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Sample records for recombinant tetravalent dengue

  1. 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

  2. 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.

  3. 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.

  4. 75 FR 6211 - Prospective Grant of Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine...

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    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...

  5. 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

  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. 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.

  8. 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.

  9. 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.

  10. Enhancing the Immunogenicity of a Tetravalent Dengue DNA Vaccine

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    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

  11. 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.

  12. A tetravalent dengue nanoparticle stimulates antibody production in mice

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    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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

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

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    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.

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

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    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.

  19. 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.

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    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.

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

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    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).

  1. 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.

  2. 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

  3. 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...

  4. 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.

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

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

    OpenAIRE

    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...

  8. 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

  9. 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

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

    Science.gov (United States)

    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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 ...

  18. 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

  19. 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

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

    Science.gov (United States)

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

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    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

  2. 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.

  3. Dengue

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    ... 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- ...

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

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    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.

  5. Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

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    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

  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.

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    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. 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.

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    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.

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

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    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.

  9. 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.

  10. 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.

  11. DENGUE VACCINE, CHALLENGES, DEVELOPMENT AND STRATEGIES

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    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

  12. 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.

  13. 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.

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

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    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

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

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    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.

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

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    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.

  17. [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.

  18. 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

  19. 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

  20. 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 ...

  1. 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

  2. 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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Recombiner

    International Nuclear Information System (INIS)

    Kikuchi, Nobuo.

    1983-01-01

    Purpose: To shorten the pre-heating time for a recombiner and obtain a uniform temperature distribution for the charged catalyst layer in a BWR type reactor. Constitution: A pre-heating heater is disposed to the outer periphery of a vessel for a recombiner packed with catalysts for recombining hydrogen and oxygen in gases flowing through a radioactive gaseous wastes processing system. Heat pipes for transmitting the heat applied to said container to the catalyst are disposed vertically and horizontally within the container. Different length of the heat pipes are combined. In this way, pre-heating time for the recombiner before the operation start and before the system switching can be shortened and the uniform pre-heating for the inside of the recombiner is also made possible. Further, heater control in the pre-heating can be carried out effectively and with ease. (Moriyama, K.)

  6. 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.

  7. Recombiner

    International Nuclear Information System (INIS)

    Osumi, Morimichi.

    1979-01-01

    Purpose: To provide a recombiner which is capable of converting hydrogen gas into water by use of high-frequency heating at comparatively low temperatures and is safe and cheap in cost. Constitution: Hydrogen gas is introduced from an outer pipeline to the main structure of a recombiner, and when it passes through the vicinity of the central part of the recombiner, it is reacted with copper oxide (CuO 2 ) heated to a temperature more than 300 0 C by a high-frequency heater, and converted gently into water by reduction operation (2H 2 + CuO 2 → Cu + 2H 2 O). The thus prepared water is exhausted through the outer pipeline to a suppression pool. A part of hydrogen gas which has not been converted completely into water by the reaction and is remaining as hydrogen is recovered through exhaust nozzles and again introduced into the main structure of the recombiner. (Yoshino, Y.)

  8. 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

  9. 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.

  10. 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 ...

  11. Recombiner

    International Nuclear Information System (INIS)

    Saalfrank, H.

    1985-01-01

    Air containing hydrogen can be oxidized by heating in a container called a recombiner, in order to avoid the collection of hydrogen. The container is long and a large number of straight heating bars are arranged in parallel in it and they are flanged to a lid. The heating bars are surrounded by tubes, in order to obtain good heat transfer by a narrow annular gap. (orig.) [de

  12. 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

  13. 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

  14. Dengue situation in Brazil by year 2000

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. 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.

  17. Prevention and Control Strategies to Counter Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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....

  3. 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.

  4. 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)

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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...

  12. 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)

  13. 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

  14. 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...

  15. 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.

  16. 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...

  17. 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, ...

  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. 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 ...

  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. 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...

  2. 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...

  3. 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

  4. 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.

  5. 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...

  6. 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)

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  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. 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.

  13. 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.

  14. 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...

  15. 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.

  16. 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

  17. Chemical interaction of tetravalent actinides simulators and the engineering barrier

    International Nuclear Information System (INIS)

    Chain, Pablo; Alba, Maria D.; Castro, Miguel A.; Pavon, Esperanza; Mar Orta, M.

    2010-01-01

    simulator with the engineering barrier at conditions close to those of the repository. The methodology used consists in the hydrothermal treatment of different natural bentonites, including FEBEX and MX-80 bentonites, with aqueous solutions of the mentioned tetravalent lanthanide elements at subcritical conditions. The reaction products have been analysed with the help of X-ray diffraction, MAS-NMR spectroscopy and scanning electron microscopy. The results show that after the hydrothermal reaction two new phases containing zirconium have been formed, ZrSiO 4 and ZrO 2 , and their ratio depend on the nature of the bentonite. It demonstrates that the already explored chemical interaction between trivalent radionuclides and bentonite barrier is also possible with the tetravalent radionuclides. (authors)

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Hydrolysis constants of tetravalent neptunium by using solvent extraction method

    International Nuclear Information System (INIS)

    Fujiwara, K.; Kohara, Y.

    2008-01-01

    The hydrolysis constants of tetravalent neptunium (Np(IV)) were determined by solvent extraction method using thenoyltrifluoroacetone(TTA). In order to avoid colloid formation, a stock solution of carrier-free 239 Np(V) was from 243 Am milked. The valence of Np in the solution was then reduced to Np(IV) by using zinc amalgam. The hydrolysis constants (β m ) of the reactions, Np 4+ + mOH - = Np(OH) m (4-m)+ was evaluated by using distribution ratios at ionic strengths (I) = 0.1, 0.5 and 1.0. All experiments were performed in oxygen-free 0.5% H 2 -N 2 atmosphere (below 1.0 ppm of O 2 ) in a glove-box at room temperature (23 ± 2 C) to avoid oxidation of Np(IV). The β m values were extrapolated to the standard state (I = 0) by using the specific ion interaction theory (SIT), and the formation constants at I = 0 were determined to be log β 1 = 13.91 ± 0.23, log β 2 = 27.13 ± 0.15, log β 3 = 37.70 ± 0.30 and log β 4 = 46.16 ± 0.30. The ion interaction coefficients were also evaluated to be ε(NpOH 3+ , ClO 4 - ) = 0.49 ± 0.15, ε(Np(OH) 2 2+ , ClO 4 - ) = 0.35 ± 0.11, and ε(Np(OH) 3 + , ClO 4 - ) = 0.29 ± 0.15. (orig.)

  5. Hydrolysis constants of tetravalent neptunium by using solvent extraction method

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, K. [Japan Atomic Energy Agency (JAEA), Naka-gun, Ibaraki-ken (Japan); Kohara, Y. [Inspection and Development Co., Naka-gun, Ibaraki-ken (Japan)

    2008-07-01

    The hydrolysis constants of tetravalent neptunium (Np(IV)) were determined by solvent extraction method using thenoyltrifluoroacetone(TTA). In order to avoid colloid formation, a stock solution of carrier-free {sup 239}Np(V) was from {sup 243}Am milked. The valence of Np in the solution was then reduced to Np(IV) by using zinc amalgam. The hydrolysis constants ({beta}{sub m}) of the reactions, Np{sup 4+} + mOH{sup -} = Np(OH){sub m}{sup (4-m)+} was evaluated by using distribution ratios at ionic strengths (I) = 0.1, 0.5 and 1.0. All experiments were performed in oxygen-free 0.5% H{sub 2}-N{sub 2} atmosphere (below 1.0 ppm of O{sub 2}) in a glove-box at room temperature (23 {+-} 2 C) to avoid oxidation of Np(IV). The {beta}{sub m} values were extrapolated to the standard state (I = 0) by using the specific ion interaction theory (SIT), and the formation constants at I = 0 were determined to be log {beta}{sub 1} = 13.91 {+-} 0.23, log {beta}{sub 2} = 27.13 {+-} 0.15, log {beta}{sub 3} = 37.70 {+-} 0.30 and log {beta}{sub 4} = 46.16 {+-} 0.30. The ion interaction coefficients were also evaluated to be {epsilon}(NpOH{sup 3+}, ClO{sub 4}{sup -}) = 0.49 {+-} 0.15, {epsilon}(Np(OH){sub 2}{sup 2+}, ClO{sub 4}{sup -}) = 0.35 {+-} 0.11, and {epsilon}(Np(OH){sub 3}{sup +}, ClO{sub 4}{sup -}) = 0.29 {+-} 0.15. (orig.)

  6. Solvothermal synthesis of tetravalent uranium with isophthalate or pyromellitate ligands

    Energy Technology Data Exchange (ETDEWEB)

    Falaise, Clement; Delille, Jason; Volkringer, Christophe; Loiseau, Thierry [Contribution from Unite de Catalyse et Chimie du Solide (UCCS) - UMR CNRS 8181, Universite de Lille, USTL-ENSCL, Villeneuve d' Ascq (France)

    2015-06-15

    Three new coordination polymers bearing tetravalent uranium have been isolated with the O-donor ligands such as isophthalate (1,3-bdc) or pyromellitate (btec). The compounds 1 and 3 have been solvothermally synthesized in N,N-dimethylformamide (DMF). The crystal structure of U(1,3-bdc){sub 2}(DMF) (1) is built up from discrete tricapped trigonal-primastic UO{sub 9} units, for which one carbonyl oxygen atom from DMF is bound to uranium. The connection of the UO{sub 9} units with the isophthalate linkers occurs in a chelating and bidentate fashion and gives rise to the formation of a 3D framework, delimiting narrow channels running along the [101] direction. Upon heating, the DMF molecules are removed, generating the second phase U(1,3-bdc){sub 2} (2) compound, closely related to 1. Indeed, the coordination environment of uranium is reduced to eight with a distorted square-antiprismatic geometry. This transition induces the relative shrinkage of the network (ΔV = 23 %). The structure of the compound U(btec)(DMF){sub 2} (3) also exhibits a 3D framework composed of an isolated bicapped square-antiprismatic UO{sub 10} unit, for which two carbonyl oxygen atoms from DMF are bonded to uranium. Pyromellitate ensures the connection of the UO{sub 10} units through the carboxylate arms in a chelating mode. This results in the formation of a network with diamond-shaped channels, developed along the c axis and encapsulating the DMF molecules. In contrast to 1, no stable phase is observed upon removing the DMF species by heating. (Copyright copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. 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...

  8. 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.

  9. 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.

  10. 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...

  11. 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 ...

  12. 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....

  13. 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...

  14. 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.

  15. 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)

  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. 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

  18. 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.

  19. THROMBOCYTOPENIA IN DENGUE HAEMORRHAGIC FEVER

    Directory of Open Access Journals (Sweden)

    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.

  20. Neurological Manifestations of Dengue Infection

    Directory of Open Access Journals (Sweden)

    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.

  1. Recombinant Programming

    OpenAIRE

    Pawlak , Renaud; Cuesta , Carlos; Younessi , Houman

    2004-01-01

    This research report presents a promising new approach to computation called Recombinant Programming. The novelty of our approach is that it separates the program into two layers of computation: the recombination and the interpretation layer. The recombination layer takes sequences as inputs and allows the programmer to recombine these sequences through the definition of cohesive code units called extensions. The output of such recombination is a mesh that can be used by the interpretation la...

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. [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.

  7. Dengue Fever Treatment

    Science.gov (United States)

    ... AIDS Influenza Malaria Respiratory Syncytial Virus (RSV) Tuberculosis Zika Virus Find a Funding Opportunity Opportunities & Announcements Types of ... For example, the entire genome sequence of the Aedes aegypti mosquito, the main carrier of dengue virus, has been decoded and is available to qualified ...

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. Micronutrients and Dengue

    OpenAIRE

    Ahmed, Sundus; Finkelstein, Julia L.; Stewart, Anna M.; Kenneth, John; Polhemus, Mark E.; Endy, Timothy P.; Cardenas, Washington; Mehta, Saurabh

    2014-01-01

    Dengue virus infection is the most widespread mosquito-borne viral infection in humans and has emerged as a serious global health challenge. In the absence of effective treatment and vaccine, host factors including nutritional status, which may alter disease progression, need investigation. The interplay between nutrition and other infections is well-established, and modulation of nutritional status often presents a simple low-cost method of interrupting transmission, reducing susceptibility,...

  16. 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.

  17. 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.

  18. 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...

  19. 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

  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. Genetic Recombination

    Science.gov (United States)

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  2. 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

  3. 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)

  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. ADE and dengue vaccination.

    Science.gov (United States)

    Martínez-Vega, Ruth Aralí; Carrasquila, Gabriel; Luna, Expedito; Ramos-Castañeda, José

    2017-07-13

    The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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

  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. 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.

