) suggests that about 2.5 billion people, representing ca. 40% of human population,are at increased risk of dengue; with more than 100 million infection cases every year. Vector-borne infections cannot be eradicated since disease causing pathogens survive in the environment. Over the last few decades dengue infection has been reported in more than 100 countries and is expanding geographically. Female Ae. Aegypti mosquito, the daytime active and a major vector for dengue virus, is associated with urban population density and regional climatic processes. However, mathematical quantification of relationships on abundance of vectors and climatic processes remain a challenge, particularly in regions where such data are not routinely collected. Here, using system dynamics based feedback mechanism, an algorithm integrating knowledge from entomological, meteorological and epidemiological processes is developed that has potential to provide ensemble simulations on risk of occurrence of dengue infection in human population. Using dataset from satellite remote sensing, the algorithm was calibrated and validated using actual dengue case data of Iquitos, Peru. We will show results on model capabilities in capturing initiation and peak in the observed time series. In addition, results from several simulation scenarios under different climatic conditions will be discussed.

  5. Dengue mortality in Colombia, 1985-2012.

    Science.gov (United States)

    Chaparro-Narváez, Pablo; León-Quevedo, Willian; Castañeda-Orjuela, Carlos Andrés

    2016-02-11

    Dengue in Colombia is an important public health problem due to the huge economic and social costs it has caused, especially during the disease outbreaks.  To describe the behavior of dengue mortality in Colombia between 1985 and 2012.  We conducted a descriptive study. Information was obtained from mortality and population projection databases provided by the Departamento Administrativo Nacional de Estadística (DANE) for the 1985-2012 period. Mortality rates, rate ratios, and case fatality rates were estimated.  A total of 1,990 dengue deaths were registered during this period in Colombia. Dengue mortality rates presented an increasing trend with statistical significance between 1985 and 1998. Higher mortality rates were reported in men both younger than 5 years and older than 65 years. Between 1995 and 2012, category 1 to 4 municipalities reported the highest mortality rates. Case fatality rates varied during the period between 0.01% and 0.39%.  Dengue is an avoidable disease that should disappear from mortality statistics as a cause of death. The event is avoidable if the proposed activities from the Estrategia de Gestión Integrada (EGI)-Dengue are implemented and evaluated. We recommend encouraging the development of an informational culture to contribute to decision making and prioritizing resource allocation.

  6. Dengue knowledge in indoor dengue patients from low socioeconomic class; etiology, symptoms, mode of transmission and prevention

    International Nuclear Information System (INIS)

    Shams, N.; Ahmed, W.; Seetlani, N.K.; Farhat, S.

    2018-01-01

    Dengue fever has emerged as an emerging public health issue during last decade bearing significant morbidity and economic burden particularly in third world countries. Current study aims to assess various domains of knowledge of indoor dengue patients. Methods: This descriptive cross-sectional study was conducted at Medicine dept. Rawal Institute of Health Sciences Islamabad and BBH Rawalpindi over 6 months. One hundred and twenty-five adult indoor confirmed cases of dengue from lower socioeconomic class were included after ethical approval. The 25-item dengue knowledge questionnaire including aetiology, symptoms, modes of transmission and prevention of dengue was filled. Results: Among 125 cases (77% males and 23% females), mean age was 30+-13 years. Mean knowledge score was 11+-5 points; with excellent knowledge in 6%, good knowledge (22%), moderate knowledge (23%), fair knowledge (34%) and poor knowledge (17%). Mosquito being a vector of dengue was identified by 78%, with peak time in afternoon (48%). Symptoms identified include fever (95%), headache (55%), muscle pain (44%), rash (33%), retro-orbital pain (32%), joint pains (28%) and abdominal pain (18%). Flies and ticks aren't the vectors of dengue according to 61% and 74% respectively, special mosquito is vector (54%), i.e., Aedes Aegypti (18%) that breeds in standing water (53%). Preventive measures identified were netting (56%), insecticide sprays (54%), covering water containers (38%), removing standing water (36%), mosquito repellents (17%), cutting down bushes (22%) and pouring chemicals in standing water (18%). Conclusion: Our patients from lower socioeconomic class, though aware of vector and mode of transmission, have insufficient knowledge of prevention and vector control measures. There is need to strengthen dengue awareness through community based programs, social media, schools and health care centres for high risk people well before the expected epidemic season about mode of transmission

  7. Dengue viremia in blood donors in Northern India: Challenges of emerging dengue outbreaks to blood transfusion safety

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    Sadhana Mangwana

    2015-01-01

    Full Text Available Backdround: Emerging infectious diseases pose threats to the general human population; including recipients of blood transfusions. Dengue is spreading rapidly to new areas and with increasing frequency of major outbreaks. Screening blood for dengue antigens in dengue-endemic countries would be costly and should, therefore, be recommended only after careful assessment of risk for infection and cost. Aim: A prospective study was conducted to establish the magnitude of the threat that dengue poses to blood safety where it is sporadic with seasonal variations, to quantify risk and to assess that whether screening is feasible and cost-effective. Materials and Methods: Nonstructural protein 1 (NS1 antigen test was done on 1709 donations during dengue outbreak in the months August to November 2013 as an additional test using Bio-Rad Platelia Dengue NS1AG test kit which is one step sandwich format microplate enzyme immunoassay using murine monoclonal antibodies for capture and revelation. Chi-square test was used to find statistical significance. Results and Conclusions: Majority cases were whole blood, replacement, male donors with 76.10% donors in <35 years age group. About 17.85% were single donor platelet donations. NS1 antigen in all donors was negative. In the past, dengue affected mainly children who do not donate blood. With the changing trend, mean age of infection increased affecting the population that does donate blood, further reducing blood donation pool. Further studies need to be done in different geographic regions of the country during dengue transmission season to establish maximum incidence of viremic donations, rates of transfusion transmission and clinical consequences in recipients. If risk is found to be substantial, decision will be taken by the policymakers at what threshold screening should be instituted to ensure safe blood transfusion.

  8. Factors affecting dengue prevention practices: nationwide survey of the Malaysian public.

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    Li Ping Wong

    Full Text Available Efforts to stamp dengue in many dengue endemic countries has met little success. There is a need to re-examine and understand how the public at large view the dengue prevention efforts. This study aimed to examine the demographic factors, theoretical constructs of the Health Belief Model and knowledge about dengue and how these influence the practice of dengue prevention.A national telephone survey was carried out with 2,512 individuals of the Malaysian public aged 18-60 years.The majority (73% of the Malaysian public had a total dengue prevention score of 51-100 (of a possible score of 1-100. Multivariate analysis suggests significant correlates of higher dengue prevention practices with demographic background, perception of susceptibility to dengue, perceived density of mosquitoes in the neighbourhood and knowledge about dengue. Households of lower income of which the majority (40.7% were from the rural areas, were associated with the highest odds [OR = 1.33; 95%CI = 1.09-1.67; p = 0.004] of dengue prevention. Dengue prevention practices were also less likely to be undertaken in neighbourhoods where the responders perceived there is no and/or low density of mosquitoes. Dengue prevention practices are also less likely to be practiced by skilled workers [OR = 0.78; 95%CI = 0.63-0.95; p = 0.029] compared to those unemployed. Higher perceived susceptibility to dengue was associated with higher dengue prevention practices and participants with higher dengue knowledge were found to have a higher level of involvement in dengue prevention practices.Results from the study suggest that in formulating approaches to contain dengue, strategies should be developed to cultivate dengue prevention practices among urban population and target areas with low density of mosquitoes where public perceived a less likely chance of getting dengue. Dengue prevention campaigns should focus on messages highlighting the risk of contracting dengue and education to increase

  9. Developing a Time Series Predictive Model for Dengue in Zhongshan, China Based on Weather and Guangzhou Dengue Surveillance Data.

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    Yingtao Zhang

    2016-02-01

    Full Text Available Dengue is a re-emerging infectious disease of humans, rapidly growing from endemic areas to dengue-free regions due to favorable conditions. In recent decades, Guangzhou has again suffered from several big outbreaks of dengue; as have its neighboring cities. This study aims to examine the impact of dengue epidemics in Guangzhou, China, and to develop a predictive model for Zhongshan based on local weather conditions and Guangzhou dengue surveillance information.We obtained weekly dengue case data from 1st January, 2005 to 31st December, 2014 for Guangzhou and Zhongshan city from the Chinese National Disease Surveillance Reporting System. Meteorological data was collected from the Zhongshan Weather Bureau and demographic data was collected from the Zhongshan Statistical Bureau. A negative binomial regression model with a log link function was used to analyze the relationship between weekly dengue cases in Guangzhou and Zhongshan, controlling for meteorological factors. Cross-correlation functions were applied to identify the time lags of the effect of each weather factor on weekly dengue cases. Models were validated using receiver operating characteristic (ROC curves and k-fold cross-validation.Our results showed that weekly dengue cases in Zhongshan were significantly associated with dengue cases in Guangzhou after the treatment of a 5 weeks prior moving average (Relative Risk (RR = 2.016, 95% Confidence Interval (CI: 1.845-2.203, controlling for weather factors including minimum temperature, relative humidity, and rainfall. ROC curve analysis indicated our forecasting model performed well at different prediction thresholds, with 0.969 area under the receiver operating characteristic curve (AUC for a threshold of 3 cases per week, 0.957 AUC for a threshold of 2 cases per week, and 0.938 AUC for a threshold of 1 case per week. Models established during k-fold cross-validation also had considerable AUC (average 0.938-0.967. The sensitivity and

  10. Developing a Time Series Predictive Model for Dengue in Zhongshan, China Based on Weather and Guangzhou Dengue Surveillance Data.

    Science.gov (United States)

    Zhang, Yingtao; Wang, Tao; Liu, Kangkang; Xia, Yao; Lu, Yi; Jing, Qinlong; Yang, Zhicong; Hu, Wenbiao; Lu, Jiahai

    2016-02-01

    Dengue is a re-emerging infectious disease of humans, rapidly growing from endemic areas to dengue-free regions due to favorable conditions. In recent decades, Guangzhou has again suffered from several big outbreaks of dengue; as have its neighboring cities. This study aims to examine the impact of dengue epidemics in Guangzhou, China, and to develop a predictive model for Zhongshan based on local weather conditions and Guangzhou dengue surveillance information. We obtained weekly dengue case data from 1st January, 2005 to 31st December, 2014 for Guangzhou and Zhongshan city from the Chinese National Disease Surveillance Reporting System. Meteorological data was collected from the Zhongshan Weather Bureau and demographic data was collected from the Zhongshan Statistical Bureau. A negative binomial regression model with a log link function was used to analyze the relationship between weekly dengue cases in Guangzhou and Zhongshan, controlling for meteorological factors. Cross-correlation functions were applied to identify the time lags of the effect of each weather factor on weekly dengue cases. Models were validated using receiver operating characteristic (ROC) curves and k-fold cross-validation. Our results showed that weekly dengue cases in Zhongshan were significantly associated with dengue cases in Guangzhou after the treatment of a 5 weeks prior moving average (Relative Risk (RR) = 2.016, 95% Confidence Interval (CI): 1.845-2.203), controlling for weather factors including minimum temperature, relative humidity, and rainfall. ROC curve analysis indicated our forecasting model performed well at different prediction thresholds, with 0.969 area under the receiver operating characteristic curve (AUC) for a threshold of 3 cases per week, 0.957 AUC for a threshold of 2 cases per week, and 0.938 AUC for a threshold of 1 case per week. Models established during k-fold cross-validation also had considerable AUC (average 0.938-0.967). The sensitivity and specificity

  11. Aedes mosquito salivary immune peptides: boost or block dengue viral infections

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    Natthanej Luplertlop

    2014-02-01

    Full Text Available Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  12. Retrospective analysis of dengue specific IgM reactive serum samples

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    Nemai Bhattacharya

    2013-04-01

    Full Text Available Objective: To conduct a retrospective analysis of dengue cases in Kolkata, on the basis of presence of anti-dengue IgM in their sera and presence or absence of anti-dengue IgG and dengue specific Non structural 1 (NS1 antigen in each of the serum sample. Methods: Sample was tested quantitatively employing ELISA technique, using Biorad test kits, with a view to get a more comprehensive picture of dengue in an urban endemic area and also to evaluate individual cases. Results: This reconstructed study revealed that of those 91 dengue cases, 70.3% (64 and 29.7% (27 were suffering from secondary and primary dengue respectively, showing that number of secondary dengue cases were much more than that of primary dengue cases with a possibility of emergence of DHF. A small proportion of cases 18.7% (17 were reactive for NS1. The duration of fever in NS1 antigen positive cases varied between 5 and 7 days. Of 17 NS1 reactive cases, 10 (10.9% and 7 (7.7% were suffering from secondary and primary dengue respectively. Conclusions: Early detection of primary and secondary dengue cases would be facilitated by utilizing all three parameters (NS1 antigen, anti-dengue IgM and IgG helping to evaluate, monitor and treat a dengue case effectively.

  13. Assessing changes in knowledge, attitude and practices on dengue diagnosis and management among primary care physicians after the largest dengue epidemic in Singapore.

    Science.gov (United States)

    Pang, Junxiong; Hildon, Zoe Jane-Lara; Thein, Tun Linn; Jin, Jing; Leo, Yee Sin

    2017-06-15

    Dengue results in high morbidity and mortality globally. The knowledge, attitude and practices (KAP) of dengue management, including diagnosis, among primary care physicians (PCPs) are important to reduce dengue transmission and burden. However, there is a lack of understanding on the impact of dengue epidemic on dengue management. Hence, the aim of this study is to examine the changes in KAP on dengue management among PCPs before and after the largest dengue epidemic in 2013 in Singapore. Surveys were mailed to 2000 and 1514 PCPs registered under the Singapore Medical Council in March of year 2011 and 2014, respectively. Survey data were then collected between April and June of that year. Chi-square or Fisher's exact test was used for comparing categorical variables. A multivariate logistic regression model was implemented to determine independent factors for frequent use of dengue diagnostic tests (DDTs). All tests were conducted at 5% level of significance. Adjusted odds ratio and corresponding 95% confidence intervals were reported, where applicable. Qualitative data were descriptively coded for themes and analysis. Among PCPs surveyed in 2011 and 2014, 89.9% and 86% had good knowledge on dengue management respectively. The usage of DDTs had increased significantly in 2014 (N = 164;56%) as compared to 2011 (N = 107;29.5%) in both private and public clinics (p Dengue Duo point-of-care test (POCT) kits was independently associated with frequent use of DDTs (adjusted odds ratio = 2.15; 95% confidence interval = 1.25-3.69). There was a significant reduction in referral of dengue patients to hospital (31.4% in 2011; 13.3% in 2014; p dengue management can be improved with availability of POCT kit, better awareness of the disease and any revised clinical guidelines. The knowledge on dengue management remained high, while the attitude and practices, particularly on the usage of DDTs improved significantly after a large epidemic. Furthermore, PCPs had more

  14. A two-plasmid strategy for engineering a dengue virus type 3 infectious clone from primary Brazilian isolate.

    Science.gov (United States)

    Santos, Jefferson J S; Cordeiro, Marli T; Bertani, Giovani R; Marques, Ernesto T A; Gil, Laura H V G

    2014-12-01

    Dengue infections represent one of the most prevalent arthropod-borne diseases worldwide, causing a wide spectrum of clinical outcomes. Engineered infectious clone is an important tool to study Dengue virus (DENV) biology. Functional full-length cDNA clones have been constructed for many positive-strand RNA viruses and have provided valuable tools for studying the molecular mechanisms involved in viral genome replication, virion assembly, virus pathogenesis and vaccine development. We report herein the successful development of an infectious clone from a primary Brazilian isolate of dengue virus 3 (DENV3) of the genotype III. Using a two-plasmid strategy, DENV3 genome was divided in two parts and cloned separately into a yeast-bacteria shuttle vector. All plasmids were assembled in yeast by homologous recombination technique and a full-length template for transcription was obtained by in vitro ligation of the two parts of the genome. Transcript-derived DENV3 is infectious upon transfection into BHK-21 cells and in vitro characterization confirmed its identity. Growth kinetics of transcript-derived DENV3 was indistinguishable from wild type DENV3. This system is a powerful tool that will help shed light on molecular features of DENV biology, as the relationship of specific mutations and DENV pathogenesis.

  15. Dengue in the Americas and Southeast Asia: do they differ? El dengue en las Américas y el sudeste asiático: ¿son diferentes?

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    Scott B. Halstead

    2006-12-01

    Full Text Available The populations of Southeast Asia (SE Asia and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF, principally in children, whereas in the Americas there were 2.8 million dengue fever (DF cases, principally in adults, and only 65 000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, -2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs.Las poblaciones de Asia suroriental y de la América tropical son similares y los cuatro tipos de virus del dengue de origen asiático son endémicos en ambas regiones. Aun así, durante períodos quinquenales comparables ocurrieron 1,16 millones de casos de dengue hemorrágico (DH en Asia suroriental, principalmente en niños, mientras que en

  16. Dengue prediction by the web: Tweets are a useful tool for estimating and forecasting Dengue at country and city level.

    Directory of Open Access Journals (Sweden)

    Cecilia de Almeida Marques-Toledo

    2017-07-01

    Full Text Available Infectious diseases are a leading threat to public health. Accurate and timely monitoring of disease risk and progress can reduce their impact. Mentioning a disease in social networks is correlated with physician visits by patients, and can be used to estimate disease activity. Dengue is the fastest growing mosquito-borne viral disease, with an estimated annual incidence of 390 million infections, of which 96 million manifest clinically. Dengue burden is likely to increase in the future owing to trends toward increased urbanization, scarce water supplies and, possibly, environmental change. The epidemiological dynamic of Dengue is complex and difficult to predict, partly due to costly and slow surveillance systems.In this study, we aimed to quantitatively assess the usefulness of data acquired by Twitter for the early detection and monitoring of Dengue epidemics, both at country and city level at a weekly basis. Here, we evaluated and demonstrated the potential of tweets modeling for Dengue estimation and forecast, in comparison with other available web-based data, Google Trends and Wikipedia access logs. Also, we studied the factors that might influence the goodness-of-fit of the model. We built a simple model based on tweets that was able to 'nowcast', i.e. estimate disease numbers in the same week, but also 'forecast' disease in future weeks. At the country level, tweets are strongly associated with Dengue cases, and can estimate present and future Dengue cases until 8 weeks in advance. At city level, tweets are also useful for estimating Dengue activity. Our model can be applied successfully to small and less developed cities, suggesting a robust construction, even though it may be influenced by the incidence of the disease, the activity of Twitter locally, and social factors, including human development index and internet access.Tweets association with Dengue cases is valuable to assist traditional Dengue surveillance at real-time and low

  17. Dengue prediction by the web: Tweets are a useful tool for estimating and forecasting Dengue at country and city level.

    Science.gov (United States)

    Marques-Toledo, Cecilia de Almeida; Degener, Carolin Marlen; Vinhal, Livia; Coelho, Giovanini; Meira, Wagner; Codeço, Claudia Torres; Teixeira, Mauro Martins

    2017-07-01

    Infectious diseases are a leading threat to public health. Accurate and timely monitoring of disease risk and progress can reduce their impact. Mentioning a disease in social networks is correlated with physician visits by patients, and can be used to estimate disease activity. Dengue is the fastest growing mosquito-borne viral disease, with an estimated annual incidence of 390 million infections, of which 96 million manifest clinically. Dengue burden is likely to increase in the future owing to trends toward increased urbanization, scarce water supplies and, possibly, environmental change. The epidemiological dynamic of Dengue is complex and difficult to predict, partly due to costly and slow surveillance systems. In this study, we aimed to quantitatively assess the usefulness of data acquired by Twitter for the early detection and monitoring of Dengue epidemics, both at country and city level at a weekly basis. Here, we evaluated and demonstrated the potential of tweets modeling for Dengue estimation and forecast, in comparison with other available web-based data, Google Trends and Wikipedia access logs. Also, we studied the factors that might influence the goodness-of-fit of the model. We built a simple model based on tweets that was able to 'nowcast', i.e. estimate disease numbers in the same week, but also 'forecast' disease in future weeks. At the country level, tweets are strongly associated with Dengue cases, and can estimate present and future Dengue cases until 8 weeks in advance. At city level, tweets are also useful for estimating Dengue activity. Our model can be applied successfully to small and less developed cities, suggesting a robust construction, even though it may be influenced by the incidence of the disease, the activity of Twitter locally, and social factors, including human development index and internet access. Tweets association with Dengue cases is valuable to assist traditional Dengue surveillance at real-time and low-cost. Tweets are

  18. Therapeutic antibodies as a treatment option for dengue fever.

    Science.gov (United States)

    Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

    2013-11-01

    Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

  19. Dengue Outbreak in Hadramout, Yemen, 2010: An Epidemiological Perspective

    Science.gov (United States)

    Ghouth, Abdulla Salim Bin; Amarasinghe, Ananda; Letson, G. William

    2012-01-01

    We analyzed surveillance data of a dengue outbreak (2010) reported to the Hadramout Health Office (Yemen) and retrospectively analyzed dengue-related epidemiological and entomological events reported in Hadramout from 2005 to 2009. A total of 630 immunoglobulin M (IgM) -confirmed dengue cases of 982 febrile cases was reported during the period from February to June of 2010; 12 cases died, giving case fatality a rate of 1.9%. Among febrile cases, the highest proportion of dengue cases (37.3%) was reported in the 15- to 24-year-old age group. The overall attack rate was 0.89/1,000. The average number of cases reported by month over the preceding 5-year period compared with the 2010 data is consistent with endemicity of dengue in the region and supports epidemic designation for the dengue activity in 2010. Recognition of endemic dengue transmission and potential for substantial dengue epidemics highlight the need for consistent laboratory-based surveillance that can support prevention and control activities accordingly. PMID:22665621

  20. Dengue infection and miscarriage: a prospective case control study.

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    Peng Chiong Tan

    Full Text Available BACKGROUND: Dengue is the most prevalent mosquito borne infection worldwide. Vertical transmissions after maternal dengue infection to the fetus and pregnancy losses in relation to dengue illness have been reported. The relationship of dengue to miscarriage is not known. METHOD: We aimed to establish the relationship of recent dengue infection and miscarriage. Women who presented with miscarriage (up to 22 weeks gestation to our hospital were approached to participate in the study. For each case of miscarriage, we recruited 3 controls with viable pregnancies at a similar gestation. A brief questionnaire on recent febrile illness and prior dengue infection was answered. Blood was drawn from participants, processed and the frozen serum was stored. Stored sera were thawed and then tested in batches with dengue specific IgM capture ELISA, dengue non-structural protein 1 (NS1 antigen and dengue specific IgG ELISA tests. Controls remained in the analysis if their pregnancies continued beyond 22 weeks gestation. Tests were run on 116 case and 341 control sera. One case (a misdiagnosed viable early pregnancy plus 45 controls (39 lost to follow up and six subsequent late miscarriages were excluded from analysis. FINDINGS: Dengue specific IgM or dengue NS1 antigen (indicating recent dengue infection was positive in 6/115 (5·2% cases and 5/296 (1·7% controls RR 3·1 (95% CI 1·0-10 P = 0·047. Maternal age, gestational age, parity and ethnicity were dissimilar between cases and controls. After adjustments for these factors, recent dengue infection remained significantly more frequently detected in cases than controls (AOR 4·2 95% CI 1·2-14 P = 0·023. INTERPRETATION: Recent dengue infections were more frequently detected in women presenting with miscarriage than in controls whose pregnancies were viable. After adjustments for confounders, the positive association remained.

  1. Research on Climate and Dengue in Malaysia: A Systematic Review.

    Science.gov (United States)

    Hii, Yien Ling; Zaki, Rafdzah Ahmad; Aghamohammadi, Nasrin; Rocklöv, Joacim

    2016-03-01

    Dengue is a climate-sensitive infectious disease. Climate-based dengue early warning may be a simple, low-cost, and effective tool for enhancing surveillance and control. Scientific studies on climate and dengue in local context form the basis for advancing the development of a climate-based early warning system. This study aims to review the current status of scientific studies in climate and dengue and the prospect or challenges of such research on a climate-based dengue early warning system in a dengue-endemic country, taking Malaysia as a case study. We reviewed the relationship between climate and dengue derived from statistical modeling, laboratory tests, and field studies. We searched electronic databases including PubMed, Scopus, EBSCO (MEDLINE), Web of Science, and the World Health Organization publications, and assessed climate factors and their influence on dengue cases, mosquitoes, and virus and recent development in the field of climate and dengue. Few studies in Malaysia have emphasized the relationship between climate and dengue. Climatic factors such as temperature, rainfall, and humidity are associated with dengue; however, these relationships were not consistent. Climate change projections for Malaysia show a mounting risk for dengue in the future. Scientific studies on climate and dengue enhance dengue surveillance in the long run. It is essential for institutions in Malaysia to promote research on climate and vector-borne diseases to advance the development of climate-based early warning systems. Together, effective strategies that improve existing research capacity, maximize the use of limited resources, and promote local-international partnership are crucial for sustaining research on climate and health.

  2. Community beliefs and practices about dengue in Puerto Rico Creencias y prácticas comunitarias relacionadas con el dengue en Puerto Rico

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    Carmen L. Pérez-Guerra

    2009-03-01

    Full Text Available OBJECTIVE: In spite of long-term endemicity and repeated government and private efforts, effective, sustained community participation for dengue prevention remains a challenge in Puerto Rico. This study explored differences found in interviews conducted in 2001 in attitudes toward dengue and its prevention by respondents' gender and whether they had a prior dengue infection. Findings may be used to develop messages to promote Aedes aegypti control practices. METHODS: From September to October 2003, 11 focus groups were conducted in San Juan, Puerto Rico. Fifty-nine persons (35 women, 24 men, > 18 years of age, who had been identified through the Puerto Rico dengue surveillance system participated in the focus groups. Analysis was based on grounded theory. RESULTS: Women considered dengue important because of its economic, emotional, and health impact, and they were concerned more often than men about insufficient garbage removal and water disposal. Participants with a previous dengue diagnosis were more concerned about risk of the disease, were more knowledgeable about dengue and its prevention, and recommended use of repellents more often than their counterparts without a previous dengue diagnosis. Barriers to sustained dengue prevention included misconceptions from outdated educational materials, " invisibility" of dengue compared with chronic diseases, and lack of acceptance of responsibility for dengue prevention. CONCLUSION: Suggested strategies to motivate residents' actions included working with government agencies to address structural problems that increase mosquito populations, improving access to information on garbage collection and water disposal through telephone hotlines, increasing publicity and information about dengue by mass media campaigns, and educating health professionals.OBJETIVO: A pesar de la prolongada endemia y los reiterados esfuerzos gubernamentales y privados, la participación efectiva y sostenida de la comunidad

  3. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

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    Pei Xuan Lee

    2016-06-01

    Full Text Available Dengue virus (DENV causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  4. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-06-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  5. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-01-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  6. Molecular surveillance of dengue in Semarang, Indonesia revealed the circulation of an old genotype of dengue virus serotype-1.

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    Sukmal Fahri

    Full Text Available Dengue disease is currently a major health problem in Indonesia and affects all provinces in the country, including Semarang Municipality, Central Java province. While dengue is endemic in this region, only limited data on the disease epidemiology is available. To understand the dynamics of dengue in Semarang, we conducted clinical, virological, and demographical surveillance of dengue in Semarang and its surrounding regions in 2012. Dengue cases were detected in both urban and rural areas located in various geographical features, including the coastal and highland areas. During an eight months' study, a total of 120 febrile patients were recruited, of which 66 were serologically confirmed for dengue infection using IgG/IgM ELISA and/or NS1 tests. The cases occurred both in dry and wet seasons. Majority of patients were under 10 years old. Most patients were diagnosed as dengue hemorrhagic fever, followed by dengue shock syndrome and dengue fever. Serotyping was performed in 31 patients, and we observed the co-circulation of all four dengue virus (DENV serotypes. When the serotypes were correlated with the severity of the disease, no direct correlation was observed. Phylogenetic analysis of DENV based on Envelope gene sequence revealed the circulation of DENV-2 Cosmopolitan genotype and DENV-3 Genotype I. A striking finding was observed for DENV-1, in which we found the co-circulation of Genotype I with an old Genotype II. The Genotype II was represented by a virus strain that has a very slow mutation rate and is very closely related to the DENV strain from Thailand, isolated in 1964 and never reported in other countries in the last three decades. Moreover, this virus was discovered in a cool highland area with an elevation of 1,001 meters above the sea level. The discovery of this old DENV strain may suggest the silent circulation of old virus strains in Indonesia.

  7. Investigational drugs in early development for treating dengue infection.

    Science.gov (United States)

    Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

    2016-09-01

    Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development. This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization's International Clinical Trials Registry Platform web portal using the search term 'dengue' on December 31(st), 2015. None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

  8. Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

    OpenAIRE

    Anna P. Durbin; Stephen S. Whitehead

    2011-01-01

    Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Past...

  9. Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

    Science.gov (United States)

    Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

    2017-10-01

    Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  10. Dengue Knowledge and Preventive Practices in Iquitos, Peru.

    Science.gov (United States)

    Paz-Soldán, Valerie A; Morrison, Amy C; Cordova Lopez, Jhonny J; Lenhart, Audrey; Scott, Thomas W; Elder, John P; Sihuincha, Moises; Kochel, Tadeusz J; Halsey, Eric S; Astete, Helvio; McCall, Philip J

    2015-12-01

    As part of a cluster-randomized trial to evaluate insecticide-treated curtains for dengue prevention in Iquitos, Peru, we surveyed 1,333 study participants to examine knowledge and reported practices associated with dengue and its prevention. Entomological data from 1,133 of these households were linked to the survey. Most participants knew that dengue was transmitted by mosquito bite (85.6%), but only few (18.6%) knew that dengue vectors bite during daytime. Most commonly recognized dengue symptoms were fever (86.6%), headache (76.4%), and muscle/joint pain (67.9%). Most commonly reported correct practices for mosquito control were cleaning homes (61.6%), using insecticide sprays (23%), and avoiding having standing water at home (12.3%). Higher education was associated with higher knowledge about dengue, including transmission and vector control. Higher socioeconomic status was associated with increased reported use of preventive practices requiring money expenditure. We were less likely to find Aedes aegypti eggs, larvae, or pupae in households that had dengue has been transmitted in Iquitos since the 1990s and the Regional Health Authority routinely fumigates households, treats domestic water containers with larvicide, and issues health education messages through mass media, knowledge of dengue transmission and household practices for prevention could be improved. © The American Society of Tropical Medicine and Hygiene.

  11. MORBIMORTALIDADE DA DENGUE EM IDOSOS NO BRASIL - DENGUE MORBIDITY AND MORTALITY IN ELDERLY IN BRAZIL

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    Annah Rachel Graciano

    2017-07-01

    Full Text Available Objective: To determine the prevalence and specific dengue coefficients of mortality in Brazil in the elderly population correlating the rates by male and female. Methods: Analytical ecological study with temporal trend of design. It was used as data sources Sistema de Informação Hospitalar, Sistema de Informação de Mortalidade and Instituto Brasileiro de Geografia e Estatística. The population corresponded to the elderly aged between 60 years to 100 attended at Brazilian public health system whom were diagnosed with dengue between 2008 and 2015. Results: The prevalence rates did not change in the general population between the years 2008 and 2015. There was a significant increase in the number of deaths from dengue. In the elderly group, the prevalence increased substantially, and the specific mortality analysis in this group showed higher values than the mortality of the general population affected by dengue. Conclusions: It is very important to underline studies on the involvement of dengue in elderly groups for the development of public politics and the creation of specific protocols for the diagnosis and treatment in that age group, considering the lack of scientific evidence to entail proper conduct in handling such patients

  12. Clinical profile and warning sign finding in children with severe dengue and non-severe dengue

    Science.gov (United States)

    Adam, A. S.; Pasaribu, S.; Wijaya, H.; Pasaribu, A. P.

    2018-03-01

    Dengue fever is one of the most important emerging vector-borne viral diseases. Approximately 500,000 out of 100 million cases develop to severe dengue infection. Patient with severe dengue (SD) can be predicted by clinical profile, laboratory and warning sign which could be saved by early interventions.This was a retrospective descriptive-analytic study to investigate clinical manifestations, laboratory and warning signs ofchildren with dengue infection in Haji Adam Malik hospital during January 2014–May 2016. Through medical records, we had selected 140 cases which fulfilled research criteria.Cases were classified as SD (n=28) and NSD (n=112). Most common clinical manifestations for NSD were abdominal pain (39.3%), myalgia (39.3%), headache (37.1%), mucosal bleeding (36.4%) while for SD were shock (15.7%), mucosal bleeding (15.7%), clinical fluid accumulation (15%), shortness of breath (14.3%). SGPT >1000IU/L (5 cases), SGOT >1000IU/L (9 cases), PT (10 cases) and aPTT (16 cases) were abnormal in SD. Severe dengue was frequently found in the range of white cell count 1000-4000/L and platelet count 20,000-50,000mm/uL. Clinical manifestations, warning sign, and laboratoryfinding, were different between SD and NSD.

  13. Current Status of Dengue Therapeutics Research and Development.

    Science.gov (United States)

    Low, Jenny G H; Ooi, Eng Eong; Vasudevan, Subhash G

    2017-03-01

    Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Multi-level analyses of spatial and temporal determinants for dengue infection.

