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  1. Rift Valley fever potential mosquito vectors and their infection status ...

    African Journals Online (AJOL)

    Background: Rift Valley fever (RVF) is a mosquito-borne viral zoonotic disease. Rift Valley fever virus (RVFV) has been isolated from more than 40 species of mosquitoes from eight genera. This study was conducted to determine the abundance of potential mosquito vectors and their RVFV infection status in Ngorongoro ...

  2. Presence of viral RNA and proteins in exosomes from the cellular clones resistant to Rift Valley Fever Virus infection.

    Directory of Open Access Journals (Sweden)

    Noor eAhsan

    2016-02-01

    Full Text Available Rift Valley Fever Virus (RVFV is a RNA virus that belongs to the genus Phlebovirus, family Bunyaviridae. It infects humans and livestock and causes Rift Valley fever. RVFV is considered an agricultural pathogen by the USDA, as it can cause up to 100% abortion in cattle and extensive death of newborns. In addition, it is designated as Category A pathogen by the CDC and the NIAID. In some human cases of RVFV infection, the virus causes fever, ocular damage, liver damage, hemorrhagic fever, and death. There are currently limited options for vaccine candidates, which include the MP-12 and clone 13 versions of RVFV. Viral infections often deregulate multiple cellular pathways that contribute to replication and host pathology. We have previously shown that latent HIV-1 and HTLV-1 infected cells secrete exosomes that contain short viral RNAs, limited number of genomic RNAs, and viral proteins. These exosomes largely target neighboring cells and activate the NF-кB pathway, leading to cell proliferation and overall better viral replication. In this manuscript, we studied the effects of exosome formation from RVFV infected cells and their function on recipient cells. We initially infected cells, isolated resistant clones, and further purified using dilution cloning. We then characterized these cells as resistant to new RVFV infection, but sensitive to other viral infections, including Venezuelan Equine Encephalitis Virus (VEEV. These clones contained normal markers (i.e. CD63 for exosomes and were able to activate the TLR pathway in recipient reporter cells. Interestingly, the exosome rich preparations, much like their host cell, contained viral RNA (L, M, and S genome. The RNAs were detected using qRT-PCR in both parental and exosomal preparations as well as in CD63 immunoprecipitates. Viral proteins such as N and a modified form of NSs were present in some of these exosomes. Finally, treatment of recipient cells (T- cells and monocytic cells showed

  3. p53 Activation following Rift Valley fever virus infection contributes to cell death and viral production.

    Directory of Open Access Journals (Sweden)

    Dana Austin

    Full Text Available Rift Valley fever virus (RVFV is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production.

  4. Interventions Against West Nile Virus, Rift Valley Fever Virus, and Crimean-Congo Hemorrhagic Fever Virus: Where Are We?

    NARCIS (Netherlands)

    Kortekaas, J.A.; Ergonul, O.; Moormann, R.J.M.

    2010-01-01

    ARBO-ZOONET is an international network financed by the European Commission's seventh framework program. The major goal of this initiative is capacity building for the control of emerging viral vector-borne zoonotic diseases, with a clear focus on West Nile virus, Rift Valley fever virus, and

  5. Surveillance of Rift Valley Fever in Iran between 2001 and 2011

    Directory of Open Access Journals (Sweden)

    Sadegh CHINIKAR

    2013-06-01

    Full Text Available Rift Valley fever virus (RVFV is an acute zoonotic viral disease that mostly affects ruminants with an occasional spillover as human infection. Following the outbreak of RVF in Saudi Arabia in 2000, surveillance of both animal and human population in Iran increased until 2011. During this period 1206 ovine, 405 caprine, 325 bovine and 28 camel samples were tested for RVFV in nine provinces in Iran. None of these samples tested IgG positive. Moreover, amongst 37 clinically suspected human cases of patients with RVF symptoms, none of these samples tested positive for RVFV. Despite the fact that no positive cases in human or animal populations were identified in Iran, surveillance and monitoring of viral haemorrhagic fevers including RVFV will continue.

  6. Surveillance of Rift Valley Fever in Iran between 2001 and 2011

    Directory of Open Access Journals (Sweden)

    Sadegh CHINIKAR

    2013-04-01

    Full Text Available Rift Valley fever virus (RVFV is an acute zoonotic viral disease that mostly affects ruminants with an occasional spillover as human infection. Following the outbreak of RVF in Saudi Arabia in 2000, surveillance of both animal and human population in Iran increased until 2011. During this period 1206 ovine, 405 caprine, 325 bovine and 28 camel samples were tested for RVFV in nine provinces in Iran. None of these samples tested IgG positive. Moreover, amongst 37 clinically suspected human cases of patients with RVF symptoms, none of these samples tested positive for RVFV. Despite the fact that no positive cases in human or animal populations were identified in Iran, surveillance and monitoring of viral haemorrhagic fevers including RVFV will continue.

  7. Acid-activated structural reorganization of the Rift Valley fever virus Gc fusion protein

    NARCIS (Netherlands)

    Boer, de S.M.; Kortekaas, J.A.; Spel, L.; Rottier, P.J.M.; Moormann, R.J.M.; Bosch, B.J.

    2012-01-01

    Entry of the enveloped Rift Valley fever virus (RVFV) into its host cell is mediated by the viral glycoproteins Gn and Gc. We investigated the RVFV entry process and its pH-dependent activation mechanism in particular using our recently developed nonspreading RVFV particle system. Entry of the virus

  8. Valley Fever

    Science.gov (United States)

    ... valley fever. These fungi are commonly found in soil in specific regions. The fungi's spores can be stirred into the air by ... species have a complex life cycle. In the soil, they grow as a mold with long filaments that break off into airborne ...

  9. Rift valley fever virus nonstructural protein NSs promotes viral RNA replication and transcription in a minigenome system.

    Science.gov (United States)

    Ikegami, Tetsuro; Peters, C J; Makino, Shinji

    2005-05-01

    Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, has a tripartite negative-strand genome (S, M, and L segments) and is an important mosquito-borne pathogen for domestic animals and humans. We established an RVFV T7 RNA polymerase-driven minigenome system in which T7 RNA polymerase from an expression plasmid drove expression of RNA transcripts for viral proteins and minigenome RNA transcripts carrying a reporter gene between both termini of the M RNA segment in 293T cells. Like other viruses of the Bunyaviridae family, replication and transcription of the RVFV minigenome required expression of viral N and L proteins. Unexpectedly, the coexpression of an RVFV nonstructural protein, NSs, with N and L proteins resulted in a significant enhancement of minigenome RNA replication. Coexpression of NSs protein with N and L proteins also enhanced minigenome mRNA transcription in the cells expressing viral-sense minigenome RNA transcripts. NSs protein expression increased the RNA replication of minigenomes that originated from S and L RNA segments. Enhancement of minigenome RNA synthesis by NSs protein occurred in cells lacking alpha/beta interferon (IFN-alpha/beta) genes, indicating that the effect of NSs protein on minigenome RNA replication was unrelated to a putative NSs protein-induced inhibition of IFN-alpha/beta production. Our finding that RVFV NSs protein augmented minigenome RNA synthesis was in sharp contrast to reports that Bunyamwera virus (genus Bunyavirus) NSs protein inhibits viral minigenome RNA synthesis, suggesting that RVFV NSs protein and Bunyamwera virus NSs protein have distinctly different biological roles in viral RNA synthesis.

  10. Treating viral hemorrhagic fever.

    NARCIS (Netherlands)

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

    2003-01-01

    Viral hemorrhagic fevers are illnesses associated with a number of geographically restricted, mostly tropical areas. Over recent decades a number of new hemorrhagic fever viruses have emerged. Advances in our understanding of the pathophysiology of these diseases have improved our initial supportive

  11. Countermeasure development for Rift Valley fever: deletion, modification or targeting of major virulence factor NSs.

    Science.gov (United States)

    Lihoradova, Olga; Ikegami, Tetsuro

    2014-01-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized by a high rate of abortion in ruminants, and febrile illness, hemorrhagic fever, retinitis and encephalitis in humans. RVF is caused by the RVF virus (RVFV), belonging to the genus Phlebovirus of the family Bunyaviridae . RVFV encodes a major virulence factor, NSs , which is dispensable for viral replication, yet required for evasion of host innate immune responses. RVFV NSs inhibits host gene upregulation at the transcriptional level, while promoting viral translation in the cytoplasm. In this article, we summarize the virology and pathology of RVF, and countermeasure development for RVF, with emphasis on NSs function and applications.

  12. Breathing Valley Fever

    Centers for Disease Control (CDC) Podcasts

    2014-02-04

    Dr. Duc Vugia, chief of the Infectious Diseases Branch in the California Department of Public Health, discusses Valley Fever.  Created: 2/4/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 2/5/2014.

  13. Seroprevalence of Sheep and Goat Pox, Peste Des Petits Ruminants and Rift Valley Fever in Saudi Arabia.

    Science.gov (United States)

    Boshra, Hani; Truong, Thang; Babiuk, Shawn; Hemida, Maged Gomaa

    2015-01-01

    Sheep and goat pox, peste des petits ruminants and Rift Valley fever are important diseases of small ruminant livestock. Sheep and goat pox, along with peste des petits ruminants, are endemic throughout most of Africa, Asia and the Middle East. Whereas Rift Valley fever is endemic in Africa, outbreaks in the Middle East have been reported over the past decade, including the Arabian Peninsula. Saudi Arabia is a major importer of livestock, and understanding the prevalence of these viral infections would be useful for disease control. In this study, sera from sheep and goats were collected from 3 regions in Saudi Arabia. They were evaluated for antibodies specific to sheep and goat pox, peste des petits ruminants and Rift Valley fever by virus neutralization assays. To the best of our knowledge, this is the first study to evaluate the seroprevalence of these viruses in sheep and goats.

  14. Seroprevalence of Sheep and Goat Pox, Peste Des Petits Ruminants and Rift Valley Fever in Saudi Arabia.

    Directory of Open Access Journals (Sweden)

    Hani Boshra

    Full Text Available Sheep and goat pox, peste des petits ruminants and Rift Valley fever are important diseases of small ruminant livestock. Sheep and goat pox, along with peste des petits ruminants, are endemic throughout most of Africa, Asia and the Middle East. Whereas Rift Valley fever is endemic in Africa, outbreaks in the Middle East have been reported over the past decade, including the Arabian Peninsula. Saudi Arabia is a major importer of livestock, and understanding the prevalence of these viral infections would be useful for disease control. In this study, sera from sheep and goats were collected from 3 regions in Saudi Arabia. They were evaluated for antibodies specific to sheep and goat pox, peste des petits ruminants and Rift Valley fever by virus neutralization assays. To the best of our knowledge, this is the first study to evaluate the seroprevalence of these viruses in sheep and goats.

  15. Rift Valley Fever.

    Science.gov (United States)

    Hartman, Amy

    2017-06-01

    Rift Valley fever (RVF) is a severe veterinary disease of livestock that also causes moderate to severe illness in people. The life cycle of RVF is complex and involves mosquitoes, livestock, people, and the environment. RVF virus is transmitted from either mosquitoes or farm animals to humans, but is generally not transmitted from person to person. People can develop different diseases after infection, including febrile illness, ocular disease, hemorrhagic fever, or encephalitis. There is a significant risk for emergence of RVF into new locations, which would affect human health and livestock industries. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

    Science.gov (United States)

    Nuss, Jonathan E; Kehn-Hall, Kylene; Benedict, Ashwini; Costantino, Julie; Ward, Michael; Peyser, Brian D; Retterer, Cary J; Tressler, Lyal E; Wanner, Laura M; McGovern, Hugh F; Zaidi, Anum; Anthony, Scott M; Kota, Krishna P; Bavari, Sina; Hakami, Ramin M

    2014-01-01

    Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV). Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry) with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90), as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  17. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

    Directory of Open Access Journals (Sweden)

    Jonathan E Nuss

    Full Text Available Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV. Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90, as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  18. Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: Implications from other RNA viruses

    Directory of Open Access Journals (Sweden)

    Shoko eNishiyama

    2015-08-01

    Full Text Available Rift Valley fever (RVF is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae. Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the United States. MP-12 displays a temperature-sensitive (ts phenotype and does not replicate at 41oC. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF.

  19. The Example of Eastern Africa: the dynamic of Rift Valley fever and tools for monitoring virus activity

    Science.gov (United States)

    Rift Valley fever is a mosquito-borne viral zoonosis that primarily affects animals but also has the capacity to infect humans. Outbreaks of this disease in eastern Africa are closely associated with periods of heavy rainfall and forecasting models and early warning systems have been developed to en...

  20. N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN

    Science.gov (United States)

    Phoenix, Inaia; Nishiyama, Shoko; Lokugamage, Nandadeva; Hill, Terence E.; Huante, Matthew B.; Slack, Olga A.L.; Carpio, Victor H.; Freiberg, Alexander N.; Ikegami, Tetsuro

    2016-01-01

    Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as a receptor for members of the phlebovirus genus. The Rift Valley fever virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)–any amino acid (X)–serine (S)/threonine (T)) at positions: N438 (Gn), and N794, N829, N1035, and N1077 (Gc). The N-glycosylation profile and significance in viral infection via DC-SIGN have not been elucidated. Gc N-glycosylation was first evaluated by using Gc asparagine (N) to glutamine (Q) mutants. Subsequently, we generated a series of recombinant RVFV MP-12 strain mutants, which encode N-to-Q mutations, and the infectivity of each mutant in Jurkat cells stably expressing DC-SIGN was evaluated. Results showed that Gc N794, N1035, and N1077 were N-glycosylated but N829 was not. Gc N1077 was heterogeneously N-glycosylated. RVFV Gc made two distinct N-glycoforms: “Gc-large” and “Gc-small”, and N1077 was responsible for “Gc-large” band. RVFV showed increased infection of cells expressing DC-SIGN compared to cells lacking DC-SIGN. Infection via DC-SIGN was increased in the presence of either Gn N438 or Gc N1077. Our study showed that N-glycans on the Gc and Gn surface glycoproteins redundantly support RVFV infection via DC-SIGN. PMID:27223297

  1. Efficient cellular release of Rift Valley fever virus requires genomic RNA.

    Directory of Open Access Journals (Sweden)

    Mary E Piper

    2011-03-01

    Full Text Available The Rift Valley fever virus is responsible for periodic, explosive epizootics throughout sub-Saharan Africa. The development of therapeutics targeting this virus is difficult due to a limited understanding of the viral replicative cycle. Utilizing a virus-like particle system, we have established roles for each of the viral structural components in assembly, release, and virus infectivity. The envelope glycoprotein, Gn, was discovered to be necessary and sufficient for packaging of the genome, nucleocapsid protein and the RNA-dependent RNA polymerase into virus particles. Additionally, packaging of the genome was found to be necessary for the efficient release of particles, revealing a novel mechanism for the efficient generation of infectious virus. Our results identify possible conserved targets for development of anti-phlebovirus therapies.

  2. Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice.

    Science.gov (United States)

    Indran, Sabarish V; Lihoradova, Olga A; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A; Tigabu, Bersabeh; Smith, Jennifer K; Zhang, Lihong; Juelich, Terry L; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

    2013-07-01

    Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV.

  3. Identification of Rift Valley Fever Virus Nucleocapsid Protein-RNA Binding Inhibitors Using a High-Throughput Screening Assay

    OpenAIRE

    Ellenbecker, Mary; Lanchy, Jean-Marc; Lodmell, J. Stephen

    2012-01-01

    Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. Currently, there is no proven effective treatment for RVFV infection and there is no licensed vaccine. Inhibition of RNA binding to the essential viral nucleocapsid (N) protein represents a potential anti-viral therapeutic strategy because all of the functions performed by N during infection involve RNA binding. To target this interactio...

  4. TRAINING PROGRAM FOR NURSING STAFF REGARDING VIRAL HEMORRHAGIC FEVERS IN A MILITARY HOSPITAL.

    Science.gov (United States)

    El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Saleh, Halla Ahmed Abdullah; Abdelfattah, Magda Abdelhamid; Morsy, Tosson Aly

    2015-08-01

    Viral hemorrhagic fevers (VHFs) refer to a group of illnesses caused by several distinct families of viruses. In general, the term "viral hemorrhagic fever" is used to describe a severe multisystem syndrome (multisystem in that multiple organ systems in the bpdy are affected). Characteristically, the overall vascular system is damaged, and the body's ability to regulate itself is impaired. These symptoms are often accompanied by hemorrhage (bleeding); however, the bleeding is it rarely life-threatening. While some types of hemorrhagic fever viruses can cause relatively mild illnesses, many of these viruses cause severe, life-threatening disease. The selected disaster diseases for this study included: 1-Crimean-Congo hemorrhagic Fever, 2-Dengue Fever, 3-Ebola Fever, 4-Hem-orrhagic Fever with renal syndrome (HFRS), 5-Hantavirus Pulmonary Syndrome, 6-Lassa Fever, 7-Marburg Fever, 8-Rift Valley Fever and 9-Yellow Fever. The educational training program was given over ten sessions to a group of Staff Nurses. The results showed that the program succeeded in enhancing nurse' knowledge, awareness, responsibility, and obligations toward patients with the Viral Hemorrhagic Fevers The results showed a significant impact of training sessions illuminated in the follow-up test on the knowledge score of nurses in all types of diseases except for the Congo hemorrhagic fever, while, statistical significance varied in some diseases in the study when it comes to the comparison between pretest and post-test. All results confirmed on the positive impact of the training program in enhancing the knowledge of nurses toward VHFs patients and their relevant. There was a significant positive impact of the training sessions on changing the attitude of nurses toward patients with VHFs. This result was confirmed on the collective level since the total scores on tests revealed significant positive impact of the study on changing the attitude of nurses toward relevant patients. The relationship

  5. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

    OpenAIRE

    Warimwe, GM; Lorenzo, G; Lopez-Gil, E; Reyes-Sandoval, A; Cottingham, MG; Spencer, AJ; Collins, KA; Dicks, MD; Milicic, A; Lall, A; Furze, J; Turner, AV; Hill, AV; Brun, A; Gilbert, SC

    2013-01-01

    BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibod...

  6. Ultrastructural study of Rift Valley fever virus in the mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Christopher; Steele, Keith E.; Honko, Anna; Shamblin, Joshua; Hensley, Lisa E. [United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States); Smith, Darci R., E-mail: darci.smith1@us.army.mil [United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States)

    2012-09-15

    Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed in the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV-host interactions and further characterize the mouse model of RVF.

  7. Ultrastructural study of Rift Valley fever virus in the mouse model

    International Nuclear Information System (INIS)

    Reed, Christopher; Steele, Keith E.; Honko, Anna; Shamblin, Joshua; Hensley, Lisa E.; Smith, Darci R.

    2012-01-01

    Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed in the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV–host interactions and further characterize the mouse model of RVF.

  8. A Novel System for Identification of Inhibitors of Rift Valley Fever Virus Replication

    OpenAIRE

    Piper, Mary E.; Gerrard, Sonja R.

    2010-01-01

    Rift Valley fever virus (RVFV) is a human and livestock pathogen endemic to sub-Saharan Africa. We have developed a T7-dependent system for the efficient production of RVFV-like particles (RVF-VLPs) based on the virulent ZH-501 strain of RVFV. The RVF-VLPs are capable of performing a single round of infection, allowing for the study of viral replication, assembly, and infectivity. We demonstrate that these RVF-VLPs are antigenically indistinguishable from authentic RVFV and respond similarly ...

  9. Immunological features underlying viral hemorrhagic fevers.

    Science.gov (United States)

    Messaoudi, Ilhem; Basler, Christopher F

    2015-10-01

    Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Hospital-based surveillance for viral hemorrhagic fevers and hepatitides in Ghana.

    Directory of Open Access Journals (Sweden)

    Joseph Humphrey Kofi Bonney

    Full Text Available BACKGROUND: Viral hemorrhagic fevers (VHF are acute diseases associated with bleeding, organ failure, and shock. VHF may hardly be distinguished clinically from other diseases in the African hospital, including viral hepatitis. This study was conducted to determine if VHF and viral hepatitis contribute to hospital morbidity in the Central and Northern parts of Ghana. METHODOLOGY/PRINCIPAL FINDINGS: From 2009 to 2011, blood samples of 258 patients with VHF symptoms were collected at 18 hospitals in Ashanti, Brong-Ahafo, Northern, Upper West, and Upper East regions. Patients were tested by PCR for Lassa, Rift Valley, Crimean-Congo, Ebola/Marburg, and yellow fever viruses; hepatitis A (HAV, B (HBV, C (HCV, and E (HEV viruses; and by ELISA for serological hepatitis markers. None of the patients tested positive for VHF. However, 21 (8.1% showed anti-HBc IgM plus HBV DNA and/or HBsAg; 37 (14% showed HBsAg and HBV DNA without anti-HBc IgM; 26 (10% showed anti-HAV IgM and/or HAV RNA; and 20 (7.8% were HCV RNA-positive. None was positive for HEV RNA or anti-HEV IgM plus IgG. Viral genotypes were determined as HAV-IB, HBV-A and E, and HCV-1, 2, and 4. CONCLUSIONS/SIGNIFICANCE: VHFs do not cause significant hospital morbidity in the study area. However, the incidence of acute hepatitis A and B, and hepatitis B and C with active virus replication is high. These infections may mimic VHF and need to be considered if VHF is suspected. The data may help decision makers to allocate resources and focus surveillance systems on the diseases of relevance in Ghana.

  11. Comparison of sampling techniques for Rift Valley Fever virus ...

    African Journals Online (AJOL)

    time for trapping potential vectors for Rift Valley Fever virus. ..... Krockel, U., Rose, A., Eiras, A.E. & Geier, M. (2006) New tools for surveillance of adult yellow fever ... baited trapping systems for sampling outdoor mosquito populations in ...

  12. Rift Valley fever virus infection in golden Syrian hamsters.

    Directory of Open Access Journals (Sweden)

    Dionna Scharton

    Full Text Available Rift Valley fever virus (RVFV is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

  13. Pathogenesis of Rift Valley Fever in Rhesus Monkeys: Role of Interferon Response

    Science.gov (United States)

    1990-01-01

    hemorrhagic fever characterized by epistaxis, petechial to purpuric cutaneous lesions, anorexia, and vomiting prior to death. The 14 remaining monkeys survived...DMI, FILE Copy Arch Virol (1990) 110: 195-212 Amhivesirology ( by Springer-Verlag 1990 00 N Pathogenesis of Rift Valley fever in rhesus monkeys: (NI...inoculated intravenously with Rift Valley fever (RVF) virus presented clinical disease syndromes similar to human cases of RVF. All 17 infected monkeys

  14. Interim Report on SNP analysis and forensic microarray probe design for South American hemorrhagic fever viruses, tick-borne encephalitis virus, henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever viruses, Rift Valley fever

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C; Gardner, S

    2012-06-05

    The goal of this project is to develop forensic genotyping assays for select agent viruses, enhancing the current capabilities for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the whole genome wide SNP analysis and microarray probe design for forensics characterization of South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.

  15. 77 FR 68783 - Prospective Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

    Science.gov (United States)

    2012-11-16

    ... Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for... Valley Fever Virus Utilizing Reverse Genetics,'' US Provisional Application 61/042,987, filed 4/7/2008, entitled ``Recombinant Rift Valley Fever (RVF) Viruses and Method of Use,'' PCT Application PCT/US2008...

  16. Inter-epidemic abundance and distribution of potential mosquito vectors for Rift Valley fever virus in Ngorongoro district, Tanzania

    OpenAIRE

    Mweya, Clement N.; Kimera, Sharadhuli I.; Mellau, Lesakit S. B.; Mboera, Leonard E. G.

    2015-01-01

    Background: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that primarily affects ruminants but also has the capacity to infect humans. Objective: To determine the abundance and distribution of mosquito vectors in relation to their potential role in the virus transmission and maintenance in disease epidemic areas of Ngorongoro district in northern Tanzania. Methods: A cross-sectional entomological investigation was carried out before the suspected RVF outbreak in October 2012. Mos...

  17. A Novel System for Identification of Inhibitors of Rift Valley Fever Virus Replication

    Directory of Open Access Journals (Sweden)

    Mary E. Piper

    2010-03-01

    Full Text Available Rift Valley fever virus (RVFV is a human and livestock pathogen endemic to sub-Saharan Africa. We have developed a T7-dependent system for the efficient production of RVFV-like particles (RVF-VLPs based on the virulent ZH-501 strain of RVFV. The RVF-VLPs are capable of performing a single round of infection, allowing for the study of viral replication, assembly, and infectivity. We demonstrate that these RVF-VLPs are antigenically indistinguishable from authentic RVFV and respond similarly to a wide array of known and previously unknown chemical inhibitors. This system should be useful for screening for small molecule inhibitors of RVFV replication.

  18. A novel system for identification of inhibitors of rift valley Fever virus replication.

    Science.gov (United States)

    Piper, Mary E; Gerrard, Sonja R

    2010-03-01

    Rift Valley fever virus (RVFV) is a human and livestock pathogen endemic to sub-Saharan Africa. We have developed a T7-dependent system for the efficient production of RVFV-like particles (RVF-VLPs) based on the virulent ZH-501 strain of RVFV. The RVF-VLPs are capable of performing a single round of infection, allowing for the study of viral replication, assembly, and infectivity. We demonstrate that these RVF-VLPs are antigenically indistinguishable from authentic RVFV and respond similarly to a wide array of known and previously unknown chemical inhibitors. This system should be useful for screening for small molecule inhibitors of RVFV replication.

  19. Dual functions of Rift Valley fever virus NSs protein: inhibition of host mRNA transcription and post-transcriptional downregulation of protein kinase PKR.

    Science.gov (United States)

    Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C J; Makino, Shinji

    2009-09-01

    Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a single-stranded, tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis, or ocular diseases. A viral nonstructural protein, NSs, is a major viral virulence factor. Past studies showed that NSs suppresses the transcription of host mRNAs, including interferon-beta mRNAs. Here we demonstrated that the NSs protein induced post-transcriptional downregulation of dsRNA-dependent protein kinase (PKR), to prevent phosphorylation of eIF2alpha and promoted viral translation in infected cells. These two biological activities of the NSs most probably have a synergistic effect in suppressing host innate immune functions and facilitate efficient viral replication in infected mammalian hosts.

  20. Rift Valley fever outbreak, Mauritania, 1998: seroepidemiologic, virologic, entomologic, and zoologic investigations.

    Science.gov (United States)

    Nabeth, P; Kane, Y; Abdalahi, M O; Diallo, M; Ndiaye, K; Ba, K; Schneegans, F; Sall, A A; Mathiot, C

    2001-01-01

    A Rift Valley fever outbreak occurred in Mauritania in 1998. Seroepidemiologic and virologic investigation showed active circulation of the Rift Valley fever virus, with 13 strains isolated, and 16% (range 1.5%-38%) immunoglobulin (Ig) M-positivity in sera from 90 humans and 343 animals (sheep, goats, camels, cattle, and donkeys). One human case was fatal.

  1. Impact of Global Climate on Rift Valley Fever and other Vector-borne Disease Outbreaks

    Science.gov (United States)

    Linthicum, K. J.

    2017-12-01

    Rift Valley fever is a viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. Since the virus was first isolated in Kenya in 1930 it has caused significant impact to animal and human health and national economies, and it is of concern to the international agricultural and public health community. In this presentation we will describe the (1) ecology of disease transmission as it relates to climate, (2) the impact of climate and other environmental conditions on outbreaks, (3) the ability to use global climate information to predict outbreaks, (4) effective response activities, and (4) the potential to mitigate globalization.

  2. Re-Emergence of Rift Valley Fever in Madagascar

    Centers for Disease Control (CDC) Podcasts

    This podcast describes the re-emergence of Rift Valley Fever in Madagascar during two rainy seasons in 2008 and 2009. CDC epidemiologist Dr. Pierre Rollin discusses what researchers learned about the outbreak and about infections in the larger population in Madagascar.

  3. Rift Valley Fever, Mayotte, 2007–2008

    Science.gov (United States)

    Giry, Claude; Gabrie, Philippe; Tarantola, Arnaud; Pettinelli, François; Collet, Louis; D’Ortenzio, Eric; Renault, Philippe; Pierre, Vincent

    2009-01-01

    After the 2006–2007 epidemic wave of Rift Valley fever (RVF) in East Africa and its circulation in the Comoros, laboratory case-finding of RVF was conducted in Mayotte from September 2007 through May 2008. Ten recent human RVF cases were detected, which confirms the indigenous transmission of RFV virus in Mayotte. PMID:19331733

  4. Viral haemorrhagic fever and vascular alterations.

    Science.gov (United States)

    Aleksandrowicz, P; Wolf, K; Falzarano, D; Feldmann, H; Seebach, J; Schnittler, H

    2008-02-01

    Pathogenesis of viral haemorrhagic fever (VHF) is closely associated with alterations of the vascular system. Among the virus families causing VHF, filoviruses (Marburg and Ebola) are the most fatal, and will be focused on here. After entering the body, Ebola primarily targets monocytes/macrophages and dendritic cells. Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells. Some underlying molecular mechanisms such as alteration of the vascular endothelial cadherin/catenin complex, tyrosine phosphorylation, expression of cell adhesion molecules, tissue factor and the effect of soluble viral proteins released from infected cells to the blood stream will be discussed.

  5. 77 FR 68783 - Prospective Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

    Science.gov (United States)

    2012-11-16

    ... Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for Disease..., filed 12/21/2007, entitled ``Development of Rift Valley Fever Virus Utilizing Reverse Genetics,'' US... (RVF) Viruses and Method of Use,'' PCT Application PCT/US2008/ 087023, filed 12/16/2008, entitled...

  6. Rift Valley fever virus seroprevalence in human rural populations of Gabon.

    Directory of Open Access Journals (Sweden)

    Xavier Pourrut

    Full Text Available BACKGROUND: Rift Valley fever (RVF is a mosquito-borne viral zoonosis caused by a phlebovirus and transmitted by Aedes mosquitoes. Humans can also be infected through direct contact with blood (aerosols or tissues (placenta, stillborn of infected animals. Although severe clinical cases can be observed, infection with RVF virus (RVFV in humans is, in most cases, asymptomatic or causes a febrile illness without serious symptoms. In small ruminants RVFV mainly causes abortion and neonatal death. The distribution of RVFV has been well documented in many African countries, particularly in the north (Egypt, Sudan, east (Kenya, Tanzania, Somalia, west (Senegal, Mauritania and south (South Africa, but also in the Indian Ocean (Madagascar, Mayotte and the Arabian Peninsula. In contrast, the prevalence of RVFV has rarely been investigated in central African countries. METHODOLOGY/PRINCIPAL FINDINGS: We therefore conducted a large serological survey of rural populations in Gabon, involving 4,323 individuals from 212 randomly selected villages (10.3% of all Gabonese villages. RVFV-specific IgG was found in a total of 145 individuals (3.3% suggesting the wide circulation of Rift Valley fever virus in Gabon. The seroprevalence was significantly higher in the lakes region than in forest and savannas zones, with respective rates of 8.3%, 2.9% and 2.2%. In the lakes region, RVFV-specific IgG was significantly more prevalent in males than in females (respectively 12.8% and 3.8% and the seroprevalence increased gradually with age in males but not in females. CONCLUSIONS/SIGNIFICANCE: Although RVFV was suggested to circulate at a relatively high level in Gabon, no outbreaks or even isolated cases have been documented in the country. The higher prevalence in the lakes region is likely to be driven by specific ecologic conditions favorable to certain mosquito vector species. Males may be more at risk of infection than females because they spend more time farming and

  7. A fusion-inhibiting peptide against Rift Valley fever virus inhibits multiple, diverse viruses.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Koehler

    Full Text Available For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III based on the protein sequence and structure. For Rift Valley fever virus (RVFV, the glycoprotein Gc (Class II fusion protein mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus, Class II (Andes virus, or Class III (vesicular stomatitis virus fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.

  8. Mapping of the mutations present in the genome of the Rift Valley fever virus attenuated MP12 strain and their putative role in attenuation.

    Science.gov (United States)

    Vialat, P; Muller, R; Vu, T H; Prehaud, C; Bouloy, M

    1997-11-01

    The MP12 attenuated strain of Rift Valley fever virus was obtained by 12 serial passages of a virulent isolate ZH548 in the presence of 5-fluorouracil (Caplen et al., 1985. Mutagen-directed attenuation of Rift Valley fever virus as a method for vaccine development. J. Gen. Virol., 66, 2271-2277). The comparison of the M segment of the two strains has already been reported by Takehara et al. (Takehara et al., 1989. Identification of mutations in the M RNA of a candidate vaccine strain of Rift Valley fever virus. Virology 169, 452-457). We have completed the comparison and found that altogether a total of nine, 12 and four nucleotides were changed in the L, M and S segments of the two strains, respectively. Three mutations induced amino acid changes in the L protein but none of them was located in the recognized motifs conserved among RNA dependent polymerases. In the S segment, a single change modified an amino acid in the NSs protein and in the M segment, seven of the mutations resulted in amino acid changes in each of the four encoded G1, G2, 14 kDa and 78 kDa proteins. Characterization of the MP12 virus indicated that determinants for attenuation were present in each segment and that they were introduced progressively during the 12 passages in the presence of the mutagen (Saluzzo and Smith, 1990. Use of reassortant viruses to map attenuating and temperature-sensitive mutations of the Rift Valley fever virus MP-12 vaccine. Vaccine 8, 369-375). Passages 4 and 7-9 were found to be essential for introduction of temperature-sensitive lesions and attenuation. In an attempt to correlate some of the mutations with the attenuated or temperature-sensitive phenotypes, we determined by sequencing the passage level at which the different mutations appeared. This work should help to address the question of the role of the viral gene products in Rift Valley fever pathogenesis.

  9. Electron microscopic identification of Zinga virus as a strain of Rift Valley fever virus.

    Science.gov (United States)

    Olaleye, O D; Baigent, C L; Mueller, G; Tomori, O; Schmitz, H

    1992-01-01

    Electron microscopic examination of a negatively stained suspension of Zinga virus showed particles 90-100 nm in diameter, enveloped with spikes 12-20 nm in length and 5 nm in diameter. Further identification of the virus by immune electron microscopy showed the reactivity of human Rift Valley fever virus-positive serum with Zinga virus. Results of this study are in agreement with earlier reports that Zinga virus is a strain of Rift Valley fever virus.

  10. Development and preliminary evaluation of a multiplexed amplification and next generation sequencing method for viral hemorrhagic fever diagnostics.

    Directory of Open Access Journals (Sweden)

    Annika Brinkmann

    2017-11-01

    Full Text Available We describe the development and evaluation of a novel method for targeted amplification and Next Generation Sequencing (NGS-based identification of viral hemorrhagic fever (VHF agents and assess the feasibility of this approach in diagnostics.An ultrahigh-multiplex panel was designed with primers to amplify all known variants of VHF-associated viruses and relevant controls. The performance of the panel was evaluated via serially quantified nucleic acids from Yellow fever virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever (CCHF virus, Ebola virus, Junin virus and Chikungunya virus in a semiconductor-based sequencing platform. A comparison of direct NGS and targeted amplification-NGS was performed. The panel was further tested via a real-time nanopore sequencing-based platform, using clinical specimens from CCHF patients.The multiplex primer panel comprises two pools of 285 and 256 primer pairs for the identification of 46 virus species causing hemorrhagic fevers, encompassing 6,130 genetic variants of the strains involved. In silico validation revealed that the panel detected over 97% of all known genetic variants of the targeted virus species. High levels of specificity and sensitivity were observed for the tested virus strains. Targeted amplification ensured viral read detection in specimens with the lowest virus concentration (1-10 genome equivalents and enabled significant increases in specific reads over background for all viruses investigated. In clinical specimens, the panel enabled detection of the causative agent and its characterization within 10 minutes of sequencing, with sample-to-result time of less than 3.5 hours.Virus enrichment via targeted amplification followed by NGS is an applicable strategy for the diagnosis of VHFs which can be adapted for high-throughput or nanopore sequencing platforms and employed for surveillance or outbreak monitoring.

  11. Development and preliminary evaluation of a multiplexed amplification and next generation sequencing method for viral hemorrhagic fever diagnostics.

    Science.gov (United States)

    Brinkmann, Annika; Ergünay, Koray; Radonić, Aleksandar; Kocak Tufan, Zeliha; Domingo, Cristina; Nitsche, Andreas

    2017-11-01

    We describe the development and evaluation of a novel method for targeted amplification and Next Generation Sequencing (NGS)-based identification of viral hemorrhagic fever (VHF) agents and assess the feasibility of this approach in diagnostics. An ultrahigh-multiplex panel was designed with primers to amplify all known variants of VHF-associated viruses and relevant controls. The performance of the panel was evaluated via serially quantified nucleic acids from Yellow fever virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever (CCHF) virus, Ebola virus, Junin virus and Chikungunya virus in a semiconductor-based sequencing platform. A comparison of direct NGS and targeted amplification-NGS was performed. The panel was further tested via a real-time nanopore sequencing-based platform, using clinical specimens from CCHF patients. The multiplex primer panel comprises two pools of 285 and 256 primer pairs for the identification of 46 virus species causing hemorrhagic fevers, encompassing 6,130 genetic variants of the strains involved. In silico validation revealed that the panel detected over 97% of all known genetic variants of the targeted virus species. High levels of specificity and sensitivity were observed for the tested virus strains. Targeted amplification ensured viral read detection in specimens with the lowest virus concentration (1-10 genome equivalents) and enabled significant increases in specific reads over background for all viruses investigated. In clinical specimens, the panel enabled detection of the causative agent and its characterization within 10 minutes of sequencing, with sample-to-result time of less than 3.5 hours. Virus enrichment via targeted amplification followed by NGS is an applicable strategy for the diagnosis of VHFs which can be adapted for high-throughput or nanopore sequencing platforms and employed for surveillance or outbreak monitoring.

  12. Single-particle cryo-electron microscopy of Rift Valley fever virus

    OpenAIRE

    Sherman, Michael B.; Freiberg, Alexander N.; Holbrook, Michael R.; Watowich, Stanley J.

    2009-01-01

    Rift Valley fever virus (RVFV; Bunyaviridae; Phlebovirus) is an emerging human veterinary pathogen causing acute hepatitis in ruminants and has the potential to Single-particle cryo-EM reconstruction of RVFV MP-12 hemorrhagic fever in humans. We report a three-dimensional reconstruction of RVFV vaccine strain MP-12 (RVFV MP-12) by cryo-electron microcopy using icosahedral symmetry of individual virions. Although the genomic core of RVFV MP-12 is apparently poorly ordered, the glycoproteins on...

  13. Spread and Control of Rift Valley Fever virus after accidental introduction in the Netherlands: a modelling study.

    NARCIS (Netherlands)

    Fischer, E.A.J.; Boender, G.J.; Koeijer, de A.A.; Nodelijk, G.; Roermund, van H.J.W.

    2011-01-01

    Rift Valley Fever (RVF) is a zoonotic vector-borne infection and causes a potentially severe disease in both humans and young animals. The Ministry of Economic Affairs, Agriculture and Innovation (EL&I) is interested in the risk of an outbreak of Rift Valley Fever virus (RVFV) for the

  14. Nuclear relocalization of polyadenylate binding protein during rift valley fever virus infection involves expression of the NSs gene.

    Science.gov (United States)

    Copeland, Anna Maria; Altamura, Louis A; Van Deusen, Nicole M; Schmaljohn, Connie S

    2013-11-01

    Rift Valley fever virus (RVFV), an ambisense member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever, an important zoonotic infection in Africa and the Middle East. Phlebovirus proteins are translated from virally transcribed mRNAs that, like host mRNA, are capped but, unlike host mRNAs, are not polyadenylated. Here, we investigated the role of PABP1 during RVFV infection of HeLa cells. Immunofluorescence studies of infected cells demonstrated a gross relocalization of PABP1 to the nucleus late in infection. Immunofluorescence microscopy studies of nuclear proteins revealed costaining between PABP1 and markers of nuclear speckles. PABP1 relocalization was sharply decreased in cells infected with a strain of RVFV lacking the gene encoding the RVFV nonstructural protein S (NSs). To determine whether PABP1 was required for RVFV infection, we measured the production of nucleocapsid protein (N) in cells transfected with small interfering RNAs (siRNAs) targeting PABP1. We found that the overall percentage of RVFV N-positive cells was not changed by siRNA treatment, indicating that PABP1 was not required for RVFV infection. However, when we analyzed populations of cells producing high versus low levels of PABP1, we found that the percentage of RVFV N-positive cells was decreased in cell populations producing physiologic levels of PABP1 and increased in cells with reduced levels of PABP1. Together, these results suggest that production of the NSs protein during RVFV infection leads to sequestration of PABP1 in the nuclear speckles, creating a state within the cell that favors viral protein production.

  15. Occurrence of rift valley fever (RVF) in Dodoma region, Tanzania ...

    African Journals Online (AJOL)

    Rift Valley Fever (RVF) is a peracute or acute febrile zoonotic ... results the patients were treated for malaria and/or meningitis based on visual/ clinical signs. ... RVF occurrence to humans by using case study definitions for RVF suspect's, and ...

  16. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

    Directory of Open Access Journals (Sweden)

    Sanchita Das

    Full Text Available CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR. The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively. The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus.

  17. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

    Science.gov (United States)

    Das, Sanchita; Rundell, Mark S; Mirza, Aashiq H; Pingle, Maneesh R; Shigyo, Kristi; Garrison, Aura R; Paragas, Jason; Smith, Scott K; Olson, Victoria A; Larone, Davise H; Spitzer, Eric D; Barany, Francis; Golightly, Linnie M

    2015-01-01

    CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

  18. A review of mosquitoes associated with Rift Valley fever virus in Madagascar.

    Science.gov (United States)

    Tantely, Luciano M; Boyer, Sébastien; Fontenille, Didier

    2015-04-01

    Rift Valley fever (RVF) is a viral zoonotic disease occurring throughout Africa, the Arabian Peninsula, and Madagascar. The disease is caused by a Phlebovirus (RVF virus [RVFV]) transmitted to vertebrate hosts through the bite of infected mosquitoes. In Madagascar, the first RVFV circulation was reported in 1979 based on detection in mosquitoes but without epidemic episode. Subsequently, two outbreaks occurred: the first along the east coast and in the central highlands in 1990 and 1991 and the most recent along the northern and eastern coasts and in the central highlands in 2008 and 2009. Despite the presence of 24 mosquitoes species potentially associated with RVFV transmission in Madagascar, little associated entomological information is available. In this review, we list the RVFV vector, Culex antennatus, as well as other taxa as candidate vector species. We discuss risk factors from an entomological perspective for the re-emergence of RVF in Madagascar. © The American Society of Tropical Medicine and Hygiene.

  19. Comparison of sampling techniques for Rift Valley Fever virus ...

    African Journals Online (AJOL)

    We investigated mosquito sampling techniques with two types of traps and attractants at different time for trapping potential vectors for Rift Valley Fever virus. The study was conducted in six villages in Ngorongoro district in Tanzania from September to October 2012. A total of 1814 mosquitoes were collected, of which 738 ...

  20. Re-Emergence of Rift Valley Fever in Madagascar

    Centers for Disease Control (CDC) Podcasts

    2010-05-27

    This podcast describes the re-emergence of Rift Valley Fever in Madagascar during two rainy seasons in 2008 and 2009. CDC epidemiologist Dr. Pierre Rollin discusses what researchers learned about the outbreak and about infections in the larger population in Madagascar.  Created: 5/27/2010 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 5/27/2010.