  9. Tetravalent thulium

    Energy Technology Data Exchange (ETDEWEB)

    Kiselev, Yu.M.; Goryachenkov, S.A.; Martynenko, L.I.; Spitsyn, V.I. (Moskovskij Gosudarstvennyj Univ. (USSR))

    It is shown by the DTA method that the CsTmCl/sub 6/ and Cs/sub 3/TmF/sub 6/ interaction with XeF/sub 2/ reagents ratio (1:6) proceeds exothermally respectively below 100 deg C and at 380 deg C. The results of IR-spectroscopic investigation and magnetic moment measurement have shown that in the first case in fluorination products there are about 50% of Tm(4) in the TmF/sub 7//sup 3 -/ form, in the second 20-30%. Lesser percent of Tm(4) in Tm(3) fluorocomplex fluorination products as compared with the Tm(3) chlorocomplex fluorination products is caused by kinetic reasons. Radiographically the Cs/sub 3/TmF/sub 6/ and Cs/sub 3/TmF/sub 7/ cubic structures similarity is shown which can be a reason of additional stabilization of the system containing Tm(4) for account of formation of solid solutions.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Chemistry of tetravalent actinides phosphates. The thorium phosphate-diphosphate as immobilisation matrix of actinides

    International Nuclear Information System (INIS)

    Dacheux, N.

    2002-01-01

    The author presents in this document its scientific works from 1992 to 2001, in order to obtain the enabling to manage scientific and chemical researches at the university Paris Sud Orsay. The first part gives an abstract of the thesis on the characterizations, lixiviation and synthesis of uranium and thorium based phosphate matrix in the framework of the search for a ceramic material usable in the radioactive waste storage. The second part presents briefly the researches realized at the CEA, devoted to a reliable, independent and accurate measure of some isotopes activity. The last part presents the abstracts of researches activities from 1996 to 2001 on the tetravalent actinides phosphates chemistry, the sintering of PDT and solid solutions of PDTU and the kinetic and thermodynamical studies of the PDT dissolution. Many references and some publication in full text are provided. (A.L.B.)

  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. The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs

    International Nuclear Information System (INIS)

    Wittel, Uwe A.; Jain, Maneesh; Goel, Apollina; Chauhan, Subhash C.; Colcher, David; Batra, Surinder K.

    2005-01-01

    Engineered multivalent single-chain Fv (scFv) constructs have been demonstrated to exhibit rapid blood clearance and better tumor penetration. To understand the short plasma half-life of multivalent single-chain antibody fragments, the pharmacokinetic properties of covalent dimeric scFv [sc(Fv) 2 ], noncovalent tetrameric scFv {[sc(Fv) 2 ] 2 } and IgG of MAb CC49 were examined. The scFvs displayed an ability to form higher molecular aggregates in vivo. A specific proteolytic cleavage of the linker sequence of the covalent dimeric or a deterioration of the noncovalent association of the dimeric scFv into tetravalent scFv constructs was not observed. In conclusion, sc(Fv) 2 and [sc(Fv) 2 ] 2 are stable in vivo and have significant potential for diagnostic and therapeutic applications

  17. Use of Tetravalent Galabiose for Inhibition of Streptococcus Suis Serotype 2 Infection in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Karen A. Krogfelt

    2013-04-01

    Full Text Available Streptococcus suis is an important swine pathogen associated with a variety of infections such as meningitis, arthritis and septicemia. The bacterium is zoonotic and has been found to cause meningitis especially in humans occupationally exposed to infected pigs. Since adhesion is a prerequisite for colonization and subsequent infection, anti-adhesion treatment seems a natural alternative to traditional treatment with antibiotics. In order to optimize the inhibitory potency a multivalency approach was taken in the inhibitor design. A synthetic tetravalent galabiose compound was chosen which had previously shown promising anti-adhesion effects with S. suis in vitro. The aim of this study was to evaluate the in vivo effects of the compound using an infection peritonitis mouse model. As such S. suis serotype 2 infection and treatment were tested in vivo and the effects were compared to the effect of treatment with penicillin.

  18. 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 ...

  19. Dengue Virus and Autophagy

    Directory of Open Access Journals (Sweden)

    Nicholas S. Heaton

    2011-08-01

    Full Text Available Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV. Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes showed that DENV replicates on endoplasmic reticulum (ER cisternae invaginations and not on classical autophagosomes. Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. DENV-induced autophagosomes deplete cellular triglycerides that are stored in lipid droplets, leading to increased β-oxidation and energy production. This is the first example of a virus triggering autophagy to modulate cellular physiology. In this review, we summarize these data and discuss new questions and implications for autophagy during DENV replication.

  20. Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chia-Yen; Chen, Gregory J.; Tai, Pei-Han; Yang, Yu-Chen [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China); Hsu, Yu-Shen, E-mail: yshsu@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Chang, Mingi, E-mail: mingi.chang@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Hsu, Chuan-Lung, E-mail: fabio@dcb.org.tw [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China)

    2016-05-13

    Bispecific antibodies (bsAbs) are second generation antibodies for therapeutic application in immunotherapy. One of the major strategies of the bsAb platform is the recruitment of immune effector T cells by incorporating an anti-CD3 domain. A bispecific T-cell engager (BiTE), with one end having an affinity for CD3 and the other end with affinity for CD19, has been approved in the US and Europe for the treatment of acute lymphoblastic leukemia. However, due to their small size and lack of Fc region, these single-chain variable fragment (scFv) bsAbs have short half-lives in vivo. Additionally, poor solubility, structural instability, and low production yields have also become major challenges in the bulk production process. To overcome these challenges, we have engineered a tetravalent bsAb with bivalent binding specificity for the CD20 and CD3 antigen in an immunoglobulin G (IgG) format. The fusion of the anti-CD3 scFvs to the CD20 antibody via a linker-hinge domain (LHD) results in improved antibody stabilization and properties. Here we demonstrate this antibody's highly efficient cancer cell elimination in a dose-dependent manner in a CD20-expressing B lymphoblastoid cell line in vitro. Our data suggest the potential clinical application of this bsAb for the treatment of CD20-expressing B cell malignancies. - Highlights: • A bispecific antibody (bsAb) can increase immunotherapeutic efficacy. • A tetravalent bsAb with binding specificity for the CD20 and CD3 antigens is proposed. • A linker-hinge domain (LHD) within the bsAb results in improved antibody properties.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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)

  7. Spectrum Recombination.

    Science.gov (United States)

    Greenslade, Thomas B., Jr.

    1984-01-01

    Describes several methods of executing lecture demonstrations involving the recombination of the spectrum. Groups the techniques into two general classes: bringing selected portions of the spectrum together using lenses or mirrors and blurring the colors by rapid movement or foreshortening. (JM)

  8. that Bind Specifically to Recombinant Envelope Protein of Dengue

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research June 2015; 14 (6): 997-1003 ... Revised accepted: 30 April 2015. Abstract ... Results: The 45 KDa, 43 KDa and 30 KDa plasma membrane proteins were identified as viral envelope targets.

  9. 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.

  10. 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...

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Controlling dengue with vaccines in Thailand.

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    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.

  18. 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.

  19. 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

  20. 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.

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

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    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.

  2. 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.

  3. 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.

  4. The inverse-trans-influence in tetravalent lanthanide and actinide bis(carbene) complexes

    Science.gov (United States)

    Gregson, Matthew; Lu, Erli; Mills, David P.; Tuna, Floriana; McInnes, Eric J. L.; Hennig, Christoph; Scheinost, Andreas C.; McMaster, Jonathan; Lewis, William; Blake, Alexander J.; Kerridge, Andrew; Liddle, Stephen T.

    2017-02-01

    Across the periodic table the trans-influence operates, whereby tightly bonded ligands selectively lengthen mutually trans metal-ligand bonds. Conversely, in high oxidation state actinide complexes the inverse-trans-influence operates, where normally cis strongly donating ligands instead reside trans and actually reinforce each other. However, because the inverse-trans-influence is restricted to high-valent actinyls and a few uranium(V/VI) complexes, it has had limited scope in an area with few unifying rules. Here we report tetravalent cerium, uranium and thorium bis(carbene) complexes with trans C=M=C cores where experimental and theoretical data suggest the presence of an inverse-trans-influence. Studies of hypothetical praseodymium(IV) and terbium(IV) analogues suggest the inverse-trans-influence may extend to these ions but it also diminishes significantly as the 4f orbitals are populated. This work suggests that the inverse-trans-influence may occur beyond high oxidation state 5f metals and hence could encompass mid-range oxidation state actinides and lanthanides. Thus, the inverse-trans-influence might be a more general f-block principle.

  5. Static electric dipole polarizabilities of tri- and tetravalent U, Np, and Pu ions.

    Science.gov (United States)

    Parmar, Payal; Peterson, Kirk A; Clark, Aurora E

    2013-11-21

    High-quality static electric dipole polarizabilities have been determined for the ground states of the hard-sphere cations of U, Np, and Pu in the III and IV oxidation states. The polarizabilities have been calculated using the numerical finite field technique in a four-component relativistic framework. Methods including Fock-space coupled cluster (FSCC) and Kramers-restricted configuration interaction (KRCI) have been performed in order to account for electron correlation effects. Comparisons between polarizabilities calculated using Dirac-Hartree-Fock (DHF), FSCC, and KRCI methods have been made using both triple- and quadruple-ζ basis sets for U(4+). In addition to the ground state, this study also reports the polarizability data for the first two excited states of U(3+/4+), Np(3+/4+), and Pu(3+/4+) ions at different levels of theory. The values reported in this work are the most accurate to date calculations for the dipole polarizabilities of the hard-sphere tri- and tetravalent actinide ions and may serve as reference values, aiding in the calculation of various electronic and response properties (for example, intermolecular forces, optical properties, etc.) relevant to the nuclear fuel cycle and material science applications.

  6. 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...

  7. 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....

  8. 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.

  9. Hemophagocytic syndrome in classic dengue fever

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    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.

  10. 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...

  11. CLINICAL AND LABORATORY PROFILE OF DENGUE FEVER

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    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

  12. 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.

  13. 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.

  14. Dengue virus transovarial transmission by Aedes aegypti

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    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.

  15. 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.

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

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    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.

  17. 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

  18. 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

  19. Chloroquine use improves dengue-related symptoms

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    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.

  20. Evaluation of several novel diamide based ligands for selective extraction of tetravalent plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Sivaramakrishna, Mallampalli; Nayak, Shashikant K. [Heavy Water Board, V.S. Bhavan, Mumbai (India); Raut, Dhaval R.; Mohapatra, Prasanta K. [Bhabha Atomic Research Center, Mumbai (India). Radiochemistry Division; Nayak, Sandip K. [Bhabha Atomic Research Center, Mumbai (India). Bioorganic Division

    2017-06-01

    The present paper describes the selective extraction of tetravalent plutonium employing several diamide ligands containing aromatic spacer groups. The ligands containing two amide functional groups attached to a 2,4,6-tri-phenyl pyridine moiety with different substituents viz.; L{sub I} (iso-butyl), L{sub II}(n-butyl), L{sub III}(n-octyl), L{sub IV} (2-ethylhexyl) at the amidic nitrogen atom were evaluated for the extraction of Pu(IV) using their nitrobenzene solutions. The distribution ratio values of Pu(IV) with the diamide ligands followed the order: L{sub II}>L{sub I}>L{sub III}>L{sub IV} and were significantly higher than those of metal ions such as Cs(I), Sr(II), Am(III) and Eu(III). The distribution ratio values of U(VI) were about 2-3 orders magnitude lower than those of Pu(IV). The extraction and stripping kinetics were found to be moderately fast and it took less than 30 min (less than 5 min for L{sub I} and L{sub IV}) to obtain equilibrium D values. The extraction was found to be increasing with the aqueous phase nitric acid concentration conforming to a solvation mechanism of extraction. The extracted species contained two ligand molecules for L{sub I} and L{sub II} while monosolvates were observed for the other two extractants. The ligands showed good radiation stability up to an absorbed dose of 630 kGy.

  1. Immobilization of tetravalent actinides in three phosphate based ceramics: britholites, TPD and monazites/brabantites

    International Nuclear Information System (INIS)

    Terra, O.; Audubert, F.; Dacheux, N.; Guy, C.; Podor, R.

    2004-01-01

    Three phosphate based ceramics were studied for the immobilization of tri- and tetravalent actinides: britholites Ca 9 Nd 1-x An x IV (PO 4 ) 5-x (SiO 4 ) 1+x F 2 , monazites/brabantites Ln 1-2x III Ca x An x IV PO 4 and Thorium Phosphate Diphosphate (TPD) Th 4-x An x IV (PO 4 ) 4 P 2 O 7 . For each material, the incorporation of Th, U(IV), or Ce(IV) in the structure was examined. This work was the early beginning of the incorporation of 239 Pu and/or 238 Pu in order to evaluate the effects of α -decay on these three crystallographic structures. The syntheses were carried out using dry chemistry methods, involving mechanical grinding then heating treatment (1100 deg C ≤ θ ≤ 1400 deg C). For britholites, we showed that the incorporation of thorium was complete for weight loading lower than 20 wt.% through the (Nd 3+ , PO 4 3- ) ↔ (Th 4+ , SiO 4 4- ) coupled substitution, leading to the preparation of solid solutions. Due to redox problems, the incorporation of uranium was limited to 5 to 8 wt.% and always led to a two-phase mixture of U-britholite and CaU 2 O 5+y . For solid solutions based on TPD and for brabantites, the syntheses dealing with the incorporation of Th and/or U(IV) were improved by dry chemistry method using three mechanical grinding-calcination cycles. For both solids, homogeneous and single phase samples of the corresponding solid solutions were obtained. Finally, dense pellets of britholites, monazites/brabantites and TAn IV PD solid solutions were prepared in order to study their chemical durability during leaching tests. (authors)

  2. 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.