    Science.gov (United States)

    Vanwambeke, Sophie O; van Benthem, Birgit H B; Khantikul, Nardlada; Burghoorn-Maas, Chantal; Panart, Kamolwan; Oskam, Linda; Lambin, Eric F; Somboon, Pradya

    2006-01-18

    Dengue is a mosquito-borne viral infection that is now endemic in most tropical countries. In Thailand, dengue fever/dengue hemorrhagic fever is a leading cause of hospitalization and death among children. A longitudinal study among 1750 people in two rural and one urban sites in northern Thailand from 2001 to 2003 studied spatial and temporal determinants for recent dengue infection at three levels (time, individual and household). Determinants for dengue infection were measured by questionnaire, land-cover maps and GIS. IgM antibodies against dengue were detected by ELISA. Three-level multi-level analysis was used to study the risk determinants of recent dengue infection. Rates of recent dengue infection varied substantially in time from 4 to 30%, peaking in 2002. Determinants for recent dengue infection differed per site. Spatial clustering was observed, demonstrating variation in local infection patterns. Most of the variation in recent dengue infection was explained at the time-period level. Location of a person and the environment around the house (including irrigated fields and orchards) were important determinants for recent dengue infection. We showed the focal nature of asymptomatic dengue infections. The great variation of determinants for recent dengue infection in space and time should be taken into account when designing local dengue control programs.

  15. Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome.

    Science.gov (United States)

    Villamor, E; Villar, L A; Lozano, A; Herrera, V M; Herrán, O F

    2017-10-01

    Vitamin D could modulate pathways leading to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). We examined the associations of serum total 25-hydroxy vitamin D [25(OH)D] and vitamin D binding protein (VDBP) concentrations in patients with uncomplicated dengue fever (DF) with risk of progression to DHF/DSS. In a case-control study nested in a cohort of DF patients who were followed during the acute episode in Bucaramanga, Colombia, we compared 25(OH)D and VDBP at onset of fever between 110 cases who progressed to DHF/DSS and 235 DF controls who did not progress. 25(OH)D concentrations were also compared between the acute sample and a sample collected >1 year post-convalescence in a subgroup. Compared with 25(OH)D ⩾75 nmol/l, adjusted odds ratios (95% CI) for progression were 0·44 (0·22-0·88) and 0·13 (0·02-1·05) for 50 to 75 nmol/l (vitamin D insufficiency) and <50 nmol/l (vitamin D deficiency), respectively (P, trend = 0·003). Mean 25(OH)D concentrations were much lower post-convalescence compared with the acute episode, regardless of case status. Compared with controls, mean VDBP was non-significantly lower in cases. We conclude that low serum 25(OH)D concentrations in DF patients predict decreased odds of progression to DHF/DSS.

  16. The prevention and control of dengue after Typhoon Haiyan

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    Charito Aumentado

    2015-11-01

    Full Text Available Objective: Many of the areas in the Philippines affected by Typhoon Haiyan are endemic for dengue; therefore, dengue prevention was a priority in the initial post-disaster risk assessment. We describe the dengue prevention and response strategies applied after Haiyan. Methods: The dengue response was implemented by a wide range of national and international stakeholders. Priorities included the rapid re-establishment of an effective surveillance system to quickly identify new dengue cases, monitor trends and determine the geographical distribution of cases. Dengue rapid diagnostic tests (RDTs were distributed to sentinel health facilities, and comprehensive vector control activities and entomological surveys were implemented. Several training sessions for key stakeholders and awareness campaigns for communities were organized. Results: There were RDT-positive dengue cases reported from urban and semi-urban areas where entomological surveys also confirmed a high density of Aedes aegypti mosquitoes. Although there was an increase in dengue cases in January 2014, the number of cases remained below the epidemic threshold throughout the remaining months of 2014. Discussion: There was no large outbreak of dengue after Typhoon Haiyan, possibly due to the targeted, multifaceted and rapid response for dengue after Haiyan. However, surveillance differed after Haiyan, making comparisons with previous years difficult. Multiple players contributed to the response that was also facilitated by close communication and coordination within the Health Cluster.

  17. Biomarkers in differentiating clinical dengue cases: A prospective cohort study

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    Gary Kim Kuan Low

    2015-12-01

    Full Text Available Objective: To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3 in differentiating clinical dengue cases. Methods: A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin has P value < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05. Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

  18. Clinical score to differentiate scrub typhus and dengue: A tool to differentiate scrub typhus and dengue

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    Shubhanker Mitra

    2017-01-01

    Full Text Available Background: Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. Materials and Methods: We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Results: Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%, total white blood cell count (7000 cells/cumm, hemoglobin (≤14 and >14 g/dL, total bilirubin (200 and ≥200 IU/dL, and altered sensorium (present or absent. Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval for model 2 was 0.84 (0.79–0.89. At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. Conclusion: In areas of high burden of ST and dengue, model 2 (the “clinical score to differentiate scrub typhus and dengue fever” is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

  19. Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue.

    Science.gov (United States)

    Mitra, Shubhanker; Gautam, Ira; Jambugulam, Mohan; Abhilash, Kundavaram Paul Prabhakar; Jayaseeelan, Vishalakshi

    2017-01-01

    Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79-0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. In areas of high burden of ST and dengue, model 2 (the "clinical score to differentiate scrub typhus and dengue fever") is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

  20. Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.

    Science.gov (United States)

    Halstead, Scott B

    2017-11-07

    During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The curve for children vaccinated at ages 2-16 years closely resembled the 1981 age specific hospitalization rate curve for Cuban children infected with DENV 2 who were sensitized by a prior DENV 1 infection. The corresponding age specific hospitalization curve for placebos experiencing heterotypic secondary dengue infections peaked at age, 9-11 years. These differing epidemiological features support the conclusion that antibody dependent enhanced (ADE) dengue disease occurred in seronegatives who were sensitized by vaccine. As hospitalizations continue to occur in all age groups Dengvaxia consumers should be warned that sensitized vaccinated seronegatives will experience enhanced dengue disease into the forseeable future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Knowledge and practice regarding dengue and chikungunya

    DEFF Research Database (Denmark)

    Kajeguka, Debora C; Desrochers, Rachelle E; Mwangi, Rose

    2017-01-01

    OBJECTIVE: To investigate knowledge and prevention practices regarding dengue and chikungunya amongst community members, as well as knowledge, treatment and diagnostic practices among healthcare workers. METHOD: We conducted a cross-sectional survey with 125 community members and 125 healthcare...... good knowledge. We conducted qualitative survey (n = 40) to further assess knowledge and practice regarding dengue and chikungunya fever. RESULTS: 15.2% (n = 19) of community members had good knowledge regarding dengue, whereas 53.6%, (n = 67) of healthcare workers did. 20.3% (n = 16) of participants...... from lowland areas and 6.5% (n = 3) from highland areas had good knowledge of dengue (χ(2) = 4.25, P = 0.03). Only 2.4% (n = 3) of all participants had a good knowledge score for chikungunya. In the qualitative study, community members expressed uncertainty about dengue and chikungunya. Some healthcare...

  2. Preparation and use of crystalline bis-monoorganic phosphonate and phosphate salts of tetravalent metals

    Science.gov (United States)

    Maya, L.

    1980-06-26

    A method of preparing and using the crystalline organic derivatives of the tetravalent metal phosphates and phosphonates provides for the contacting of an aqueous solution of a metal nitrate, with a solution of an organophosphorus acid for a period of time at room temperature that is sufficient for the formation of a metal phosphate product, and thereafter recovering said product. According to the invention, the product of the disclosed process is used in effecting analytical separations, such as ion exchange and chromatography.

  3. Re-assess Vector Indices Threshold as an Early Warning Tool for Predicting Dengue Epidemic in a Dengue Non-endemic Country.

    Directory of Open Access Journals (Sweden)

    Fong-Shue Chang

    Full Text Available Despite dengue dynamics being driven by complex interactions between human hosts, mosquito vectors and viruses that are influenced by climate factors, an operational model that will enable health authorities to anticipate the outbreak risk in a dengue non-endemic area has not been developed. The objectives of this study were to evaluate the temporal relationship between meteorological variables, entomological surveillance indices and confirmed dengue cases; and to establish the threshold for entomological surveillance indices including three mosquito larval indices [Breteau (BI, Container (CI and House indices (HI] and one adult index (AI as an early warning tool for dengue epidemic.Epidemiological, entomological and meteorological data were analyzed from 2005 to 2012 in Kaohsiung City, Taiwan. The successive waves of dengue outbreaks with different magnitudes were recorded in Kaohsiung City, and involved a dominant serotype during each epidemic. The annual indigenous dengue cases usually started from May to June and reached a peak in October to November. Vector data from 2005-2012 showed that the peak of the adult mosquito population was followed by a peak in the corresponding dengue activity with a lag period of 1-2 months. Therefore, we focused the analysis on the data from May to December and the high risk district, where the inspection of the immature and mature mosquitoes was carried out on a weekly basis and about 97.9% dengue cases occurred. The two-stage model was utilized here to estimate the risk and time-lag effect of annual dengue outbreaks in Taiwan. First, Poisson regression was used to select the optimal subset of variables and time-lags for predicting the number of dengue cases, and the final results of the multivariate analysis were selected based on the smallest AIC value. Next, each vector index models with selected variables were subjected to multiple logistic regression models to examine the accuracy of predicting the

  4. Dengue Contingency Planning: From Research to Policy and Practice

    Science.gov (United States)

    Runge-Ranzinger, Silvia; Kroeger, Axel; Olliaro, Piero; McCall, Philip J.; Sánchez Tejeda, Gustavo; Lloyd, Linda S.; Hakim, Lokman; Bowman, Leigh R.; Horstick, Olaf; Coelho, Giovanini

    2016-01-01

    Background Dengue is an increasingly incident disease across many parts of the world. In response, an evidence-based handbook to translate research into policy and practice was developed. This handbook facilitates contingency planning as well as the development and use of early warning and response systems for dengue fever epidemics, by identifying decision-making processes that contribute to the success or failure of dengue surveillance, as well as triggers that initiate effective responses to incipient outbreaks. Methodology/Principal findings Available evidence was evaluated using a step-wise process that included systematic literature reviews, policymaker and stakeholder interviews, a study to assess dengue contingency planning and outbreak management in 10 countries, and a retrospective logistic regression analysis to identify alarm signals for an outbreak warning system using datasets from five dengue endemic countries. Best practices for managing a dengue outbreak are provided for key elements of a dengue contingency plan including timely contingency planning, the importance of a detailed, context-specific dengue contingency plan that clearly distinguishes between routine and outbreak interventions, surveillance systems for outbreak preparedness, outbreak definitions, alert algorithms, managerial capacity, vector control capacity, and clinical management of large caseloads. Additionally, a computer-assisted early warning system, which enables countries to identify and respond to context-specific variables that predict forthcoming dengue outbreaks, has been developed. Conclusions/Significance Most countries do not have comprehensive, detailed contingency plans for dengue outbreaks. Countries tend to rely on intensified vector control as their outbreak response, with minimal focus on integrated management of clinical care, epidemiological, laboratory and vector surveillance, and risk communication. The Technical Handbook for Surveillance, Dengue Outbreak

  5. Vaccine platform recombinant measles virus.

    Science.gov (United States)

    Mühlebach, Michael D

    2017-10-01

    The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

  6. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Path to a Dengue Vaccine: Learning from Human Natural Dengue Infection Studies and Vaccine Trials.

    Science.gov (United States)

    de Silva, Aravinda M; Harris, Eva

    2018-06-01

    Dengue virus (DENV) is the most common arthropod-borne viral disease of humans. Although effective vaccines exist against other flaviviral diseases like yellow fever and Japanese encephalitis, dengue vaccine development is complicated by the presence of four virus serotypes and the possibility of partial immunity enhancing dengue disease severity. Several live attenuated dengue vaccines are being tested in human clinical trials. Initial results are mixed, with variable efficacy depending on DENV serotype and previous DENV exposure. Here, we highlight recent discoveries about the human antibody response to DENV and propose guidelines for advancing development of safe and effective dengue vaccines. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  7. Investigation of spatiotemporal relationship between dengue fever and drought

    Science.gov (United States)

    Lee, Chieh-Han; Yu, Hwa-Lung

    2016-04-01

    Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. Otherwise, another nearby city, Tainan City, had reported the biggest outbreak in 2015. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

  8. Multi-level analyses of spatial and temporal determinants for dengue infection

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    Oskam Linda

    2006-01-01

    Full Text Available Abstract Background Dengue is a mosquito-borne viral infection that is now endemic in most tropical countries. In Thailand, dengue fever/dengue hemorrhagic fever is a leading cause of hospitalization and death among children. A longitudinal study among 1750 people in two rural and one urban sites in northern Thailand from 2001 to 2003 studied spatial and temporal determinants for recent dengue infection at three levels (time, individual and household. Methods Determinants for dengue infection were measured by questionnaire, land-cover maps and GIS. IgM antibodies against dengue were detected by ELISA. Three-level multi-level analysis was used to study the risk determinants of recent dengue infection. Results Rates of recent dengue infection varied substantially in time from 4 to 30%, peaking in 2002. Determinants for recent dengue infection differed per site. Spatial clustering was observed, demonstrating variation in local infection patterns. Most of the variation in recent dengue infection was explained at the time-period level. Location of a person and the environment around the house (including irrigated fields and orchards were important determinants for recent dengue infection. Conclusion We showed the focal nature of asymptomatic dengue infections. The great variation of determinants for recent dengue infection in space and time should be taken into account when designing local dengue control programs.

  9. Household costs of dengue illness: secondary outcomes from a randomised controlled trial of dengue prevention in Guerrero state, Mexico.

    Science.gov (United States)

    Legorreta-Soberanis, José; Paredes-Solís, Sergio; Morales-Pérez, Arcadio; Nava-Aguilera, Elizabeth; Serrano-de Los Santos, Felipe René; Dimas-Garcia, Diana Lisseth; Ledogar, Robert J; Cockcroft, Anne; Andersson, Neil

    2017-05-30

    Dengue is a serious public health problem with an important economic impact. This study used data from a cluster randomised controlled trial of community mobilisation for dengue prevention to estimate the household costs of treatment of dengue illness. It examined the economic impact of the trial intervention in the three coastal regions of Mexico's Guerrero State. The 2010 baseline survey covered households in a random sample of 90 clusters in the coastal regions; the clusters were randomly allocated to intervention or control and re-surveyed in 2012. The surveys asked about dengue cases in the last 12 months, expenditures on their treatment, and work or school days lost by patients and care givers. We did not assign monetary value to days lost, since a lost day to a person of low earning power is of equal or higher value to that person than to one who earns more. The 12,312 households in 2010 reported 1020 dengue cases in the last 12 months (1.9% of the sample population). Most (78%) were ambulatory cases, with a mean cost of USD 51 and 10.8 work/school days, rising to USD 96 and 11.4 work/school days if treated by a private physician. Hospitalised cases cost USD 28-94 in government institutions and USD 392 in private hospitals (excluding additional inpatient charges), as well as 9.6-17.3 work/school days. Dengue cases cost households an estimated 412,825 work/school days throughout the three coastal regions. In the follow up survey, 6.1% (326/5349) of households in intervention clusters and 7.9% (405/5139) in control clusters reported at least one dengue case. The mean of days lost per case was similar in intervention and control clusters, but the number of days lost from dengue and all elements of costs for dengue cases per 1000 population were lower in intervention clusters. If the total population of the three coastal regions had received the intervention, some 149,401 work or school days lost per year could have been prevented. The economic effect of

  10. Pediatric ischemic stroke due to dengue vasculitis.

    Science.gov (United States)

    Nanda, Subrat Kumar; Jayalakshmi, Sita; Mohandas, Surath

    2014-10-01

    Dengue infection is an important arboviral infection in southeast Asia, especially in India. Neurological manifestations of dengue are increasingly recognized. We report an ischemic stroke due to dengue vasculitis in an 8-year-old child. We present a girl with a short febrile illness followed by episodic severe headache, with gradually progressive hemiparesis and visual impairment. Her brain magnetic resonance imaging revealed multiple infarctions in the anterior and posterior circulation. The magnetic resonance angiogram revealed irregular narrowing of bilateral middle cerebral arteries, right anterior cerebral artery, left posterior cerebral, and bilateral vertebral arteries suggestive of vasculitis. Her dengue serology was strongly positive for immunoglobulin M with 68.9 panbio units. The rest of the evaluation for pediatric stroke was unremarkable. She was treated with intravenous followed by oral corticosteroids and recovered totally with resolution of vasculitis on magnetic resonance angiogram over the next 3 months. This child illustrates possible immune-mediated vasculitis caused by dengue infection which is rather a rare presentation in a child who subsequently recovered well. One should consider dengue in childhood strokes in endemic regions. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Nine year trends of dengue virus infection in Mumbai, Western India.

    Science.gov (United States)

    Shastri, Jayanthi; Williamson, Manita; Vaidya, Nilima; Agrawal, Sachee; Shrivastav, Om

    2017-01-01

    Dengue virus (DENV) causes a wide range of diseases in humans, from acute febrile illness Dengue fever (DF) to life-threatening Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Factors believed to be responsible for spread of Dengue virus infection include explosive population growth, unplanned urban overpopulation with inadequate public health systems, poor standing water and vector control, climate changes and increased international recreational, business, military travel to endemic areas. All of these factors must be addressed to control the spread of Dengue and other mosquito-borne infections. The detection of Dengue virus RNA by reverse transcriptase PCR (RT-PCR) in human serum or plasma samples is highly indicative of acute Dengue fever. Moreover, the method is able to identify the Dengue virus serotype by demonstrating defined sequence homologies in the viral genomic RNA. During the nine year period of this study analysis, 6767 strongly suspected cases were tested by RT-PCR. 1685 (24.9%) were Dengue PCR positive and confirmed as Dengue cases. Observations on the seasonality were based on the nine year's data as the intensity of sampling was at its maximum during monsoon season. Dengue typing was done on 100 positive samples after storage of Dengue RNA at - 80°C. Dengue serotypes were detected in 69 samples of which Dengue 2 was most predominant. 576 samples were processed for NS1 antigen and PCR simultaneously. 19/576 were positive (3.3 %) for NS1 as well as by PCR. 23/576 samples were negative for NS1 antigen, but were positive by RT-PCR. The remaining 534 samples which were negative for NS1 antigen were also negative by Dengue RT-PCR. In this study we sought to standardize rapid, sensitive, and specific fluorogenic probe-based RT-PCR assay to screen and serotype a representative range of Dengue viruses that are found in and around Mumbai. Qualitative Dengue virus TaqMan assays could have tremendous utility for the epidemiological

  12. Binuclear trivalent and tetravalent uranium halides and cyanides supported by cyclooctatetraene ligands

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cong-Zhi; Wu, Qun-Yan; Lan, Jian-Hui; Shi, Wei-Qun [Chinese Academy of Sciences, Beijing (China). Laboratory of Nuclear Energy Chemistry and Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; Chai, Zhi-Fang [Chinese Academy of Sciences, Beijing (China). Laboratory of Nuclear Energy Chemistry and Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; Soochow Univ., Suzhou (China). School of Radiological and Interdisciplinary Sciences (RAD-X); Gibson, John K. [Lawrence Berkeley National Laboratory, CA (United States). Chemical Sciences Division

    2017-03-01

    Although the first organoactinide chloride Cp{sub 3}UCl (Cp = η{sup 5}-C{sub 5}H{sub 5}) was synthesized more than 50 years ago, binuclear uranium halides remain very rare in organoactinide chemistry. Herein, a series of binuclear trivalent and tetravalent uranium halides and cyanides with cyclooctatetraene ligands, (COT){sub 2}U{sub 2}X{sub n} (COT = η{sup 8}-C{sub 8}H{sub 8}; X=F, Cl, CN; n=2, 4), have been systematically studied using scalar-relativistic density functional theory (DFT). The structures with bridging halide or cyanide ligands were predicted to be the most stable complexes of (COT){sub 2}U{sub 2}X{sub n}, and all the complexes show weak antiferromagnetic interactions between the uranium centers. However, for each species, there is no significant uranium-uranium bonding interaction. The bonding between the metal and the ligands shows some degree of covalent character, especially between the metal and terminal halide or cyanide ligands. The U-5f and 6d orbitals are predominantly involved in the metal-ligand bonding. All the (COT){sub 2}U{sub 2}X{sub n} species were predicted to be more stable compared to the mononuclear half-sandwich complexes at room temperature in the gas phase such that (COT){sub 2}U{sub 2}X{sub 4} might be accessible through the known (COT){sub 2}U complex. The tetravalent derivatives (COT){sub 2}U{sub 2}X{sub 4} are more energetically favorable than the trivalent (COT){sub 2}U{sub 2}X{sub 2} analogs, which may be attributed to the greater number of strong metal-ligand bonds in the former complexes.

  13. Manifestações otorrinolaringológicas em pacientes com dengue Otolaryngological manifestations of patients with dengue

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    Cristiane K. Denis

    2003-10-01

    Full Text Available O Dengue é uma doença febril aguda, causada por um arbovírus, transmitida pelo mosquito Aedes aegypti. Apresenta manifestações clássicas como febre, mialgia, epistaxe, odinofagia, vertigem e zumbido. Constitui um sério problema de saúde pública, chegando a taxas de incidência de 50 a 70% da população no Estado do Rio de Janeiro. OBJETIVO: O objetivo do nosso estudo foi avaliar pacientes com dengue, que apresentam sintomatologia otorrinolaringológica como manifestação inicial. FORMA DE ESTUDO: Coorte Longitudinal. MATERIAL E MÉTODO: Foi realizado um estudo prospectivo, incluindo 30 pacientes com dengue, com sorologia comprovada, que manifestaram queixas otorrinolaringológicas. RESULTADOS: Os sinais e sintomas foram odinofagia (60%, coriza (50%, obstrução nasal (46,6%, otalgia (36,6%, vertigem (20%, epistaxe (13,3% zumbido (6,6%, alteração de glândula salivar (6,6% e gengivorragia (3,3%. CONCLUSÃO: Na vigência de epidemias, a suspeita clínica do dengue é importante, principalmente pelas inúmeras manifestações na área de otorrinolaringologia.Dengue is an acute fever disease caused by an arbovirus, and transmitted by the mosquito Aedes aegypti. Clinical picture usually starts with classic manifestations such as fever, myalgia, epistaxis, sore throat, vertigo and tinnitus. This disease has became a serious health public problem, reaching incidence rates of 50 to 70% in Rio de Janeiro State. AIM: Our objective was to evaluate patients with dengue, presenting otolaryngological symptoms as the first clinical manifestation. STUDY DESIGN: Longitudinal Cohort. MATERIAL AND METHOD: Thirty patients with serologically confirmed Dengue were included in this prospective study. RESULTS: The most important otolaryngological signs and symptoms were sore throat (60%, hyaline rhinorrhea (50%, nasal obstruction (46.6%, earache (36.6%, vertigo (20%, epistaxis (13.3%, tinnitus (6.6%, salivary gland diseases (6.6% and bleeding gum (3

  14. Cost of dengue outbreaks: literature review and country case studies.

    Science.gov (United States)

    Stahl, Hans-Christian; Butenschoen, Vicki Marie; Tran, Hien Tinh; Gozzer, Ernesto; Skewes, Ronald; Mahendradhata, Yodi; Runge-Ranzinger, Silvia; Kroeger, Axel; Farlow, Andrew

    2013-11-06

    Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save--through early response activities--resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks. Economic evidence on dengue outbreaks was gathered by conducting a literature review and collecting information on the costs of recent dengue outbreaks in 4 countries: Peru, Dominican Republic, Vietnam, and Indonesia. The literature review distinguished between costs of dengue illness including cost of dengue outbreaks, cost of interventions and cost-effectiveness of interventions. Seventeen publications on cost of dengue showed a large range of costs from 0.2 Million US$ in Venezuela to 135.2 Million US$ in Brazil. However, these figures were not standardized to make them comparable. Furthermore, dengue outbreak costs are calculated differently across the publications, and cost of dengue illness is used interchangeably with cost of dengue outbreaks. Only one paper from Australia analysed the resources saved through active dengue surveillance. Costs of vector control interventions have been reported in 4 studies, indicating that the costs of such interventions are lower than those of actual outbreaks. Nine papers focussed on the cost-effectiveness of dengue vaccines or dengue vector control; they do not provide any direct information on cost of dengue outbreaks, but their modelling methodologies could guide future research on cost-effectiveness of national surveillance systems.The country case studies--conducted in very different geographic and health system settings - unveiled rough estimates for 2011 outbreak costs of: 12 million US$ in Vietnam, 6.75 million US$ in Indonesia, 4.5 million US$ in Peru and 2.8 million US$ in Dominican Republic (all in 2012 US$). The proportions of the different cost components (vector control

  15. Incidence of dengue virus infection among Japanese travellers, 2006 to 2010

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    Yuki Tada

    2012-06-01

    Full Text Available Introduction: Dengue continues to be a global public health concern. In Japan, although dengue cases are currently seen only among travellers returning from endemic areas, the number of reported cases is rising according to the national case-based surveillance system. We evaluated the characteristics of dengue cases imported into Japan and the relationship between the incidence of infection and season of travel to popular destinations.Methods: Dengue cases reported to the national surveillance system were retrospectively examined. The number of reported cases per number of Japanese travellers to a dengue-endemic country was calculated to estimate the country-specific incidence of imported dengue virus infection. The incidence of dengue infection among Japanese travellers was compared between dengue high season and low season in each country using relative risk (RR and associated 95% confidence intervals (CI.Results: Among 540 Japanese residents who were reported as dengue cases from 2006 to 2010, the majority had travelled to Indonesia, India, the Philippines and Thailand. The RR of dengue infection among Japanese travellers during dengue high season versus low season was 4.92 (95% CI: 3.01–8.04 for the Philippines, 2.76 (95% CI: 1.67–4.54 for Thailand and 0.37 (95% CI: 0.15–0.92 for Indonesia.Discussion: Overall, higher incidence of imported cases appeared to be related to historic dengue high seasons. Travellers planning to visit dengue-endemic countries should be aware of historic dengue seasonality and the current dengue situation.

  16. Validation of dengue infection severity score

    Directory of Open Access Journals (Sweden)

    Pongpan S

    2014-03-01

    Full Text Available Surangrat Pongpan,1,2 Jayanton Patumanond,3 Apichart Wisitwong,4 Chamaiporn Tawichasri,5 Sirianong Namwongprom1,6 1Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Occupational Medicine, Phrae Hospital, Phrae, Thailand; 3Clinical Epidemiology Program, Faculty of Medicine, Thammasat University, Bangkok, Thailand; 4Department of Social Medicine, Sawanpracharak Hospital, Nakorn Sawan, Thailand; 5Clinical Epidemiology Society at Chiang Mai, Chiang Mai, Thailand; 6Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Objective: To validate a simple scoring system to classify dengue viral infection severity to patients in different settings. Methods: The developed scoring system derived from 777 patients from three tertiary-care hospitals was applied to 400 patients in the validation data obtained from another three tertiary-care hospitals. Percentage of correct classification, underestimation, and overestimation was compared. The score discriminative performance in the two datasets was compared by analysis of areas under the receiver operating characteristic curves. Results: Patients in the validation data were different from those in the development data in some aspects. In the validation data, classifying patients into three severity levels (dengue fever, dengue hemorrhagic fever, and dengue shock syndrome yielded 50.8% correct prediction (versus 60.7% in the development data, with clinically acceptable underestimation (18.6% versus 25.7% and overestimation (30.8% versus 13.5%. Despite the difference in predictive performances between the validation and the development data, the overall prediction of the scoring system is considered high. Conclusion: The developed severity score may be applied to classify patients with dengue viral infection into three severity levels with clinically acceptable under- or overestimation. Its impact when used in routine

  17. Host genetics and dengue fever.

    Science.gov (United States)

    Xavier-Carvalho, Caroline; Cardoso, Cynthia Chester; de Souza Kehdy, Fernanda; Pacheco, Antonio Guilherme; Moraes, Milton Ozório

    2017-12-01

    Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the genetic profile of the infected patient. However, the mechanisms that lead to severe disease and eventually death have not been determined, and a great challenge is the early identification of patients who are more likely to progress to a worse health condition. Studies performed in regions with cyclic outbreaks such as Cuba, Brazil, and Colombia have demonstrated that African ancestry confers protection against severe dengue. Highlighting the host genetics as an important factor in infectious diseases, a large number of association studies between genetic polymorphisms and dengue outcomes have been published in the last two decades. The most widely used approach involves case-control studies with candidate genes, such as the HLA locus and genes for receptors, cytokines, and other immune mediators. Additionally, a Genome-Wide Association Study (GWAS) identified SNPs associated with African ethnicity that had not previously been identified in case-control studies. Despite the increasing number of publications in America, Africa, and Asia, the results are quite controversial, and a meta-analysis is needed to assess the consensus among the studies. SNPs in the MICB, TNF, CD209, FcγRIIA, TPSAB1, CLEC5A, IL10 and PLCE1 genes are associated with the risk or protection of severe dengue, and the findings have been replicated in different populations. A thorough understanding of the viral, human genetic, and immunological mechanisms of dengue and how they interact is essential for effectively preventing dengue, but also managing and treating patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. First Iranian imported case of dengue

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    Masoud Mardani

    2013-01-01

    Full Text Available Dengue fever, a mosquito-borne flavivirus infection, is endemic in Southeast Asia. Currently, incidences have been increasing among adults. There have been no published reports of dengue fever from Iran. Widespread connection between different countries may predispose them for acquisition of infection. The patient was a 58-year-old Iranian woman with acute unexplained high-grade fever for 4 days, associated with skin rash, after returning from Southeast Asia. CBC showed WBC = 1600/mm 3 and platelet count 99,000/mm 3 . The patient also had hematuria. ELISA immunoglobulin M (IgM antibodies to dengue and serum RT-PCR for dengue virus was positive. The patient managed with conservative treatment and due to good general condition and improvement specific antiviral treatment was not started. She became afebrile at the 3 rd day of hospitalization and discharged with good general condition on fourth day. She was afebrile after two weeks follow-up. Dengue fever has been increasing among adults. It should be suspected, when a patient presents with acute febrile illness and skin rashes returning from endemic region. Conservative treatment may be conducted in uncomplicated cases .

  19. Evaluation of neurological complications using who warning signs for dengue disease severity

    International Nuclear Information System (INIS)

    Akmal, A.; Tauseef, A.; Akram, T.

    2015-01-01

    In 2009 a new classification of dengue was proposed by WHO Tropical Disease Research, which classifies dengue into dengue (D), dengue with warning signs (DW) and severe dengue (SD). This classification highlights the warning signs of dengue disease severity. Neurological complications are one of the most serious complications of dengue disease. This study was carried out to see association of neurological complications of dengue patients with WHO warning signs for dengue disease severity, and their outcome. Methods: It was a cross-sectional analytical study and included 180 diagnosed and registered cases of dengue hemorrhagic fever. The participants were subjected to a detailed clinical evaluation, laboratory assessment including blood counts, hematocrit, serology for dengue fever and sonography at 24 hours and 48 hours of their admission. Results: Twenty-six percent patients were suffering from neurological complications due to dengue. The warning signs for dengue disease severity like altered sensorium (85.5%, p=0.001), raised hematocrit (n=47, p=0.029), gall bladder wall thickening, pleural effusion and ascites on sonographic report (n=47, p=0.024), were strongly associated with the neurological complications. Conclusion: Our study reveals significant association of WHO warning signs for dengue disease severity with neurological complications of dengue disease. (author)

  20. Towards antiviral therapies for treating dengue virus infections.

    Science.gov (United States)

    Kaptein, Suzanne Jf; Neyts, Johan

    2016-10-01

    Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Impacto económico del dengue y del dengue hemorrágico en el Estado de Zulia, Venezuela, 1997-2003 Economic impact of dengue and dengue hemorrhagic fever in the State of Zulia, Venezuela, 1997-2003

    Directory of Open Access Journals (Sweden)

    Germán Añez

    2006-05-01

    Full Text Available OBJETIVOS: Determinar los costos directos e indirectos asociados con la atención de los casos de dengue y de dengue hemorrágico o síndrome de choque por dengue (DH/SCD entre los años 1997 y 2003 en el Estado de Zulia, Venezuela. MÉTODOS: El número total de pacientes con dengue y DH/SCD se obtuvo de los registros de la Dirección Regional de Epidemiología del Estado de Zulia y de los informes de casos confirmados en la Sección de Virología del Instituto de Investigaciones Clínicas Dr. Américo Negrette, de la Facultad de Medicina, Universidad del Zulia, Maracaibo, entre el 1.° de enero de 1997 y el 31 de diciembre de 2003. Como costos directos se consideraron el costo de la atención médica de urgencia de todos los casos y los costos de hospitalización de los casos con DH/SCD (costo por día-cama y costos de laboratorio. Los costos asociados con la ausencia laboral de los enfermos mayores de 15 años y de las madres acompañantes de los enfermos menores de 15 años conformaron los costos indirectos, ajustados según la proporción de hombres y mujeres en la fuerza laboral activa del país. Para el cálculo se utilizó el salario mínimo anual y los resultados se expresaron en dólares estadounidenses, según la tasa de cambio promedio de cada año. RESULTADOS: En el período estudiado se atendieron 33 857 casos de dengue y de DH/SCD; de ellos, 30 251 (89,35% fueron de dengue y 3 606 (10,65% de DH/SCD. Seis de estos fallecieron (letalidad 0,2 por 100 casos de DH/SCD. Los costos directos fueron US$ 474 251,70; de esa suma, US$ 132 042,30 correspondieron a la atención en los servicios de urgencia y US$ 342 209,40 a los gastos de hospitalización de los casos con DH/SCD. Los costos indirectos ascendieron a US$ 873 825,84 y representaron 64,8% del gasto total (US$ 1 348 077,54 relacionado con esta enfermedad en los años estudiados. CONCLUSIONES: Este es el primer estudio acerca del impacto económico del dengue en el Estado de Zulia y

  2. Dengue infections in non-immune travellers to Thailand.

    Science.gov (United States)

    Massad, E; Rocklov, J; Wilder-Smith, A

    2013-02-01

    Dengue is the most frequent arboviral disease and is expanding geographically. Dengue is also increasingly being reported in travellers, in particular in travellers to Thailand. However, data to quantify the risk of travellers acquiring dengue when travelling to Thailand are lacking. Using mathematical modelling, we set out to estimate the risk of non-immune persons acquiring dengue when travelling to Thailand. The model is deterministic with stochastic parameters and assumes a Poisson distribution for the mosquitoes' biting rate and a Gamma distribution for the probability of acquiring dengue from an infected mosquito. From the force of infection we calculated the risk of dengue acquisition for travellers to Thailand arriving in a typical year (averaged over a 17-year period) in the high season of transmission. A traveller arriving in the high season of transmission and remaining for 7 days has a risk of acquiring dengue of 0·2% (95% CI 0·16-0·23), whereas the risk for travel of 15 and 30 days' duration is 0·46% (95% CI 0·41-0·50) and 0·81% (95% CI 0·76-0·87), respectively. Our data highlight that the risk of non-immune travellers acquiring dengue in Thailand is substantial. The incidence of 0·81% after a 1-month stay is similar to that reported in prospective seroconversion studies in Israeli travellers to Thailand, highlighting that our models are consistent with actual data. Risk estimates based on mathematical modelling offer more detailed information depending on various travel scenarios, and will help the travel medicine provider give better evidence-based advice for travellers to dengue-endemic countries.