  1. FEVER IN CHILDREN WITH RESPIRATORY VIRAL INFECTIONS: EFFECTIVE AND SAFE METHODS OF TREATMENT

    Directory of Open Access Journals (Sweden)

    T. E. Taranushenko

    2013-01-01

    Full Text Available One of the most important — the problem of treatment of fever in children with respiratory viral infections — is discussed in this article. It is fever as one of the first symptoms of disease which often frightens parents and leads to inappropriate and excess usage of antipyretic agents, which in its turn can cause unfavorable consequences. The authors represent their own data on frequency of antipyretic drugs usage in children with respiratory viral infections, as well as the answers of pediatricians to the questionnaires on methods of choice in temperature normalization. According to the modern Russian as well as European and American clinical guidelines on treatment of fever in children the management of selection of patients demanding antipyretic treatment is detailed, indications and contraindications to such therapy are described, the most effective methods of temperature normalization in children with acute respiratory infection are discussed. The authors suggested the data on recommended dosages of paracetamol, which were revised in 2011 by the UK Medicines Control Agency, to be very useful. The current information on advantages of ibuprofen in comparison to paracetamol in treatment of fever in children with respiratory viral infections is shown. The main target of this article is understanding and acceptance by pediatricians of the modern recommendation on differential and reasonable approach to administration of antipyretic drugs in children with respiratory viral infections.

  2. Simultaneous detection of IgG antibodies associated with viral hemorrhagic fever by a multiplexed Luminex-based immunoassay.

    Science.gov (United States)

    Wu, Wei; Zhang, Shuo; Qu, Jing; Zhang, Quanfu; Li, Chuan; Li, Jiandong; Jin, Cong; Liang, Mifang; Li, Dexin

    2014-07-17

    Viral hemorrhagic fevers (VHFs) are worldwide diseases caused by several kinds of viruses. With the emergence of new viruses, advanced diagnostic methods are urgently needed for identification of VHFs. Based on Luminex xMAP technology, a rapid, sensitive, multi-pathogen and high-throughput method which could simultaneously detect hemorrhagic fever viruses (HFVs) specific IgG antibodies was developed. Recombinant antigens of nine HFVs including Hantaan virus (HTNV), Seoul virus (SEOV), Puumala virus (PUUV), Andes virus (ANDV), Sin Nombre virus (SNV), Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) and dengue virus (DENV) were produced and purified from a prokaryotic expression system and the influence of the coupling amount was investigated. Cross-reactions among antigens and their rabbit immune sera were evaluated. Serum samples collected from 51 laboratory confirmed hemorrhagic fever with renal syndrome (HFRS) patients, 43 confirmed SFTS patients and 88 healthy donors were analyzed. Results showed that recombinant nucleocapsid protein of the five viruses belonging to the genus Hantavirus, had serological cross-reactivity with their corresponding rabbit immune sera, but not apparent with immune sera of other four viruses. Evaluation of this new method with clinical serum samples showed 98.04% diagnostic sensitivity for HFRS, 90.70% for SFTS detection and the specificity was ranging from 66.67% to 100.00%. The multiplexed Luminex-based immunoassay has firstly been established in our study, which provides a potentially reliable diagnostic tool for IgG antibody detection of VHFs. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Pathogenic effects of Rift Valley fever virus NSs gene are alleviated in cultured cells by expressed antiviral short hairpin RNAs.

    Science.gov (United States)

    Scott, Tristan; Paweska, Janusz T; Arbuthnot, Patrick; Weinberg, Marc S

    2012-01-01

    Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, may cause severe hepatitis, encephalitis and haemorrhagic fever in humans. There are currently no available licensed vaccines or therapies to treat the viral infection in humans. RNA interference (RNAi)-based viral gene silencing offers a promising approach to inhibiting replication of this highly pathogenic virus. The small (S) segment of the RVFV tripartite genome carries the genetic determinates for pathogenicity during infection. This segment encodes the non-structural S (NSs) and essential nucleocapsid (N) genes. To advance RNAi-based inhibition of RVFV replication, we designed several Pol III short hairpin RNA (shRNA) expression cassettes against the NSs and N genes, including a multimerized plasmid vector that included four shRNA expression cassettes. Effective target silencing was demonstrated using full- and partial-length target reporter assays, and confirmed by western blot analysis of exogenous N and NSs expression. Small RNA northern blots showed detectable RNAi guide strand formation from single and multimerized shRNA constructs. Using a cell culture model of RVFV replication, shRNAs targeting the N gene decreased intracellular nucleocapsid protein concentration and viral replication. The shRNAs directed against the NSs gene reduced NSs protein concentrations and alleviated NSs-mediated cytotoxicity, which may be caused by host transcription suppression. These data are the first demonstration that RNAi activators have a potential therapeutic benefit for countering RVFV infection.

  4. Vaccines against viral hemorrhagic fevers: non-human primate models.

    Science.gov (United States)

    Carrion, Ricardo; Patterson, Jean L

    2011-06-01

    Viral hemorrhagic fevers are a group of disease syndromes caused by infection with certain RNA viruses. The disease is marked by a febrile response, malaise, coagulopathy and vascular permeability culminating in death. Case fatality rates can reach 90% depending on the etiologic agent. Currently, there is no approved antiviral treatment. Because of the high case fatality, risk of importation and the potential to use these agents as biological weapons, development of countermeasures to these agents is a high priority. The sporadic nature of disease outbreaks and the ethical issues associated with conducting a human trial for such diseases make human studies impractical; therefore, development of countermeasures must occur in relevant animal models. Non-human primates are superior models to study infectious disease because their immune system is similar to humans and they are good predictors of efficacy in vaccine development and other intervention strategies. This review article summarizes viral hemorrhagic fever non-human primate models.

  5. Risk analysis of inter-species reassortment through a Rift Valley fever phlebovirus MP-12 vaccine strain.

    Directory of Open Access Journals (Sweden)

    Hoai J Ly

    Full Text Available Rift Valley fever (RVF is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula. The causative agent, Rift Valley fever phlebovirus (RVFV, belongs to the genus Phlebovirus in the family Phenuiviridae and causes high rates of abortions in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral maintenance by mosquito vectors has led to sporadic RVF outbreaks in ruminants and humans in endemic countries, and effective vaccination of animals and humans may minimize the impact of this disease. A live-attenuated MP-12 vaccine strain is one of the best characterized RVFV strains, and was conditionally approved as a veterinary vaccine in the U.S. Live-attenuated RVF vaccines including MP-12 strain may form reassortant strains with other bunyavirus species. This study thus aimed to characterize the occurrence of genetic reassortment between the MP-12 strain and bunyavirus species closely related to RVFV. The Arumowot virus (AMTV and Gouleako goukovirus (GOLV, are transmitted by mosquitoes in Africa. The results of this study showed that GOLV does not form detectable reassortant strains with the MP-12 strain in co-infected C6/36 cells. The AMTV also did not form any reassortant strains with MP-12 strain in co-infected C6/36 cells, due to the incompatibility among N, L, and Gn/Gc proteins. A lack of reassortant formation could be due to a functional incompatibility of N and L proteins derived from heterologous species, and due to a lack of packaging via heterologous Gn/Gc proteins. The MP-12 strain did, however, randomly exchange L-, M-, and S-segments with a genetic variant strain, rMP12-GM50, in culture cells. The MP-12 strain is thus unlikely to form any reassortant strains with AMTV or GOLV in nature.

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

    Directory of Open Access Journals (Sweden)

    Soegeng Soegijanto

    2018-04-01

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

  7. A skin test survey of valley fever in Tijuana, Mexico.

    Science.gov (United States)

    Fredrich, B E

    1989-01-01

    Results of a study of the prevalence of valley fever among 1128 residents of Tijuana, Baja California are presented. Children from primary and middle schools (n = 497) and adults from technical institutes and maquiladoras (assembly plants) were tested for reaction to both spherulin and coccidioidin during 1985-1986, and they completed a questionnaire containing 23 variables on their socio-environment. Place of residence was mapped. The population sampled is largely middle class. Discriminant analysis indicates the distribution of positive cases is not clustered, nor can it be correlated with geomorphic factors such as mesa tops, canyons, or valley bottoms.

  8. Vertical transmission of Rift Valley Fever Virus without detectable maternal viremia

    NARCIS (Netherlands)

    Antonis, A.F.G.; Kortekaas, J.A.; Kant-Eenbergen, H.C.M.; Vloet, R.P.M.; Vogel-Brink, A.; Stockhofe, N.; Moormann, R.J.M.

    2013-01-01

    Rift Valley fever virus (RVFV) is a zoonotic bunyavirus that causes abortions in domesticated ruminants. Sheep breeds exotic to endemic areas are reportedly the most susceptible to RVFV infection. Within the scope of a risk assessment program of The Netherlands, we investigated the susceptibility of

  9. Risk of transmission of viral haemorrhagic fevers and the insecticide ...

    African Journals Online (AJOL)

    ... of transmission of viral haemorrhagic fevers and the insecticide susceptibility status of Ae. aegypti in some sites in Accra, Ghana. Design: Larval surveys were carried to inspect containers within households and estimate larval indices and adult Aedes mosquitoes were collected using human landing collection technique.

  10. Identification of Rift Valley fever virus nucleocapsid protein-RNA binding inhibitors using a high-throughput screening assay.

    Science.gov (United States)

    Ellenbecker, Mary; Lanchy, Jean-Marc; Lodmell, J Stephen

    2012-09-01

    Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. Currently, there is no proven effective treatment for RVFV infection, and there is no licensed vaccine. Inhibition of RNA binding to the essential viral nucleocapsid (N) protein represents a potential antiviral therapeutic strategy because all of the functions performed by N during infection involve RNA binding. To target this interaction, we developed a fluorescence polarization-based high-throughput drug-screening assay and tested 26 424 chemical compounds for their ability to disrupt an N-RNA complex. From libraries of Food and Drug Administration-approved drugs, druglike molecules, and natural product extracts, we identified several lead compounds that are promising candidates for medicinal chemistry.

  11. MassTag Polymerase Chain Reaction for Differential Diagnosis of Viral Hemorrhagic Fevers

    National Research Council Canada - National Science Library

    Palacios, Gustavo; Briese, Thomas; Kapoor, Vishal; Jabado, Omar; Liu, Zhiqiang; Venter, Marietjie; Zhai, Junhui; Renwick, Neil; Grolla, Allen; Geisbert, Thomas W; Drosten, Christian; Towner, Johnathan; Ju, Jingyue; Paweska, Janusz; Nichol, Stuart T; Swanepel, Robert; Feldmann, Heinz; Jahrling, Peter B; Lipkin, W. I

    2006-01-01

    Viral hemorrhagic fevers are associated with high rates of illness and death. Although therapeutic options are limited, early differential diagnosis has implications for containment and may aid in clinical management...

  12. The role of signal transducer and activator of transcription 3 in Rift Valley fever virus infection

    International Nuclear Information System (INIS)

    Pinkham, Chelsea; An, Soyeon; Lundberg, Lindsay; Bansal, Neha; Benedict, Ashwini; Narayanan, Aarthi; Kehn-Hall, Kylene

    2016-01-01

    Rift Valley fever (RVF) is a zoonotic disease that can cause severe illness in humans and livestock, triggering spontaneous abortion in almost 100% of pregnant ruminants. In this study, we demonstrate that signal transducer and activator of transcription 3 (STAT3) is phosphorylated on its conserved tyrosine residue (Y705) following RVFV infection. This phosphorylation was dependent on a major virulence factor, the viral nonstructural protein NSs. Loss of STAT3 had little effect on viral replication, but rather resulted in cells being more susceptible to RVFV-induced cell death. Phosphorylated STAT3 translocated to the nucleus, coinciding with inhibition of fos, jun, and nr4a2 gene expression, and the presence of STAT3 and NSs at the nr4a2 promoter. NSs was found predominantly in the cytoplasm of STAT3 null cells, indicating that STAT3 influences NSs nuclear localization. Collectively, these data demonstrate that STAT3 functions in a pro-survival capacity through modulation of NSs localization. - Highlights: • STAT3 is phosphorylated on tyrosine residue 705 following RVFV infection. • Phosphorylation of STAT3 was dependent on the viral protein NSs. • STAT3 -/- MEFs were more susceptible to RVFV-induced cell death. • Loss of STAT3 led to an increase in pro-apoptotic gene expression. • STAT3 functions in a pro-survival capacity by modulation of NSs localization.

  13. The role of signal transducer and activator of transcription 3 in Rift Valley fever virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Pinkham, Chelsea; An, Soyeon; Lundberg, Lindsay; Bansal, Neha; Benedict, Ashwini; Narayanan, Aarthi; Kehn-Hall, Kylene, E-mail: kkehnhal@gmu.edu

    2016-09-15

    Rift Valley fever (RVF) is a zoonotic disease that can cause severe illness in humans and livestock, triggering spontaneous abortion in almost 100% of pregnant ruminants. In this study, we demonstrate that signal transducer and activator of transcription 3 (STAT3) is phosphorylated on its conserved tyrosine residue (Y705) following RVFV infection. This phosphorylation was dependent on a major virulence factor, the viral nonstructural protein NSs. Loss of STAT3 had little effect on viral replication, but rather resulted in cells being more susceptible to RVFV-induced cell death. Phosphorylated STAT3 translocated to the nucleus, coinciding with inhibition of fos, jun, and nr4a2 gene expression, and the presence of STAT3 and NSs at the nr4a2 promoter. NSs was found predominantly in the cytoplasm of STAT3 null cells, indicating that STAT3 influences NSs nuclear localization. Collectively, these data demonstrate that STAT3 functions in a pro-survival capacity through modulation of NSs localization. - Highlights: • STAT3 is phosphorylated on tyrosine residue 705 following RVFV infection. • Phosphorylation of STAT3 was dependent on the viral protein NSs. • STAT3 -/- MEFs were more susceptible to RVFV-induced cell death. • Loss of STAT3 led to an increase in pro-apoptotic gene expression. • STAT3 functions in a pro-survival capacity by modulation of NSs localization.

  14. Blood Meal Analysis of Mosquitoes Involved in a Rift Valley fever Outbreak

    Science.gov (United States)

    Background: Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Bloodfed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the bloodmeals. Bloodmeals from individual mosquito abdomens were sc...

  15. Material Proximities and Hotspots: Toward an Anthropology of Viral Hemorrhagic Fevers

    Science.gov (United States)

    Brown, Hannah; Kelly, Ann H

    2014-01-01

    This article outlines a research program for an anthropology of viral hemorrhagic fevers (collectively known as VHFs). It begins by reviewing the social science literature on Ebola, Marburg, and Lassa fevers and charting areas for future ethnographic attention. We theoretically elaborate the hotspot as a way of integrating analysis of the two routes of VHF infection: from animal reservoirs to humans and between humans. Drawing together recent anthropological investigations of human–animal entanglements with an ethnographic interest in the social production of space, we seek to enrich conceptualizations of viral movement by elaborating the circumstances through which viruses, humans, objects, and animals come into contact. We suggest that attention to the material proximities—between animals, humans, and objects—that constitute the hotspot opens a frontier site for critical and methodological development in medical anthropology and for future collaborations in VHF management and control. PMID:24752909

  16. Detection and identification of Rift Valley fever virus in mosquito vectors by quantitative real-time PCR.

    Science.gov (United States)

    Mwaengo, D; Lorenzo, G; Iglesias, J; Warigia, M; Sang, R; Bishop, R P; Brun, A

    2012-10-01

    Diagnostic methods allowing for rapid identification of pathogens are crucial for controlling and preventing dissemination after disease outbreaks as well as for use in surveillance programs. For arboviruses, detection of the presence of virus in their arthropod hosts is important for monitoring of viral activity and quantitative information is useful for modeling of transmission dynamics. In this study, molecular detection of Rift Valley fever virus (RVFV) in mosquito samples from the 2006 to 2007 East African outbreaks was performed using quantitative real-time PCR assay (qRT-PCR). Specific RVFV sequence-based primer/fluorogenic (TaqMan) probe sets were derived from the L and S RNA segments of the virus. Both primer-probe L and S segment-based combinations detected genomic RVFV sequences, with generally comparable levels of sensitivity. Viral loads from three mosquito species, Aedes mcintoshi, Aedes ochraceus and Mansonia uniformis were estimated and significant differences of between 5- and 1000-fold were detected between Ae. mcintoshi and M. uniformis using both the L and S primer-probe-based assays. The genetic relationships of the viral sequences in mosquito samples were established by partial M segment sequencing and assigned to the two previously described viral lineages defined by analysis of livestock isolates obtained during the 2006-2007 outbreak, confirming that similar viruses were present in both the vector and mammalian host. The data confirms the utility of qRT-PCR for identification and initial quantification of virus in mosquito samples during RVFV outbreaks. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Distinct virulence of Rift Valley fever phlebovirus strains from different genetic lineages in a mouse model.

    Directory of Open Access Journals (Sweden)

    Tetsuro Ikegami

    Full Text Available Rift Valley fever phlebovirus (RVFV causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2-3 dpi. Recombinant SA51 (rSA51 and Zinga (rZinga strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies.

  18. Development of a novel, single-cycle replicable rift valley Fever vaccine.

    Directory of Open Access Journals (Sweden)

    Shin Murakami

    2014-03-01

    Full Text Available Rift Valley fever virus (RVFV (genus Phlebovirus, family Bunyaviridae is an arbovirus that causes severe disease in humans and livestock in sub-Saharan African countries. Although the MP-12 strain of RVFV is a live attenuated vaccine candidate, neuroinvasiveness and neurovirulence of MP-12 in mice may be a concern when vaccinating certain individuals, especially those that are immunocompromised. We have developed a novel, single-cycle replicable MP-12 (scMP-12, which carries an L RNA, M RNA mutant encoding a mutant envelope protein lacking an endoplasmic reticulum retrieval signal and defective for membrane fusion function, and S RNA encoding N protein and green fluorescent protein. The scMP-12 underwent efficient amplification, then formed plaques and retained the introduced mutation after serial passages in a cell line stably expressing viral envelope proteins. However, inoculation of the scMP-12 into naïve cells resulted in a single round of viral replication, and production of low levels of noninfectious virus-like particles. Intracranial inoculation of scMP-12 into suckling mice did not cause clinical signs or death, a finding which demonstrated that the scMP-12 lacked neurovirulence. Mice immunized with a single dose of scMP-12 produced neutralizing antibodies, whose titers were higher than in mice immunized with replicon particles carrying L RNA and S RNA encoding N protein and green fluorescent protein. Moreover, 90% of the scMP-12-immunized mice were protected from wild-type RVFV challenge by efficiently suppressing viremia and replication of the challenge virus in the liver and the spleen. These data demonstrated that scMP-12 is a safe and immunogenic RVFV vaccine candidate.

  19. History of U.S. Military Contributions to the Study of Viral Hemorrhagic Fevers

    National Research Council Canada - National Science Library

    Thomas, Stephen J; Lawler, James V; Endy, Timothy P

    2005-01-01

    .... The characteristics of the viral hemorrhagic fever viruses as arthropod or rodent-borne viruses that can result in human illnesses with high morbidity and mortality rates make these viruses a unique...

  20. An Epidemiological Model of Rift Valley Fever with Spatial Dynamics

    Directory of Open Access Journals (Sweden)

    Tianchan Niu

    2012-01-01

    Full Text Available As a category A agent in the Center for Disease Control bioterrorism list, Rift Valley fever (RVF is considered a major threat to the United States (USA. Should the pathogen be intentionally or unintentionally introduced to the continental USA, there is tremendous potential for economic damages due to loss of livestock, trade restrictions, and subsequent food supply chain disruptions. We have incorporated the effects of space into a mathematical model of RVF in order to study the dynamics of the pathogen spread as affected by the movement of humans, livestock, and mosquitoes. The model accounts for the horizontal transmission of Rift Valley fever virus (RVFV between two mosquito and one livestock species, and mother-to-offspring transmission of virus in one of the mosquito species. Space effects are introduced by dividing geographic space into smaller patches and considering the patch-to-patch movement of species. For each patch, a system of ordinary differential equations models fractions of populations susceptible to, incubating, infectious with, or immune to RVFV. The main contribution of this work is a methodology for analyzing the likelihood of pathogen establishment should an introduction occur into an area devoid of RVF. Examples are provided for general and specific cases to illustrate the methodology.

  1. Single-particle cryo-electron microscopy of Rift Valley fever virus

    International Nuclear Information System (INIS)

    Sherman, Michael B.; Freiberg, Alexander N.; Holbrook, Michael R.; Watowich, Stanley J.

    2009-01-01

    Rift Valley fever virus (RVFV; Bunyaviridae; Phlebovirus) is an emerging human and veterinary pathogen causing acute hepatitis in ruminants and has the potential to cause hemorrhagic fever in humans. We report a three-dimensional reconstruction of RVFV vaccine strain MP-12 (RVFV MP-12) by cryo-electron microcopy using icosahedral symmetry of individual virions. Although the genomic core of RVFV MP-12 is apparently poorly ordered, the glycoproteins on the virus surface are highly symmetric and arranged on a T = 12 icosahedral lattice. Our RVFV MP-12 structure allowed clear identification of inter-capsomer contacts and definition of possible glycoprotein arrangements within capsomers. This structure provides a detailed model for phleboviruses, opens new avenues for high-resolution structural studies of the bunyavirus family, and aids the design of antiviral diagnostics and effective subunit vaccines.

  2. Single-particle cryo-electron microscopy of Rift Valley fever virus.

    Science.gov (United States)

    Sherman, Michael B; Freiberg, Alexander N; Holbrook, Michael R; Watowich, Stanley J

    2009-04-25

    Rift Valley fever virus (RVFV; Bunyaviridae; Phlebovirus) is an emerging human and veterinary pathogen causing acute hepatitis in ruminants and has the potential to cause hemorrhagic fever in humans. We report a three-dimensional reconstruction of RVFV vaccine strain MP-12 (RVFV MP-12) by cryo-electron microcopy using icosahedral symmetry of individual virions. Although the genomic core of RVFV MP-12 is apparently poorly ordered, the glycoproteins on the virus surface are highly symmetric and arranged on a T=12 icosahedral lattice. Our RVFV MP-12 structure allowed clear identification of inter-capsomer contacts and definition of possible glycoprotein arrangements within capsomers. This structure provides a detailed model for phleboviruses, opens new avenues for high-resolution structural studies of the bunyavirus family, and aids the design of antiviral diagnostics and effective subunit vaccines.

  3. Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2alpha phosphorylation.

    Science.gov (United States)

    Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C J; Makino, Shinji

    2009-02-01

    Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-beta mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or alpha-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)-mediated eukaryotic initiation factor (eIF)2alpha phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2alpha accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2alpha phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2alpha phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.

  4. Mosquito host choices on livestock amplifiers of Rift Valley fever virus in Kenya

    Science.gov (United States)

    Animal hosts may vary in their attraction and acceptability as components of the host location process for assessing biting rates of vectors and risk of exposure to pathogens. However, these parameters remain poorly understood for mosquito vectors of the Rift Valley fever (RVF), an arboviral disease...

  5. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam

    NARCIS (Netherlands)

    Phuong, Hoang Lan; Nga, Tran T. T.; van Doornum, Gerard J.; Groen, Jan; Binh, Tran Q.; Giao, Phan T.; Hung, Le Q.; Nams, Nguyen V.; Kager, P. A.; de Vries, Peter J.

    2010-01-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control

  6. A Systematic Scoping Study of the Socio-Economic Impact of Rift Valley Fever

    NARCIS (Netherlands)

    Peyre, M.; Chevalier, V.; Abdo-Salem, S.; Velthuis, A.; Antoine-Moussiaux, N.; Thiry, E.; Roger, F.

    2015-01-01

    Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants. RVF virus has been reported in most African countries, as well as in the Arabic Peninsula. This paper reviews the different types of socio-economic impact induced by RVF disease and the attempts to

  7. Experimental transmission of West Nile Virus and Rift Valley Fever Virus by Culex pipiens from Lebanon.

    Directory of Open Access Journals (Sweden)

    Renée Zakhia

    2018-01-01

    Full Text Available West Nile virus (WNV and Rift Valley fever virus (RVFV are two emerging arboviruses transmitted by Culex pipiens species that includes two biotypes: pipiens and molestus. In Lebanon, human cases caused by WNV and RVFV have never been reported. However, the introduction of these viruses in the country is likely to occur through the migratory birds and animal trades. In this study, we evaluated the ability of Cx. pipiens, a predominant mosquito species in urban and rural regions in Lebanon, to transmit WNV and RVFV. Culex egg rafts were collected in the West Bekaa district, east of Lebanon and adult females of Cx. pipiens were experimentally infected with WNV and RVFV Clone 13 strain at titers of 1.6×108 and 1.33×107 plaque forming units (PFU/mL, respectively. We estimated viral infection, dissemination and transmission at 3, 7, 14 and 19 days post infection (dpi. Results showed that infection was higher for WNV than for RVFV from 3 dpi to 19 dpi. Viral dissemination and transmission started from 3 dpi for WNV; and only from 19 dpi for RVFV. Moreover, Cx. pipiens were able to excrete in saliva a higher number of viral particles of WNV (1028 ± 405 PFU/saliva at 19 dpi than RVFV (42 PFU/saliva at 19 dpi. Cx. pipiens from Lebanon are efficient experimental vectors of WNV and to a lower extent, RVFV. These findings should stimulate local authorities to establish an active entomological surveillance in addition to animal surveys for both viruses in the country.

  8. Transmission of Rift Valley fever virus from European-breed lambs to Culex pipiens mosquitoes

    NARCIS (Netherlands)

    Vloet, Rianka P.M.; Vogels, Chantal B.F.; Koenraadt, Constantianus J.M.; Pijlman, Gorben P.; Eiden, Martin; Gonzales, Jose L.; Keulen, van Lucien J.M.; Wichgers Schreur, Paul J.; Kortekaas, Jeroen

    2017-01-01

    Background: Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus of the genus Phlebovirus that is highly pathogenic to ruminants and humans. The disease is currently confined to Africa and the Arabian Peninsula, but globalization and climate change may facilitate introductions of the virus

  9. Rift Valley fever outbreak--Kenya, November 2006-January 2007.

    Science.gov (United States)

    2007-02-02

    In mid-December 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the Kenya Ministry of Health (KMOH) from Garissa District in North Eastern Province (NEP). By December 20, a total of 11 deaths had been reported. Of serum samples collected from the first 19 patients, Rift Valley fever (RVF) virus RNA or immunoglobulin M (IgM) antibodies against RVF virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, Ebola, Crimean-Congo hemorrhagic fever, and dengue viruses. The outbreak was confirmed by isolation of RVF virus from six of the specimens. Humans can be infected with RVF virus from bites of mosquitoes or other arthropod vectors that have fed on animals infected with RVF virus, or through contact with viremic animals, particularly livestock. Reports of livestock deaths and unexplained animal abortions in NEP provided further evidence of an RVF outbreak. On December 20, an investigation was launched by KMOH, the Kenya Field Epidemiology and Laboratory Training Program (FELTP), the Kenya Medical Research Institute (KEMRI), the Walter Reed Project of the U.S. Army Medical Research Unit, CDC-Kenya's Global Disease Detection Center, and other partners, including the World Health Organization (WHO) and Médecins Sans Frontières (MSF). This report describes the findings from that initial investigation and the control measures taken in response to the RVF outbreak, which spread to multiple additional provinces and districts, resulting in 404 cases with 118 deaths as of January 25, 2007.

  10. Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2alpha phosphorylation.

    Directory of Open Access Journals (Sweden)

    Tetsuro Ikegami

    2009-02-01

    Full Text Available Rift Valley fever virus (RVFV (genus Phlebovirus, family Bunyaviridae is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-beta mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD or alpha-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR-mediated eukaryotic initiation factor (eIF2alpha phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2alpha accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2alpha phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2alpha phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.

  11. The persistence of rift valley fever in the Jazan region of Saudi Arabia.

    Science.gov (United States)

    Elfadil, A A; Hasab-Allah, K A; Dafa-Allah, O M; Elmanea, A A

    2006-12-01

    A survey was conducted in the Jazan region of Saudi Arabia to investigate the presence of Rift Valley fever (RVF) in sheep and goats, by clinical identification of suspected herds and detection of immunoglobulin M (IgM) antibodies to RVF virus. The level of herd immunity was identified by detecting immunoglobulin G (IgG) antibodies. Rift Valley fever was diagnosed in six out of eight districts included in the survey. Twenty-two animals from 17 herds tested positive for the presence of IgM antibodies against RVF in these districts. The infection rate ranged from 0.12% in the Sabya district to 1.04% in the Jizan district. The level of herd immunity ranged from 22.2% in Jizan to 39.3% in the Alarda district. It can be concluded that the presence of IgM antibodies in clinically suspected herds suggests persistent RVF infection in the Jazan region. Thus, RVF control programmes should be continued to prevent the recurrence of outbreaks in the region and the possible further spread of infection to other regions of Saudi Arabia.

  12. Roles of African swine fever virus structural proteins in viral infection

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    Jia Ning

    2017-06-01

    Full Text Available African swine fever virus (ASFV is a large, double-stranded DNA virus and the sole member of the Asfarviridae family. ASFV infects domestic pigs, wild boars, warthogs, and bush pigs, as well as soft ticks (Ornithodoros erraticus, which likely act as a vector. The major target is swine monocyte-macrophage cells. The virus can cause high fever, haemorrhagic lesions, cyanosis, anorexia, and even fatalities in domestic pigs. Currently, there is no vaccine and effective disease control strategies against its spread are culling infected pigs and maintaining high biosecurity standards. African swine fever (ASF spread to Europe from Africa in the middle of the 20th century, and later also to South America and the Caribbean. Since then, ASF has spread more widely and thus is still a great challenge for swine breeding. The genome of ASFV ranges in length from about 170 to 193 kbp depending on the isolate and contains between 150 and 167 open reading frames (ORFs. The ASFV genome encodes 150 to 200 proteins, around 50 of them structural. The roles of virus structural proteins in viral infection have been described. These proteins, such as pp220, pp62, p72, p54, p30, and CD2v, serve as the major component of virus particles and have roles in attachment, entry, and replication. All studies on ASFV proteins lay a good foundation upon which to clarify the infection mechanism and develop vaccines and diagnosis methods. In this paper, the roles of ASFV structural proteins in viral infection are reviewed.

  13. Emerging vector-borne diseases in dromedaries in Tunisia: West Nile, bluetongue, epizootic haemorrhagic disease and Rift Valley fever

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    Thameur B. Hassine

    2017-03-01

    Full Text Available A total of 118 sera were collected during 2016 from two groups of dromedaries from Kebili and Medenine governorates in the south of Tunisia. The aim of this study was to provide the first serological investigation of four emerging vector-borne diseases in two groups of dromedaries in Tunisia. Sera were tested by ELISA and serum neutralisation test to identify West Nile virus (WNV, bluetongue virus (BTV, epizootic haemorrhagic disease virus (EHDV and Rift Valley fever virus (RVFV. In the first group, the seroprevalence for BTV was 4.6%, while in the second group, it was 25.8% for WNV and 9.7% for BTV. Only serotype 1 was detected for BTV in the two groups. No evidence for circulation of RVF and EHD viruses was revealed. Results indicated that dromedaries can be infected with BTV and WNV, suggesting that this species might play a significant role in the epizootiology of these viral diseases in Tunisia and neighbouring countries.

  14. Emerging vector-borne diseases in dromedaries in Tunisia: West Nile, bluetongue, epizootic haemorrhagic disease and Rift Valley fever.

    Science.gov (United States)

    Hassine, Thameur B; Amdouni, Jihane; Monaco, Federica; Savini, Giovanni; Sghaier, Soufien; Selimen, Imed B; Chandoul, Walid; Hamida, Khaled B; Hammami, Salah

    2017-03-31

    A total of 118 sera were collected during 2016 from two groups of dromedaries from Kebili and Medenine governorates in the south of Tunisia. The aim of this study was to provide the first serological investigation of four emerging vector-borne diseases in two groups of dromedaries in Tunisia. Sera were tested by ELISA and serum neutralisation test to identify West Nile virus (WNV), bluetongue virus (BTV), epizootic haemorrhagic disease virus (EHDV) and Rift Valley fever virus (RVFV). In the first group, the seroprevalence for BTV was 4.6%, while in the second group, it was 25.8% for WNV and 9.7% for BTV. Only serotype 1 was detected for BTV in the two groups. No evidence for circulation of RVF and EHD viruses was revealed. Results indicated that dromedaries can be infected with BTV and WNV, suggesting that this species might play a significant role in the epizootiology of these viral diseases in Tunisia and neighbouring countries.

  15. Biochemical and biophysical characterization of cell-free synthesized Rift Valley fever virus nucleoprotein capsids enables in vitro screening to identify novel antivirals.

    Science.gov (United States)

    Broce, Sean; Hensley, Lisa; Sato, Tomoharu; Lehrer-Graiwer, Joshua; Essrich, Christian; Edwards, Katie J; Pajda, Jacqueline; Davis, Christopher J; Bhadresh, Rami; Hurt, Clarence R; Freeman, Beverly; Lingappa, Vishwanath R; Kelleher, Colm A; Karpuj, Marcela V

    2016-05-14

    Viral capsid assembly involves the oligomerization of the capsid nucleoprotein (NP), which is an essential step in viral replication and may represent a potential antiviral target. An in vitro transcription-translation reaction using a wheat germ (WG) extract in combination with a sandwich ELISA assay has recently been used to identify small molecules with antiviral activity against the rabies virus. Here, we examined the application of this system to viruses with capsids with a different structure, such as the Rift Valley fever virus (RVFV), the etiological agent of a severe emerging infectious disease. The biochemical and immunological characterization of the in vitro-generated RVFV NP assembly products enabled the distinction between intermediately and highly ordered capsid structures. This distinction was used to establish a screening method for the identification of potential antiviral drugs for RVFV countermeasures. These results indicated that this unique analytical system, which combines nucleoprotein oligomerization with the specific immune recognition of a highly ordered capsid structure, can be extended to various viral families and used both to study the early stages of NP assembly and to assist in the identification of potential antiviral drugs in a cost-efficient manner. Reviewed by Jeffry Skolnick and Noah Isakov. For the full reviews please go to the Reviewers' comments section.

  16. The use of Nanotrap particles in the enhanced detection of Rift Valley fever virus nucleoprotein.

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    Nazly Shafagati

    Full Text Available Rift Valley fever virus (RVFV is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. While there are several diagnostic methodologies available for RVFV detection, many are not sensitive enough to diagnose early infections. Furthermore, detection may be hindered by high abundant proteins such as albumin. Previous findings have shown that Nanotrap particles can be used to significantly enhance detection of various small analytes of low abundance. We have expanded upon this repertoire to show that this simple and efficient sample preparation technology can drastically improve the detection of the RVFV nucleoprotein (NP, the most abundant and widely used viral protein for RVFV diagnostics.After screening multiple Nanotrap particle architectures, we found that one particle, NT45, was optimal for RVFV NP capture, as demonstrated by western blotting. NT45 significantly enhanced detection of the NP at levels undetectable without the technology. Importantly, we demonstrated that Nanotrap particles are capable of concentrating NP in a number of matrices, including infected cell lysates, viral supernatants, and animal sera. Specifically, NT45 enhanced detection of NP at various viral titers, multiplicity of infections, and time points. Our most dramatic results were observed in spiked serum samples, where high abundance serum proteins hindered detection of NP without Nanotrap particles. Nanotrap particles allowed for sample cleanup and subsequent detection of RVFV NP. Finally, we demonstrated that incubation of our samples with Nanotrap particles protects the NP from degradation over extended periods of time (up to 120 hours and at elevated temperatures (at 37ºC.This study demonstrates that Nanotrap particles are capable of drastically lowering the limit of detection for RVFV NP by capturing, concentrating, and preserving RVFV NP in clinically relevant matrices. These studies can be extended to

  17. Effect of environmental temperature on the vector competence of mosquitoes for Rift Valley fever virus

    Science.gov (United States)

    Environmental temperature has been shown to affect the ability of mosquitoes to transmit numerous arboviruses and for Rift Valley fever virus (RVFV) in particular. We evaluated the effect of incubation temperatures ranging from 14-26ºC on infection, dissemination, and transmission rates for Culex ta...

  18. Restriction of Rift Valley Fever Virus Virulence in Mosquito Cells

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    Sonja R. Gerrard

    2010-02-01

    Full Text Available Arboviruses are maintained in a natural cycle that requires blood-sucking arthropod and vertebrate hosts. Arboviruses are believed to persistently infect their arthropod host without overt pathology and cause acute infection with viremia in their vertebrate host. We have focused on elucidating how a specific arbovirus, Rift Valley fever (RVF virus, causes cytopathic effect in cells derived from vertebrates and non-cytopathic infection in cells derived from arthropods. We demonstrate that the vertebrate virulence factor, NSs, is functional in arthropod cells but is expressed at significantly lower levels in infected arthropod versus infected vertebrate cells.

  19. HMGB1 Is a Potential Biomarker for Severe Viral Hemorrhagic Fevers.

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    Katarina Resman Rus

    2016-06-01

    Full Text Available Hemorrhagic fever with renal syndrome (HFRS and Crimean-Congo hemorrhagic fever (CCHF are common representatives of viral hemorrhagic fevers still often neglected in some parts of the world. Infection with Dobrava or Puumala virus (HFRS and Crimean-Congo hemorrhagic fever virus (CCHFV can result in a mild, nonspecific febrile illness or as a severe disease with hemorrhaging and high fatality rate. An important factor in optimizing survival rate in patients with VHF is instant recognition of the severe form of the disease for which significant biomarkers need to be elucidated. To determine the prognostic value of High Mobility Group Box 1 (HMGB1 as a biomarker for disease severity, we tested acute serum samples of patients with HFRS or CCHF. Our results showed that HMGB1 levels are increased in patients with CCHFV, DOBV or PUUV infection. Above that, concentration of HMGB1 is higher in patients with severe disease progression when compared to the mild clinical course of the disease. Our results indicate that HMGB1 could be a useful prognostic biomarker for disease severity in PUUV and CCHFV infection, where the difference between the mild and severe patients group was highly significant. Even in patients with severe DOBV infection concentrations of HMGB1 were 2.8-times higher than in the mild group, but the difference was not statistically significant. Our results indicated HMGB1 as a potential biomarker for severe hemorrhagic fevers.

  20. Febres hemorrágicas por vírus no Brasil Viral hemorrhagic fevers in Brazil

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    Luiz Tadeu Moraes Figueiredo

    2006-04-01

    Full Text Available Chamando a atenção para as febres hemorrágicas por vírus, que em sua maioria tem escassa informação divulgada e provavelmente são subnotificadas, mostra-se neste artigo casos clínicos das 4 doenças deste tipo que ocorrem no Brasil: febre amarela, dengue hemorrágico/síndrome de choque do dengue, febre hemorrágica por arenavírus e síndrome pulmonar e cardiovascular por hantavírus. Também, relevantes aspectos clínicos, laboratoriais e epidemiológicos destas viroses são aqui abordados. São doenças que têm alta letalidade e induzem extravasamento capilar e coagulopatia, que podem ser evidenciados pela elevação do hematócrito e plaquetopenia. A suspeita clínica e o tratamento precoce são fundamentais à sobrevida dos pacientes.To call atention to viral hemorrhagic fevers, diseases that are mostly underdivulged and, probably, undereported, we present here case reports of the 4 diseases of this kind that occur in Brazil: yellow fever, dengue haemorrhagic fever/dengue shock syndrome, arenavirus haemorrhagic fever and hantavirus cardiopulmonary syndrome. Relevant clinical, epidemiological and laboratorial diagnostic aspects of these viral haemorrhagic fevers are also shown here. These diseases have a high case fatality rate, induce capillary leaking and blood coagulation disturbances that are evidenced by hemoconcentrantion and thrombocytopenia. An early clinical diagnosis and treatment is fundamental for patient survival.

  1. [Microbiological surveillance: viral hemorrhagic fever in Central African Republic: current serological data in man].

    Science.gov (United States)

    Nakounné, E; Selekon, B; Morvan, J

    2000-01-01

    An investigation was conducted between 1994 and 1997 in forested areas of the Central African Republic (CAR) to determine the seroprevalence of IgG antibodies against several haemorrhagic fever viruses present in the region. Sera were obtained from 1762 individuals in two groups (Pygmy and Bantu locuted populations) living in 4 forested areas in the south of the country. Sera were tested for IgG antibodies against Ebola, Marburg, Rift Valley fever (RVF), Yellow fever (YF) and Hantaviruses by enzyme immunoassay (EIA), and against Lassa virus by immunofluorescent assay. The prevalence of IgG antibodies was 5.9% for Ebola, 2% for Marburg, 6.9% pour RVF, 6.5% for YF, 2% for Hantaan. No antibodies were detected against Lassa, Seoul, Puumala and Thottapalayam viruses. No IgM antibodies were detected against RVF and YF viruses. The distribution of antibodies appears to be related to tropical rain forest areas. This study indicates that several haemorrhagic fever viruses are endemic in forested areas of the CAR and could emerge due to environmental modification.

  2. Four-segmented Rift Valley fever virus-based vaccines can be applied safely in ewes during pregnancy

    NARCIS (Netherlands)

    Wichgers Schreur, Paul J.; Keulen, van Lucien; Kant-Eenbergen, Jet; Kortekaas, Jeroen

    2017-01-01

    Rift Valley fever virus (RVFV) causes severe and recurrent outbreaks on the African continent and the Arabian Peninsula and continues to expand its habitat. This mosquito-borne virus, belonging to the genus Phlebovirus of the family Bunyaviridae contains a tri-segmented negative-strand RNA

  3. 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.

  4. Potential for Mosquitoes (Diptera: Culicidae) From Florida to Transmit Rift Valley Fever Virus

    Science.gov (United States)

    2013-09-01

    signiÞcant disease and economic disruption. Rift Valley fever virus (RVFV), whichhasbeen responsible fornumerousoutbreaksof severe disease in ruminants and...is predominately a disease of domestic ruminants (cattle, goats, and sheep), where infection in pregnant animals usually results in abortion, and...www.cdc.gov/EID/ content /13/8/e1.htm). Britch, S.C.,K. J.Linthicum,A.Anyamba,C. J.Tucker,E.W. Pak, F. A. Maloney, K. Cobb, E. Stanwix, J. Humphries, A

  5. Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oral administration of the transgenic plants.

    Science.gov (United States)

    Kalbina, Irina; Lagerqvist, Nina; Moiane, Bélisario; Ahlm, Clas; Andersson, Sören; Strid, Åke; Falk, Kerstin I

    2016-11-01

    The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula. The economic impact of this pathogen due to livestock losses, as well as its relevance to public health, underscores the importance of developing effective and easily distributed vaccines. Vaccines that can be delivered orally are of particular interest. Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virus antigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein. Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Western blotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicity in mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportion of the mice elicited specific IgG antibody responses, as compared to the control animals that were fed wild-type plants and of which none sero-converted. Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virus proteins, and that the plants are immunogenic when given orally to mice. These are promising findings and provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Knowledge, attitudes and practices on Rift Valley fever among agro pastoral communities in Kongwa and Kilombero districts, Tanzania.