  3. Investigation into formation of nanoparticles of tetravalent neptunium in slightly alkaline aqueous solution

    International Nuclear Information System (INIS)

    Husar, Richard

    2015-01-01

    Considering the worldwide growing discharge of minor actinides and the current need for geological disposal facilities for radioactive waste, this work provides a contribution to the safety case concerning Np transport if it would be released from deep repository sites and moving from alkaline cement conditions (near-field) to more neutral environmental conditions (far-field). The reducing conditions in a nuclear waste repository render neptunium tetravalent, which is assumed to be immobile in aqueous environment due to the low solubility solution of Np(IV). For tetravalent actinide nuclides, the most significant transport should occur via colloidal particles. This work demonstrates the formation of intrinsic neptunium dioxide nanocrystals and amorphous Np(IV) silica colloids under environmentally relevant conditions. The dissociation of the initial soluble Np(IV) complex (i.e. [Np(IV)(CO 3 ) 5 ] 6- ) induces the intrinsic formation of nanocrystalline NpO 2 in the solution phase. The resulting irregularly shaped nanocrystals with an average size of 4 nm exhibit a face-centered cubic (fcc), fluorite-type structure (space group Fm anti 3m). The NCs tend to agglomerate under ambient conditions due to the weakly charged hydrodynamic surface at neutral pH (zetapotential ζ ∝0 mV). The formation of micron-sized agglomerates, composed of nanocrystals of 2-5 nm in size, and the subsequent precipitation cause immobilization of the major amount of Np(IV) in the Np carbonate system. Agglomeration of NpO 2 nanocrystals in dependence on time was indicated by PCS and UV-vis absorption spectroscopy with the changes of baseline characteristics and absorption maximum at 742 nm. Hitherto, unknown polynuclear species as intermediate species of NpO 2 nanocrystal formation were isolated from solution and observed by HR-TEM. These polynuclear Np species appear as dimers, trimers and hexanuclear compounds in analogy with those reported for other actinides. Intrinsic formation of NpO 2

  4. Dengue related maculopathy and foveolitis.

    Science.gov (United States)

    Juanarita, Jaafar; Azmi, Mohd Noor Raja; Azhany, Yaakub; Liza-Sharmini, Ahmad Tajudin

    2012-09-01

    A 24 year-old Malay lady presented with high grade fever, myalgia, generalized rashes, severe headache and was positive for dengue serology test. Her lowest platelet count was 45 × 10(9) cells/L. She complained of sudden onset of painlessness, profound loss of vision bilaterally 7 days after the onset of fever. On examination, her right eye best corrected vision was 6/30 and left eye was 6/120. Her anterior segment examination was unremarkable. Funduscopy revealed there were multiple retinal haemorrhages found at posterior pole of both fundi and elevation at fovea area with subretinal fluid. Systemic examination revealed normal findings except for residual petechial rashes. She was managed conservatively. Her vision improved tremendously after 2 months. The retinal hemorrhages and foveal elevation showed sign of resolving. Ocular manifestations following dengue fever is rare. However, bilateral visual loss can occur if both fovea are involved.

  5. Blood banking e Dengue fever

    OpenAIRE

    Ramos, Estácio F.

    2008-01-01

    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,...

  6. 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.

  7. 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).

  8. A model of dengue fever

    Directory of Open Access Journals (Sweden)

    Boutayeb A

    2003-02-01

    Full Text Available Abstract Background Dengue is a disease which is now endemic in more than 100 countries of Africa, America, Asia and the Western Pacific. It is transmitted to the man by mosquitoes (Aedes and exists in two forms: Dengue Fever and Dengue Haemorrhagic Fever. The disease can be contracted by one of the four different viruses. Moreover, immunity is acquired only to the serotype contracted and a contact with a second serotype becomes more dangerous. Methods The present paper deals with a succession of two epidemics caused by two different viruses. The dynamics of the disease is studied by a compartmental model involving ordinary differential equations for the human and the mosquito populations. Results Stability of the equilibrium points is given and a simulation is carried out with different values of the parameters. The epidemic dynamics is discussed and illustration is given by figures for different values of the parameters. Conclusion The proposed model allows for better understanding of the disease dynamics. Environment and vaccination strategies are discussed especially in the case of the succession of two epidemics with two different viruses.

  9. 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

  10. 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

  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. 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 ...

  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. [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.

  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. 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.

  17. 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.

  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. 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...

  20. 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

  1. 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.

  2. 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...

  3. 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.

  4. 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

  5. Solid-state syntheses and single-crystal characterizations of three tetravalent thorium and uranium silicates

    International Nuclear Information System (INIS)

    Jin, Geng Bang; Soderholm, L.

    2015-01-01

    Colorless crystals of ThSiO 4 (huttonite) (1) and (Ca 0.5 Na 0.5 ) 2 NaThSi 8 O 20 (2) have been synthesized by the solid-state reactions of ThO 2 , CaSiO 3 , and Na 2 WO 4 at 1073 K. Green crystals of (Ca 0.5 Na 0.5 ) 2 NaUSi 8 O 20 (3) have been synthesized by the solid-state reactions of UO 2 , CaSiO 3 , and Na 2 WO 4 at 1003 K. All three compounds have been characterized by single-crystal X-ray diffraction. Compound 1 adopts a monazite-type three-dimensional condensed structure, which is built from edge- and corner-shared ThO 9 polyhedra and SiO 4 tetrahedra. Compounds 2 and 3 are isostructural and they crystallize in a steacyite-type structure. The structure consists of discrete pseudocubic [Si 8 O 20 ] 8− polyanions, which are connected by An 4+ cations into a three-dimensional framework. Each An atom coordinates to eight monodentate [Si 8 O 20 ] 8− moieties in a square antiprismatic geometry. Na + and Ca 2+ ions reside in the void within the framework. Raman spectra of 1, 2, and 3 were collected on single crystal samples. 1 displays more complex vibrational bands than thorite. Raman spectra of 2 and 3 are analogous with most of vibrational bands located at almost the same regions. - Graphical abstract: A Raman spectrum and crystal structures of (Ca 0.5 Na 0.5 ) 2 NaAnSi 8 O 20 (An=Th, U), which contain pseudocubic [Si 8 O 20 ] 8− polyanions and eight-coordinate An 4+ cations. - Highlights: • Single crystal growth of three tetravalent actinide silicates from melts. • Single-crystal structures and Raman spectra of (Ca 0.5 Na 0.5 ) 2 NaAnSi 8 O 20 (An=Th, U). • First report of Raman spectrum of huttonite on single crystal samples

  6. Solubility product of tetravalent neptunium hydrous oxide and its ionic strength dependence

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, K.; Mori, T. [Japan Nuclear Cycle Development Institute (JNC), 4-33, Muramatsu, Tokai-mura, Naka-gun, Ibaraki-ken, 319-1194 (Japan); Kohara, Y. [Inspection and Development Company, 4-33, Muramatsu, Tokaimura, Naka-gun, Ibaraki-ken, 319-1112 (Japan)

    2005-07-01

    Full text of publication follows: Solubility products (K{sub sp}) are key parameters in the context of reliable assessment of actinides migration in the repository conditions of high level radioactive waste. Neptunium (Np(IV)) is one of the most important actinide elements in the assessment, because of its inventory and the long half-life. A few previous data for Np(IV) solubility are varied widely due to experimental difficulties related to the extremely low solubility. We carried out batch-type experiments under nitrogen atmosphere using a glovebox. Np(V) was reduced to Np(III) by bubbling 0.5 ppm H{sub 2} / N{sub 2} gas through the solution for 30 days in the presence of platinum black as catalyst. After reducing treatment, the Np(III) converted to Np(IV) by auto-oxidation within approximately three days. The solubilities of the Np(IV) were measured in the pHc ranging from 2 to 4, at room temperature (23 {+-} 2 deg. C), in ionic strength(I) = 0.1, 0.5, 1.0 and 2.0 M NaClO{sub 4}. The equilibrium condition was confirmed by over-saturation and under-saturation method. After the equilibrium, the pH{sub c} and the E{sub h} value of the suspension were measured. The suspension was then filtered using a filter with a NMWL of 3000 (less than 2 nm{phi}). The Np radio activity in the filtrate was determined by alpha spectrometry and absorption spectra of Np(IV). The solubility decreased with increasing pHc and the hydrolysis species are predominantly formed. From the obtained results, the solubility products (K{sub sp}) of Np hydroxide, for the reaction, NpO{sub 2} . xH{sub 2}O {r_reversible} Np{sup 4+} + 4OH{sup -} + (x-2)H{sub 2}O, at I = 0.1, 0.5, 1.0 and 2.0 were determined by using formation constants ({beta}{sub n}(I)), which were determined for the reaction, Np{sup 4+} + nOH{sup -} {r_reversible} Np(OH){sub n}{sup (4-n)+}. By using the specific interaction theory (SIT), the solubility product of tetravalent Np hydrous oxide is calculated to be log K{sub sp}{sup 0

  7. 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.

  8. A PATIENT DENGUE HEMORRHAGIC FEVER WITH SPASMS

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 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

  11. 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.

  12. 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)

  13. 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?

  14. 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...

  15. 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.

  16. Chemistry of tetravalent actinides phosphates. The thorium phosphate-diphosphate as immobilisation matrix of actinides; Chimie des phosphates d'actinides tetravalents. Le phosphate-diphosphate de thorium en tant que matrice d'imobilisation des actinides

    Energy Technology Data Exchange (ETDEWEB)

    Dacheux, N

    2002-07-01

    The author presents in this document its scientific works from 1992 to 2001, in order to obtain the enabling to manage scientific and chemical researches at the university Paris Sud Orsay. The first part gives an abstract of the thesis on the characterizations, lixiviation and synthesis of uranium and thorium based phosphate matrix in the framework of the search for a ceramic material usable in the radioactive waste storage. The second part presents briefly the researches realized at the CEA, devoted to a reliable, independent and accurate measure of some isotopes activity. The last part presents the abstracts of researches activities from 1996 to 2001 on the tetravalent actinides phosphates chemistry, the sintering of PDT and solid solutions of PDTU and the kinetic and thermodynamical studies of the PDT dissolution. Many references and some publication in full text are provided. (A.L.B.)

  17. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

  19. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  20. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  1. 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.

  2. 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

  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. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  5. Dengue Fever in the United States

    Centers for Disease Control (CDC) Podcasts

    Dr. Amesh Adalja, an associate at the Center for Biosecurity and clinical assistant professor at the University of Pittsburgh School, of Medicine, discusses dengue fever outbreaks in the United States.

  6. Electrochemical investigation of tetravalent uranium β-diketones for active materials of all-uranium redox flow battery

    International Nuclear Information System (INIS)

    Yamamura, Tomoo; Shiokawa, Yoshinobu; Ikeda, Yasuhisa

    2002-01-01

    For active materials of the all-uranium redox flow battery for the power storage, tetravalent uranium β-diketones were investigated. The electrode reactions of U(ba) 4 and U(btfa) 4 were examined in comparison with that of U(acac) 4 , where ba denotes benzoylacetone, btfa benzoyltrifluoroacetone and acac acetylacetone. The cyclic voltammograms of U(ba) 4 and U(btfa) 4 solutions indicate that there are two series of redox reactions corresponding to the complexes with different coordination numbers of four and three. The electrode kinetics of the U(IV)/U(III) redox reactions for btfa complexes is examined. The obtained result supports that the uranium β-diketone complexes examined in the present study will serve as excellent active materials for negative electrolyte in the redox flow battery. (author)

  7. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    Science.gov (United States)

    1980-01-01

    1973). Sabin (1948) showed that attenuated dpngiie, passed through mosquitoes, did not revert to pathogenicity frnr man. -7- Thus even if the vaccine ...AD-A138 518 PATHOGENESIS OF DENGUE VACCINE YIRUSES IN MOSQUITOES 1/ (U) YALE UNIV NEW HAVEN CONN SCHOOL OF MEDICINE B J BEATY ET AL. 9i JAN 80 DRND7...34 ’ UNCLASSIFIED 0{) AD 0Pathogenesis of dengue vaccine viruses in mosquitoes -First Annual Report Barry I. Beaty, Ph.D. Thomas H. G

  8. A Rapporteur's Summary : Research on Dengue Vaccine

    OpenAIRE

    Kitamura, Takashi

    1994-01-01

    Dengue virus is a member of flavivirus group. Diseases caused by flaviviruses have been a scourge of mankind for long history of human kind; with yellow fever at the top, followed by dengue fever, Japanese encephalitis (JE) and Russian spring-summer encephalitis (RSSE). Due to the dvevelopment of a safe and efficacious live-attenuated vaccine against yellow fever as a first laboratory-designed virus vaccine, this disease is no longer a threat in countries where adequate vaccination is practic...