  3. The 2012 dengue outbreak in Madeira: exploring the origins.

    Science.gov (United States)

    Wilder-Smith, A; Quam, M; Sessions, O; Rocklov, J; Liu-Helmersson, J; Franco, L; Khan, K

    2014-02-27

    In 2012, Madeira reported its first major outbreak of dengue. To identify the origin of the imported dengue virus, we investigated the interconnectivity via air travel between dengue-endemic countries and Madeira, and compared available sequences against GenBank. There were 22,948 air travellers to Madeira in 2012, originating from twenty-nine dengue-endemic countries; 89.6% of these international travellers originated from Venezuela and Brazil. We developed an importation index that takes into account both travel volume and the extent of dengue incidence in the country of origin. Venezuela and Brazil had by far the highest importation indices compared with all other dengue-endemic countries. The importation index for Venezuela was twice as high as that for Brazil. When taking into account seasonality in the months preceding the onset of the Madeira outbreak, this index was even seven times higher for Venezuela than for Brazil during this time. Dengue sequencing shows that the virus responsible for the Madeira outbreak was most closely related to viruses circulating in Venezuela, Brazil and Columbia. Applying the importation index, Venezuela was identified as the most likely origin of importation of dengue virus via travellers to Madeira. We propose that the importation index is a new additional tool that can help to identify and anticipate the most probable country of origin for importation of dengue into currently non-endemic countries.

  4. Estratificación de una ciudad hiperendémica en dengue hemorrágico Stratification of a city with hyperendemic dengue hemorrhagic fever

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    Roberto Barrera

    2000-10-01

    Full Text Available La gran heterogeneidad ambiental de viviendas y barrios en los centros urbanos donde se cría Aedes aegypti, principal vector del dengue, junto con la escasez de recursos y de personal entrenado en el control de mosquitos constituyen retos para cualquier iniciativa destinada a controlar el dengue hemorrágico (DH. Una adecuada vigilancia epidemiológica puede servir de base para comenzar a estratificar los centros urbanos e identificar las zonas críticas donde deben concentrarse las tareas de control. En este estudio, se estratificó una ciudad hiperendémica en dengue hemorrágico (Maracay, Venezuela con la ayuda de un sistema de información geográfica (SIG y el análisis de la persistencia, la incidencia y la prevalencia del dengue mediante diagnósticos clínicos registrados de 1993 a 1998. Maracay tiene cerca de un millón de habitantes que viven en unos 349 barrios de 6 poblaciones que integran el Área Metropolitana, donde se notificaron 10 576 casos de dengue, 2 593 casos de DH y 8 defunciones. La incidencia de DH mostró una relación directa con la incidencia del dengue, el número de habitantes y la densidad poblacional. El patrón espacial de la incidencia del dengue fue estable durante los años estudiados y se encontraron relaciones positivas y significativas de la incidencia del dengue por barrio entre pares de años. La persistencia del dengue se relacionó directamente con la incidencia mensual por barrio. Estos patrones espaciales facilitaron la estratificación de la ciudad en tres estratos: 68 barrios sin dengue aparente, 226 barrios con baja persistencia y prevalencia, y 55 barrios con alta persistencia y prevalencia. Se recomienda otorgar alta prioridad de control a estos 55 barrios que ocupan 35% del área urbana y presentaron 70% de todos los casos de dengue.Any effort to control dengue hemorrhagic fever (DHF faces a number of challenges. Among these are the great environmental heterogeneity of homes and neighborhoods

  5. Energy level schemes of f{sup N} electronic configurations for the di-, tri-, and tetravalent lanthanides and actinides in a free state

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C.-G. [College of Sciences, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China); Brik, M.G., E-mail: mikhail.brik@ut.ee [College of Sciences, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China); Institute of Physics, University of Tartu, Ravila 14C, Tartu 50411 (Estonia); Institute of Physics, Jan Dlugosz University, Armii Krajowej 13/15, PL-42200 Czestochowa (Poland); Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668 Warsaw (Poland); Liu, D.-X.; Feng, B.; Tian, Ya [College of Sciences, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China); Suchocki, A. [Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668 Warsaw (Poland)

    2016-02-15

    The energy level diagrams are theoretically constructed for the di-, tri-, tetravalent lanthanide and actinide ions, using the Hartree–Fock calculated parameters of the Coulomb and spin–orbit interactions within f{sup N} (N=1…13) electron configurations. These diagrams are analogous to Dieke's diagram, which was obtained experimentally. They can be used for an analysis of the optical spectra of all considered groups of ions in various environments. Systematic variation of some prominent energy levels (especially those ones with a potential for emission transitions) along the isoelectronic 4f/5f ions is considered. - Highlights: • Energy level schemes for di-, tri, tetravalent lanthanides/actinides are calculated. • Systematic variation of the characteristic energy levels across the series is considered. • Potentially interesting emission transitions are identified.

  6. Estimation of the Basic Reproductive Ratio for Dengue Fever at the Take-Off Period of Dengue Infection.

    Science.gov (United States)

    Jafaruddin; Indratno, Sapto W; Nuraini, Nuning; Supriatna, Asep K; Soewono, Edy

    2015-01-01

    Estimating the basic reproductive ratio ℛ 0 of dengue fever has continued to be an ever-increasing challenge among epidemiologists. In this paper we propose two different constructions to estimate ℛ 0 which is derived from a dynamical system of host-vector dengue transmission model. The construction is based on the original assumption that in the early states of an epidemic the infected human compartment increases exponentially at the same rate as the infected mosquito compartment (previous work). In the first proposed construction, we modify previous works by assuming that the rates of infection for mosquito and human compartments might be different. In the second construction, we add an improvement by including more realistic conditions in which the dynamics of an infected human compartments are intervened by the dynamics of an infected mosquito compartment, and vice versa. We apply our construction to the real dengue epidemic data from SB Hospital, Bandung, Indonesia, during the period of outbreak Nov. 25, 2008-Dec. 2012. We also propose two scenarios to determine the take-off rate of infection at the beginning of a dengue epidemic for construction of the estimates of ℛ 0: scenario I from equation of new cases of dengue with respect to time (daily) and scenario II from equation of new cases of dengue with respect to cumulative number of new cases of dengue. The results show that our first construction of ℛ 0 accommodates the take-off rate differences between mosquitoes and humans. Our second construction of the ℛ 0 estimation takes into account the presence of infective mosquitoes in the early growth rate of infective humans and vice versa. We conclude that the second approach is more realistic, compared with our first approach and the previous work.

  7. Dengue surveillance in Veterans Affairs healthcare facilities, 2007-2010.

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    Patricia L Schirmer

    Full Text Available BACKGROUND: Although dengue is endemic in Puerto Rico (PR, 2007 and 2010 were recognized as epidemic years. In the continental United States (US, outside of the Texas-Mexico border, there had not been a dengue outbreak since 1946 until dengue re-emerged in Key West, Florida (FL, in 2009-2010. The objective of this study was to use electronic and manual surveillance systems to identify dengue cases in Veterans Affairs (VA healthcare facilities and then to clinically compare dengue cases in Veterans presenting for care in PR and in FL. METHODOLOGY: Outpatient encounters from 1/2007-12/2010 and inpatient admissions (only available from 10/2009-12/2010 with dengue diagnostic codes at all VA facilities were identified using VA's Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE. Additional case sources included VA data from Centers for Disease Control and Prevention BioSense and VA infection preventionists. Case reviews were performed. Categorical data was compared using Mantel-Haenszel or Fisher Exact tests and continuous variables using t-tests. Dengue case residence was mapped. FINDINGS: Two hundred eighty-eight and 21 PR and FL dengue cases respectively were identified. Of 21 FL cases, 12 were exposed in Key West and 9 were imported. During epidemic years, FL cases had significantly increased dengue testing and intensive care admissions, but lower hospitalization rates and headache or eye pain symptoms compared to PR cases. There were no significant differences in clinical symptoms, laboratory abnormalities or outcomes between epidemic and non-epidemic year cases in FL and PR. Confirmed/probable cases were significantly more likely to be hospitalized and have thrombocytopenia or leukopenia compared to suspected cases. CONCLUSIONS: Dengue re-introduction in the continental US warrants increased dengue surveillance and education in VA. Throughout VA, under-testing of suspected cases highlights the need to

  8. Dengue neonatal en el Perú: Reporte de un caso Neonatal dengue in Peru: a case report

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    Hermann Silva Delgado

    2011-03-01

    Full Text Available Se presenta el caso de un neonato de sexo femenino, a término, producto de madre fallecida al séptimo día de su puerperio, por falla multiorgánica debido a dengue grave confirmado por detección de antígeno NS1 e IgM. La recién nacida (RN no tuvo complicaciones, pero a partir del cuarto día de vida desarrolló fiebre, ictericia, manifestaciones de extravasación de plasma, hepatomegalia, ascitis, plaquetopenia y otros signos de síndrome de respuesta inflamatoria sistémica. Su evolución final fue favorable con tratamiento instaurado. Se demuestra con PCR en tiempo real, la presencia del virus dengue serotipo 2 en sangre de la RN, confirmándose el primer caso de dengue neonatal reportado en el Perú.We present the case of a full-term female newborn, whose mother died seven days postpartum from multi-organ failure due to severe dengue confirmed by NS1 antigen detection and positive IgM. The newborn did not have any complication, but at the fourth day of life she developed fever, jaundice, signs of plasma leakage, thrombocytopenia, hepatomegaly, ascitis, and others signs of systemic inflammation response syndrome. She fully recovered with supportive treatment. The RT-PCR test of a peripheral blood sample revealed a positive result for the dengue virus serotype 2, confirming the first case of neonatal dengue reported in Peru.

  9. Cost of dengue outbreaks: literature review and country case studies

    Science.gov (United States)

    2013-01-01

    Background Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save – through early response activities – resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks. Methods Economic evidence on dengue outbreaks was gathered by conducting a literature review and collecting information on the costs of recent dengue outbreaks in 4 countries: Peru, Dominican Republic, Vietnam, and Indonesia. The literature review distinguished between costs of dengue illness including cost of dengue outbreaks, cost of interventions and cost-effectiveness of interventions. Results Seventeen publications on cost of dengue showed a large range of costs from 0.2 Million US$ in Venezuela to 135.2 Million US$ in Brazil. However, these figures were not standardized to make them comparable. Furthermore, dengue outbreak costs are calculated differently across the publications, and cost of dengue illness is used interchangeably with cost of dengue outbreaks. Only one paper from Australia analysed the resources saved through active dengue surveillance. Costs of vector control interventions have been reported in 4 studies, indicating that the costs of such interventions are lower than those of actual outbreaks. Nine papers focussed on the cost-effectiveness of dengue vaccines or dengue vector control; they do not provide any direct information on cost of dengue outbreaks, but their modelling methodologies could guide future research on cost-effectiveness of national surveillance systems. The country case studies – conducted in very different geographic and health system settings - unveiled rough estimates for 2011 outbreak costs of: 12 million US$ in Vietnam, 6.75 million US$ in Indonesia, 4.5 million US$ in Peru and 2.8 million US$ in Dominican Republic (all in 2012 US$). The proportions of the

  10. Towards a climate-driven dengue decision support system for Thailand

    Science.gov (United States)

    Lowe, Rachel; Cazelles, Bernard; Paul, Richard; Rodó, Xavier

    2014-05-01

    Dengue is a peri-urban mosquito-transmitted disease, ubiquitous in the tropics and the subtropics. The geographic distribution of dengue and its more severe form, dengue haemorrhagic fever (DHF), have expanded dramatically in the last decades and dengue is now considered to be the world's most important arboviral disease. Recent demographic changes have greatly contributed to the acceleration and spread of the disease along with uncontrolled urbanization, population growth and increased air travel, which acts as a mechanism for transporting and exchanging dengue viruses between endemic and epidemic populations. The dengue vector and virus are extremely sensitive to environmental conditions such as temperature, humidity and precipitation that influence mosquito biology, abundance and habitat and the virus replication speed. In order to control the spread of dengue and impede epidemics, decision support systems are required that take into account the multi-faceted array of factors that contribute to increased dengue risk. Due to availability of seasonal climate forecasts, that predict the average climate conditions for forthcoming months/seasons in both time and space, there is an opportunity to incorporate precursory climate information in a dengue decision support system to aid epidemic planning months in advance. Furthermore, oceanic indicators from teleconnected areas in the Pacific and Indian Ocean, that can provide some indication of the likely prevailing climate conditions in certain regions, could potentially extend predictive lead time in a dengue early warning system. In this paper we adopt a spatio-temporal Bayesian modelling framework for dengue in Thailand to support public health decision making. Monthly cases of dengue in the 76 provinces of Thailand for the period 1982-2012 are modelled using a multi-layered approach. Environmental explanatory variables at various spatial and temporal resolutions are incorporated into a hierarchical model in order to

  11. COMPROMISO DE GANGLIOS BASALES EN DENGUE HEMORRÁGICO

    Directory of Open Access Journals (Sweden)

    Camilo Cortés Mora

    2016-11-01

    Full Text Available

    El dengue es una infección viral sistémica transmitida a los humanos por la hembra del mosquito Aedes aegypti. Alrededor del 10% de los pacientes con dengue pueden presentar alteraciones neurológicas durante o después de la infección. Existen unos signos conocidos como signos de alarma, los cuales, asociados al antecedente epidemiológico (procedencia de zona endémica, pueden ayudar a sospechar la infección. A continuación, se presentan algunas generalidades sobre el virus, las formas clínicas, las complicaciones y el análisis de una revisión sistemática de 65 historias clínicas de pacientes con diagnóstico de dengue o dengue hemorrágico. A partir de ellos, se encontró que se evidenciaron signos y síntomas neurológicos en 4 de los 39 casos que cumplieron los criterios de inclusión. Esta revisión permitió detectar un caso de hemorragia en la cabeza del núcleo caudado, asociada a la trombocitopenia marcada, inducida por el virus del dengue.

    BASAL GANGLIA INVOLVEMENT IN DENGUE HEMORRHAGIC FEVER (DHF

    ABSTRACT

    Dengue fever is a systemic viral infection transmitted to humans by the female Aedes aegypti mosquito. About 10% of patients with dengue fever may develop neurological disorders during or after infection. There are some signs known as warning signs, which, associated to the epidemiological background (origin of endemic area, may help to suspect the infection in those patients from endemic areas. Here are some generalities of the virus, its clinical forms, complications and the analysis of a systematic review of 65 clinical records of patients diagnosed with dengue and / or dengue hemorrhagic fever. From these patients, it was found that neurological signs and symptoms were evident in 4 of the 39 cases that fulfilled inclusion criteria. This review allowed to detect a case of hemorrhage in the head of the Caudate Nucleus associated with thrombocytopenia, induced by

  12. Dengue in Nicaragua, 1994: reintroduction of serotype 3 in the Americas Dengue en Nicaragua, 1994: reintroducción del serotipo 3 en las Américas

    Directory of Open Access Journals (Sweden)

    María G. Guzmán

    1997-03-01

    Full Text Available The principal aim of the report presented here is to describe the reappearance of dengue serotype 3 in the Americas, following a 17-year absence, through the recent experience of Nicaragua. In all, 356 serum samples obtained through Nicaragua's dengue monitoring system in October 1994 during an epidemic were examined. Anti-dengue IgM antibodies were detected in 43% of these, with sera from 12 of the 18 areas covered by Nicaragua's local integrated health care systems yielding positive results. In addition, dengue virus was isolated from 5 of 24 sera obtained from patients with hemorrhagic symptoms, dengue 3 being isolated from 3 of these samples and dengue 1 from the other 2. A diagnosis of dengue with hemorrhagic manifestations or of hemorrhagic dengue was supported or confirmed by laboratory findings obtained from 26 of 39 patients hospitalized in León or Managua. The most frequent symptoms of 18 patients diagnosed as having dengue with hemorrhagic manifestations were fever, headache, vomiting, myalgia, arthralgia, and epistaxis. The remaining eight patients, diagnosed as having probable hemorrhagic dengue, exhibited fever, general malaise, hemorrhaging, thrombocytopenia, hemoconcentration, and hemagglutination-inhibition antibody titers ranging from 640 to 20 480. Overall, the reappearance of dengue serotype 3 in the Region was confirmed, together with its ability to produce cases of hemorrhagic dengue. At least in Nicaragua, it is apparent that the introduction of dengue serotype 3 has prompted an increase in the number of classical dengue and hemorrhagic dengue cases, a scenario that might constitute the grim prelude to future developments in the Americas if urgent attention is not given to controlling the disease's mosquito vector.El objetivo principal de este informe fue describir la reaparición del serotipo 3 del dengue en las Américas después de 17 años de ausencia, tal como se observó recientemente en Nicaragua. Se examinaron en

  13. International Dengue Vaccine Communication and Advocacy: Challenges and Way Forward.

    Science.gov (United States)

    Carvalho, Ana; Van Roy, Rebecca; Andrus, Jon

    2016-01-01

    Dengue vaccine introduction will likely occur soon. However, little has been published on international dengue vaccine communication and advocacy. More effort at the international level is required to review, unify and strategically disseminate dengue vaccine knowledge to endemic countries' decision makers and potential donors. Waiting to plan for the introduction of new vaccines until licensure may delay access in developing countries. Concerted efforts to communicate and advocate for vaccines prior to licensure are likely challenged by unknowns of the use of dengue vaccines and the disease, including uncertainties of vaccine impact, vaccine access and dengue's complex pathogenesis and epidemiology. Nevertheless, the international community has the opportunity to apply previous best practices for vaccine communication and advocacy. The following key strategies will strengthen international dengue vaccine communication and advocacy: consolidating existing coalitions under one strategic umbrella, urgently convening stakeholders to formulate the roadmap for integrated dengue prevention and control, and improving the dissemination of dengue scientific knowledge.

  14. Evaluation of Pyrethrin Formulations on Dengue/Dengue Haemorrhagic Fever Vectors in the Laboratory and Sublethal Effects

    Directory of Open Access Journals (Sweden)

    S Sulaiman

    2007-12-01

    Full Text Available In Southeast Asia, Aedes aegypti (L. has been incriminated as principal vector of dengue viruses and Ae. albopictus as the secondary vector of dengue fever. Therefore, the aim of this study was to investigate the effectiveness of three for-mula¬tions of pyrethrin derived from Tanacetum cinerariaefolium against the dengue/dengue haemorrhagic fever vectors Aedes aegypti and Ae. albopictus in the laboratory. The testings employed 2 methodologies: the WHO Larval Bioassay and WHO Adult Bioassay. The results showed that all the three pyrethrin formulations had larvicidal and adulticidal activi-ties. The impact of the sublethal doses of pyrethrin formulations on Aedes spp. larvae resulted in 4-6% of alive adult emergence compared to 90% of Ae. aegypti emerging adults and 96% Ae. albopictus alive adult emergence in the control. The impact of sublethal doses of the pyrethrin formulations caused very low fecundity on both Aedes spp. compared to the control (P< 0.05.

  15. Evaluation of Pyrethrin Formulations on Dengue/Dengue Haemorrhagic Fever Vectors in the Laboratory and Sublethal Effects

    Directory of Open Access Journals (Sweden)

    S Sulaiman

    2007-11-01

    Full Text Available In Southeast Asia, Aedes aegypti (L. has been incriminated as principal vector of dengue viruses and Ae. albopictus as the secondary vector of dengue fever. Therefore, the aim of this study was to investigate the effectiveness of three for-mula¬tions of pyrethrin derived from Tanacetum cinerariaefolium against the dengue/dengue haemorrhagic fever vectors Aedes aegypti and Ae. albopictus in the laboratory. The testings employed 2 methodologies: the WHO Larval Bioassay and WHO Adult Bioassay. The results showed that all the three pyrethrin formulations had larvicidal and adulticidal activi-ties. The impact of the sublethal doses of pyrethrin formulations on Aedes spp. larvae resulted in 4-6% of alive adult emergence compared to 90% of Ae. aegypti emerging adults and 96% Ae. albopictus alive adult emergence in the control. The impact of sublethal doses of the pyrethrin formulations caused very low fecundity on both Aedes spp. compared to the control (P< 0.05.

  16. Diabetes mellitus increases severity of thrombocytopenia in dengue-infected patients.

    Science.gov (United States)

    Chen, Chung-Yuan; Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yaun-Jinn; Hsiao, Pi-Jung; Shin, Shyi-Jang

    2015-02-10

    Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54±51.69 vs. 86.58±63.4 (p≤0.001), 43.98±44.09 vs. 64.52±45.06 (p=0.002), 43.86±35.75 vs. 62.72±51.2 (p=0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of -13.981 (95% confidence interval (CI) -27.587, -0.374), -26.847 (95% CI -37.562, -16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of -2.947 (p=0.004), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients. Dengue patients with diabetes tended to have more severe

  17. Economic and disease burden of dengue in Mexico.

    Directory of Open Access Journals (Sweden)

    Eduardo A Undurraga

    2015-03-01

    Full Text Available Dengue imposes a substantial economic and disease burden in most tropical and subtropical countries. Dengue incidence and severity have dramatically increased in Mexico during the past decades. Having objective and comparable estimates of the economic burden of dengue is essential to inform health policy, increase disease awareness, and assess the impact of dengue prevention and control technologies.We estimated the annual economic and disease burden of dengue in Mexico for the years 2010-2011. We merged multiple data sources, including a prospective cohort study; patient interviews and macro-costing from major hospitals; surveillance, budget, and health data from the Ministry of Health; WHO cost estimates; and available literature. We conducted a probabilistic sensitivity analysis using Monte Carlo simulations to derive 95% certainty levels (CL for our estimates. Results suggest that Mexico had about 139,000 (95%CL: 128,000-253,000 symptomatic and 119 (95%CL: 75-171 fatal dengue episodes annually on average (2010-2011, compared to an average of 30,941 symptomatic and 59 fatal dengue episodes reported. The annual cost, including surveillance and vector control, was US$170 (95%CL: 151-292 million, or $1.56 (95%CL: 1.38-2.68 per capita, comparable to other countries in the region. Of this, $87 (95%CL: 87-209 million or $0.80 per capita (95%CL: 0.62-1.12 corresponds to illness. Annual disease burden averaged 65 (95%CL: 36-99 disability-adjusted life years (DALYs per million population. Inclusion of long-term sequelae, co-morbidities, impact on tourism, and health system disruption during outbreaks would further increase estimated economic and disease burden.With this study, Mexico joins Panama, Puerto Rico, Nicaragua, and Thailand as the only countries or areas worldwide with comprehensive (illness and preventive empirical estimates of dengue burden. Burden varies annually; during an outbreak, dengue burden may be significantly higher than that of

  18. Economic and disease burden of dengue in Mexico.

    Science.gov (United States)

    Undurraga, Eduardo A; Betancourt-Cravioto, Miguel; Ramos-Castañeda, José; Martínez-Vega, Ruth; Méndez-Galván, Jorge; Gubler, Duane J; Guzmán, María G; Halstead, Scott B; Harris, Eva; Kuri-Morales, Pablo; Tapia-Conyer, Roberto; Shepard, Donald S

    2015-03-01

    Dengue imposes a substantial economic and disease burden in most tropical and subtropical countries. Dengue incidence and severity have dramatically increased in Mexico during the past decades. Having objective and comparable estimates of the economic burden of dengue is essential to inform health policy, increase disease awareness, and assess the impact of dengue prevention and control technologies. We estimated the annual economic and disease burden of dengue in Mexico for the years 2010-2011. We merged multiple data sources, including a prospective cohort study; patient interviews and macro-costing from major hospitals; surveillance, budget, and health data from the Ministry of Health; WHO cost estimates; and available literature. We conducted a probabilistic sensitivity analysis using Monte Carlo simulations to derive 95% certainty levels (CL) for our estimates. Results suggest that Mexico had about 139,000 (95%CL: 128,000-253,000) symptomatic and 119 (95%CL: 75-171) fatal dengue episodes annually on average (2010-2011), compared to an average of 30,941 symptomatic and 59 fatal dengue episodes reported. The annual cost, including surveillance and vector control, was US$170 (95%CL: 151-292) million, or $1.56 (95%CL: 1.38-2.68) per capita, comparable to other countries in the region. Of this, $87 (95%CL: 87-209) million or $0.80 per capita (95%CL: 0.62-1.12) corresponds to illness. Annual disease burden averaged 65 (95%CL: 36-99) disability-adjusted life years (DALYs) per million population. Inclusion of long-term sequelae, co-morbidities, impact on tourism, and health system disruption during outbreaks would further increase estimated economic and disease burden. With this study, Mexico joins Panama, Puerto Rico, Nicaragua, and Thailand as the only countries or areas worldwide with comprehensive (illness and preventive) empirical estimates of dengue burden. Burden varies annually; during an outbreak, dengue burden may be significantly higher than that of the pre

  19. Treatment of dengue fever

    OpenAIRE

    Rajapakse, Senaka; Rodrigo,Chaturaka; Rajapakse,Anoja Chamarie

    2012-01-01

    Senaka Rajapakse,1,2 Chaturaka Rodrigo,1 Anoja Rajapakse31Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka; 2Lincoln County Hospital, United Lincolnshire NHS Trust, Lincoln, UK; 3Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Mansfield, UKAbstract: The endemic area for dengue fever extends over 60 countries, and approximately 2.5 billion people are at risk of infection. The incidence of dengue has multiplied many times over the last five decad...

  20. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Challenges of a Dengue Vaccine.

    Science.gov (United States)

    Screaton, Gavin; Mongkolsapaya, Juthathip

    2017-07-17

    A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  1. Developing a Social Autopsy Tool for Dengue Mortality: A Pilot Study

    Science.gov (United States)

    Arauz, María José; Ridde, Valéry; Hernández, Libia Milena; Charris, Yaneth; Carabali, Mabel; Villar, Luis Ángel

    2015-01-01

    Background Dengue fever is a public health problem in the tropical and sub-tropical world. Dengue cases have grown dramatically in recent years as well as dengue mortality. Colombia has experienced periodic dengue outbreaks with numerous dengue related-deaths, where the Santander department has been particularly affected. Although social determinants of health (SDH) shape health outcomes, including mortality, it is not yet understood how these affect dengue mortality. The aim of this pilot study was to develop and pre-test a social autopsy (SA) tool for dengue mortality. Methods and Findings The tool was developed and pre-tested in three steps. First, dengue fatal cases and ‘near misses’ (those who recovered from dengue complications) definitions were elaborated. Second, a conceptual framework on determinants of dengue mortality was developed to guide the construction of the tool. Lastly, the tool was designed and pre-tested among three relatives of fatal cases and six near misses in 2013 in the metropolitan zone of Bucaramanga. The tool turned out to be practical in the context of dengue mortality in Colombia after some modifications. The tool aims to study the social, individual, and health systems determinants of dengue mortality. The tool is focused on studying the socioeconomic position and the intermediary SDH rather than the socioeconomic and political context. Conclusions The SA tool is based on the scientific literature, a validated conceptual framework, researchers’ and health professionals’ expertise, and a pilot study. It is the first time that a SA tool has been created for the dengue mortality context. Our work furthers the study on SDH and how these are applied to neglected tropical diseases, like dengue. This tool could be integrated in surveillance systems to provide complementary information on the modifiable and avoidable death-related factors and therefore, be able to formulate interventions for dengue mortality reduction. PMID:25658485

  2. Evolving herbal formulations in management of dengue fever.

    Science.gov (United States)

    Singh, Pawan Kumar; Rawat, Pooja

    Dengue is endemic in more than 100 countries and it is estimated that annually above 390 million infections occur globally. During the period between 1996-2015, a massive increase of more than 500 per cent has been recorded in number of dengue cases reported in India. Till date, there are no specific globally accepted treatments for dengue fever in any system of medicine. Dengue does not cause very high mortality if properly handled and is currently being managed by clinicians through various adjuvant and alternative therapeutic options. Various plant based preparations have been used in different parts of India for combating dengue and are simultaneously also being scientifically validated by researchers. However, number of such scientific validation studies on phytomedicines are very less in India. Out of twenty-two plants reported against dengue, only four have been studied scientifically. Azadirachta indica, Carica papaya, Hippophae rhamnoides and Cissampelos pareira extracts were found effective and demonstrated improvement in clinical symptoms and direct inhibitory effect on dengue virus. C. papaya clinical trial showed increase in platelet count and faster recovery. These plants may be explored further as probable candidates for drug discovery against dengue. There is a need to search more such herbal formulations, which are being practiced at local level, document properly and validate them scientifically to confirm efficacy, mechanistic action and safety, before use. The herbal formulations being used by communities are the low hanging fruits which may provide alternative or adjuvant therapy if proper validation, value addition and product development steps are followed. This paper aims to review the recent status of dengue cases, deaths and evolving curative herbal solutions adapted and reported from India to combat the disease. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights

  3. Forecast of dengue incidence using temperature and rainfall.

    Directory of Open Access Journals (Sweden)

    Yien Ling Hii

    Full Text Available An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever. The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore.We developed a time series Poisson multivariate regression model using weekly mean temperature and cumulative rainfall over the period 2000-2010. Weather data were modeled using piecewise linear spline functions. We analyzed various lag times between dengue and weather variables to identify the optimal dengue forecasting period. Autoregression, seasonality and trend were considered in the model. We validated the model by forecasting dengue cases for week 1 of 2011 up to week 16 of 2012 using weather data alone. Model selection and validation were based on Akaike's Information Criterion, standardized Root Mean Square Error, and residuals diagnoses. A Receiver Operating Characteristics curve was used to analyze the sensitivity of the forecast of epidemics. The optimal period for dengue forecast was 16 weeks. Our model forecasted correctly with errors of 0.3 and 0.32 of the standard deviation of reported cases during the model training and validation periods, respectively. It was sensitive enough to distinguish between outbreak and non-outbreak to a 96% (CI = 93-98% in 2004-2010 and 98% (CI = 95%-100% in 2011. The model predicted the outbreak in 2011 accurately with less than 3% possibility of false alarm.We have developed a weather-based dengue forecasting model that allows warning 16 weeks in advance of dengue epidemics with high sensitivity and specificity. We demonstrate that models using temperature and rainfall could be simple, precise, and low cost tools for dengue forecasting which could be used to enhance decision making on the timing, scale of vector control operations, and utilization of limited resources.