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    Shabani, Sasita S; Ezekiel, Mangi J; Mohamed, Mohamed; Moshiro, Candida S

    2015-08-21

    Rift valley fever (RVF) is a re-emerging viral vector-borne disease with rapid global socio-economic impact. A large RVF outbreak occurred in Tanzania in 2007 and affected more than half of the regions with high (47 %) case fatality rate. Little is known about RVF and its dynamics. A cross sectional study was conducted to assess the knowledge, attitudes and practices regarding RVF in Kongwa and Kilombero districts, Tanzania. We conducted a cross sectional survey among a randomly selected sample of individuals in 2011. We administered questionnaires to collect data on demographic characteristics, knowledge on symptoms, mode of transmission, prevention, attitudes and health seeking practices. A total of 463 community members participated in this study. The mean (±SD) age was 39.8 ± 14.4 years and 238 (51.4 %) were female. Majority of respondents had heard of RVF. However, only 8.8 % knew that mosquitoes were transmitting vectors. Male respondents were more likely to have greater knowledge about RVF. A small proportion mentioned clinical signs and symptoms of RVF in animals while 73.7 % mentioned unhealthy practices related to handling and consumption of dead animals. Thorough boiling of milk and cooking of meat were commonly mentioned as preventive measures for RVF. Majority (74.6 %) sought care for febrile illness at health facilities. Few (24.3 %) reported the use of protective gears to handle dead/sick animal while 15.5 % were consuming dead animals. Our study highlights the need to address the limited knowledge about RVF and promoting appropriate and timely health seeking practices. Rift valley fever outbreaks can be effectively managed with collaborative efforts of lay and professional communities with a shared perception that it poses a serious threat to public and animal health. The fact that this study was conducted in "high risk transmission areas" warrants further inquiry in other geographic regions with relatively low risk of RVF.

  7. Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR.

    Science.gov (United States)

    Nishiyama, Shoko; Slack, Olga A L; Lokugamage, Nandadeva; Hill, Terence E; Juelich, Terry L; Zhang, Lihong; Smith, Jennifer K; Perez, David; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

    2016-11-16

    Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker.

  8. Ecological niche modelling of Rift Valley fever virus vectors in Baringo, Kenya

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    Alfred O. Ochieng

    2016-11-01

    Full Text Available Background: Rift Valley fever (RVF is a vector-borne zoonotic disease that has an impact on human health and animal productivity. Here, we explore the use of vector presence modelling to predict the distribution of RVF vector species under climate change scenario to demonstrate the potential for geographic spread of Rift Valley fever virus (RVFV. Objectives: To evaluate the effect of climate change on RVF vector distribution in Baringo County, Kenya, with an aim of developing a risk map for spatial prediction of RVF outbreaks. Methodology: The study used data on vector presence and ecological niche modelling (MaxEnt algorithm to predict the effect of climatic change on habitat suitability and the spatial distribution of RVF vectors in Baringo County. Data on species occurrence were obtained from longitudinal sampling of adult mosquitoes and larvae in the study area. We used present (2000 and future (2050 Bioclim climate databases to model the vector distribution. Results: Model results predicted potential suitable areas with high success rates for Culex quinquefasciatus, Culex univitattus, Mansonia africana, and Mansonia uniformis. Under the present climatic conditions, the lowlands were found to be highly suitable for all the species. Future climatic conditions indicate an increase in the spatial distribution of Cx. quinquefasciatus and M. africana. Model performance was statistically significant. Conclusion: Soil types, precipitation in the driest quarter, precipitation seasonality, and isothermality showed the highest predictive potential for the four species.

  9. Outbreak of viral hemorrhagic fever caused by dengue virus type 3 in Al-Mukalla, Yemen.

    Science.gov (United States)

    Madani, Tariq A; Abuelzein, El-Tayeb M E; Al-Bar, Hussein M S; Azhar, Esam I; Kao, Moujahed; Alshoeb, Haj O; Bamoosa, Alabd R

    2013-03-14

    Investigations were conducted by the authors to explore an outbreak of viral hemorrhagic fever (VHF) reported in 2010 from Al-Mukalla city, the capital of Hadramout in Yemen. From 15-17 June 2010, the outbreak investigation period, specimens were obtained within 7 days after onset of illness of 18 acutely ill patients hospitalized with VHF and 15 household asymptomatic contacts of 6 acute cases. Additionally, 189 stored sera taken from acutely ill patients with suspected VHF hospitalized in the preceding 12 months were obtained from the Ministry of Health of Yemen. Thus, a total of 222 human specimens were collected; 207 specimens from acute cases and 15 specimens from contacts. All samples were tested with RT-PCR for dengue (DENV), Alkhumra (ALKV), Rift Valley Fever (RVFV), Yellow Fever (YFV), and Chikungunya (CHIKV) viruses. Samples were also tested for DENV IgM, IgG, and NS1-antigen. Medical records of patients were reviewed and demographic, clinical, and laboratory data was collected. Of 207 patients tested, 181 (87.4%) patients were confirmed to have acute dengue with positive dengue NS1-antigen (97 patients, 46.9%) and/or IgM (163 patients, 78.7%). Of the 181 patients with confirmed dengue, 100 (55.2%) patients were IgG-positive. DENV RNA was detected in 2 (1%) patients with acute symptoms; both samples were molecularly typed as DENV type 3. No other VHF viruses were detected. For the 15 contacts tested, RT-PCR tests for the five viruses were negative, one contact was dengue IgM positive, and another one was dengue IgG positive. Of the 181 confirmed dengue patients, 120 (66.3%) patients were males and the median age was 24 years. The most common manifestations included fever (100%), headache (94.5%), backache (93.4%), malaise (88.4%), arthralgia (85.1%), myalgia (82.3%), bone pain (77.9%), and leukopenia (76.2%). Two (1.1%) patients died. DENV-3 was confirmed to be the cause of an outbreak of VHF in Al-Mukalla. It is important to use both IgM and NS1-antigen

  10. Outbreak of viral hemorrhagic fever caused by dengue virus type 3 in Al-Mukalla, Yemen

    Science.gov (United States)

    2013-01-01

    Background Investigations were conducted by the authors to explore an outbreak of viral hemorrhagic fever (VHF) reported in 2010 from Al-Mukalla city, the capital of Hadramout in Yemen. Methods From 15–17 June 2010, the outbreak investigation period, specimens were obtained within 7 days after onset of illness of 18 acutely ill patients hospitalized with VHF and 15 household asymptomatic contacts of 6 acute cases. Additionally, 189 stored sera taken from acutely ill patients with suspected VHF hospitalized in the preceding 12 months were obtained from the Ministry of Health of Yemen. Thus, a total of 222 human specimens were collected; 207 specimens from acute cases and 15 specimens from contacts. All samples were tested with RT-PCR for dengue (DENV), Alkhumra (ALKV), Rift Valley Fever (RVFV), Yellow Fever (YFV), and Chikungunya (CHIKV) viruses. Samples were also tested for DENV IgM, IgG, and NS1-antigen. Medical records of patients were reviewed and demographic, clinical, and laboratory data was collected. Results Of 207 patients tested, 181 (87.4%) patients were confirmed to have acute dengue with positive dengue NS1-antigen (97 patients, 46.9%) and/or IgM (163 patients, 78.7%). Of the 181 patients with confirmed dengue, 100 (55.2%) patients were IgG-positive. DENV RNA was detected in 2 (1%) patients with acute symptoms; both samples were molecularly typed as DENV type 3. No other VHF viruses were detected. For the 15 contacts tested, RT-PCR tests for the five viruses were negative, one contact was dengue IgM positive, and another one was dengue IgG positive. Of the 181 confirmed dengue patients, 120 (66.3%) patients were males and the median age was 24 years. The most common manifestations included fever (100%), headache (94.5%), backache (93.4%), malaise (88.4%), arthralgia (85.1%), myalgia (82.3%), bone pain (77.9%), and leukopenia (76.2%). Two (1.1%) patients died. Conclusions DENV-3 was confirmed to be the cause of an outbreak of VHF in Al

  11. The Rift Valley fever: could re-emerge in Egypt again?

    Science.gov (United States)

    El-Bahnasawy, Mamdouh; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

    2013-04-01

    The Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus of the family of Bunyaviridae, genus Phlebovirus. RVF is an acute, febrile disease affecting humans and a wide range of animals. The virus is trans-mitted through the bites from mosquitoes and exposure to viremic blood, body fluids, or contact with tissues of infected animals or by inhaling natural virus aerosols, also possibly by consumption of infected unpasteurized milk. The RVF-virus replicate at the site introduction and in local lymphatic followed by viremia and spread to other organs as the liver and central nervous system, causing the hepatic necrosis and eosinophilia cytoplasmic degeneration. The main signs and symptoms are fever, headache, myalgia, arthralgia, photophobia, bradycardia, conjunctivitis and flushing face. Main complications include jaundice, hemorrhagic, meningoencephalitis and retinal lesions. Generally speaking, in the 21st Century, the vector-borne infectious diseases, was accepted as the disaster issues with the considerable significant morbidity and mortality. These facts should be considered by the public health, veterinary and agricultural authorities

  12. Identification of a major non-structural protein in the nuclei of Rift Valley fever virus-infected cells.

    Science.gov (United States)

    Struthers, J K; Swanepoel, R

    1982-06-01

    A non-structural protein of mol. wt. 34 X 10(3) was demonstrated in the nuclei of Rift Valley fever virus-infected Vero cells by SDS-polyacrylamide gel electro-phoresis. The protein appears to correspond to the virus-induced antigen demonstrated by indirect immunofluorescence in intranuclear inclusions.

  13. Chemotactic and inflammatory responses in the liver and brain are associated with pathogenesis of Rift Valley fever virus infection in the mouse.

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    Kimberly K Gray

    Full Text Available Rift Valley fever virus (RVFV is a major human and animal pathogen associated with severe disease including hemorrhagic fever or encephalitis. RVFV is endemic to parts of Africa and the Arabian Peninsula, but there is significant concern regarding its introduction into non-endemic regions and the potentially devastating effect to livestock populations with concurrent infections of humans. To date, there is little detailed data directly comparing the host response to infection with wild-type or vaccine strains of RVFV and correlation with viral pathogenesis. Here we characterized clinical and systemic immune responses to infection with wild-type strain ZH501 or IND vaccine strain MP-12 in the C57BL/6 mouse. Animals infected with live-attenuated MP-12 survived productive viral infection with little evidence of clinical disease and minimal cytokine response in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion of lymphocytes and platelets and elicited a strong, systemic cytokine response which correlated with high virus titers and significant tissue pathology. Lymphopenia and platelet depletion were indicators of disease onset with indications of lymphocyte recovery correlating with increases in G-CSF production. RVFV is hepatotropic and in these studies significant clinical and histological data supported these findings; however, significant evidence of a pro-inflammatory response in the liver was not apparent. Rather, viral infection resulted in a chemokine response indicating infiltration of immunoreactive cells, such as neutrophils, which was supported by histological data. In brains of ZH501 infected mice, a significant chemokine and pro-inflammatory cytokine response was evident, but with little pathology indicating meningoencephalitis. These data suggest that RVFV pathogenesis in mice is associated with a loss of liver function due to liver necrosis and hepatitis yet the long-term course of disease for those that

  14. Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus.

    Science.gov (United States)

    Lihoradova, Olga A; Indran, Sabarish V; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

  15. Hospital preparations for viral hemorrhagic fever patients and experience gained from admission of an Ebola patient

    NARCIS (Netherlands)

    Haverkort, J. J Mark; Minderhoud, A.L.C (Ben); Wind, Jelte D D; Leenen, Luke P H; Hoepelman, Andy I M; Ellerbroek, Pauline M.

    2016-01-01

    The Major Incident Hospital of the University Medical Centre of Utrecht has a longstanding history of preparing for the management of highly pathogenic and infectious organisms. An assessment of the hospital’s preparations for an outbreak of viral hemorrhagic fever and its experience during

  16. Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins.

    Science.gov (United States)

    Ly, Hoai J; Ikegami, Tetsuro

    2016-07-02

    Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-β promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses.

  17. An unexpected recurrent transmission of Rift Valley fever virus in cattle in a temperate and mountainous area of Madagascar.

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    Veronique Chevalier

    2011-12-01

    Full Text Available Rift Valley fever is an acute, zoonotic viral disease of domestic ruminants, caused by a phlebovirus (Bunyaviridae family. A large outbreak occurred in Madagascar in 2008-2009. The goal of the present study was to evaluate the point prevalence of antibodies against Rift Valley Fever Virus (RVFV in cattle in the Anjozorobe district, located in the wet and temperate highland region of Madagascar and yet heavily affected by the disease, and analyse environmental and trade factors potentially linked to RVFV transmission. A serological study was performed in 2009 in 894 bovines. For each bovine, the following variables were recorded: age, location of the night pen, minimum distance from the pen to the nearest water point and the forest, nearest water point type, and herd replacement practices. The serological data were analyzed using a generalized linear mixed model. The overall anti-RVFV IgG seroprevalence rate was 28% [CI95% 25-31]. Age was statistically linked to prevalence (p = 10(-4, being consistent with a recurrent RVFV circulation. Distance from the night pen to the nearest water point was a protective factor (p = 5.10(-3, which would be compatible with a substantial part of the virus transmission being carried out by nocturnal mosquito vectors. However, water point type did not influence the risk of infection: several mosquito species are probably involved. Cattle belonging to owners who purchase animals to renew the herd were significantly more likely to have seroconverted than others (p = 0.04: cattle trade may contribute to the introduction of the virus in this area. The minimum distance of the night pen to the forest was not linked to the prevalence. This is the first evidence of a recurrent transmission of RVFV in such an ecosystem that associates a wet, temperate climate, high altitude, paddy fields, and vicinity to a dense rain forest. Persistence mechanisms need to be further investigated.

  18. Emergence of viral hemorrhagic fevers: Is recent outbreak of crimean congo hemorrhagic fever in India an indication?

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    C Lahariya

    2012-01-01

    Full Text Available The emerging and re-emerging diseases are posing a great health risk for the last few years. One such category of diseases is viral haemorrhagic fevers (VHFs, which have emerged in the new territories, worldwide. Crimean Congo Hemorrhagic Fever (CCHF cases, for the first time in India, were reported from Gujarat, in January 2011. The emergence of diseases not reported earlier, pose great economic and social challenge, burden health system, and create panic reaction. Nonetheless, with recent experience in control of epidemic diseases, and advances in basic scientific knowledge; the public health community is better prepared for these unexpected events. This review provides information to physicians on CCHF for managing outbreak, and identifies public health measures to prevent emergence and re-emergence of VHFs (including CCHF in future. The authors suggest that though, there are a few challenging and unanswered questions, the public health preparedness still remains the key to control emerging and re-emerging diseases. The countries where virus activities have been reported need to be prepared accordingly.

  19. The Consequences of Reconfiguring the Ambisense S Genome Segment of Rift Valley Fever Virus on Viral Replication in Mammalian and Mosquito Cells and for Genome Packaging

    Science.gov (United States)

    Elliott, Richard M.

    2014-01-01

    Rift Valley fever virus (RVFV, family Bunyaviridae) is a mosquito-borne pathogen of both livestock and humans, found primarily in Sub-Saharan Africa and the Arabian Peninsula. The viral genome comprises two negative-sense (L and M segments) and one ambisense (S segment) RNAs that encode seven proteins. The S segment encodes the nucleocapsid (N) protein in the negative-sense and a nonstructural (NSs) protein in the positive-sense, though NSs cannot be translated directly from the S segment but rather from a specific subgenomic mRNA. Using reverse genetics we generated a virus, designated rMP12:S-Swap, in which the N protein is expressed from the NSs locus and NSs from the N locus within the genomic S RNA. In cells infected with rMP12:S-Swap NSs is expressed at higher levels with respect to N than in cells infected with the parental rMP12 virus. Despite NSs being the main interferon antagonist and determinant of virulence, growth of rMP12:S-Swap was attenuated in mammalian cells and gave a small plaque phenotype. The increased abundance of the NSs protein did not lead to faster inhibition of host cell protein synthesis or host cell transcription in infected mammalian cells. In cultured mosquito cells, however, infection with rMP12:S-Swap resulted in cell death rather than establishment of persistence as seen with rMP12. Finally, altering the composition of the S segment led to a differential packaging ratio of genomic to antigenomic RNA into rMP12:S-Swap virions. Our results highlight the plasticity of the RVFV genome and provide a useful experimental tool to investigate further the packaging mechanism of the segmented genome. PMID:24550727

  20. Genetic Evidence for an Interferon-Antagonistic Function of Rift Valley Fever Virus Nonstructural Protein NSs

    Science.gov (United States)

    Bouloy, Michèle; Janzen, Christian; Vialat, Pierre; Khun, Huot; Pavlovic, Jovan; Huerre, Michel; Haller, Otto

    2001-01-01

    Rift Valley fever virus (RVFV), a phlebovirus of the family Bunyaviridae, is a major public health threat in Egypt and sub-Saharan Africa. The viral and host cellular factors that contribute to RVFV virulence and pathogenicity are still poorly understood. All pathogenic RVFV strains direct the synthesis of a nonstructural phosphoprotein (NSs) that is encoded by the smallest (S) segment of the tripartite genome and has an undefined accessory function. In this report, we show that MP12 and clone 13, two attenuated RVFV strains with mutations in the NSs gene, were highly virulent in IFNAR−/− mice lacking the alpha/beta interferon (IFN-α/β) receptor but remained attenuated in IFN-γ receptor-deficient mice. Both attenuated strains proved to be excellent inducers of early IFN-α/β production. In contrast, the virulent strain ZH548 failed to induce detectable amounts of IFN-α/β and replicated extensively in both IFN-competent and IFN-deficient mice. Clone 13 has a defective NSs gene with a large in-frame deletion. This defect in the NSs gene results in expression of a truncated protein which is rapidly degraded. To investigate whether the presence of the wild-type NSs gene correlated with inhibition of IFN-α/β production, we infected susceptible IFNAR−/− mice with S gene reassortant viruses. When the S segment of ZH548 was replaced by that of clone 13, the resulting reassortants became strong IFN inducers. When the defective S segment of clone 13 was exchanged with the wild-type S segment of ZH548, the reassortant virus lost the capacity to stimulate IFN-α/β production. These results demonstrate that the ability of RVFV to inhibit IFN-α/β production correlates with viral virulence and suggest that the accessory protein NSs is an IFN antagonist. PMID:11152510

  1. Rift Valley fever: current challenges and future prospects

    Directory of Open Access Journals (Sweden)

    Himeidan YE

    2016-03-01

    Full Text Available Yousif E Himeidan Vector Control Unit, Africa Technical Research Centre, Vector Health International, Arusha, Tanzania Abstract: Rift Valley fever (RVF is a zoonotic, mosquito-borne viral disease that affects human health and causes significant losses in the livestock industry. Recent outbreaks have led to severe human infections with high mortality rates. There are many challenges to applying effective preventive and control measures, including weak infrastructure of health facilities, lack of capacity and support systems for field logistics and communication, access to global expert organizations, and insufficient information on the epidemiological and reservoir status of the RVF virus. The health systems in East African countries are underdeveloped, with gaps in adaptability to new, more accurate and rapid techniques, and well-trained staff that affect their capacity to monitor and evaluate the disease. Surveillance and response systems are inadequate in providing accurate information in a timely manner for decision making to deal with the scope of interrupting the disease transmission by applying mass animal vaccination, and other preventive measures at the early stage of an outbreak. The historical vaccines are unsuitable for use in newborn and gestating livestock, and the recent ones require a booster and annual revaccination. Future live-attenuated RVF vaccines should possess lower safety concerns regardless of the physiologic state of the animal, and provide rapid and long-term immunity after a single dose of vaccination. In the absence of an effective vaccination program, prevention and control measures must be immediately undertaken after an alert is generated. These measures include enforcing and adapting standard protocols for animal trade and movement, extensive vector control, safe disposal of infected animals, and modification of human–animal contact behavior. Directing control efforts on farmers and workers who deal with

  2. [Rift Valley fever: sporadic infection of French military personnel outside currently recognized epidemic zones].

    Science.gov (United States)

    Durand, J P; Richecoeur, L; Peyrefitte, C; Boutin, J P; Davoust, B; Zeller, H; Bouloy, M; Tolou, H

    2002-01-01

    For three years the arbovirus surveillance unit of the Tropical Medicine Institute of the French Army Medical Corps (French acronym IMTSSA) in Marseille, France has been investigating causes of benign non-malarial febrile syndromes in French military personnel serving outside mainland France. The methodology used in N'Djamena consisted of sending frozen specimens collected concomitant with viremia, to Marseille for culture. During the rainy season of 2001, specimens were collected from a total of 50 febrile soldiers. Cultures allowed isolation and identification of two strains of Rift Valley virus. The risk of contamination exists not only in the field but also in mainland hospital departments treating infected patients. Routine serological diagnosis for Rift Valley fever must be DISCUSSED for all patients in the field or returning from Africa.

  3. Rift Valley fever virus NS{sub S} gene expression correlates with a defect in nuclear mRNA export

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Anna Maria; Van Deusen, Nicole M.; Schmaljohn, Connie S., E-mail: Connie.s.schmaljohn.civ@mail.mil

    2015-12-15

    We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NS{sub S} gene, but not the N, G{sub N} or NS{sub M} genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NS{sub S}, confirming that expression of NS{sub S} is likely responsible for this phenomenon. - Highlights: • Rift Valley fever virus (RVFV) infection alters the localization of host mRNA. • mRNA accumulates in the nuclei of RVFV-infected but not mock-infected cells. • NS{sub S} is likely responsible for mRNA relocalization to the nucleus.

  4. Arthropod-borne viral infections associated with a fever outbreak in the northern province of Sudan.

    Science.gov (United States)

    Watts, D M; el-Tigani, A; Botros, B A; Salib, A W; Olson, J G; McCarthy, M; Ksiazek, T G

    1994-08-01

    An outbreak of acute febrile illness occurred during August and September 1989 in the Northern Province of Sudan coinciding with a high population density of phlebotomine sandflies. An investigation was conducted to determine whether arboviruses were associated with human illness during this outbreak. Sera were obtained from 185 febrile individuals and tested for IgG and IgM antibody to selected arboviruses by enzyme immunoassay (EIA). The prevalence of IgG antibody was 59% for West Nile (WN), 53% for Sandfly Fever Sicilian (SFS), 32% for Sandfly Fever Naples (SFN), 39% for Yellow Fever (YF), 24% for dengue-2 (DEN-2), 23% for Rift Valley Fever (RVF), 12% for Chikungunya (CHIK) and 5% for Crimean-Congo haemorrhagic Fever (CCHF) viruses. Antibody prevalences tended to increase with age for WN and YF viruses. Antibody rates were about the same for males and females for most of the viruses tested. The prevalence of IgM antibody to SFN was 24% and reciprocal IgM titre exceeded 12,800 for some individuals suggesting that this virus was the cause of recent infection. The prevalence of IgM antibody for the other viruses did not exceed 5%. The study indicated that several arboviruses were endemic and some of them may have caused human disease in the Northern Province of Sudan.

  5. NSs protein of severe fever with thrombocytopenia syndrome virus suppresses interferon production through different mechanism than Rift Valley fever virus.

    Science.gov (United States)

    Zhang, S; Zheng, B; Wang, T; Li, A; Wan, J; Qu, J; Li, C H; Li, D; Liang, M

    Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified Phlebovirus that causes severe fever with thrombocytopenia syndrome. Our study demonstrated that SFTSV NSs functioned as IFN antagonist mainly by suppressing TBK1/IKKε-IRF3 signaling pathway. NSs interacted with and relocalized TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures and this interaction could effectively inhibit downstream phosphorylation and dimerization of interferon regulatory factor 3 (IRF3), resulting in the suppression of antiviral signaling and IFN induction. Functional sites of SFTSV NSs binding with TBK1 were then studied and results showed that NSs had lost their IFN-inhibiting activity after deleting the 25 amino acids in N-terminal. Furthermore, the mechanism of Rift Valley fever virus (RVFV) NSs blocking IFN-β response were also investigated. Preliminary results showed that RVFV NSs proteins could neither interact nor co-localize with TBK1 in cytoplasm, but suppressed its expression levels, phosphorylation and dimerization of IRF3 in the subsequent steps, resulting in inhibition of the IFN-β production. Altogether, our data demonstrated the probable mechanism used by SFTSV to inhibit IFN responses which was different from RVFV and pointed toward a novel mechanism for RVFV suppressing IFN responses.

  6. Remote Sensing Contributions to Prediction and Risk Assessment of Natural Disasters Caused by Large Scale Rift Valley Fever Outbreaks

    Science.gov (United States)

    Anyamba, Assaf; Linthicum, Kenneth J.; Small, Jennifer; Britch, S. C.; Tucker, C. J.

    2012-01-01

    Remotely sensed vegetation measurements for the last 30 years combined with other climate data sets such as rainfall and sea surface temperatures have come to play an important role in the study of the ecology of arthropod-borne diseases. We show that epidemics and epizootics of previously unpredictable Rift Valley fever are directly influenced by large scale flooding associated with the El Ni o/Southern Oscillation. This flooding affects the ecology of disease transmitting arthropod vectors through vegetation development and other bioclimatic factors. This information is now utilized to monitor, model, and map areas of potential Rift Valley fever outbreaks and is used as an early warning system for risk reduction of outbreaks to human and animal health, trade, and associated economic impacts. The continuation of such satellite measurements is critical to anticipating, preventing, and managing disease epidemics and epizootics and other climate-related disasters.

  7. Innate Immune Response to Rift Valley Fever Virus in Goats

    Science.gov (United States)

    Nfon, Charles K.; Marszal, Peter; Zhang, Shunzhen; Weingartl, Hana M.

    2012-01-01

    Rift Valley fever (RVF), a re-emerging mosquito-borne disease of ruminants and man, was endemic in Africa but spread to Saudi Arabia and Yemen, meaning it could spread even further. Little is known about innate and cell-mediated immunity to RVF virus (RVFV) in ruminants, which is knowledge required for adequate vaccine trials. We therefore studied these aspects in experimentally infected goats. We also compared RVFV grown in an insect cell-line and that grown in a mammalian cell-line for differences in the course of infection. Goats developed viremia one day post infection (DPI), which lasted three to four days and some goats had transient fever coinciding with peak viremia. Up to 4% of peripheral blood mononuclear cells (PBMCs) were positive for RVFV. Monocytes and dendritic cells in PBMCs declined possibly from being directly infected with virus as suggested by in vitro exposure. Infected goats produced serum IFN-γ, IL-12 and other proinflammatory cytokines but not IFN-α. Despite the lack of IFN-α, innate immunity via the IL-12 to IFN-γ circuit possibly contributed to early protection against RVFV since neutralising antibodies were detected after viremia had cleared. The course of infection with insect cell-derived RVFV (IN-RVFV) appeared to be different from mammalian cell-derived RVFV (MAM-RVFV), with the former attaining peak viremia faster, inducing fever and profoundly affecting specific immune cell subpopulations. This indicated possible differences in infections of ruminants acquired from mosquito bites relative to those due to contact with infectious material from other animals. These differences need to be considered when testing RVF vaccines in laboratory settings. PMID:22545170

  8. Chikungunya fever: A re-emerging viral infection

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    Chhabra M

    2008-01-01

    Full Text Available Chikungunya (CHIK fever is a re-emerging viral disease characterized by abrupt onset of fever with severe arthralgia followed by constitutional symptoms and rash lasting for 1-7 days. The disease is almost self-limiting and rarely fatal. Chikungunya virus (CHIKV is a RNA virus belonging to family Togaviridae, genus Alphavirus. Molecular characterization has demonstrated two distinct lineages of strains which cause epidemics in Africa and Asia. These geographical genotypes exhibit differences in the transmission cycles. In contrast to Africa where sylvatic cycle is maintained between monkeys and wild mosquitoes, in Asia the cycle continues between humans and the Aedes aegypti mosquito. CHIKV is known to cause epidemics after a period of quiescence. The first recorded epidemic occurred in Tanzania in 1952-1953. In Asia, CHIK activity was documented since its isolation in Bangkok, Thailand in 1958. Virus transmission continued till 1964. After hiatus, the virus activity re-appeared in the mid-1970s and declined by 1976. In India, well-documented outbreaks occurred in 1963 and 1964 in Kolkata and southern India, respectively. Thereafter, a small outbreak of CHIK was reported from Sholapur district, Maharashtra in 1973. CHIKV emerged in the islands of South West Indian Ocean viz. French island of La Reunion, Mayotee, Mauritius and Seychelles which are reporting the outbreak since February, 2005. After quiescence of about three decades, CHIKV re-emerged in India in the states of Andhra Pradesh, Karnataka, Maharashtra, Madhya Pradesh and Tamil Nadu since December, 2005. Cases have also been reported from Rajasthan, Gujarat and Kerala. The outbreak is still continuing. National Institute of Communicable Diseases has conducted epidemiological, entomological and laboratory investigations for confirmation of the outbreak. These have been discussed in detail along with the major challenges that the country faced during the current outbreak.

  9. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

    Science.gov (United States)

    Warimwe, George M; Lorenzo, Gema; Lopez-Gil, Elena; Reyes-Sandoval, Arturo; Cottingham, Matthew G; Spencer, Alexandra J; Collins, Katharine A; Dicks, Matthew D J; Milicic, Anita; Lall, Amar; Furze, Julie; Turner, Alison V; Hill, Adrian V S; Brun, Alejandro; Gilbert, Sarah C

    2013-12-05

    Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

  10. NSs protein of rift valley fever virus induces the specific degradation of the double-stranded RNA-dependent protein kinase.

    Science.gov (United States)

    Habjan, Matthias; Pichlmair, Andreas; Elliott, Richard M; Overby, Anna K; Glatter, Timo; Gstaiger, Matthias; Superti-Furga, Giulio; Unger, Hermann; Weber, Friedemann

    2009-05-01

    Rift Valley fever virus (RVFV) continues to cause large outbreaks of acute febrile and often fatal illness among humans and domesticated animals in Africa, Saudi Arabia, and Yemen. The high pathogenicity of this bunyavirus is mainly due to the viral protein NSs, which was shown to prevent transcriptional induction of the antivirally active type I interferons (alpha/beta interferon [IFN-alpha/beta]). Viruses lacking the NSs gene induce synthesis of IFNs and are therefore attenuated, whereas the noninducing wild-type RVFV strains can only be inhibited by pretreatment with IFN. We demonstrate here in vitro and in vivo that a substantial part of the antiviral activity of IFN against RVFV is due to a double-stranded RNA-dependent protein kinase (PKR). PKR-mediated virus inhibition, however, was much more pronounced for the strain Clone 13 with NSs deleted than for the NSs-expressing strain ZH548. In vivo, Clone 13 was nonpathogenic for wild-type (wt) mice but could regain pathogenicity if mice lacked the PKR gene. ZH548, in contrast, killed both wt and PKR knockout mice indiscriminately. ZH548 was largely resistant to the antiviral properties of PKR because RVFV NSs triggered the specific degradation of PKR via the proteasome. The NSs proteins of the related but less virulent sandfly fever Sicilian virus and La Crosse virus, in contrast, had no such anti-PKR activity despite being efficient suppressors of IFN induction. Our data suggest that RVFV NSs has gained an additional anti-IFN function that may explain the extraordinary pathogenicity of this virus.

  11. Identification of mutations in the M RNA of a candidate vaccine strain of Rift Valley fever virus.

    Science.gov (United States)

    Takehara, K; Min, M K; Battles, J K; Sugiyama, K; Emery, V C; Dalrymple, J M; Bishop, D H

    1989-04-01

    The M RNA species of a candidate vaccine strain of Rift Valley fever virus (RVFV ZH-548M12), derived by consecutive high level mutagenesis using 5-fluorouracil (H. Caplen, C. J. Peters, and D. H. L. Bishop, J. Gen. Virol., 66, 2271-2277, 1985), has been cloned and the cDNA sequenced. The data have been compared to those obtained for the parent virus strain RVFV ZH-548 as well as the previously published data for RVFV ZH-501 (M. S. Collett, A. F. Purchio, K. Keegan, S. Frazier, W. Hays, D. K. Anderson, M. D. Parker, C. Schmaljohn, J. Schmidt, and J. M. Dalrymple, Virology, 144, 228-245, 1985). Some eight nucleotide and three amino acid differences were identified between the M RNAs of ZH-501 and ZH-548. Between the M RNAs of ZH-548 and that of the M12 mutant there were 12 nucleotide and 7 amino acid changes. Unique to the mutant virus is a new AUG codon upstream of that which initiates the open reading frame of the RVFV M gene product (the viral glycoprotein precursor). The significance of this and other differences in the mutant RNA with regard to the derivation and potential attenuation of the candidate vaccine is discussed.

  12. Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR.

    Science.gov (United States)

    Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V; Lokugamage, Nandadeva; Head, Jennifer A; Ikegami, Tetsuro

    2013-01-20

    Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Fever with Rashes.

    Science.gov (United States)

    Soman, Letha

    2018-07-01

    Fever with rashes is one of the commonest clinical problems a general practitioner or pediatrician has to face in day-to-day clinical practice. It can be a mild viral illness or a life-threatening illness like meningococcemia or Dengue hemorrhagic fever or it can be one with a lifelong consequence like Kawasaki disease. It is very important to arrive at a clinical diagnosis as early as possible with the minimum investigational facilities. The common causes associated with fever and rashes are infections, viral followed by other infections. There can be so many non-infectious causes also for fever and rashes like auto immune diseases, drug allergies etc. The type of rashes, their appearance in relation to the fever and pattern of spread to different parts of body and the disappearance, all will help in making a diagnosis. Often the diagnosis is clinical. In certain situations laboratory work up becomes essential.

  14. Rift Valley Fever Outbreaks in Mauritania and Related Environmental Conditions

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    Cyril Caminade

    2014-01-01

    Full Text Available Four large outbreaks of Rift Valley Fever (RVF occurred in Mauritania in 1998, 2003, 2010 and 2012 which caused lots of animal and several human deaths. We investigated rainfall and vegetation conditions that might have impacted on RVF transmission over the affected regions. Our results corroborate that RVF transmission generally occurs during the months of September and October in Mauritania, similarly to Senegal. The four outbreaks were preceded by a rainless period lasting at least a week followed by heavy precipitation that took place during the second half of the rainy season. First human infections were generally reported three to five weeks later. By bridging the gap between meteorological forecasting centers and veterinary services, an early warning system might be developed in Senegal and Mauritania to warn decision makers and health services about the upcoming RVF risk.

  15. Wetlands, wild Bovidae species richness and sheep density delineate risk of Rift Valley fever outbreaks in the African continent and Arabian Peninsula.

    Directory of Open Access Journals (Sweden)

    Michael G Walsh

    2017-07-01

    Full Text Available Rift Valley fever (RVF is an emerging, vector-borne viral zoonosis that has significantly impacted public health, livestock health and production, and food security over the last three decades across large regions of the African continent and the Arabian Peninsula. The potential for expansion of RVF outbreaks within and beyond the range of previous occurrence is unknown. Despite many large national and international epidemics, the landscape epidemiology of RVF remains obscure, particularly with respect to the ecological roles of wildlife reservoirs and surface water features. The current investigation modeled RVF risk throughout Africa and the Arabian Peninsula as a function of a suite of biotic and abiotic landscape features using machine learning methods. Intermittent wetland, wild Bovidae species richness and sheep density were associated with increased landscape suitability to RVF outbreaks. These results suggest the role of wildlife hosts and distinct hydrogeographic landscapes in RVF virus circulation and subsequent outbreaks may be underestimated. These results await validation by studies employing a deeper, field-based interrogation of potential wildlife hosts within high risk taxa.

  16. [Viral encephalitis virus, a new bioterrorist menace].

    Science.gov (United States)

    Rigaudeau, Sophie; Micol, Romain; Bricaire, François; Bossi, Philippe

    2005-01-29

    Often responsible for little known infections, today viral encephalitis viruses appear as a new bioterrorist menace, because of their easy production and their great pathogenic potential. Spraying is the best way to permit the rapid diffusion of certain encephalitis viruses. Diagnosis of viral encephalitis, predominating in tropical surroundings, is difficult. In the majority of cases, symptoms differ little from those of common flu. With supplementary examinations, the biological abnormalities are usually non-specific. There are no characteristic images on scans or MRI. Identification of the virus in the nasopharynx, blood or cerebrospinal fluid, in serology, PCR or RT-PCR permits confirmation of the virus. Treatment is essentially symptomatic and relies on appropriate reanimation measures. Ribavirin can be indicated in some cases such as the Rift Valley fever, but is formally contraindicated in West Nile encephalitis. The aim of terrorist groups who would use this type of weapon is more to provoke panic and disorganisation than to kill as many people as possible.

  17. A dynamic, climate-driven model of Rift Valley fever

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    Joseph Leedale

    2016-03-01

    Full Text Available Outbreaks of Rift Valley fever (RVF in eastern Africa have previously occurred following specific rainfall dynamics and flooding events that appear to support the emergence of large numbers of mosquito vectors. As such, transmission of the virus is considered to be sensitive to environmental conditions and therefore changes in climate can impact the spatiotemporal dynamics of epizootic vulnerability. Epidemiological information describing the methods and parameters of RVF transmission and its dependence on climatic factors are used to develop a new spatio-temporal mathematical model that simulates these dynamics and can predict the impact of changes in climate. The Liverpool RVF (LRVF model is a new dynamic, process-based model driven by climate data that provides a predictive output of geographical changes in RVF outbreak susceptibility as a result of the climate and local livestock immunity. This description of the multi-disciplinary process of model development is accessible to mathematicians, epidemiological modellers and climate scientists, uniting dynamic mathematical modelling, empirical parameterisation and state-of-the-art climate information.

  18. Culex pipiens, an experimental efficient vector of West Nile and Rift Valley fever viruses in the Maghreb region.

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    Fadila Amraoui

    Full Text Available West Nile fever (WNF and Rift Valley fever (RVF are emerging diseases causing epidemics outside their natural range of distribution. West Nile virus (WNV circulates widely and harmlessly in the old world among birds as amplifying hosts, and horses and humans as accidental dead-end hosts. Rift Valley fever virus (RVFV re-emerges periodically in Africa causing massive outbreaks. In the Maghreb, eco-climatic and entomologic conditions are favourable for WNV and RVFV emergence. Both viruses are transmitted by mosquitoes belonging to the Culex pipiens complex. We evaluated the ability of different populations of Cx. pipiens from North Africa to transmit WNV and the avirulent RVFV Clone 13 strain. Mosquitoes collected in Algeria, Morocco, and Tunisia during the summer 2010 were experimentally infected with WNV and RVFV Clone 13 strain at titers of 10(7.8 and 10(8.5 plaque forming units/mL, respectively. Disseminated infection and transmission rates were estimated 14-21 days following the exposure to the infectious blood-meal. We show that 14 days after exposure to WNV, all mosquito st developed a high disseminated infection and were able to excrete infectious saliva. However, only 69.2% of mosquito strains developed a disseminated infection with RVFV Clone 13 strain, and among them, 77.8% were able to deliver virus through saliva. Thus, Cx. pipiens from the Maghreb are efficient experimental vectors to transmit WNV and to a lesser extent, RVFV Clone 13 strain. The epidemiologic importance of our findings should be considered in the light of other parameters related to mosquito ecology and biology.

  19. Analysis of HDAC6 and BAG3-Aggresome Pathways in African Swine Fever Viral Factory Formation

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    Raquel Muñoz-Moreno

    2015-04-01

    Full Text Available African swine fever virus (ASFV is a double-stranded DNA virus causing a hemorrhagic fever disease with high mortality rates and severe economic losses in pigs worldwide. ASFV replicates in perinuclear sites called viral factories (VFs that are morphologically similar to cellular aggresomes. This fact raises the possibility that both VFs and aggresomes may be the same structure. However, little is known about the process involved in the formation of these viral replication platforms. In order to expand our knowledge on the assembly of ASFV replication sites, we have analyzed the involvement of both canonical aggresome pathways in the formation of ASFV VFs: HDAC6 and BAG3. HDAC6 interacts with a component of the dynein motor complex (dynactin/p150Glued and ubiquitinated proteins, transporting them to the microtubule-organizing center (MTOC and leading to aggresome formation, while BAG3 is mediating the recruitment of non-ubiquitinated proteins through a similar mechanism. Tubacin-mediated HDAC6 inhibition and silencing of BAG3 pathways, individually or simultaneously, did not prevent ASFV VF formation. These findings show that HDAC6 and Bag3 are not required for VFs formation suggesting that aggresomes and VFs are not the same structures. However, alternative unexplored pathways may be involved in the formation of aggresomes.

  20. Appendicular perforation in dengue fever: our experience

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    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.

  1. A network-based meta-population approach to model Rift Valley fever epidemics.

    Science.gov (United States)

    Xue, Ling; Scott, H Morgan; Cohnstaedt, Lee W; Scoglio, Caterina

    2012-08-07

    Rift Valley fever virus (RVFV) has been expanding its geographical distribution with important implications for both human and animal health. The emergence of Rift Valley fever (RVF) in the Middle East, and its continuing presence in many areas of Africa, has negatively impacted both medical and veterinary infrastructures and human morbidity, mortality, and economic endpoints. Furthermore, worldwide attention should be directed towards the broader infection dynamics of RVFV, because suitable host, vector and environmental conditions for additional epidemics likely exist on other continents; including Asia, Europe and the Americas. We propose a new compartmentalized model of RVF and the related ordinary differential equations to assess disease spread in both time and space; with the latter driven as a function of contact networks. Humans and livestock hosts and two species of vector mosquitoes are included in the model. The model is based on weighted contact networks, where nodes of the networks represent geographical regions and the weights represent the level of contact between regional pairings for each set of species. The inclusion of human, animal, and vector movements among regions is new to RVF modeling. The movement of the infected individuals is not only treated as a possibility, but also an actuality that can be incorporated into the model. We have tested, calibrated, and evaluated the model using data from the recent 2010 RVF outbreak in South Africa as a case study; mapping the epidemic spread within and among three South African provinces. An extensive set of simulation results shows the potential of the proposed approach for accurately modeling the RVF spreading process in additional regions of the world. The benefits of the proposed model are twofold: not only can the model differentiate the maximum number of infected individuals among different provinces, but also it can reproduce the different starting times of the outbreak in multiple locations

  2. NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR.

    Science.gov (United States)

    Kainulainen, Markus; Lau, Simone; Samuel, Charles E; Hornung, Veit; Weber, Friedemann

    2016-07-01

    Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we demonstrate that NSs

  3. A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence.

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    Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R; Kehn-Hall, Kylene; Omichinski, James G

    2015-05-12

    Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

  4. Non-infectious plasmid engineered to simulate multiple viral threat agents.

    Science.gov (United States)

    Carrera, Monica; Sagripanti, Jose-Luis

    2009-07-01

    The aim of this study was to design and construct a non-virulent simulant to replace several pathogenic viruses in the development of detection and identification methods in biodefense. A non-infectious simulant was designed and engineered to include the nucleic acid signature of VEEV (Venezuelan Equine Encephalitis virus), Influenza virus, Rift Valley Fever virus, Machupo virus, Lassa virus, Yellow Fever virus, Ebola virus, Eastern Equine Encephalitis virus, Junin virus, Marburg virus, Dengue virus, and Crimean-Congo virus, all in a single construct. The nucleic acid sequences of all isolates available for each virus species were aligned using ClustalW software in order to obtain conserved regions of the viral genomes. Specific primers were designed to permit the identification and differentiation between viral threat agents. A chimera of 3143 base pairs was engineered to produce 13 PCR amplicons of different sizes. PCR amplification of the simulant with virus-specific primers revealed products of the predicted length, in bands of similar intensity, and without detectable unspecific products by electrophoresis analysis. The simulant described could reduce the need to use infectious viruses in the development of detection and diagnostic methods, and could also be useful as a non-virulent positive control in nucleic acid-based tests against biological threat agents.

  5. 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...

  6. Common host-derived chemicals increase catches of disease-transmitting mosquitoes and can improve early warning systems for rift valley fever virus

    Science.gov (United States)

    Rift Valley fever (RVF), a mosquito-borne zoonosis, is a major public health problem in sub-Saharan Africa. The emergence and re-emergence of the disease in the last 20 years especially in East Africa, poses a looming health threat which is likely to spread to beyond Africa. This threat is exacerbat...

  7. Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift valley fever virus in human small airway epithelial cells.