  9. Acute atrial fibrillation during dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Henrique Horta Veloso

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  10. Acute atrial fibrillation during dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Veloso Henrique Horta

    2003-01-01

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  11. 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.

  12. Incorporation of tetravalent actinides in three phosphated matrices: britholite, monazite/brabandite and thorium phosphate diphosphate (β-TPD)

    International Nuclear Information System (INIS)

    Terra, O.

    2005-03-01

    Three phosphate based ceramics were studied for the immobilization of tri- and tetravalent actinides: britholite Ca 9 Nd 1-x An x IV (PO 4 ) 5-x (SiO 4 ) 1+x F 2 , monazite/brabantite solid solutions Ln 1-2x III Ca x An x IP O 4 and Thorium Phosphate Diphosphate (β-TPD) Th 4- xAn x IV (PO 4 ) 4 P 2 O 7 . For each material, the incorporation of thorium and uranium (IV) was studied as a surrogate of plutonium. This work was the early beginning of the incorporation of 239 Pu and/or 238 Pu in order to evaluate the effects of α-decay on the three crystallographic structures. The incorporation of tetravalent cations was carried out by dry chemistry methods, using mechanical grinding to improve the reactivity of the initial mixture then the homogeneity of final solid prepared after calcination at high temperature (1200-1400 deg C). For britholites, the thorium incorporation was complete for weight loading up to 20 wt.%, leading to the preparation of homogeneous and single phase solid solutions when using the coupled substitution (Nd 3+ , PO 4 3- ) ↔ (Th 4+ , SiO 4 4- ). Due to redox problems, the incorporation of uranium was limited to 5 to 8 wt.% and always led to a two-phase mixture of U-britholite and CaU 2 O 5+y . The preparation of homogeneous solid solutions of β-TUPD and of brabantites containing thorium and uranium samples was successfully obtained using three steps of mechanical grinding/calcination. For each matrix, dense pellets were prepared prior to the study of their chemical behaviour during leaching tests. The chemical durability of brabantites and β-TUPD were found to be close to that reported in literature. The formation of neo-formed phases was also evidenced onto the surface of Th-britholite samples. (author)

  13. 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.

  14. The effects of urban growth on dengue

    Directory of Open Access Journals (Sweden)

    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

  15. 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.

  16. 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.

  17. Facing dengue fever - our first experience

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  3. Non-HLA gene polymorphisms and their implications on dengue ...

    African Journals Online (AJOL)

    Harapan Harapan

    2012-09-23

    controlled immuno- logical responses. Genetic variants involved in viral entry, replication and innate immunity pathways play an important role in the causal pathway of dengue hemorrhagic fever/dengue shock syndrome.

  4. 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.

  5. 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.

  6. Epidemiological trends of dengue in mainland China, 2005–2015

    Directory of Open Access Journals (Sweden)

    Jimin Sun

    2017-04-01

    Conclusions: Although the number of dengue cases has increased and the affected areas have expanded in recent years, dengue is still an imported disease and does not present an endemic trend in mainland China.

  7. Rare case of acute dengue encephalitis with correlated MRI findings

    International Nuclear Information System (INIS)

    Mathew, Rishi Philip; Basti, Ram Shenoy; Hegde, Pavan; Devdas, Jaidev M.; Khan, Habeeb Ullah; Bukelo, Mario Joseph

    2014-01-01

    Dengue encephalitis is extremely rare, with most patients showing no significant abnormality on neuroimaging (CT/MRI). We report one of the very few documented cases of dengue encephalitis, with abnormal signal intensities on all major sequences on brain MRI.

  8. Stochastic dynamics of dengue epidemics.

    Science.gov (United States)

    de Souza, David R; Tomé, Tânia; Pinho, Suani T R; Barreto, Florisneide R; de Oliveira, Mário J

    2013-01-01

    We use a stochastic Markovian dynamics approach to describe the spreading of vector-transmitted diseases, such as dengue, and the threshold of the disease. The coexistence space is composed of two structures representing the human and mosquito populations. The human population follows a susceptible-infected-recovered (SIR) type dynamics and the mosquito population follows a susceptible-infected-susceptible (SIS) type dynamics. The human infection is caused by infected mosquitoes and vice versa, so that the SIS and SIR dynamics are interconnected. We develop a truncation scheme to solve the evolution equations from which we get the threshold of the disease and the reproductive ratio. The threshold of the disease is also obtained by performing numerical simulations. We found that for certain values of the infection rates the spreading of the disease is impossible, for any death rate of infected mosquitoes.

  9. 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.

  10. A case of acute liver failure in dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

  12. 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.

  13. 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 ...

  14. 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.

  15. Photoionization and Recombination

    Science.gov (United States)

    Nahar, Sultana N.

    2000-01-01

    Theoretically self-consistent calculations for photoionization and (e + ion) recombination are described. The same eigenfunction expansion for the ion is employed in coupled channel calculations for both processes, thus ensuring consistency between cross sections and rates. The theoretical treatment of (e + ion) recombination subsumes both the non-resonant recombination ("radiative recombination"), and the resonant recombination ("di-electronic recombination") processes in a unified scheme. In addition to the total, unified recombination rates, level-specific recombination rates and photoionization cross sections are obtained for a large number of atomic levels. Both relativistic Breit-Pauli, and non-relativistic LS coupling, calculations are carried out in the close coupling approximation using the R-matrix method. Although the calculations are computationally intensive, they yield nearly all photoionization and recombination parameters needed for astrophysical photoionization models with higher precision than hitherto possible, estimated at about 10-20% from comparison with experimentally available data (including experimentally derived DR rates). Results are electronically available for over 40 atoms and ions. Photoionization and recombination of He-, and Li-like C and Fe are described for X-ray modeling. The unified method yields total and complete (e+ion) recombination rate coefficients, that can not otherwise be obtained theoretically or experimentally.

  16. Chemistry of tetravalent plutonium and zirconium. Hydrolysis, solubility, colloid formation and redox reactions

    International Nuclear Information System (INIS)

    Cho, Hye-Ryun

    2006-01-01

    The chemical properties of plutonium and zirconium are important in order to assess nuclear waste disposals with respect to isolation and immobilization of radionuclides. In this study, the hydrolysis, solubility and colloid formation of tetravalent plutonium and zirconium are investigated in 0.5 M HCl/NaCl solution using several complementary methods and the redox behavior of plutonium is investigated in acidic conditions as well. The solubilities of Pu(IV) and Zr(IV) are determined from the onset of colloid formation as a function of pH and metal concentration using LIBD (laser-induced breakdown detection). The investigation of the solubility of Zr(IV) is carried out at different concentrations (log [Zr] = -3 ∝ -7.6) and in a wide pH range (pH = 3 - 9) yielding log K sp (Zr(IV)) = -53.1 ± 0.5 based on the assumption that only mononuclear hydrolysis species exist in solution. Comparing the present results with literature data, the solubilities of Zr can be split in two groups, a crystalline phase with lower solubility and an amorphous phase (Zr(OH) 4 (am)) with higher solubility. The data obtained in the present work set an upper limit for the solubility of freshly formed Zr(OH) 4 (am). To understand this difference of solubilities, the geometrical structure of the dominant solution species is investigated as a function of pH using XAFS (X-ray absorption fine structure). The samples at pH >2, still below the solubility limit determined by LIBD, contain the polynuclear Zr(IV) species probably due to the high concentration ([Zr] = 1 mM) and their structure do not resemble any reported simple ZrO 2 structure. The Zr(IV) colloid species in oversaturated solution under this experimental condition resembles amorphous Zr(IV) hydroxide rather than crystalline ZrO 2 . The solubility of Pu(IV) is investigated in acidic solution below pH 2. Considering only mononuclear hydrolysis species, log K sp (Pu(IV)) = -58.3 ± 0.4 is obtained. Since Pu(IV) is not redox stable even

  17. 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

  18. Current perspectives on the spread of dengue in India

    Directory of Open Access Journals (Sweden)

    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

  19. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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 ...

  2. 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.

  3. 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.

  4. Spontaneous muscle hematomas in a patient with Dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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

  7. 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.

  8. Validation of dengue infection severity score

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    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

  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. 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.

  11. 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.

  12. 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)

  13. 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

  14. 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.

  15. 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 .

  16. Dengue: muscle biopsy findings in 15 patients

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    S.M.F. Malheiros

    1993-06-01

    Full Text Available Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry in 15 patients (4 males, median age 23 years (range 14-47 with classic dengue fever, serologically confirmed, during the bra-zilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

  17. 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.

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  1. 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.

  2. 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.

  3. Clinical, serological and echocardiographic examination of healthy field dogs before and after vaccination with a commercial tetravalent leptospirosis vaccine.

    Science.gov (United States)

    Spiri, Andrea M; Rodriguez-Campos, Sabrina; Matos, José M; Glaus, Tony M; Riond, Barbara; Reusch, Claudia E; Hofmann-Lehmann, Regina; Willi, Barbara

    2017-05-25

    Leptospirosis is a re-emerging bacterial zoonosis caused by spirochetes of the genus Leptospira. Severe disease has been reported in dogs in Europe despite vaccination with bivalent Leptospira vaccines. Recently, a tetravalent canine Leptospira vaccine (Nobivac® L4) was licenced in Europe. The goal of this study was to investigate clinical signs, microscopic agglutination test (MAT) titres, haematology, blood biochemistry, cardiac (c) Troponin I levels and echocardiography before and after vaccination with this tetravalent vaccine. Forty-eight healthy dogs were prospectively enrolled and vaccinated twice, 3-4 weeks apart (T0 and T1). Before vaccination (T0) and 16-31 days after the second vaccination (T2), MAT (n = 48), haematology (n = 48), blood biochemistry (n = 36) and cTroponin I measurements (n = 29) were performed, and MAT was repeated 347-413 days after the second vaccination (T3, n = 44). Echocardiography was performed before the first and second vaccination (T0 and T1, n = 24). Mild and transient clinical signs within 5 days following the first and second vaccination occurred in 23% and 10% of the dogs, respectively. Before the first vaccination (T0), all dogs showed negative MAT titres for the tested serovars except for Canicola (50% with titres 100-400). At T2, positive MAT titres to the serovars Canicola (100%), Australis (89%), Grippotyphosa (86%), Bratislava (60%), Autumnalis (58%), Copenhageni (42%), Pomona (12%), Pyrogenes (8%) and Icterohaemorrhagiae (2%) were found. Median to high titres (≥ 400) were most common to the serovar Canicola (92%) and less common to the serovars Australis (41%), Grippotyphosa (21%), Bratislava (12%), Autumnalis (4%), Pyrogenes (4%) and Pomona (2%). At T3, positive MAT titres (titre range: 100-400) were found in 2-18% of the dogs to serovars of the vaccine serogroups and in 2-18% of the dogs to the non-vaccine serovars Pomona, Autumnalis, Pyrogenes and Ballum. Haematology, blood biochemistry, c

  4. Epitope focused immunogens and recombinant antibody ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Combining cutting-edge immunology and protein engineering methods, this ... for dengue patients and improved vaccines for the control of dengue fever and East ... the Canadian Institutes for Health Research, the Israel Science Foundation, ...

  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. Recombination of cluster ions

    Science.gov (United States)

    Johnsen, Rainer

    1993-01-01

    Some of our recent work on molecular band emissions from recombination of molecular dimer ions (N4(+) and CO(+) CO) is discussed. Much of the experimental work was done by Y. S. Cao; the results on N4(+) recombination have been published. A brief progress report is given on our ongoing measurements of neutral products of recombination using the flowing-afterglow Langmuir-probe technique in conjunction with laser-induced fluorescence.

  7. [Imported dengue: an emerging arbovirosis in Spain].

    Science.gov (United States)

    Ramos Geldres, T T; García López-Hortelano, M; Baquero-Artigao, F; Montero Vega, D; López Quintana, B; Mellado Peña, M J

    2015-01-01

    Dengue is caused by one of 4 serotypes of dengue virus. Only imported cases have been reported in Spain. The main clinical findings are fever and exanthema, although there may be severe forms, particularly in secondary infections. Five children with a primary, non severe dengue infection are presented. The diagnosis was based on clinical suspicion and epidemiological history, and confirmed by immunochromatography and ELISA tests. The outcome was favourable in all cases. It is important to consider this diagnosis in international travellers that present with fever within the 14 days of returning from an endemic area, in order to get an early diagnosis, adequate treatment and a good prognosis. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  8. Dengue fever in pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Phupong Vorapong

    2001-12-01

    Full Text Available Abstract Background Dengue, a mosquito-borne flavivirus infection, is endemic in Southeast Asia. Currently, the incidence has been increasing among adults. Case presentation A 26-year-old Thai woman, G1P0 31 weeks pregnancy, presented with epigastric pain for 1 day. She also had a high-grade fever for 4 days. The physical examination, complete blood counts as well as serology confirmed dengue fever. The patient was under conservative treatment despite severe thrombocytopenia. She was well at the 3rd day of discharge and 1-week follow-up. The pregnancy continued until term without any complication and she delivered vaginally a healthy female baby. Conclusions More cases of dengue infection in pregnancy can be found due to the increasing incidence during adulthood. It should be suspected when a pregnant woman presents with symptoms and signs like in a non-pregnant. Conservative treatment should be conducted unless there are any complications.