  4. Forecast of dengue incidence using temperature and rainfall.

    Science.gov (United States)

    Hii, Yien Ling; Zhu, Huaiping; Ng, Nawi; Ng, Lee Ching; Rocklöv, Joacim

    2012-01-01

    An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever. The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore. We developed a time series Poisson multivariate regression model using weekly mean temperature and cumulative rainfall over the period 2000-2010. Weather data were modeled using piecewise linear spline functions. We analyzed various lag times between dengue and weather variables to identify the optimal dengue forecasting period. Autoregression, seasonality and trend were considered in the model. We validated the model by forecasting dengue cases for week 1 of 2011 up to week 16 of 2012 using weather data alone. Model selection and validation were based on Akaike's Information Criterion, standardized Root Mean Square Error, and residuals diagnoses. A Receiver Operating Characteristics curve was used to analyze the sensitivity of the forecast of epidemics. The optimal period for dengue forecast was 16 weeks. Our model forecasted correctly with errors of 0.3 and 0.32 of the standard deviation of reported cases during the model training and validation periods, respectively. It was sensitive enough to distinguish between outbreak and non-outbreak to a 96% (CI = 93-98%) in 2004-2010 and 98% (CI = 95%-100%) in 2011. The model predicted the outbreak in 2011 accurately with less than 3% possibility of false alarm. We have developed a weather-based dengue forecasting model that allows warning 16 weeks in advance of dengue epidemics with high sensitivity and specificity. We demonstrate that models using temperature and rainfall could be simple, precise, and low cost tools for dengue forecasting which could be used to enhance decision making on the timing, scale of vector control operations, and utilization of limited resources.

  5. Drugs for dengue: a patent review (2010-2014).

    Science.gov (United States)

    Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

    2014-11-01

    Almost half the global population is estimated to be at risk of contracting dengue infection. Of the 400 million infections estimated to occur annually, 4 million can be potentially life-threatening leading to vascular leakage and shock. The only treatment available to severe dengue patients is fluid replacement therapy and supportive care. A drug for treating dengue is an urgent need. This article endeavors to provide an overview of the experimental dengue drugs being developed around the world as reflected in the recent patent literature spanning the last few years (2010-2014). Dengue drug development is essentially in its infancy and currently hobbled by multiple factors including a poor understanding of the molecular mechanism of severe disease and lack of reliable small animal model for preclinical drug evaluation. More intense R&D coupled to setting up product development partnerships to facilitate the efficient movement of a drug molecule from the laboratory to the clinic is needed to make antiviral therapy for dengue a reality in the coming future.

  6. Potential biomarkers for the clinical prognosis of severe dengue

    Directory of Open Access Journals (Sweden)

    Mayara Marques Carneiro da Silva

    2013-09-01

    Full Text Available Currently, several assays can confirm acute dengue infection at the point-of-care. However, none of these assays can predict the severity of the disease symptoms. A prognosis test that predicts the likelihood of a dengue patient to develop a severe form of the disease could permit more efficient patient triage and treatment. We hypothesise that mRNA expression of apoptosis and innate immune response-related genes will be differentially regulated during the early stages of dengue and might predict the clinical outcome. Aiming to identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear cells of mild and severe dengue patients during the febrile stage of the disease to measure the expression levels of selected genes by quantitative polymerase chain reaction. The selected candidate biomarkers were previously identified by our group as differentially expressed in microarray studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially expressed between patients who developed clinical symptoms associated with the mild type of dengue and patients who showed clinical symptoms associated with severe dengue. We suggest that this gene expression panel could putatively serve as biomarkers for the clinical prognosis of dengue haemorrhagic fever.

  7. Demam Berdarah Dengue: Epidemiologi, Patogenesis, dan Faktor Risiko Penularan

    Directory of Open Access Journals (Sweden)

    Aryu Candra

    2013-02-01

    Full Text Available Abstract. Dengue hemorrhagic fever is an infectious disease resulting spectrum of clinical manifestations that vary from the lightest, dengue fever, hemorrhagic fever and dengue fever are accompanied by shock or dengue shock syndrome. Its caused by dengue virus, transmit­ted by Aedes mosquitoes. The case is spread in the tropics, especially in Southeast Asia, Central America, America and the Caribbean, many causes of death in children 90% of them attacking children under 15 years old. Until now pathogenesis is unclear. There are two theo ries or hypotheses immunopatogenesis DHF and DSS is still controversial which secondary infections (secondary heterologus in­fection and antibody-dependent enhancement. Risk factors for dengue transmission are rapid urban population growth, mobilization of the population because of improved transportation facilities and disrupted or weakened so that population control. Another risk factor is poverty which result in people not has the ability to provide adecent home and healthy, drinking water supply and proper waste disposal.Keywords: dengue hemorrhagic fever (DHF, epidemiology of DHF, pathogenesis of DHF, transmission risk factors of DHF

  8. Ag29(BDT)12(TPP)4: A Tetravalent Nanocluster

    KAUST Repository

    AbdulHalim, Lina G.

    2015-06-24

    The bottom-up assembly of nanoparticles into diverse ordered solids is a challenge because it requires nanoparticles, which are often quasi-spherical, to have interaction anisotropy akin to atoms and molecules. Typically, anisotropy has been introduced by changing the shape of the inorganic nanoparticle core. Here, we present the design, self-assembly, optical properties and total structural determination of Ag29(BDT)12(TPP)4, an atomically precise tetravalent nanocluster (NC) (BDT: 1,3-benzenedithiols; TPP: triphenylphosphine). It features four unique tetrahedrally symmetrical binding surface sites facilitated by the supramolecular assembly of 12 BDT—wide footprint bidentate thiols—in the ligand shell. When each of these sites was selectively functionalized by a single phosphine ligand, particle stability, synthetic yield and the propensity to self-assemble into macroscopic crystals increased. The solid crystallized NCs have a substantially narrowed optical bandgap compared to that of the solution state, suggesting strong inter-particle electronic coupling occurs in the solid state.

  9. Ag29(BDT)12(TPP)4: A Tetravalent Nanocluster

    KAUST Repository

    AbdulHalim, Lina G.; Bootharaju, Megalamane Siddaramappa; Tang, Qing; Del Gobbo, Silvano; AbdulHalim, Rasha; Eddaoudi, Mohamed; Jiang, De-en; Bakr, Osman

    2015-01-01

    The bottom-up assembly of nanoparticles into diverse ordered solids is a challenge because it requires nanoparticles, which are often quasi-spherical, to have interaction anisotropy akin to atoms and molecules. Typically, anisotropy has been introduced by changing the shape of the inorganic nanoparticle core. Here, we present the design, self-assembly, optical properties and total structural determination of Ag29(BDT)12(TPP)4, an atomically precise tetravalent nanocluster (NC) (BDT: 1,3-benzenedithiols; TPP: triphenylphosphine). It features four unique tetrahedrally symmetrical binding surface sites facilitated by the supramolecular assembly of 12 BDT—wide footprint bidentate thiols—in the ligand shell. When each of these sites was selectively functionalized by a single phosphine ligand, particle stability, synthetic yield and the propensity to self-assemble into macroscopic crystals increased. The solid crystallized NCs have a substantially narrowed optical bandgap compared to that of the solution state, suggesting strong inter-particle electronic coupling occurs in the solid state.

  10. Dengue fever with rectus sheath hematoma: A case report

    Directory of Open Access Journals (Sweden)

    Anurag Sharma

    2014-01-01

    Full Text Available Dengue fever, also known as breakbone fever, is an infectious tropical disease caused by the Dengue virus. It is associated with a number of complications, which are well documented. However, Dengue fever associated with rectus sheath hematoma (RSH is a very rare complication. Only one case report has been published prior supporting the association of Dengue fever with RSH. We report a case of Dengue fever who presented with RSH and was successfully treated conservatively. RSH is also an uncommon cause of acute abdominal pain. It is accumulation of blood in the sheath of the rectus abdominis, secondary to rupture of an epigastric vessel or muscle tear.

  11. Spectrum of Maternofetal Outcomes during Dengue Infection in Pregnancy: An Insight

    Directory of Open Access Journals (Sweden)

    Swati Sharma

    2016-01-01

    Full Text Available Dengue is a vector transmitted viral infection; tropical and subtropical countries see outbreaks of dengue each year. There is a paucity of literature on effects of dengue infection on pregnancy outcome and this prompted us to undertake a study for better understanding of pregnancy implications with dengue infection. Pregnant women admitted during the seasonal outbreak of dengue between September 2015 and October 2015 were studied and maternal and fetal outcomes in sixteen NS1Ag positive women were analysed. Out of sixteen women diagnosed with dengue fever, three had dengue shock syndrome (DSS and eight had dengue haemorrhagic fever (DHF. The most common obstetric complication seen in 43% of the cases was oligohydramnios. Bleeding manifestations occurred in seven women and there were three maternal deaths. Perinatal complications included three intrauterine deaths, six nursery admissions, and one neonatal death. Thus dengue infection was associated with high maternal and perinatal mortality. In view of poor obstetric outcomes, this viral infection warrants early admission and prompt management.

  12. Dengue Returns

    Centers for Disease Control (CDC) Podcasts

    2016-08-25

    Dr. Tyler Sharp, a CDC epidemiologist, discusses dengue in southern Texas.  Created: 8/25/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/25/2016.

  13. Rural-urban comparisons of dengue seroprevalence in Malaysia

    Directory of Open Access Journals (Sweden)

    Cheng Hoon Chew

    2016-08-01

    Full Text Available Abstract Background Each year an estimated 390 million dengue infections occur worldwide. In Malaysia, dengue is a growing public health concern but estimate of its disease burden remains uncertain. We compared the urban-rural difference of dengue seroprevalence and determined age-specific dengue seroprevalence in Malaysia. Methods We undertook analysis on 11,821 subjects from six seroprevalence surveys conducted in Malaysia between 2001 and 2013, which composed of five urban and two rural series. Results Prevalence of dengue increased with age in both urban and rural locations in Malaysia, which exceeded 90 % among those aged 70 years or beyond. The age-specific rates of the 5 urban surveys overlapped without clear separation among them, while prevalence was lower in younger subjects in rural series than in urban series, the trend reversed in older subjects. There were no differences in the seroprevalence by gender, ethnicity or region. Poisson regression model confirmed the prevalence have not changed in urban areas since 2001 but in rural areas, there was a significant positive time trend such that by year 2008, rural prevalence was as high as in urban areas. Conclusion Dengue seroprevalence has stabilized but persisted at a high level in urban areas since 2001, and is fast stabilizing in rural areas at the same high urban levels by 2008. The cumulative seroprevalence of dengue exceeds 90 % by the age of 70 years, which translates into 16.5 million people or 55 % of the total population in Malaysia, being infected by dengue by 2013.

  14. Rural-urban comparisons of dengue seroprevalence in Malaysia.

    Science.gov (United States)

    Chew, Cheng Hoon; Woon, Yuan Liang; Amin, Faridah; Adnan, Tassha H; Abdul Wahab, Asmah Hani; Ahmad, Zul Edzhar; Bujang, Mohd Adam; Abdul Hamid, Abdul Muneer; Jamal, Rahman; Chen, Wei Seng; Hor, Chee Peng; Yeap, Lena; Hoo, Ling Ping; Goh, Pik Pin; Lim, Teck Onn

    2016-08-18

    Each year an estimated 390 million dengue infections occur worldwide. In Malaysia, dengue is a growing public health concern but estimate of its disease burden remains uncertain. We compared the urban-rural difference of dengue seroprevalence and determined age-specific dengue seroprevalence in Malaysia. We undertook analysis on 11,821 subjects from six seroprevalence surveys conducted in Malaysia between 2001 and 2013, which composed of five urban and two rural series. Prevalence of dengue increased with age in both urban and rural locations in Malaysia, which exceeded 90 % among those aged 70 years or beyond. The age-specific rates of the 5 urban surveys overlapped without clear separation among them, while prevalence was lower in younger subjects in rural series than in urban series, the trend reversed in older subjects. There were no differences in the seroprevalence by gender, ethnicity or region. Poisson regression model confirmed the prevalence have not changed in urban areas since 2001 but in rural areas, there was a significant positive time trend such that by year 2008, rural prevalence was as high as in urban areas. Dengue seroprevalence has stabilized but persisted at a high level in urban areas since 2001, and is fast stabilizing in rural areas at the same high urban levels by 2008. The cumulative seroprevalence of dengue exceeds 90 % by the age of 70 years, which translates into 16.5 million people or 55 % of the total population in Malaysia, being infected by dengue by 2013.

  15. Findings at brain MRI in children with dengue fever and neurological symptoms

    International Nuclear Information System (INIS)

    Rastogi, Ruchi; Garg, Bhavya

    2016-01-01

    Dengue is a flavivirus of the genus arbovirus with four serotypes, from DEN 1 to DEN 4. There has been an increase in incidence of dengue infection in children in the tropics and subtropics. Dengue has a variable clinical presentation, with many patients being asymptomatic. Its clinical manifestations in children vary from fever and arthralgia to life-threatening dengue hemorrhagic fever and dengue shock syndrome. We describe MRI findings in children with neurological involvement including dengue encephalopathy, acute hypoxic injury and dengue encephalitis. Dengue encephalopathy is usually secondary to multisystem derangement such as shock, hepatitis, coagulopathy and concurrent bacterial infection and is relatively common. Dengue encephalitis from direct neuronal invasion is rare. Nonspecific changes are seen on brain MRI in dengue infection. Clinical and laboratory findings as well as outcome do not necessarily correspond with brain MRI findings. (orig.)

  16. Findings at brain MRI in children with dengue fever and neurological symptoms

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Ruchi; Garg, Bhavya [Indraprastha Apollo Hospitals, Department of Radiodiagnosis, New Delhi (India)

    2016-01-15

    Dengue is a flavivirus of the genus arbovirus with four serotypes, from DEN 1 to DEN 4. There has been an increase in incidence of dengue infection in children in the tropics and subtropics. Dengue has a variable clinical presentation, with many patients being asymptomatic. Its clinical manifestations in children vary from fever and arthralgia to life-threatening dengue hemorrhagic fever and dengue shock syndrome. We describe MRI findings in children with neurological involvement including dengue encephalopathy, acute hypoxic injury and dengue encephalitis. Dengue encephalopathy is usually secondary to multisystem derangement such as shock, hepatitis, coagulopathy and concurrent bacterial infection and is relatively common. Dengue encephalitis from direct neuronal invasion is rare. Nonspecific changes are seen on brain MRI in dengue infection. Clinical and laboratory findings as well as outcome do not necessarily correspond with brain MRI findings. (orig.)

  17. Nine year trends of dengue virus infection in Mumbai, Western India

    Directory of Open Access Journals (Sweden)

    Jayanthi Shastri

    2017-01-01

    Methods and Results: During the nine year period of this study analysis, 6767 strongly suspected cases were tested by RT-PCR. 1685 (24.9% were Dengue PCR positive and confirmed as Dengue cases. Observations on the seasonality were based on the nine year's data as the intensity of sampling was at its maximum during monsoon season. Dengue typing was done on 100 positive samples after storage of Dengue RNA at – 80°C. Dengue serotypes were detected in 69 samples of which Dengue 2 was most predominant. 576 samples were processed for NS1 antigen and PCR simultaneously. 19/576 were positive (3.3 % for NS1 as well as by PCR . 23/576 samples were negative for NS1 antigen, but were positive by RT-PCR. The remaining 534 samples which were negative for NS1 antigen were also negative by Dengue RT-PCR. Conclusion: In this study we sought to standardize rapid, sensitive, and specific fluorogenic probe-based RT-PCR assay to screen and serotype a representative range of Dengue viruses that are found in and around Mumbai. Qualitative Dengue virus TaqMan assays could have tremendous utility for the epidemiological investigation of Dengue illness and especially for the study of the viremic response with candidate live-attenuated dengue virus vaccines.

  18. Assessing the methods needed for improved dengue mapping: a SWOT analysis.

    Science.gov (United States)

    Attaway, David Frost; Jacobsen, Kathryn H; Falconer, Allan; Manca, Germana; Waters, Nigel M

    2014-01-01

    Dengue fever, a mosquito-borne viral infection, is a growing threat to human health in tropical and subtropical areas worldwide. There is a demand from public officials for maps that capture the current distribution of dengue and maps that analyze risk factors to predict the future burden of disease. To identify relevant articles, we searched Google Scholar, PubMed, BioMed Central, and WHOLIS (World Health Organization Library Database) for published articles with a specific set of dengue criteria between January 2002 and July 2013. After evaluating the currently available dengue models, we identified four key barriers to the creation of high-quality dengue maps: (1) data limitations related to the expense of diagnosing and reporting dengue cases in places where health information systems are underdeveloped; (2) issues related to the use of socioeconomic proxies in places with limited dengue incidence data; (3) mosquito ranges which may be changing as a result of climate changes; and (4) the challenges of mapping dengue events at a variety of scales. An ideal dengue map will present endemic and epidemic dengue information from both rural and urban areas. Overcoming the current barriers requires expanded collaboration and data sharing by geographers, epidemiologists, and entomologists. Enhanced mapping techniques would allow for improved visualizations of dengue rates and risks.

  19. Activity of andrographolide against dengue virus.

    Science.gov (United States)

    Panraksa, Patcharee; Ramphan, Suwipa; Khongwichit, Sarawut; Smith, Duncan R

    2017-03-01

    Dengue is the most prevalent arthropod-transmitted viral illness of humans, with an estimated 100 million symptomatic infections occurring each year and more than 2.5 billion people living at risk of infection. There are no approved antiviral agents against dengue virus, and there is only limited introduction of a dengue vaccine in some countries. Andrographolide is derived from Andrographis paniculata, a medicinal plant traditionally used to treat a number of conditions including infections. The antiviral activity of andrographolide against dengue virus (DENV) serotype 2 was evaluated in two cell lines (HepG2 and HeLa) while the activity against DENV 4 was evaluated in one cell line (HepG2). Results showed that andrographolide had significant anti-DENV activity in both cell lines, reducing both the levels of cellular infection and virus output, with 50% effective concentrations (EC 50 ) for DENV 2 of 21.304 μM and 22.739 μM for HepG2 and HeLa respectively. Time of addition studies showed that the activity of andrographolide was confined to a post-infection stage. These results suggest that andrographolide has the potential for further development as an anti-viral agent for dengue virus infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Dengue Virus Genome Uncoating Requires Ubiquitination.

    Science.gov (United States)

    Byk, Laura A; Iglesias, Néstor G; De Maio, Federico A; Gebhard, Leopoldo G; Rossi, Mario; Gamarnik, Andrea V

    2016-06-28

    The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. Dengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade

  1. Dengue-associated telogen effluvium: A report of 14 patients

    Directory of Open Access Journals (Sweden)

    Chia-Bao Chu

    2017-09-01

    Conclusions: Physicians should be aware of dengue-associated TE especially in dengue endemic areas or after a dengue outbreak. Thorough medical history, examination and laboratory tests should be obtained to yield correct diagnosis or to identify coexistence of two hair diseases.

  2. A model of immunomodulatory for dengue infection mm

    Science.gov (United States)

    Zulfa, Annisa; Handayani, Dewi; Nuraini, Nuning

    2018-03-01

    An immunomodulatory model for dengue infection is constructed in this paper. This study focuses on T-cell compartments and B cells that are immune cells involved in the dengue infection process. Dengue virus-infected monocyte cells release interferons to signal T-cells to activate B-cells and produce antibodies. Immunomodulator acts as a treatment control and aims to increase the numbers of antibodies so it is expected to reduce the number of infected monocyte cells by dengue virus. Numerical simulation shows that the greater the rate of f (t) the immune cells will be stimulated to suppress the number of infected cells.

  3. Post encephalitic parkinsonism following dengue viral infection

    OpenAIRE

    Bopeththa, B. V. K. M.; Ralapanawa, U.

    2017-01-01

    Background Incidence of dengue fever as well as dengue hemorrhagic fever is increasing in Sri Lanka especially among elderly population. As the number of cases is rising, rare complications of dengue illness also can be seen in clinical practice when compared to the past few years. Prompt identification and treatment of such complications is challenging due to lack of awareness and unavailability of standard treatment. Case presentation 69 years old man presented with acute onset fever and wa...

  4. Projections of increased and decreased dengue incidence under climate change.

    Science.gov (United States)

    Williams, C R; Mincham, G; Faddy, H; Viennet, E; Ritchie, S A; Harley, D

    2016-10-01

    Dengue is the world's most prevalent mosquito-borne disease, with more than 200 million people each year becoming infected. We used a mechanistic virus transmission model to determine whether climate warming would change dengue transmission in Australia. Using two climate models each with two carbon emission scenarios, we calculated future dengue epidemic potential for the period 2046-2064. Using the ECHAM5 model, decreased dengue transmission was predicted under the A2 carbon emission scenario, whereas some increases are likely under the B1 scenario. Dengue epidemic potential may decrease under climate warming due to mosquito breeding sites becoming drier and mosquito survivorship declining. These results contradict most previous studies that use correlative models to show increased dengue transmission under climate warming. Dengue epidemiology is determined by a complex interplay between climatic, human host, and pathogen factors. It is therefore naive to assume a simple relationship between climate and incidence, and incorrect to state that climate warming will uniformly increase dengue transmission, although in general the health impacts of climate change will be negative.

  5. Pichia pastoris-expressed dengue 2 envelope forms virus-like particles without pre-membrane protein and induces high titer neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Shailendra Mani

    Full Text Available Dengue is a mosquito-borne viral disease with a global prevalence. It is caused by four closely-related dengue viruses (DENVs 1-4. A dengue vaccine that can protect against all four viruses is an unmet public health need. Live attenuated vaccine development efforts have encountered unexpected interactions between the vaccine viruses, raising safety concerns. This has emphasized the need to explore non-replicating dengue vaccine options. Virus-like particles (VLPs which can elicit robust immunity in the absence of infection offer potential promise for the development of non-replicating dengue vaccine alternatives. We have used the methylotrophic yeast Pichia pastoris to develop DENV envelope (E protein-based VLPs. We designed a synthetic codon-optimized gene, encoding the N-terminal 395 amino acid residues of the DENV-2 E protein. It also included 5' pre-membrane-derived signal peptide-encoding sequences to ensure proper translational processing, and 3' 6× His tag-encoding sequences to facilitate purification of the expressed protein. This gene was integrated into the genome of P. pastoris host and expressed under the alcohol oxidase 1 promoter by methanol induction. Recombinant DENV-2 protein, which was present in the insoluble membrane fraction, was extracted and purified using Ni(2+-affinity chromatography under denaturing conditions. Amino terminal sequencing and detection of glycosylation indicated that DENV-2 E had undergone proper post-translational processing. Electron microscopy revealed the presence of discrete VLPs in the purified protein preparation after dialysis. The E protein present in these VLPs was recognized by two different conformation-sensitive monoclonal antibodies. Low doses of DENV-2 E VLPs formulated in alum were immunogenic in inbred and outbred mice eliciting virus neutralizing titers >1,1200 in flow cytometry based assays and protected AG129 mice against lethal challenge (p<0.05. The formation of immunogenic DENV-2 E

  6. Dengue Haemorrhagic Encephalitis: Rare Case Report with Review of Literature.

    Science.gov (United States)

    Kutiyal, Aditya Singh; Malik, Chetanya; Hyanki, Gitika

    2017-07-01

    Dengue is an endemic arboviral infection prevalent especially in tropical countries including Southern and Southeast Asia. Central Nervous System (CNS) involvement in dengue infection is uncommon. Haemorrhagic encephalitis is a rare presentation in dengue. This is a case of a 58-year-old male who presented with fever, petechial rash and altered sensorium. Dengue serology IgM was reactive and MRI brain was suggestive of haemorrhagic encephalitis. Patient was managed in Intensive Care Unit (ICU) but eventually succumbed to his illness. We report this fatal outcome of a common viral infection with unusual neurological presentation to propose an association between dengue and neurotropism and the need to look at dengue infection beyond its classical features.

  7. Retrospective analysis of dengue specific IgM reactive serum samples

    OpenAIRE

    Nemai Bhattacharya; Bhaswati Bandyopadhyay; Indranil Bhattacharjee; Hiranmoy Mukherjee; Srabani Talukdar; Ruby Mondal; Netai Pramanick; Goutam Chandra; Amiya K. Hati

    2013-01-01

    Objective: To conduct a retrospective analysis of dengue cases in Kolkata, on the basis of presence of anti-dengue IgM in their sera and presence or absence of anti-dengue IgG and dengue specific Non structural 1 (NS1) antigen in each of the serum sample. Methods: Sample was tested quantitatively employing ELISA technique, using Biorad test kits, with a view to get a more comprehensive picture of dengue in an urban endemic area and also to evaluate individual cases. Results: Th...

  8. Dengue in travellers: applicability of the 1975-1997 and the 2009 WHO classification system of dengue fever

    NARCIS (Netherlands)

    Wieten, Rosanne W.; Vlietstra, Wytze; Goorhuis, Abraham; van Vugt, Michèle; Hodiamont, Caspar J.; Leenstra, Tjalling; de Vries, Peter J.; Janssen, Saskia; van Thiel, Pieter P.; Stijnis, Kees; Grobusch, Martin P.

    2012-01-01

    Objectives The aim of this study was to assess the applicability and benefits of the new WHO dengue fever guidelines in clinical practice, for returning travellers. Methods We compared differences in specificity and sensitivity between the old and the new guidelines for diagnosing dengue and

  9. Evaluation of the WHO 2009 classification for diagnosis of acute dengue in a large cohort of adults and children in Sri Lanka during a dengue-1 epidemic.

    Directory of Open Access Journals (Sweden)

    Champica K Bodinayake

    2018-02-01

    Full Text Available Dengue is a leading cause of fever and mimics other acute febrile illnesses (AFI. In 2009, the World Health Organization (WHO revised criteria for clinical diagnosis of dengue.The new WHO 2009 classification of dengue divides suspected cases into three categories: dengue without warning signs, dengue with warning signs and severe dengue. We evaluated the WHO 2009 classification vs physicians' subjective clinical diagnosis (gestalt clinical impression in a large cohort of patients presenting to a tertiary care center in southern Sri Lanka hospitalized with acute febrile illness. We confirmed acute dengue in 388 patients (305 adults ≥ 18 years and 83 children, including 103 primary and 245 secondary cases, of 976 patients prospectively enrolled with AFI. At presentation, both adults and children with acute dengue were more likely than those with other AFI to have leukopenia and thrombocytopenia. Additionally, adults were more likely than those with other AFI to have joint pain, higher temperatures, and absence of crackles on examination whereas children with dengue were more likely than others to have sore throat, fatigue, oliguria, and elevated hematocrit and transaminases. Similarly, presence of joint pain, thrombocytopenia, and absence of cough were independently associated with secondary vs primary dengue in adults whereas no variables were different in children. The 2009 WHO dengue classification was more sensitive than physicians' clinical diagnosis for identification of acute dengue (71.5% vs 67.1%, but was less specific. However, despite the absence of on-site diagnostic confirmation of dengue, clinical diagnosis was more sensitive on discharge (75.2%. The 2009 WHO criteria classified almost 75% as having warning signs, even though only 9 (2.3% patients had evidence of plasma leakage and 16 (4.1% had evidence of bleeding.In a large cohort with AFI, we identified features predictive of dengue vs other AFI and secondary vs primary dengue

  10. Immunological evaluation in nonhuman primates of formulations based on the chimeric protein P64k-domain III of dengue 2 and two components of Neisseria meningitidis.

    Science.gov (United States)

    Valdés, Iris; Hermida, Lisset; Martín, Jorge; Menéndez, Tamara; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Niebla, Olivia; López, Carlos; Bernardo, Lídice; Sánchez, Jorge; Romero, Yaremis; Martínez, Rafael; Guzmán, María G; Guillén, Gerardo

    2009-02-11

    The main problem in the development of successful vaccines against dengue based on recombinant proteins is the necessity to use potent adjuvants to reach a proper functional immune response. Our group reported the expression, characterization and immunological evaluation of the recombinant protein PD5, which contains the domain III of the Envelope protein from dengue 2 virus fused to the carrier protein P64k. This construct completely protected monkeys against viral challenge when the Freund's adjuvant was employed. Therefore, to define suitable formulations for human use, the present work relies on the evaluation of PD5, produced with a high purity and under GMP conditions, when formulated either with outer membrane vesicles (OMV) or the serogroup A capsular polysaccharide (CPS-A) from Neisseria meningitidis, both adsorbed on aluminium hydroxide. The antibody response to the formulation containing the CPS-A was clearly superior to that of the formulation with OMV. The experiment of in vivo protection supported this evidence, since only the group immunized with PD5 and CPS-A was partially protected upon viral challenge. This is the first study in which the polysaccharide A of N. meningitidis is successfully employed as adjuvant for viral antigens.

  11. Diabetes Mellitus Increases Severity of Thrombocytopenia in Dengue-Infected Patients

    Directory of Open Access Journals (Sweden)

    Chung-Yuan Chen

    2015-02-01

    Full Text Available Background: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. Methods: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Results: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54 ± 51.69 vs. 86.58 ± 63.4 (p ≤ 0.001, 43.98 ± 44.09 vs. 64.52 ± 45.06 (p = 0.002, 43.86 ± 35.75 vs. 62.72 ± 51.2 (p = 0.012. Diabetes mellitus, death, dengue shock syndrome (DSS and dengue hemorrhagic fever (DHF and increased glutamic-pyruvate transaminase (GPT levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of −13.981 (95% confidence interval (CI −27.587, −0.374, −26.847 (95% CI −37.562, −16.132, and 0.054 (95% CI 0.015, 0.094 respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of −2.947 (p = 0.004, 2.801 (p = 0.005, and −3.568 (p ≤ 0.001, respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in

  12. Dengue em crianças: da notificação ao óbito Dengue en niños: de la notificación al óbito Dengue in children: from notification to death

    Directory of Open Access Journals (Sweden)

    Adriana Helena M. Abe

    2012-06-01

    Full Text Available OBJETIVO: Descrever aspectos históricos, epidemiológicos e clínicos da dengue em crianças, demonstrando a importância das notificações e conhecimento destas para prevenir a evolução de gravidade e os óbitos nessa população. FONTES DE DADOS: Revisão narrativa dos principais trabalhos publicados sobre dengue e dengue em crianças. Buscaram-se estudos nas seguintes bases de dados: Lilacs, SciELO, Medline e Scopus, além de documentos oficiais do Ministério da Saúde. A busca incluiu trabalhos publicados no período de janeiro de 1980 a março de 2011. Os descritores utilizados foram: dengue, dengue em criança, dengue em pediatria e notificação de doenças. SÍNTESE DOS DADOS: Todos os artigos encontrados foram avaliados e procurou-se estabelecer uma linha de tempo e principais informações alusivas ao tema, fatores referentes ao vírus e ao vetor também foram incluídos; informações sobre as características clínicas e importância das notificações foram apontadas, além da relevante investigação e elucidação de todos os óbitos notificados. Existe um grande número de estudos sobre o assunto, porém foi dada maior ênfase àqueles pertinentes às crianças. CONCLUSÕES: O conhecimento desta doença, que se configura como principal doença emergente e reemergente na atualidade, é fundamental para diagnóstico precoce, tratamento oportuno e prevenção de óbitos. Há uma lacuna na notificação adequada em Pediatria, assim como no detalhamento dos óbitos em crianças vítimas de dengue.OBJETIVO: Describir aspectos históricos, epidemiológicos y clínicos del dengue en niños, demostrando la importancia de las notificaciones y conocimiento de estas para la prevención de evolución de gravedad y óbitos en esta población. FUENTES DE DATOS: Revisión narrativa de los principales trabajos publicados sobre dengue y dengue en niños. Se buscaron estudios en las siguientes bases de datos: Lilacs, SciELO, Medline y Scopus

  13. Epidemia de dengue en Nicaragua, 1985 Epidemic dengue in Nicaragua 1985

    Directory of Open Access Journals (Sweden)

    G. Kouri

    1991-10-01

    Full Text Available En el segundo semestre de 1985, coincidiendo con el período de lluvias se produjo en Nicaragua una epidemia de Dengue en la que se reportaron 17,483 casos. La mayor morbilidad y las más elevadas tasas de ataque se registraron entre Agosto y Noviembre, siendo afectadas fundamentalmente las regiones II (León y Chinandega, III (Managua y IV (Masaya, Granada, Carazo, Rivas que acumularon el 89% de los reportes. Estas regiones se corresponden precisamente con las zonas más densamente pobladas ubicadas en la costa del Pacífico, en donde se encuentran los núcleos urbanos mas importantes y populosos del país. León y Chinandega fueron las ciudades mas afectadas, pues reportaron el 41% del total de casos registrados. El 66.8% de los casos eran adultos y el 57.6% del sexo femenino. La tasa global de ataque para el país fue de 55.24 x 10.000 habitantes. Una campaña de lucha antivectorial, fue iniciada de inmediato, manteniéndose en forma intensiva hasta el mes de Octubre. Al final de este período la morbilidad disminuyó considerablemente y la enfermedad entró en una fase de escasos reportes y posiblemente de endemia. Se reportaron 7 adultos fallecidos que fueron considerados como portadores de una FHD/SCD por un grupo mixto de patólogos y clínicos teniendo en cuenta la experiencia adquirida en los pacientes adultos durante la epidemia ocurrida en Cuba en 1981. El brote fue interpretado como una epidemia de Dengue Clásico en la cual se produjeron 7 casos fatales. Se aislaron los serotipos 1 y 2 del Dengue en sueros de fase aguda de pacientes y el serotipo 1 en el de uno de los fallecidos.In the second half of the year 1985, during the rainy season, an epidemic of Dengue Fever was recognized in Nicaragua. A total of 17.483 cases were reported by the health services. The highest morbidity and attack rates were reported between August and November of the same year. Regions II (Leon and Chinandega, III (Managua and IV (Masaya, Granada, Carazo y

  14. Is dengue a disease of poverty? A systematic review.

    Science.gov (United States)

    Mulligan, Kate; Dixon, Jenna; Sinn, Chi-Ling Joanna; Elliott, Susan J

    2015-02-01

    Policy prescriptions for combating dengue fever tend to focus on addressing environmental and social conditions of poverty. However, while poverty has long been considered a determinant of dengue, the research evidence for such a relationship is not well established. Results of a systematic review of the research literature designed to identify and assess the current state of the empirical evidence for the dengue-poverty link reveal a mixed story. Of 260 peer-reviewed articles referencing dengue-poverty relationships, only 12 English-language studies empirically assessed these relationships. Our analysis covering various social and economic conditions of poverty showed no clear associations with dengue rates. While nine of the 12 studies demonstrated some positive associations between measures of dengue and poverty (measured inconsistently through income, education, structural housing condition, overcrowding, and socioeconomic status), nine also presented null results and five with negative results. Of the five studies relating to access to water and sanitation, four reported null associations. Income and physical housing conditions were more consistently correlated with dengue outcomes than other poverty indicators. The small size of this sample, and the heterogeneity of measures and scales used to capture conditions of poverty, make it difficult to assess the strength and consistency of associations between various poverty indicators and dengue outcomes. At present, the global body of eligible English-language peer-reviewed literature investigating dengue-poverty relationships is too small to support a definitive relationship. We conclude that more research, particularly using standardized measures of both outcomes and indicators, is needed to support evidence-informed policies and approaches.