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    Taissia G Popova

    Full Text Available Rift valley fever virus (RVFV infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK and downstream transcriptional factors [STAT1 (Y701, ATF2 (T69/71, MSK1 (S360 and CREB (S133]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46 correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473, along with phosphorylation of FOX 01/03 (T24/31 which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication.

  8. Role of Culex and Anopheles mosquito species as potential vectors of rift valley fever virus in Sudan outbreak, 2007

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    Galal Fatma H

    2010-03-01

    Full Text Available Abstract Background Rift Valley fever (RVF is an acute febrile arthropod-borne viral disease of man and animals caused by a member of the Phlebovirus genus, one of the five genera in the family Bunyaviridae. RVF virus (RVFV is transmitted between animals and human by mosquitoes, particularly those belonging to the Culex, Anopheles and Aedes genera. Methods Experiments were designed during RVF outbreak, 2007 in Sudan to provide an answer about many raised questions about the estimated role of vector in RVFV epidemiology. During this study, adult and immature mosquito species were collected from Khartoum and White Nile states, identified and species abundance was calculated. All samples were frozen individually for further virus detection. Total RNA was extracted from individual insects and RVF virus was detected from Culex, Anopheles and Aedes species using RT-PCR. In addition, data were collected about human cases up to November 24th, 2007 to asses the situation of the disease in affected states. Furthermore, a historical background of the RVF outbreaks was discussed in relation to global climatic anomalies and incriminated vector species. Results A total of 978 mosquitoes, belonging to 3 genera and 7 species, were collected during Sudan outbreak, 2007. Anopheles gambiae arabiensis was the most frequent species (80.7% in White Nile state. Meanwhile, Cx. pipiens complex was the most abundant species (91.2% in Khartoum state. RT-PCR was used and successfully amplified 551 bp within the M segment of the tripartite negative-sense single stranded RNA genome of RVFV. The virus was detected in female, male and larval stages of Culex and Anopheles species. The most affected human age interval was 15-29 years old followed by ≥ 45 years old, 30-44 years old, and then 5-14 years old. Regarding to the profession, housewives followed by farmers, students, shepherd, workers and the free were more vulnerable to the infection. Furthermore, connection between

  9. Blood Meal Analysis of and Virus Detection in Mosquitoes Collected during a Rift Valley fever Epizootic/Epidemic: Implications for epidemic disease transmission dynamics

    Science.gov (United States)

    Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Bloodfed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the bloodmeals. Bloodmeals from individual mosquito abdomens were screened for v...

  10. The yellow fever 17D vaccine virus: molecular basis of viral attenuation and its use as an expression vector

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    Galler R.

    1997-01-01

    Full Text Available The yellow fever (YF virus is the prototype flavivirus. The use of molecular techniques has unraveled the basic mechanisms of viral genome structure and expression. Recent trends in flavivirus research include the use of infectious clone technology with which it is possible to recover virus from cloned cDNA. Using this technique, mutations can be introduced at any point of the viral genome and their resulting effect on virus phenotype can be assessed. This approach has opened new possibilities to study several biological viral features with special emphasis on the issue of virulence/attenuation of the YF virus. The feasibility of using YF virus 17D vaccine strain, for which infectious cDNA is available, as a vector for the expression of heterologous antigens is reviewed

  11. Early risk assessment for viral haemorrhagic fever: experience at the Hospital for Tropical Diseases, London, UK.

    Science.gov (United States)

    Woodrow, Charles J; Eziefula, Alice C; Agranoff, Dan; Scott, Geoffrey M; Watson, Julie; Chiodini, Peter L; Lockwood, Diana N J; Grant, Alison D

    2007-01-01

    To implement a policy of systematic screening for viral haemorrhagic fever (VHF) among travellers returning from African countries with fever, commencing at initial clinical contact. A protocol based on UK Advisory Committee on Dangerous Pathogens guidance was developed collaboratively by medical, nursing and laboratory staff. Audit was carried out to quantify resource demands and effects on time to diagnose malaria, the main differential diagnosis. A protocol is now implemented for all patients presenting to HTD with fever, with clear guidelines for interaction with clinical and laboratory staff at each stage. The protocol required moderate amounts of clinical and laboratory staff time and resulted in some additional hospital admissions. The time to a diagnosis of malaria increased from a median of 90 (range 50-125) min in patients without VHF risk to a median of 140 (range 101-225) min (p=0.0025) in those assessed as at risk. Although all acute medical services need to have robust procedures for early detection of patients with serious transmissible conditions, few implement such a policy. Our protocol requires increased human and other resources but has no important impact on the rapidity of diagnosis of malaria, and is now embedded in local practice.

  12. Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan bats.

    Science.gov (United States)

    Kading, Rebekah C; Kityo, Robert M; Mossel, Eric C; Borland, Erin M; Nakayiki, Teddie; Nalikka, Betty; Nyakarahuka, Luke; Ledermann, Jeremy P; Panella, Nicholas A; Gilbert, Amy T; Crabtree, Mary B; Peterhans, Julian Kerbis; Towner, Jonathan S; Amman, Brian R; Sealy, Tara K; Nichol, Stuart T; Powers, Ann M; Lutwama, Julius J; Miller, Barry R

    2018-01-01

    Introduction: A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011-2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT). Sera from up to 626 bats were screened for antibodies against each virus. Results and Discussion:  Key findings include the presence of neutralizing antibodies against RVFV in 5/52 (9.6%) of little epauletted fruit bats ( Epomophorus labiatus ) captured from Kawuku and 3/54 (5.6%) Egyptian rousette bats from Kasokero cave. Antibodies reactive to flaviviruses were widespread across bat taxa and sampling locations. Conclusion: The data presented demonstrate the widespread exposure of bats in Uganda to arboviruses, and highlight particular virus-bat associations that warrant further investigation.

  13. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

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    Moataz Alhaj

    2016-01-01

    Full Text Available Rift Valley Fever (RVF is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA, a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.

  14. Rift Valley Fever Risk Map Model and Seroprevalence in Selected Wild Ungulates and Camels from Kenya

    Science.gov (United States)

    Britch, Seth C.; Binepal, Yatinder S.; Ruder, Mark G.; Kariithi, Henry M.; Linthicum, Kenneth J.; Anyamba, Assaf; Small, Jennifer L.; Tucker, Compton J.; Ateya, Leonard O.; Oriko, Abuu A.; hide

    2013-01-01

    Since the first isolation of Rift Valley fever virus (RVFV) in the 1930s, there have been multiple epizootics and epidemics in animals and humans in sub-Saharan Africa. Prospective climate-based models have recently been developed that flag areas at risk of RVFV transmission in endemic regions based on key environmental indicators that precede Rift Valley fever (RVF) epizootics and epidemics. Although the timing and locations of human case data from the 2006-2007 RVF outbreak in Kenya have been compared to risk zones flagged by the model, seroprevalence of RVF antibodies in wildlife has not yet been analyzed in light of temporal and spatial predictions of RVF activity. Primarily wild ungulate serum samples from periods before, during, and after the 2006-2007 RVF epizootic were analyzed for the presence of RVFV IgM and/or IgG antibody. Results show an increase in RVF seropositivity from samples collected in 2007 (31.8%), compared to antibody prevalence observed from 2000-2006 (3.3%). After the epizootic, average RVF seropositivity diminished to 5% in samples collected from 2008-2009. Overlaying maps of modeled RVF risk assessments with sampling locations indicated positive RVF serology in several species of wild ungulate in or near areas flagged as being at risk for RVF. Our results establish the need to continue and expand sero-surveillance of wildlife species Kenya and elsewhere in the Horn of Africa to further calibrate and improve the RVF risk model, and better understand the dynamics of RVFV transmission.

  15. Rift Valley fever virus NSS gene expression correlates with a defect in nuclear mRNA export.

    Science.gov (United States)

    Copeland, Anna Maria; Van Deusen, Nicole M; Schmaljohn, Connie S

    2015-12-01

    We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NSS gene, but not the N, GN or NSM genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NSS, confirming that expression of NSS is likely responsible for this phenomenon. Published by Elsevier Inc.

  16. Relating coccidioidomycosis (valley fever) incidence to soil moisture conditions.

    Science.gov (United States)

    Coopersmith, E J; Bell, J E; Benedict, K; Shriber, J; McCotter, O; Cosh, M H

    2017-04-17

    Coccidioidomycosis (also called Valley fever) is caused by a soilborne fungus, Coccidioides spp. , in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe illness and death can occur when the infection spreads to other regions of the body. Previous analyses have attempted to connect the incidence of coccidioidomycosis to broadly available climatic measurements, such as precipitation or temperature. However, with the limited availability of long-term, in situ soil moisture data sets, it has not been feasible to perform a direct analysis of the relationships between soil moisture levels and coccidioidomycosis incidence on a larger temporal and spatial scale. Utilizing in situ soil moisture gauges throughout the southwest from the U.S. Climate Reference Network and a model with which to extend those estimates, this work connects periods of higher and lower soil moisture in Arizona and California between 2002 and 2014 to the reported incidence of coccidioidomycosis. The results indicate that in both states, coccidioidomycosis incidence is related to soil moisture levels from previous summers and falls. Stated differently, a higher number of coccidioidomycosis cases are likely to be reported if previous bands of months have been atypically wet or dry, depending on the location.

  17. Modelling the effects of seasonality and socioeconomic impact on the transmission of Rift Valley fever virus

    Science.gov (United States)

    Xiao, Yanyu; Beier, John C.; Cantrell, Robert Stephen; Cosner, Chris; DeAngelis, Donald L.; Ruan, Shigui

    2015-01-01

    Rift Valley fever (RVF) is an important mosquito-borne viral zoonosis in Africa and the Middle East that causes human deaths and significant economic losses due to huge incidences of death and abortion among infected livestock. Outbreaks of RVF are sporadic and associated with both seasonal and socioeconomic effects. Here we propose an almost periodic three-patch model to investigate the transmission dynamics of RVF virus (RVFV) among ruminants with spatial movements. Our findings indicate that, in Northeastern Africa, human activities, including those associated with the Eid al Adha feast, along with a combination of climatic factors such as rainfall level and hydrological variations, contribute to the transmission and dispersal of the disease pathogen. Moreover, sporadic outbreaks may occur when the two events occur together: 1) abundant livestock are recruited into areas at risk from RVF due to the demand for the religious festival and 2) abundant numbers of mosquitoes emerge. These two factors have been shown to have impacts on the severity of RVF outbreaks. Our numerical results present the transmission dynamics of the disease pathogen over both short and long periods of time, particularly during the festival time. Further, we investigate the impact on patterns of disease outbreaks in each patch brought by festival- and seasonal-driven factors, such as the number of livestock imported daily, the animal transportation speed from patch to patch, and the death rate induced by ceremonial sacrifices. In addition, our simulations show that when the time for festival preparation starts earlier than usual, the risk of massive disease outbreaks rises, particularly in patch 3 (the place where the religious ceremony will be held).

  18. Infection of inbred rat strains with Rift Valley fever virus: development of a congenic resistant strain and observations on age-dependence of resistance.

    Science.gov (United States)

    Anderson, G W; Rosebrock, J A; Johnson, A J; Jennings, G B; Peters, C J

    1991-05-01

    A congenic rat strain (WF.LEW) was derived from the susceptible Wistar-Furth (WF) (background strain) and the resistant LEW (donor strain) inbred strains and was used to evaluate the phenotypic expression of a dominant Mendelian gene that confers resistance to fatal hepatic disease caused by the ZH501 strain of Rift Valley fever virus (RVFV). Resistance to hepatic disease developed gradually with age, with full expression at approximately 10 weeks in the WF.LEW and LEW rat strains. The ZH501 strain caused fatal hepatitis in WF rats regardless of age. However, resistance to the SA75 RVFV strain (relatively non-pathogenic for adult rats), was age- and dose-dependent in both WF and LEW rats. The resistance gene transferred to the newly derived WF.LEW congenic rat strain appears to amplify age-dependent resistance of adult rats, resulting in protection against fatal hepatic disease caused by the virulent ZH501 strain. The congenic rat strain will be a valuable asset in elucidating the mechanism of resistance to Rift Valley fever virus governed by the dominant Mendelian gene.

  19. Rift Valley fever virus epidemic in Kenya, 2006/2007: the entomologic investigations.

    Science.gov (United States)

    Sang, Rosemary; Kioko, Elizabeth; Lutomiah, Joel; Warigia, Marion; Ochieng, Caroline; O'Guinn, Monica; Lee, John S; Koka, Hellen; Godsey, Marvin; Hoel, David; Hanafi, Hanafi; Miller, Barry; Schnabel, David; Breiman, Robert F; Richardson, Jason

    2010-08-01

    In December 2006, Rift Valley fever (RVF) was diagnosed in humans in Garissa Hospital, Kenya and an outbreak reported affecting 11 districts. Entomologic surveillance was performed in four districts to determine the epidemic/epizootic vectors of RVF virus (RVFV). Approximately 297,000 mosquitoes were collected, 164,626 identified to species, 72,058 sorted into 3,003 pools and tested for RVFV by reverse transcription-polymerase chain reaction. Seventy-seven pools representing 10 species tested positive for RVFV, including Aedes mcintoshi/circumluteolus (26 pools), Aedes ochraceus (23 pools), Mansonia uniformis (15 pools); Culex poicilipes, Culex bitaeniorhynchus (3 pools each); Anopheles squamosus, Mansonia africana (2 pools each); Culex quinquefasciatus, Culex univittatus, Aedes pembaensis (1 pool each). Positive Ae. pembaensis, Cx. univittatus, and Cx. bitaeniorhynchus was a first time observation. Species composition, densities, and infection varied among districts supporting hypothesis that different mosquito species serve as epizootic/epidemic vectors of RVFV in diverse ecologies, creating a complex epidemiologic pattern in East Africa.

  20. Serologic evidence of exposure to Rift Valley fever virus detected in Tunisia

    Directory of Open Access Journals (Sweden)

    A. Bosworth

    2016-01-01

    Full Text Available Rift Valley fever virus (RVFv is capable of causing dramatic outbreaks amongst economically important animal species and is capable of causing severe symptoms and mortality in humans. RVFv is known to circulate widely throughout East Africa; serologic evidence of exposure has also been found in some northern African countries, including Mauritania. This study aimed to ascertain whether RVFv is circulating in regions beyond its known geographic range. Samples from febrile patients (n=181 and nonfebrile healthy agricultural and slaughterhouse workers (n=38 were collected during the summer of 2014 and surveyed for exposure to RVFv by both serologic tests and PCR. Of the 219 samples tested, 7.8% of nonfebrile participants showed immunoglobulin G reactivity to RVFv nucleoprotein and 8.3% of febrile patients showed immunoglobulin M reactivity, with the latter samples indicating recent exposure to the virus. Our results suggest an active circulation of RVFv and evidence of human exposure in the population of Tunisia.

  1. Rift Valley fever in Kenya: history of epizootics and identification of vulnerable districts.

    Science.gov (United States)

    Murithi, R M; Munyua, P; Ithondeka, P M; Macharia, J M; Hightower, A; Luman, E T; Breiman, R F; Njenga, M Kariuki

    2011-03-01

    Since Kenya first reported Rift Valley fever (RVF)-like disease in livestock in 1912, the country has reported the most frequent epizootics of RVF disease. To determine the pattern of disease spread across the country after its introduction in 1912, and to identify regions vulnerable to the periodic epizootics, annual livestock disease records at the Department of Veterinary Services from 1910 to 2007 were analysed in order to document the number and location of RVF-infected livestock herds. A total of 38/69 (55%) administrative districts in the country had reported RVF epizootics by the end of 2007. During the 1912-1950 period, the disease was confined to a district in Rift Valley province that is prone to flooding and where livestock were raised in proximity with wildlife. Between 1951 and 2007, 11 national RVF epizootics were recorded with an average inter-epizootic period of 3·6 years (range 1-7 years); in addition, all epizootics occurred in years when the average annual rainfall increased by more than 50% in the affected districts. Whereas the first two national epizootics in 1951 and 1955 were confined to eight districts in the Rift Valley province, there was a sustained epizootic between 1961 and 1964 that spread the virus to over 30% of the districts across six out of eight provinces. The Western and Nyanza provinces, located on the southwestern region of the country, had never reported RVF infections by 2007. The probability of a district being involved in a national epizootic was fivefold higher (62%) in districts that had previously reported disease compared to districts that had no prior disease activity (11%). These findings suggests that once introduced into certain permissive ecologies, the RVF virus becomes enzootic, making the region vulnerable to periodic epizootics that were probably precipitated by amplification of resident virus associated with heavy rainfall and flooding.

  2. Acute atrial fibrillation during dengue hemorrhagic fever

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    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.

  3. Acute atrial fibrillation during dengue hemorrhagic fever

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    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.

  4. Inter-epidemic acquisition of Rift Valley fever virus in humans in Tanzania.

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    Robert David Sumaye

    2015-02-01

    Full Text Available BACKGROUND: In East Africa, epidemics of Rift Valley fever (RVF occur in cycles of 5-15 years following unusually high rainfall. RVF transmission during inter-epidemic periods (IEP generally passes undetected in absence of surveillance in mammalian hosts and vectors. We studied IEP transmission of RVF and evaluated the demographic, behavioural, occupational and spatial determinants of past RVF infection. METHODOLOGY: Between March and August 2012 we collected blood samples, and administered a risk factor questionnaire among 606 inhabitants of 6 villages in the seasonally inundated Kilombero Valley, Tanzania. ELISA tests were used to detect RVFV IgM and IgG antibodies in serum samples. Risk factors were examined by mixed effects logistic regression. FINDINGS: RVF virus IgM antibodies, indicating recent RVFV acquisition, were detected in 16 participants, representing 2.6% overall and in 22.5% of inhibition ELISA positives (n = 71. Four of 16 (25.0% IgM positives and 11/71 (15.5% of individuals with inhibition ELISA sero-positivity reported they had had no previous contact with host animals. Sero-positivity on inhibition ELISA was 11.7% (95% CI 9.2-14.5 and risk was elevated with age (odds ratio (OR 1.03 per year; 95% CI 1.01-1.04, among milkers (OR 2.19; 95% CI 1.23-3.91, and individuals eating raw meat (OR 4.17; 95% CI 1.18-14.66. Households keeping livestock had a higher probability of having members with evidence of past infection (OR = 3.04, 95% CI = 1.42-6.48 than those that do not keep livestock. CONCLUSION: There is inter-epidemic acquisition of RVFV in Kilombero Valley inhabitants. In the wake of declining malaria incidence, these findings underscore the need for clinicians to consider RVF in the differential diagnosis for febrile illnesses. Several types of direct contact with livestock are important risk factors for past infection with RVFV in this study's population. However, at least part of RVFV transmission appears to have occurred

  5. Combining hydrology and mosquito population models to identify the drivers of Rift Valley fever emergence in semi-arid regions of West Africa.

    Science.gov (United States)

    Soti, Valérie; Tran, Annelise; Degenne, Pascal; Chevalier, Véronique; Lo Seen, Danny; Thiongane, Yaya; Diallo, Mawlouth; Guégan, Jean-François; Fontenille, Didier

    2012-01-01

    Rift Valley fever (RVF) is a vector-borne viral zoonosis of increasing global importance. RVF virus (RVFV) is transmitted either through exposure to infected animals or through bites from different species of infected mosquitoes, mainly of Aedes and Culex genera. These mosquitoes are very sensitive to environmental conditions, which may determine their presence, biology, and abundance. In East Africa, RVF outbreaks are known to be closely associated with heavy rainfall events, unlike in the semi-arid regions of West Africa where the drivers of RVF emergence remain poorly understood. The assumed importance of temporary ponds and rainfall temporal distribution therefore needs to be investigated. A hydrological model is combined with a mosquito population model to predict the abundance of the two main mosquito species (Aedes vexans and Culex poicilipes) involved in RVFV transmission in Senegal. The study area is an agropastoral zone located in the Ferlo Valley, characterized by a dense network of temporary water ponds which constitute mosquito breeding sites. The hydrological model uses daily rainfall as input to simulate variations of pond surface areas. The mosquito population model is mechanistic, considers both aquatic and adult stages and is driven by pond dynamics. Once validated using hydrological and entomological field data, the model was used to simulate the abundance dynamics of the two mosquito species over a 43-year period (1961-2003). We analysed the predicted dynamics of mosquito populations with regards to the years of main outbreaks. The results showed that the main RVF outbreaks occurred during years with simultaneous high abundances of both species. Our study provides for the first time a mechanistic insight on RVFV transmission in West Africa. It highlights the complementary roles of Aedes vexans and Culex poicilipes mosquitoes in virus transmission, and recommends the identification of rainfall patterns favourable for RVFV amplification.

  6. Combining hydrology and mosquito population models to identify the drivers of Rift Valley fever emergence in semi-arid regions of West Africa.

    Directory of Open Access Journals (Sweden)

    Valérie Soti

    Full Text Available BACKGROUND: Rift Valley fever (RVF is a vector-borne viral zoonosis of increasing global importance. RVF virus (RVFV is transmitted either through exposure to infected animals or through bites from different species of infected mosquitoes, mainly of Aedes and Culex genera. These mosquitoes are very sensitive to environmental conditions, which may determine their presence, biology, and abundance. In East Africa, RVF outbreaks are known to be closely associated with heavy rainfall events, unlike in the semi-arid regions of West Africa where the drivers of RVF emergence remain poorly understood. The assumed importance of temporary ponds and rainfall temporal distribution therefore needs to be investigated. METHODOLOGY/PRINCIPAL FINDINGS: A hydrological model is combined with a mosquito population model to predict the abundance of the two main mosquito species (Aedes vexans and Culex poicilipes involved in RVFV transmission in Senegal. The study area is an agropastoral zone located in the Ferlo Valley, characterized by a dense network of temporary water ponds which constitute mosquito breeding sites. The hydrological model uses daily rainfall as input to simulate variations of pond surface areas. The mosquito population model is mechanistic, considers both aquatic and adult stages and is driven by pond dynamics. Once validated using hydrological and entomological field data, the model was used to simulate the abundance dynamics of the two mosquito species over a 43-year period (1961-2003. We analysed the predicted dynamics of mosquito populations with regards to the years of main outbreaks. The results showed that the main RVF outbreaks occurred during years with simultaneous high abundances of both species. CONCLUSION/SIGNIFICANCE: Our study provides for the first time a mechanistic insight on RVFV transmission in West Africa. It highlights the complementary roles of Aedes vexans and Culex poicilipes mosquitoes in virus transmission, and recommends

  7. Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent Protein Kinase PKR

    OpenAIRE

    Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V.; Lokugamage, Nandadeva; Head, Jennifer A.; Ikegami, Tetsuro

    2012-01-01

    Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general tr...

  8. Laboratory safe detection of nucleocapsid protein of Rift Valley fever virus in human and animal specimens by a sandwich ELISA.

    Science.gov (United States)

    Jansen van Vuren, P; Paweska, J T

    2009-04-01

    A safe laboratory procedure, based on a sandwich ELISA (sAg-ELISA), was developed and evaluated for the detection of nucleocapsid protein (NP) of Rift Valley fever virus (RVFV) in specimens inactivated at 56 degrees C for 1h in the presence of 0.5% Tween-20 (v/v) before testing. Polyclonal capture and detection immune sera were generated respectively in sheep and rabbits immunized with recombinant NP antigen. The assay was highly repeatable and specific; it detected strains of RVFV from the entire distributional range of the disease, isolated over a period of 53 years; no cross-reactivity with genetically related African phleboviruses or other members of the family Bunyaviridae was observed. In specimens spiked with RVFV, including human and animal sera, homogenates of liver and spleen tissues of domestic ruminants, and Anopheles mosquito homogenates, the sAg-ELISA detection limit ranged from log(10)10(2.2) to 10(3.2) TCID(50)/reaction volume. The ELISA detected NP antigen in spiked bovine and sheep liver homogenates up to at least 8 days of incubation at 37 degrees C whereas infectious virus could not be detected at 48h incubation in these adverse conditions. Compared to virus isolation from sera from RVF patients and sheep infected experimentally, the ELISA had 67.7% and 70% sensitivity, and 97.97% and 100% specificity, respectively. The assay was 100% accurate when testing tissues of various organs from mice infected experimentally and buffalo foetuses infected naturally. The assay was able to detect NP antigen in infective culture supernatants 16-24h before cytopathic effects were observed microscopically and as early as 8h after inoculation with 10(5.8) TCID(50)/ml of RVFV. This ability renders the assay for rapid identification of the virus when its primary isolation is attempted in vitro. As a highly specific, safe and simple assay format, the sAg-ELISA represents a valuable diagnostic tool for use in less equipped laboratories in Africa, and for routine

  9. Behavioural fever is a synergic signal amplifying the innate immune response.

    Science.gov (United States)

    Boltaña, Sebastian; Rey, Sonia; Roher, Nerea; Vargas, Reynaldo; Huerta, Mario; Huntingford, Felicity Anne; Goetz, Frederick William; Moore, Janice; Garcia-Valtanen, Pablo; Estepa, Amparo; Mackenzie, S

    2013-09-07

    Behavioural fever, defined as an acute change in thermal preference driven by pathogen recognition, has been reported in a variety of invertebrates and ectothermic vertebrates. It has been suggested, but so far not confirmed, that such changes in thermal regime favour the immune response and thus promote survival. Here, we show that zebrafish display behavioural fever that acts to promote extensive and highly specific temperature-dependent changes in the brain transcriptome. The observed coupling of the immune response to fever acts at the gene-environment level to promote a robust, highly specific time-dependent anti-viral response that, under viral infection, increases survival. Fish that are not offered a choice of temperatures and that therefore cannot express behavioural fever show decreased survival under viral challenge. This phenomenon provides an underlying explanation for the varied functional responses observed during systemic fever. Given the effects of behavioural fever on survival and the fact that it exists across considerable phylogenetic space, such immunity-environment interactions are likely to be under strong positive selection.

  10. Multilevel Methodology for Simulation of Spatio-Temporal Systems with Heterogeneous Activity; Application to Spread of Valley Fever Fungus

    Science.gov (United States)

    Jammalamadaka, Rajanikanth

    2009-01-01

    This report consists of a dissertation submitted to the faculty of the Department of Electrical and Computer Engineering, in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Graduate College, The University of Arizona, 2008. Spatio-temporal systems with heterogeneity in their structure and behavior have two major problems associated with them. The first one is that such complex real world systems extend over very large spatial and temporal domains and consume so many computational resources to simulate that they are infeasible to study with current computational platforms. The second one is that the data available for understanding such systems is limited because they are spread over space and time making it hard to obtain micro and macro measurements. This also makes it difficult to get the data for validation of their constituent processes while simultaneously considering their global behavior. For example, the valley fever fungus considered in this dissertation is spread over a large spatial grid in the arid Southwest and typically needs to be simulated over several decades of time to obtain useful information. It is also hard to get the temperature and moisture data (which are two critical factors on which the survival of the valley fever fungus depends) at every grid point of the spatial domain over the region of study. In order to address the first problem, we develop a method based on the discrete event system specification which exploits the heterogeneity in the activity of the spatio-temporal system and which has been shown to be effective in solving relatively simple partial differential equation systems. The benefit of addressing the first problem is that it now makes it feasible to address the second problem. We address the second problem by making use of a multilevel methodology based on modeling and simulation and systems theory. This methodology helps us in the construction of models with different resolutions (base and

  11. Factors associated with severe human Rift Valley fever in Sangailu, Garissa County, Kenya.

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    A Desirée LaBeaud

    2015-03-01

    Full Text Available Mosquito-borne Rift Valley fever virus (RVFV causes acute, often severe, disease in livestock and humans. To determine the exposure factors and range of symptoms associated with human RVF, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Kenya.A systematic survey of the total populations of six Northeastern Kenyan villages was performed. Among 1082 residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13-17%. Prevalence did not vary significantly among villages. Subject age was a significant factor, with 31% (154/498 of adults seropositive vs. only 2% of children ≤15 years (12/583. Seroprevalence was higher among men (18% than women (13%. Factors associated with seropositivity included a history of animal exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and eye symptoms. Using cluster analysis in RVFV positive participants, a more severe symptom phenotype was empirically defined as having somatic symptoms of acute fever plus eye symptoms, and possibly one or more meningoencephalitic or hemorrhagic symptoms. Associated with this more severe disease phenotype were older age, village, recent illness, and loss of a family member during the last outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93-13.61, P = 0.065, disposing of livestock abortus (aOR = 4.11, CI95% 0.63-26.79, P = 0.14, and village location (P = 0.009 were independently associated with the severe disease phenotype.Our results demonstrate that a significant proportion of the population in northeastern Kenya has been infected with RVFV. Village and certain animal husbandry activities were associated with more severe disease. Older age, male gender, herder occupation, killing and butchering livestock, and poor visual acuity were useful markers for increased RVFV infection. Formal vision testing may therefore prove to be a helpful, low-technology tool

  12. Identification of pathogens for differential diagnosis of fever with jaundice in the Central African Republic: a retrospective assessment, 2008-2010.

    Science.gov (United States)

    Gadia, Christelle Luce Bobossi; Manirakiza, Alexandre; Tekpa, Gaspard; Konamna, Xavier; Vickos, Ulrich; Nakoune, Emmanuel

    2017-11-29

    Febrile jaundice results clinically in generalized yellow coloration of the teguments and mucous membranes due to excess plasma bilirubin, accompanied by fever. Two types are found: conjugated and unconjugated bilirubin jaundice. Jaundice is a sign in several diseases due to viruses (viral hepatitis and arbovirus), parasites (malaria) and bacteria (leptospirosis). In the Central African Republic (CAR), only yellow fever is included on the list of diseases for surveillance. The aim of this study was to identify the other pathogens that can cause febrile jaundice, for better management of patients. Between 2008 and 2010, 198 sera negative for yellow fever IgM were randomly selected from 2177 samples collected during yellow fever surveillance. Laboratory analyses targeted four groups of pathogens: hepatitis B, C, delta and E viruses; dengue, chikungunya, Zika, Crimean-Congo haemorrhagic fever, West Nile and Rift Valley arboviruses; malaria parasites; and bacteria (leptospirosis). Overall, 30.9% sera were positive for hepatitis B, 20.2% for hepatitis E, 12.3% for hepatitis C and 8.2% for malaria. The majority of positive sera (40.4%) were from people aged 16-30 years. Co-infection with at least two of these pathogens was also found. These findings suggest that a systematic investigation should be undertaken of infectious agents that cause febrile jaundice in the CAR.

  13. Lassa fever – full recovery without ribavarin treatment: a case report ...

    African Journals Online (AJOL)

    Her close contacts showed no evidence of Lassa virus infection. Conclusion: This report adds to the literature on the natural history of Lassa fever; and that individuals may survive Lassa fever with conservative management of symptoms of the disease and its complications. Keywords: Lassa fever; viral hemorrhagic fever, ...

  14. Clinical features and patient management of Lujo hemorrhagic fever.

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    Nivesh H Sewlall

    Full Text Available In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries.We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins, N-acetylcysteine, and recombinant factor VIIa.Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks

  15. Landscape Genetics of Aedes mcintoshi (Diptera: Culicidae), an Important Vector of Rift Valley Fever Virus in Northeastern Kenya.

    Science.gov (United States)

    Campbell, Lindsay P; Alexander, Alana M

    2017-09-01

    Rift Valley fever virus (RVFV) is a vector-borne, zoonotic disease that affects humans, wild ungulates, and domesticated livestock in Africa and the Arabian Peninsula. Rift Valley fever virus exhibits interepizootic and epizootic phases, the latter defined by widespread virus occurrence in domesticated livestock. Kenya appears to be particularly vulnerable to epizootics, with 11 outbreaks occurring between 1951 and 2007. The mosquito species Aedes mcintoshi (subgenus Neomelaniconion) is an important primary vector for RVFV in Kenya. Here, we investigate associations between genetic diversity and differentiation of one regional subclade of Ae. mcintoshi in Northeastern Kenya with environmental variables, using a multivariate statistical approach. Using CO1 (cytochrome oxidase subunit 1) sequence data deposited in GenBank, we found no evidence of isolation by distance contributing to genetic differentiation across the study area. However, we did find significant CO1 subpopulation structure and associations with recent mean precipitation values. In addition, variation in genetic diversity across our seven sample sites was associated with both precipitation and percentage clay in the soil. The large number of haplotypes found in this data set indicates that a great deal of diversity remains unsampled in this region. Additional sampling across a larger geographic area, combined with next-generation sequencing approaches that better characterize the genome, would provide a more robust assessment of genetic diversity and differentiation. Further understanding of the genetic structure of Ae. mcintoshi could provide useful information regarding the potential for RVFV to spread across East African landscapes. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. 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...

  17. The nonstructural protein NSs induces a variable antibody response in domestic ruminants naturally infected with Rift Valley fever virus.

    Science.gov (United States)

    Fernandez, José-Carlos; Billecocq, Agnès; Durand, Jean Paul; Cêtre-Sossah, Catherine; Cardinale, Eric; Marianneau, Philippe; Pépin, Michel; Tordo, Noël; Bouloy, Michèle

    2012-01-01

    Rift Valley fever (RVF) is an emerging zoonosis in Africa which has spread to Egypt, the Arabian Peninsula, Madagascar, and Comoros. RVF virus (RVFV) (Bunyaviridae family, Phlebovirus genus) causes a wide range of symptoms in humans, from benign fever to fatal hemorrhagic fever. Ruminants are severely affected by the disease, which leads to a high rate of mortality in young animals and to abortions and teratogenesis in pregnant females. Diagnostic tests include virus isolation and genome or antibody detection. During RVFV infection, the nucleoprotein encapsidating the tripartite RNA genome is expressed in large amounts and raises a robust antibody response, while the envelope glycoproteins elicit neutralizing antibodies which play a major role in protection. Much less is known about the antigenicity/immunogenicity of the nonstructural protein NSs, which is a major virulence factor. Here we have developed a competitive enzyme-linked immunosorbent assay (ELISA) enabling detection of low levels of NSs-specific antibodies in naturally infected or vaccinated ruminants. Detection of the NSs antibodies was validated by Western blotting. Altogether, our data showed that the NSs antibodies were detected in only 55% of animals naturally infected by RVFV, indicating that NSs does not induce a consistently high immune response. These results are discussed in light of differentiation between infected and vaccinated animals (DIVA) tests distinguishing naturally infected animals and those vaccinated with NSs-defective vaccines.

  18. Rift Valley fever virus: strategies for maintenance, survival and vertical transmission in mosquitoes.

    Science.gov (United States)

    Lumley, Sarah; Horton, Daniel L; Hernandez-Triana, Luis L M; Johnson, Nicholas; Fooks, Anthony R; Hewson, Roger

    2017-05-01

    Rift Valley fever virus (RVFV) is a mosquito-borne arbovirus causing severe disease in humans and ruminants. Spread of RVFV out of Africa has raised concerns that it could emerge in Europe or the USA. Virus persistence is dependent on successful infection of, replication in, and transmission to susceptible vertebrate and invertebrate hosts, modulated by virus-host and vector-virus interactions. The principal accepted theory for the long-term maintenance of RVFV involves vertical transmission (VT) of virus to mosquito progeny, with the virus surviving long inter-epizootic periods within the egg. This VT hypothesis, however, is yet to be comprehensively proven. Here, evidence for and against the VT of RVFV is reviewed along with the identification of factors limiting its detection in natural and experimental data. The observations of VT for other arboviruses in the genera Alphavirus, Flavivirus and Orthobunyavirus are discussed within the context of RVFV. The review concludes that VT of RVFV is likely but that current data are insufficient to irrefutably prove this hypothesis.

  19. The eukaryotic translation initiation factor 3 subunit E binds to classical swine fever virus NS5A and facilitates viral replication.

    Science.gov (United States)

    Liu, Xiaofeng; Wang, Xiaoyu; Wang, Qian; Luo, Mingyang; Guo, Huancheng; Gong, Wenjie; Tu, Changchun; Sun, Jinfu

    2018-02-01

    Classical swine fever virus (CSFV) NS5A protein is a multifunctional protein, playing critical roles in viral RNA replication, translation and assembly. To further explore its functions in viral replication, interaction of NS5A with host factors was assayed using a his-tag "pull down" assay coupled with shotgun LC-MS/MS. Host protein translation initiation factor 3 subunit E was identified as a binding partner of NS5A, and confirmed by co-immunoprecipitation and co-localization analysis. Overexpression of eIF3E markedly enhanced CSFV genomic replication, viral protein expression and production of progeny virus, and downregulation of eIF3E by siRNA significantly decreased viral proliferation in PK-15 cells. Luciferase reporter assay showed an enhancement of translational activity of the internal ribosome entry site of CSFV by eIF3E and a decrease in cellular translation by NS5A. These data indicate that eIF3E plays an important role in CSFV replication, thereby identifying it as a potential target for inhibition of the virus. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Distribution and abundance of key vectors of Rift Valley fever and other arboviruses in two ecologically distinct counties in Kenya.

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    Rosemary Sang

    2017-02-01

    Full Text Available Rift Valley fever (RVF is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences. Humans become infected through mosquito bites and contact with infected livestock. The virus is maintained between outbreaks through vertically infected eggs of the primary vectors of Aedes species which emerge following rains with extensive flooding. Infected female mosquitoes initiate transmission among nearby animals, which amplifies virus, thereby infecting more mosquitoes and moving the virus beyond the initial point of emergence. With each successive outbreak, RVF has been found to expand its geographic distribution to new areas, possibly driven by available vectors. The aim of the present study was to determine if RVF virus (RVFV transmission risk in two different ecological zones in Kenya could be assessed by looking at the species composition, abundance and distribution of key primary and secondary vector species and the level of virus activity.Mosquitoes were trapped during short and long rainy seasons in 2014 and 2015 using CO2 baited CDC light traps in two counties which differ in RVF epidemic risk levels(high risk Tana-River and low risk Isiolo,cryo-preserved in liquid nitrogen, transported to the laboratory, and identified to species. Mosquito pools were analyzed for virus infection using cell culture screening and molecular analysis.Over 69,000 mosquitoes were sampled and identified as 40 different species belonging to 6 genera (Aedes, Anopheles, Mansonia, Culex, Aedeomyia, Coquillettidia. The presence and abundance of Aedes mcintoshi and Aedes ochraceus, the primary mosquito vectors associated with RVFV transmission in outbreaks, varied significantly between Tana-River and Isiolo. Ae. mcintoshi was abundant in Tana-River and Isiolo but notably, Aedes ochraceus found in relatively high numbers in Tana-River (n = 1,290, was totally

  1. Marburg haemorrhagic fever: recent advances | AdegborO | African ...

    African Journals Online (AJOL)

    With the exception of a vaccine for yellow fever and ribavirin, which is used for treatment of some arenaviral infections, no specific chemotherapy for viral hemorrhagic fever exists. Only supportive treatment is possible The filoviruses, Marburg virus (MARV) and Ebola virus (EBOV), have been associated with hemorrhagic ...

  2. Inter-epidemic abundance and distribution of potential mosquito vectors for Rift Valley fever virus in Ngorongoro district, Tanzania.

    Science.gov (United States)

    Mweya, Clement N; Kimera, Sharadhuli I; Mellau, Lesakit S B; Mboera, Leonard E G

    2015-01-01

    Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that primarily affects ruminants but also has the capacity to infect humans. To determine the abundance and distribution of mosquito vectors in relation to their potential role in the virus transmission and maintenance in disease epidemic areas of Ngorongoro district in northern Tanzania. A cross-sectional entomological investigation was carried out before the suspected RVF outbreak in October 2012. Mosquitoes were sampled both outdoors and indoors using the Centre for Disease Control (CDC) light traps and Mosquito Magnets baited with attractants. Outdoor traps were placed in proximity with breeding sites and under canopy in banana plantations close to the sleeping places of animals. A total of 1,823 mosquitoes were collected, of which 87% (N=1,588) were Culex pipiens complex, 12% (N=226) Aedes aegypti, and 0.5% (N=9) Anopheles species. About two-thirds (67%; N=1,095) of C. pipiens complex and nearly 100% (N=225) of A. aegypti were trapped outdoors using Mosquito Magnets. All Anopheles species were trapped indoors using CDC light traps. There were variations in abundance of C. pipiens complex and A. aegypti among different ecological and vegetation habitats. Over three quarters (78%) of C. pipiens complex and most (85%) of the A. aegypti were trapped in banana and maize farms. Both C. pipiens complex and A. aegypti were more abundant in proximity with cattle and in semi-arid thorn bushes and lower Afro-montane. The highest number of mosquitoes was recorded in villages that were most affected during the RVF epidemic of 2007. Of the tested 150 pools of C. pipiens complex and 45 pools of A. aegypti, none was infected with RVF virus. These results provide insights into unique habitat characterisation relating to mosquito abundances and distribution in RVF epidemic-prone areas of Ngorongoro district in northern Tanzania.

  3. Rotavirus infection as a frequent cause of neonatal fever.

    Science.gov (United States)

    Kang, Ha-Na; Park, Hyun Kyung; Lee, Hyun-Ju; Moon, Jin-Hwa; Oh, Jae Won; Kim, Chang-Ryul

    2018-04-01

    Fever rather than diarrhea or vomiting was the most common symptom of neonatal rotavirus (RV) infection in our previous study. We investigated whether RV infection is a major cause of neonatal fever and compared the clinical characteristics of bacterial infection, viral infection and unknown causes of neonatal fever. We reviewed the electronic medical records of 48 newborns aged ≤28 days who were admitted to the Special Care Nursery of Hanyang University Guri Hospital for fever (≥38°C) from 2005 to 2009. All the newborns underwent complete blood count, urinalysis, C-reactive protein, cultures of blood, urine, and cerebrospinal fluid as well as stool RV enzyme-linked immunosorbent assay. Respiratory virus polymerase chain reaction for cough or rhinorrhea, and stool culture for diarrhea were also done. All the babies were term, with mean age 13 ± 8 days and peak body temperature 38.5 ± 0.5°C. The causes of neonatal fever were viral (44%), bacterial (10%) and unknown (46%). The viral infections included RV (n = 12), enterovirus (n = 6), respiratory syncytial virus (n = 2), and rhinovirus (n = 1). All the rotavirus genotypes were G4P[6]. Only three of 12 RV-infected febrile newborns had diarrhea. The bacterial infections included three cases of urinary tract infection (Escherichia coli, n = 2; Klebsiella pneumoniae, n = 1), and two cases of sepsis complicated with meningitis (all Streptococcus agalactiae). RV infection is the most common single cause of neonatal fever. It may be necessary to include stool RV tests for febrile newborns. © 2017 Japan Pediatric Society.

  4. Lassa fever or lassa hemorrhagic fever risk to humans from rodent-borne zoonoses.

    Science.gov (United States)

    El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

    2015-04-01

    Viral hemorrhagic fevers (VHFs) typically manifest as rapidly progressing acute febrile syndromes with profound hemorrhagic manifestations and very high fatality rates. Lassa fever, an acute hemorrhagic fever characterized by fever, muscle aches, sore throat, nausea, vomiting, diarrhea and chest and abdominal pain. Rodents are important reservoirs of rodent-borne zoonosis worldwide. Transmission rodents to humans occur by aerosol spread, either from the genus Mastomys rodents' excreta (multimammate rat) or through the close contact with infected patients (nosocomial infection). Other rodents of the genera Rattus, Mus, Lemniscomys, and Praomys are incriminated rodents hosts. Now one may ask do the rodents' ectoparasites play a role in Lassa virus zoonotic transmission. This paper summarized the update knowledge on LHV; hopping it might be useful to the clinicians, nursing staff, laboratories' personals as well as those concerned zoonoses from rodents and rodent control.