  9. Anti dengue education: a experience report

    Directory of Open Access Journals (Sweden)

    Marise Maleck

    2017-11-01

    Full Text Available Aedes aegypti (L., 1762 is the main vector recognized as a dengue virus transmitter. This vector, once adapted to human habits, finds it easy to reproduce in homes that have open water containers, easily found in city streets and garbage dumps. Educational institutions play a fundamental role in the formation of young people as disseminator citizens in favor of health improvement practices. In order to promote education for the control of the dengue virus mosquito vector, this work was developed through recreational and educational activities in Central-South Rio de Janeiro state public and private schools, cities, cultural centers and public spaces. The results showed positive responses above 80% of the Aedes-dengue-control issue. The project had 2500 participants. The Antidengue Education Project demonstrated that education is an effective tool regarding education, health and the environment.

  10. [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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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...

  20. X-ray absorption spectroscopic study of trivalent and tetravalent actinides in solution at varying pH values

    Energy Technology Data Exchange (ETDEWEB)

    Brendebach, B.; Banik, N.L.; Marquardt, C.M.; Rothe, J.; Denecke, M.A.; Geckeis, H. [Forschungszentrum Karlsruhe (Germany). Inst. fuer Nukleare Entsorgung

    2009-07-01

    We perform X-ray absorption spectroscopy (XAS) investigations to monitor the stabilization of redox sensitive trivalent and tetravalent actinide ions in solution at acidic conditions in a pH range from 0 to 3 after treatment with holding reductants, hydroxylamine hydrochloride (NH{sub 2}OHHCl) and Rongalite (sodium hydroxymethanesulfinate, CH{sub 3}NaO{sub 3}S). X-ray absorption near edge structure (XANES) measurements clearly demonstrate the stability of the actinide species for several hours under the given experimental conditions. Hence, structural parameters can be accurately derived by extended X-ray absorption fine structure (EXAFS) investigations. The coordination structure of oxygen atoms belonging to water ligands surrounding the actinide ions does not change with increasing pH value (approximately 11 O atoms at 2.42 A in the case of U(IV) at pH 1, 9 0 atoms at 2.52 A for Np(III) at pH 1.5, and 10 O atoms at 2.49 A for Pu(III) up to pH 3), indicating that hydrolysis reactions are suppressed under the given chemical conditions. (orig.)

  1. Synthetic Smectite Colloids: Characterization of Nanoparticles after Co-Precipitation in the Presence of Lanthanides and Tetravalent Elements (Zr, Th

    Directory of Open Access Journals (Sweden)

    Muriel Bouby

    2015-09-01

    Full Text Available The magnesian smectite hectorite is a corrosion product frequently detected in nuclear waste glass alteration experiments. The structural incorporation of a single trivalent lanthanide was previously demonstrated. Hectorite was presently synthesized, for the first time, in the presence of several lanthanides (La, Eu, Yb following a multi-step synthesis protocol. The smallest-sized particles (nanoparticles, NPs were isolated by centrifugation and analyzed by asymmetrical flow field-flow fractionation (AsFlFFF coupled to ICP-MS, in order to obtain information on the elemental composition and distribution as a function of the size. Nanoparticles can be separated from the bulk smectite phase. The particles are able to accommodate even the larger-sized lanthanides such as La, however, with lower efficiency. We, therefore, assume that the incorporation proceeds by substitution for octahedral Mg accompanied by a concomitant lattice strain that increases with the size of the lanthanides. The presence of a mixture does not seem to affect the incorporation extent of any specific element. Furthermore, syntheses were performed where in addition the tetravalent zirconium or thorium elements were admixed, as this oxidation state may prevail for many actinide ions in a nuclear waste repository. The results show that they can be incorporated as well.

  2. Study of lifetimes of fluorescence levels of tetravalent uranium in the incommensurate phase of thorium tetrabromide and tetrachloride

    International Nuclear Information System (INIS)

    Milicic, A.

    1989-01-01

    The lifetimes of radiative levels of tetravalent uranium in the incommensurate phase of thorium tetrahalides have been measured as a function of different parameters: site symmetry, temperature and concentration. The incommensurate phase of thorium tetrabromide and tetrachloride is characterized by a continuous distribution of site symmetries induced by a continuous and weak displacement of the halides around the thorium (uranium) ions. At low temperature, 4.2 K, the lifetime variation as a function of excited classes of symmetry is governed by the radiative process probability as well as the energy transfer between uranium ions in different sites. At higher temperature, a model based on a Boltzmann equilibrium between closed energy levels is able to reproduce the experimental lifetime variation as a function of the temperature, for a given class of symmetry. For the variation of lifetime as a function of uranium ion concentrations, at high dilution and in the case of U 4+ : ThBr 4 , there is a competition between the energy transfer and thermal population of excited states [fr

  3. Clinical Study of New Tetravalent (Type A, B, E, and F) Botulinum Toxoid Vaccine Derived from M Toxin in Japan.

    Science.gov (United States)

    Torii, Yasushi; Sugimoto, Nakaba; Kohda, Tomoko; Kozaki, Shunji; Morokuma, Kazunori; Horikawa, Yoshikane; Ginnaga, Akihiro; Yamamoto, Akihiko; Takahashi, Motohide

    2017-07-24

    Botulinum toxin is the most poisonous substance known, and is believed to be a highly lethal as a biological weapon; researchers of the toxin are exposed to this hazard. Botulinum toxoid vaccines have been produced and used in Japan. However, since clinical studies involving these vaccines were conducted before establishment of the Ethical Guidelines for Clinical Research in Japan, their immunogenicity and safety were not systematically assessed. In this study, we produced a new tetravalent (type A, B, E, and F) botulinum toxoid vaccine, the first ever to be derived from M toxin, and conducted quality control tests with reference to the Minimum Requirements in Japan for adsorbed tetanus toxoid vaccine. Subsequently, a clinical study using the new vaccine in 48 healthy adult volunteers was conducted according to the guidelines in Japan. No clinically serious adverse event was noted. Neutralizing antibody titers for each type of toxin in the participants' sera, 1 month after the 4th injection were more than 0.25 IU/mL, indicating sufficient protection. This study demonstrated that the vaccine has marked immunogenicity and is safe for use in humans.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. The prevention and control of dengue after Typhoon Haiyan

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. 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.

  11. 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.

  12. 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...

  13. Dengue Fever in the United States

    Centers for Disease Control (CDC) Podcasts

    2012-04-09

    Dr. Amesh Adalja, an associate at the Center for Biosecurity and clinical assistant professor at the University of Pittsburgh School, of Medicine, discusses dengue fever outbreaks in the United States.  Created: 4/9/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/16/2012.

  14. Multiobjective Genetic Algorithm applied to dengue control.

    Science.gov (United States)

    Florentino, Helenice O; Cantane, Daniela R; Santos, Fernando L P; Bannwart, Bettina F

    2014-12-01

    Dengue fever is an infectious disease caused by a virus of the Flaviridae family and transmitted to the person by a mosquito of the genus Aedes aegypti. This disease has been a global public health problem because a single mosquito can infect up to 300 people and between 50 and 100 million people are infected annually on all continents. Thus, dengue fever is currently a subject of research, whether in the search for vaccines and treatments for the disease or efficient and economical forms of mosquito control. The current study aims to study techniques of multiobjective optimization to assist in solving problems involving the control of the mosquito that transmits dengue fever. The population dynamics of the mosquito is studied in order to understand the epidemic phenomenon and suggest strategies of multiobjective programming for mosquito control. A Multiobjective Genetic Algorithm (MGA_DENGUE) is proposed to solve the optimization model treated here and we discuss the computational results obtained from the application of this technique. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Dengue vaccine: come let's fight the menace.

    Science.gov (United States)

    Chawla, Sumit; Sahoo, Soumya Swaroop; Singh, Inderjeet; Verma, Madhur; Gupta, Vikas; Kumari, Sneh

    2015-01-01

    Although dengue has a global distribution, the World Health Organization (WHO) South-East Asia region together with Western Pacific region bears nearly 75% of the current global disease burden. Globally, the societal burden has been estimated to be approximately 528 to 1300 disability-adjusted life years (DALY) per million to populations in endemic regions Dengue is believed to infect 50 to 100 million people worldwide a year with half a million life-threatening infections requiring hospitalization, resulting in approximately 12,500 to 25,000 deaths. Despite being known for decades and nearly half the world's population is at risk for infection with as many as 100 million cases occurring annually, the pitiable state is that we still have no antiviral drugs to treat it and no vaccines to prevent it. In recent years, however, the development of dengue vaccines has accelerated dramatically in tandem with the burgeoning dengue problem with a rejuvenated vigour. However, recent progress in molecular-based vaccine strategies, as well as a renewed commitment by the World Health Organization (WHO) to co-ordinate global efforts on vaccine development, finally provides hope that control of this serious disease may be at hand. Today, several vaccines are in various stages of advanced development, with clinical trials currently underway on 5 candidate vaccines. Trials in the most advanced stages are showing encouraging preliminary data, and the leading candidate could be licensed as early as 2015.

  16. Dengue fever | Tavodova | South Sudan Medical Journal

    African Journals Online (AJOL)

    South Sudan Medical Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 5, No 1 (2012) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Dengue fever. Milada Tavodova. Abstract. No Abstract ...

  17. 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.

  18. Dengue Virus Genome Uncoating Requires Ubiquitination

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    Laura A. Byk

    2016-06-01

    Full Text Available 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.

  19. 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.

  20. Manifestações mucocutâneas da dengue Mucocutaneous manifestations of dengue

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    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

  1. 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

  2. Acute neuromuscular weakness associated with dengue infection

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    Harmanjit Singh Hira

    2012-01-01

    Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

  3. 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.

  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. 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.

  6. 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.

  7. 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.

  8. 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.

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

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    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

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

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    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

  11. 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

  12. 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

  13. 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...

  14. Imported dengue virus serotype 1 from Madeira to Finland 2012.

    Science.gov (United States)

    Huhtamo, E; Korhonen, Em; Vapalahti, O

    2013-02-21

    Imported dengue cases originating from the Madeiran outbreak are increasingly reported. In 2012 five Finnish travellers returning from Madeira were diagnosed with dengue fever. Viral sequence data was obtained from two patients. The partial C-preM sequences (399 and 396 bp respectively) were found similar to that of an autochthonous case from Madeira. The partial E-gene sequence (933 bp) which was identical among the two patients grouped phylogenetically with South American strains of dengue virus serotype 1.

  15. 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.

  16. Dengue hemorrhagic fever and acute hepatitis: a case report

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    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.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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

  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. Activated recombinant adenovirus proteinases

    Science.gov (United States)

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  4. Hadron correlations from recombination

    Energy Technology Data Exchange (ETDEWEB)

    Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

    2005-01-01

    Quark recombination is a successful model to describe the hadronization of a deconfined quark gluon plasma. Jet-like dihadron correlations measured at RHIC provide a challenge for this picture. We discuss how correlations between hadrons can arise from correlations between partons before hadronization. An enhancement of correlations through the recombination process, similar to the enhancement of elliptic flow is found. Hot spots from completely or partially quenched jets are a likely source of such parton correlations.

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

    Directory of Open Access Journals (Sweden)

    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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Synergistic extraction of tetravalent actinides by mixtures of a β-diketone and a neutral donor : a review [Paper No. : IIIA-2

    International Nuclear Information System (INIS)

    Patil, S.K.; Ramakrishna, V.V.

    1979-01-01

    Synergistic extraction of metal ions by mixtures of a β-diketone and a neutral donor has been studied extensively. Due to large synergistic enhancement of extraction both the formulas of the extractable species and the adduct formation constants with various neutral donors have been ascertained. Relatively few such studies have been devoted to the extraction of tetravalent actinides and these are reviewed critically in the present paper. In addition the work on synergistic extraction of tetravelent actinides by HTTA in admixture with several neutral donors carried out at Radiochemistry Division, BARC, is included. Attempts are made to explain the observed trends in the adduct formation constants. (author)

  9. Oxide perovskites with tetravalent dysprosium and compounds of the type Ba/sub 3/RE/sub 4/O/sub 9/ (RE = Rare Earth Element)

    Energy Technology Data Exchange (ETDEWEB)

    Brauer, G; Kristen, H [Freiburg Univ. (Germany, F.R.)

    1980-03-01

    In analogy to our investigations concerning tetravalent Nd in oxide perovskites, we also tried to stabilize dysprosium(IV) by incorporation in host-lattices with the perovskite structure. As host-lattices we used BaCeO/sub 3/, BaTbO/sub 3/, and SrTbO/sub 3/. Only in Ba(Ce, Dy)O/sub 3/ we could trace Dy(IV) with certainty. Among the prepared mixed oxides, also the phase Ba/sub 3/Dy/sub 4/O/sub 9/ occured. The lattice parameters of several phases of this latter type were redetermined.