  15. Contribution to the physicochemical investigation of monovalent thallium and tetravalent uranium fluorides

    International Nuclear Information System (INIS)

    Hsini, M.S.

    1983-07-01

    Ionic transport properties are studied in monovalent elements and tetravalent uranium fluorides and oxyfluorides. Crystal structure of the oxyfluoride: TlUsub(2.75)OF 10 was determined by X-ray diffraction on a monocrystal. The particular role played by oxygen is evidenced in the stabilization of the crystal structure based on an original arrangement of Archimedes antiprisms: UOF 7 corresponding to a long distance order oxygen-fluorine in the anionic network. Electric conductivity measurements in AC by the complex impedance method or in DC by the Van der Pauw method allowed performance estimation of these materials which are solid electrolytes. Correlations between electrical properties and structure give information in basic diffusion mechanism in these materials [fr

  16. Evaluation of concurrent malaria and dengue infections among febrile patients

    Directory of Open Access Journals (Sweden)

    Parul D Shah

    2017-01-01

    Full Text Available Context: Despite a wide overlap between endemic areas for two important vector-borne infections, malaria and dengue, published reports of co-infections are scarce till date. Aims: To find the incidence of dengue and malaria co-infection as well as to ascertain the severity of such dengue and malaria co-infection based on clinical and haematological parameters. Setting and Design: Observational, retrospective cross-sectional study was designed including patients who consulted the tertiary care hospital of Ahmedabad seeking treatment for fever compatible with malaria and/or dengue. Subjects and Methods: A total of 8364 serum samples from clinically suspected cases of fever compatible with malaria and/or dengue were collected. All samples were tested for dengue NS-1 antigen before 5 days of onset of illness and for dengue IgM after 5 days of onset of illness. In all samples, malaria diagnosis was based on the identification of Plasmodium parasites on a thin and thick blood films microscopy. Results: Only 10.27% (859 patients with fever were tested positive for dengue and 5.1% (434 were tested positive for malaria. 3.14% (27 dengue cases show concurrent infection with malarial parasites. Hepatomegaly and jaundice 37.03% (10, haemorrhagic manifestations 18.51% (5 and kidney failure 3.7% (1, haemoglobin <12 g/dl 100% (27 and thrombocytopenia (platelet count <150,000/cmm 96.29% (26 were common in malaria and dengue co-infections and were much more common in Plasmodium falciparum infections. Conclusion: All febrile patients must be tested for malaria and dengue, both otherwise one of them will be missed in case of concurrent infections which could lead to severe diseases with complications.

  17. Crystalline insoluble acid salts of tetravalent metals

    International Nuclear Information System (INIS)

    Alberti, G.; Bernasconi, M.G.; Casciola, M.; Costantino, U.

    1980-01-01

    Several titration curves of crystalline acid salts of tetravalent metals show an evident decrease in the pH of the supernatant solution with an increasing addition of metal hydroxide. This phenomenon, very unusual for common organic ion-exchangers, seems to be quite general for inorganic ion-exchangers with layered structure of α-type. In order to throw light on this phenomenon, a detailed investigation was carried out on the titration curves of α-Zr(HPO 4 ) 2 .H 2 O with various metal hydroxides, particularly KOH. To obtain the presence of a distinct minimum in the titration curve, three conditions seem to be necessary: (1) high activation energy for H + /Msup(Z+) exchange (which, in turn, depends on the relative size of Msup(Z+) and size of the windows connecting the cavities), (2) formation of solid solution having high M-content and (3) formation of a phase, with a large inter-layer distance, in the external parts of the crystals. This last point is particularly important since the enlargement of the external part of the crystals lowers the activation energy for the exchange of large cations. Thus, once started, the exchange can take place at lower pH' values. (author)

  18. Economic and Disease Burden of Dengue in Mexico

    Science.gov (United States)

    Undurraga, Eduardo A.; Betancourt-Cravioto, Miguel; Ramos-Castañeda, José; Martínez-Vega, Ruth; Méndez-Galván, Jorge; Gubler, Duane J.; Guzmán, María G.; Halstead, Scott B.; Harris, Eva; Kuri-Morales, Pablo; Tapia-Conyer, Roberto; Shepard, Donald S.

    2015-01-01

    Background Dengue imposes a substantial economic and disease burden in most tropical and subtropical countries. Dengue incidence and severity have dramatically increased in Mexico during the past decades. Having objective and comparable estimates of the economic burden of dengue is essential to inform health policy, increase disease awareness, and assess the impact of dengue prevention and control technologies. Methods and Findings We estimated the annual economic and disease burden of dengue in Mexico for the years 2010–2011. We merged multiple data sources, including a prospective cohort study; patient interviews and macro-costing from major hospitals; surveillance, budget, and health data from the Ministry of Health; WHO cost estimates; and available literature. We conducted a probabilistic sensitivity analysis using Monte Carlo simulations to derive 95% certainty levels (CL) for our estimates. Results suggest that Mexico had about 139,000 (95%CL: 128,000–253,000) symptomatic and 119 (95%CL: 75–171) fatal dengue episodes annually on average (2010–2011), compared to an average of 30,941 symptomatic and 59 fatal dengue episodes reported. The annual cost, including surveillance and vector control, was US$170 (95%CL: 151–292) million, or $1.56 (95%CL: 1.38–2.68) per capita, comparable to other countries in the region. Of this, $87 (95%CL: 87–209) million or $0.80 per capita (95%CL: 0.62–1.12) corresponds to illness. Annual disease burden averaged 65 (95%CL: 36–99) disability-adjusted life years (DALYs) per million population. Inclusion of long-term sequelae, co-morbidities, impact on tourism, and health system disruption during outbreaks would further increase estimated economic and disease burden. Conclusion With this study, Mexico joins Panama, Puerto Rico, Nicaragua, and Thailand as the only countries or areas worldwide with comprehensive (illness and preventive) empirical estimates of dengue burden. Burden varies annually; during an outbreak

  19. Dengue severity in the elderly in Puerto Rico

    Directory of Open Access Journals (Sweden)

    Enid J. García-Rivera

    2003-06-01

    Full Text Available OBJECTIVE: Severe dengue affects all age groups in the Americas, but little detailed information is available about this disease in the elderly. The objective of this article is to describe the disease in this age group. METHODS: We reviewed suspected dengue-case investigation forms submitted with diagnostic samples as well as clinical reports from infection control nurses in Puerto Rico, for the period of 1994 through 1999. RESULTS: We assigned the laboratory-positive case-patients to four age groups: infants (1 year: 554, youth (2 to 18 years: 6 857, adults (19 to 64 years: 9 433, and elderly (> 65 years: 822. Regardless of infecting serotype, the elderly were more likely to have been hospitalized (48% vs. 33% (P <0.01 and were less likely to show hemorrhage (26% vs. 33% (P <0.01. On multivariate analysis, controlling for gender and the presence of hemorrhage, the elderly had a higher risk for hospitalization and death than did the youths and the adults. CONCLUSIONS: The elderly appear to be more likely than youth and younger adults to develop severe illness when infected with the dengue virus, in a pattern similar to that of infants. The clinical evaluation of elderly patients with dengue must include a careful assessment of increased capillary permeability and occult hemorrhage in order to avoid complications from delayed identification and treatment of severe dengue infection. These findings are of increasing importance for dengue epidemiology and medical care in view of the expanding nature of dengue and dengue hemorrhagic fever in a world that also has a growing number and proportion of elderly persons.

  20. Nine year trends of dengue virus infection in Mumbai, Western India

    OpenAIRE

    Shastri, Jayanthi; Williamson, Manita; Vaidya, Nilima; Agrawal, Sachee; Shrivastav, Om

    2017-01-01

    Introduction: Dengue virus (DENV) causes a wide range of diseases in humans, from acute febrile illness Dengue fever (DF) to life-threatening Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Factors believed to be responsible for spread of Dengue virus infection include explosive population growth, unplanned urban overpopulation with inadequate public health systems, poor standing water and vector control, climate changes and increased international recreational, business, milit...

  1. Dengue Virus 1 Outbreak in Buenos Aires, Argentina, 2016.

    Science.gov (United States)

    Tittarelli, Estefanía; Lusso, Silvina B; Goya, Stephanie; Rojo, Gabriel L; Natale, Mónica I; Viegas, Mariana; Mistchenko, Alicia S; Valinotto, Laura E

    2017-10-01

    The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. Phylogenetic, phylodynamic, and phylogeographic analyses of 82 samples from dengue patients revealed co-circulation of 2 genotype V dengue virus lineages, suggesting that this virus has become endemic to the Buenos Aires metropolitan area.

  2. Transmission Dinamics Model Of Dengue Fever

    Science.gov (United States)

    Debora; Rendy; Rahmi

    2018-01-01

    Dengue fever is an endemic disease that is transmitted through the Aedes aegypti mosquito vector. The disease is present in more than 100 countries in America, Africa, and Asia, especially tropical countries. Differential equations can be used to represent the spread of dengue virus occurring in time intervals and model in the form of mathematical models. The mathematical model in this study tries to represent the spread of dengue fever based on the data obtained and the assumptions used. The mathematical model used is a mathematical model consisting of Susceptible (S), Infected (I), Viruses (V) subpopulations. The SIV mathematical model is then analyzed to see the solution behaviour of the system.

  3. Autoimmune features caused by dengue fever: a case report

    Directory of Open Access Journals (Sweden)

    Denis Leonardo Fontes Jardim

    Full Text Available Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 level and positive antinuclear antibody; cryoglobulins were also positive. The numerous autoimmune features of this patient were a diagnostic challenge, since she was a young woman and could be easily mistaken for a rheumatologic patient in a newly open disease. Dengue infection probably was a triggering event causing an abnormal immune response. Therefore, dengue should be suspected in patients with hematological disorders and autoimmune features in endemic regions or those who have travelled to those regions.

  4. Underrecognition of Dengue during 2013 Epidemic in Luanda, Angola.

    Science.gov (United States)

    Sharp, Tyler M; Moreira, Rosa; Soares, Maria José; Miguel da Costa, Lúis; Mann, Jennifer; DeLorey, Mark; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L; Colón, Candimar; Margolis, Harold S; de Caravalho, Adelaide; Tomashek, Kay M

    2015-08-01

    During the 2013 dengue epidemic in Luanda, Angola, 811 dengue rapid diagnostic test-positive cases were reported to the Ministry of Health. To better understand the magnitude of the epidemic and identify risk factors for dengue virus (DENV) infection, we conducted cluster surveys around households of case-patients and randomly selected households 6 weeks after the peak of the epidemic. Of 173 case cluster participants, 16 (9%) exhibited evidence of recent DENV infection. Of 247 random cluster participants, 25 (10%) had evidence of recent DENV infection. Of 13 recently infected participants who had a recent febrile illness, 7 (54%) had sought medical care, and 1 (14%) was hospitalized with symptoms consistent with severe dengue; however, none received a diagnosis of dengue. Behavior associated with protection from DENV infection included recent use of mosquito repellent or a bed net. These findings suggest that the 2013 dengue epidemic was larger than indicated by passive surveillance data.

  5. Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

    Science.gov (United States)

    Parkash, Om; Hanim Shueb, Rafidah

    2015-01-01

    Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed. PMID:26492265

  6. Dengue in the United States of America: A Worsening Scenario?

    Directory of Open Access Journals (Sweden)

    Germán Añez

    2013-01-01

    Full Text Available Dengue is a febrile illness caused by any of the four dengue virus types (DENV-1 to -4, genus Flavivirus, family Flaviviridae mainly transmitted by the mosquito Aedes aegypti. DENV can be transmitted by blood transfusion. Dengue has been historically present in the continental United States (US, in the state of Hawaii, and in the US insular territories in the Caribbean and the Pacific. During the second half of the 20th century, most of the cases reported in the US were imported cases brought to the country by travelers. Since 2009, cases of autochthonous dengue have been recognized in the state of Florida after 75 years of absence, followed by intensification of transmission in endemic places including the US territories of US Virgin Islands and Puerto Rico, which experienced a large dengue epidemic in 2010. The widespread distribution of dengue mosquito vectors, deficient mosquito control measures and increased frequency of DENV-infected visitors to the US coming from dengue-endemic locations or places experiencing epidemics appear to be jointly responsible for the emergence and reemergence of dengue in the US and its territories.

  7. Vaccines licensed and in clinical trials for the prevention of dengue.

    Science.gov (United States)

    Torresi, J; Ebert, G; Pellegrini, M

    2017-05-04

    Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1-80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans.

  8. [Dengue, Zika and Chikungunya].

    Science.gov (United States)

    Kantor, Isabel N

    2016-01-01

    Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation.

  9. Dengue fever in the San Juan Bay Estuary: Evaluating the ...

    Science.gov (United States)

    Dengue is transmitted by Aedes aegypti, a species that thrives in cities. Here we ask which elements within the urban environment could be managed to reduce the potential for Dengue occurrence. In particular, we study the potential of wetlands in the SJBE to buffer from vector proliferation. Wetlands provide ecosystem services such as heat and water hazard mitigation, water purification and habitat for a diversity of species, all of which are factors that have been shown to affect Dengue vectors. As such, we hypothesize that within coastal neighborhoods in the SJBE wetlands, ecosystem services lead to lower Dengue occurrence. We test this hypothesis using Dengue data from 2010-2013, which includes the largest epidemic in PR history. Our analytical model includes relevant socio-economic factors and environmental controls that may also affect Dengue dynamics. Results indicated a negative effect of neighborhood mangrove cover and a positive effect of percent flood area on Dengue prevalence. Moreover, heat hazards were positively correlated with dengue prevalence and negatively correlated with neighborhood mangrove cover. Dengue prevalence did not correlate with herbaceous wetlands, or with the ecosystem services of water quality or vertebrate species richness. Mosquito borne diseases are an increasingly important health concern, which pose great challenges for safe and sustainable control and eradication. This reality calls for management approaches that consider m

  10. Dengue Haemorrhagic Fever presenting as Acute Abdomen

    OpenAIRE

    Al-Araimi, Hanaa; Al-Jabri, Amal; Mehmoud, Arshad; Al-Abri, Seif

    2011-01-01

    We describe a case of a 38 year-old Sri Lankan female who was referred to the surgeon on call with a picture of acute abdomen. She presented with a three-day history of fever, headache, abdominal pain and diarrhoea; however, the physical examination was not consistent with acute abdomen. Her platelet count was 22 ×109/L. A diagnosis of dengue haemorrhagic fever (DHF) was made and dengue serology was positive. Dengue epidemics have been associated with a variety of gastrointestinal symptoms an...

  11. Seroprevalence of Anti-Dengue Virus 2 Serocomplex antibodies in ...

    African Journals Online (AJOL)

    Introduction: There has been a recent increase in the spread of dengue to rural areas. Rural parts of western kenya are naturally prone to mosquito-borne diseases, however, limited research has been documented on infections with dengue. This study therefore investigated the presence of antibodies against dengue virus ...

  12. [Coexistence of acute appendicitis and dengue fever: A case report].

    Science.gov (United States)

    Osuna-Ramos, Juan Fidel; Silva-Gracia, Carlos; Maya-Vacio, Gerardo Joel; Romero-Utrilla, Alejandra; Ríos-Burgueño, Efrén Rafael; Velarde-Félix, Jesús Salvador

    2017-12-01

    Dengue is the most important human viral disease transmitted by mosquitoes. It can be asymptomatic or it can present in any of its 3clinical forms: Dengue fever, dengue haemorrhagic fever and dengue shock syndrome. However, some atypical manifestations have been reported in surgical emergencies caused by acute appendicitis in patients with dengue fever. We report the case of an 18-year-old Mexican male who presented to the emergency department of the General Hospital of Culiacan, Sinaloa, with symptoms of dengue fever, accompanied by crampy abdominal pain with positive Rovsing and Dunphy signs. Dengue infection was confirmed by a positive NS1 antigen test performed by enzyme-linked immunosorbent assay. An abdominal ultrasound revealed an appendicular process; as the abdominal pain in the right side kept increasing, an open appendectomy was performed. Abundant inflammatory liquid was observed during the surgery, and the pathology laboratory reported an oedematous appendix with fibrinopurulent plaques, which agreed with acute ulcerative appendicitis. The patient was discharged fully recovered without complications during the follow-up period. Acute abdominal pain can be caused in some cases by dengue infection. This can be confusing, which can lead to unnecessary surgical interventions, creating additional morbidities and costs for the patient. This unusual and coincident acute appendicitis with dengue highlights the importance of performing careful clinical studies for appropriate decision making, especially in dengue endemic regions during an outbreak of this disease. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  13. Risk factors for concurrent bacteremia in adult patients with dengue.

    Science.gov (United States)

    Thein, Tun-Linn; Ng, Ee-Ling; Yeang, Ming S; Leo, Yee-Sin; Lye, David C

    2017-06-01

    Bacteremia in dengue may occur with common exposure to pathogens in association with severe organ impairment or severe dengue, which may result in death. Cohort studies identifying risk factors for concurrent bacteremia among patients with dengue are rare. We conducted a retrospective case-control study of adult patients with dengue who were admitted to the Department of Infectious Diseases at Tan Tock Seng Hospital, Singapore from 2004 to 2008. For each case of dengue with concurrent bacteremia (within the first 72 hours of admission), we selected four controls without bacteremia, who were matched on year of infection and dengue confirmation method. Conditional logistic regression was performed to identify risk factors for concurrent bacteremia. Among 9,553 patients with dengue, 29 (0.3%) had bacteremia. Eighteen of these patients (62.1%) had concurrent bacteremia. The predominant bacteria were Staphylococcus aureus, one of which was a methicillin-resistant strain. Dengue shock syndrome occurred more frequently and hospital stay was longer among cases than among controls. Three cases did not survive, whereas none of the controls died. In multivariate analysis, being critically ill at hospital presentation was independently associated with 15 times the likelihood of a patient with dengue having concurrent bacteremia. Concurrent bacteremia in adult patients with dengue is uncommon but presents atypically and results in more deaths and longer hospital stay. Given the associated mortality, collection of blood cultures and empiric antibiotic therapy may be considered in patients who are critically ill. Copyright © 2015. Published by Elsevier B.V.

  14. Increased Levels of Txa₂ Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue.

    Science.gov (United States)

    Oliveira, Eneida S; Colombarolli, Stella G; Nascimento, Camila S; Batista, Izabella C A; Ferreira, Jorge G G; Alvarenga, Daniele L R; de Sousa, Laís O B; Assis, Rafael R; Rocha, Marcele N; Alves, Érica A R; Calzavara-Silva, Carlos E

    2018-02-28

    The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus -induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage.

  15. Cost and disease burden of Dengue in Cambodia

    Directory of Open Access Journals (Sweden)

    Beauté Julien

    2010-08-01

    Full Text Available Abstract Background Dengue is endemic in Cambodia (pop. estimates 14.4 million, a country with poor health and economic indicators. Disease burden estimates help decision makers in setting priorities. Using recent estimates of dengue incidence in Cambodia, we estimated the cost of dengue and its burden using disability adjusted life years (DALYs. Methods Recent population-based cohort data were used to calculate direct and productive costs, and DALYs. Health seeking behaviors were taken into account in cost estimates. Specific age group incidence estimates were used in DALYs calculation. Results The mean cost per dengue case varied from US$36 - $75 over 2006-2008 respectively, resulting in an overall annual cost from US$3,327,284 in 2008 to US$14,429,513 during a large epidemic in 2007. Patients sustain the highest share of costs by paying an average of 78% of total costs and 63% of direct medical costs. DALY rates per 100,000 individuals ranged from 24.3 to 100.6 in 2007-2008 with 80% on average due to premature mortality. Conclusion Our analysis confirmed the high societal and individual family burden of dengue. Total costs represented between 0.03 and 0.17% of Gross Domestic Product. Health seeking behavior has a major impact on costs. The more accurate estimate used in this study will better allow decision makers to account for dengue costs particularly among the poor when balancing the benefits of introducing a potentially effective dengue vaccine.

  16. Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions

    Science.gov (United States)

    Martelli, Celina Maria Turchi; Siqueira, Joao Bosco; Parente, Mirian Perpetua Palha Dias; Zara, Ana Laura de Sene Amancio; Oliveira, Consuelo Silva; Braga, Cynthia; Pimenta, Fabiano Geraldo; Cortes, Fanny; Lopez, Juan Guillermo; Bahia, Luciana Ribeiro; Mendes, Marcia Costa Ooteman; da Rosa, Michelle Quarti Machado; de Siqueira Filha, Noemia Teixeira; Constenla, Dagna; de Souza, Wayner Vieira

    2015-01-01

    Background Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. Methods We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients’ medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). Results We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012–2013) in the societal perspective was US$ 468 million (90% CL: 349–590) or US$ 1,212 million (90% CL: 904–1,526) after adjusting for under-reporting. Considering the time series of dengue (2009–2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). Conclusions The economic burden

  17. Crystallization and X-ray diffraction analysis of human CLEC5A (MDL-1), a dengue virus receptor

    International Nuclear Information System (INIS)

    Watson, Aleksandra A.; O’Callaghan, Christopher A.

    2009-01-01

    Recombinant human CLEC5A was crystallized in the trigonal space group P3 1 and X-ray diffraction data were collected to 1.56 Å resolution. The human C-type lectin-like protein CLEC5A (also known as MDL-1) is expressed on the surface of myeloid cells and plays a critical role in dengue-virus-induced disease by signalling through the transmembrane adaptor protein DAP12. The C-type lectin-like domain of CLEC5A was expressed in Escherichia coli, refolded and purified. Recombinant CLEC5A crystals were grown by sitting-drop vapour diffusion using polyethylene glycol 6000 as a precipitant. After optimization, crystals were grown which diffracted to 1.56 Å using synchrotron radiation. The results presented in this paper suggest that crystals producing diffraction of this quality will be suitable for structural determination of human CLEC5A

  18. Clinical and laboratory findings in patients with dengue associated with hepatopathy Achados clínicos e laboratoriais em pacientes com dengue associada à hepatopatia

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    Delso do Nascimento

    2011-12-01

    Full Text Available INTRODUCTION: Hepatic disorders caused by dengue infection may progress to severe manifestations, including mortality and morbidity. Cytokines are involved in it, such as the migration inhibitory factor of macrophages (MIF, tumor necrosis factor (TNF, natural killer cells (NK, B lymphocytes, and macrophages. METHODS: This study was carried out from January to April 2007 at a public hospital from the Federal University of Mato Grosso do Sul, Campo Grande, Brazil. Sixty-eight patients were studied concerning hepatic alterations, with 56 reported having classic dengue, 6 with hemorrhagic dengue grade I, and 6 with hemorrhagic dengue grade II. RESULTS: Among the 56 with classic dengue, 83.3% had aspartate aminotransferase (AST alterations, and 69.6% had altered alanine aminotransferase (ALT. For those with hemorrhagic dengue grade I, 100% had AST alterations, and 83.3% had altered ALT. All the patients with hemorrhagic dengue grade II had AST and ALT alterations. AST variations reached 22.0 and 907.0, with an average value of 164.6. For ALT, we found variations between 25.0 and 867.0, with an average value of 166.07. There had been statistical significance between dengue clinical shapes and hepatic function markers. CONCLUSIONS: We conclude that the infection was predominant in adults, females, and in those with low income and education. The liver enzymes were of larger amount in hemorrhagic dengue, but there was weak statistical evidence of the clinical manifestations and transaminases. Major signs and clinical symptoms were fever, headache, myalgia, arthralgia, weakness, severe pain behind the eyes, and rashes.INTRODUÇÃO: Afecções hepáticas causadas pela infecção da dengue podem evoluir para quadro grave, incluindo mortalidade e morbidade. O mecanismo de lesão do fígado está relacionado com a exacerbação da resposta imune. As citocinas estão envolvidas nele como fator inibidor da migração de macrófagos (MIF, fator de necrose

  19. Health System for Dengue Control : Early Case Detection and Focal Control

    OpenAIRE

    Umenai, Takusei; Nishigaki, Masaru; Osaka, Ken; Miura, Hiroko; Ishii, Katsumi

    1994-01-01

    "Aedes aegypti and dengue virus infection continue to spread in the tropical and subtropical world. Since there is no effective dengue vaccine, mosquito control and dengue patient treatment are the most important and practical way for dengue control. Many attempts have been made to control Aedes aegypti (adultcidal and larvicidal) to prevent dengue epidemic by large vertically-organized teams of workers. However, most of these methods have not been successful in the aspect of continuation of ...

  20. Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity.

    Science.gov (United States)

    Lee, Linda K; Gan, Victor C; Lee, Vernon J; Tan, Adriana S; Leo, Yee Sin; Lye, David C

    2012-01-01

    Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT ≥ 1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT ≥ 1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve=0.62; 95% confidence interval [CI]: 0.57-0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve=0.56; 95% CI: 0.52-0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.

  1. Factors determining dengue outbreak in Malaysia.

    Science.gov (United States)

    Ahmad, Rohani; Suzilah, Ismail; Wan Najdah, Wan Mohamad Ali; Topek, Omar; Mustafakamal, Ibrahim; Lee, Han Lim

    2018-01-01

    A large scale study was conducted to elucidate the true relationship among entomological, epidemiological and environmental factors that contributed to dengue outbreak in Malaysia. Two large areas (Selayang and Bandar Baru Bangi) were selected in this study based on five consecutive years of high dengue cases. Entomological data were collected using ovitraps where the number of larvae was used to reflect Aedes mosquito population size; followed by RT-PCR screening to detect and serotype dengue virus in mosquitoes. Notified cases, date of disease onset, and number and type of the interventions were used as epidemiological endpoint, while rainfall, temperature, relative humidity and air pollution index (API) were indicators for environmental data. The field study was conducted during 81 weeks of data collection. Correlation and Autoregressive Distributed Lag Model were used to determine the relationship. The study showed that, notified cases were indirectly related with the environmental data, but shifted one week, i.e. last 3 weeks positive PCR; last 4 weeks rainfall; last 3 weeks maximum relative humidity; last 3 weeks minimum and maximum temperature; and last 4 weeks air pollution index (API), respectively. Notified cases were also related with next week intervention, while conventional intervention only happened 4 weeks after larvae were found, indicating ample time for dengue transmission. Based on a significant relationship among the three factors (epidemiological, entomological and environmental), estimated Autoregressive Distributed Lag (ADL) model for both locations produced high accuracy 84.9% for Selayang and 84.1% for Bandar Baru Bangi in predicting the actual notified cases. Hence, such model can be used in forestalling dengue outbreak and acts as an early warning system. The existence of relationships among the entomological, epidemiological and environmental factors can be used to build an early warning system for the prediction of dengue outbreak so

  2. Mounting dengue awareness: A cost effective Strategy for prevention

    Directory of Open Access Journals (Sweden)

    Kajal Srivastava

    2015-12-01

    Full Text Available Background: Dengue is a serious illness which takes toll on human health every year. The best way to prevent it is by increasing awareness among common people. This study was conducted to assess the level of knowledge, attitudes and practices regarding dengue fever in people urban heath training centre in Pune, Maharashtra. Methods: A cross-sectional study was conducted among patients attending OPD of Urban heath training centre of department of community medicine, Pune situated in Ajmera, Pimpri, Pune. Through convenience sampling, a questionnaire was administered to patients after taking their informed consent. Results: A total of 100 patients were interviewed. Among knowledge 83% had heard about dengue and the most common source of information was TV & radio (72.3% Most of them were aware regarding mosquito bite being the mode of dengue transmission (80.7%. 22% were unaware regarding biting time of mosquito while 22% said night is the biting time of dengue mosquito. 62.7% were using coils for mosquito bite prevention followed by mosquito net (43.4% and spray (31.3%.. Conclusion: This study revealed that most of the study population is aware of dengue illness and increasing education level is having positive attitude on dengue illness.

  3. Mounting dengue awareness: A cost effective Strategy for prevention

    Directory of Open Access Journals (Sweden)

    Kajal Srivastava

    2015-12-01

    Full Text Available Background: Dengue is a serious illness which takes toll on human health every year. The best way to prevent it is by increasing awareness among common people. This study was conducted to assess the level of knowledge, attitudes and practices regarding dengue fever in people urban heath training centre in Pune, Maharashtra. Methods: A cross-sectional study was conducted among patients attending OPD of Urban heath training centre of department of community medicine, Pune situated in Ajmera, Pimpri, Pune. Through convenience sampling, a questionnaire was administered to patients after taking their informed consent. Results: A total of 100 patients were interviewed. Among knowledge 83% had heard about dengue and the most common source of information was TV & radio (72.3% Most of them were aware regarding mosquito bite being the mode of dengue transmission (80.7%. 22% were unaware regarding biting time of mosquito while 22% said night is the biting time of dengue mosquito. 62.7% were using coils for mosquito bite prevention followed by mosquito net (43.4% and spray (31.3%.. Conclusion: This study revealed that most of the study population is aware of dengue illness and increasing education level is having positive attitude on dengue illness.

  4. Dengue fatality prediction using data mining | Rahim | Journal of ...

    African Journals Online (AJOL)

    The aim of this research is to study the current implementation of dengue outbreak control in Malaysia and predict dengue fever cases using data mining techniques. Real data on dengue fever and weather are collected from the Ministry of Health in its Perak Tengah district office and Perak Meteorological office respectively ...

  5. Identification of natural antimicrobial agents to treat dengue infection: In vitro analysis of latarcin peptide activity against dengue virus.

    Science.gov (United States)

    Rothan, Hussin A; Bahrani, Hirbod; Rahman, Noorsaadah Abd; Yusof, Rohana

    2014-05-31

    Although there have been considerable advances in the study of dengue virus, no vaccines or anti-dengue drugs are currently available for humans. Therefore, new approaches are necessary for the development of potent anti-dengue drugs. Natural antimicrobial peptides (AMPs) with potent antiviral activities are potential hits-to-leads for antiviral drug discovery. We performed this study to identify and characterise the inhibitory potential of the latarcin peptide (Ltc 1, SMWSGMWRRKLKKLRNALKKKLKGE) against dengue virus replication in infected cells. The Ltc 1 peptide showed a significantly inhibitory effect against the dengue protease NS2B-NS3pro at 37°C, a physiological human temperature, (IC50, 12.68 ± 3.2 μM), and greater inhibitory effect was observed at 40°C, a temperature similar to a high fever (IC50, 6.58 ± 4.1 μM). A greater reduction in viral load (p.f.u./ml) was observed at simultaneous (0.7 ± 0.3 vs. 7.2 ± 0.5 control) and post-treatment (1.8 ± 0.7 vs. 6.8 ± 0.6 control) compared to the pre-treatment (4.5 ± 0.6 vs. 6.9 ± 0.5 control). Treatment with the Ltc 1 peptide reduced the viral RNA in a dose-dependent manner with EC50 values of 8.3 ± 1.2, 7.6 ± 2.7 and 6.8 ± 2.5 μM at 24, 48 and 72 h, respectively. The Ltc 1 peptide exhibited significant inhibitory effects against dengue NS2B-NS3pro and virus replication in the infected cells. Therefore, further investigation is necessary to develop the Ltc 1 peptide as a new anti-dengue therapeutic.

  6. Dengue in the elderly: a review.

    Science.gov (United States)

    Lin, Ray Junhao; Lee, Tau Hong; Leo, Yee Sin

    2017-08-01

    Changing dengue epidemiological trends have resulted in a shift in the disease burden to the adult population. Older adults suffer from poorer outcomes as compared to their younger counterparts, making clinical management of this sub-population particularly challenging. Areas covered: We present a review of the current literature on the changing epidemiology of dengue in the elderly, the atypical features of the clinical disease in this population with emphasis on severe disease presentations and challenges in the current management strategies. Expert commentary: Dengue in the elderly is an increasingly important yet greatly understudied area. There is an urgent need to refine the current diagnostic criteria to improve diagnosis, classification of disease severity and identify individuals in this population who are likely to progress to severe disease. Management strategies in this population would have to be adjusted to account for the increased number of co-morbidities. The role of the available dengue vaccines in this group is uncertain, and more studies into their safety and efficacy are critically needed.