  5. Identification of Dengue and Chikungunya Cases Among Suspected Cases of Yellow Fever in the Democratic Republic of the Congo.

    Science.gov (United States)

    Makiala-Mandanda, Sheila; Ahuka-Mundeke, Steve; Abbate, Jessica L; Pukuta-Simbu, Elisabeth; Nsio-Mbeta, Justus; Berthet, Nicolas; Leroy, Eric Maurice; Becquart, Pierre; Muyembe-Tamfum, Jean-Jacques

    2018-05-16

    For more than 95% of acute febrile jaundice cases identified through surveillance for yellow fever, a reemerging arthropod-borne viral disease, no etiological exploration is ever done. The aim of this study was to test for other arthropod-borne viruses that can induce the same symptoms in patients enrolled in the yellow fever surveillance in the Democratic Republic of the Congo (DRC). Of 652 patients included in the surveillance of yellow fever in DRC from January 2003 to January 2012, 453 patients that tested negative for yellow fever virus (YFV) immunoglobulin M (IgM) antibodies were selected for the study. Real-time polymerase chain reaction was performed for the detection of dengue, West Nile, Chikungunya, O'nyong-nyong, Rift Valley fever, Zika, and YFV. The average age of patients was 22.1 years. We reported 16 cases (3.5%; confidence interval [CI]: 0.8-5.2) of dengue (serotypes 1 and 2) and 2 cases (0.4%; CI: 0.0-1.0) of Chikungunya. Three patients were co-infected with the two serotypes of dengue virus. Three cases of dengue were found in early July 2010 from the city of Titule (Oriental province) during a laboratory-confirmed outbreak of yellow fever, suggesting simultaneous circulation of dengue and yellow fever viruses. This study showed that dengue and Chikungunya viruses are potential causes of acute febrile jaundice in the DRC and highlights the need to consider dengue and Chikungunya diagnosis in the integrated disease surveillance and response program in the DRC. A prospective study is necessary to establish the epidemiology of these diseases.

  6. Rift Valley fever: Real or perceived threat for Zambia?

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    George Dautu

    2012-06-01

    Full Text Available Rift Valley fever (RVF in Zambia was first reported in 1974 during an epizootic of cattle and sheep that occurred in parts of Central, Southern and Copperbelt Provinces. In 1990, the disease was documented in nine districts of the provinces of Zambia. In the last two decades, there have been no reports of RVF. This long period without reported clinical disease raises questions as to whether RVF is a current or just a perceived threat. To address this question, World Organisation for Animal Health (OIE disease occurrence data on RVF for the period 2005−2010 in the Southern Africa Development Community (SADC was analysed. From the analysis, it was evident that most countries that share a common border with Zambia had reported at least one occurrence of the disease during the period under review. Due to the absence of natural physical barriers between Zambia and most of her neighbours, informal livestock trade and movements is a ubiquitous reality. Analysis of the rainfall patterns also showed that Zambia received rains sufficient to support a mosquito population large enough for high risk of RVF transmission. The evidence of disease occurrence in nearby countries coupled with animal movement, and environmental risk suggests that RVF is a serious threat to Zambia. In conclusion, the current occurrence of RVF in Zambia is unclear, but there are sufficient indications that the magnitude of the circulating infection is such that capacity building in disease surveillance and courses on recognition of the disease for field staff is recommended. Given the zoonotic potential of RVF, these measures are also a prerequisite for accurate assessment of the disease burden in humans.

  7. Reprint of "Epidemiology of brucellosis, Q Fever and Rift Valley Fever at the human and livestock interface in northern Côte d'Ivoire".

    Science.gov (United States)

    Kanouté, Youssouf B; Gragnon, Biégo G; Schindler, Christian; Bonfoh, Bassirou; Schelling, Esther

    2017-11-01

    Northern Côte d'Ivoire is the main livestock breeding zone and has the highest livestock cross-border movements in Côte d'Ivoire. The aim of this study was to provide updated epidemiological data on three neglected zoonotic diseases, namely brucellosis, Q Fever and Rift Valley Fever (RVF). We conducted three-stage cross-sectional cluster surveys in livestock and humans between 2012 and 2014 in a random selection of 63 villages and a sample of 633 cattle, 622 small ruminants and 88 people. We administered questionnaires to capture risk factors and performed serological tests including the Rose Bengal Plate Test (RBPT), Brucella spp. indirect and competitive ELISAs, Coxiella burnetii indirect ELISA and RVF competitive ELISA. The human seroprevalence for Brucella spp. was 5.3%. RBPT-positive small ruminants tested negative by the indirect ELISA. The seroprevalence of Brucella spp. in cattle adjusted for clustering was 4.6%. Cattle aged 5-8 years had higher odds of seropositivity (OR=3.5) than those aged ≤4years. The seropositivity in cattle was associated with having joint hygromas (OR=9), sharing the pastures with small ruminants (OR=5.8) and contact with pastoralist herds (OR=11.3). The seroprevalence of Q Fever was 13.9% in cattle, 9.4% in sheep and 12.4% in goats. The seroprevalence of RVF was 3.9% in cattle, 2.4% in sheep and 0% in goats. Seropositive ewes had greater odds (OR=4.7) of abortion than seronegative ones. In cattle, a shorter distance between the night pens and nearest permanent water bodies was a protective factor (OR=0.1). The study showed that the exposure to the three zoonoses is rather low in northern Côte d'Ivoire. Within a One Health approach, cost-benefit and cost-effectiveness of control measures should be assessed for an integrated control. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. [Alarm symptoms of meningitis in children with fever].

    NARCIS (Netherlands)

    D.H.F. Geurts (Dorien); H.A. Moll (Henriëtte)

    2011-01-01

    textabstractA 15-year-old girl presented with fever and pain in her legs. A viral infection was suspected, but within 24 hours she became confused and developed meningeal signs, based on which she was diagnosed as having meningitis. Within a few hours a 6-month-old boy developed fever, a grey

  9. DNA-Binding Properties of African Swine Fever Virus pA104R, a Histone-Like Protein Involved in Viral Replication and Transcription.

    Science.gov (United States)

    Frouco, Gonçalo; Freitas, Ferdinando B; Coelho, João; Leitão, Alexandre; Martins, Carlos; Ferreira, Fernando

    2017-06-15

    African swine fever virus (ASFV) codes for a putative histone-like protein (pA104R) with extensive sequence homology to bacterial proteins that are implicated in genome replication and packaging. Functional characterization of purified recombinant pA104R revealed that it binds to single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) over a wide range of temperatures, pH values, and salt concentrations and in an ATP-independent manner, with an estimated binding site size of about 14 to 16 nucleotides. Using site-directed mutagenesis, the arginine located in pA104R's DNA-binding domain, at position 69, was found to be relevant for efficient DNA-binding activity. Together, pA104R and ASFV topoisomerase II (pP1192R) display DNA-supercoiling activity, although none of the proteins by themselves do, indicating that the two cooperate in this process. In ASFV-infected cells, A104R transcripts were detected from 2 h postinfection (hpi) onward, reaching a maximum concentration around 16 hpi. pA104R was detected from 12 hpi onward, localizing with viral DNA replication sites and being found exclusively in the Triton-insoluble fraction. Small interfering RNA (siRNA) knockdown experiments revealed that pA104R plays a critical role in viral DNA replication and gene expression, with transfected cells showing lower viral progeny numbers (up to a reduction of 82.0%), lower copy numbers of viral genomes (-78.3%), and reduced transcription of a late viral gene (-47.6%). Taken together, our results strongly suggest that pA104R participates in the modulation of viral DNA topology, probably being involved in viral DNA replication, transcription, and packaging, emphasizing that ASFV mutants lacking the A104R gene could be used as a strategy to develop a vaccine against ASFV. IMPORTANCE Recently reintroduced in Europe, African swine fever virus (ASFV) causes a fatal disease in domestic pigs, causing high economic losses in affected countries, as no vaccine or treatment is currently

  10. Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments.

    Science.gov (United States)

    Barski, Michal; Brennan, Benjamin; Miller, Ona K; Potter, Jane A; Vijayakrishnan, Swetha; Bhella, David; Naismith, James H; Elliott, Richard M; Schwarz-Linek, Ulrich

    2017-09-15

    Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83-248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation. Mutations of key crystal fibril interface residues in viruses encoding full-length NSs completely abrogated intranuclear filament formation in infected cells. We propose the fibrillar arrangement of the NSs core domain in crystals reveals the molecular basis of assembly of this key virulence factor in cell nuclei. Our findings have important implications for fundamental understanding of RVFV virulence.

  11. Identification of suitable areas for the occurrence of Rift Valley fever outbreaks in Spain using a multiple criteria decision framework.

    Science.gov (United States)

    Sánchez-Vizcaíno, Fernando; Martínez-López, Beatriz; Sánchez-Vizcaíno, José Manuel

    2013-07-26

    Rift Valley fever (RVF) is a mosquito-borne viral disease that may produce a considerable impact on the economy in affected countries. In the last decades, the geographic distribution of RVF virus has increased including most of the countries in Africa, Arabia Saudi and Yemen. This situation has raised the concerns regarding its potential introduction in the European Union (EU) countries where the high number of susceptible species and competent vectors may contribute to the spread of the disease and challenge its rapid control. Thus, the identification of the areas and time periods with highest suitability for RVF outbreak occurrence would be useful for improving the early detection and rapid response of the disease into free countries. The objective of this study was to identify suitable areas for the occurrence of RVF outbreaks in Spain using a multiple criteria decision making model based on weighted linear combination of factors in geographical information systems (GIS). To the best of the author's knowledge this is the first comprehensive GIS-based framework that provides risk maps for RVF suitability in an EU country. Spanish zones with the highest suitability for RVF were concentrated in the regions of Extremadura, south-western Castile and Leon, eastern Galicia, Asturias, Cantabria, Basque Country, northern-central and southern region of Andalusia and in the Balearic Islands. October and May were the most suitable months for RVF outbreak occurrence. Methods and results presented here may be useful to target risk-based surveillance strategies and to more cost-effectively control potential RVFV incursions into Spain. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Functional analysis of Rift Valley fever virus NSs encoding a partial truncation.

    Science.gov (United States)

    Head, Jennifer A; Kalveram, Birte; Ikegami, Tetsuro

    2012-01-01

    Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210-230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6-30, 31-55, 56-80, 81-105, 106-130, 131-155, 156-180, 181-205, 206-230, 231-248 or 249-265 lack functions of IFN-β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81-105, 106-130, 131-155, 156-180, 181-205, 206-230 or 231-248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.

  13. Functional analysis of Rift Valley fever virus NSs encoding a partial truncation.

    Directory of Open Access Journals (Sweden)

    Jennifer A Head

    Full Text Available Rift Valley fever virus (RVFV, belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR. NSs self-associates at the C-terminus 17 aa., while NSs at aa.210-230 binds to Sin3A-associated protein (SAP30 to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6-30, 31-55, 56-80, 81-105, 106-130, 131-155, 156-180, 181-205, 206-230, 231-248 or 249-265 lack functions of IFN-β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81-105, 106-130, 131-155, 156-180, 181-205, 206-230 or 231-248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.

  14. Pediatric Viral Exanthema: A Review Article

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    Mohammed Jafar Saffar

    2017-04-01

    Full Text Available Context Many diseases caused by viral agents are associated with fever and cutaneous manifestations. Viral exanthema is a widespread nonspecific skin rash, commonly characterized by generalized eruption of erythematous macules and papular lesions. Although these rashes are mostly benign and self-limited, some may be serious and life-threatening. Differentiation between severe and benign types is clinically important and life-saving. Evidence Acquisition In this narrative review, electronic databases, including Google Scholar, Science Direct, PubMed (including Medline, Web of Science, Scientific Information Database, and Scopus, were searched. We conducted a narrative review of papers published on pediatric viral exanthema during 2000 - 2016. The used keywords included “viral exanthema”, “fever”, and “skin rash”. Articles on skin rash, caused by drug reactions or nonviral exanthema, were excluded. Results Different viral agents can cause different types of skin reactions. Cutaneous manifestations and skin rashes can be categorized, based on the form of the rash (macular, papular, vesicular, blistery, petechial, and purpuric or the general term, which denotes illnesses such as measles-like morbilliform rash, rubella or rubelliform rash, and scarlatiniform rash, a scarlet-fever like infection. Conclusions Based on the findings, a systematic approach relying on accurate history-taking and analysis of epidemiological cues and rash characteristics is of great significance.

  15. Risk factors associated with human Rift Valley fever infection: systematic review and meta-analysis.

    Science.gov (United States)

    Nicholas, Dennis E; Jacobsen, Kathryn H; Waters, Nigel M

    2014-12-01

    To identify risk factors for human Rift Valley fever virus (RVFV) infection. A systematic review identified 17 articles reporting on 16 studies examining risk factors for RVFV. Pooled odds ratios (pOR) were calculated for exposures examined in four or more studies. Being male [pOR = 1.4 (1.0, 1.8)], contact with aborted animal tissue [pOR = 3.4 (1.6, 7.3)], birthing an animal [pOR = 3.2 (2.4, 4.2)], skinning an animal [pOR = 2.5 (1.9, 3.2)], slaughtering an animal [pOR = 2.4 (1.4, 4.1)] and drinking raw milk [pOR = 1.8 (1.2, 2.6)] were significantly associated with RVF infection after meta-analysis. Other potential risk factors include sheltering animals in the home and milking an animal, which may both involve contact with animal body fluids. Based on the identified risk factors, use of personal protective equipment and disinfectants by animal handlers may help reduce RVFV transmission during outbreaks. Milk pasteurisation and other possible preventive methods require further investigation. © 2014 John Wiley & Sons Ltd.

  16. Modeling the Impact of Climate Change on the Dynamics of Rift Valley Fever

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    Saul C. Mpeshe

    2014-01-01

    Full Text Available A deterministic SEIR model of rift valley fever (RVF with climate change parameters was considered to compute the basic reproduction number ℛ0 and investigate the impact of temperature and precipitation on ℛ0. To study the effect of model parameters to ℛ0, sensitivity and elasticity analysis of ℛ0 were performed. When temperature and precipitation effects are not considered, ℛ0 is more sensitive to the expected number of infected Aedes spp. due to one infected livestock and more elastic to the expected number of infected livestock due to one infected Aedes spp. When climatic data are used, ℛ0 is found to be more sensitive and elastic to the expected number of infected eggs laid by Aedes spp. via transovarial transmission, followed by the expected number of infected livestock due to one infected Aedes spp. and the expected number of infected Aedes spp. due to one infected livestock for both regions Arusha and Dodoma. These results call for attention to parameters regarding incubation period, the adequate contact rate of Aedes spp. and livestock, the infective periods of livestock and Aedes spp., and the vertical transmission in Aedes species.

  17. Modeling the Impact of Climate Change on the Dynamics of Rift Valley Fever

    Science.gov (United States)

    Mpeshe, Saul C.; Luboobi, Livingstone S.; Nkansah-Gyekye, Yaw

    2014-01-01

    A deterministic SEIR model of rift valley fever (RVF) with climate change parameters was considered to compute the basic reproduction number ℛ 0 and investigate the impact of temperature and precipitation on ℛ 0. To study the effect of model parameters to ℛ 0, sensitivity and elasticity analysis of ℛ 0 were performed. When temperature and precipitation effects are not considered, ℛ 0 is more sensitive to the expected number of infected Aedes spp. due to one infected livestock and more elastic to the expected number of infected livestock due to one infected Aedes spp. When climatic data are used, ℛ 0 is found to be more sensitive and elastic to the expected number of infected eggs laid by Aedes spp. via transovarial transmission, followed by the expected number of infected livestock due to one infected Aedes spp. and the expected number of infected Aedes spp. due to one infected livestock for both regions Arusha and Dodoma. These results call for attention to parameters regarding incubation period, the adequate contact rate of Aedes spp. and livestock, the infective periods of livestock and Aedes spp., and the vertical transmission in Aedes species. PMID:24795775

  18. Congo crimean hemorrhagic fever in balochistan

    International Nuclear Information System (INIS)

    Durrani, A.B.; Shaikh, M.; Khan, Z.

    2007-01-01

    To observe the pattern and mortality of Congo-Crimean Hemorrhagic Fever (CCHF) in Balochistan. Two hundred and twenty-six febrile patients with bleeding of sudden onset, with initial signs and symptoms including headache, high fever, back pain, joint pain, stomach pain, vomiting, red eyes, flushed face, red throat and petechiae on the palate of both sexes were screened for CCHF over a period of 10 years. Clinical criteria for initial diagnosis directed the subsequent diagnostic work-up. The ages of these patients ranged from 7 years to 74 years. Sixty-three percent of these patients were positive for CCHF. Males were 68% of the total patients. Over the years, CCHF showed a gradual increase ranging from 43% to 80%. Total mortality was 15%, all being secondary cases. Death was not observed in primary CCHF cases. In this study, suspicion of viral hemorrhagic fever was raised in 62% cases at the time of admission and the patients were immediately isolated, noninvasive procedures were instigated and barrier nursing was implemented. None of the family and hospital staff members who had close contact with the patient became ill, while those who were not suspected initially (38%) infected the health care workers and the family members. Although CCHF is rare, this study stresses the need for proper health facilities in Pakistan and to include VHF (viral hemorrhagic fevers) in the differential diagnosis of unexplained fever with hemorrhagic tendencies of sudden onset. (author)

  19. Inter-epidemic transmission of Rift Valley fever in livestock in the Kilombero River Valley, Tanzania: a cross-sectional survey.

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    Robert D Sumaye

    Full Text Available BACKGROUND: In recent years, evidence of Rift Valley fever (RVF transmission during inter-epidemic periods in parts of Africa has increasingly been reported. The inter-epidemic transmissions generally pass undetected where there is no surveillance in the livestock or human populations. We studied the presence of and the determinants for inter-epidemic RVF transmission in an area experiencing annual flooding in southern Tanzania. METHODOLOGY: A cross-sectional sero-survey was conducted in randomly selected cattle, sheep and goats in the Kilombero river valley from May to August 2011, approximately four years after the 2006/07 RVF outbreak in Tanzania. The exposure status to RVF virus (RVFV was determined using two commercial ELISA kits, detecting IgM and IgG antibodies in serum. Information about determinants was obtained through structured interviews with herd owners. FINDINGS: An overall seroprevalence of 11.3% (n = 1680 was recorded; 5.5% in animals born after the 2006/07 RVF outbreak and 22.7% in animals present during the outbreak. There was a linear increase in prevalence in the post-epidemic annual cohorts. Nine inhibition-ELISA positive samples were also positive for RVFV IgM antibodies indicating a recent infection. The spatial distribution of seroprevalence exhibited a few hotspots. The sex difference in seroprevalence in animals born after the previous epidemic was not significant (6.1% vs. 4.6% for females and males respectively, p = 0.158 whereas it was significant in animals present during the outbreak (26.0% vs. 7.8% for females and males respectively, p15 km from the flood plain were more likely to have antibodies than those living <5 km (OR 1.92; 95% CI 1.04-3.56. Species, breed, herd composition, grazing practices and altitude were not associated with seropositivity. CONCLUSION: These findings indicate post-epidemic transmission of RVFV in the study area. The linear increase in seroprevalence in the post-epidemic annual cohorts

  20. Hemorrhagic Fever with Renal Syndrome (HFRS)

    Science.gov (United States)

    ... Care includes careful management of the patient’s fluid (hydration) and electrolyte (e.g., sodium, potassium, chloride) levels, ... TG, Peters CJ. Viral Hemorrhagic Fevers. Seminars in Pediatric Infectious Diseases 1997;8(Suppl 1):64-73 . ...

  1. International travel between global urban centres vulnerable to yellow fever transmission.

    Science.gov (United States)

    Brent, Shannon E; Watts, Alexander; Cetron, Martin; German, Matthew; Kraemer, Moritz Ug; Bogoch, Isaac I; Brady, Oliver J; Hay, Simon I; Creatore, Maria I; Khan, Kamran

    2018-05-01

    To examine the potential for international travel to spread yellow fever virus to cities around the world. We obtained data on the international flight itineraries of travellers who departed yellow fever-endemic areas of the world in 2016 for cities either where yellow fever was endemic or which were suitable for viral transmission. Using a global ecological model of dengue virus transmission, we predicted the suitability of cities in non-endemic areas for yellow fever transmission. We obtained information on national entry requirements for yellow fever vaccination at travellers' destination cities. In 2016, 45.2 million international air travellers departed from yellow fever-endemic areas of the world. Of 11.7 million travellers with destinations in 472 cities where yellow fever was not endemic but which were suitable for virus transmission, 7.7 million (65.7%) were not required to provide proof of vaccination upon arrival. Brazil, China, India, Mexico, Peru and the United States of America had the highest volumes of travellers arriving from yellow fever-endemic areas and the largest populations living in cities suitable for yellow fever transmission. Each year millions of travellers depart from yellow fever-endemic areas of the world for cities in non-endemic areas that appear suitable for viral transmission without having to provide proof of vaccination. Rapid global changes in human mobility and urbanization make it vital for countries to re-examine their vaccination policies and practices to prevent urban yellow fever epidemics.

  2. Immunogenicity of a recombinant Rift Valley fever MP-12-NSm deletion vaccine candidate in calves.

    Science.gov (United States)

    Morrill, John C; Laughlin, Richard C; Lokugamage, Nandadeva; Wu, Jing; Pugh, Roberta; Kanani, Pooja; Adams, L Garry; Makino, Shinji; Peters, C J

    2013-10-09

    The safety and immunogenicity of an authentic recombinant (ar) of the live, attenuated MP-12 Rift Valley fever (RVF) vaccine virus with a large deletion of the NSm gene in the pre-Gn region of the M RNA segment (arMP-12ΔNSm21/384) was tested in 4-6 month old Bos taurus calves. Phase I of this study evaluated the neutralizing antibody response, measured by 80% plaque reduction neutralization (PRNT80), and clinical response of calves to doses of 1 × 10(1) through 1 × 10(7) plaque forming units (PFU) administered subcutaneously (s.c.). Phase II evaluated the clinical and neutralizing antibody response of calves inoculated s.c. or intramuscularly (i.m.) with 1 × 10(3), 1 × 10(4) or 1 × 10(5)PFU of arMP-12ΔNSm21/384. No significant adverse clinical events were observed in the animals in these studies. Of all specimens tested, only one vaccine viral isolate was recovered and that virus retained the introduced deletion. In the Phase I study, there was no statistically significant difference in the PRNT80 response between the dosage groups though the difference in IgG response between the 1 × 10(1)PFU group and the 1 × 10(5)PFU group was statistically significant (pPFU dose group showing the least response. The Phase II study also showed no statistically significant difference in PRNT80 response between the dosage groups though the difference in RVFV-specific IgG values was significantly increased (pPFU versus those inoculated s.c. with 1 × 10(3) or 1 × 10(5)PFU. Although the study groups were small, these data suggest that 1 × 10(4) or 1 × 10(5)PFU of arMP-12ΔNSm21/384 administered i.m. to calves will consistently stimulate a presumably protective PRNT80 response for at least 91 days post inoculation. Further studies of arMP-12ΔNSm21/384 are warranted to explore its suitability as an efficacious livestock vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Viral findings in adult hematological patients with neutropenia.

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    Lars Ohrmalm

    Full Text Available BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159 were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22% and NPA (18% with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL (p<0.01 and patients with fever (p<0.001 were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS (p<0.0001. CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia.

  4. Ebola hemorrhagic fever associated with novel virus strain, Uganda, 2007-2008.

    Science.gov (United States)

    Wamala, Joseph F; Lukwago, Luswa; Malimbo, Mugagga; Nguku, Patrick; Yoti, Zabulon; Musenero, Monica; Amone, Jackson; Mbabazi, William; Nanyunja, Miriam; Zaramba, Sam; Opio, Alex; Lutwama, Julius J; Talisuna, Ambrose O; Okware, Sam I

    2010-07-01

    During August 2007-February 2008, the novel Bundibugyo ebolavirus species was identified during an outbreak of Ebola viral hemorrhagic fever in Bundibugyo district, western Uganda. To characterize the outbreak as a requisite for determining response, we instituted a case-series investigation. We identified 192 suspected cases, of which 42 (22%) were laboratory positive for the novel species; 74 (38%) were probable, and 77 (40%) were negative. Laboratory confirmation lagged behind outbreak verification by 3 months. Bundibugyo ebolavirus was less fatal (case-fatality rate 34%) than Ebola viruses that had caused previous outbreaks in the region, and most transmission was associated with handling of dead persons without appropriate protection (adjusted odds ratio 3.83, 95% confidence interval 1.78-8.23). Our study highlights the need for maintaining a high index of suspicion for viral hemorrhagic fevers among healthcare workers, building local capacity for laboratory confirmation of viral hemorrhagic fevers, and institutionalizing standard precautions.

  5. Animal viral diseases and global change: Bluetongue and West Nile fever as paradigms

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    Miguel Angel eJimenez-Clavero

    2012-06-01

    Full Text Available Environmental changes have an undoubted influence on the appearance, distribution and evolution of infectious diseases, and notably on those transmitted by vectors. Global change refers to environmental changes arising from human activities affecting the fundamental mechanisms operating in the biosphere. This paper discusses the changes observed in recent times with regard to some important arboviral (arthropod-borne viral diseases of animals, and the role global change could have played in these variations. Two of the most important arboviral diseases of animals, bluetongue and West Nile fever/encephalitis, have been selected as models. In both cases, in the last 15 years an important leap forward has been observed, which has lead to considering them emerging diseases in different parts of the world. Bluetongue, affecting domestic ruminants, has recently afflicted livestock in Europe in an unprecedented epizootic, causing enormous economic losses. West Nile fever/encephalitis affects wildlife (birds, domestic animals (equines and humans, thus, beyond the economic consequences of its occurrence, as a zoonotic disease, it poses an important public health threat. West Nile virus has expanded in the last 12 years worldwide, and particularly in the Americas, where it first occurred in 1999, extending throughout the Americas relentlessly since then, causing a severe epidemic of disastrous consequences for public health, wildlife and livestock. In Europe, West Nile virus is known long time ago, but it is since the last years of the XXth century that its incidence has risen substantially. Circumstances such as global warming, changes in land use and water management, increase in travel, trade of animals, and others, can have an important influence in the observed changes in both diseases. The following question is raised: What is the contribution of global changes to the current increase of these diseases in the world?

  6. 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.

  7. 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.

  8. Data-driven modeling to assess receptivity for Rift Valley Fever virus.

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    Christopher M Barker

    2013-11-01

    Full Text Available Rift Valley Fever virus (RVFV is an enzootic virus that causes extensive morbidity and mortality in domestic ruminants in Africa, and it has shown the potential to invade other areas such as the Arabian Peninsula. Here, we develop methods for linking mathematical models to real-world data that could be used for continent-scale risk assessment given adequate data on local host and vector populations. We have applied the methods to a well-studied agricultural region of California with [Formula: see text]1 million dairy cattle, abundant and competent mosquito vectors, and a permissive climate that has enabled consistent transmission of West Nile virus and historically other arboviruses. Our results suggest that RVFV outbreaks could occur from February-November, but would progress slowly during winter-early spring or early fall and be limited spatially to areas with early increases in vector abundance. Risk was greatest in summer, when the areas at risk broadened to include most of the dairy farms in the study region, indicating the potential for considerable economic losses if an introduction were to occur. To assess the threat that RVFV poses to North America, including what-if scenarios for introduction and control strategies, models such as this one should be an integral part of the process; however, modeling must be paralleled by efforts to address the numerous remaining gaps in data and knowledge for this system.

  9. Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses.

    Science.gov (United States)

    Chang, Jinhong; Warren, Travis K; Zhao, Xuesen; Gill, Tina; Guo, Fang; Wang, Lijuan; Comunale, Mary Ann; Du, Yanming; Alonzi, Dominic S; Yu, Wenquan; Ye, Hong; Liu, Fei; Guo, Ju-Tao; Mehta, Anand; Cuconati, Andrea; Butters, Terry D; Bavari, Sina; Xu, Xiaodong; Block, Timothy M

    2013-06-01

    Host cellular endoplasmic reticulum α-glucosidases I and II are essential for the maturation of viral glycosylated envelope proteins that use the calnexin mediated folding pathway. Inhibition of these glycan processing enzymes leads to the misfolding and degradation of these viral glycoproteins and subsequent reduction in virion secretion. We previously reported that, CM-10-18, an imino sugar α-glucosidase inhibitor, efficiently protected the lethality of dengue virus infection of mice. In the current study, through an extensive structure-activity relationship study, we have identified three CM-10-18 derivatives that demonstrated superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever. Moreover, the three novel imino sugars significantly reduced the mortality of two of the most pathogenic hemorrhagic fever viruses, Marburg virus and Ebola virus, in mice. Our study thus proves the concept that imino sugars are promising drug candidates for the management of viral hemorrhagic fever caused by variety of viruses. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase.

    Science.gov (United States)

    Mudhasani, Rajini; Tran, Julie P; Retterer, Cary; Kota, Krishna P; Whitehouse, Chris A; Bavari, Sina

    2016-02-01

    Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)(FBXW11) E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCF(FBXW11) E3 ligase. We further show that disrupting the assembly of the SCF(FBXW11-NSs) E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCF(FBXW11-NSs) E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCF(FBXW11) complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.

  11. International Network for Capacity Building for the Control of Emerging Viral Vector-Borne Zoonotic Diseases: Arbo-Zoonet

    NARCIS (Netherlands)

    Ahmed, J.; Bouloy, M.; Ergonul, O.; Fooks, A.R.; Paweska, J.; Chevalier, V.; Drosten, C.; Moormann, R.J.M.; Tordo, N.; Vatansever, Z.; Calistri, P.; Estrada-Pena, A.; Mirazimi, A.; Unger, H.; Yin, H.; Seitzer, U.

    2009-01-01

    Arboviruses are arthropod-borne viruses, which include West Nile fever virus (WNFV), a mosquito-borne virus, Rift Valley fever virus (RVFV), a mosquito-borne virus, and Crimean-Congo haemorrhagic fever virus (CCHFV), a tick-borne virus. These arthropod-borne viruses can cause disease in different

  12. Nutritional management in Ebola haemorrhagic fever

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    Kamon Chaiyasit

    2015-06-01

    Full Text Available Ebola haemorrhagic fever is a viral infection causing a major health problem worldwide. In this short article, the authors briefly review and discuss on the nutritional management (energy, protein, fat and micronutrient in management of Ebola infection.

  13. Wolbachia Effects on Rift Valley Virus Infection in Culex tarsalis Mosquitoes

    Science.gov (United States)

    2017-04-25

    Wolbachia density in mosquitoes. 109" 110" Materials and Methods 111" Ethics statement 112" TR-17-113 Mosquitoes were maintained on commercially available...fever virus. 379" Vet Med Today. 2009; 883–893. 380" 29. Wilson M. Rift Valley fever virus ecology and the epidemiology of disease emergence. 381

  14. Hospital Preparations for Viral Hemorrhagic Fever Patients and Experience Gained from Admission of an Ebola Patient.

    Science.gov (United States)

    Haverkort, J J Mark; Minderhoud, A L C Ben; Wind, Jelte D D; Leenen, Luke P H; Hoepelman, Andy I M; Ellerbroek, Pauline M

    2016-02-01

    The Major Incident Hospital of the University Medical Centre of Utrecht has a longstanding history of preparing for the management of highly pathogenic and infectious organisms. An assessment of the hospital's preparations for an outbreak of viral hemorrhagic fever and its experience during admission of a patient with Ebola virus disease showed that the use of the buddy system, frequent training, and information sessions for staff and their relatives greatly increased the sense of safety and motivation among staff. Differing procedures among ambulance services limited the number of services used for transporting patients. Waste management was the greatest concern, and destruction of waste had to be outsourced. The admission of an Ebola patient proceeded without incident but led to considerable demands on staff. The maximum time allowed for wearing personal protective equipment was 45 minutes to ensure safety, and an additional 20 minutes was needed for recovery.

  15. Identification of potential vectors of and detection of antibodies against Rift Valley fever virus in livestock during interepizootic periods.

    Science.gov (United States)

    Rostal, Melinda K; Evans, Alina L; Sang, Rosemary; Gikundi, Solomon; Wakhule, Lilian; Munyua, Peninah; Macharia, Joseph; Feikin, Daniel R; Breiman, Robert F; Njenga, M Kariuki

    2010-05-01

    To evaluate the prevalence of Rift Valley fever virus (RVFV) antibodies in livestock and presence of competent mosquito vectors of RVFV during an interepizootic period (IEP) in Kenya. 208 sheep and 84 goats ranging in age from 4 months to 15 years, from 2 breeding herds. Blood specimens were collected from the sheep and goats during the 1999-2006 IEP in Rift Valley Province, and serum was harvested. Serum specimens were tested for IgG and IgM antibodies against RVFV by use of an ELISA. In addition, 7,134 mosquitoes were trapped in Naivasha, Nairobi, and Northeastern Province, and speciation was performed. No animals were seropositive for IgM against RVFV. Of the animals born after the 1997-1998 epizootic, 18% (34/188) of sheep were seropositive for IgG against RVFV, compared with 3% (2/75) of goats. Seventy percent (8,144/11,678) of the mosquitoes collected were of the Culex subgenera; 18% (2,102/11,678) were Aedes spp. Detection of IgG in the sera of sheep and goats born after the 1997-1998 epizootic and before the 2006 epizootic indicated that virus activity existed during the IEP. Detection of Aedes mosquitoes, which are competent vectors of RVFV, suggested that a cryptic vector-to-vertebrate cycle may exist during IEPs.

  16. Inter-epidemic abundance and distribution of potential mosquito vectors for Rift Valley fever virus in Ngorongoro district, Tanzania

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    Clement N. Mweya

    2015-01-01

    Full Text Available Background: Rift Valley fever (RVF is a mosquito-borne viral zoonosis that primarily affects ruminants but also has the capacity to infect humans. Objective: To determine the abundance and distribution of mosquito vectors in relation to their potential role in the virus transmission and maintenance in disease epidemic areas of Ngorongoro district in northern Tanzania. Methods: A cross-sectional entomological investigation was carried out before the suspected RVF outbreak in October 2012. Mosquitoes were sampled both outdoors and indoors using the Centre for Disease Control (CDC light traps and Mosquito Magnets baited with attractants. Outdoor traps were placed in proximity with breeding sites and under canopy in banana plantations close to the sleeping places of animals. Results: A total of 1,823 mosquitoes were collected, of which 87% (N=1,588 were Culex pipiens complex, 12% (N=226 Aedes aegypti, and 0.5% (N=9 Anopheles species. About two-thirds (67%; N=1,095 of C. pipiens complex and nearly 100% (N=225 of A. aegypti were trapped outdoors using Mosquito Magnets. All Anopheles species were trapped indoors using CDC light traps. There were variations in abundance of C. pipiens complex and A. aegypti among different ecological and vegetation habitats. Over three quarters (78% of C. pipiens complex and most (85% of the A. aegypti were trapped in banana and maize farms. Both C. pipiens complex and A. aegypti were more abundant in proximity with cattle and in semi-arid thorn bushes and lower Afro-montane. The highest number of mosquitoes was recorded in villages that were most affected during the RVF epidemic of 2007. Of the tested 150 pools of C. pipiens complex and 45 pools of A. aegypti, none was infected with RVF virus. Conclusions: These results provide insights into unique habitat characterisation relating to mosquito abundances and distribution in RVF epidemic-prone areas of Ngorongoro district in northern Tanzania.

  17. High content image-based screening of a protease inhibitor library reveals compounds broadly active against Rift Valley fever virus and other highly pathogenic RNA viruses.

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    Rajini Mudhasani

    2014-08-01

    Full Text Available High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥ 50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362, which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their

  18. 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.

  19. Association between nasal shedding and fever that influenza A (H3N2) induces in dogs.

    Science.gov (United States)

    Song, Daesub; Moon, Hyoungjoon; Jung, Kwonil; Yeom, Minjoo; Kim, Hyekwon; Han, Sangyoon; An, Dongjun; Oh, Jinsik; Kim, Jongman; Park, Bongkyun; Kang, Bokyu

    2011-01-05

    Avian origin canine influenza virus was reported in Korea. The dog to dog contact transmission of the avian origin canine influenza virus (CIV) H3N2 and CIV H3N8 was shown by experimental contact transmission. This study was focused on viral excretion and fever in order to elucidate the epidemiological associations which might be helpful to control the disease transmissions in CIV outbreak in dogs. An influenza seronegative 10-week-old Beagle dog was experimentally inoculated with the canine influenza virus A/canine/01/2007, subtype H3N2. Eight hours after inoculation, the infected dog was cohoused with seven uninfected Beagle dogs. Clinical signs including fever were recorded for 14 days post inoculation. The infected dog and four of seven contact dogs in the study showed clinical signs (sneezing, nasal discharge and coughing) during the study. Viral shedding occurred in all of the animals tested and began on 1 to 6 DPI in dogs with clinical signs. Elevated body temperatures above 39.5 °C (geometric mean temperature of 39.86 °C ± 0.49) were observed in all symptomatic dogs. The mean viral titer during fever was 2.99 log EID₅₀/ml, which was significantly higher than the viral titer detected in the non fever. The data show that contact dogs with a canine influenza infected dog shed different levels of virus in their nasal excretions and demonstrate that clinical signs, including fever, significantly correlate with the viral shedding.

  20. Association between nasal shedding and fever that influenza A (H3N2 induces in dogs

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    Oh Jinsik

    2011-01-01

    Full Text Available Abstract Background Avian origin canine influenza virus was reported in Korea. The dog to dog contact transmission of the avian origin canine influenza virus (CIV H3N2 and CIV H3N8 was shown by experimental contact transmission. This study was focused on viral excretion and fever in order to elucidate the epidemiological associations which might be helpful to control the disease transmissions in CIV outbreak in dogs. Methods An influenza seronegative 10-week-old Beagle dog was experimentally inoculated with the canine influenza virus A/canine/01/2007, subtype H3N2. Eight hours after inoculation, the infected dog was cohoused with seven uninfected Beagle dogs. Clinical signs including fever were recorded for 14 days post inoculation. Results The infected dog and four of seven contact dogs in the study showed clinical signs (sneezing, nasal discharge and coughing during the study. Viral shedding occurred in all of the animals tested and began on 1 to 6 DPI in dogs with clinical signs. Elevated body temperatures above 39.5°C (geometric mean temperature of 39.86°C±0.49 were observed in all symptomatic dogs. The mean viral titer during fever was 2.99 log EID50/ml, which was significantly higher than the viral titer detected in the non fever. Conclusions The data show that contact dogs with a canine influenza infected dog shed different levels of virus in their nasal excretions and demonstrate that clinical signs, including fever, significantly correlate with the viral shedding.

  1. Mutation of adjacent cysteine residues in the NSs protein of Rift Valley fever virus results in loss of virulence in mice.

    Science.gov (United States)

    Monteiro, Gaby E R; Jansen van Vuren, Petrus; Wichgers Schreur, Paul J; Odendaal, Lieza; Clift, Sarah J; Kortekaas, Jeroen; Paweska, Janusz T

    2018-04-02

    The NSs protein encoded by the S segment of Rift Valley fever virus (RVFV) is the major virulence factor, counteracting the host innate antiviral defence. It contains five highly conserved cysteine residues at positions 39, 40, 149, 178 and 194, which are thought to stabilize the tertiary and quaternary structure of the protein. Here, we report significant differences between clinical, virological, histopathological and host gene responses in BALB/c mice infected with wild-type RVFV (wtRVFV) or a genetic mutant having a double cysteine-to-serine substitution at residues 39 and 40 of the NSs protein (RVFV-C39S/C40S). Mice infected with the wtRVFV developed a fatal acute disease; characterized by high levels of viral replication, severe hepatocellular necrosis, and massive up-regulation of transcription of genes encoding type I and -II interferons (IFN) as well as pro-apoptotic and pro-inflammatory cytokines. The RVFV-C39S/C40S mutant did not cause clinical disease and its attenuated virulence was consistent with virological, histopathological and host gene expression findings in BALB/c mice. Clinical signs in mice infected with viruses containing cysteine-to-serine substitutions at positions 178 or 194 were similar to those occurring in mice infected with the wtRVFV, while a mutant containing a substitution at position 149 caused mild, non-fatal disease in mice. As mutant RVFV-C39S/C40S showed an attenuated phenotype in mice, the molecular mechanisms behind this attenuation were further investigated. The results show that two mechanisms are responsible for the attenuation; (1) loss of the IFN antagonistic propriety characteristic of the wtRVFV NSs and (2) the inability of the attenuated mutant to degrade Proteine Kinase R (PKR). Copyright © 2018. Published by Elsevier B.V.

  2. THE MEANING OF FEVER IN CHILDREN

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    A. S. Polyakova

    2015-01-01

    Full Text Available Fever is a normal physiological response to illness in young children and it is often associated with a self-limiting viral infection. Fever is not a diagnosis, but a symptom of illness. A diagnosis of the underlying illness is essential to institute appropriate treatment. Although it is a normal response, that facilitates and accelerates recovery, some people, including many doctors, believe that fever should be treated to reduce temperature without determining the underlying illness causing the fever. Antipyretics should be used to make the child more comfortable and not used routinely with the sole aim of reducing the temperature. This article aims to acquaint primary healthcare workers and general practitioners with last guidelines to assist the measurement of body temperature, deciding on when to refer and the appropriate use of antipyretic medication in children, efficacy and safety of paracetamol and ibuprofen in oral and rectal forms. 

  3. Risk of transmission of viral haemorrhagic fevers and the insecticide susceptibilitystatus of aedes aegypti (linnaeus) in some sites in Accra, Ghana.

    Science.gov (United States)

    Suzuki, Takashi; Osei, Joseph H; Sasaki, Akihiro; Adimazoya, Michelle; Appawu, Maxwell; Boakye, Daniel; Ohta, Nobuo; Dadzie, Samuel

    2016-09-01

    Dengue is one of the emerging diseases that can mostly only be controlled by vector control since there is no vaccine for the disease. Although, Dengue has not been reported in Ghana, movement of people from neighbouring countries where the disease has been reported can facilitate transmission of the disease. This study was carried on the University of Ghana campus to determine the risk of transmission of viral haemorrhagic fevers and the insecticide susceptibility status of Ae. aegypti in some sites in Accra, Ghana. Larval surveys were carried to inspect containers within households and estimate larval indices and adult Aedes mosquitoes were collected using human landing collection technique. WHO tube assays was used to assess the insecticide susceptibility status of Aedes mosquitoes. Ae. aegypti were the most prevalent species, 75.5% and followed by Ae. vittatus , 23.9 %. Ae. albopictus and Ae. granti were in smaller numbers. Household index (HI), Breteau index (BI), and container index were calculated as 8.2%, 11.2% and 10.3% respectively with man-vector contact rate of 0.67 bites/man-hour estimated for the area. The mortalities recorded for Ae. aegypti from WHO tube assays was 88%, 94%, 80% and 99% for DDT (4%), deltamethrin (0.05%), lambdacyhalothrin (0.05%) and permethrin (0.75%) respectively. The survey results indicated that the density of Aedes mosquitoes was considered to be sufficient to promote an outbreak of viral haemorrhagic fevers on Legon Campus. Aedes mosquitoes were found to be resistant to DDT, deltamethrin and lamdacyhalothrin, but susceptible to permethrin. This study was supported in part by Japan Initiative for Global Research Network on Infectious Diseases (J-Grid).