  10. 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

  11. 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.

  12. 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.

  13. Sensorineural hearing loss in hemorrhagic dengue?

    Directory of Open Access Journals (Sweden)

    Bruna Natália Freire Ribeiro

    2015-01-01

    Discussion and conclusion: This is the first case report that brings together DHF and sudden hearing loss. In the development of this case no other cause to sudden hearing loss was found and the correlation between dengue and hearing loss was questioned. In the literature review was found that some viruses, as mumps virus, varicella-zoster virus and HSV-1 and HSV-2 are related to sudden hearing loss, all of them fit in the viral theory. Besides the viral theory of sudden hearing loss, there is the vascular theory that is the occlusion of the end artery that supplies the cochlea. DHF has a vascular commitment, and the hypothesis of a vascular cause could be elicited in this case. Many studies in this area are needed and this article has the objective of elicit the discussion about the subject. Could dengue be associated with sensorineural hearing loss?

  14. Desarrollo de agentes inmunizantes contra el dengue

    Directory of Open Access Journals (Sweden)

    Francisco J. López Antuñano

    2000-05-01

    Full Text Available El complejo de los cuatro flavivirus del dengue es transmitido principalmente por el mosquito Aedes aegypti. Se han atribuido epidemias a la actividad de A. albopictus, A. polynesiensis y a varias especies del complejo A. scutellaris. Los factores de riesgo que determinan la probabilidad de enfermar o morir por dengue están relacionados tanto con el huésped (características genéticas, estado inmunitario, forma de vida y condiciones de salud, saneamiento básico de la vivienda y abastecimiento de agua potable como con el virus (variabilidad genética de cepas entre y dentro de los serotipos, diferente capacidad patógena y distribución geográfica. A pesar de la falta de conocimiento sobre la inmunobiopatología del dengue, se han hecho importantes avances para conseguir una respuesta inmunitaria protectora con virus atenuados y con antígenos obtenidos por medio de tecnologías recombinantes. Desde los años 40, se ha intentado desarrollar vacunas contra el dengue. La inmunidad que se adquiere por infección natural es específica para cada serotipo y se han documentado infecciones por tres serotipos diferentes en la misma persona, por lo que probablemente sea necesaria una vacuna tetravalente. En voluntarios se han probado vacunas contra los cuatro serotipos que han sido inmunógenas y seguras. Aunque las vacunas con virus atenuados son prometedoras, son necesarios nuevos estudios sobre su eficacia y seguridad. Actualmente están en curso estudios para producir vacunas contra el virus del dengue mediante tecnologías de ADN recombinante y otras técnicas de biología molecular, utilizando como antígenos proteínas estructurales (principalmente la glicoproteína E y no estructurales. Con el mismo propósito se han usado varios vectores de expresión, como Escherichia coli, baculovirus, virus de la vacuna y virus de la fiebre amarilla. Lamentablemente, no se han obtenido resultados satisfactorios en el hombre. La necesidad de desarrollar

  15. The Medicinal Chemistry of Dengue Virus.

    Science.gov (United States)

    Behnam, Mira A M; Nitsche, Christoph; Boldescu, Veaceslav; Klein, Christian D

    2016-06-23

    The dengue virus and related flaviviruses are an increasing global health threat. In this perspective, we comment on and review medicinal chemistry efforts aimed at the prevention or treatment of dengue infections. We include target-based approaches aimed at viral or host factors and results from phenotypic screenings in cellular assay systems for viral replication. This perspective is limited to the discussion of results that provide explicit chemistry or structure-activity relationship (SAR), or appear to be of particular interest to the medicinal chemist for other reasons. The discovery and development efforts discussed here may at least partially be extrapolated toward other emerging flaviviral infections, such as West Nile virus. Therefore, this perspective, although not aimed at flaviviruses in general, should also be able to provide an overview of the medicinal chemistry of these closely related infectious agents.

  16. Dengue Virus Glycosylation: What Do We Know?

    Directory of Open Access Journals (Sweden)

    Sally S. L. Yap

    2017-07-01

    Full Text Available In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E and non-structural protein 1 (NS1 are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.

  17. 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.

  18. Dengue risk factors and community participation in Binh Thuan Province, Vietnam, a household survey

    NARCIS (Netherlands)

    Phuong, Hoang Lan; de Vries, Peter J.; Boonshuyar, Chaweewon; Binh, Tran Q.; Nam, Nguyen V.; Kager, Piet A.

    2008-01-01

    To look for risk factors for dengue and community participation in dengue control in Binh Thuan Province, Vietnam, three communes with a low incidence of dengue and three with a high incidence, in Binh Thuan Province, were compared. Knowledge, perception and preventive practice of dengue were

  19. Pharmacological intervention for dengue virus infection.

    Science.gov (United States)

    Lai, Jenn-Haung; Lin, Yi-Ling; Hsieh, Shie-Liang

    2017-04-01

    Dengue virus (DENV) infection has a considerable health impact in tropical and subtropical countries worldwide. Escalation of infection rates greatly increases morbidity and mortality, most commonly from deaths due to dengue hemorrhagic fever and dengue shock syndrome. Although the development of an effective, long-lasting vaccine has been a major aim for control and prevention of DENV infection, the currently licensed vaccine has limitations and is less than satisfactory. Thus, there remains an important need to identify effective and tolerable medications for treatment of DENV-infected patients both in the early phase, to prevent progression to fatal outcomes, and to minimize deaths after patients develop severe complications. This review will address several specific points, including (1) approaches to identify anti-DENV medications, (2) recent advances in the development of potential compounds targeting DENV infection, (3) experience with clinical trials of regimens for DENV infection, (4) some available medications of potential for clinical trials against DENV infection, (5) reasons for unsuccessful outcomes and challenges of anti-DENV treatments, and (6) directions for developing or selecting better anti-DENV strategies. This review provides useful guidance for clinicians selecting drugs for DENV-infected patients with severe manifestations or potential fatal disease progression, and for basic researchers seeking to develop effective anti-DENV regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Regulation of Meiotic Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gregory p. Copenhaver

    2011-11-09

    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  1. 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

  2. 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.

  3. 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.

  4. New Data on Joint Extraction of Nitric Acid, Uranium(VI) and Tetravalent Elements by Diluted TBP and New Approach to Modeling of their Distribution

    International Nuclear Information System (INIS)

    Zilberman, B.Ya.; Fedorov, Yu.S.; Puzikov, E.A.; Blazheva, I.V.

    2008-01-01

    HNO 3 and U(IV) extraction by diluted TBP (tributyl phosphate) appeared significantly higher than believed earlier, requiring correction of mathematical model for extraction of all the species. The proposed model of HNO 3 extraction includes its dissolving in the extracted water, as well as its abduction to UO 2 (NO 3 ) 2 (TBP) 2 . Extraction of U(VI) and tetravalent elements is considered as reaction of their hydrated or partially hydrolyzed forms, the latter could be extracted themselves or as neutral forms with water liberation. The equation of element chemical reaction for modeling is determined by the slope of the linear part of the S-shaped curve representing D/S 2 function as a plot of HNO 3 concentration, where D is a distribution coefficient of the micro-component and S is a TBP concentration free of HNO 3 . The description of tetravalent element extraction in U(VI) presence needs the assumption of cation-cation interaction of element hydrolyzed forms with U(VI) in aqueous phase. Zr distribution is affected by micellar effects. (authors)

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Dengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells

    Science.gov (United States)

    Colpitts, Tonya M.; Barthel, Sebastian; Wang, Penghua; Fikrig, Erol

    2011-01-01

    Dengue virus (DENV) is a member of the Flaviviridae and a globally (re)emerging pathogen that causes serious human disease. There is no specific antiviral or vaccine for dengue virus infection. Flavivirus capsid (C) is a structural protein responsible for gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. Flaviviral replication is known to occur in the cytoplasm yet a large portion of capsid protein localizes to the nucleus during infection. The reasons for the nuclear presences of capsid are not completely understood. Here, we expressed mature DENV C in a tandem affinity purification assay to identify potential binding partners in human liver cells. DENV C targeted the four core histones, H2A, H2B, H3 and H4. DENV C bound recombinant histones in solution and colocalized with histones in the nucleus and cytoplasm of liver cells during DENV infection. We show that DENV C acts as a histone mimic, forming heterodimers with core histones, binding DNA and disrupting nucleosome formation. We also demonstrate that DENV infection increases the amounts of core histones in livers cells, which may be a cellular response to C binding away the histone proteins. Infection with DENV additionally alters levels of H2A phosphorylation in a time-dependent manner. The interactions of C and histones add an interesting new role for the presence of C in the nucleus during DENV infection. PMID:21909430

  9. Knowledge of dengue among students in Universiti Sultan Zainal ...

    African Journals Online (AJOL)

    Reducing the vector population not only organization responsible, individual itself plays as important role in dengue prevention and control. Upon the understanding of the value of baseline data, a cross-sectional study was carried out in the dengue hotspot areas in Universiti Sultan Zainal Abidin (UniSZA). The study results ...

  10. 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.

  11. Emergence of Dengue virus serotype 3 on Mayotte Island, Indian ...

    African Journals Online (AJOL)

    A serosurvey carried out in 2006 in Mayotte, a French overseas collectivity in the Indian Ocean, confirmed previous circulation of dengue virus (DENV) on the island, but since the set up of a laboratory-based surveillance of dengue-like illness in 2007, no case of DENV has been confirmed. In response to an outbreak of ...

  12. Isolation of Ancestral Sylvatic Dengue Virus Type 1, Malaysia

    Science.gov (United States)

    Teoh, Boon-Teong; Sam, Sing-Sin; Abd-Jamil, Juraina

    2010-01-01

    Ancestral sylvatic dengue virus type 1, which was isolated from a monkey in 1972, was isolated from a patient with dengue fever in Malaysia. The virus is neutralized by serum of patients with endemic DENV-1 infection. Rare isolation of this virus suggests a limited spillover infection from an otherwise restricted sylvatic cycle. PMID:21029545

  13. Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever.

    NARCIS (Netherlands)

    Gorp, E. van; Setiati, T.E.; Mairuhu, A.T.; Suharti, C.; Cate, H.H.; Dolmans, W.M.V.; Meer, J.W.M. van der; Hack, C.E.; Brandjes, D.P.

    2002-01-01

    The mechanisms contributing to bleeding complications in dengue hemorrhagic fever were studied by investigating the pattern of activation of the coagulation and fibrinolytic systems in 50 children with severe dengue hemorrhagic fever. Thirteen patients (26%) died, and activation of coagulation was

  14. Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever

    NARCIS (Netherlands)

    van Gorp, Eric C. M.; Setiati, Tatty E.; Mairuhu, Albert T. A.; Suharti, Catharina; Cate Ht, Hugo ten; Dolmans, Wil M. V.; van der Meer, Jos W. M.; Hack, C. Erik; Brandjes, Dees P. M.

    2002-01-01

    The mechanisms contributing to bleeding complications in dengue hemorrhagic fever were studied by investigating the pattern of activation of the coagulation and fibrinolytic systems in 50 children with severe dengue hemorrhagic fever. Thirteen patients (26%) died, and activation of coagulation was

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Immune Activation in the Pathogenesis of Dengue Virus Infection

    NARCIS (Netherlands)

    C.A.M. van de Weg (Cornelia A.M.)

    2014-01-01

    markdownabstract__Abstract__ Dengue virus (DENV) is a positive-stranded RNA virus and belongs to the Flaviviridae family. The virus is transmitted by the bite of an infected Aedes-mosquito and circulates in tropical and subtropical areas around the world. The incidence of dengue has risen

  1. Dengue virus exposure among blood donors in Ghana | Narkwa ...

    African Journals Online (AJOL)

    Dengue is an urban arbovirus whose aetiologic agent is the flavivirus 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. Ghana is endemic for Aedes aegypti mosquitoes and probably dengue viruses. Due to limited data ...

  2. Deranged liver among Sudanese patients with dengue virus ...

    African Journals Online (AJOL)

    Background: Deranged liver is a well-recognized feature of dengue infection, often demonstrated by coagulopathy and mild to moderate increase in transaminase levels although jaundice and fulminant hepatic failure are generally uncommon. Objective: This study aimed to evaluate the hepatic effect of dengue fever ...

  3. Ludwig's angina after severe thrombocytopenic purpura associated with dengue fever

    Directory of Open Access Journals (Sweden)

    Maria Antonia Campos

    2014-01-01

    Full Text Available Here, we report a case of Ludwig's angina, which required surgery because of toothache. The patient had dengue and severe thrombocytopenia as confirmed by clinical and laboratory diagnoses. However, dengue is not included among the predisposing factors for Ludwig's angina.