  7. Immature dengue virus: a veiled pathogen?

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    Izabela A Rodenhuis-Zybert

    2010-01-01

    Full Text Available Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher in patients with secondary infection compared to those with primary infection. This suggests that immature dengue virus may play a role in disease pathogenesis. Interestingly, however, numerous functional studies have revealed that immature particles lack the ability to infect cells. In this report, we show that fully immature dengue particles become highly infectious upon interaction with prM antibodies. We demonstrate that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells. In addition, enzymatic activity of furin is critical to render the internalized immature virus infectious. Together, these data suggest that during a secondary infection or primary infection of infants born to dengue-immune mothers, immature particles have the potential to be highly infectious and hence may contribute to the development of severe disease.

  8. Dengue Deaths in Puerto Rico: Lessons Learned from the 2007 Epidemic

    Science.gov (United States)

    Tomashek, Kay M.; Gregory, Christopher J.; Rivera Sánchez, Aidsa; Bartek, Matthew A.; Garcia Rivera, Enid J.; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L.; Sun, Wellington

    2012-01-01

    Background The incidence and severity of dengue in Latin America has increased substantially in recent decades and data from Puerto Rico suggests an increase in severe cases. Successful clinical management of severe dengue requires early recognition and supportive care. Methods Fatal cases were identified among suspected dengue cases reported to two disease surveillance systems and from death certificates. To be included, fatal cases had to have specimen submitted for dengue diagnostic testing including nucleic acid amplification for dengue virus (DENV) in serum or tissue, immunohistochemical testing of tissue, and immunoassay detection of anti-DENV IgM from serum. Medical records from laboratory-positive dengue fatal case-patients were reviewed to identify possible determinants for death. Results Among 10,576 reported dengue cases, 40 suspect fatal cases were identified, of which 11 were laboratory-positive, 14 were laboratory-negative, and 15 laboratory-indeterminate. The median age of laboratory-positive case-patients was 26 years (range 5 months to 78 years), including five children aged Dengue was listed on the death certificate in only 5 instances. Conclusions During a dengue epidemic in an endemic area, none of the 11 laboratory-positive case-patients who died were managed according to current WHO Guidelines. Management issues identified in this case-series included failure to recognize warning signs for severe dengue and shock, prolonged ED stays, and infrequent patient monitoring. PMID:22530072

  9. Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of dengue viruses obtained during surveillance in Indonesia.

    Science.gov (United States)

    Aryati, Aryati; Trimarsanto, Hidayat; Yohan, Benediktus; Wardhani, Puspa; Fahri, Sukmal; Sasmono, R Tedjo

    2013-12-29

    Early diagnosis of dengue infection is crucial for better management of the disease. Diagnostic tests based on the detection of dengue virus (DENV) Non Structural Protein 1 (NS1) antigen are commercially available with different sensitivities and specificities observed in various settings. Dengue is endemic in Indonesia and clinicians are increasingly using the NS1 detection for dengue confirmation. This study described the performance of Panbio Dengue Early NS1 and IgM Capture ELISA assays for dengue detection during our surveillance in eight cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its relationship with the NS1 detection. The NS1 and IgM/IgG ELISA assays were used for screening and confirmation of dengue infection during surveillance in 2010-2012. Collected serum samples (n = 440) were subjected to RT-PCR and virus isolation, in which 188 samples were confirmed for dengue infection. The positivity of the ELISA assays were correlated with the RT-PCR results to obtain the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were sequenced and their genetic characteristics were studied. Using molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied when correlated with city/geographical origins and DENV serotype, in which the lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1 assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48 isolates revealed the presence of polymorphisms of the NS1 genes which apparently did not influence the NS1 sensitivity. We observed a relatively low sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples. The detection rate increased significantly

  10. Progress in the Identification of Dengue Virus Entry/Fusion Inhibitors

    Directory of Open Access Journals (Sweden)

    Carolina De La Guardia

    2014-01-01

    Full Text Available Dengue fever, a reemerging disease, is putting nearly 2.5 billion people at risk worldwide. The number of infections and the geographic extension of dengue fever infection have increased in the past decade. The disease is caused by the dengue virus, a flavivirus that uses mosquitos Aedes sp. as vectors. The disease has several clinical manifestations, from the mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, there is no approved drug for the treatment of dengue disease or an effective vaccine to fight the virus. Therefore, the search for antivirals against dengue virus is an active field of research. As new possible receptors and biological pathways of the virus biology are discovered, new strategies are being undertaken to identify possible antiviral molecules. Several groups of researchers have targeted the initial step in the infection as a potential approach to interfere with the virus. The viral entry process is mediated by viral proteins and cellular receptor molecules that end up in the endocytosis of the virion, the fusion of both membranes, and the release of viral RNA in the cytoplasm. This review provides an overview of the targets and progress that has been made in the quest for dengue virus entry inhibitors.

  11. Surface water areas significantly impacted 2014 dengue outbreaks in Guangzhou, China

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Huaiyu; Huang, Shanqian [State Key Laboratory of Remote Sensing Science, College of Global Change and Earth System Science, Beijing Normal University, Beijing (China); Zhou, Sen [Ministry of Education Key Laboratory for Earth System Modelling, Center for Earth System Science, Tsinghua University, Beijing (China); Department of Pediatrics, Harvard Medical School, Boston, MA (United States); Bi, Peng [Discipline of Public Health, University of Adelaide, Adelaide (Australia); Yang, Zhicong, E-mail: yangzc@gzcdc.org.cn [Guangzhou Center for Disease Control and Prevention, Guangzhou (China); Li, Xiujun [School of Public Health, Shandong University, Jinan (China); Chen, Lifan [State Key Laboratory of Remote Sensing Science, College of Global Change and Earth System Science, Beijing Normal University, Beijing (China); Cazelles, Bernard [UMMISCO, UMI 209 IRD – UPMC, 93142 Bondy (France); Eco-Evolutionary Mathematic, IBENS UMR 8197, ENS, 75230 Paris Cedex 05 (France); Yang, Jing [State Key Laboratory of Remote Sensing Science, College of Global Change and Earth System Science, Beijing Normal University, Beijing (China); Luo, Lei; Jing, Qinlong [Guangzhou Center for Disease Control and Prevention, Guangzhou (China); Yuan, Wenping [State Key Laboratory of Earth Surface Processes and Resource Ecology, College of Global Change and Earth System Science, Beijing Normal University, Beijing (China); Pei, Yao; Sun, Zhe [Ministry of Education Key Laboratory for Earth System Modelling, Center for Earth System Science, Tsinghua University, Beijing (China); Yue, Tianxiang [State Key Laboratory of Resources and Environment Information System, Chinese Academy of Sciences, Beijing (China); Kwan, Mei-Po [Department of Geography and Geographic Information Science, University of Illinois at Urbana-Champaign, Champaign, IL 61820 (United States); and others

    2016-10-15

    Dengue transmission in urban areas is strongly influenced by a range of biological and environmental factors, yet the key drivers still need further exploration. To better understand mechanisms of environment–mosquito–urban dengue transmission, we propose an empirical model parameterized and cross-validated from a unique dataset including viral gene sequences, vector dynamics and human dengue cases in Guangzhou, China, together with a 36-year urban environmental change maps investigated by spatiotemporal satellite image fusion. The dengue epidemics in Guangzhou are highly episodic and were not associated with annual rainfall over time. Our results indicate that urban environmental changes, especially variations in surface area covered by water in urban areas, can substantially alter the virus population and dengue transmission. The recent severe dengue outbreaks in Guangzhou may be due to the surge in an artificial lake construction, which could increase infection force between vector (mainly Aedes albopictus) and host when urban water area significantly increased. Impacts of urban environmental change on dengue dynamics may not have been thoroughly investigated in the past studies and more work needs to be done to better understand the consequences of urbanization processes in our changing world. - Highlights: • Urban dengue outbreak is associated with water area in Guangzhou, 1978–2014. • Surface water area can alter population size of dengue virus in urban area. • Urban dengue outbreak is not associated with annual rainfall in Guangzhou. • Spatiotemporal satellite image fusion can investigate urban environmental change. • Urban environmental change could induce virus, vector, and dengue epidemic change.

  12. Surface water areas significantly impacted 2014 dengue outbreaks in Guangzhou, China

    International Nuclear Information System (INIS)

    Tian, Huaiyu; Huang, Shanqian; Zhou, Sen; Bi, Peng; Yang, Zhicong; Li, Xiujun; Chen, Lifan; Cazelles, Bernard; Yang, Jing; Luo, Lei; Jing, Qinlong; Yuan, Wenping; Pei, Yao; Sun, Zhe; Yue, Tianxiang; Kwan, Mei-Po

    2016-01-01

    Dengue transmission in urban areas is strongly influenced by a range of biological and environmental factors, yet the key drivers still need further exploration. To better understand mechanisms of environment–mosquito–urban dengue transmission, we propose an empirical model parameterized and cross-validated from a unique dataset including viral gene sequences, vector dynamics and human dengue cases in Guangzhou, China, together with a 36-year urban environmental change maps investigated by spatiotemporal satellite image fusion. The dengue epidemics in Guangzhou are highly episodic and were not associated with annual rainfall over time. Our results indicate that urban environmental changes, especially variations in surface area covered by water in urban areas, can substantially alter the virus population and dengue transmission. The recent severe dengue outbreaks in Guangzhou may be due to the surge in an artificial lake construction, which could increase infection force between vector (mainly Aedes albopictus) and host when urban water area significantly increased. Impacts of urban environmental change on dengue dynamics may not have been thoroughly investigated in the past studies and more work needs to be done to better understand the consequences of urbanization processes in our changing world. - Highlights: • Urban dengue outbreak is associated with water area in Guangzhou, 1978–2014. • Surface water area can alter population size of dengue virus in urban area. • Urban dengue outbreak is not associated with annual rainfall in Guangzhou. • Spatiotemporal satellite image fusion can investigate urban environmental change. • Urban environmental change could induce virus, vector, and dengue epidemic change.

  13. The influence of climate variables on dengue in Singapore.

    Science.gov (United States)

    Pinto, Edna; Coelho, Micheline; Oliver, Leuda; Massad, Eduardo

    2011-12-01

    In this work we correlated dengue cases with climatic variables for the city of Singapore. This was done through a Poisson Regression Model (PRM) that considers dengue cases as the dependent variable and the climatic variables (rainfall, maximum and minimum temperature and relative humidity) as independent variables. We also used Principal Components Analysis (PCA) to choose the variables that influence in the increase of the number of dengue cases in Singapore, where PC₁ (Principal component 1) is represented by temperature and rainfall and PC₂ (Principal component 2) is represented by relative humidity. We calculated the probability of occurrence of new cases of dengue and the relative risk of occurrence of dengue cases influenced by climatic variable. The months from July to September showed the highest probabilities of the occurrence of new cases of the disease throughout the year. This was based on an analysis of time series of maximum and minimum temperature. An interesting result was that for every 2-10°C of variation of the maximum temperature, there was an average increase of 22.2-184.6% in the number of dengue cases. For the minimum temperature, we observed that for the same variation, there was an average increase of 26.1-230.3% in the number of the dengue cases from April to August. The precipitation and the relative humidity, after analysis of correlation, were discarded in the use of Poisson Regression Model because they did not present good correlation with the dengue cases. Additionally, the relative risk of the occurrence of the cases of the disease under the influence of the variation of temperature was from 1.2-2.8 for maximum temperature and increased from 1.3-3.3 for minimum temperature. Therefore, the variable temperature (maximum and minimum) was the best predictor for the increased number of dengue cases in Singapore.

  14. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

    Science.gov (United States)

    Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

    2016-01-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved the prognosis performance (AUC = 0.92, sensitivity = 77.8%, specificity = 95.8%), suggesting this duplex panel as accurate metrics for the early prognosis of DHF. PMID:27055163

  15. A case of acute liver failure in dengue hemorrhagic fever

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    Rama Biswas

    2013-07-01

    Full Text Available Dengue is an arboviral disease endemic in many parts of the world. The clinical presentation of dengue viral infection ranges from asymptomatic illness to fatal dengue shock syndrome. Although, it is known to cause hepatic involvement, it occasionally results in acute hepatic failure. We report a case of dengue hemorrhagic fever presenting with acute liver failure. The case recovered completely after treatment. Ibrahim Med. Coll. J. 2013; 7(2: 41-42

  16. Change in Dengue and Japanese Encephalitis Seroprevalence Rates in Sri Lanka

    Science.gov (United States)

    Jeewandara, Chandima; Gomes, Laksiri; Paranavitane, S. A.; Tantirimudalige, Mihiri; Panapitiya, Sumedha Sandaruwan; Jayewardene, Amitha; Fernando, Samitha; Fernando, R. H.; Prathapan, Shamini

    2015-01-01

    Background Sri Lanka has been affected by epidemics of dengue infections for many decades and the incidence and severity of dengue infections have been rising each year. Therefore, we investigated the age stratified seroprevalence of dengue infections in order to facilitate future dengue vaccine strategies. In addition, since the symptomatic dengue infections have increased during the past few decades, we also investigated the possible association with Japanese Encephalitis Virus (JEV) antibody seropositivity with symptomatic dengue in a community cohort in Sri Lanka. Methods 1689 healthy individuals who were attending a primary health care facility were recruited. Dengue and JEV antibody status was determined in all individuals and JEV vaccination status was recorded. Results 1152/1689 (68.2%) individuals were seropositive for dengue and only 133/1152 (11.5%) of them had been hospitalized to due to dengue. A significant and positive correlation was observed for dengue antibody seropositivity and age in children (Spearmans R = 0.84, p = 0.002) and in adults (Spearmans R = 0.96, p = 0.004). We observed a significant rise in the age stratified seroprevalence rates in children over a period of 12 years. For instance, in year 2003 the annual seroconversion rate was 1.5% per annum, which had risen to 3.79% per annum by 2014. We also found that both adults (pdengue were more likely to be seropositive for JEV antibodies. However, 244 (91.4%) of adults who were seropositive for JEV had not had the JEV vaccine. Conclusions Dengue seroprevalence rates have risen significantly over the last 12 years in Sri Lanka, possibly due to increased transmission. As individuals who were hospitalized due to dengue were more likely to be seropositive for JEV, the possibility of cross-reactive assays and/or of JEV infection on immunity to the DENV and clinical disease severity should be further investigated. PMID:26696417

  17. Approaches to Refining Estimates of Global Burden and Economics of Dengue

    Science.gov (United States)

    Shepard, Donald S.; Undurraga, Eduardo A.; Betancourt-Cravioto, Miguel; Guzmán, María G.; Halstead, Scott B.; Harris, Eva; Mudin, Rose Nani; Murray, Kristy O.; Tapia-Conyer, Roberto; Gubler, Duane J.

    2014-01-01

    Dengue presents a formidable and growing global economic and disease burden, with around half the world's population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and persons affected. Variations in the transmission of four different viruses and interactions among vector density and host's immune status, age, pre-existing medical conditions, all contribute to the disease's complexity. This systematic review aims to identify and examine estimates of dengue disease burden and costs, discuss major sources of uncertainty, and suggest next steps to improve estimates. Economic analysis of dengue is mainly concerned with costs of illness, particularly in estimating total episodes of symptomatic dengue. However, national dengue disease reporting systems show a great diversity in design and implementation, hindering accurate global estimates of dengue episodes and country comparisons. A combination of immediate, short-, and long-term strategies could substantially improve estimates of disease and, consequently, of economic burden of dengue. Suggestions for immediate implementation include refining analysis of currently available data to adjust reported episodes and expanding data collection in empirical studies, such as documenting the number of ambulatory visits before and after hospitalization and including breakdowns by age. Short-term recommendations include merging multiple data sources, such as cohort and surveillance data to evaluate the accuracy of reporting rates (by health sector, treatment, severity, etc.), and using covariates to extrapolate dengue incidence to locations with no or limited reporting. Long-term efforts aim at strengthening capacity to document dengue transmission using serological methods to systematically analyze and relate to epidemiologic data. As promising tools

  18. Characterization of Dengue Virus Infections Among Febrile Children Clinically Diagnosed With a Non-Dengue Illness, Managua, Nicaragua.

    Science.gov (United States)

    Waggoner, Jesse J; Gresh, Lionel; Mohamed-Hadley, Alisha; Balmaseda, Angel; Soda, K James; Abeynayake, Janaki; Sahoo, Malaya K; Liu, Yuanyuan; Kuan, Guillermina; Harris, Eva; Pinsky, Benjamin A

    2017-06-15

    We sought to characterize dengue virus (DENV) infections among febrile children enrolled in a pediatric cohort study who were clinically diagnosed with a non-dengue illness ("C cases"). DENV infections were detected and viral load quantitated by real-time reverse transcription-polymerase chain reaction in C cases presenting between January 2007 and January 2013. One hundred forty-one of 2892 C cases (4.88%) tested positive for DENV. Of all febrile cases in the study, DENV-positive C cases accounted for an estimated 52.0% of patients with DENV viremia at presentation. Compared with previously detected, symptomatic dengue cases, DENV-positive C cases were significantly less likely to develop long-lasting humoral immune responses to DENV, as measured in healthy annual serum samples (79.7% vs 47.8%; P dengue. These findings have important implications for DENV transmission modeling, immunology, and epidemiologic surveillance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. Corticosteroids in the treatment of dengue shock syndrome

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    Rajapakse S

    2014-05-01

    Full Text Available Senaka Rajapakse,1 Chaturaka Rodrigo,1 Sachith Maduranga,1 Anoja Chamarie Rajapakse21Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka; 2Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Sutton-in-Ashfield, Nottinghamshire, UKAbstract: Dengue infection causes significant morbidity and mortality in over 100 countries worldwide, and its incidence is on the rise. The pathophysiological basis for the development of severe dengue, characterized by plasma leakage and the “shock syndrome” are poorly understood. No specific treatment or vaccine is available, and careful monitoring and judicious administration of fluids forms the mainstay of management at present. It is postulated that vascular endothelial dysfunction, induced by cytokine and chemical mediators, is an important mechanism of plasma leakage. Although corticosteroids are potent modulators of the immune system, their role in pharmacological doses in modulating the purported immunological effects that take place in severe dengue has been a subject of controversy. The key evidence related to the role of corticosteroids for various manifestations of dengue are reviewed here. In summary, there is currently no high-quality evidence supporting the beneficial effects of corticosteroids for treatment of shock, prevention of serious complications, or increasing platelet counts. Non-randomized trials of corticosteroids given as rescue medication for severe shock have shown possible benefit. Nonetheless, the evidence base is small, and good-quality trials are lacking. We reiterate the need for well-designed and adequately powered randomized controlled trials of corticosteroids for the treatment of dengue shock.Keywords: dengue, dengue shock, shock, corticosteroids, vascular leak, thrombocytopenia

  20. Predictive value of proteinuria in adult dengue severity.

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    Farhad F Vasanwala

    2014-02-01

    Full Text Available BACKGROUND: Dengue is an important viral infection with different presentations. Predicting disease severity is important in triaging patients requiring hospital care. We aim to study the value of proteinuria in predicting the development of dengue hemorrhagic fever (DHF, utility of urine dipstick test as a rapid prognostic tool. METHODOLOGY AND PRINCIPAL FINDINGS: Adult patients with undifferentiated fever (n = 293 were prospectively enrolled at the Infectious Disease Research Clinic at Tan Tock Seng Hospital, Singapore from January to August 2012. Dengue infection was confirmed in 168 (57% by dengue RT-PCR or NS1 antigen detection. Dengue cases had median fever duration of 6 days at enrollment. DHF was diagnosed in 34 cases according to the WHO 1997 guideline. Dengue fever (DF patients were predominantly younger and were mostly seen in the outpatient setting with higher platelet level. Compared to DF, DHF cases had significantly higher peak urine protein creatinine ratio (UPCR during clinical course (26 vs. 40 mg/mmol; p<0.001. We obtained a UPCR cut-off value of 29 mg/mmol based on maximum AUC in ROC curves of peak UPCR for DF versus DHF, corresponding to 76% sensitivity and 60% specificity. Multivariate analysis with other readily available clinical and laboratory variables increased the AUC to 0.91 with 92% sensitivity and 80% specificity. Neither urine dipstick at initial presentation nor peak urine dipstick value during the entire illness was able to discriminate between DF and DHF. CONCLUSIONS: Proteinuria measured by a laboratory-based UPCR test may be sensitive and specific in prognosticating adult dengue patients.

  1. THE CHANGING CLINICAL PERFORMANCE OF DENGUE VIRUS INFECTION IN THE YEAR 2009

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    Soegeng Soegijanto

    2012-01-01

    Full Text Available Background: Dengue (DEN virus, the most important arthropod-borne human pathogen, represents a serious public health threat. DEN virus is transmitted to humans by the bite of the domestic mosquito, Aedes aegypti, and circulates in nature as four distinct serological types DEN-1 to 4. The aim of Study: To identify Dengue Virus Serotype I which showed mild clinical performance in five years before and afterward showed severe clinical performance. Material and Method: Prospective and analytic observational study had been done in Dr. Soetomo Hospital and the ethical clearance was conduct on January 01, 2009. The population of this research is all cases of dengue virus infection. Diagnosis were done based on WHO 1997. All of these cases were examined for IgM & IgG anti Dengue Virus and then were followed by PCR examination to identify Dengue Virus serotype. Result and Discussion: DEN 2 was predominant virus serotype with produced a spectrum clinical illness from asymptomatic, mild illness to classic dengue fever (DF to the most severe form of illness (DHF. But DEN 1 usually showed mild illness. Helen at al (2009–2010 epidemiologic study of Dengue Virus Infection in Health Centre Surabaya and Mother and Child Health Soerya Sidoarjo found many cases of Dengue Hemorrhagic Fever were caused by DEN 1 Genotype IV. Amor (2009 study in Dr. Soetomo Hospital found DEN 1 showed severe clinical performance of primary Dengue Virus Infection as Dengue Shock Syndrome two cases and one unusual case. Conclusion: The epidemiologic study of Dengue Virus Infection in Surabaya and Sidoarjo; in the year 2009 found changing predominant Dengue Virus Serotype from Dengue Virus II to Dengue Virus 1 Genotype IV which showed a severe clinical performance coincident with primary infection.

  2. Immature dengue virus : functional properties and potential contribution to disease

    NARCIS (Netherlands)

    Da Silva-Voorham, Júlia Maria

    2013-01-01

    Beter inzicht in mechanismen achter infectieziekte dengue Dengue (‘knokkelkoorts’) is een veelvoorkomende, tropische infectieziekte die wordt overgebracht door muggen. Naar schatting raken jaarlijks zo’n vijftig tot honderd miljoen mensen besmet. Meestal gaat dengue vanzelf over, maar in zo’n

  3. Dengue and Chikungunya Vector Control Pocket Guide

    Science.gov (United States)

    This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

  4. Economic value of dengue vaccine in Thailand.

    Science.gov (United States)

    Lee, Bruce Y; Connor, Diana L; Kitchen, Sarah B; Bacon, Kristina M; Shah, Mirat; Brown, Shawn T; Bailey, Rachel R; Laosiritaworn, Yongjua; Burke, Donald S; Cummings, Derek A T

    2011-05-01

    With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

  5. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

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    Ghazi A. Jamjoom

    2016-01-01

    Full Text Available Background Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. Methods Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. Results The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939 and 37% (68/184 in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1% reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others

  6. Increased Levels of Txa2 Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue

    Science.gov (United States)

    Oliveira, Eneida S.; Colombarolli, Stella G.; Nascimento, Camila S.; Batista, Izabella C. A.; Ferreira, Jorge G. G.; Alvarenga, Daniele L. R.; de Sousa, Laís O. B.; Assis, Rafael R.; Rocha, Marcele N.; Alves, Érica A. R.; Calzavara-Silva, Carlos E.

    2018-01-01

    The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus-induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage. PMID:29495587

  7. First isolation of dengue virus from the 2010 epidemic in Nepal.

    Science.gov (United States)

    Pandey, Basu D; Nabeshima, Takeshi; Pandey, Kishor; Rajendra, Saroj P; Shah, Yogendra; Adhikari, Bal R; Gupta, Govinda; Gautam, Ishan; Tun, Mya M N; Uchida, Reo; Shrestha, Mahendra; Kurane, Ichiro; Morita, Kouichi

    2013-09-01

    Dengue is an emerging disease in Nepal and was first observed as an outbreak in nine lowland districts in 2006. In 2010, however, a large epidemic of dengue occurred with 4,529 suspected and 917 serologically-confirmed cases and five deaths reported in government hospitals in Nepal. The collection of demographic information was performed along with an entomological survey and clinical evaluation of the patients. A total of 280 serum samples were collected from suspected dengue patients. These samples were subjected to routine laboratory investigations and IgM-capture ELISA for dengue serological identification, and 160 acute serum samples were used for virus isolation, RT-PCR, sequencing and phylogenetic analysis. The results showed that affected patients were predominately adults, and that 10% of the cases were classified as dengue haemorrhagic fever/ dengue shock syndrome. The genetic characterization of dengue viruses isolated from patients in four major outbreak areas of Nepal suggests that the DENV-1 strain was responsible for the 2010 epidemic. Entomological studies identified Aedes aegypti in all epidemic areas. All viruses belonged to a monophyletic single clade which is phylogenetically close to Indian viruses. The dengue epidemic started in the lowlands and expanded to the highland areas. To our knowledge, this is the first dengue isolation and genetic characterization reported from Nepal.

  8. Mathematical Modelling of Immune Parameters in the Evolution of Severe Dengue

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    M. K. Premaratne

    2017-01-01

    Full Text Available Aims. Predicting the risk of severity at an early stage in an individual patient will be invaluable in preventing morbidity and mortality caused by dengue. We hypothesized that such predictions are possible by analyzing multiple parameters using mathematical modeling. Methodology. Data from 11 adult patients with dengue fever (DF and 25 patients with dengue hemorrhagic fever (DHF were analyzed. Multivariate statistical analysis was performed to study the characteristics and interactions of parameters using dengue NS1 antigen levels, dengue IgG antibody levels, platelet counts, and lymphocyte counts. Fuzzy logic fundamentals were used to map the risk of developing severe forms of dengue. The cumulative effects of the parameters were incorporated using the Hamacher and the OWA operators. Results. The operator classified the patients according to the severity level during the time period of 96 hours to 120 hours after the onset of fever. The accuracy ranged from 53% to 89%. Conclusion. The results show a robust mathematical model that explains the evolution from dengue to its serious forms in individual patients. The model allows prediction of severe cases of dengue which could be useful for optimal management of patients during a dengue outbreak. Further analysis of the model may also deepen our understanding of the pathways towards severe illness.

  9. Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

    Science.gov (United States)

    Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

    2013-12-02

    Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All

  10. The effects of urban growth on dengue

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    Marco Aurélio Pereira Horta

    2014-09-01

    Full Text Available Objective: To analyze the spatial and temporal dynamics of dengue in Coronel Fabriciano, Minas Gerais State, Brazil, and to associate cases to the growth of urban areas and loss of natural areas in recent years. Methods: This is a descriptive, exploratory study, with a quantitative approach. Dengue cases of 2009 were obtained from the Health Municipal Secretariat, including the suspected and confirmed cases. Shape files were obtained, containing information about the municipal boundary, boundary of the urban area, census tracts, areas with buildings and natural areas. Based on the distribution of dengue cases, the Kernel estimator was used to measure data dispersion. Results: Dengue cases reported were georeferenced in GIS (Geographic Information System environment. The landscape showed changes in the units of urban area and pasture, as an urban growth over the pasture matrix. No changes were observed in the areas of remaining forest and eucalyptus. There are cases spatially spread with a tendency to form clusters. Conclusion: Cases of dengue were observed spatially clustered in the northern region of the city, where new neighborhoods have emerged in recent years, following the population growth without proper structure of urbanization and urban planning. In addition, urban growth have reduced the margin of watercourses providing a bare soil, suitable for accumulation of trash and formation of breeding sites for mosquitoes. Efficient public policies and appropriate urban planning might reduce the impact of dengue in endemic regions. doi: http://dx.doi.org/10.5020/18061230.2013.p539

  11. Unusual dengue virus 3 epidemic in Nicaragua, 2009.

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    Gamaliel Gutierrez

    2011-11-01

    Full Text Available The four dengue virus serotypes (DENV1-4 cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009-January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009-10, compared to 13-65 cases in 2004-9. In both studies, significantly more patients experienced "compensated shock" (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse in 2009-10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001 and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001. Signs of poor peripheral perfusion presented significantly earlier (1-2 days in 2009-10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years - similar to the cohort study. DENV-3 predominated in 2008-9, 2009-10, and 2010-11, and full-length sequencing revealed no major genetic changes from 2008-9 to 2010-11. In 2008-9 and 2010-11, typical dengue was observed; only in 2009-10 was unusual presentation noted. Multivariate analysis revealed only "2009-10" as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral

  12. Research on Climate and Dengue in Malaysia: A Systematic Review

    OpenAIRE

    Hii, Yien Ling; Zaki, Rafdzah Ahmad; Aghamohammadi, Nasrin; Rockl?v, Joacim

    2016-01-01

    Background & Objectives Dengue is a climate-sensitive infectious disease. Climate-based dengue early warning may be a simple, low-cost, and effective tool for enhancing surveillance and control. Scientific studies on climate and dengue in local context form the basis for advancing the development of a climate-based early warning system. This study aims to review the current status of scientific studies in climate and dengue and the prospect or challenges of such research on a climate-based de...

  13. Host cell responses to dengue virus infection

    NARCIS (Netherlands)

    Diosa Toro, Mayra

    2017-01-01

    Dengue (ook wel knokkelkoorts) is de meest voorkomende virale infectieziekte dat wordt overgedragen door muggen in de wereld met naar schatting 390 miljoen infecties per jaar. Ondanks de grote klinische impact en economische schade van het dengue virus is er nog steeds geen behandeling beschikbaar.

  14. Dengue fever as a cause of hemophagocytic lymphohistiocytosis

    OpenAIRE

    Hein, Noely; Bergara, Gabriel Heiser; Moura, Nathalie Bianchini Vieira; Cardoso, D?bora Morais; Hirose, Maki; Ferronato, Angela Esp?sito; Pastorino, Ant?nio Carlos; Lo, Denise Swei; Gilio, Alfredo Elias

    2015-01-01

    Dengue is endemic in more than 100 countries in Southeast Asia, the Americas, the western Pacific, Africa and the eastern Mediterranean regions. The virus is transmitted by Aedes mosquitoes. Dengue disease is the most prevalent arthropod-borne viral disease in humans and is a global and national public health concern in several countries. A seasonal pattern of dengue disease is consistently observed. The highest incidences usually correspond to the period of highest rainfall and humidity, pro...

  15. Differential Dengue Tropism & Neutralization: Potential Mechanisms of Pathogenesis

    Science.gov (United States)

    2006-01-04

    Venezuela, 1990- 1997]. Acta Cient Venez 49 Suppl 1, 33-7. Smith, G.W. and Wright, P.J. (1985) Synthesis of proteins and glycoproteins in dengue type 2...R. Tilley, G. Lloyd, C. Finlayson, H. Tolley, P. Newman, P. Rice, and T. S. Harrison. 2003. Dengue hemorrhagic fever with fulminant hepatic...George, and S. Devi. 1993. Fulminant hepatitis in dengue infection. Southeast Asian J Trop Med Public Health 24:467-71. 180. Mady, B. J., D. V. Erbe, I

  16. The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

    Science.gov (United States)

    Aguiar, Maíra; Stollenwerk, Nico; Halstead, Scott B

    2016-12-01

    With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia), was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9-16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy) was noted for children younger than 9 years of age. Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE). An age structured model was developed based on Sanofi's recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1) Vaccinate 4 or 20% of individuals, ages 9-45 years, seropositives and seronegatives, and 2) vaccinate 4 or 20% of individuals, ages 9-45 years, who are dengue immune only. Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably.

  17. The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

    Directory of Open Access Journals (Sweden)

    Maíra Aguiar

    2016-12-01

    Full Text Available With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia, was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9-16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy was noted for children younger than 9 years of age.Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE. An age structured model was developed based on Sanofi's recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1 Vaccinate 4 or 20% of individuals, ages 9-45 years, seropositives and seronegatives, and 2 vaccinate 4 or 20% of individuals, ages 9-45 years, who are dengue immune only.Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably.

  18. A case of dengue-related osteonecrosis of the maxillary dentoalveolar bone.

    Science.gov (United States)

    Al-Namnam, N M; Nambiar, P; Shanmuhasuntharam, P; Harris, M

    2017-06-01

    Dengue is a mosquito transmitted flaviviral infection which can give rise to severe haemorrhage (dengue haemorrhagic fever) and with capillary leakage induces hypovolaemic shock (dengue shock syndrome). Although dengue symptoms and complications have been known for many decades, there has only been one documented case of osteonecrosis of the maxilla which was treated by excision of the necrotic bone. In this case of dengue infection, extensive maxillary osteonecrosis and minimal root resorption appeared to follow factitious injury with a toothpick but resolved with non-surgical management. © 2016 Australian Dental Association.