  4. Climate change and the emergence of vector-borne diseases in Europe: case study of dengue fever.

    Science.gov (United States)

    Bouzid, Maha; Colón-González, Felipe J; Lung, Tobias; Lake, Iain R; Hunter, Paul R

    2014-08-22

    Dengue fever is the most prevalent mosquito-borne viral disease worldwide. Dengue transmission is critically dependent on climatic factors and there is much concern as to whether climate change would spread the disease to areas currently unaffected. The occurrence of autochthonous infections in Croatia and France in 2010 has raised concerns about a potential re-emergence of dengue in Europe. The objective of this study is to estimate dengue risk in Europe under climate change scenarios. We used a Generalized Additive Model (GAM) to estimate dengue fever risk as a function of climatic variables (maximum temperature, minimum temperature, precipitation, humidity) and socioeconomic factors (population density, urbanisation, GDP per capita and population size), under contemporary conditions (1985-2007) in Mexico. We then used our model estimates to project dengue incidence under baseline conditions (1961-1990) and three climate change scenarios: short-term 2011-2040, medium-term 2041-2070 and long-term 2071-2100 across Europe. The model was used to calculate average number of yearly dengue cases at a spatial resolution of 10 × 10 km grid covering all land surface of the currently 27 EU member states. To our knowledge, this is the first attempt to model dengue fever risk in Europe in terms of disease occurrence rather than mosquito presence. The results were presented using Geographical Information System (GIS) and allowed identification of areas at high risk. Dengue fever hot spots were clustered around the coastal areas of the Mediterranean and Adriatic seas and the Po Valley in northern Italy. This risk assessment study is likely to be a valuable tool assisting effective and targeted adaptation responses to reduce the likely increased burden of dengue fever in a warmer world.

  5. Hemorrhagic fever with renal syndrome and coexisting hantavirus pulmonary syndrome

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    Young Min Hong

    2012-06-01

    Full Text Available Hemorrhagic fever with renal syndrome (HFRS is an acute viral disease with fever, hemorrhage and renal failure caused by hantavirus infection. Hantavirus induces HFRS or hantavirus pulmonary syndrome (HPS. HPS progression to a life-threatening pulmonary disease is found primarily in the USA and very rarely in South Korea. Here, we report a case of HFRS and coexisting HPS.

  6. Yellow fever: an update.

    Science.gov (United States)

    Monath, T P

    2001-08-01

    Yellow fever, the original viral haemorrhagic fever, was one of the most feared lethal diseases before the development of an effective vaccine. Today the disease still affects as many as 200,000 persons annually in tropical regions of Africa and South America, and poses a significant hazard to unvaccinated travellers to these areas. Yellow fever is transmitted in a cycle involving monkeys and mosquitoes, but human beings can also serve as the viraemic host for mosquito infection. Recent increases in the density and distribution of the urban mosquito vector, Aedes aegypti, as well as the rise in air travel increase the risk of introduction and spread of yellow fever to North and Central America, the Caribbean and Asia. Here I review the clinical features of the disease, its pathogenesis and pathophysiology. The disease mechanisms are poorly understood and have not been the subject of modern clinical research. Since there is no specific treatment, and management of patients with the disease is extremely problematic, the emphasis is on preventative vaccination. As a zoonosis, yellow fever cannot be eradicated, but reduction of the human disease burden is achievable through routine childhood vaccination in endemic countries, with a low cost for the benefits obtained. The biological characteristics, safety, and efficacy of live attenuated, yellow fever 17D vaccine are reviewed. New applications of yellow fever 17D virus as a vector for foreign genes hold considerable promise as a means of developing new vaccines against other viruses, and possibly against cancers.

  7. Spatial, seasonal and climatic predictive models of Rift Valley fever disease across Africa.

    Science.gov (United States)

    Redding, David W; Tiedt, Sonia; Lo Iacono, Gianni; Bett, Bernard; Jones, Kate E

    2017-07-19

    Understanding the emergence and subsequent spread of human infectious diseases is a critical global challenge, especially for high-impact zoonotic and vector-borne diseases. Global climate and land-use change are likely to alter host and vector distributions, but understanding the impact of these changes on the burden of infectious diseases is difficult. Here, we use a Bayesian spatial model to investigate environmental drivers of one of the most important diseases in Africa, Rift Valley fever (RVF). The model uses a hierarchical approach to determine how environmental drivers vary both spatially and seasonally, and incorporates the effects of key climatic oscillations, to produce a continental risk map of RVF in livestock (as a proxy for human RVF risk). We find RVF risk has a distinct seasonal spatial pattern influenced by climatic variation, with the majority of cases occurring in South Africa and Kenya in the first half of an El Niño year. Irrigation, rainfall and human population density were the main drivers of RVF cases, independent of seasonal, climatic or spatial variation. By accounting more subtly for the patterns in RVF data, we better determine the importance of underlying environmental drivers, and also make space- and time-sensitive predictions to better direct future surveillance resources.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'. © 2017 The Authors.

  8. Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers

    Directory of Open Access Journals (Sweden)

    Masayuki Saijo

    2012-10-01

    Full Text Available The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World (OW and New World (NW complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever (VHF in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques for these virus infections in institutes without BSL-4 facilities. To overcome these difficulties, antibody detection systems in the form of an enzyme-linked immunosorbent assay (ELISA and an indirect immunofluorescence assay were developed using recombinant nucleoproteins (rNPs derived from these viruses. Furthermore, several antigen-detection assays were developed. For example, novel monoclonal antibodies (mAbs to the rNPs of Lassa and Junin viruses were generated. Sandwich antigen-capture (Ag-capture ELISAs using these mAbs as capture antibodies were developed and confirmed to be sensitive and specific for detecting the respective arenavirus NPs. These rNP-based assays were proposed to be useful not only for an etiological diagnosis of VHFs, but also for seroepidemiological studies on VHFs. We recently developed arenavirus neutralization assays using vesicular stomatitis virus (VSV-based pseudotypes bearing arenavirus recombinant glycoproteins. The goal of this article is to review the recent advances in developing laboratory diagnostic assays based on recombinant viral proteins for the diagnosis of VHFs and epidemiological studies on the VHFs caused by arenaviruses.

  9. Planning for Rift Valley fever virus: use of geographical information systems to estimate the human health threat of white-tailed deer (Odocoileus virginianus-related transmission

    Directory of Open Access Journals (Sweden)

    Sravan Kakani

    2010-11-01

    Full Text Available Rift Valley fever (RVF virus is a mosquito-borne phlebovirus of the Bunyaviridae family that causes frequent outbreaks of severe animal and human disease in sub-Saharan Africa, Egypt and the Arabian Peninsula. Based on its many known competent vectors, its potential for transmission via aerosolization, and its progressive spread from East Africa to neighbouring regions, RVF is considered a high-priority, emerging health threat for humans, livestock and wildlife in all parts of the world. Introduction of West Nile virus to North America has shown the potential for “exotic” viral pathogens to become embedded in local ecological systems. While RVF is known to infect and amplify within domestic livestock, such as taurine cattle, sheep and goats, if RVF virus is accidentally or intentionally introduced into North America, an important unknown factor will be the role of local wildlife in the maintenance or propagation of virus transmission. We examined the potential impact of RVF transmission via white-tailed deer (Odocoileus virginianus in a typical north-eastern United States urban-suburban landscape, where livestock are rare but where these potentially susceptible, ungulate wildlife are highly abundant. Model results, based on overlap of mosquito, human and projected deer densities, indicate that a significant proportion (497/1186 km2, i.e. 42% of the urban and peri-urban landscape could be affected by RVF transmission during the late summer months. Deer population losses, either by intervention for herd reduction or by RVF-related mortality, would substantially reduce these likely transmission zones to 53.1 km2, i.e. by 89%.

  10. Rift Valley fever virus infections in Egyptian cattle and their prevention.

    Science.gov (United States)

    Mroz, C; Gwida, M; El-Ashker, M; Ziegler, U; Homeier-Bachmann, T; Eiden, M; Groschup, M H

    2017-12-01

    Rift Valley fever virus (RVFV) causes consistently severe outbreaks with high public health impacts and economic losses in livestock in many African countries and has also been introduced to Saudi Arabia and Yemen. Egypt with its four large outbreaks in the last 40 years represents the northernmost endemic area of RVFV. The purpose of this study was to provide an insight into the current anti-RVFV antibody status in immunized as well as non-immunized dairy cattle from the Nile Delta of Egypt. During 2013-2015, a total of 4,167 dairy cattle from four governorates including Dakahlia, Damietta, Gharbia and Port Said were investigated. All cattle were born after 2007 and therewith after the last reported Egyptian RVFV outbreak in 2003. The samples derived from vaccinated animals from 26 different dairy farms as well as non-immunized cattle from 27 different smallholding flocks. All samples were examined following a three-part analysis including a commercially available competition ELISA, an in-house immunofluorescence assay and a virus neutralization test. Additionally, a subset of samples was analysed for acute infections using IgM ELISA and real-time reverse transcriptase PCR. The results indicated that the RVFV is still circulating in Egypt as about 10% of the non-immunized animals exhibited RVFV-specific antibodies. Surprisingly, the antibody prevalence in immunized animals was not significantly higher than that in non-vaccinated animals which points out the need for further evaluation of the vaccination programme. Due to the substantial role of livestock in the amplification and transmission of RVFV, further recurrent monitoring of the antibody prevalence in susceptible species is highly warranted. © 2017 Blackwell Verlag GmbH.

  11. Relationship of climate, geography, and geology to the incidence of Rift Valley fever in Kenya during the 2006-2007 outbreak.

    Science.gov (United States)

    Hightower, Allen; Kinkade, Carl; Nguku, Patrick M; Anyangu, Amwayi; Mutonga, David; Omolo, Jared; Njenga, M Kariuki; Feikin, Daniel R; Schnabel, David; Ombok, Maurice; Breiman, Robert F

    2012-02-01

    We estimated Rift Valley fever (RVF) incidence as a function of geological, geographical, and climatological factors during the 2006-2007 RVF epidemic in Kenya. Location information was obtained for 214 of 340 (63%) confirmed and probable RVF cases that occurred during an outbreak from November 1, 2006 to February 28, 2007. Locations with subtypes of solonetz, calcisols, solonchaks, and planosols soil types were highly associated with RVF occurrence during the outbreak period. Increased rainfall and higher greenness measures before the outbreak were associated with increased risk. RVF was more likely to occur on plains, in densely bushed areas, at lower elevations, and in the Somalia acacia ecological zone. Cases occurred in three spatial temporal clusters that differed by the date of associated rainfall, soil type, and land usage.

  12. Cellular Hsp27 interacts with classical swine fever virus NS5A protein and negatively regulates viral replication by the NF-κB signaling pathway.

    Science.gov (United States)

    Ling, Shifeng; Luo, Mingyang; Jiang, Shengnan; Liu, Jiayu; Ding, Chunying; Zhang, Qinghuan; Guo, Huancheng; Gong, Wenjie; Tu, Changchun; Sun, Jinfu

    2018-05-01

    Classical swine fever virus (CSFV) nonstructural protein NS5A is a multifunctional protein functioning in regulation of viral genome replication, protein translation and assembly by interaction with viral or host proteins. Here, heat shock protein 27 (Hsp27) has been identified as a novel binding partner of NS5A by using His tag "pull down" coupled with shotgun LC-MS/MS, with interaction of both proteins further confirmed by co-immunoprecipitation and laser confocal assays. In PK-15 cells, silencing of Hsp27 expression by siRNA enhanced CSFV replication, and upregulation of Hsp27 inhibited viral proliferation. Additionally, we have shown that overexpression of Hsp27 increased NF-κB signaling induced by TNFα. Blocking NF-κB signaling in PK-15 cells overexpressing Hsp27 by ammonium pyrrolidinedithiocarbamate (PDTC) eliminated the inhibition of CSFV replication by Hsp27. These findings clearly demonstrate that the inhibition of CSFV replication by Hsp27 is mediated via the NF-κB signaling pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Crimean-Congo Haemorrhagic Fever in Kosova : a fatal case report

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    Raka Lul

    2006-10-01

    Full Text Available Abstract Crimean-Congo haemorrhagic fever (CCHF is an often fatal viral infection described in about 30 countries around the world. The authors report a fatal case of Crimean-Congo hemorrhagic fever (CCHF observed in a patient from Kosova. The diagnosis of CCHF was confirmed by reverse transcription-PCR. Late diagnosis decreased the efficacy of treatment and patient died due to severe complications of infection.

  14. 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.

  15. [Marburg and Ebola hemorrhagic fevers--pathogens, epidemiology and therapy].

    Science.gov (United States)

    Stock, Ingo

    2014-09-01

    Marburg and Ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. They are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. Elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. Marburg and Ebola hemorrhagic fevers are caused by (Lake victoria) Marburg virus and different species of Ebola viruses, respectively. They are enveloped, single-stranded RNA viruses and belong to the family of filoviridae. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, ranging from 25 to 90% or more. Outbreaks of Marburg and Ebola hemorrhagic fever occur in certain regions of equatorial Africa at irregular intervals. Since 2000, the number of outbreaks has increased. In 2014, the biggest outbreak of a filovirus-induced hemorrhagic fever that has been documented so far occurred from March to July 2014 in Guinea, Sierra Leone, Liberia and Nigeria. The outbreak was caused by a new variant of Zaire Ebola-Virus, affected more than 2600 people (stated 20 August) and was associated with case-fatality rates of up to 67% (Guinea). Treatment of Marburg and Ebola hemorrhagic fevers is symptomatic and supportive, licensed antiviral agents are currently not available. Recently, BCX4430, a promising synthetic adenosine analogue with high in vitro and in vivo activity against filoviruses and other RNA viruses, has been described. BCX4430 inhibits viral RNA polymerase activity and protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. Nucleic acid-based products, recombinant vaccines and antibodies appear to be less suitable for the treatment of Marburg and Ebola hemorrhagic fevers.

  16. Validation of an IgM antibody capture ELISA based on a recombinant nucleoprotein for identification of domestic ruminants infected with Rift Valley fever virus.

    Science.gov (United States)

    Williams, Roy; Ellis, Charlotte Elizabeth; Smith, Shirley Jacqueline; Potgieter, Christiaan Abraham; Wallace, David; Mareledwane, Vuyokazi Epipodia; Majiwa, Phelix Antipas Ochola

    2011-11-01

    The presence of competent vectors in some countries currently free of Rift Valley fever (RVF) and global changes in climate, travel and trade have increased the risk of RVF spreading to new regions and have emphasised the need for accurate and reliable diagnostic tools for early diagnosis during RVF outbreaks. Highly sensitive viral detection systems like PCR have a limited use during outbreaks because of the short duration of viraemia, whereas antibodies like specific IgM which are serological indicators of acute infection, can be detected for up to 50 days after infection. Using the highly conserved and immunogenic recombinant nucleoprotein of RVF virus in an IgM capture ELISA, the risk of laboratory infection associated with traditional serological methods is avoided. The use of pre-coated/pre-blocked ELISA plates and the conjugation of the recombinant nucleoprotein with horseradish peroxidase simplified and shortened the assay procedure. Results showed the assay to be highly reproducible with a lower detection limit equal to that of a commercial competition ELISA. By receiver operating characteristic (ROC) curve analysis the area under curve (AUC) index was determined as 1.0 and the diagnostic sensitivity and specificity at a PP cut-off value of 4.1 as 100% and 99.78% respectively. The results of this study demonstrated that the IgM capture ELISA is a safe, reliable and highly accurate diagnostic tool which can be used on its own or in parallel with other methods for the early diagnosis of RVF virus infection and also for monitoring of immune responses in vaccinated domestic ruminants. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Rescue of infectious rift valley fever virus entirely from cDNA, analysis of virus lacking the NSs gene, and expression of a foreign gene.

    Science.gov (United States)

    Ikegami, Tetsuro; Won, Sungyong; Peters, C J; Makino, Shinji

    2006-03-01

    Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) has a tripartite negative-strand genome, causes a mosquito-borne disease that is endemic in sub-Saharan African countries and that also causes large epidemics among humans and livestock. Furthermore, it is a bioterrorist threat and poses a risk for introduction to other areas. In spite of its danger, neither veterinary nor human vaccines are available. We established a T7 RNA polymerase-driven reverse genetics system to rescue infectious clones of RVFV MP-12 strain entirely from cDNA, the first for any phlebovirus. Expression of viral structural proteins from the protein expression plasmids was not required for virus rescue, whereas NSs protein expression abolished virus rescue. Mutants of MP-12 partially or completely lacking the NSs open reading frame were viable. These NSs deletion mutants replicated efficiently in Vero and 293 cells, but not in MRC-5 cells. In the latter cell line, accumulation of beta interferon mRNA occurred after infection by these NSs deletion mutants, but not after infection by MP-12. The NSs deletion mutants formed larger plaques than MP-12 did in Vero E6 cells and failed to shut off host protein synthesis in Vero cells. An MP-12 mutant carrying a luciferase gene in place of the NSs gene replicated as efficiently as MP-12 did, produced enzymatically active luciferase during replication, and stably retained the luciferase gene after 10 virus passages, representing the first demonstration of foreign gene expression in any bunyavirus. This reverse genetics system can be used to study the molecular virology of RVFV, assess current vaccine candidates, produce new vaccines, and incorporate marker genes into animal vaccines.

  18. First recorded outbreak of yellow fever in Kenya, 1992-1993. II. Entomologic investigations.

    Science.gov (United States)

    Reiter, P; Cordellier, R; Ouma, J O; Cropp, C B; Savage, H M; Sanders, E J; Marfin, A A; Tukei, P M; Agata, N N; Gitau, L G; Rapuoda, B A; Gubler, D J

    1998-10-01

    The first recorded outbreak of yellow fever in Kenya occurred from mid-1992 through March 1993 in the south Kerio Valley, Rift Valley Province. We conducted entomologic studies in February-March 1993 to identify the likely vectors and determine the potential for transmission in the surrounding rural and urban areas. Mosquitoes were collected by landing capture and processed for virus isolation. Container surveys were conducted around human habitation. Transmission was mainly in woodland of varying density, at altitudes of 1,300-1,800 m. The abundance of Aedes africanus in this biotope, and two isolations of virus from pools of this species, suggest that it was the principal vector in the main period of the outbreak. A third isolate was made from a pool of Ae. keniensis, a little-known species that was collected in the same biotope. Other known yellow fever vectors that were collected in the arid parts of the valley may have been involved at an earlier stage of the epidemic. Vervet monkeys and baboons were present in the outbreak area. Peridomestic mosquito species were absent but abundant at urban sites outside the outbreak area. The entomologic and epidemiologic evidence indicate that this was a sylvatic outbreak in which human cases were directly linked to the epizootic and were independent of other human cases. The region of the Kerio Valley is probably subject to recurrent wandering epizootics of yellow fever, although previous episodes of scattered human infection have gone unrecorded. The risk that the disease could emerge as an urban problem in Kenya should not be ignored.

  19. An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine

    OpenAIRE

    Wauters, Robert H.; Hernandez, Camellia L.; Petersen, Maureen M.

    2017-01-01

    Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation.

  20. An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine.

    Science.gov (United States)

    Wauters, Robert H; Hernandez, Camellia L; Petersen, Maureen M

    2017-09-19

    Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation.

  1. Establishment of recombinase polymerase amplification assay for five hemorrhagic fever-related viruses

    Directory of Open Access Journals (Sweden)

    Xue-feng CAO

    2017-08-01

    Full Text Available Objective To establish a one-step recombinase polymerase amplification (RPA method for pathogen screening and rapid detection in the field targeting for five hemorrhagic fever related viruses (Zaire ebola virus, Sudan ebola virus, Marburg virus, Lassa virus and Yellow fever virus. Methods The specific nucleic acid (NA fragments of each virus were selected as target genes by genome sequence analysis, and the primers and probes for RPA assays were designed according to the sequence. A series of diluted template genes were used for RPA detection to determine the sensitivity. The hemorrhagic fever-related viral nucleic acids were used for RPA detection to determine the specificity. The amplification experiments were carried out at different temperature ranging from 37℃ to 42℃ to validate the reaction temperature range. Results The RPA reaction systems of the five hemorrhagic fever viruses could effectively amplify the target genes, the sensitivities were between 1.5×102 and 1.5×103 copies. No cross reactions existed with the other hemorrhagic fever-related viral genes. Meanwhile, RPA assay could effectively amplify the target genes at 37-42℃. Conclusion The isothermal RPA assays of five hemorrhagic fever viruses are established, which may amply target genes fast and react at a wide temperature range, and be potentially useful for in field pathogens detection. DOI: 10.11855/j.issn.0577-7402.2017.06.09

  2. Intracellular Detection of Viral Transcription and Replication Using RNA FISH

    Science.gov (United States)

    2016-05-26

    Chapter 14. Intracellular detection of viral transcription and replication using RNA FISH i. Summary/Abstract Many hemorrhagic fever viruses...only allow entirely new investigations into the replication of these viruses, but also how this method can be applied to any virus with a known...localization, TurboFISH, hemorrhagic fever virus replication 1. Introduction RNA FISH was developed as a method to visualize cellular RNA by binding a

  3. Potential for North American mosquitoes (Diptera: Culicidae) to transmit rift valley fever virus.

    Science.gov (United States)

    Turell, Michael J; Wilson, William C; Bennett, Kristine E

    2010-09-01

    To determine which arthropods should be targeted for control should Rift Valley fever virus (RVFV) be detected in North America, we evaluated Culex erraticus (Dyar and Knab), Culex erythrothorax Dyar, Culex nigripalpus Theobald, Culex pipiens L., Culex quinquefasciatus Say, Culex tarsalis Coquillett, Aedes dorsalis (Wiedemann), Aedes vexans (Meigen), Anopheles quadrimaculatus Say, and Culicoides sonorensis Wirth and Jones from the western, midwestern, and southern United States for their ability to transmit RVFV. Female mosquitoes were allowed to feed on adult hamsters inoculated with RVFV, after which engorged mosquitoes were incubated for 7-21 d at 260C, then allowed to refeed on susceptible hamsters, and tested to determine infection, dissemination, and transmission rates. Other specimens were inoculated intrathoracically, held for 7 d, and then allowed to feed on a susceptible hamster to check for a salivary gland barrier. When exposed to hamsters with viremias > or =10(8.8) plaque-forming units/ml blood, Cx. tarsalis transmitted RVFV efficiently (infection rate = 93%, dissemination rate = 56%, and estimated transmission rate = 52%). In contrast, when exposed to the same virus dose, none of the other species tested transmitted RVFV efficiently. Estimated transmission rates for Cx. erythrothorax, Cx. pipiens, Cx. erraticus, and Ae. dorsalis were 10, 8, 4, and 2%, respectively, and for the remaining species were feeding preference, longevity, and foraging behavior should be considered when determining the potential role that these species could play in RVFV transmission.

  4. Environmental change and Rift Valley fever in eastern Africa: projecting beyond HEALTHY FUTURES

    Directory of Open Access Journals (Sweden)

    David Taylor

    2016-03-01

    Full Text Available Outbreaks of Rift Valley fever (RVF, a relatively recently emerged zoonosis endemic to large parts of sub-Saharan Africa that has the potential to spread beyond the continent, have profound health and socio-economic impacts, particularly in communities where resilience is already low. Here output from a new, dynamic disease model [the Liverpool RVF (LRVF model], driven by downscaled, bias-corrected climate change data from an ensemble of global circulation models from the Inter-Sectoral Impact Model Intercomparison Project run according to two radiative forcing scenarios [representative concentration pathway (RCP4.5 and RCP8.5], is combined with results of a spatial assessment of social vulnerability to the disease in eastern Africa. The combined approach allowed for analyses of spatial and temporal variations in the risk of RVF to the end of the current century. Results for both scenarios highlight the high-risk of future RVF outbreaks, including in parts of eastern Africa to date unaffected by the disease. The results also highlight the risk of spread from/to countries adjacent to the study area, and possibly farther afield, and the value of considering the geography of future projections of disease risk. Based on the results, there is a clear need to remain vigilant and to invest not only in surveillance and early warning systems, but also in addressing the socio-economic factors that underpin social vulnerability in order to mitigate, effectively, future impacts.

  5. [Crimean-Congo hemorrhagic fever].

    Science.gov (United States)

    Saijo, Masayuki; Moriikawa, Shigeru; Kurane, Ichiro

    2004-12-01

    Crimean-Congo hemorrhagic fever (CCHF) is an acute infectious disease caused by CCHF virus (CCHFV), a member of the family Bunyaviridae, genus Nairovirus. The case fatality rate of CCHF ranges from 10-40%. Because CCHF is not present in Japan, many Japanese virologists and clinicians are not very familiar with this disease. However, there remains the possibility of an introduction of CCHFV or other hemorrhagic fever viruses into Japan from surrounding endemic areas. Development of diagnostic laboratory capacity for viral hemorrhagic fevers is necessary even in countries without these diseases. At the National Institute of Infectious Diseases, Tokyo, Japan, laboratory-based systems such as recombinant protein-based antibody detection, antigen-capture and pathological examination have been developed. In this review article, epidemiologic and clinical data on CCHF in the Xinjiang Uygur Autonomous Region, compiled through field investigations and diagnostic testing utilizing the aforementioned laboratory systems, are presented. CCHFV infections are closely associated with the environmental conditions, life styles, religion, occupation, and human economic activities. Based on these data, preventive measures for CCHFV infections are also discussed.

  6. Crimean-Congo Hemorrhagic Fever

    Directory of Open Access Journals (Sweden)

    Emadi Koochak H

    2003-10-01

    Full Text Available Crimean-Congo hemorrhagic fever (CCHF was first described in the Crimea in 1944 and then in 1956 in congo. CCHF is a viral hemorrhagic fever of the Nairovirus group that belongs to Bunyaviridae family virus. It is transmitted to human by tick bite. The most efficient and common tick that is the vectors of CCHF is a member of the Hyalomma genus which infected many mammals such as livestock, this tick is the main reservoire of virus in nature. Humans also become infected with CCHF virus by direct contact with blood or other infected tissues from livestock or human patients (nosocomial infection. Disease has been found in saharic Africa, Eastern Europe, Pakistan, India and Middle East (specially Iran and Iraq. This disease recently spread in Iran so in 1999 to 2001 at least 222 suspected case(81 definite case reported that led to the death of 15 of 81 cases. It is estimated that 30 percent of the country's cattle are contaminated with this virus."nIn humans, after a short incubation period it appears suddenly with fever, chills, myalgia and GI symptoms followed by severe bleeding and DIC that led to death .If the patient improved, has a long {2-4 weeks convalescence period. Disease diagnosed by clinical manifestations, serologic tests, viral culture and PCR and its specific treatment is oral ribavirin for 10 days, for prevention of disease personal protective measures from tick bite, spraying poison of mews to reduce of ticks crowd, isolation of patients and dis-infection of contaminated personal equipments that who suffering from CCHF is recommended.

  7. Uncommon and Neglected Venezuelan Viral Diseases: Etiologic Agents, Physiopathological, Clinical and Epidemiological Characteristics

    Directory of Open Access Journals (Sweden)

    Juan C. Gabaldon-Figueira

    2015-10-01

    Full Text Available Abstract (english Viral infectious diseases are common in Venezuela, influenza, dengue, yellow fever, HIV infection, viral Hepatitis, chikungunya fever and many others represent public health problems in the country and therefore, have been well documented. However, other rarer and even unique or lethal viral illnesses present in Venezuela are usually poorly understood or even unknown. This review described Venezuelan Hemorrhagic Fever, Venezuelan Equine Encephalitis, Hantavirus Infections and Mayaro fever, named as neglected diseases, emphasizing the etiologic agents and their most relevant pathogenic mechanisms, clinical and epidemiological characteristics. Although there is not an official report about the re-emergence of these diseases, falling living standards and unsanitary conditions, together with limited accessibility to hygiene products and medical supplies, put us on alert about the re-emergence of these neglected diseases. Resumen (español Las enfermedades infecciosas virales son comunes en Venezuela, influenza, dengue, fiebre amarilla, infección por VIH, hepatitis viral, fiebre chikungunya y muchas otras representan problemas de salud pública en el país y por lo tanto, han sido bien documentadas. Sin embargo, otras enfermedades virales más raras e incluso únicas y letales presentes en Venezuela son generalmente poco estudiadas y hasta desconocidas. Esta revisión describe alguna de estas enfermedades olvidadas tales como la fiebre hemorrágica venezolana, la encefalitis equina venezolana, las infecciones por hantavirus y la fiebre de Mayaro, haciendo hincapié en los agentes etiológicos y en sus mecanismos patogénicos más relevantes, características clínicas y epidemiológicas. Aunque no hay informes oficiales sobre el resurgimiento de estas enfermedades, la caída de los niveles de vida y las condiciones insalubres, junto con el acceso limitado a los productos de higiene y suministros médicos, debe alertar sobre el

  8. HEMORRHAGIC-FEVER VIRUS-INFECTIONS IN AN ISOLATED RAIN-FOREST AREA OF CENTRAL LIBERIA - LIMITATIONS OF THE INDIRECT IMMUNOFLUORESCENCE SLIDE TEST FOR ANTIBODY SCREENING IN AFRICA

    NARCIS (Netherlands)

    van der Waals, F. W.; Pomeroy, K. L.; Goudsmit, J.; Asher, D. M.; Gajdusek, D. C.

    1986-01-01

    Serum samples from 119 healthy individuals and 106 epilepsy patients inhabiting Grand Bassa County, Liberia, were tested for antibodies to hemorrhagic fever viruses (HFV) by indirect immunofluorescence. E6 Vero cells infected with Lassa fever virus (LAS), Rift Valley Fever virus (RVF), Congo

  9. Accelerating vaccine development for African swine fever virus ...

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

    Photo: IDRC / Bartay The challenge African swine fever (ASF) is a highly infectious hemorrhagic viral disease that wipes out entire herds of infected pigs. ASF is widespread in at least half of sub-Saharan Africa, and threatens food security due to devastating economic losses.

  10. Ebola Viral Hemorrhagic Disease Outbreak in West Africa- Lessons ...

    African Journals Online (AJOL)

    ... to contain the Ebola epidemic. Key words: Ebola, viral hemorrhagic fever, West Africa, lessons, Uganda .... the corresponding surveillance systems for detecting priority diseases. ... A major outbreak of Yellow Fe- ver was reported in five ...

  11. A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein.

    Science.gov (United States)

    Guo, Fang; Wu, Shuo; Julander, Justin; Ma, Julia; Zhang, Xuexiang; Kulp, John; Cuconati, Andrea; Block, Timothy M; Du, Yanming; Guo, Ju-Tao; Chang, Jinhong

    2016-09-21

    Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past two decades, which highlights the pressing need for antiviral therapeutics. In a high throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound, which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV infected cultures with 2 μM of BDAA reduced the virion production by greater than 2 logs, the compound is not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug resistant viruses revealed that substitution of proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine or alanine confers YFV resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, substitution of P219 with glycine confers BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 localizes at the endoplasmic reticulum lumen side of the fifth putative trans-membrane domain of NS4B and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed important role and structural basis for NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs and attenuated viral infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever. Yellow fever is an acute viral hemorrhagic disease which threatens approximately one billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than seven decades, the low vaccination rate fails to prevent outbreaks in at

  12. [Prevalence and risk factors of respiratory viral infection in acute exacerbation of chronic obstructive pulmonary disease].

    Science.gov (United States)

    Du, X B; Ma, X; Gao, Y; Wen, L F; Li, J; Wang, Z Z; Liu, S

    2017-04-12

    Objective: To study the prevalence of respiratory viral infection in chronic obstructive pulmonary disease(COPD) exacerbations and to find the factors associated with susceptibility to viral infections. Methods: Eighty patients with exacerbations of COPD and 50 stable COPD patients were recruited. Nasopharyngeal swabs were tested for a range of 18 different respiratory viruses using PCR. Results: Among the COPD exacerbations, viral infection was detected in 18 episodes (22.5%) . The most common virus was rhinovirus (33.3%), followed by coronavirus(27.8%), parainfluenza(22.2%), metapneumovirus(11.1%) and influenza virus B(5.6%). The prevalence of viral infection was 8% in the stable COPD patients. In multivariate regression analysis fever was found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 4.99, 95% CI 1.51-16.48, P =0.008). Conclusion: Viral respiratory pathogens were more often detected in respiratory specimens from hospitalized patients with AECOPD than those with stable COPD. Rhinovirus was the most common infecting agent identified. The symptom of fever was associated with viral detection.

  13. Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection.

    Directory of Open Access Journals (Sweden)

    Mary B Crabtree

    Full Text Available BACKGROUND: Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. METHODOLOGY AND PRINCIPAL FINDINGS: Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. CONCLUSIONS/SIGNIFICANCE: In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes.

  14. Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection.

    Science.gov (United States)

    Crabtree, Mary B; Kent Crockett, Rebekah J; Bird, Brian H; Nichol, Stuart T; Erickson, Bobbie Rae; Biggerstaff, Brad J; Horiuchi, Kalanthe; Miller, Barry R

    2012-01-01

    Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes.

  15. Ebola haemorrhagic fever

    Science.gov (United States)

    Feldmann, Heinz; Geisbert, Thomas W

    2012-01-01

    Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The exception is the species Reston Ebola virus, which has not been associated with human disease and is found in the Philippines. Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism. Ebola virus is thought to also have a detrimental effect on the great ape population in Africa. Case-fatality rates of the African species in man are as high as 90%, with no prophylaxis or treatment available. Ebola virus infections are characterised by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock. PMID:21084112

  16. Aerosol exposure to Rift Valley fever virus causes earlier and more severe neuropathology in the murine model, which has important implications for therapeutic development.

    Directory of Open Access Journals (Sweden)

    Christopher Reed

    Full Text Available Rift Valley fever virus (RVFV is an important mosquito-borne veterinary and human pathogen that can cause severe disease including acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. Currently, no licensed vaccine or therapeutics exist to treat this potentially deadly disease. Detailed studies describing the pathogenesis of RVFV following aerosol exposure have not been completed and candidate therapeutics have not been evaluated following an aerosol exposure. These studies are important because while mosquito transmission is the primary means for human infection, it can also be transmitted by aerosol or through mucosal contact. Therefore, we directly compared the pathogenesis of RVFV following aerosol exposure to a subcutaneous (SC exposure in the murine model by analyzing survival, clinical observations, blood chemistry, hematology, immunohistochemistry, and virus titration of tissues. Additionally, we evaluated the effectiveness of the nucleoside analog ribavirin administered prophylactically to treat mice exposed by aerosol and SC. The route of exposure did not significantly affect the survival, chemistry or hematology results of the mice. Acute hepatitis occurred despite the route of exposure. However, the development of neuropathology occurred much earlier and was more severe in mice exposed by aerosol compared to SC exposed mice. Mice treated with ribavirin and exposed SC were partially protected, whereas treated mice exposed by aerosol were not protected. Early and aggressive viral invasion of brain tissues following aerosol exposure likely played an important role in ribavirin's failure to prevent mortality among these animals. Our results highlight the need for more candidate antivirals to treat RVFV infection, especially in the case of a potential aerosol exposure. Additionally, our study provides an account of the key pathogenetic differences in RVF disease following two potential

  17. Climate Influence on Emerging Risk Areas for Rift Valley Fever Epidemics in Tanzania.

    Science.gov (United States)

    Mweya, Clement N; Mboera, Leonard E G; Kimera, Sharadhuli I

    2017-07-01

    Rift Valley Fever (RVF) is a climate-related arboviral infection of animals and humans. Climate is thought to represent a threat toward emerging risk areas for RVF epidemics globally. The objective of this study was to evaluate influence of climate on distribution of suitable breeding habitats for Culex pipiens complex, potential mosquito vector responsible for transmission and distribution of disease epidemics risk areas in Tanzania. We used ecological niche models to estimate potential distribution of disease risk areas based on vectors and disease co-occurrence data approach. Climatic variables for the current and future scenarios were used as model inputs. Changes in mosquito vectors' habitat suitability in relation to disease risk areas were estimated. We used partial receiver operating characteristic and the area under the curves approach to evaluate model predictive performance and significance. Habitat suitability for Cx. pipiens complex indicated broad-scale potential for change and shift in the distribution of the vectors and disease for both 2020 and 2050 climatic scenarios. Risk areas indicated more intensification in the areas surrounding Lake Victoria and northeastern part of the country through 2050 climate scenario. Models show higher probability of emerging risk areas spreading toward the western parts of Tanzania from northeastern areas and decrease in the southern part of the country. Results presented here identified sites for consideration to guide surveillance and control interventions to reduce risk of RVF disease epidemics in Tanzania. A collaborative approach is recommended to develop and adapt climate-related disease control and prevention strategies.

  18. Acupuncture therapy for fever induced by viral upper respiratory tract infection (URTI) in military medical service: a case series.

    Science.gov (United States)

    Kwon, SeungWon; Shin, KyoungHo; Jung, WooSang; Moon, SangKwan; Cho, KiHo

    2014-12-01

    We report the cases of eight military patients with fever (≥38°C) induced by viral upper respiratory tract infection (URTI) who requested treatment with acupuncture in the military medical service room. All patients were treated immediately after diagnosis with classical acupuncture (GV14, GB20, TE8 points) and a new type of acupuncture, equilibrium acupuncture (Feibing and Ganmao points). After one treatment session (20 min), reduction of body temperature was confirmed in all patients. Accompanying symptoms such as headache, myalgia and nasal obstruction also showed a tendency to decrease. Within 3 days of treatment, six of the eight patients had recovered from the URTI. No adverse effects of acupuncture treatment were reported. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus.

    Science.gov (United States)

    Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G

    2013-03-01

    In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ~10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular epidemiology of SFTSV before and after its identification is limited. To address this we undertake phylogenetic, evolutionary and structural analyses of all available SFTSV genetic sequences, including a new SFTSV complete genome isolated from a patient from Henan in 2011. Our discovery of a mosaic L segment sequence, which is descended from two major circulating lineages of SFTSV in China, represents the first evidence that homologous recombination plays a role in SFTSV evolution. Selection analyses indicate that negative selection is predominant in SFTSV genes, yet differences in selective forces among genes are consistent between Phlebovirus species. Further analysis reveals structural conservation between SFTSV and Rift Valley fever virus in the residues of their nucleocapsids that are responsible for oligomerisation and RNA-binding, suggesting the viruses share similar modes of higher-order assembly. We reconstruct the epidemic history of SFTSV using molecular clock and coalescent-based methods, revealing that the extant SFTSV lineages originated 50-150 years ago, and that the viral population experienced a recent growth phase that concurs with and extends the earliest serological reports of SFTSV infection. Taken together, our combined structural and phylogenetic analyses shed light into the evolutionary behaviour of SFTSV in the context of other, better-known, pathogenic Phleboviruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    International Nuclear Information System (INIS)

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made

  1. Virus survival in slurry: Analysis of the stability of foot-and-mouth disease, classical swine fever, bovine viral diarrhoea and swine influenza viruses

    DEFF Research Database (Denmark)

    Bøtner, Anette; Belsham, Graham

    2012-01-01

    of an outbreak of disease before it has been recognized. The survival of foot-and-mouth disease virus, classical swine fever virus, bovine viral diarrhoea virus and swine influenza virus, which belong to three different RNA virus families plus porcine parvovirus (a DNA virus) was examined under controlled...... conditions. For each RNA virus, the virus survival in farm slurry under anaerobic conditions was short (generally ≤1h) when heated (to 55°C) but each of these viruses could retain infectivity at cool temperatures (5°C) for many weeks. The porcine parvovirus survived considerably longer than each of the RNA...... viruses under all conditions tested. The implications for disease spread are discussed....

  2. [Two Crimean-Congo hemorrhagic fever cases without history of tick contact from Ankara region].

    Science.gov (United States)

    Kaya Kiliç, Esra; Yilmaz, Umut; Cesur, Salih; Koçak Tufan, Zeliha; Kurtoğlu, Yasemin; Bulut, Cemal; Kinikli, Sami; Irmak, Hasan; Demiröz, Ali Pekcan

    2009-10-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease presenting with flu-like symptoms, fever, hemorrhage and petechia. The virus (CCHFV) is a member of the Nairovirus genera of Bunyaviridae family and can be transmitted to humans by Hyalomma tick-bite, by exposure to infected blood and fomites of patient with CCHF or contact with animal tissue in viremic phase. In this study we present two cases with CCHF but without history of tick bite or exposure to infected fomites, even not coming from endemic areas. The first case was a 67 years old male patient presented with fever, fatique and shortness of breath. Physical examination revealed rales in right lower segments of lung. Laboratory findings showed elevation of liver enzymes with thrombocytopenia and prolonged prothrombin time. Serological markers for viral hepatitis, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were negative. The patient was found to be IgM and RNA positive for CCHFV by ELISA and polymerase chain reaction (PCR) methods, respectively. His history indicated a contact with livestock. The second patient was a 60 years old male dealing with husbandry. He had fever, fatique and myalgia. Physical examination revealed petechial rash on legs. Laboratory findings showed elevated liver enzymes, prolonged phrothrombin time and thrombocytopenia. Viral hepatitis markers, CMV-IgM and EBV-IgM were found negative. He was also found to be IgM and RNA positive for CCHFV in the reference laboratory. In conclusion, CCHF should be considered in the differential diagnosis of patients who contact with livestock and present with fever, fatigue, rash, elevated liver enzymes, thrombocytopenia and prolonged prothrombin time eventhough they do not reside in endemic areas for CCHF.

  3. Ecological niche modeling and land cover risk areas for rift valley fever vector, culex tritaeniorhynchus giles in Jazan, Saudi Arabia.

    Science.gov (United States)

    Sallam, Mohamed F; Al Ahmed, Azzam M; Abdel-Dayem, Mahmoud S; Abdullah, Mohamed A R

    2013-01-01

    The mosquito, Culex tritaeniorhynchus Giles is a prevalent and confirmed Rift Valley Fever virus (RVFV) vector. This vector, in association with Aedimorphus arabiensis (Patton), was responsible for causing the outbreak of 2000 in Jazan Province, Saudi Arabia. Larval occurrence records and a total of 19 bioclimatic and three topographic layers imported from Worldclim Database were used to predict the larval suitable breeding habitats for this vector in Jazan Province using ArcGIS ver.10 and MaxEnt modeling program. Also, a supervised land cover classification from SPOT5 imagery was developed to assess the land cover distribution within the suitable predicted habitats. Eleven bioclimatic and slope attributes were found to be the significant predictors for this larval suitable breeding habitat. Precipitation and temperature were strong predictors of mosquito distribution. Among six land cover classes, the linear regression model (LM) indicated wet muddy substrate is significantly associated with high-very high suitable predicted habitats (R(2) = 73.7%, Presearchers.

  4. Prediction, assessment of the Rift Valley fever activity in East and Southern Africa 2006-2008 and possible vector control strategies.

    Science.gov (United States)

    Anyamba, Assaf; Linthicum, Kenneth J; Small, Jennifer; Britch, Seth C; Pak, Edwin; de La Rocque, Stephane; Formenty, Pierre; Hightower, Allen W; Breiman, Robert F; Chretien, Jean-Paul; Tucker, Compton J; Schnabel, David; Sang, Rosemary; Haagsma, Karl; Latham, Mark; Lewandowski, Henry B; Magdi, Salih Osman; Mohamed, Mohamed Ally; Nguku, Patrick M; Reynes, Jean-Marc; Swanepoel, Robert

    2010-08-01

    Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Niño/Southern Oscillation (ENSO) phenomenon, which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and regional elevated sea surface temperatures, elevated rainfall, and satellite derived-normalized difference vegetation index data, we predicted with lead times of 2-4 months areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to March 2008. Predictions were confirmed by entomological field investigations of virus activity and by reported cases of RVF in human and livestock populations. This represents the first series of prospective predictions of RVF outbreaks and provides a baseline for improved early warning, control, response planning, and mitigation into the future.