  4. Socio-demographic determinants of dengue infection during an ...

    African Journals Online (AJOL)

    Dell

    4Southern African Centre for Infectious Disease Surveillance, Africa Centre of Excellence for Infectious Diseases of. Humans and ..... Erlanger, T.E., Keiser, J. & Utzinger, J. (2008) Effect of dengue vector control interventions on ... Dengue fever among hospitalized febrile patients in northern Tanzania. American Journal of.

  5. Genetic analysis of imported dengue virus strains by Iranian travelers

    Directory of Open Access Journals (Sweden)

    Nariman Shahhosseini

    2016-11-01

    Full Text Available Dengue virus sequences used in this study were obtained from two Iranian patients who were both with a history of traveling to Malaysia. The maximum likelihood phylogenetic tree demonstrated that two sequences were grouped into dengue virus 1. Specifically, strains IranDF1 and Iran-DF2 clustered in genotype I and III, respectively.

  6. Climate Variability, Social Change and Dengue in Bangladesh ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Researchers will carry out a serological study in nine city wards in Dhaka with different levels of dengue virus transmission; a clinical study of suspected cases of dengue in two hospitals; entomological surveys in the nine wards already mentioned; and an ethnographic study in three wards to examine the social and ...

  7. Dengue as a cause of acute undifferentiated fever in Vietnam

    NARCIS (Netherlands)

    Phuong, H.L.; de Vries, P.J.; Nga, T.T.T.; Giao, P.T.; Hung, L.Q.; Binh, T.Q.; Nam, N.V.; Nagelkerke, N.; Kager, P.A.

    2006-01-01

    Background: Dengue is a common cause of fever in the tropics but its contribution to the total burden of febrile illnesses that is presented to primary health facilities in endemic regions such as Vietnam, is largely unknown. We aimed to report the frequency of dengue as a cause of fever in Binh

  8. Dengue fever associated with acute scrotal oedema: two case reports

    International Nuclear Information System (INIS)

    Shamim, M.; Naqvi, S.Z.G.

    2011-01-01

    Scrotal oedema associated with dengue fever is a rare and self limiting condition resolving in a few days without any complication or sequelae. This is a report of two cases of dengue fever associated with acute scrotal and penile oedema. (author)

  9. 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.

  10. Dengue as a cause of acute undifferentiated fever in Vietnam

    NARCIS (Netherlands)

    Phuong, Hoang Lan; de Vries, Peter J.; Nga, Tran T. T.; Giao, Phan T.; Hung, Le Q.; Binh, Tran Q.; Nam, Nguyen V.; Nagelkerke, Nico; Kager, Piet A.

    2006-01-01

    BACKGROUND: Dengue is a common cause of fever in the tropics but its contribution to the total burden of febrile illnesses that is presented to primary health facilities in endemic regions such as Vietnam, is largely unknown. We aimed to report the frequency of dengue as a cause of fever in Binh

  11. 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.

  12. Climate Variability, Social Change and Dengue in Bangladesh ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Since the year 2000, the major cities of Bangladesh have experienced a resurgence of dengue. Dengue is a major public health concern because of its epidemic potential in any one year, and because of the limited understanding of disease transmission dynamics in the country. This project aims to advance knowledge on ...

  13. 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.)

  14. 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.)

  15. Recombinational repair: workshop summary

    International Nuclear Information System (INIS)

    Howard-Flanders, P.

    1983-01-01

    Recombinational repair may or may not be synonymous with postreplication repair. Considerable progress has been made in the study of the relevant enzymes, particularly those from bacteria. In this workshop we focus on the recombination enzyme RecA protein. What structural changes take place in the protein and in DNA during repair. How does homologous pairing take place. How is ATP hydrolysis coupled to the stand exchange reaction and the formation of heteroduplx DNA. Turning to another enzyme needed for certain kinds of bacterial recombination, we will ask whether the purified recB protein and recC protein complement each other and are sufficient for exonuclease V activity. In higher cells, we would like to know whether sister exchanges, which occur in bacteria after uv irradiation, are also seen in animal cells

  16. 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

  17. 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.

  18. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    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

  19. 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.

  20. 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.

  1. 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.

  2. Evidence for the Inhibition of Dengue Virus Binding in the Presence of Silver Nanoparticles

    Science.gov (United States)

    2015-03-26

    with DENV are known to increase in severity from Dengue Fever to Dengue Hemorrhagic Fever or Dengue Shock Syndrome. Currently, no vaccines or...DENV is a member of the Flavivirus family, as is the yellow fever virus (the family’s prototype), West Nile, Japanese encephalitis virus, and many...perspective/2013/10/ researchers - identify-fifth-dengue-subtype. [20] C. Moore, “UTMB Galveston Researchers Discover First New Dengue Fever Serotype In 50

  3. 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...

  4. 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 ...

  5. Molecular epidemiology of type 1 and 2 dengue viruses in Brazil from 1988 to 2001

    OpenAIRE

    Pires Neto,R.J.; Lima,D.M.; de Paula,S.O.; Lima,C.M.; Rocco,I.M.; Fonseca,B.A.L.

    2005-01-01

    Dengue is a mosquito-borne viral infection that in recent decades has become a major international public health concern. Epidemic dengue fever reemerged in Brazil in 1981. Since 1990 more than one dengue virus serotype has been circulating in this tropical country and increasing rates of dengue hemorrhagic fever and dengue shock syndrome have been detected every year. Some evidence supports the association between the introduction of a new serotype and/or genotype in a region and the appeara...

  6. 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...

  7. Factors related to severe dengue during an epidemic in Vitoria, State of Espirito Santo, Brazil, 2011

    OpenAIRE

    Vicente, Creuza Rachel; Lauar, Julia Castanheira; Santos, Bruna Silva; Cobe, Victor Marchesi; Cerutti Junior, Crispim

    2013-01-01

    Introduction The prognosis of dengue depends on early diagnosis and treatment, which can help prevent severe forms whose characteristics were evaluated here. Methods A cross-sectional study was conducted involving dengue cases in Vitória, State of Espírito Santo, Brazil, in 2011. Results Two health regions registered 56.3% of 371 cases of severe dengue. Of these cases, 21.3% presented with dengue hemorrhagic fever. There were associations between dengue hemorrhagic fever with yo...

  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. [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.

  10. Aspectos del dengue investigados en Santander

    Directory of Open Access Journals (Sweden)

    Ruth Martínez

    2004-03-01

    Full Text Available

    Entre 1998 y 2003 se registraron en Colombia 256,831 casos de dengue (22,834 de dengue hemorrágico DH de los cuales 41,325 (36% fueron en Santander (3,265 DH (1,2. En este período ocurrieron brotes en 1998 y 2001 observándose incremento de casos severos en el segundo (2. Por otro lado, existen inconvenientes con el diagnóstico que dificultan el manejo clínico oportuno y la vigilancia epidemiológica. Como consecuencia, los siguientes aspectos han sido investigados:

    1 Contribución de la circulación de los serotipos/genotipos al incremento del dengue hemorrágico, considerando que la entrada o emergencia de éstos se han asociado con epidemias (3. Entre 1998 y 2004 se hicieron 1,180 intentos de aislamiento viral en células C6/36 (4, detectándose los 4 serotipos. El DEN-2 se aisló todos los años con mayor frecuencia durante los brotes (43% y 40% de los cepas; el DEN-1 se detectó entre 1998 y 2001, siendo el prevalente en el primer brote (57%, pero el menos en el segundo (4%; el DEN-3 se detectó en el brote del 2001 con similar frecuencia al DEN-2 (36%, por primera vez en Colombia luego de 23 años ausente, y fue el prevalerte entre 2002-2004 (92% de los aislados, aunque en estos años no se reportó incremento del DH (2; el DEN-4 se aisló solo en el 2000 (27% y en el brote del 2001 (20%. El genotipo de cada serotipo se identificó por análisis de RSS-PCR (5,6. Se encontraron el subtipo A (ó III, C (ó I y B (ó II de los serotipos 2, 1 y 4, similares a los que están circulando en países de América y oriundos del Asia. Los DEN-3 fueron del subtipo C (ó III iguales al virus que entró en América en 1994 oriundo de Sri-Lanka, India. Los genotipos del 2 y 3 encontrados en Santander producen con mayor frecuencia DH (3,7.

    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)

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

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    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.

  12. Urbanização e ecologia do dengue Urbanization and dengue ecology

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    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

  13. Parton recombination model

    International Nuclear Information System (INIS)

    Hwa, R.C.

    1978-08-01

    Low P/sub T/ meson production in hadronic collisions is described in the framework of the parton model. The recombination of quark and antiquark is suggested as the dominant mechanism in the large x region. Phenomenological evidences for the mechanism are given. The application to meson initiated reactions yields the quark distribution in mesons. 21 references

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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

  18. Mathematical analysis of dengue virus antibody dynamics

    Science.gov (United States)

    Perera, Sulanie; Perera, SSN

    2018-03-01

    Dengue is a mosquito borne viral disease causing over 390 million infections worldwide per annum. Even though information on how infection is controlled and eradicated from the body is lacking, antibodies are thought to play a major role in clearing the virus. In this paper, a non-linear conceptual dynamical model with humoral immune response and absorption effect has been proposed for primary dengue infection. We have included the absorption of pathogens into uninfected cells since this effect causes the virus density in the blood to decrease. The time delay that arises in the production of antibodies was accounted and is introduced through a continuous function. The basic reproduction number R0 is computed and a detailed stability analysis is done. Three equilibrium states, namely the infection free equilibrium, no immune equilibrium and the endemic equilibrium were identified and the existence and the stability conditions of these steady states were obtained. Numerical simulations proved the results that were obtained. By establishing the characteristic equation of the model at infection free equilibrium, it was observed that the infection free equilibrium is locally asymptotically stable if R0 1. Stability regions are identified for infection free equilibrium state with respect to the external variables and it is observed as the virus burst rate increases, the stability regions would decrease. These results implied that for higher virus burst rates, other conditions in the body must be strong enough to eliminate the disease completely from the host. The effect of time delay of antibody production on virus dynamics is discussed. It was seen that as the time delay in production of antibodies increases, the time for viral decline also increased. Also it was observed that the virus count goes to negligible levels within 7 - 14 days after the onset of symptoms as seen in dengue infections.

  19. Aedes albopictus and the reemergence of Dengue

    Directory of Open Access Journals (Sweden)

    Rezza Giovanni

    2012-01-01

    Full Text Available Abstract Dengue is a vector-borne disease that is estimated to affect millions of individuals each year in tropical and subtropical areas, and it is reemerging in areas that have been disease-free for relatively long periods of time. In this issue of the journal, Peng et al. report on a Dengue outbreak in a city in southern China that had been disease-free for more than two decades. The infection, which was due to serotype 1, was introduced by a traveler from South-east Asia and transmitted by Aedes albopictus, the Asian tiger mosquito. Compared to Aedes aegypti, which is the most important vector of Dengue, Ae albopictus is a less competent vector of arboviruses, and the epidemics it causes are milder. However, Ae albopictus is becoming an increasingly important vector because of its rapidly changing global distribution. In particular, the worldwide trade in second hand tires, which often contain water and are an ideal place for eggs and larvae, has been a key factor in the large-scale conquest of Ae albopictus, which easily adapts to new environments, even in a temperate climate. This expansion is creating new opportunities for viruses to circulate in new areas, becoming a common cause of epidemics in Ae aegypti-free countries, from Hawaii to Mauritius. The outbreak in China, like similar events, was mild and short-lived. Because epidemics due to Ae albopictus are milder, the replacement of Ae aegypti with the tiger mosquito could even result in public-health benefits. However, there is no solid evidence of this, and the milder course of the outbreak could be in part explained by the relatively short duration of the hot season in some affected areas. Since it is almost impossible to prevent Ae albopictus from being introduced in a country, mosquito-control measures at local level remain the most effective means of controlling arbovirus outbreaks.

  1. 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.

  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. Clinical and virological characteristics of dengue in Surabaya, Indonesia.

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. Cost and disease burden of Dengue in Cambodia

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    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.

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

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    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

  7. STUDY OF ULTRASOUND FINDING IN DENGUE FEVER

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    Sunita Bajaj

    2016-10-01

    Full Text Available BACKGROUND Dengue fever (DF is a viral haemorrhagic fever causing severe morbidity and mortality in affected patients. The aim of the study is to describe the role of ultrasonography (USG in the assessment of patients with Dengue fever, and its complications and to prove ultrasound is useful in the diagnosis during an epidemic. MATERIALS AND METHODS It is a prospective study was conducted in 2016 comprising of 178 patients who were serologically positive for dengue, radiological investigations were conducted in all cases. RESULTS Out of 178 patients Males (N=117 are more effected subjects in the study. female: Male ratio is 1:2. Hepatomegaly 74.1% which is most common findings in study, 113 (63.4% had GB wall thickening 98 had ascites (55%, 32 had pleural effusion (17.9%. most commonly seen in the age group of 20-39 years. Hepatomegaly was the most common finding noted in 67 patients (37.6%, followed by GB wall thickening in 65 patients (36.1%. Hepatomegaly was more common in 0-19 is 56 patients with 31.4% years age group Ascites in >40 years age group (16.8%. Hepatomegaly was seen in most of the patients whose platelet count was <40,000. (94.7%. GB wall thickening (88.5% common findings seen in patients whose platelet count was <40,000. In patients with platelet count of 40,000-80,000, Ascites is most common finding (87.5%, followed by Splenomegaly (60.7%. In patients whose platelet count was 80,000-150,000, Ascites (50% was more common than Splenomegaly (45.8%. In three patients with platelet count more than 150,000, no sonological abnormality was detected. CONCLUSIONS Ultrasound findings of hepatic changes, GB wall oedema, splenomegaly, ascites and pleural effusion in patients presenting with signs and symptoms of Dengue fever during an epidemic are diagnostic. Contributing in the differential diagnosis with other causes of febrile disease.