  19. Spatial patterns of dengue cases in Brazil.

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    Fernando Jose Antonio

    Full Text Available Dengue infection plays a central role in our society, since it is the most prevalent vector-borne viral disease affecting humans. We statistically investigated patterns concerning the spatial spreading of dengue epidemics in Brazil, as well as their temporal evolution in all Brazilian municipalities for a period of 12 years. We showed that the distributions of cases in municipalities follow power laws persistent in time and that the infection scales linearly with the population of the municipalities. We also found that the average number of dengue cases does not have a clear dependence on the longitudinal position of municipalities. On the other hand, we found that the average distribution of cases varies with the latitudinal position of municipalities, displaying an almost constant growth from high latitudes until reaching the Tropic of Capricorn leveling to a plateau closer to the Equator. We also characterized the spatial correlation of the number of dengue cases between pairs of municipalities, where our results showed that the spatial correlation function decays with the increase of distance between municipalities, following a power-law with an exponential cut-off. This regime leads to a typical dengue traveling distance. Finally, we considered modeling this last behaviour within the framework of a Edwards-Wilkinson equation with a fractional derivative on space.

  20. Molecular surveillance of dengue in Minas Gerais provides insights on dengue virus 1 and 4 circulation in Brazil.

    Science.gov (United States)

    Dutra, Karina Rocha; Drumond, Betânia Paiva; de Rezende, Izabela Maurício; Nogueira, Maurício Lacerda; de Oliveira Lopes, Débora; Calzavara Silva, Carlos Eduardo; Siqueira Ferreira, Jaqueline Maria; Dos Santos, Luciana Lara

    2017-06-01

    Dengue, caused by any of the four types of Dengue virus (DENV) is the most important arbovirus in the world. In this study we performed a molecular surveillance of dengue during the greatest dengue outbreak that took place in Divinópolis, Minas Gerais state, Southeast Brazil, in 2013. Samples from 100 patients with clinical symptoms of dengue were studied and 26 were positive. The capsid/premembrane (CprM) and envelope gene sequences of some samples were amplified and sequenced. Molecular analyses demonstrated that two DENV-1 lineages, belonging to genotype V were introduced and co-circulated in Divinópolis. When compared to each other, those lineages presented high genetic diversity and showed unique amino acids substitutions in the envelope protein, including in domains I, II, and III. DENV-4 strains from Divinópolis clustered within genotype IIb and the most recent common ancestor was probably introduced into the city three years before the 2013 epidemic. Here we demonstrated for the first time the circulation of DENV-4 and the co-circulation of two DENV-1 lineages in Midwest region of Minas Gerais, Brazil. Moreover our analysis indicated the introduction of five DENV-1 lineages, genotype V into Brazil, in different times. J. Med. Virol. 89:966-973, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. All Serotypes of Dengue Viruses Circulating in Kuala Lumpur, Malaysia

    OpenAIRE

    M.H. Chew; M.M. Rahman; J. Jelip; M.R. Hassan; I. Isahak

    2012-01-01

    Dengue is a severe disease caused by dengue virus (DENV), transmitted to human being by infected Aedes mosquitoes. It is a major public health concern in Southeast Asia due to its fatality in the form of hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The objective of the study was to isolate and identify dengue virus serotypes prevalent in endemic areas of Kuala Lumpur and Selangor in Malaysia by virus culture, indirect immunoflurecent assay and molecular techniques. A total number ...

  2. Construction and characterisation of a complete reverse genetics system of dengue virus type 3

    Directory of Open Access Journals (Sweden)

    Jefferson Jose da Silva Santos

    2013-12-01

    Full Text Available Dengue virulence and fitness are important factors that determine disease outcome. However, dengue virus (DENV molecular biology and pathogenesis are not completely elucidated. New insights on those mechanisms have been facilitated by the development of reverse genetic systems in the past decades. Unfortunately, instability of flavivirus genomes cloned in Escherichia coli has been a major problem in these systems. Here, we describe the development of a complete reverse genetics system, based on the construction of an infectious clone and replicon for a low passage DENV-3 genotype III of a clinical isolate. Both constructs were assembled into a newly designed yeast- E. coli shuttle vector by homologous recombination technique and propagated in yeast to prevent any possible genome instability in E. coli . RNA transcripts derived from the infectious clone are infectious upon transfection into BHK-21 cells even after repeated passages of the plasmid in yeast. Transcript-derived DENV-3 exhibited growth kinetics, focus formation size comparable to original DENV-3 in mosquito C6/36 cell culture. In vitro characterisation of DENV-3 replicon confirmed its identity and ability to replicate transiently in BHK-21 cells. The reverse genetics system reported here is a valuable tool that will facilitate further molecular studies in DENV replication, virus attenuation and pathogenesis.

  3. Associations between Dengue Hospitalizations and Climate in Can Tho, Vietnam, 2001-2011

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    Nguyen P. Toai

    2016-07-01

    Full Text Available In Vietnam, dengue fever is a major cause of hospitalization with over one million cases reported between 1991 and 2004. Changes in the incidence of dengue in Can Tho city due to increased temperature and changes in precipitation, are anticipated. In an effort to better characterize the relationship between climate and dengue, we examine the associations between weather variables and dengue hospitalizations in Can Tho between 2001 and 2011. Monthly data on hospitalized dengue cases and means of temperature, rainfall and humidity were recorded from 2001 to 2011. We used the Box-Jenkins approach to modelling of time series to assess the association between these factors. This model was validated by the Portmanteau test. Our results revealed that the highest dengue incidences in Can Tho occur between July and December. After adjusting for seasonality, the rate of dengue hospitalizations was significantly associated with relative humidity with a lag of one month. Rainfall and temperature were not predictors of dengue hospitalization rate. In conclusion, these data suggest that maximum relative humidity (with a one month lag is an important determinant of dengue hospitalizations. Enhanced vector control during months with high humidity may be an important approach to prevent dengue transmission.

  4. Symmetry transition via tetravalent impurity and investigations on magnetic properties of Li0.5Fe2.5O4

    Science.gov (United States)

    Kounsalye, Jitendra S.; Kharat, Prashant B.; Chavan, Apparao R.; Humbe, Ashok V.; Borade, R. M.; Jadhav, K. M.

    2018-04-01

    The present study, deals with the phase symmetry transformation of lithium ferrite after introducing tetravalent (Ti4+) impurity. The sol-gel auto combustion technique was adopted for the synthesis of nanoparticle samples with generic chemical formula Li0.5Fe2.5O4 and Li0.55Ti0.10Fe2.35O4. The synthesized nanoparticles were characterized by X-ray diffraction (XRD) technique for structural analysis. The XRD patterns show the single phase cubic structure without any impurity phase but the P4332 to Fd-3m transformation was observed after introducing Ti4+ impurity. The Nano size of the synthesized particles was confirmed by crystallite size ( 20nm) calculated using Debye-Scherrer's formula. The Fourier transform infrared spectroscopy (FTIR) studies shows shifting of band frequencies which reflect the structural changes after tetravalent substitutional impurities. The magnetic properties were studied through pulse field hysteresis loop (M-H loop) technique at room temperature, the M-H loops showdecrease in magnetic properties afternonmagnetic Ti4+ ion substitution. This is attributed to transition of inverse spinel structure of lithium ferrite to random spinel structure.

  5. Phage-Displayed Peptides Selected to Bind Envelope Glycoprotein Show Antiviral Activity against Dengue Virus Serotype 2

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    Carolina de la Guardia

    2017-01-01

    Full Text Available Dengue virus is a growing public health threat that affects hundreds of million peoples every year and leave huge economic and social damage. The virus is transmitted by mosquitoes and the incidence of the disease is increasing, among other causes, due to the geographical expansion of the vector’s range and the lack of effectiveness in public health interventions in most prevalent countries. So far, no highly effective vaccine or antiviral has been developed for this virus. Here we employed phage display technology to identify peptides able to block the DENV2. A random peptide library presented in M13 phages was screened with recombinant dengue envelope and its fragment domain III. After four rounds of panning, several binding peptides were identified, synthesized, and tested against the virus. Three peptides were able to block the infectivity of the virus while not being toxic to the target cells. Blind docking simulations were done to investigate the possible mode of binding, showing that all peptides appear to bind domain III of the protein and may be mostly stabilized by hydrophobic interactions. These results are relevant to the development of novel therapeutics against this important virus.

  6. Peripheral gangrene in a case of severe dengue

    African Journals Online (AJOL)

    ergot alkaloids or other related medications. ... The spectrum of disease manifestations in dengue fever is wide. ... dengue shock syndrome and multiorgan failure. .... McGouran RC, Emmerson GA. Symmetrical peripheral gangrene. Br Heart J.

  7. Anti-GBM disease and ANCA during dengue infection.

    Science.gov (United States)

    Lizarraga, Karlo J; Florindez, Jorge A; Daftarian, Pirouz; Andrews, David M; Ortega, Luis M; Mendoza, Jair Munoz; Contreras, Gabriel N; Nayer, Ali

    2015-02-01

    Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

  8. Treatment Effectiveness of Amantadine Against Dengue Virus Infection.

    Science.gov (United States)

    Lin, Chieh-Cheng; Chen, Wen-Ching

    2016-12-05

    BACKGROUND About 400 million cases of dengue, a mosquito-borne disease, are reported annually, but no drug is yet available for treatment. In 1988, at Feng Lin Clinic, Taiwan, we encountered about 10,000 cases and tested various drugs before confirming an antiviral effect of amantadine against dengue virus in vitro. After we administered amantadine to patients for 1-2 days, most achieved full remission. None experienced potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome. Herein, we present 34 cases from recent clinical experience that show amantadine's unusual effect against dengue virus infection. CASE REPORT We divided 34 patients with symptoms of dengue fever, confirmed by a screening test, into 3 groups: 6 Category 1 patients received amantadine at onset, 21 Category 2 patients received amantadine within 2-6 days, and 7 Contrast group patients received no amantadine because they visited other clinics or were admitted to a large hospital. When Category 1 patients were treated with amantadine 100 mg 3 times per day, all symptoms dramatically subsided within 1-2 days. In Category 2 patients, most symptoms diminished within 1-2 days after starting the same regimen. In the Contrast group, all symptoms persisted 7 days after onset. White blood cell and platelet counts in Category 1 and 2 patients recovered to normal range, but remained below low normal in the Contrast group. CONCLUSIONS Amantadine is effective and should be given as soon as possible to stop the disease course if dengue fever is confirmed through screening or clinical signs and symptoms. A well-designed larger sample study is warranted to test this effectiveness.

  9. Health beliefs and practices related to dengue fever: a focus group study.

    Science.gov (United States)

    Wong, Li Ping; AbuBakar, Sazaly

    2013-01-01

    This qualitative study aimed to provide an in-depth understanding of the meaning of dengue fever (DF) amongst people living in a dengue endemic region, dengue prevention and treatment-seeking behaviours. The Health Belief Model was used as a framework to explore and understand dengue prevention behaviours. A total of 14 focus group discussions were conducted with 84 Malaysian citizens of different socio-demographic backgrounds between 16(th) December, 2011 and 12(th) May, 2012. The study revealed that awareness about DF and prevention measures were high. The pathophysiology of dengue especially dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) were rarely known; as a result, it was seen as deadly by some but was also perceived as easily curable by others without a basis of understanding. Young adults and elderly participants had a low perception of susceptibility to DF. In general, the low perceived susceptibility emerged as two themes, namely a perceived natural ability to withstand infection and a low risk of being in contact with the dengue virus vector, Aedes spp. mosquitoes. The barriers to sustained self-prevention against dengue prevention that emerged in focus groups were: i) lack of self-efficacy, ii) lack of perceived benefit, iii) low perceived susceptibility, and iv) unsure perceived susceptibility. Low perceived benefit of continued dengue prevention practices was a result of lack of concerted action against dengue in their neighborhood. Traditional medical practices and home remedies were widely perceived and experienced as efficacious in treating DF. Behavioural change towards attaining sustainability in dengue preventive practices may be enhanced by fostering comprehensive knowledge of dengue and a change in health beliefs. Wide use of unconventional therapy for DF warrants the need to enlighten the public to limit their reliance on unproven alternative treatments.

  10. A novel indirect ELISA for diagnosis of dengue fever

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    Rohan Narayan

    2016-01-01

    Full Text Available Background & objectives: Dengue fever (DF is associated with significant morbidity and mortality in the tropical and sub-tropical regions of the world. Since there are no effective antiviral drugs for treatment, clinicians often rely on the accurate diagnosis of dengue fever to begin supportive therapy at early stages of the illness. The objective of this study was to develop an in-house dengue virus serotype 2 (DENV-2 non-structural protein- 5 (NS5 based indirect ELISA. Methods: DENV-2 was raised in Vero cells and the viral proteins were separated and subsequently the NS5 protein was eluted. Serum samples from primary and secondary dengue fever patients; and acute and convalescent samples from Japanese encephalitis (JE and West Nile virus (WNV cases were used to validate the ELISA. Results: The assay was found to be 100 per cent specific in detecting DENV-2 specific antibodies from patient′s serum. However, in terms of sensitivity, the assay could detect IgM antibodies only from 90 per cent of the primary dengue samples. The IgM/IgG ratio of the primary and secondary samples was 7.24 and 0.64, respectively. Interpretation & conclusions: The results indicate that the DENV-2 NS5 ELISA is dengue group specific and can be used to differentiate dengue infection from other circulating Flavivirus infections. This NS5 ELISA can also be used to distinguish between primary and secondary dengue fever on the basis of IgM/IgG ratios. Further studies with larger sample sizes and different DENV serotypes are required to validate the ELISA.

  11. Dengue Hemorrhagic Fever: Epidemiology, Pathogenesis, and Its Transmission Risk Factors

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    Aryu Candra

    2010-12-01

    Full Text Available Dengue hemorrhagic fever is an infectious disease resulting spectrum of clinical manifestations that vary from the lightest, dengue fever, hemorrhagic fever and dengue fever are accompanied by shock or dengue shock syndrome. Its caused by dengue virus, transmitted by Aedes mosquitoes. The case is spread in the tropics, especially in Southeast Asia, Central America, America and the Caribbean, many causes of death in children 90% of them attacking children under 15 years old. Until now pathogenesis is unclear. There are two theories or hypotheses immuno-patogenesis DHF and DSS is still controversial which secondary infections (secondary heterologus infection and antibody-dependent enhancement. Risk factors for dengue transmission are rapid urban population growth, mobilization of the population because of improved transportation facilities and disrupted or weakened so that population control. Another risk factor is poverty which result in people not has the ability to provide a decent home and healthy, drinking water supply and proper waste disposal.

  12. Maternal, Fetal, and Neonatal Outcomes in Pregnant Dengue Patients in Mexico

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    Carlos Machain-Williams

    2018-01-01

    Full Text Available To increase our understanding of the consequences of dengue virus infection during pregnancy, a retrospective analysis was performed on the medical records of all completed pregnancies (live births and pregnancy losses at nine public hospitals in the Gulf of Mexico from January to October 2013. Eighty-two patients developed clinical, laboratory-confirmed dengue virus infections while pregnant. Of these, 54 (65.9% patients were diagnosed with dengue without warning signs, 15 (18.3% patients were diagnosed with dengue with warning signs, and 13 (15.9% patients had severe dengue. Five (38.5% patients with severe dengue experienced fetal distress and underwent emergency cesarean sections. Four patients delivered apparently healthy infants of normal birthweight while the remaining patient delivered a premature infant of low birthweight. Patients died of multiple organ failure during or within 10 days of the procedure. Severe dengue was also associated with obstetric hemorrhage (30.8%, four cases, preeclampsia (15.4%, two cases, and eclampsia (7.7%, one case. These complications were less common or absent in patients in the other two disease categories. Additionally, nonsevere dengue was not associated with maternal mortality, fetal distress, or adverse neonatal outcomes. In summary, the study provides evidence that severe dengue during pregnancy is associated with a high rate of fetal distress, cesarean delivery, and maternal mortality.

  13. Demographic and clinico-epidemiological features of dengue fever in Faisalabad, Pakistan.

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    Faiz Ahmed Raza

    Full Text Available This cross-sectional study was carried out to explore the epidemiological and clinical features of dengue fever in Faisalabad, Pakistan during 2011 and 2012. During the study period, anti-dengue IgM positive cases were reported in the post-monsoon period during the months of August-December. Certain hotspots for the dengue infection were identified in the city that coincide with the clusters of densely populated urban regions of the city. Out of total 299 IgM positive patients (male 218 and female 81; there were 239 dengue fever (DF and 60 dengue hemorrhagic fever (DHF patients. There was decrease in the median age of dengue patients from 31 years in 2011 to 21.5 years in 2012 (p<0.001. Abdominal pain was seen in 35% DHF patients followed by nausea in 28.3%, epistaxis in 25% and rash in 20% patients (p<0.05. Patients reported to be suffering from high-grade fever for an average of 8.83 days in DHF as compared to 5.82 days in DF before being hospitalized. Co-morbidities were found to be risk factor for the development of DHF in dengue patients. Clinical and laboratory features of dengue cases studied could be used for the early identification of patients at risk of severe dengue fever.

  14. Clinical and laboratory factors associated with mortality in dengue.

    Science.gov (United States)

    Saroch, Atul; Arya, Vivek; Sinha, Nitin; Taneja, R S; Sahai, Pooja; Mahajan, R K

    2017-04-01

    Dengue is endemic in more than 100 countries, giving rise to an increased number of deaths in the last five years in the South-East Asian region. We report our findings from a retrospective study of adults admitted with confirmed dengue at our institution. We studied the clinical and laboratory parameters associated with mortality in these patients. Of the 172 hospitalised patients studied, 156 (90.69 %) recovered while 16 (9.3%) died. Univariate analysis showed altered sensorium on presentation, lower haemoglobin and haematocrit levels, higher serum creatinine, higher serum transaminase and lower serum albumin levels to be significantly associated with mortality in dengue. Further, using stepwise multivariate logistic regression, altered sensorium ( P = 0.006) and hypoalbuminemia ( P = 0.013) were identified as independent predictors of mortality in dengue. Identification of these parameters early in the course of disease should prompt intensification of treatment in dengue cases.

  15. Can internet search queries be used for dengue fever surveillance in China?

    Science.gov (United States)

    Guo, Pi; Wang, Li; Zhang, Yanhong; Luo, Ganfeng; Zhang, Yanting; Deng, Changyu; Zhang, Qin; Zhang, Qingying

    2017-10-01

    China experienced an unprecedented outbreak of dengue fever in 2014, and the number of cases reached the highest level over the past 25 years. Traditional sentinel surveillance systems of dengue fever in China have an obvious drawback that the average delay from receipt to dissemination of dengue case data is roughly 1-2 weeks. In order to exploit internet search queries to timely monitor dengue fever, we analyzed data of dengue incidence and Baidu search query from 31 provinces in mainland China during the period of January 2011 to December 2014. We found that there was a strong correlation between changes in people's online health-seeking behavior and dengue fever incidence. Our study represents the first attempt demonstrating a strong temporal and spatial correlation between internet search trends and dengue epidemics nationwide in China. The findings will help the government to strengthen the capacity of traditional surveillance systems for dengue fever. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. An epidemic of dengue-1 in a remote village in rural Laos.

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    Audrey Dubot-Pérès

    Full Text Available In the Lao PDR (Laos, urban dengue is an increasingly recognised public health problem. We describe a dengue-1 virus outbreak in a rural northwestern Lao forest village during the cool season of 2008. The isolated strain was genotypically "endemic" and not "sylvatic," belonging to the genotype 1, Asia 3 clade. Phylogenetic analyses of 37 other dengue-1 sequences from diverse areas of Laos between 2007 and 2010 showed that the geographic distribution of some strains remained focal overtime while others were dispersed throughout the country. Evidence that dengue viruses have broad circulation in the region, crossing country borders, was also obtained. Whether the outbreak arose from dengue importation from an urban centre into a dengue-naïve community or crossed into the village from a forest cycle is unknown. More epidemiological and entomological investigations are required to understand dengue epidemiology and the importance of rural and forest dengue dynamics in Laos.

  17. A brief review on dengue molecular virology, diagnosis, treatment and prevalence in Pakistan

    OpenAIRE

    Idrees, Sobia; Ashfaq, Usman A

    2012-01-01

    Dengue virus infection is a serious health problem infecting 2.5 billion people worldwide. Dengue is now endemic in more than 100 countries, including Pakistan. Each year hundreds of people get infected with dengue in Pakistan. Currently, there is no vaccine available for the prevention of Dengue virus infection due to four viral serotypes. Dengue infection can cause death of patients in its most severity, meanwhile many antiviral compounds are being tested against dengue virus infection to e...

  18. Competitive inhibitor of cellular alpha-glucosidases protects mice from lethal dengue virus infection

    OpenAIRE

    Chang, Jinhong; Schul, Wouter; Yip, Andy; Xu, Xiaodong; Guo, Ju-Tao; Block, Timothy M.

    2011-01-01

    Dengue virus infection causes diseases in people, ranging from the acute febrile illness Dengue fever, to life-threatening Dengue Hemorrhagic Fever/Dengue Shock Syndrome. We previously reported that a host cellular α-glucosidases I and II inhibitor, imino sugar CM-10-18, potently inhibited dengue virus replication in cultured cells, and significantly reduced viremia in dengue virus infected AG129 mice. In this report we show that CM-10-18 also significantly protects mice from death and/or dis...

  19. Dengue hemorrhagic fever and acute hepatitis: a case report

    Directory of Open Access Journals (Sweden)

    Maria Paula Gomes Mourão

    Full Text Available Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

  20. Dengue hemorrhagic fever and acute hepatitis: a case report.

    Science.gov (United States)

    Mourão, Maria Paula Gomes; Lacerda, Marcus Vinícius Guimarães de; Bastos, Michele de Souza; Albuquerque, Bernardino Cláudio de; Alecrim, Wilson Duarte

    2004-12-01

    Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

  1. The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

    Directory of Open Access Journals (Sweden)

    Deborah Hl Ng

    Full Text Available Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration was present in 572 (20.1% of patients. Dengue hemorrhagic fever (DHF, dengue shock syndrome (DSS and severe dengue (SD were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT and aspartate transaminase (AST, higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT were significantly associated with prolonged fever but not platelet count or prothrombin time (PT. Saddleback fever was present in 165 (5.8%. Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF, while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore

  2. Virus isolation for diagnosing dengue virus infections in returning travelers

    NARCIS (Netherlands)

    Teichmann, D.; Göbels, K.; Niedrig, M.; Sim-Brandenburg, J.-W.; Làge-Stehr, J.; Grobusch, M. P.

    2003-01-01

    Dengue fever is recognized as one of the most frequent imported acute febrile illnesses affecting European tourists returning from the tropics. In order to assess the value of virus isolation for the diagnosis of dengue fever, 70 cases of dengue fever confirmed in German travelers during the period

  3. International dispersal of dengue through air travel: importation risk for Europe.

    Directory of Open Access Journals (Sweden)

    Jan C Semenza

    2014-12-01

    Full Text Available The worldwide distribution of dengue is expanding, in part due to globalized traffic and trade. Aedes albopictus is a competent vector for dengue viruses (DENV and is now established in numerous regions of Europe. Viremic travellers arriving in Europe from dengue-affected areas of the world can become catalysts of local outbreaks in Europe. Local dengue transmission in Europe is extremely rare, and the last outbreak occurred in 1927-28 in Greece. However, autochthonous transmission was reported from France in September 2010, and from Croatia between August and October 2010.We compiled data on areas affected by dengue in 2010 from web resources and surveillance reports, and collected national dengue importation data. We developed a hierarchical regression model to quantify the relationship between the number of reported dengue cases imported into Europe and the volume of airline travellers arriving from dengue-affected areas internationally.In 2010, over 5.8 million airline travellers entered Europe from dengue-affected areas worldwide, of which 703,396 arrived at 36 airports situated in areas where Ae. albopictus has been recorded. The adjusted incidence rate ratio for imported dengue into European countries was 1.09 (95% CI: 1.01-1.17 for every increase of 10,000 travellers; in August, September, and October the rate ratios were 1.70 (95%CI: 1.23-2.35, 1.46 (95%CI: 1.02-2.10, and 1.35 (95%CI: 1.01-1.81, respectively. Two Italian cities where the vector is present received over 50% of all travellers from dengue-affected areas, yet with the continuing vector expansion more cities will be implicated in the future. In fact, 38% more travellers arrived in 2013 into those parts of Europe where Ae. albopictus has recently been introduced, compared to 2010.The highest risk of dengue importation in 2010 was restricted to three months and can be ranked according to arriving traveller volume from dengue-affected areas into cities where the vector is

  4. International dispersal of dengue through air travel: importation risk for Europe.

    Science.gov (United States)

    Semenza, Jan C; Sudre, Bertrand; Miniota, Jennifer; Rossi, Massimiliano; Hu, Wei; Kossowsky, David; Suk, Jonathan E; Van Bortel, Wim; Khan, Kamran

    2014-12-01

    The worldwide distribution of dengue is expanding, in part due to globalized traffic and trade. Aedes albopictus is a competent vector for dengue viruses (DENV) and is now established in numerous regions of Europe. Viremic travellers arriving in Europe from dengue-affected areas of the world can become catalysts of local outbreaks in Europe. Local dengue transmission in Europe is extremely rare, and the last outbreak occurred in 1927-28 in Greece. However, autochthonous transmission was reported from France in September 2010, and from Croatia between August and October 2010. We compiled data on areas affected by dengue in 2010 from web resources and surveillance reports, and collected national dengue importation data. We developed a hierarchical regression model to quantify the relationship between the number of reported dengue cases imported into Europe and the volume of airline travellers arriving from dengue-affected areas internationally. In 2010, over 5.8 million airline travellers entered Europe from dengue-affected areas worldwide, of which 703,396 arrived at 36 airports situated in areas where Ae. albopictus has been recorded. The adjusted incidence rate ratio for imported dengue into European countries was 1.09 (95% CI: 1.01-1.17) for every increase of 10,000 travellers; in August, September, and October the rate ratios were 1.70 (95%CI: 1.23-2.35), 1.46 (95%CI: 1.02-2.10), and 1.35 (95%CI: 1.01-1.81), respectively. Two Italian cities where the vector is present received over 50% of all travellers from dengue-affected areas, yet with the continuing vector expansion more cities will be implicated in the future. In fact, 38% more travellers arrived in 2013 into those parts of Europe where Ae. albopictus has recently been introduced, compared to 2010. The highest risk of dengue importation in 2010 was restricted to three months and can be ranked according to arriving traveller volume from dengue-affected areas into cities where the vector is present. The

  5. Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection.

    Science.gov (United States)

    Cui, Liang; Hou, Jue; Fang, Jinling; Lee, Yie Hou; Costa, Vivian Vasconcelos; Wong, Lan Hiong; Chen, Qingfeng; Ooi, Eng Eong; Tannenbaum, Steven R; Chen, Jianzhu; Ong, Choon Nam

    2017-07-15

    Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend-most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly

  6. A hospital-based study of hepatic dysfunction in children with dengue fever

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    Surjeet Singh

    2015-12-01

    Full Text Available Objective: To study the hepatic dysfunction in children with dengue infection and find out its correlation with the severity of dengue fever. Methods: Seventy-two cases of dengue fever as per the World Health Organization aged from 2 months to 18 years of age guidelines serologically confirmed by dengue NS1 antigen detection or dengue IgM capture ELISA were studied for their hepatic dysfunction after excluding malaria, enteric fever, hepatitis A and hepatitis B. The duration of the study was from April 2013 to March 2014. Results: These 72 cases were grouped into severe dengue, dengue fever with warning sign and dengue fever without warning sign as per the World Health Organization guidelines. The spectrums of hepatic manifestations included hepatomegaly (66%, hepatic tenderness (44%, jaundice (9.72%, raised levels of aspartate transaminase (86%, alanine transaminase (90%, alkaline phosphatase (39%, prolonged prothrombin time (11% and reduced levels of serum albumin (66%. Conclusions: Tender hepatomegaly and elevated liver enzymes were seen more frequently in severe dengue. There was significant derangement between liver function and tender hepatomegaly. Altered liver function may be evident even in the absence of hepatomegaly.

  7. Self-reported pain intensity with the numeric reporting scale in adult dengue.

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    Joshua G X Wong

    Full Text Available BACKGROUND: Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. METHODS: Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. RESULTS: A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients' day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. CONCLUSION: Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient's progression to severe disease.

  8. Phylogenetic analysis of Dengue virus 1 isolated from South Minas Gerais, Brazil

    OpenAIRE

    Drumond, Betania Paiva; Fagundes, Luiz Gustavo da Silva; Rocha, Raissa Prado; Fumagalli, Marcilio Jorge; Araki, Carlos Shigueru; Colombo, Tatiana Elisa; Nogueira, Mauricio Lacerda; Castilho, Thiago Elias; Silveira, Nelson José Freitas da; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

    2016-01-01

    Abstract Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients who experience secondary infection with a different serotype can progress to a more severe form of the disease, called dengue hemorrhagic fever. The four Dengue virus serotypes (1–4) are antigenically and genetically...

  9. Clinical and virological characteristics of dengue in Surabaya, Indonesia.

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    Puspa Wardhani

    Full Text Available Dengue disease is still a major health problem in Indonesia. Surabaya, the second largest city in the country, is endemic for dengue. We report here on dengue disease in Surabaya, investigating the clinical manifestations, the distribution of dengue virus (DENV serotypes, and the relationships between clinical manifestations and the genetic characteristics of DENV. A total of 148 patients suspected of having dengue were recruited during February-August 2012. One hundred one (68% of them were children, and 47 (32% were adults. Dengue fever (DF and Dengue hemorrhagic fever (DHF were equally manifested in all of the patients. We performed DENV serotyping on all of the samples using real-time RT-PCR. Of 148, 79 (53% samples were detected as DENV positive, with DENV-1 as the predominant serotype (73%, followed by DENV-2 (8%, DENV-4 (8%, and DENV-3 (6%, while 5% were mixed infections. Based on the Envelope gene sequences, we performed phylogenetic analyses of 24 isolates to genotype the DENV circulating in Surabaya in 2012, and the analysis revealed that DENV-1 consisted of Genotypes I and IV, DENV-2 was of the Cosmopolitan genotype, the DENV-3 viruses were of Genotype I, and DENV-4 was detected as Genotype II. We correlated the infecting DENV serotypes with clinical manifestations and laboratory parameters; however, no significant correlations were found. Amino acid analysis of Envelope protein did not find any unique mutations related to disease severity.

  10. Clinical and virological characteristics of dengue in Surabaya, Indonesia.

    Science.gov (United States)

    Wardhani, Puspa; Aryati, Aryati; Yohan, Benediktus; Trimarsanto, Hidayat; Setianingsih, Tri Y; Puspitasari, Dwiyanti; Arfijanto, Muhammad Vitanata; Bramantono, Bramantono; Suharto, Suharto; Sasmono, R Tedjo

    2017-01-01

    Dengue disease is still a major health problem in Indonesia. Surabaya, the second largest city in the country, is endemic for dengue. We report here on dengue disease in Surabaya, investigating the clinical manifestations, the distribution of dengue virus (DENV) serotypes, and the relationships between clinical manifestations and the genetic characteristics of DENV. A total of 148 patients suspected of having dengue were recruited during February-August 2012. One hundred one (68%) of them were children, and 47 (32%) were adults. Dengue fever (DF) and Dengue hemorrhagic fever (DHF) were equally manifested in all of the patients. We performed DENV serotyping on all of the samples using real-time RT-PCR. Of 148, 79 (53%) samples were detected as DENV positive, with DENV-1 as the predominant serotype (73%), followed by DENV-2 (8%), DENV-4 (8%), and DENV-3 (6%), while 5% were mixed infections. Based on the Envelope gene sequences, we performed phylogenetic analyses of 24 isolates to genotype the DENV circulating in Surabaya in 2012, and the analysis revealed that DENV-1 consisted of Genotypes I and IV, DENV-2 was of the Cosmopolitan genotype, the DENV-3 viruses were of Genotype I, and DENV-4 was detected as Genotype II. We correlated the infecting DENV serotypes with clinical manifestations and laboratory parameters; however, no significant correlations were found. Amino acid analysis of Envelope protein did not find any unique mutations related to disease severity.

  11. Fulminant hepatic failure in an infant with severe dengue infection.

    Science.gov (United States)

    Soundravally, R; Narayanan, P; Bhat, B Vishnu; Soundraragavan, Jayanthi; Setia, Sajita

    2010-04-01

    Fulminant hepatic failure due to dengue infection is rare, although mild liver dysfunction is common. Here we report a fatal case of fulminant hepatitis in an infant infected with dengue 3 serotype. Attention must be given to the use of hepatotoxic drugs in some cases of dengue especially in infants.