  5. Detection of Rift Valley Fever Virus Interepidemic Activity in Some Hotspot Areas of Kenya by Sentinel Animal Surveillance, 2009–2012

    Directory of Open Access Journals (Sweden)

    Jacqueline Kasiiti Lichoti

    2014-01-01

    Full Text Available Rift Valley fever virus causes an important zoonotic disease of humans and small ruminants in Eastern Africa and is spread primarily by a mosquito vector. In this region, it occurs as epizootics that typically occur at 5–15-year intervals associated with unusual rainfall events. It has hitherto been known that the virus is maintained between outbreaks in dormant eggs of the mosquito vector and this has formed the basis of understanding of the epidemiology and control strategies of the disease. We show here that seroconversion and sporadic acute disease do occur during the interepidemic periods (IEPs in the absence of reported cases in livestock or humans. The finding indicates that previously undetected low-level virus transmission during the IEPs does occur and that epizootics may also be due to periodic expansion of mosquito vectors in the presence of both circulating virus and naïve animals.

  6. Complex Virus-Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview.

    Science.gov (United States)

    Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

    2017-07-05

    Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV-host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus-host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding.

  7. Spatio-Temporal modelling of Dengue Fever in Zulia state, Venezuela

    OpenAIRE

    Cabrera, Maritza

    2014-01-01

    Over half of the world's population are at risk of infection from dengue fever (Guha-Sapir2005). This viral disease is transmitted by the female Aedes aegypti mosquito and is the major source of human death in the world when compared with any other vector borne disease (Gubler1998a). The first important epidemic of dengue haemorrhagic fever (DHF) in America was reported in Cuba in 1981 and subsequently in Venezuela during 1989 and 1990 (Oletta2006, Brightmer1998). There has been a trend of in...

  8. Identification of central Kenyan Rift Valley Fever virus vector habitats with Landsat TM and evaluation of their flooding status with airborne imaging radar

    Science.gov (United States)

    Pope, K. O.; Sheffner, E. J.; Linthicum, K. J.; Bailey, C. L.; Logan, T. M.; Kasischke, E. S.; Birney, K.; Njogu, A. R.; Roberts, C. R.

    1992-01-01

    Rift Valley Fever (RVF) is a mosquito-borne virus that affects livestock and humans in Africa. Landsat TM data are shown to be effective in identifying dambos, intermittently flooded areas that are potential mosquite breeding sites, in an area north of Nairobi, Kenya. Positive results were obtained from a limited test of flood detection in dambos with airborne high resolution L, C, and X band multipolarization SAR imagery. L and C bands were effective in detecting flooded dambos, but LHH was by far the best channel for discrimination between flooded and nonflooded sites in both sedge and short-grass environments. This study demonstrates the feasibility of a combined passive and active remote sensing program for monitoring the location and condition of RVF vector habitats, thus making future control of the disease more promising.

  9. Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever.

    Science.gov (United States)

    Bray, Mike; Geisbert, Thomas W

    2005-08-01

    Ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. Recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. However, they cannot restrict viral replication, possibly because of suppression of interferon responses. Infected dendritic cells also secrete proinflammatory mediators, but cannot initiate antigen-specific responses. In consequence, virus disseminates to these and other cell types throughout the body, causing multifocal necrosis and a syndrome resembling septic shock. Massive "bystander" apoptosis of natural killer and T cells further impairs immunity. These findings suggest that modifying host responses would be an effective therapeutic strategy, and treatment of infected macaques with a tissue-factor inhibitor reduced both inflammation and viral replication and improved survival.

  10. Using reverse genetics to manipulate the NSs gene of the Rift Valley fever virus MP-12 strain to improve vaccine safety and efficacy.

    Science.gov (United States)

    Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V; Ikegami, Tetsuro

    2011-11-01

    Rift Valley fever virus (RVFV), which causes hemorrhagic fever, neurological disorders or blindness in humans, and a high rate abortion and fetal malformation in ruminants, has been classified as a HHS/USDA overlap select agent and a risk group 3 pathogen. It belongs to the genus Phlebovirus in the family Bunyaviridae and is one of the most virulent members of this family. Several reverse genetics systems for the RVFV MP-12 vaccine strain as well as wild-type RVFV strains, including ZH548 and ZH501, have been developed since 2006. The MP-12 strain (which is a risk group 2 pathogen and a non-select agent) is highly attenuated by several mutations in its M- and L-segments, but still carries virulent S-segment RNA, which encodes a functional virulence factor, NSs. The rMP12-C13type (C13type) carrying 69% in-frame deletion of NSs ORF lacks all the known NSs functions, while it replicates as efficient as does MP-12 in VeroE6 cells lacking type-I IFN. NSs induces a shut-off of host transcription including interferon (IFN)-beta mRNA and promotes degradation of double-stranded RNA-dependent protein kinase (PKR) at the post-translational level. IFN-beta is transcriptionally upregulated by interferon regulatory factor 3 (IRF-3), NF-kB and activator protein-1 (AP-1), and the binding of IFN-beta to IFN-alpha/beta receptor (IFNAR) stimulates the transcription of IFN-alpha genes or other interferon stimulated genes (ISGs), which induces host antiviral activities, whereas host transcription suppression including IFN-beta gene by NSs prevents the gene upregulations of those ISGs in response to viral replication although IRF-3, NF-kB and activator protein-1 (AP-1) can be activated by RVFV7. Thus, NSs is an excellent target to further attenuate MP-12, and to enhance host innate immune responses by abolishing the IFN-beta suppression function. Here, we describe a protocol for generating a recombinant MP-12 encoding mutated NSs, and provide an example of a screening method to identify

  11. Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus

    Science.gov (United States)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically de...

  12. Search Results | Page 4 | IDRC - International Development ...

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

    Results 31 - 40 of 8530 ... Rift Valley fever (RVF) is a viral disease of goats, sheep, cattle, and humans. ... Development EDUCATION ... Addressing Africa's unmet need for family planning by intensifying sexual and reproductive and adolescent health research. ... Community knowledge, commitment, and resources are shaping ...

  13. [Relationship between viral load of human bocavirus and clinical characteristics in children with acute lower respiratory tract infection].

    Science.gov (United States)

    Ding, Xiao-Fang; Zhang, Bing; Zhong, Li-Li; Xie, Le-Yun; Xiao, Ni-Guang

    2017-03-01

    To investigate the prevalence of human bocavirus (HBoV) in children with acute lower respiratory tract infection and to explore the relationship between the viral load of HBoV and the clinical characteristics of acute lower respiratory tract infection in children. A total of 1 554 nasopharyngeal aspirates from children who were hospitalized due to acute lower respiratory tract infection between March 2011 and March 2014 were collected. Quantitative real-time PCR was used to detect 12 RNA and 2 DNA viruses, adenovirus (ADV) and HBoV, and to measure the viral load of HBoV in HBoV-positive children. A comprehensive analysis was performed with reference to clinical symptoms and indicators. In the 1 554 specimens, 1 212 (77.99%) were positive for viruses, and 275 (17.70%) were HBoV-positive. In HBoV-positive cases, 94.9% were aged infection, and 230 (83.64%) had mixed infection. There was no significant difference in viral load between children with single infection and mixed infection (P>0.05). The patients with fever had a significantly higher viral load than those without fever (Pacute lower respiratory tract infection (P>0.05). HBoV is one of the important pathogens of acute lower respiratory tract infection in children. Children with a higher viral load of HBoV are more likely to experience symptoms such as fever and wheezing. However, the severity of disease and mixed infection are not significantly related to viral load.

  14. CLINICAL EFFICACY OF IBUPROFEN IN THERAPY FOR VIRAL UPPER RESPIRATORY TRACT INFECTIONS IN INFANTS

    Directory of Open Access Journals (Sweden)

    I.O. Skugarevskaya

    2006-01-01

    Full Text Available A study of use of ibuprofen in cases of viral upper respiratory tract infections (Vuri in children of early childhood has proved its' safety and efficacy. This medical agent has not only terminate fever but also diminished some other symptoms of Vuri.Key words: ibuprofen, viral upper respiratory tract infections, children.

  15. Should clinical case definitions of influenza in hospitalized older adults include fever?

    Science.gov (United States)

    Falsey, Ann R; Baran, Andrea; Walsh, Edward E

    2015-08-01

    Influenza is a major cause of morbidity and mortality in elderly persons. Fever is included in all standard definitions of influenza-like illness (ILI), yet older patients may have diminished febrile response to infection. Therefore, we examined the utility of various thresholds to define fever for case definitions of influenza in persons ≥ 65 years of age. Data from two prospective surveillance studies for respiratory viral infection in adults hospitalized with acute cardiopulmonary illnesses with or without fever were examined. The highest temperature reported prior to admission or measured during the first 24 h after admission was recorded. The diagnosis of influenza was made by a combination of viral culture, reverse-transcription polymerase chain reaction, antigen testing, and serology. A total of 2410 subjects (66% ≥ 65 years of age) were enrolled; 281 had influenza (261 influenza A, 19 influenza B, and one mixed influenza A and B). The commonly used definition of ILI (fever ≥ 37·8°C and cough) resulted in 57% sensitivity and 71% specificity in older adults. Receiver operating characteristic curves examining the various temperature thresholds combined with cough and/or sore throat showed the optimal balance between sensitivity and specificity to be 37·9°C (AUC 0·71) and 37·3°C (AUC 0·66), in younger and older persons, respectively. Clinical decision rules using the presence of cough and fever may be helpful when screening for influenza or empiric antiviral treatment when rapid influenza testing is not available; however, lower fever thresholds may be considered for elderly subjects. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  16. [Alarm symptoms of meningitis in children with fever].

    Science.gov (United States)

    Geurts, Dorien H F; Moll, Henriette A

    2011-01-01

    A 15-year-old girl presented with fever and pain in her legs. A viral infection was suspected, but within 24 hours she became confused and developed meningeal signs, based on which she was diagnosed as having meningitis. Within a few hours a 6-month-old boy developed fever, a grey colour, bulging fontanel, cold hands and feet, and was groaning. He too appeared to have meningitis. It is important to recognize this serious infection in children with fever, since delay of diagnosis and treatment may result in serious complications. Recognition is difficult because of non-specific symptoms on presentation and a lack of alarm symptoms early in the course of the disease. Alarm symptoms of serious infection in children are cyanosis, rapid breathing, decreased capillary refill, petechial rash, meningeal signs, leg pain and decreased consciousness. If serious infection is uncertain in a child with fever, parents should be advised on the potential course of the disease, the alarm symptoms and the need to seek medical help in time.

  17. Advanced Vaccine Candidates for Lassa Fever

    Directory of Open Access Journals (Sweden)

    Igor S. Lukashevich

    2012-10-01

    Full Text Available Lassa virus (LASV is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF. LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

  18. NSs protein of rift valley fever virus promotes posttranslational downregulation of the TFIIH subunit p62.

    Science.gov (United States)

    Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

    2011-07-01

    Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.

  19. Acute psychosis followed by fever: Malignant neuroleptic syndrome or viral encephalitis?

    Directory of Open Access Journals (Sweden)

    Stojanović Zvezdana

    2014-01-01

    Full Text Available Introduction. Neuroleptic malignant syndrome is rare, but potentially fatal idiosyncratic reaction to antipsychotic medications. It is sometimes difficult to diagnose some clinical cases as neuroleptic malignant syndrome and differentiate it from the acute viral encephalitis. Case report. We reported a patient diagnosed with acute psychotic reaction which appeared for the first time. The treatment started with typical antipsychotic, which led to febrility. The clinical presentation of the patient was characterised by the signs and symptoms that might have indicated the neuroleptic malignant syndrome as well as central nervous system viral disease. In order to make a detailed diagnosis additional procedures were performed: electroencephalogram, magnetic resonance imaging of the head, lumbar puncture and a serological test of the cerebrospinal fluid. Considering that after the tests viral encephalitis was ruled out and the diagnosis of neuroleptic malignant syndrome made, antipsychotic therapy was immediately stopped. The patient was initially treated with symptomatic therapy and after that with atypical antipsychotic and electroconvulsive therapy, which led to complete recovery. Conclusion. We present the difficulties of early diagnosis at the first episode of acute psychotic disorder associated with acute febrile condition. Concerning the differential diagnosis it is necessary to consider both neuroleptic malignant syndrome and viral encephalitis, i.e. it is necessary to make the neuroradiological diagnosis and conduct cerebrospinal fluid analysis and blood test. In neuroleptic malignant syndrome treatment a combined use of electroconvulsive therapy and low doses of atypical antipsychotic are confirmed to be successful.

  20. Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus.

    Science.gov (United States)

    Soto-Acosta, Rubén; Bautista-Carbajal, Patricia; Syed, Gulam H; Siddiqui, Aleem; Del Angel, Rosa M

    2014-09-01

    Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome. A DENV replicative cycle relies on host lipid metabolism; specifically, DENV infection modulates cholesterol and fatty acid synthesis, generating a lipid-enriched cellular environment necessary for viral replication. Thus, the aim of this work was to evaluate the anti-DENV effect of the Nordihydroguaiaretic acid (NDGA), a hypolipidemic agent with antioxidant and anti-inflammatory properties. A dose-dependent inhibition in viral yield and NS1 secretion was observed in supernatants of infected cells treated for 24 and 48 h with different concentrations of NDGA. To evaluate the effect of NDGA in DENV replication, a DENV4 replicon transfected Vero cells were treated with different concentrations of NDGA. NDGA treatment significantly reduced DENV replication, reiterating the importance of lipids in viral replication. NDGA treatment also led to reduction in number of lipid droplets (LDs), the neutral lipid storage organelles involved in DENV morphogenesis that are known to increase in number during DENV infection. Furthermore, NDGA treatment resulted in dissociation of the C protein from LDs. Overall our results suggest that NDGA inhibits DENV infection by targeting genome replication and viral assembly. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin

    Energy Technology Data Exchange (ETDEWEB)

    Capodagli, Glenn C.; McKercher, Marissa A.; Baker, Erica A.; Masters, Emily M.; Brunzelle, Joseph S.; Pegan, Scott D. (Denver); (NWU)

    2014-10-02

    Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(-)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 {angstrom}, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.

  2. Detection panel for identification of twelve hemorrhagic viruses using real-time RT-PCR.

    Science.gov (United States)

    Fajfr, M; Neubauerová, V; Pajer, P; Kubíčková, P; Růžek, D

    2014-09-01

    Viral hemorrhagic fevers are caused by viruses from four viral families and develop diseases with high fatality rates. However, no commercial diagnostic assay for these pathogens is available. We developed real-time RT-PCR assays for viruses Ebola, Marburg, Lassa, Guanarito, Machupo, Junin, Sabiá, Seoul, Puumala, Hantaan, Crimean-Congo hemorrhagic fever virus and Rift Valley fever virus. The assays were optimized for identical reaction conditions and can be performed using several types of real-time PCR instruments, both capillary and plate, including a portable Ruggedized Advanced Pathogen Identification Device (R.A.P.I.D.) (Idaho Technology, Inc.). In combination with primers and probes from previously published studies, we present a simple system for rapid identification of hemorrhagic filoviruses, arenaviruses and bunyaviruses with sufficient sensitivity for first contact laboratory and diagnosis under field conditions.

  3. Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B.

    Science.gov (United States)

    Liu, Yanling; Xiong, Yujiao; Huang, Wenxiang; Jia, Bei

    2014-05-12

    We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy.

  4. Investigation of hemorrhagic fever viruses inside wild populations of ticks: One of the pioneer studies in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Rania Ali El Hadi Mohamed

    2017-05-01

    Full Text Available Objective: To screen hemorrhagic fever viruses inside wild populations of ticks collected from Riyadh, Saudi Arabia between January and March 2016. Methods: Ticks were identified depending on their morphological features using classical keys then grouped into pools. Ticks in each pool were processed separately using the sterile pestles and mortars. Viral RNA was extracted using Qiagen RNeasy Mini Kit and Qiagen RNAeasy Columns (Qiagen, Hilden, Germany according to the instructions of manufacturers. A total number of 1 282 hard ticks were collected, and 582 of them were precisely identified then screened for the presence of arboviruses using quantitative real-time PCR. The four species were screened for six viruses: Rift Valley fever virus (RVFV, Chikungunya virus (CHIKV, Crimean-Congo hemorrhagic fever virus (CCHFV, Alkhurma virus (INKV, Sindbis virus (SINV, and Pan Hanta virus (HANTA. CT value for the negative control (RNA free water was zero. Negative and positive controls were tested for each test to confirm the specificity of the selected primer pairs. SYBR Green One step RT-PCR Master Mix (KAPA Biosystems, Boston, MA was tested along with primers. Results: Ticks identification resulted into four species: Hyalomma schulzei, Hyalomma onatoli, Boophilus kdhlsi, and Hyalomm dromedarii. All the ticks’ species (except Boophilus kdhlsi were positive for the following viruses: SINV, RVFV, CHIKV, and CCHFV. While HANTA viruses have been detected in a single species (Hyalomm dromedarii. Conclusions: According to our knowledge this research may be one of the pioneer studies in Kingdom of Saudi Arabia. Incrimination of the above mentioned ticks species as well as their vectorial capacity are highly recommended for investigation in the upcoming researches.

  5. Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.

    Science.gov (United States)

    Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

    2014-03-01

    The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

  6. Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA Translation.

    Science.gov (United States)

    Jeeva, Subbiah; Cheng, Erdong; Ganaie, Safder S; Mir, Mohammad A

    2017-08-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5' UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease. Copyright © 2017 American Society for Microbiology.

  7. Dengue as a cause of fever during pregnancy: a report of two cases

    Directory of Open Access Journals (Sweden)

    Ariani Impieri Souza

    2016-06-01

    Full Text Available Abstract: Dengue infection has not been routinely investigated among pregnant women and parturients with acute febrile syndrome in endemic settings. Here, we report two cases of dengue fever detected at the time of delivery in parturients enrolled in a cohort prospective study conducted in a hospital in Recife, Brazil. The parturients reported fever onset within seven days prior to delivery, and dengue infection was confirmed upon detection of viral ribonucleic acid (RNA by using the reverse transcriptase-polymerase chain reaction. Dengue infection should be considered as a diagnostic possibility in cases of fever during pregnancy and labor, especially in endemic areas.

  8. Isolated unilateral sixth cranial nerve palsy: A rare presentation of dengue fever

    Directory of Open Access Journals (Sweden)

    Yang Liang Boo

    2016-11-01

    Full Text Available Dengue fever is a common mosquito-borne viral infection endemic in tropical and subtropical countries. Neurological manifestations in dengue infection are relatively uncommon, and include encephalitis, encephalopathy, neuromuscular disorders and neuro-ocular disorders. Cranial mononeuropathy is a rare manifestation of dengue infection. A 40-year-old man was diagnosed with isolated, unilateral sixth cranial nerve palsy complicating dengue infection. The patient was managed accordingly, and full ocular recovery was observed. This was the first reported case of isolated sixth cranial nerve palsy associated with dengue fever in Malaysia. It is important for clinicians to consider dengue as a differential diagnosis in patients presenting with fever and sixth cranial nerve palsy.

  9. The AFHSC-Division of GEIS Operations Predictive Surveillance Program: a multidisciplinary approach for the early detection and response to disease outbreaks.

    Science.gov (United States)

    Witt, Clara J; Richards, Allen L; Masuoka, Penny M; Foley, Desmond H; Buczak, Anna L; Musila, Lillian A; Richardson, Jason H; Colacicco-Mayhugh, Michelle G; Rueda, Leopoldo M; Klein, Terry A; Anyamba, Assaf; Small, Jennifer; Pavlin, Julie A; Fukuda, Mark M; Gaydos, Joel; Russell, Kevin L; Wilkerson, Richard C; Gibbons, Robert V; Jarman, Richard G; Myint, Khin S; Pendergast, Brian; Lewis, Sheri; Pinzon, Jorge E; Collins, Kathrine; Smith, Matthew; Pak, Edwin; Tucker, Compton; Linthicum, Kenneth; Myers, Todd; Mansour, Moustafa; Earhart, Ken; Kim, Heung Chul; Jiang, Ju; Schnabel, Dave; Clark, Jeffrey W; Sang, Rosemary C; Kioko, Elizabeth; Abuom, David C; Grieco, John P; Richards, Erin E; Tobias, Steven; Kasper, Matthew R; Montgomery, Joel M; Florin, Dave; Chretien, Jean-Paul; Philip, Trudy L

    2011-03-04

    The Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System Operations (AFHSC-GEIS) initiated a coordinated, multidisciplinary program to link data sets and information derived from eco-climatic remote sensing activities, ecologic niche modeling, arthropod vector, animal disease-host/reservoir, and human disease surveillance for febrile illnesses, into a predictive surveillance program that generates advisories and alerts on emerging infectious disease outbreaks. The program's ultimate goal is pro-active public health practice through pre-event preparedness, prevention and control, and response decision-making and prioritization. This multidisciplinary program is rooted in over 10 years experience in predictive surveillance for Rift Valley fever outbreaks in Eastern Africa. The AFHSC-GEIS Rift Valley fever project is based on the identification and use of disease-emergence critical detection points as reliable signals for increased outbreak risk. The AFHSC-GEIS predictive surveillance program has formalized the Rift Valley fever project into a structured template for extending predictive surveillance capability to other Department of Defense (DoD)-priority vector- and water-borne, and zoonotic diseases and geographic areas. These include leishmaniasis, malaria, and Crimea-Congo and other viral hemorrhagic fevers in Central Asia and Africa, dengue fever in Asia and the Americas, Japanese encephalitis (JE) and chikungunya fever in Asia, and rickettsial and other tick-borne infections in the U.S., Africa and Asia.

  10. The AFHSC-Division of GEIS Operations Predictive Surveillance Program: a multidisciplinary approach for the early detection and response to disease outbreaks

    Science.gov (United States)

    2011-01-01

    The Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System Operations (AFHSC-GEIS) initiated a coordinated, multidisciplinary program to link data sets and information derived from eco-climatic remote sensing activities, ecologic niche modeling, arthropod vector, animal disease-host/reservoir, and human disease surveillance for febrile illnesses, into a predictive surveillance program that generates advisories and alerts on emerging infectious disease outbreaks. The program’s ultimate goal is pro-active public health practice through pre-event preparedness, prevention and control, and response decision-making and prioritization. This multidisciplinary program is rooted in over 10 years experience in predictive surveillance for Rift Valley fever outbreaks in Eastern Africa. The AFHSC-GEIS Rift Valley fever project is based on the identification and use of disease-emergence critical detection points as reliable signals for increased outbreak risk. The AFHSC-GEIS predictive surveillance program has formalized the Rift Valley fever project into a structured template for extending predictive surveillance capability to other Department of Defense (DoD)-priority vector- and water-borne, and zoonotic diseases and geographic areas. These include leishmaniasis, malaria, and Crimea-Congo and other viral hemorrhagic fevers in Central Asia and Africa, dengue fever in Asia and the Americas, Japanese encephalitis (JE) and chikungunya fever in Asia, and rickettsial and other tick-borne infections in the U.S., Africa and Asia. PMID:21388561

  11. [Yellow fever: reemerging in the state of Sao Paulo, Brazil, 2009].

    Science.gov (United States)

    Mascheretti, Melissa; Tengan, Ciléa H; Sato, Helena Keiko; Suzuki, Akemi; de Souza, Renato Pereira; Maeda, Marina; Brasil, Roosecelis; Pereira, Mariza; Tubaki, Rosa Maria; Wanderley, Dalva M V; Fortaleza, Carlos Magno Castelo Branco; Ribeiro, Ana Freitas

    2013-10-01

    To describe the investigation of a sylvatic yellow fever outbreak in the state of Sao Paulo and the main control measures undertaken. This is a descriptive study of a sylvatic yellow fever outbreak in the Southwestern region of the state from February to April 2009. Suspected and confirmed cases in humans and in non-human primates were evaluated. Entomological investigation in sylvatic environment involved capture at ground level and in the tree canopy to identify species and detect natural infections. Control measures were performed in urban areas to control Aedes aegypti . Vaccination was directed at residents living in areas with confirmed viral circulation and also at nearby cities according to national recommendation. Twenty-eight human cases were confirmed (39.3% case fatality rate) in rural areas of Sarutaiá, Piraju, Tejupá, Avaré and Buri. The deaths of 56 non-human primates were also reported, 91.4% were Allouatta sp. Epizootics was confirmed in two non-human primates in the cities of Itapetininga and Buri. A total of 1,782 mosquitoes were collected, including Haemagogus leucocelaenus , Hg. janthinomys/capricornii , and Sabethes chloropterus, Sa. purpureus and Sa. undosus . Yellow fever virus was isolated from a group of Hg. Leucocelaenus from Buri. Vaccination was carried out in 49 cities, with a total of 1,018,705 doses. Nine serious post-vaccination adverse events were reported. The cases occurred between February and April 2009 in areas with no recorded yellow fever virus circulation in over 60 years. The outbreak region occurred outside the original recommended vaccination area with a high percentage of susceptible population. The fast adoption of control measures interrupted the human transmission within a month and the confirmation of viral circulation in humans, monkeys and mosquitoes. The results allowed the identification of new areas of viral circulation but further studies are required to clarify the dynamics of the spread of this disease.

  12. Nonstructural NSs protein of rift valley fever virus interacts with pericentromeric DNA sequences of the host cell, inducing chromosome cohesion and segregation defects.

    Science.gov (United States)

    Mansuroglu, Z; Josse, T; Gilleron, J; Billecocq, A; Leger, P; Bouloy, M; Bonnefoy, E

    2010-01-01

    Rift Valley fever virus (RVFV) is an emerging, highly pathogenic virus; RVFV infection can lead to encephalitis, retinitis, or fatal hepatitis associated with hemorrhagic fever in humans, as well as death, abortions, and fetal deformities in animals. RVFV nonstructural NSs protein, a major factor of the virulence, forms filamentous structures in the nuclei of infected cells. In order to further understand RVFV pathology, we investigated, by chromatin immunoprecipitation, immunofluorescence, fluorescence in situ hybridization, and confocal microscopy, the capacity of NSs to interact with the host genome. Our results demonstrate that even though cellular DNA is predominantly excluded from NSs filaments, NSs interacts with some specific DNA regions of the host genome such as clusters of pericentromeric gamma-satellite sequence. Targeting of these sequences by NSs was correlated with the induction of chromosome cohesion and segregation defects in RVFV-infected murine, as well as sheep cells. Using recombinant nonpathogenic virus rZHDeltaNSs210-230, expressing a NSs protein deleted of its region of interaction with cellular factor SAP30, we showed that the NSs-SAP30 interaction was essential for NSs to target pericentromeric sequences, as well as for induction of chromosome segregation defects. The effect of RVFV upon the inheritance of genetic information is discussed with respect to the pathology associated with fetal deformities and abortions, highlighting the main role played by cellular cofactor SAP30 on the establishment of NSs interactions with host DNA sequences and RVFV pathogenesis.

  13. Simultaneous Genomic Detection of Multiple Enteric Bacterial and Viral Pathogens, Including Sars-CoV and RVFV

    National Research Council Canada - National Science Library

    Payne, S; Peters, C. J. (Clarence James), 1940; Makino, S; Oliver, K; Weiss, C; Kornguth, S; Carruthers, L; Chin, R

    2004-01-01

    ...) associated with the SARS-associated coronavirus (SARS-CoV) and Rift Valley Fever Virus (RVFV) has been developed. This system is based upon the Luminex xMAP" System, a multiplexed assay platform that combines high sample throughput...

  14. Comparison of Rift Valley fever virus replication in North American livestock and wildlife cell lines.

    Science.gov (United States)

    Gaudreault, Natasha N; Indran, Sabarish V; Bryant, P K; Richt, Juergen A; Wilson, William C

    2015-01-01

    Rift Valley fever virus (RVFV) causes disease outbreaks across Africa and the Arabian Peninsula, resulting in high morbidity and mortality among young domestic livestock, frequent abortions in pregnant animals, and potentially severe or fatal disease in humans. The possibility of RVFV spreading to the United States or other countries worldwide is of significant concern to animal and public health, livestock production, and trade. The mechanism for persistence of RVFV during inter-epidemic periods may be through mosquito transovarial transmission and/or by means of a wildlife reservoir. Field investigations in endemic areas and previous in vivo studies have demonstrated that RVFV can infect a wide range of animals, including indigenous wild ruminants of Africa. Yet no predominant wildlife reservoir has been identified, and gaps in our knowledge of RVFV permissive hosts still remain. In North America, domestic goats, sheep, and cattle are susceptible hosts for RVFV and several competent vectors exist. Wild ruminants such as deer might serve as a virus reservoir and given their abundance, wide distribution, and overlap with livestock farms and human populated areas could represent an important risk factor. The objective of this study was to assess a variety of cell lines derived from North American livestock and wildlife for susceptibility and permissiveness to RVFV. Results of this study suggest that RVFV could potentially replicate in native deer species such as white-tailed deer, and possibly a wide range of non-ruminant animals. This work serves to guide and support future animal model studies and risk model assessment regarding this high-consequence zoonotic pathogen.

  15. Author Details

    African Journals Online (AJOL)

    Relative performance of buffered Rose Bengal plate test (RBPT) and slow (tube) agglutination test (SAT) for detection of Brucella abortus antibodies in indigenous boran cattle in Tanzania Abstract · Vol 28 (2013): Special Issue - Articles Spatial distribution of non-clinical Rift Valley fever viral activity in domestic and wild ...

  16. The Yellow Fever Vaccine: A History

    OpenAIRE

    Frierson, J. Gordon

    2010-01-01

    After failed attempts at producing bacteria-based vaccines, the discovery of a viral agent causing yellow fever and its isolation in monkeys opened new avenues of research. Subsequent advances were the attenuation of the virus in mice and later in tissue culture; the creation of the seed lot system to avoid spontaneous mutations; the ability to produce the vaccine on a large scale in eggs; and the removal of dangerous contaminants. An important person in the story is Max Theiler, who was Prof...

  17. Animal viral diseases and global change: bluetongue and West Nile fever as paradigms.

    Science.gov (United States)

    Jiménez-Clavero, Miguel Á

    2012-01-01

    Environmental changes have an undoubted influence on the appearance, distribution, and evolution of infectious diseases, and notably on those transmitted by vectors. Global change refers to environmental changes arising from human activities affecting the fundamental mechanisms operating in the biosphere. This paper discusses the changes observed in recent times with regard to some important arboviral (arthropod-borne viral) diseases of animals, and the role global change could have played in these variations. Two of the most important arboviral diseases of animals, bluetongue (BT) and West Nile fever/encephalitis (WNF), have been selected as models. In both cases, in the last 15 years an important leap forward has been observed, which has lead to considering them emerging diseases in different parts of the world. BT, affecting domestic ruminants, has recently afflicted livestock in Europe in an unprecedented epizootic, causing enormous economic losses. WNF affects wildlife (birds), domestic animals (equines), and humans, thus, beyond the economic consequences of its occurrence, as a zoonotic disease, it poses an important public health threat. West Nile virus (WNV) has expanded in the last 12 years worldwide, and particularly in the Americas, where it first occurred in 1999, extending throughout the Americas relentlessly since then, causing a severe epidemic of disastrous consequences for public health, wildlife, and livestock. In Europe, WNV is known long time ago, but it is since the last years of the twentieth century that its incidence has risen substantially. Circumstances such as global warming, changes in land use and water management, increase in travel, trade of animals, and others, can have an important influence in the observed changes in both diseases. The following question is raised: What is the contribution of global changes to the current increase of these diseases in the world?

  18. Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge.

    Science.gov (United States)

    Gowen, Brian B; Bailey, Kevin W; Scharton, Dionna; Vest, Zachery; Westover, Jonna B; Skirpstunas, Ramona; Ikegami, Tetsuro

    2013-05-01

    Rift Valley fever virus (RVFV) causes severe disease in humans and livestock. There are currently no approved antivirals or vaccines for the treatment or prevention of RVF disease in humans. A major virulence factor of RVFV is the NSs protein, which inhibits host transcription including the interferon (IFN)-β gene and promotes the degradation of dsRNA-dependent protein kinase, PKR. We analyzed the efficacy of the live-attenuated MP-12 vaccine strain and MP-12 variants that lack the NSs protein as post-exposure vaccinations. Although parental MP-12 failed to elicit a protective effect in mice challenged with wild-type (wt) RVFV by the intranasal route, significant protection was demonstrated by vaccination with MP-12 strains lacking NSs when they were administered at 20-30 min post-exposure. Viremia and virus replication in liver, spleen and brain were also inhibited by post-exposure vaccination with MP-12 lacking NSs. The protective effect was mostly lost when vaccination was delayed 6 or 24 h after intranasal RVFV challenge. When mice were challenged subcutaneously, efficacy of MP-12 lacking NSs was diminished, most likely due to more rapid dissemination of wt RVFV. Our findings suggest that post-exposure vaccination with MP-12 lacking NSs may be developed as a novel post-exposure treatment to prevent RVF. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Yellow fever, Asia and the East African slave trade.

    Science.gov (United States)

    Cathey, John T; Marr, John S

    2014-05-01

    Yellow fever is endemic in parts of sub-Saharan Africa and South America, yet its principal vectors--species of mosquito of the genus Aedes--are found throughout tropical and subtropical latitudes. Phylogenetic analyses indicate that yellow fever originated in Africa and that its spread to the New World coincided with the slave trade, but why yellow fever has never appeared in Asia remains a mystery. None of several previously proposed explanations for its absence there is considered satisfactory. We contrast the trans-Atlantic slave trade, and trade across the Sahara and to the Arabian Peninsula and Mesopotamia, with that to Far East and Southeast Asian ports before abolition of the African slave trade, and before the scientific community understood the transmission vector of yellow fever and the viral life cycle, and the need for shipboard mosquito control. We propose that these differences in slave trading had a primary role in the avoidance of yellow fever transmission into Asia in the centuries before the 20(th) century. The relatively small volume of the Black African slave trade between Africa and East and Southeast Asia has heretofore been largely ignored. Although focal epidemics may have occurred, the volume was insufficient to reach the threshold for endemicity.

  20. Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses.

    Science.gov (United States)

    Hastie, Kathryn M; Bale, Shridhar; Kimberlin, Christopher R; Saphire, Erica Ollmann

    2012-04-01

    The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention. Copyright © 2012. Published by Elsevier B.V.

  1. Construction and characterization of a recombinant yellow fever virus stably expressing Gaussia luciferase

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    TELISSA C. KASSAR

    Full Text Available ABSTRACT Yellow fever is an arthropod-borne viral disease that still poses high public health concerns, despite the availability of an effective vaccine. The development of recombinant viruses is of utmost importance for several types of studies, such as those aimed to dissect virus-host interactions and to search for novel antiviral strategies. Moreover, recombinant viruses expressing reporter genes may greatly facilitate these studies. Here, we report the construction of a recombinant yellow fever virus (YFV expressing Gaussia luciferase (GLuc (YFV-GLuc. We show, through RT-PCR, sequencing and measurement of GLuc activity, that stability of the heterologous gene was maintained after six passages. Furthermore, a direct association between GLuc expression and viral replication was observed (r2=0.9967, indicating that measurement of GLuc activity may be used to assess viral replication in different applications. In addition, we evaluated the use of the recombinant virus in an antiviral assay with recombinant human alfa-2b interferon. A 60% inhibition of GLuc expression was observed in cells infected with YFV-GLuc and incubated with IFN alfa-2b. Previously tested on YFV inhibition by plaque assays indicated a similar fold-decrease in viral replication. These results are valuable as they show the stability of YFV-GLuc and one of several possible applications of this construct.

  2. Reported 5 cases of Crimean-Congo hemorrhagic fever in Fars province in 2011

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    Fatemeh Rezaei

    2012-09-01

    Full Text Available Crimean-Congo Hemorrhagic Fever (CCHF is a viral hemorrhagic disease and a zoonosis disease that has been developed in people who deal with animals such as cattle and butchers. The diagnosis of CCHF is performed by detection of human antibodies (IgG and IgM against CCHF virus. Five Patients with CCHF occurred in Fath Abad’s village (in Fars province in the summer of 2011. All patients were men and aged 25-46 years old. Three patients were farmer and two other ones were butchers. The samples were sent to the National Reference Laboratory for Arboviruses and Viral Haemorrhagic Fevers (Pasteur Institute of Iran in Tehran. The result of laboratory test for all patients was positive. None of the patients had died. Since the CCHF is rare, present study was aimed to assess the causes of the disease’s epidemic and clinical and laboratory symptoms stones.

  3. Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments.

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    Paul J Wichgers Schreur

    2016-08-01

    Full Text Available The bunyavirus genome comprises a small (S, medium (M, and large (L RNA segment of negative polarity. Although genome segmentation confers evolutionary advantages by enabling genome reassortment events with related viruses, genome segmentation also complicates genome replication and packaging. Accumulating evidence suggests that genomes of viruses with eight or more genome segments are incorporated into virions by highly selective processes. Remarkably, little is known about the genome packaging process of the tri-segmented bunyaviruses. Here, we evaluated, by single-molecule RNA fluorescence in situ hybridization (FISH, the intracellular spatio-temporal distribution and replication kinetics of the Rift Valley fever virus (RVFV genome and determined the segment composition of mature virions. The results reveal that the RVFV genome segments start to replicate near the site of infection before spreading and replicating throughout the cytoplasm followed by translocation to the virion assembly site at the Golgi network. Despite the average intracellular S, M and L genome segments approached a 1:1:1 ratio, major differences in genome segment ratios were observed among cells. We also observed a significant amount of cells lacking evidence of M-segment replication. Analysis of two-segmented replicons and four-segmented viruses subsequently confirmed the previous notion that Golgi recruitment is mediated by the Gn glycoprotein. The absence of colocalization of the different segments in the cytoplasm and the successful rescue of a tri-segmented variant with a codon shuffled M-segment suggested that inter-segment interactions are unlikely to drive the copackaging of the different segments into a single virion. The latter was confirmed by direct visualization of RNPs inside mature virions which showed that the majority of virions lack one or more genome segments. Altogether, this study suggests that RVFV genome packaging is a non-selective process.

  4. Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007.

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    Caroline Ochieng

    Full Text Available Arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in Kenya and East Africa. In this study, we used 1,091 HIV-negative blood specimens from the 2007 Kenya AIDS Indicator Survey (KAIS 2007 to test for the presence of IgG antibodies to dengue virus (DENV, chikungunya virus (CHIKV and Rift Valley fever virus (RVFV.The KAIS 2007 was a national population-based survey conducted by the Government of Kenya to provide comprehensive information needed to address the HIV/AIDS epidemic. Antibody testing for arboviruses was performed on stored blood specimens from KAIS 2007 through a two-step sandwich IgG ELISA using either commercially available kits or CDC-developed assays. Out of the 1,091 samples tested, 210 (19.2% were positive for IgG antibodies against at least one of the three arboviruses. DENV was the most common of the three viruses tested (12.5% positive, followed by RVFV and CHIKV (4.5% and 0.97%, respectively. For DENV and RVFV, the participant's province of residence was significantly associated (P≤.01 with seropositivity. Seroprevalence of DENV and RVFV increased with age, while there was no correlation between province of residence/age and seropositivity for CHIKV. Females had twelve times higher odds of exposure to CHIK as opposed to DENV and RVFV where both males and females had the same odds of exposure. Lack of education was significantly associated with a higher odds of previous infection with either DENV or RVFV (p <0.01. These data show that a number of people are at risk of arbovirus infections depending on their geographic location in Kenya and transmission of these pathogens is greater than previously appreciated. This poses a public health risk, especially for DENV.

  5. Exploratory space-time analyses of Rift Valley Fever in South Africa in 2008-2011.

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    Raphaëlle Métras

    Full Text Available Rift Valley fever (RVF is a zoonotic arbovirosis for which the primary hosts are domestic livestock (cattle, sheep and goats. RVF was first described in South Africa in 1950-1951. Mechanisms for short and long distance transmission have been hypothesised, but there is little supporting evidence. Here we describe RVF occurrence and spatial distribution in South Africa in 2008-11, and investigate the presence of a contagious process in order to generate hypotheses on the different mechanisms of transmission.A total of 658 cases were extracted from World Animal Health Information Database. Descriptive statistics, epidemic curves and maps were produced. The space-time K-function was used to test for evidence of space-time interaction. Five RVF outbreak waves (one in 2008, two in 2009, one in 2010 and one in 2011 of varying duration, location and size were reported. About 70% of cases (n = 471 occurred in 2010, when the epidemic was almost country-wide. No strong evidence of space-time interaction was found for 2008 or the second wave in 2009. In the first wave of 2009, a significant space-time interaction was detected for up to one month and over 40 km. In 2010 and 2011 a significant intense, short and localised space-time interaction (up to 3 days and 15 km was detected, followed by one of lower intensity (up to 2 weeks and 35 to 90 km.The description of the spatiotemporal patterns of RVF in South Africa between 2008 and 2011 supports the hypothesis that during an epidemic, disease spread may be supported by factors other than active vector dispersal. Limitations of under-reporting and space-time K-function properties are discussed. Further spatial analyses and data are required to explain factors and mechanisms driving RVF spread.

  6. Computed tomographic brain scan findings in Q fever encephalitis

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    Gomez Aranda, F.; Romero Acebal, M.; Maestre Moreno, J.; Pachon Diaz, J.; Lopez Cortes, L.; Navarro Rodriguez, A.

    1984-07-01

    Neurological involvement in Q Fever is unusual. We present a case of encephalitis due to Coxiella Burnetii with neuroradiologic findings on CT not described previously, consisting in areas of decreased absorption coefficient in the subcortical white matter of both hemispheres, predominantly in the right. Differential diagnosis must be established from viral encephalitis, of similar clinical presentation, which may show similar CT lesions to those in this case.

  7. Crimean-Congo hemorrhagic fever in Iran and neighboring countries

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    Chinikar, S; Ghiasi, Seyed Mojtaba; Hewson, R

    2010-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease that is asymptomatic in infected livestock, but a serious threat to humans. Human infections begin with nonspecific febrile symptoms, but progress to a serious hemorrhagic syndrome with a case fatality rate of 2-50%. Although the ...... in Iran and neighboring countries and provide evidence of over 5000 confirmed cases of CCHF in a single period/season....

  8. A fatal yellow fever virus infection in China: description and lessons

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    Chen, Zhihai; Liu, Lin; Lv, Yanning; Zhang, Wei; Li, Jiandong; Zhang, Yi; Di, Tian; Zhang, Shuo; Liu, Jingyuan; Li, Jie; Qu, Jing; Hua, Wenhao; Li, Chuan; Wang, Peng; Zhang, Quanfu; Xu, Yanli; Jiang, Rongmeng; Wang, Qin; Chen, Lijuan; Wang, Shiwen; Pang, Xinghuo; Liang, Mifang; Ma, Xuejun; Li, Xingwang; Wang, Quanyi; Zhang, Fujie; Li, Dexin

    2016-01-01

    Yellow fever (YF) is a viral disease endemic to the tropical regions of Africa and South America. An outbreak of YF has been occurring in Angola, since the beginning of 2016. In March 2016, a 32-year-old Chinese man who returned from Angola was hospitalized and diagnosed with the first case of imported YF in China. Clinical observations, blood viral RNA detection, serological testing and treatments for the patient were performed daily. The virus was isolated in Vero cells, and the complete viral genome was sequenced and analyzed using the next-generation genomic sequencing platform. The patient presented with hemorrhagic fever, jaundice and oliguria at day 3 after onset, which rapidly progressed to multisystem organ failure with extremely elevated liver, pancreatic and myocardial enzymes. The patient died despite the intensive supportive treatments that were performed. A liver biopsy showed severe and multilobular necrosis. Viral RNA was detectable throughout the clinical course of the disease. Whole-genomic sequence analysis revealed that the virus belongs to the Angola71 genotype. Although the virus has been circulating in Angola for 45 years, only 14 amino-acid substitutions and no amino-acid changes were observed in the membrane and envelope proteins compared with the virus collected in 1971. The presence of this imported YF case in China indicated that with the increase in business travel among countries, YF outbreaks in Africa can lead to the international spread of the disease. The production and use of YF vaccines is, therefore, an urgent issue. PMID:27406389

  9. THROMBOCYTOPENIA IN DENGUE HAEMORRHAGIC FEVER

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    I Wayan Putu Sutirta-Yasa

    2013-04-01

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

  10. Tri-phasic fever in dengue fever.

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    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.