  8. Forecast of dengue incidence using temperature and rainfall.

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    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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome.

    Science.gov (United States)

    Wan Jamaludin, Wan Fariza; Periyasamy, Petrick; Wan Mat, Wan Rahiza; Abdul Wahid, S Fadilah

    2015-08-01

    Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. 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...

  18. Spatial-temporal analysis of dengue deaths: identifying social vulnerabilities

    Directory of Open Access Journals (Sweden)

    Maria do Socorro da Silva

    Full Text Available Abstract: INTRODUCTION Currently, dengue fever, chikungunya fever, and zika virus represent serious public health issues in Brazil, despite efforts to control the vector, the Aedes aegypti mosquito. METHODS: This was a descriptive and ecological study of dengue deaths occurring from 2002 to 2013 in São Luis, Maranhão, Brazil. Geoprocessing software was used to draw maps, linking the geo-referenced deaths with urban/social data at census tract level. RESULTS: There were 74 deaths, concentrated in areas of social vulnerability. CONCLUSIONS: The use of geo-technology tools pointed to a concentration of dengue deaths in specific intra-urban areas.

  19. Dengue infection in pregnancy and its impact on the placenta

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    Christiane Fernandes Ribeiro

    2017-02-01

    Full Text Available A histopathological and immunohistochemical study was conducted in placental tissues and retained products of conception from 24 patients with confirmed dengue infection during pregnancy. The immunohistochemical assay was positive for dengue virus in 19 placental and three ovular remnants analyzed. The light microscopic findings were signs of hypoxia, choriodeciduitis, deciduitis and intervillositis and the viral antigens were found in cytoplasmic of the trophoblast, villous stroma and decidua. Our results suggest that immunohistochemistry could be used as a laboratory confirmation method for dengue in pregnant women, especially in endemic areas when embedded material is the only material available.

  20. 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

  1. Dengue infection severity score – improvised disease management

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    Mahmood SU

    2016-08-01

    Full Text Available Syed Uzair Mahmood,1 Maryam Jamil Syed,1 Aisha Jamal,1 Maria Shoaib2 1Sindh Medical College, Jinnah Sindh Medical University, Karachi, Pakistan; 2Dow Medical College, Dow University of Health Sciences, Karachi, PakistanWe would like to add our views regarding the paper “Validation of Dengue infection severity score” by Pongpan et al.1 As the paper outlines, the purpose of the Dengue Severity Score is to classify individuals with dengue infection into three levels of severity with clinically acceptable underestimation or overestimation. View the original paper by Pongpan and colleagues. 

  2. Fundus Findings in Dengue Fever: A Case Report

    Directory of Open Access Journals (Sweden)

    Berna Şahan

    2015-10-01

    Full Text Available Dengue fever is a flavivirus infection transmitted through infected mosquitoes, and is endemic in Southeast Asia, Central and South America, the Pacific, Africa and the Eastern Mediterranean region. A 41-year-old male patient had visual impairment after travelling to Thailand, which is one of the endemic areas. Cotton wool spots were observed on fundus examination. Fundus fluorescein angiography showed minimal vascular leakage from areas near the cotton wool spots and dot hemorrhages in the macula. Dengue fever should be considered in patients with visual complaints who traveled to endemic areas of dengue fever. (Turk J Ophthalmol 2015; 45: 223-225

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

    OpenAIRE

    Scott B. Halstead

    2006-01-01

    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 ampli...

  4. Spatial-temporal analysis of dengue deaths: identifying social vulnerabilities.

    Science.gov (United States)

    Silva, Maria do Socorro da; Branco, Maria Dos Remédios Freitas Carvalho; Aquino, José; Queiroz, Rejane Christine de Sousa; Bani, Emanuele; Moreira, Emnielle Pinto Borges; Medeiros, Maria Nilza Lima; Rodrigues, Zulimar Márita Ribeiro

    2017-01-01

    Currently, dengue fever, chikungunya fever, and zika virus represent serious public health issues in Brazil, despite efforts to control the vector, the Aedes aegypti mosquito. This was a descriptive and ecological study of dengue deaths occurring from 2002 to 2013 in São Luis, Maranhão, Brazil. Geoprocessing software was used to draw maps, linking the geo-referenced deaths with urban/social data at census tract level. There were 74 deaths, concentrated in areas of social vulnerability. The use of geo-technology tools pointed to a concentration of dengue deaths in specific intra-urban areas.

  5. 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

  6. Myalgia Cruris Epidemica: an unusual presentation of dengue fever.

    Science.gov (United States)

    Ahmad, Rashidi; Abdul Latiff, Abdul Kursi; Abdul Razak, Salmi

    2007-11-01

    We describe a 5-year-old girl who had sudden onset difficulty in walking after 3 days of febrile illness. In the emergency department her creatine kinase level was elevated but urine myoglobin was normal. She was diagnosed as having benign acute childhood myositis. Because of poor oral intake and dehydration, she was admitted to the pediatric ward. The next day she had a petechial rash over the antecubital fossa, and dengue IgM back was positive. She was treated conservatively and recovered uneventfully. Despite dengue fever being endemic in Malaysia, this is the first case report of myositis following dengue infection in Malaysia.

  7. 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....

  8. 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.

  9. Site directed recombination

    Science.gov (United States)

    Jurka, Jerzy W.

    1997-01-01

    Enhanced homologous recombination is obtained by employing a consensus sequence which has been found to be associated with integration of repeat sequences, such as Alu and ID. The consensus sequence or sequence having a single transition mutation determines one site of a double break which allows for high efficiency of integration at the site. By introducing single or double stranded DNA having the consensus sequence flanking region joined to a sequence of interest, one can reproducibly direct integration of the sequence of interest at one or a limited number of sites. In this way, specific sites can be identified and homologous recombination achieved at the site by employing a second flanking sequence associated with a sequence proximal to the 3'-nick.

  10. Nonradiative recombination in semiconductors

    CERN Document Server

    Abakumov, VN; Yassievich, IN

    1991-01-01

    In recent years, great progress has been made in the understandingof recombination processes controlling the number of excessfree carriers in semiconductors under nonequilibrium conditions. As a result, it is now possible to give a comprehensivetheoretical description of these processes. The authors haveselected a number of experimental results which elucidate theunderlying physical problems and enable a test of theoreticalmodels. The following topics are dealt with: phenomenological theory ofrecombination, theoretical models of shallow and deep localizedstates, cascade model of carrier captu

  11. 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.

  12. Recombination epoch revisited

    International Nuclear Information System (INIS)

    Krolik, J.H.

    1989-01-01

    Previous studies of cosmological recombination have shown that this process produces as a by-product a highly superthermal population of Ly-alpha photons which retard completion of recombination. Cosmological redshifting was thought to determine the frequency distribution of the photons, while two-photon decay of hydrogen's 2s state was thought to control their numbers. It is shown here that frequency diffusion due to photon scattering dominate the cosmological redshift in the frequency range near line center which fixes the ratio of ground state to excited state population, while incoherent scattering into the far-red damping wing effectively destroys Ly-alpha photons as a rate which is competitive with two-photon decay. The former effect tends to hold back recombination, while the latter tends to accelerate it; the net results depends on cosmological parameters, particularly the combination Omega(b) h/sq rt (2q0), where Omega(b) is the fraction of the critical density provided by baryons. 18 references

  13. Dielectronic recombination theory

    International Nuclear Information System (INIS)

    LaGattuta, K.J.

    1991-01-01

    A theory now in wide use for the calculation of dielectronic recombination cross sections (σ DR ) and rate coefficients (α DR ) was one introduced originally by Feshbach for nuclear physics applications, and then later adapted for atomic scattering problems by Hahn. In the following, we briefly review this theory in a very general form, which allows one to account for the effects of overlapping and interacting resonances, as well as continuum-continuum coupling. An extension of our notation will then also allow for the inclusion of the effects of direct radiative recombination, along with a treatment of the interference between radiative and dielectronic recombination. Other approaches to the calculation of σ DR have been described by Fano and by Seaton. We will not consider those theories here. Calculations of α DR have progressed considerably over the last 25 years, since the early work of Burgess. Advances in the reliability of theoretical predictions have also been promoted recently b a variety of direct laboratory measurements of σ DR . While the measurements of σ DR for δn ≠ 0 excitations have tended to agree very well with calculations, the case of δn = 0 has been much problematic. However, by invoking a mechanism originally proposed by Jacobs, which takes into account the effect of stray electric fields on high Rydberg states (HRS) participating in the DR process, new calculations have improved the agreement between theory and experiment for these cases. Nevertheless, certain discrepancies still remain

  14. DENGUE, CHIKUNGUNYA E EBOLA: VIROSES AMBIENTAIS

    Directory of Open Access Journals (Sweden)

    Thereza Cristina Ferreira Camello

    2014-12-01

    Full Text Available DOI: 10.12957/sustinere.2014.14122Várias viroses emergentes ou reemergentes podem ser veiculadas por mosquitos. Aedes aegypti e Aedes albopictus, os mesmos que transmitem o vírus da dengue e da febre amarela, podem disseminar o vírus Chikungunya que este ano no Brasil já fez cerca de 1000 casos confirmados. A doença tem parâmetros semelhantes aos da Dengue, e embora a taxa de letalidade seja muito baixa, sequelas podem permanecer no individuo por um ano. Em 2014 a partir de setembro o mundo observou perplexo a ressurgência de um vírus hemorrágico letal, em uma das piores epidemias já ocorridas no continente africano. O vírus Ebola atingiu mais de 6000 pessoas. Estudos no sentido de melhorar as estratégias de contenção da disseminação de vetores e dos vírus devem ser estabelecidas, enquanto aguardamos a produção de vacinas eficazes. O mundo não é imune a uma infecção endêmica, localizada no interior de um continente e não estamos preparados para atender uma demanda deste porte.

  15. Clinical implications and treatment of dengue.

    Science.gov (United States)

    Chawla, Pooja; Yadav, Amrita; Chawla, Viney

    2014-03-01

    Dengue is a common pathogenic disease often proving fatal, more commonly affecting the tropics. Aedes mosquito is the vector for this disease, and outbreaks of dengue often cause mass damage to life. The current review is an effort to present an insight into the causes, etiology, symptoms, transmission, diagnosis, major organs affected, mitigation and line of treatment of this disease with special emphasis on drugs of natural origin. The disease has a potential to spread as an endemic, often claiming several lives and thus requires concerted efforts to work out better treatment options. Traditional medicine offers an alternative solution and could be explored as a safer treatment option. Development of a successful vaccine and immunization technique largely remains a challenge and a better antiviral approach needs to be worked out to complement the supportive therapy. No single synthetic molecule has found to be wholly effective enough to offer curative control and the line of treatment mostly utilizes a combination of fluid replacement and antipyretics-analgesics like molecules to provide symptomatic relief. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  16. 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...

  17. Roles of Interferons in Pregnant Women with Dengue Infection: Protective or Dangerous Factors

    Directory of Open Access Journals (Sweden)

    Hao Zhang

    2017-01-01

    Full Text Available Dengue infection is a serious public health problem in tropical and subtropical areas. With the recent outbreaks of Zika disease and its reported correlation with microcephaly, the large number of pregnancies with dengue infection has become a serious concern. This review describes the epidemiological characteristics of pregnancy with dengue and the initial immune response to dengue infection, especially in IFNs production in this group of patients. Dengue is much more prevalent in pregnant women compared with other populations. The severity of dengue is correlated with the level of IFNs, while the serum IFN level must be sufficiently high to maintain the pregnancy and to inhibit virus replication.

  18. 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

  19. 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

  20. Retrospective search for dengue vector mosquito Aedes albopictus in areas visited by a German traveler who contracted dengue in Japan

    Directory of Open Access Journals (Sweden)

    Mutsuo Kobayashi

    2014-09-01

    Full Text Available A German traveler developed dengue fever in late August 2013, following a direct flight from Germany. Autochthonous dengue virus (DENV infection has not been reported in Japan. To evaluate the risk of autochthonous DENV transmission in Japan, the authors performed a retrospective search of the five areas visited by the German patient to determine the population density of dengue vector mosquito, Aedes albopictus. The annual mean temperature of each area was higher than 12 °C, which is considered suitable for the establishment of A. albopictus populations. Our retrospective search revealed the population density of A. albopictus to be high in the urban areas of Japan.