  12. Dengue data and surveillance in Tanzania: a systematic literature review.

    Science.gov (United States)

    Ward, Tara; Samuel, Moody; Maoz, Dorit; Runge-Ranzinger, Silvia; Boyce, Ross; Toledo, Joao; Velayudhan, Raman; Horstick, Olaf

    2017-08-01

    Although there is evidence that dengue virus is circulating in Tanzania, the country lacks a dengue surveillance system. Consequently, the true estimate of dengue seroprevalence, as well as the incidence in the population, the frequency and magnitude of outbreaks is unknown. This study therefore sought to systematically review available dengue data from Tanzania. The systematic review was conducted and reported using the PRISMA tool. Five databases (PubMed, Embase, Web of Science, WHOLIS and Google Scholar) were searched for articles using various keywords on the illness, data and geographical location. Identified articles were assessed for inclusion based on predefined eligibility criteria. Data were extracted from included articles, analysed and reported. Based on the 10 seroprevalence studies in defined populations with estimates of acute confirmed infections that were included in the review, the estimated seroprevalence of past dengue infection in Tanzania ranged from 50.6% in a health facility-based study to 11% in a population-based study. Acute confirmed infections of dengue were estimated to be as high as 38.2% of suspected cases. Only one study reported on an outbreak. It is evident that dengue needs to become part of regular disease surveillance in Tanzania. Control measures need to be instituted with a focus on building human resource capacity and integrating dengue control measures in ongoing health programmes, for both preventive and curative interventions. Systematic reviews are valuable in assessing health issues when surveillance data are not available. © 2017 John Wiley & Sons Ltd.

  13. Dengue, zika, chikungunya y el desarrollo de vacunas

    OpenAIRE

    Kantor, Isabel N

    2018-01-01

    Dengue (DENV), zika (ZIKV) y chikungunya (CHIKV), tres arbovirosis transmitidas por mosquitos Aedes, se han propagado en las últimas décadas en zonas tropicales y subtropicales húmedas. El dengue es epidémico en áreas subtropicales de la Argentina. Después de la infección por DENV hay inmunidad duradera contra el serotipo infectante, pero aumenta el riesgo de enfermedad grave por los otros tres. La vacuna recombinante tetravalente, Dengvaxia® previene el dengue grave y la hospitalización en s...

  14. Achados ultra-sonográficos abdominais em pacientes com dengue Abdominal ultrasound findings in patients with dengue fever

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    Karen Amaral do Vabo

    2004-06-01

    Full Text Available OBJETIVO: Apresentar os achados ultra-sonográficos abdominais em pacientes com dengue e compará-los aos descritos na literatura. MATERIAIS E MÉTODOS: Foram realizados exames ultra-sonográficos abdominais de 38 pacientes, 25 do sexo feminino e 13 do sexo masculino, com idade média de 35 anos, com diagnóstico de dengue sorologicamente confirmado. Os achados foram comparados com os descritos na literatura. RESULTADOS: Os achados ultra-sonográficos mais relevantes foram espessamento difuso da parede da vesícula biliar em 18 casos (47,4%, líquido livre na cavidade abdominal e/ou pélvica em 12 (31,6%, esplenomegalia em 11 (28,9%, hepatomegalia em 10 (26,3% e líquido pericolecístico em 10 (26,3%. Vinte e seis por cento dos pacientes apresentaram exames ultra-sonográficos normais. CONCLUSÃO: Os achados ultra-sonográficos abdominais são uma ferramenta adicional útil na confirmação de casos suspeitos de dengue hemorrágica e na detecção precoce da gravidade e da progressão da doença, sendo de extrema importância para o radiologista o conhecimento destes possíveis achados.OBJECTIVE: To review the abdominal ultrasound findings in patients with serologically proven dengue fever and to compare the results with data from the literature. MATERIALS AND METHODS: Thirty-eight patients with serologically proven dengue fever, 25 female and 13 male, mean age of 35 years, were submitted to abdominal ultrasound. The ultrasound findings were compared with data from the literature. RESULTS: The most relevant ultrasound findings were diffuse gallbladder wall thickening in 18 cases (47.4%, abdominal and/or pelvic free fluid in 12 (31.6%, splenomegaly in 11 (28.9%, hepatomegaly in 10 (26.3% and perivesicular fluid in 10 (26.3%. Twenty-six percent of the patients had normal abdominal ultrasound. CONCLUSION: Abdominal sonography is a useful additional diagnostic tool for the confirmation of suspected cases of dengue hemorrhagic fever and for the

  15. Knowledge and attitudes in Puerto Rico concerning dengue prevention Conocimientos y actitudes en Puerto Rico en torno a la prevención del dengue

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    Carmen L. Pérez-Guerra

    2005-04-01

    Full Text Available OBJECTIVE: Dengue has been endemic in Puerto Rico for three decades. Multiple educational and community-based efforts have been developed to inform the population about dengue prevention. We undertook this study to understand the community members' knowledge, attitudes, and practices related to dengue prevention and to elicit their ideas for future prevention campaigns. METHODS: A qualitative study based on grounded theory analysis was conducted between February and May of 2001. The study involved a total of 34 participants in four group interviews who had been identified through the Puerto Rico dengue surveillance system. RESULTS: In general, participants had correct knowledge about dengue prevention, but they did not associate the mosquitoes inside their houses with Aedes aegypti. Participants insisted that "neighbors" needed to control larval habitats, and the participants also asked the Government to fumigate. CONCLUSIONS: The patterns of knowledge and opinion that emerged in the discussions can be arranged along an axis going from high levels of correct knowledge to low levels of correct knowledge about dengue and dengue hemorrhagic fever and related practices. There were few participants at either extreme. Three themes explained these patterns: misconceptions about dengue (based on previously delivered information, the "invisibility" of dengue (as compared to other diseases, and responsibility (individual and Government. Four strategies for preventive behaviors were recommended: developing community groups to identify community priorities on prevention, developing volunteer groups to deliver prevention messages, making house visits to demonstrate specific control measures, and conducting a complementary media campaign to support these strategies.OBJETIVO: El dengue ha sido endémico en Puerto Rico durante tres decenios, y varias iniciativas educativas y comunitarias se han puesto en marcha con objeto de informar a la población sobre la

  16. The health and economic impact of dengue in Latin America El impacto sanitario y económico del dengue en Latinoamérica

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    Jaime R. Torres

    2007-01-01

    Full Text Available In the last two decades, all countries in the tropical regions of Latin America have experienced marked increases in the incidence of both classic dengue and dengue hemorrhagic fever. Major risk factors for the occurrence of dengue in the region, as well as some regional peculiarities in its clinical expression, such as the extensive involvement of older age groups, have been defined. While little information exists on the economic impact of dengue in the region in terms of disease burden, the estimated loss associated with the disease is on the same order of magnitude as tuberculosis, sexually transmitted diseases (excluding HIV/AIDS, Chagas disease, leishmaniasis, or intestinal helminths. Therefore, similar priority should be given in the allocation of resources for dengue research and control. Data on cost-efficacy and cost-benefit analysis of dengue control programs in Latin America are scarce; however, the cost per DALY averted by control programs during endemic periods appears low, as compared to other mosquito-borne diseases like yellow fever, leishmaniasis, or malaria. Additionally, the cost-benefit ratio of the control programs has proven to be positive.En las últimas dos décadas, todos los países de las regiones tropicales de Latinoamérica han registrado un fuerte aumento en la incidencia de dengue clásica y dengue hemorrágica. Ya fueron identificados los principales factores de riesgo para la ocurrencia de dengue en la región, así como algunas peculiaridades regionales en su expresión clínica, como el comprometimiento frecuente de grupos de la tercera edad. Pese a la falta de información sobre el impacto económico del dengue en la región en términos de gastos por la enfermedad, las pérdidas estimadas asociadas con la misma son del mismo orden de magnitud que los de la tuberculosis, enfermedades sexualmente transmisibles (excluyendo VIH/SIDA, enfermedad de Chagas, leishmaniasis o parasitosis intestinales. Por tanto, la

  17. Dengue-yellow fever sera cross-reactivity; challenges for diagnosis

    OpenAIRE

    Houghton-Triviño, Natalia; Montaña, Diana; Castellanos, Jaime

    2008-01-01

    Objective The Flavivirus genera share epitopes inducing cross-reactive antibodies leading to great difficulty in differentially diagnosing flaviviral infections. This work was aimed at evaluating the complexity of dengue and yellow fever serological differential diagnosis. Material and methods Dengue antibody capture ELISA and a yellow fever neutralisation test were carried out on 13 serum samples obtained from yellow fever patients, 20 acute serum samples from dengue patients and 19 voluntan...

  18. Spontaneous muscle hematomas in a patient with Dengue hemorrhagic fever

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    Jency Maria Koshy

    2014-01-01

    Full Text Available Dengue hemorrhagic fever (DHF and Dengue shock syndrome manifest in various forms, ranging from petechial skin hemorrhage to life threatening cerebral, pulmonary, gastrointestinal and genitourinary hemorrhages. However it is very rare to have muscle hematomas in DHF. We report a rare case of spontaneous Iliopsoas hematoma complicating Dengue hemorrhagic fever.

  19. Dextran fractional clearance studies in acute dengue infection.

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    Julie Nguyen-Pouplin

    2011-08-01

    Full Text Available Although increased capillary permeability is the major clinical feature associated with severe dengue infections the mechanisms underlying this phenomenon remain unclear. Dextran clearance methodology has been used to investigate the molecular sieving properties of the microvasculature in clinical situations associated with altered permeability, including during pregnancy and in various renal disorders. In order to better understand the characteristics of the vascular leak associated with dengue we undertook formal dextran clearance studies in Vietnamese dengue patients and healthy volunteers.We carried out serial clearance studies in 15 young adult males with acute dengue and evidence of vascular leakage a during the phase of maximal leakage and b one and three months later, as well as in 16 healthy control subjects. Interestingly we found no difference in the clearance profiles of neutral dextran solutions among the dengue patients at any time-point or in comparison to the healthy volunteers.The surface glycocalyx layer, a fibre-matrix of proteoglycans, glycosaminoglycans, and plasma proteins, forms a complex with the underlying endothelial cells to regulate plasma volume within circumscribed limits. It is likely that during dengue infections loss of plasma proteins from this layer alters the permeability characteristics of the complex; physical and/or electrostatic interactions between the dextran molecules and the glycocalyx structure may temporarily restore normal function, rendering the technique unsuitable for assessing permeability in these patients. The implications for resuscitation of patients with dengue shock syndrome (DSS are potentially important. It is possible that continuous low-dose infusions of dextran may help to stabilize the permeability barrier in patients with profound or refractory shock, reducing the need for repeated boluses, limiting the total colloid volume required. Formal clinical studies should help to assess

  20. Anamnestic immune response to dengue and decreased severity of yellow fever

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    Ricardo O Izurieta

    2009-01-01

    Full Text Available A protective immunity against yellow fever, from cross-reactive dengue antibodies, has been hypothesized as an explanation for the absence of yellow fever in Southern Asia where dengue immunity is almost universal. This study evaluates the association between protective immunity from cross-reactive dengue antibodies with yellow fever infection and severity of the disease. The study population consisted of military personnel of a jungle garrison and its detachments located in the Ecuadorian Amazonian rainforest. The cross-sectional study employed interviews as well as seroepidemiological methods. Humoral immune response to yellow fever, Mayaro, Venezuelan equine encephalitis, Oropouche, and dengue 2 infections was assessed by evaluating IgM and IgG specific antibodies. Log-linear regression analysis was used to evaluate age and presence of antibodies, against dengue type 2 virus, as predictors of yellow fever infection or severe disease. During the seroepidemiological survey, presence of dengue antibodies among yellow fever cases were observed in 77.3% cases from the coastal region, where dengue is endemic, 14.3% cases from the Amazon and 16.7 % cases from the Andean region. Dengue cross-reactive antibodies were not significantly associated with yellow fever infection but significantly associated with severity of the disease. The findings of this study suggest that previous exposure to dengue infection may have induced an anamnestic immune response that did not prevent yellow fever infection but greatly reduced the severity of the disease.

  1. PREDICTION OF DENGUE FEVER EPIDEMIC SPREADING USING DYNAMICS TRANSMISSION VECTOR MODEL

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    Retno Widyaningrum

    2014-05-01

    Full Text Available Increasing number of dengue cases in Surabaya shows that its city has high potential of dengue fever epidemic. Although some policies were designed by Surabaya Health Department, such as fogging and mosquito’s nest eradication, but these efforts still out of target because of inaccurate predictions. Ineffectiveness eradication of dengue fever epidemic is caused by lack of information and knowledge on environmental conditions in Surabaya. Developing spread and prediction system to minimize dengue fever epidemic is necessary to be conducted immediately. Spread and prediction system can improve eradication and prevention accuracy. The transmission dynamics vector simulation will be used as an approach to draw a complex system ofmosquito life cycle in which involve a lot offactors. Dynamics transmission model used to build model in mosquito model (oviposition rate and pre adult mosquito, infected and death cases in dengue fever. The model of mosquito and infected population can represent system. The output of this research is website of spread and prediction system of dengue fever epidemics to predict growth rate of Aedes Aegypti mosquito, infected, and death population because of dengue fever epidemics. The deviation of infected population is 0,519. The model of death cases in dengue fever is less precision with the deviation 1,229. Death cases model need improvement by adding some variables that influence to dengue fever death cases. Spread ofdengue fever prediction will help the government, health department to decide the best policies in minimizing the spread ofdengue fever epidemics.

  2. Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication.

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    Hussin A Rothan

    Full Text Available Dengue virus (DENV broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1 and plectasin (PLSN were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro with half-maximal inhibitory concentration (IC50 0.5±0.1 μM. The real-time proliferation assay (RTCA and the end-point proliferation assay (MTT assay showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities.

  3. Maternal and perinatal outcomes of dengue in PortSudan, Eastern Sudan

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    Elbashir Hagir M

    2010-07-01

    Full Text Available Abstract Aim To investigate maternal and perinatal outcomes (maternal death, preterm delivery, low birth weight and perinatal mortality of dengue at PortSudan and Elmawani hospitals in the eastern Sudan. Method This was a retrospective Cohort study where medical files of women with dengue were reviewed. Results There were 10820 deliveries and 78 (0.7% pregnant women with confirmed dengue IgM serology at the mean (SD gestational age of 29.4(8.2 weeks. While the majority of these women had dengue fever (46, 58.9%, hemorrhagic fever and dengue shock syndrome were the presentations in 18 (23.0% and 12, (15.3% of these women, respectively. There were 17(21.7% maternal deaths. Fourteen (17.9% of these 78 women had preterm deliveries and 19 (24.3% neonates were admitted to neonatal intensive care unit. Nineteen (24.3% women gave birth to low birth weight babies. There were seven (8.9% perinatal deaths. Eight (10.2% patients delivered by caesarean section due to various obstetrical indications. Conclusion Thus dengue has poor maternal and perinatal outcomes in this setting. Preventive measures against dengue should be employed in the region, and more research on dengue during pregnancy is needed.

  4. Reduction of Tetravalent Plutonium in the Presence of Acetohydroxamic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Tkac, Peter [Radiation Center, Oregon State University, Corvallis, OR (United States); Precek, Martin [Department of Chemistry, Oregon State University, Corvallis, OR (United States); Paulenova, Alena [Department of Nuclear Engineering and Radiation Health Physics, Oregon State University, Corvallis, OR (United States)

    2009-06-15

    Acetohydroxamic acid (AHA) has been proposed as a salt-free stripping reagent in the modified PUREX process for the spent nuclear fuel re-processing. AHA is a capable reductant of Np(VI) and Pu(VI) and a strong complexant for tetravalent neptunium and plutonium; hence, its behavior must be studied in detail. For better characterization of the all relevant chemical processes and successful design of the future separation flowsheets it is important to predict the speciation and partitioning of Pu between the organic and aqueous phases in the proposed extraction systems containing acetohydroxamic acid. The hydrolytic instability of hydroxamic group under acidic conditions causes a slow degradation of AHA followed by formation of acetic acid and hydroxylamine which also acts as a reductant of Pu(IV). The complexes of Pu(IV) with AHA are very strong; however, under acidic conditions, the chelate ring prevents the acidic hydrolysis only temporarily. The decomposition of Pu-aceto-hydroxamate complex and reduction of Pu(IV) to Pu(III) observed for these systems was investigated in the present paper. Reduction of Pu(IV) in the presence of AHA was monitored by Vis-NIR spectroscopy in the range of 400-700 nm. All complexes between Pu(IV) and AHA have a very intense absorption in this region; therefore, for a better resolution of spectra, all experiments were performed under low AHA:Pu ratios, where only two species, non-complexed Pu(IV) and Pu(IV)-mono-aceto-hydroxamate complex, are initially present in relevant concentrations. To characterize the rate and the reaction mechanism, spectra were collected as a function of time for different initial concentrations of reactants and analyzed at several wavelengths using the data on extinction coefficients for all absorbing species. The extinction coefficient for Pu(IV)-AHA complex was resolved by fitting the absorption spectra with the chemical equilibrium modeling software FITEQL 4.0. The analysis of the experimental data obtained

  5. Prevalence of dengue and chikungunya virus infections in north-eastern Tanzania

    DEFF Research Database (Denmark)

    Kajeguka, Debora C; Kaaya, Robert D; Mwakalinga, Steven

    2016-01-01

    BACKGROUND: In spite of increasing reports of dengue and chikungunya activity in Tanzania, limited research has been done to document the general epidemiology of dengue and chikungunya in the country. This study aimed at determining the sero-prevalence and prevalence of acute infections of dengue......-like symptoms at health facilities at Bondo dispensary (Bondo, Tanga), Hai hospital (Hai, Kilimanjaro) and TPC hospital (Lower Moshi). Participants who were malaria negative using rapid diagnostic tests (mRDT) were screened for sero-positivity towards dengue and chikungunya Immunoglobulin G and M (IgG and Ig......M) using ELISA-based kits. Participants with specific symptoms defined as probable dengue and/or chikungunya by WHO (fever and various combinations of symptoms such as headache, rash, nausea/vomit, and joint pain) were further screened for acute dengue and chikungunya infections by PCR. RESULTS: Out...

  6. The revised WHO dengue case classification: does the system need to be modified?

    Science.gov (United States)

    Hadinegoro, Sri Rezeki S

    2012-05-01

    There has been considerable debate regarding the value of both the 1997 and 2009 World Health Organization (WHO) dengue case classification criteria for its diagnosis and management. Differentiation between classic dengue fever (DF) and dengue haemorrhagic fever (DHF) or severe dengue is a key aspect of dengue case classification. The geographic expansion of dengue and its increased incidence in older age groups have contributed to the limited applicability of the 1997 case definitions. Clinical experience of dengue suggests that the illness presents as a spectrum of disease instead of distinct phases. However, despite the rigid grouping of dengue into DF, DHF and dengue shock syndrome (DSS), overlap between the different manifestations has often been observed, which has affected clinical management and triage of patients. The findings of the DENCO study evaluating the 1997 case definitions formed the basis of the revised 2009 WHO case definitions, which classified the illness into dengue with and without warning signs and severe dengue. Although the revised scheme is more sensitive to the diagnosis of severe dengue, and beneficial to triage and case management, there remain issues with its applicability. It is considered by many to be too broad, requiring more specific definition of warning signs. Quantitative research into the predictive value of these warning signs on patient outcomes and the cost-effectiveness of the new classification system is required to ascertain whether the new classification system requires further modification, or whether elements of both classification systems can be combined.

  7. Imported dengue from 2013 Angola outbreak: Not just serotype 1 was detected.

    Science.gov (United States)

    Abreu, Cândida; Silva-Pinto, André; Lazzara, Daniela; Sobrinho-Simões, Joana; Guimarães, João Tiago; Sarmento, António

    2016-06-01

    All the reports from Angola's 2013 dengue outbreak revealed serotype 1. However, previously dengue serotypes 1-4 have been reported in Africa and in 2014 serotype 4 was reported in Angola. To report dengue serotypes in patients returning from Angola during 2013 outbreak. Retrospective, cross-sectional study. We serotyped the dengue by an in house Polymerase Chain Reaction technique in randomly selected cases. From the 2013 Angola's dengue outbreak we treated 47 adult patients. None had history of past dengue. A combo kit test for dengue revealed positive NS1 antigen in 39 and IgM antibodies in 8. From 17 randomly patients tested by RNA Real Time-PCR, 11 were positive: 7 for DENV-1, 2 for DENV-2, 1 for DENV-3 (co-infected with DENV-1) and 1 for DENV-4. None had a complicated or fatal evolution. Unlike previous reports the 4 serotypes were detected, and this resulted in a different epidemiological situation, raising the risk of future outbreaks of severe dengue. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

    OpenAIRE

    Maíra Aguiar; Nico Stollenwerk; Scott B Halstead

    2016-01-01

    Background With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteu...

  9. An Accurate Gaussian Process-Based Early Warning System for Dengue Fever

    OpenAIRE

    Albinati, Julio; Meira Jr, Wagner; Pappa, Gisele Lobo

    2016-01-01

    Dengue fever is a mosquito-borne disease present in all Brazilian territory. Brazilian government, however, lacks an accurate early warning system to quickly predict future dengue outbreaks. Such system would help health authorities to plan their actions and to reduce the impact of the disease in the country. However, most attempts to model dengue fever use parametric models which enforce a specific expected behaviour and fail to capture the inherent complexity of dengue dynamics. Therefore, ...

  10. Preliminary study of dengue virus infection in Iran

    DEFF Research Database (Denmark)

    Chinikar, Sadegh; Ghiasi, Seyed Mojtaba; Shah-Hosseini, Nariman

    2012-01-01

    Dengue fever is one of the most important arthropod-borne viral diseases of public health significance. It is endemic in most tropical and subtropical parts of the world, many of which are popular tourist destinations. The presence of dengue infection was examined in Iranian patients who were...... abroad. Of these, six cases were from the Sistan and Baluchistan province in southeast Iran and neighbouring Pakistan. Travellers play a key role in the epidemiology of dengue infection in Iran and it is recommended that travellers to endemic areas take precautionary measures to avoid mosquito bites....

  11. Socio-demographic, ecological factors and dengue infection trends in Australia.

    Science.gov (United States)

    Akter, Rokeya; Naish, Suchithra; Hu, Wenbiao; Tong, Shilu

    2017-01-01

    Dengue has been a major public health concern in Australia. This study has explored the spatio-temporal trends of dengue and potential socio- demographic and ecological determinants in Australia. Data on dengue cases, socio-demographic, climatic and land use types for the period January 1999 to December 2010 were collected from Australian National Notifiable Diseases Surveillance System, Australian Bureau of Statistics, Australian Bureau of Meteorology, and Australian Bureau of Agricultural and Resource Economics and Sciences, respectively. Descriptive and linear regression analyses were performed to observe the spatio-temporal trends of dengue, socio-demographic and ecological factors in Australia. A total of 5,853 dengue cases (both local and overseas acquired) were recorded across Australia between January 1999 and December 2010. Most the cases (53.0%) were reported from Queensland, followed by New South Wales (16.5%). Dengue outbreak was highest (54.2%) during 2008-2010. A highest percentage of overseas arrivals (29.9%), households having rainwater tanks (33.9%), Indigenous population (27.2%), separate houses (26.5%), terrace house types (26.9%) and economically advantage people (42.8%) were also observed during 2008-2010. Regression analyses demonstrate that there was an increasing trend of dengue incidence, potential socio-ecological factors such as overseas arrivals, number of households having rainwater tanks, housing types and land use types (e.g. intensive uses and production from dryland agriculture). Spatial variation of socio-demographic factors was also observed in this study. In near future, significant increase of temperature was also projected across Australia. The projected increased temperature as well as increased socio-ecological trend may pose a future threat to the local transmission of dengue in other parts of Australia if Aedes mosquitoes are being established. Therefore, upgraded mosquito and disease surveillance at different ports should

  12. Isolated unilateral sixth cranial nerve palsy: A rare presentation of dengue fever

    Directory of Open Access Journals (Sweden)

    Yang Liang Boo

    2016-11-01

    Full Text Available Dengue fever is a common mosquito-borne viral infection endemic in tropical and subtropical countries. Neurological manifestations in dengue infection are relatively uncommon, and include encephalitis, encephalopathy, neuromuscular disorders and neuro-ocular disorders. Cranial mononeuropathy is a rare manifestation of dengue infection. A 40-year-old man was diagnosed with isolated, unilateral sixth cranial nerve palsy complicating dengue infection. The patient was managed accordingly, and full ocular recovery was observed. This was the first reported case of isolated sixth cranial nerve palsy associated with dengue fever in Malaysia. It is important for clinicians to consider dengue as a differential diagnosis in patients presenting with fever and sixth cranial nerve palsy.

  13. Socio-economic, Knowledge Attitude Practices (KAP), household related and demographic based appearance of non-dengue infected individuals in high dengue risk areas of Kandy District, Sri Lanka.

    Science.gov (United States)

    Udayanga, Lahiru; Gunathilaka, Nayana; Iqbal, M C M; Pahalagedara, Kusumawathie; Amarasinghe, Upali S; Abeyewickreme, Wimaladharma

    2018-02-21

    Socio-economic, demographic factors and Knowledge Attitude Practices (KAPs) have been recognized as critical factors that influence the incidence and transmission of dengue epidemics. However, studies that characterize above features of a risk free or low risk population are rare. Therefore, the present study was conducted to characterize the household related, demographic, socio-economic factors and KAPs status of five selected dengue free communities. An analytical cross-sectional survey was conducted on selected demographic, socio-economic, household related and KAPs in five selected dengue free communities living in dengue risk areas within Kandy District, Central Province, Sri Lanka. Household heads of 1000 randomly selected houses were interviewed in this study. Chi-square test for independence, cluster analysis and Principal Coordinates (PCO) analysis were used for data analysis. Knowledge and awareness regarding dengue, (prevention of the vector breeding, bites of mosquitoes, disease symptoms and waste management) and attitudes of the community (towards home gardening, composting, waste management and maintenance of a clean and dengue free environment) are associated with the dengue free status of the study populations. The vector controlling authorities should focus on socio-economic, demographic and KAPs in stimulating the community to cooperate in the integrated vector management strategies to improve vector control and reduce transmission of dengue within Kandy District.

  14. Dengue fever/dengue haemorrhagic fever in Filipino children: clinical experience during the 1983-1984 epidemic.

    Science.gov (United States)

    Songco, R S; Hayes, C G; Leus, C D; Manaloto, C O

    1987-09-01

    A total of 377 Filipino children out of a total of 5,427 admissions from October 31, 1983 to March 31, 1984 were found to have dengue fever/dengue haemorrhagic fever The present clinical presentation of these infections was basically similar to that in previous epidemics but hepatomegaly and pleural effusion were less frequent and cardiac involvement, more frequent. The discrepancies between the clinical syndromes and HI antibody responses were evident; thus, the values used for the interpretation of the antibody titers must be reassessed.

  15. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    International Nuclear Information System (INIS)

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made

  16. [Epidemiological dynamics of Dengue on Easter Island].

    Science.gov (United States)

    Canals, Mauricio; González, Christian; Canals, Andrea; Figueroa, Daniela

    2012-08-01

    Dengue is considered an emerging disease with an increasing prevalence especially in South America. In 2002, an epidemic of classic Dengue (DENV-1) occurred unexpectedly on Easter Island, where it had never been detected before. It reappeared in 2006-2007 and 2008, 2009 and 2011. The aim of this study was to estimate the most relevant parameters of the epidemiological dynamics of transmission of Dengue on Easter Island and to model the dynamics since 2002, comparing the predictions with the actual situation observed. Of the total cases, 52.27% were females and 47.73% men. The average age of infection was 31.38 ± 18.37 years, similar in men and women. We estimated the reproductive number R0 = 3.005 with an IC0,95 = [1.92, 4.61]. The inter-epidemic period reached an estimated T = 5.20 to 6.8 years. The case simulation showed recurrent epidemics with decreasing magnitude (damped oscillations), which is a known phenomenon in models of dengue and malaria. There was good qualitative fit to the epidemiological dynamics from 2002 onwards. It accurately predicted the rise in cases between 2006 and 2011. The predicted number of cases during the 2002 epidemic is greater than the confirmed cases and the predicted epidemic was faster than notified cases. Interepidemic period in the simulation was 6.72 years between 2002 and 2008 and 4.68 years between 2008 and 2013. From the theoretical perspective, the first epidemic had affected 94% of the population (approximately 3500 cases), but 639 were reported suggesting underreporting and a lot of sub-clinical cases occurred. Future epidemic of decreasing size are expected, although the main danger are epidemics of hemorrhagic dengue fever resulting from the introduction of different dengue virus serotypes.

  17. An in-depth analysis of original antigenic sin in dengue virus infection.

    Science.gov (United States)

    Midgley, Claire M; Bajwa-Joseph, Martha; Vasanawathana, Sirijitt; Limpitikul, Wannee; Wills, Bridget; Flanagan, Aleksandra; Waiyaiya, Emily; Tran, Hai Bac; Cowper, Alison E; Chotiyarnwong, Pojchong; Chotiyarnwon, Pojchong; Grimes, Jonathan M; Yoksan, Sutee; Malasit, Prida; Simmons, Cameron P; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2011-01-01

    The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.

  18. Molecular surveillance of Dengue in Sukabumi, West Java province, Indonesia.

    Science.gov (United States)

    Nusa, Roy; Prasetyowati, Heni; Meutiawati, Febrina; Yohan, Benediktus; Trimarsanto, Hidayat; Setianingsih, Tri Yuli; Sasmono, R Tedjo

    2014-06-11

    Dengue is endemic and affects people in all Indonesian provinces. Increasing dengue cases have been observed every year in Sukabumi in West Java province. Despite the endemicity, limited data is available on the genetic of dengue viruses (DENV) circulating in the country. To understand the dynamics of dengue disease, we performed molecular and serological surveillance of dengue in Sukabumi. A total of 113 patients were recruited for this study. Serological data were obtained using anti-dengue IgM and IgG tests plus dengue NS1 antigen detection. Dengue detection and serotyping were performed using real-time RT-PCR. Viruses were isolated and the envelope genes were sequenced. Phylogenetic and evolutionary analyses were performed to determine the genotype of the viruses and their evolutionary rates. Real-time RT-PCR detected DENV in 25 (22%) of 113 samples. Serotyping revealed the predominance of DENV-2 (16 isolates, 64%), followed by DENV-1 (5 isolates, 20%), and DENV-4 (4 isolates, 16%). No DENV-3 was detected in the samples. Co-circulation of genotype I and IV of DENV-1 was observed. The DENV-2 isolates all belonged to the Cosmopolitan genotype, while DENV-4 isolates were grouped into genotype II. Overall, their evolutionary rates were similar to DENV from other countries. We revealed the distribution of DENV serotypes and genotypes in Sukabumi. Compared to data obtained from other cities in Indonesia, we observed the differing predominance of DENV serotypes but similar genotype distribution, where the infecting viruses were closely related with Indonesian endemic viruses isolated previously.

  19. Dengue in Rio Grande do Sul, Brazil: 2014 to 2016.

    Science.gov (United States)

    Gregianini, Tatiana Schaffer; Tumioto-Giannini, Gabriela Luchiari; Favreto, Cátia; Plentz, Luciana Ciarelli; Ikuta, Nilo; da Veiga, Ana B Gorini

    2018-01-01

    The first autochthonous dengue case in Rio Grande do Sul (RS), Southern Brazil, occurred in 2007. In 2008 and 2009, only imported cases were reported in RS, but from 2010 to 2013, reports of autochthonous infections increased significantly. This study analyzes and discusses laboratory, demographic, and clinical data regarding dengue cases in RS, from 2014 to 2016. This study analyzed 13,420 serum samples from notified patients with suspicion of dengue fever in RS from 2014 to 2016. Seasonality of positive cases, viral serotypes, and clinical and epidemiological aspects were analyzed. There was no difference in gender (P = .4); dengue fever occurred mainly in adults, with similar distribution among age groups. The number of dengue virus (DENV) cases increased from 89 cases in 2014 to 2518 in 2016. Dengue virus 1 was the most prevalent circulating serotype during this period (97.5% of cases). Dengue virus infections show peaks in March and April (late summer and early autumn), after periods of high temperatures and rainfall. In 2014, dengue cases were concentrated in the northwestern and eastern regions of RS, and in 2015 and 2016, the northern region also confirmed a high number of cases. With increase in DENV circulation in RS, a rise in the number of autochthonous infections was also observed, mainly in highly urbanized areas. This study revealed that circulation of DENV in RS increased significantly in 2015 and 2016, with a rise in the number of autochthonous infections and cocirculation with Chikungunya and Zika viruses, recently introduced into RS. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Dengue en Panamá, 1993

    OpenAIRE

    QUIROZ, EVELIA; ORTEGA, MARITZA; GUZMÁN, MARÍA GUADALUPE; VÁZQUEZ, SUSANA; PELEGRINO, JOSÉ LUIS; CAMPOS, CORNELIO; BAYARD, VICENTE; VÁZQUEZ, MANUEL; KOURÍ, GUSTAVO

    1997-01-01

    Hasta 1993, Panamá era el único país de Centroamérica que había detectado transmisión autóctona de virus dengue sin experimentar una epidemia explosiva, pese a estar reinfestado con el mosquito Aedes aegypti desde 1985. En este trabajo se describen las características de este primer brote reportado el 19 de noviembre de 1993 y se demuestra que las epidemias se presentan a pesar de mantener un Programa de Vigilancia y Control para Dengue -que contempla bajos niveles de infestación del Aedes ae...