  11. Predicting distribution of Aedes aegypti and Culex pipiens complex, potential vectors of Rift Valley fever virus in relation to disease epidemics in East Africa

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    Clement Nyamunura Mweya

    2013-10-01

    Full Text Available Background: The East African region has experienced several Rift Valley fever (RVF outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. Methods: Diverse ecological niche modelling techniques have been developed for this purpose: we present a maximum entropy (Maxent approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Results: Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Conclusion: Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods.

  12. Predicting distribution of Aedes aegypti and Culex pipiens complex, potential vectors of Rift Valley fever virus in relation to disease epidemics in East Africa.

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    Mweya, Clement Nyamunura; Kimera, Sharadhuli Iddi; Kija, John Bukombe; Mboera, Leonard E G

    2013-01-01

    The East African region has experienced several Rift Valley fever (RVF) outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. DIVERSE ECOLOGICAL NICHE MODELLING TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy (Maxent) approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods.

  13. Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases?

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    MacNeil, Adam; Rollin, Pierre E.

    2012-01-01

    Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the “classic” NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease. PMID:22761967

  14. A case report of crimean congo hemorrhagic Fever in ostriches in iran

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    Mostafavi, Ehsan; Chinikar, Sadegh; Moradi, Maryam

    2013-01-01

    Crimean Congo hemorrhagic fever (CCHF) is a viral zoonosis, which is usually transmitted via tick bites or close contact with infected blood or tissue. This disease can cause a case fatality rate of up to 25%-30% in humans. CCHF Infection in birds is less documented. An ostrich can reproduce...

  15. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

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    Roberto G. Pozner

    2013-01-01

    Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  16. Fatal yellow fever in a traveler returning from Venezuela, 1999.

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    2000-04-14

    On September 28, 1999, a previously healthy 48-year-old man from California sought care at a local emergency department (ED) and was hospitalized with a 2-day history of fever (102 F [38.9 C]), chills, headache, photophobia, diffuse myalgias, joint pains, nausea, vomiting, constipation, upper abdominal discomfort, and general weakness. On September 26, he had returned from a 10-day trip to Venezuela. On September 29, an infectious disease physician from the ED contacted the Marin County Health Department (MCHD) about the patient's symptoms; MCHD reported his illness to the California Department of Health Services (CDHS) as a suspected case of viral hemorrhagic fever. This report describes the investigation of the case.

  17. Rift Valley fever in a zone potentially occupied by Aedes vexans in Senegal: dynamics and risk mapping

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    Cécile Vignolles

    2009-05-01

    Full Text Available This paper presents an analysis of the interaction between the various variables associated with Rift Valley fever (RVF such as the mosquito vector, available hosts and rainfall distribution. To that end, the varying zones potentially occupied by mosquitoes (ZPOM, rainfall events and pond dynamics, and the associated exposure of hosts to the RVF virus by Aedes vexans, were analyzed in the Barkedji area of the Ferlo, Senegal, during the 2003 rainy season. Ponds were identified by remote sensing using a high-resolution SPOT-5 satellite image. Additional data on ponds and rainfall events from the Tropical Rainfall Measuring Mission were combined with in-situ entomological and limnimetric measurements, and the localization of vulnerable ruminant hosts (data derived from QuickBird satellite. Since “Ae. vexans productive events” are dependent on the timing of rainfall for their embryogenesis (six days without rain are necessary to trigger hatching, the dynamic spatio-temporal distribution of Ae. vexans density was based on the total rainfall amount and pond dynamics. Detailed ZPOM mapping was obtained on a daily basis and combined with aggressiveness temporal profiles. Risks zones, i.e. zones where hazards and vulnerability are combined, are expressed by the percentages of parks where animals are potentially exposed to mosquito bites. This new approach, simply relying upon rainfall distribution evaluated from space, is meant to contribute to the implementation of a new, operational early warning system for RVF based on environmental risks linked to climatic and environmental conditions.

  18. NSs Protein of Rift Valley Fever Virus Promotes Posttranslational Downregulation of the TFIIH Subunit p62▿

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    Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

    2011-01-01

    Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus. PMID:21543505

  19. Development of a broad-spectrum antiviral with activity against Ebola virus.

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    Aman, M Javad; Kinch, Michael S; Warfield, Kelly; Warren, Travis; Yunus, Abdul; Enterlein, Sven; Stavale, Eric; Wang, Peifang; Chang, Shaojing; Tang, Qingsong; Porter, Kevin; Goldblatt, Michael; Bavari, Sina

    2009-09-01

    We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.

  20. Dengue fever with hepatitis E and hepatitis A infection.

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    Yakoob, Javed; Jafri, Wasim; Siddiqui, Shaheer; Riaz, Mehmood

    2009-03-01

    Infection with dengue viruses produces a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal haemorrhagic disease. Important risk factors include the strain and serotype of the infecting virus, as well as the age, immune status, and genetic predisposition of the patient. The teaching point in this case study was Dengue fever which occurred concomitantly with Hepatitis A and Hepatitis E virus infection.

  1. Dengue viral RNA levels in peripheral blood mononuclear cells are associated with disease severity and preexisting dengue immune status.

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    Anon Srikiatkhachorn

    Full Text Available Infection with dengue viruses (DENV causes a wide range of manifestations from asymptomatic infection to a febrile illness called dengue fever (DF, to dengue hemorrhagic fever (DHF. The in vivo targets of DENV and the relation between the viral burden in these cells and disease severity are not known.The levels of positive and negative strand viral RNA in peripheral blood monocytes, T/NK cells, and B cells and in plasma of DF and DHF cases were measured by quantitative RT-PCR.Positive strand viral RNA was detected in monocytes, T/NK cells and B cells with the highest amounts found in B cells. Viral RNA levels in CD14+ cells and plasma were significantly higher in DHF compared to DF, and in cases with a secondary infection compared to those undergoing a primary infection. The distribution of viral RNA among cell subpopulations was similar in DF and DHF cases. Small amounts of negative strand RNA were found in a few cases only. The severity of plasma leakage correlated with viral RNA levels in plasma and in CD14+ cells.B cells were the principal cells containing DENV RNA in peripheral blood, but overall there was little active DENV RNA replication detectable in peripheral blood mononuclear cells (PBMC. Secondary infection and DHF were associated with higher viral burden in PBMC populations, especially CD14+ monocytes, suggesting that viral infection of these cells may be involved in disease pathogenesis.

  2. Protective Role of Cytotoxic T Lymphocytes in Filovirus Hemorrhagic Fever

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    Kelly Lyn Warfield

    2011-01-01

    Full Text Available Infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, Marburg (MARV, and Ebola virus (EBOV, leaves the host with a short timeframe in which to mouse a protective immune response. In lethal cases, uncontrolled viral replication and virus-induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. Vaccination studies in animals have demonstrated an association of IgG and neutralizing antibody responses against the protective glycoprotein antigen with survival from lethal challenge. More recently, studies in animal models of filovirus hemorrhagic fever have established that induction of a strong filovirus-specific cytotoxic T lymphocyte (CTL response can facilitate complete viral clearance. In this review, we describe assays used to discover CTL responses after vaccination or live filovirus infection in both animal models and human clinical trials. Unfortunately, little data regarding CTL responses have been collected from infected human survivors, primarily due to the low frequency of disease and the inability to perform these studies in the field. Advancements in assays and technologies may allow these studies to occur during future outbreaks.

  3. A temperature-limited assessment of the risk of Rift Valley fever transmission and establishment in the continental United States of America

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    Sarah K. Konrad

    2012-05-01

    Full Text Available The rapid spread of West Nile virus across North America after its introduction in 1999 highlights the potential for foreign arboviruses to become established in the United States of America. Of particular concern is Rift Valley fever virus (RVFV, which has been responsible for multiple African epidemics resulting in death of both humans and livestock, as well as major economic disruption due to livestock loss and trade restrictions. Modern globalization, travel, and commerce allow viruses to easily jump from one continent to another; and it is likely only a matter of time before RVFV reaches North American shores. We used a degree-day model in combination with livestock population data and a pathways analysis to identify regions and times where RVFV is most likely to enter and become established in the United States of America. Transmission risk of the disease varies across the country from 325 annual risk days in parts of Florida to zero risk days in the far North and in high mountain regions. Areas of particular concern are where there are a high number of possible transmission days, a large livestock population, and proximity to likely locations for the disease to enter the country via mosquito vector or human host. These areas should be monitored closely during transmission “risk seasons” so that if the virus does enter the country and begins to become established, it can be quickly controlled and eliminated before spreading further. Areas most at risk include the Baltimore and New York City metro areas as well as much of the region between these urban centers; most of Texas, especially around Houston; Florida; Atlanta; southwest Nebraska; southern California and Arizona; and the central valley of California.

  4. Circulation of antibodies against yellow fever virus in a simian population in the area of Porto Primavera Hydroelectric Plant, São Paulo, Brazil.

    Science.gov (United States)

    Lima, Maura Antonia; Romano-Lieber, Nicolina Silvana; Duarte, Ana Maria Ribeiro de Castro

    2010-01-01

    Yellow fever (YF) is an acute viral infectious disease transmitted by mosquitoes which occurs in two distinct epidemiological cycles: sylvatic and urban. In the sylvatic cycle, the virus is maintained by monkey's infection and transovarian transmission in vectors. Surveillance of non-human primates is required for the detection of viral circulation during epizootics, and for the identification of unaffected or transition areas. An ELISA (enzyme-linked immunosorbent assay) was standardized for estimation of the prevalence of IgG antibodies against yellow fever virus in monkey sera (Alouatta caraya) from the reservoir area of Porto Primavera Hydroelectric Plant, in the state of São Paulo, Brazil. A total of 570 monkey sera samples were tested and none was reactive to antibodies against yellow fever virus. The results corroborate the epidemiology of yellow fever in the area. Even though it is considered a transition area, there were no reports to date of epizootics or yellow fever outbreaks in humans. Also, entomological investigations did not detect the presence of vectors of this arbovirus infection. ELISA proved to be fast, sensitive, an adequate assay, and an instrument for active search in the epidemiological surveillance of yellow fever allowing the implementation of prevention actions, even before the occurrence of epizootics.

  5. Clinical and laboratory features of dengue virus-infected travellers previously vaccinated against yellow fever

    NARCIS (Netherlands)

    Teichmann, Dieter; Göbels, Klaus; Niedrig, Matthias; Grobusch, Martin P.

    2003-01-01

    Dengue is a mosquito-borne viral infection endemic throughout the tropics and subtropics. The global prevalence of dengue has grown dramatically in recent years and it has become a major international public health concern. The close taxonomic relationships between yellow fever and dengue viruses

  6. High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo.

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    Makiala-Mandanda, Sheila; Le Gal, Frédéric; Ngwaka-Matsung, Nadine; Ahuka-Mundeke, Steve; Onanga, Richard; Bivigou-Mboumba, Berthold; Pukuta-Simbu, Elisabeth; Gerber, Athenaïs; Abbate, Jessica L; Mwamba, Dieudonné; Berthet, Nicolas; Leroy, Eric Maurice; Muyembe-Tamfum, Jean-Jacques; Becquart, Pierre

    2017-05-01

    The majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 10 5 IU/ml for HBV (range, 769 to 9.82 × 10 9 IU/ml) and 1.4 × 10 6 IU/ml for HDV (range, 3.1 × 10 2 to 2.9 × 10 8 IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC. Copyright © 2017 Makiala-Mandanda et al.

  7. Neurological complications of dengue fever: Experience from a tertiary center of north India

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    Rajesh Verma

    2011-01-01

    Full Text Available Introduction: Dengue, an acute viral disease transmitted by Aedes mosquitoes, is highly endemic in many tropical and subtropical areas of the world. Neurological complications of dengue infection have been observed more frequently in the recent past and some studies highlighted varied neurological complications arising in the course of dengue illness. In this retrospective study, we report various neurological complications observed during the last 2 years in patients of dengue fever. Materials and Methods: The patients presenting with neurological complications with positive serology (IgM antibody for dengue infection were consecutively recruited from the Department of Neurology/Medicine from a tertiary center of Lucknow, India. These patients were subjected to a detailed clinical evaluation, laboratory assessment including blood count, hematocrit, coagulation parameters, biochemical assays, serology for dengue fever, enzyme-linked immunosorbent assay for human immunodeficiency virus and other relevant investigations. Results: Twenty-six patients with neurological complications associated with confirmed dengue infection were observed during the last 2 years. Eighteen of these patients were male. Of the 26 patients, 10 patients were suffering from brachial neuritis, four patients had encephalopathy, three patients were consistent with the diagnosis of Guillain Barre syndrome, three patients had hypokalemic paralysis associated with dengue fever and two patients had acute viral myositis. Opsoclonus-myoclonus syndrome was diagnosed in two patients, myelitis in one patient and acute disseminated encephalo-myelitis also in one patient. Conclusion: Dengue fever was associated with widespread neurological complications. Brachial neuritis and opsoclonus-myoclonus syndrome were observed for the first time in this study.

  8. Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar.

    Science.gov (United States)

    Aye, Khin Saw; Charngkaew, Komgrid; Win, Ne; Wai, Kyaw Zin; Moe, Kyaw; Punyadee, Nuntaya; Thiemmeca, Somchai; Suttitheptumrong, Aroonroong; Sukpanichnant, Sanya; Prida, Malasit; Halstead, Scott B

    2014-06-01

    Vascular permeability, thrombocytopenia, liver pathology, complement activation, and altered hemostasis accompanying a febrile disease are the hallmarks of the dengue hemorrhagic fever/dengue shock syndrome, a major arthropod-borne viral disease that causes significant morbidity and mortality throughout tropical countries. We studied tissues from 13 children who died of acute dengue hemorrhagic fever/dengue shock syndrome at the Childrens' Hospital, Yangon, Myanmar. Dengue viral RNA from each of the 4 dengue viruses (DENVs) was detected by reverse transcriptase polymerase chain reaction in 11 cases, and dengue viral proteins (envelope, NS1, or NS3) were detected in 1 or more tissues from all 13 cases. Formalin-fixed and frozen tissues were studied for evidence of virus infection using monoclonal antibodies against DENV structural and nonstructural antigens (E, NS1, and nonsecreting NS3). In the liver, DENV infection occurred in hepatocytes and Kupffer cells but not in endothelial cells. Liver damage was associated with deposition on hepatocytes of complement components of both classical and alternative pathways. Evidence of dengue viral replication was observed in macrophage-like cells in spleens and lymph nodes. No dengue antigens were detected in endothelial cells in any organ. Germinal centers of the spleen and lymph nodes showed a marked reduction in the number of lymphocytes that were replaced by eosinophilic deposits, which contained dengue antigens as well as immunoglobulins, and complement components (C3, C1q, and C9). The latter findings had previously been reported but overlooked as a diagnostic feature. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Association between sepsis and Rocky Mountain spotted fever.

    Science.gov (United States)

    Bacci, Marcelo Rodrigues; Namura, José Jorge

    2012-12-06

    Rocky Mountain spotted fever (RMSF) is a disease caused by the Gram-negative coccobacillus Rickettsia ricketsii which has been on the rise since the last decade in the USA. The symptoms are common to the many viral diseases, and the classic triad of fever, rash and headache is not always present when RMSF is diagnosed. It may progress to severe cases such as renal failure, disseminated intravascular coagulation and septicaemia. This report aims to present a fulminant case of RMSF associated with sepsis. It describes a female patient's case that quickly progressed to sepsis and death. The patient showed non-specific symptoms for 5 days before being admitted to a hospital. The fact that she lived in an area highly infested with Amblyomma aureolatum ticks was unknown to the medical staff until the moment she died.

  10. Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs*

    Science.gov (United States)

    Sun, Qiyu; Qi, Xian; Zhang, Yan; Wu, Xiaodong; Liang, Mifang; Li, Chuan; Li, Dexin; Cardona, Carol J.; Xing, Zheng

    2016-01-01

    Synaptogyrin-2 is a non-neuronal member of the synaptogyrin family involved in synaptic vesicle biogenesis and trafficking. Little is known about the function of synaptogyrin-2. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, and leukocytopenia with high mortality, caused by a novel tick-borne phlebovirus in the family Bunyaviridae. Our previous studies have shown that the viral nonstructural protein NSs forms inclusion bodies (IBs) that are involved in viral immune evasion, as well as viral RNA replication. In this study, we sought to elucidate the mechanism by which NSs formed the IBs, a lipid droplet-based structure confirmed by NSs co-localization with perilipin A and adipose differentiation-related protein (ADRP). Through a high throughput screening, we identified synaptogyrin-2 to be highly up-regulated in response to SFTS bunyavirus (SFTSV) infection and to be a promoter of viral replication. We demonstrated that synaptogyrin-2 interacted with NSs and was translocated into the IBs, which were reconstructed from lipid droplets into large structures in infection. Viral RNA replication decreased, and infectious virus titers were lowered significantly when synaptogyrin-2 was silenced in specific shRNA-expressing cells, which correlated with the reduced number of the large IBs restructured from regular lipid droplets. We hypothesize that synaptogyrin-2 is essential to promoting the formation of the IBs to become virus factories for viral RNA replication through its interaction with NSs. These findings unveil the function of synaptogyrin-2 as an enhancer in viral infection. PMID:27226560

  11. Dengue fever treatment with Carica papaya leaves extracts.

    Science.gov (United States)

    Ahmad, Nisar; Fazal, Hina; Ayaz, Muhammad; Abbasi, Bilal Haider; Mohammad, Ijaz; Fazal, Lubna

    2011-08-01

    The main objective of the current study is to investigate the potential of Carica papaya leaves extracts against Dengue fever in 45 year old patient bitten by carrier mosquitoes. For the treatment of Dengue fever the extract was prepared in water. 25 mL of aqueous extract of C. papaya leaves was administered to patient infected with Dengue fever twice daily i.e. morning and evening for five consecutive days. Before the extract administration the blood samples from patient were analyzed. Platelets count (PLT), White Blood Cells (WBC) and Neutrophils (NEUT) decreased from 176×10(3)/µL, 8.10×10(3)/µL, 84.0% to 55×10(3)/µL, 3.7×10(3)/µL and 46.0%. Subsequently, the blood samples were rechecked after the administration of leaves extract. It was observed that the PLT count increased from 55×10(3)/µL to 168×10(3)/µL, WBC from 3.7×10(3)/µL to 7.7×10(3)/µL and NEUT from 46.0% to 78.3%. From the patient feelings and blood reports it showed that Carica papaya leaves aqueous extract exhibited potential activity against Dengue fever. Furthermore, the different parts of this valuable specie can be further used as a strong natural candidate against viral diseases.

  12. Co-housing of Rift Valley fever virus infected lambs with immunocompetent or immunosuppressed lambs does not result in virus transmission

    Directory of Open Access Journals (Sweden)

    Paul J Wichgers Schreur

    2016-03-01

    Full Text Available Rift Valley fever virus (RVFV is transmitted among susceptible animals by mosquito vectors. Although the virus can be isolated from nasal and oral swabs of infected animals and is known to be highly infectious when administered experimentally via oral or respiratory route, horizontal transmission of the virus is only sporadically reported in literature. We considered that immunosuppression resulting from stressful conditions in the field may increase the susceptibility to horizontally transmitted RVFV. Additionally, we reasoned that horizontal transmission may induce immune responses that could affect the susceptibility of contact-exposed animals to subsequent infection via mosquito vectors. To address these two hypotheses, viremic lambs were brought into contact with sentinel lambs. One group of sentinel lambs was treated with the immunosuppressive synthetic glucocorticosteroid dexamethasone and monitored for signs of disease and presence of virus in the blood and target organs. Another group of contact-exposed sentinel lambs remained untreated for three weeks and was subsequently challenged with RVFV. We found that none of the dexamethasone-treated contact-exposed lambs developed detectable viremia, antibody responses or significant increases in cytokine mRNA levels. Susceptibility of immunocompetent lambs to RVFV infection was not influenced by previous contact-exposure. Our results are discussed in light of previous findings.

  13. Overlapping CD8+ and CD4+ T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach.

    Science.gov (United States)

    Adhikari, Utpal Kumar; Rahman, M Mizanur

    2017-12-01

    Rift Valley fever virus (RVFV) is an emergent arthropod-borne zoonotic infectious viral pathogen which causes fatal diseases in the humans and ruminants. Currently, no effective and licensed vaccine is available for the prevention of RVFV infection in endemic as well as in non-endemic regions. So, an immunoinformatics-driven genome-wide screening approach was performed for the identification of overlapping CD8+ and CD4+ T-cell epitopes and also linear B-cell epitopes from the conserved sequences of the nucleocapsid (N) and glycoprotein (G) of RVFV. We identified overlapping 99.39% conserved 1 CD8+ T-cell epitope (MMHPSFAGM) from N protein and 100% conserved 7 epitopes (AVFALAPVV, LAVFALAPV, FALAPVVFA, VFALAPVVF, IAMTVLPAL, FFDWFSGLM, and FLLIYLGRT) from G protein and also identified IL-4 and IFN-γ induced (99.39% conserved) 1 N protein CD4+ T-cell epitope (HMMHPSFAGMVDPSL) and 100% conserved 5 G protein CD4+ T-cell epitopes (LPALAVFALAPVVFA, PALAVFALAPVVFAE, GIAMTVLPALAVFAL, GSWNFFDWFSGLMSW, and FFLLIYLGRTGLSKM). The overlapping CD8+ and CD4+ T-cell epitopes were bound with most conserved HLA-C*12:03 and HLA-DRB1*01:01, respectively with the high binding affinity (kcal/mol). The combined population coverage analysis revealed that the allele frequencies of these epitopes are high in endemic and non-endemic regions. Besides, we found 100% conserved and non-allergenic 2 decamer B-cell epitopes, GVCEVGVQAL and RVFNCIDWVH of G protein had the sequence similarity with the nonamer CD8+ T-cell epitopes, VCEVGVQAL and RVFNCIDWV, respectively. Consequently, these epitopes may be used for the development of epitope-based peptide vaccine against emerging RVFV. However, in vivo and in vitro experiments are required for their efficient use as a vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. TerraSAR-X high-resolution radar remote sensing: an operational warning system for Rift Valley fever risk.

    Science.gov (United States)

    Vignolles, Cécile; Tourre, Yves M; Mora, Oscar; Imanache, Laurent; Lafaye, Murielle

    2010-11-01

    In the vicinity of the Barkedji village (in the Ferlo region of Senegal), the abundance and aggressiveness of the vector mosquitoes for Rift Valley fever (RVF) are strongly linked to rainfall events and associated ponds dynamics. Initially, these results were obtained from spectral analysis of high-resolution (~10 m) Spot-5 images, but, as a part of the French AdaptFVR project, identification of the free water dynamics within ponds was made with the new high-resolution (down to 3-meter pixels), Synthetic Aperture Radar satellite (TerraSAR-X) produced by Infoterra GmbH, Friedrichshafen/Potsdam, Germany. During summer 2008, within a 30 x 50 km radar image, it was found that identified free water fell well within the footprints of ponds localized by optical data (i.e. Spot-5 images), which increased the confidence in this new and complementary remote sensing technique. Moreover, by using near real-time rainfall data from the Tropical Rainfall Measuring Mission (TRMM), NASA/JAXA joint mission, the filling-up and flushing-out rates of the ponds can be accurately determined. The latter allows for a precise, spatio-temporal mapping of the zones potentially occupied by mosquitoes capable of revealing the variability of pond surfaces. The risk for RVF infection of gathered bovines and small ruminants (~1 park/km(2)) can thus be assessed. This new operational approach (which is independent of weather conditions) is an important development in the mapping of risk components (i.e. hazards plus vulnerability) related to RVF transmission during the summer monsoon, thus contributing to a RVF early warning system.

  15. Predicting Rift Valley Fever Inter-epidemic Activities and Outbreak Patterns: Insights from a Stochastic Host-Vector Model.

    Directory of Open Access Journals (Sweden)

    Sansao A Pedro

    2016-12-01

    Full Text Available Rift Valley fever (RVF outbreaks are recurrent, occurring at irregular intervals of up to 15 years at least in East Africa. Between outbreaks disease inter-epidemic activities exist and occur at low levels and are maintained by female Aedes mcintoshi mosquitoes which transmit the virus to their eggs leading to disease persistence during unfavourable seasons. Here we formulate and analyse a full stochastic host-vector model with two routes of transmission: vertical and horizontal. By applying branching process theory we establish novel relationships between the basic reproduction number, R0, vertical transmission and the invasion and extinction probabilities. Optimum climatic conditions and presence of mosquitoes have not fully explained the irregular oscillatory behaviour of RVF outbreaks. Using our model without seasonality and applying van Kampen system-size expansion techniques, we provide an analytical expression for the spectrum of stochastic fluctuations, revealing how outbreaks multi-year periodicity varies with the vertical transmission. Our theory predicts complex fluctuations with a dominant period of 1 to 10 years which essentially depends on the efficiency of vertical transmission. Our predictions are then compared to temporal patterns of disease outbreaks in Tanzania, Kenya and South Africa. Our analyses show that interaction between nonlinearity, stochasticity and vertical transmission provides a simple but plausible explanation for the irregular oscillatory nature of RVF outbreaks. Therefore, we argue that while rainfall might be the major determinant for the onset and switch-off of an outbreak, the occurrence of a particular outbreak is also a result of a build up phenomena that is correlated to vertical transmission efficiency.

  16. TerraSAR-X high-resolution radar remote sensing: an operational warning system for Rift Valley fever risk

    Directory of Open Access Journals (Sweden)

    Cécile Vignolles

    2010-11-01

    Full Text Available In the vicinity of the Barkedji village (in the Ferlo region of Senegal, the abundance and aggressiveness of the vector mosquitoes for Rift Valley fever (RVF are strongly linked to rainfall events and associated ponds dynamics. Initially, these results were obtained from spectral analysis of high-resolution (~10 m Spot-5 images, but, as a part of the French AdaptFVR project, identification of the free water dynamics within ponds was made with the new high-resolution (down to 3-meter pixels, Synthetic Aperture Radar satellite (TerraSAR-X produced by Infoterra GmbH, Friedrichshafen/Potsdam, Germany. During summer 2008, within a 30 x 50 km radar image, it was found that identified free water fell well within the footprints of ponds localized by optical data (i.e. Spot-5 images, which increased the confidence in this new and complementary remote sensing technique. Moreover, by using near real-time rainfall data from the Tropical Rainfall Measuring Mission (TRMM, NASA/JAXA joint mission, the filling-up and flushingout rates of the ponds can be accurately determined. The latter allows for a precise, spatio-temporal mapping of the zones potentially occupied by mosquitoes capable of revealing the variability of pond surfaces. The risk for RVF infection of gathered bovines and small ruminants (~1 park/km2 can thus be assessed. This new operational approach (which is independent of weather conditions is an important development in the mapping of risk components (i.e. hazards plus vulnerability related to RVF transmission during the summer monsoon, thus contributing to a RVF early warning system.

  17. Collective immunity of the population from endemic zones of hemorrhagic fever with renal syndrome in Kosovo.

    Science.gov (United States)

    Muçaj, Sefedin; Kabashi, Serbeze; Ahmeti, Salih; Dedushaj, Isuf; Ramadani, Naser; Avsic-Zupanc, Tatjana

    2009-01-01

    Hemorrhagic fever with renal syndrome (HFRS), also known as mice fever is an acute viral zoonosis and it appears in the natural focus after the human contact with Hantaan virus infected mice. The objective (purpose) of this study was to investigate the prevalence of specific antibodies in HFRS, in convalescent persons (collective immunity in endemic hearths). In this project we applied the epidemiological method of studying with retrospective-perspective, the serological method for determination and detecting antibodies from the persons of epidemical focus and statistical methods. The disease diagnosis is based on the epidemiological, clinical and serological records. The collected samples have been sent to referral laboratory in Medical Faculty-Institute of Microbiology Ljubljana for laboratory confirmation. From the results we came to conclusion that in the territory of Republic of Kosovo, the HFRS is still a serious health, economic and biological problem. The lethality rate from HFRS in 1986 was 15.4%, 1986-89 10.8%, from 1995-2006 8.70%. The lowest rates of morbidity, mortality and lethality of HFRS compared with the previous periods of time, prove collective immunity growth in Dukagjini valley. For collective immunity research and to conduct the persistence of antibodies for viral corresponding (relative) antigen, after the disease, the samples were collected in the time period of May-June 2008, with 203 persons that were tested with serological method IIF (Indirect immune fluorescence) from which 187 cases (92.1%) resulted sero-negative and 16 cases (7.9%) resulted sero-positive with HFRS. This proves the collective immunity increase for HFRS. From 13 recovered patients previously diagnosed with HFRS (1986-1989-1995), levels of antibodies were screened in 2008 with IIF. Out of 13 persons, positive antibodies were found in 10 cases, while 3 cases were negative for antibodies (HTN, PUU, and DOB). After 13, 19 and 22 years HTN, PUU and DOB antibodies persisted

  18. Rift Valley fever dynamics in Senegal: a project for pro-active adaptation and improvement of livestock raising management

    Directory of Open Access Journals (Sweden)

    Murielle Lafaye

    2013-11-01

    Full Text Available The multi-disciplinary French project “Adaptation à la Fièvre de la Vallée du Rift” (AdaptFVR has concluded a 10-year constructive interaction between many scientists/partners involved with the Rift Valley fever (RVF dynamics in Senegal. The three targeted objectives reached were (i to produce - in near real-time - validated risk maps for parked livestock exposed to RVF mosquitoes/vectors bites; (ii to assess the impacts on RVF vectors from climate variability at different time-scales including climate change; and (iii to isolate processes improving local livestock management and animal health. Based on these results, concrete, pro-active adaptive actions were taken on site, which led to the establishment of a RVF early warning system (RVFews. Bulletins were released in a timely fashion during the project, tested and validated in close collaboration with the local populations, i.e. the primary users. Among the strategic, adaptive methods developed, conducted and evaluated in terms of cost/benefit analyses are the larvicide campaigns and the coupled bio-mathematical (hydrological and entomological model technologies, which are being transferred to the staff of the “Centre de Suivi Ecologique” (CSE in Dakar during 2013. Based on the results from the AdaptFVR project, other projects with similar conceptual and modelling approaches are currently being implemented, e.g. for urban and rural malaria and dengue in the French Antilles.

  19. Search Results | Page 84 | IDRC - International Development ...

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

    Results 831 - 840 of 1187 ... South of Sahara 187 Apply South of Sahara filter · North of Sahara 139 .... Farmers find ways to reap the financial and nutritional benefits of millets ... Rift Valley fever (RVF) is a viral disease of goats, sheep, cattle, and humans.It is endemic in large parts of Africa, with outbreaks occurring in three to ...

  20. Roles of viroplasm-like structures formed by nonstructural protein NSs in infection with severe fever with thrombocytopenia syndrome virus.

    Science.gov (United States)

    Wu, Xiaodong; Qi, Xian; Liang, Mifang; Li, Chuan; Cardona, Carol J; Li, Dexin; Xing, Zheng

    2014-06-01

    Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging bunyavirus that causes a hemorrhagic fever with a high mortality rate. The virus is likely tick-borne and replicates primarily in hemopoietic cells, which may lead to disregulation of proinflammatory cytokine induction and loss of leukocytes and platelets. The viral genome contains L, M, and S segments encoding a viral RNA polymerase, glycoproteins G(n) and G(c), nucleoprotein (NP), and a nonstructural S segment (NSs) protein. NSs protein is involved in the regulation of host innate immune responses and suppression of IFNβ-promoter activities. In this article, we demonstrate that NSs protein can form viroplasm-like structures (VLSs) in infected and transfected cells. NSs protein molecules interact with one another, interact with NP, and were associated with viral RNA in infected cells, suggesting that NSs protein may be involved in viral replication. Furthermore, we observed that NSs-formed VLS colocalized with lipid droplets and that inhibitors of fatty acid biosynthesis decreased VLS formation or viral replication in transfected and infected cells. Finally, we have demonstrated that viral dsRNAs were also localized in VLS in infected cells, suggesting that NSs-formed VLS may be implicated in the replication of SFTS bunyavirus. These findings identify a novel function of nonstructural NSs in SFTSV-infected cells where it is a scaffolding component in a VLS functioning as a virus replication factory. This function is in addition to the role of NSs protein in modulating host responses that will broaden our understanding of viral pathogenesis of phleboviruses. © FASEB.

  1. A comparison of indirect immunofluorescence and electron microscopy for the diagnosis of some haemorrhagic viruses in cell cultures.

    Science.gov (United States)

    El Mekki, A A; van der Groen, G

    1981-09-01

    Yellow fever, dengue (types 1, 2 and 4), Chikungunya, Rift Valley fever, Ebola, Marburg, and Lassa viruses were inoculated into susceptible cell cultures and daily investigated by indirect immunofluorescence (IFA) and electron microscopy (EM) with a view to achieve an early detection-identification of these agents. Compared to the other cell lines tested (Vero, BHK-21 and Aedes albopictus), CV-1 cells were found to be more sensitive. Viral antigens were detected by IFA from a few hours post inoculation (CHIK and RVF) to a maximum of 3 days (YF and EBO). For most of the viruses studied, the cytopathic effect (CPE) commenced 2-3 days after the detection of viral antigens. Virus particles were detected by EM only in the case of EBO, MBG and LAS, before any CPE was observed in cell cultures.

  2. 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)

  3. Simian Hemorrhagic Fever Virus Cell Entry Is Dependent on CD163 and Uses a Clathrin-Mediated Endocytosis-Like Pathway

    OpenAIRE

    Caì, Yíngyún; Postnikova, Elena N.; Bernbaum, John G.; Yú, Shuǐqìng; Mazur, Steven; Deiuliis, Nicole M.; Radoshitzky, Sheli R.; Lackemeyer, Matthew G.; McCluskey, Adam; Robinson, Phillip J.; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L.; Lauck, Michael; Friedrich, Thomas C.

    2014-01-01

    Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A ...

  4. Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs.

    Science.gov (United States)

    Sun, Qiyu; Qi, Xian; Zhang, Yan; Wu, Xiaodong; Liang, Mifang; Li, Chuan; Li, Dexin; Cardona, Carol J; Xing, Zheng

    2016-07-29

    Synaptogyrin-2 is a non-neuronal member of the synaptogyrin family involved in synaptic vesicle biogenesis and trafficking. Little is known about the function of synaptogyrin-2. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, and leukocytopenia with high mortality, caused by a novel tick-borne phlebovirus in the family Bunyaviridae. Our previous studies have shown that the viral nonstructural protein NSs forms inclusion bodies (IBs) that are involved in viral immune evasion, as well as viral RNA replication. In this study, we sought to elucidate the mechanism by which NSs formed the IBs, a lipid droplet-based structure confirmed by NSs co-localization with perilipin A and adipose differentiation-related protein (ADRP). Through a high throughput screening, we identified synaptogyrin-2 to be highly up-regulated in response to SFTS bunyavirus (SFTSV) infection and to be a promoter of viral replication. We demonstrated that synaptogyrin-2 interacted with NSs and was translocated into the IBs, which were reconstructed from lipid droplets into large structures in infection. Viral RNA replication decreased, and infectious virus titers were lowered significantly when synaptogyrin-2 was silenced in specific shRNA-expressing cells, which correlated with the reduced number of the large IBs restructured from regular lipid droplets. We hypothesize that synaptogyrin-2 is essential to promoting the formation of the IBs to become virus factories for viral RNA replication through its interaction with NSs. These findings unveil the function of synaptogyrin-2 as an enhancer in viral infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. [YEL-AND meningoencephalitis in a 4-year-old boy consecutive to a yellow-fever vaccine].

    Science.gov (United States)

    Gerin, M; Wroblewski, I; Bost-Bru, C; N'guyen, M-A; Debillon, T

    2014-04-01

    Yellow fever is a vector-borne disease transmitted by an endemic mosquito in sub-Saharan Africa and tropical South America. It causes fever and possibly liver and renal failure with hemorrhagic signs, which may be fatal. The yellow-fever vaccine is an attenuated vaccine that is recommended for all travelers over the age of 9 months in high-risk areas. Adverse effects have been reported: minor symptoms (such as viral syndrome), hypersensitivity reactions, and major symptoms such as viscerotropic disease (YEL-AVD) and neurotropic disease (YEL-AND). The yellow-fever vaccine-associated autoimmune disease with central nervous system involvement (such as acute disseminated encephalomyelitis) associates fever and headaches, neurologic dysfunction, seizures, cerebrospinal fluid (CSF) pleocytosis, and elevated protein, with neuroimaging consistent with multifocal areas of demyelization. The presence of antibodies or virus in CSF, within 1-30 days following vaccination, and the exclusion of other causes is necessary for diagnosis. We describe herein the case of a 4-year-old child who presented with severe encephalitis consecutive to a yellow-fever vaccine, with favorable progression. Diagnosis is based on the chronology of clinical and paraclinical signs and the presence of yellow-fever-specific antibodies in CSF. The treatment consists of symptomatic treatment and immunoglobulin injection. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Sorting out pestiviral phylogeny: A tale of viral swarms, red herrings, and sons of Bs

    Science.gov (United States)

    Initially three species, border disease virus (BDV), bovine viral diarrhea virus (BVDV), and classical swine fever virus (CSFV), were recognized in the pestivirus genus. These three species were defined by their host of origin, and to a lesser extent by clinical presentation. Subsequently, attempts ...

  7. Yellow Fever Outbreak - Kongo Central Province, Democratic Republic of the Congo, August 2016.

    Science.gov (United States)

    Otshudiema, John O; Ndakala, Nestor G; Mawanda, Elande-Taty K; Tshapenda, Gaston P; Kimfuta, Jacques M; Nsibu, Loupy-Régence N; Gueye, Abdou S; Dee, Jacob; Philen, Rossanne M; Giese, Coralie; Murrill, Christopher S; Arthur, Ray R; Kebela, Benoit I

    2017-03-31

    On April 23, 2016, the Democratic Republic of the Congo's (DRC's) Ministry of Health declared a yellow fever outbreak. As of May 24, 2016, approximately 90% of suspected yellow fever cases (n = 459) and deaths (45) were reported in a single province, Kongo Central Province, that borders Angola, where a large yellow fever outbreak had begun in December 2015. Two yellow fever mass vaccination campaigns were conducted in Kongo Central Province during May 25-June 7, 2016 and August 17-28, 2016. In June 2016, the DRC Ministry of Health requested assistance from CDC to control the outbreak. As of August 18, 2016, a total of 410 suspected yellow fever cases and 42 deaths were reported in Kongo Central Province. Thirty seven of the 393 specimens tested in the laboratory were confirmed as positive for yellow fever virus (local outbreak threshold is one laboratory-confirmed case of yellow fever). Although not well-documented for this outbreak, malaria, viral hepatitis, and typhoid fever are common differential diagnoses among suspected yellow fever cases in this region. Other possible diagnoses include Zika, West Nile, or dengue viruses; however, no laboratory-confirmed cases of these viruses were reported. Thirty five of the 37 cases of yellow fever were imported from Angola. Two-thirds of confirmed cases occurred in persons who crossed the DRC-Angola border at one market city on the DRC side, where ≤40,000 travelers cross the border each week on market day. Strategies to improve coordination between health surveillance and cross-border trade activities at land borders and to enhance laboratory and case-based surveillance and health border screening capacity are needed to prevent and control future yellow fever outbreaks.

  8. 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

  9. Sandfly fever in Afghanistan-a sometimes overlooked disease of military importance: a case series and review of the literature.

    Science.gov (United States)

    Downs, John W; Flood, Daniel T; Orr, Nicholas H; Constantineau, Jason A; Caviness, James W

    2017-01-01

    Sandfly fever, sometimes known as pappataci fever or Phlebotomus fever, is a vector transmitted viral illness with a history of affecting naïve military formations that travel through or fight in areas in which the infection is endemic. We present a series of 4 hospitalized cases of sandfly fever (2 presumptive, 2 laboratory confirmed) that were admitted to a Role 3 hospital in Afghanistan for evaluation and treatment following medical evacuation from a forward area for marked fevers and malaise. Laboratory evaluation of these cases was significant for leukopenia and thrombocytopenia, consistent with historical descriptions of sandfly fever. In the correct geographic and clinical setting, the finding of mild leukopenia among a cluster of febrile patients should prompt the clinician to at least consider a diagnosis of sandfly fever. A cluster investigation conducted by preventive medicine personnel identified numerous other presumed cases of sandfly fever in this forward special operations camp. Response efforts emphasized enforcement of standard vector-borne disease control measures by operational leadership in order to limit effect on tactical operations. We review historical instances of sandfly fever affecting military operations, and present a review of clinical presentation, transmission, management, and prevention.

  10. Uncovering Viral Protein-Protein Interactions and their Role in Arenavirus Life Cycle

    Directory of Open Access Journals (Sweden)

    Nora López

    2012-09-01

    Full Text Available The Arenaviridae family includes widely distributed pathogens that cause severe hemorrhagic fever in humans. Replication and packaging of their single-stranded RNA genome involve RNA recognition by viral proteins and a number of key protein-protein interactions. Viral RNA synthesis is directed by the virus-encoded RNA dependent-RNA polymerase (L protein and requires viral RNA encapsidation by the Nucleoprotein. In addition to the role that the interaction between L and the Nucleoprotein may have in the replication process, polymerase activity appears to be modulated by the association between L and the small multifunctional Z protein. Z is also a structural component of the virions that plays an essential role in viral morphogenesis. Indeed, interaction of the Z protein with the Nucleoprotein is critical for genome packaging. Furthermore, current evidence suggests that binding between Z and the viral envelope glycoprotein complex is required for virion infectivity, and that Z homo-oligomerization is an essential step for particle assembly and budding. Efforts to understand the molecular basis of arenavirus life cycle have revealed important details on these viral protein-protein interactions that will be reviewed in this article.

  11. Characterization of the receptor-binding domain of Ebola glycoprotein in viral entry.

    Science.gov (United States)

    Wang, Jizhen; Manicassamy, Balaji; Caffrey, Michael; Rong, Lijun

    2011-06-01

    Ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality. Viral entry/infection is initiated by binding of glycoprotein GP protein on Ebola virion to host cells, followed by fusion of virus-cell membrane also mediated by GP. Using an human immunodeficiency virus (HIV)-based pseudotyping system, the roles of 41 Ebola GP1 residues in the receptor-binding domain in viral entry were studied by alanine scanning substitutions. We identified that four residues appear to be involved in protein folding/structure and four residues are important for viral entry. An improved entry interference assay was developed and used to study the role of these residues that are important for viral entry. It was found that R64 and K95 are involved in receptor binding. In contrast, some residues such as I170 are important for viral entry, but do not play a major role in receptor binding as indicated by entry interference assay and/or protein binding data, suggesting that these residues are involved in post-binding steps of viral entry. Furthermore, our results also suggested that Ebola and Marburg viruses share a common cellular molecule for entry.

  12. Role of toll like receptors in bacterial and viral diseases – A systemic ...

    African Journals Online (AJOL)

    Background: Toll like receptors are key-receptors of the innate immune system, but their role against bacterial and viral infections are yet to be understood. Aim: The present study is aimed to investigate the diversity and frequency distribution of 10 TLR genes among typhoid fever and HIV+ patients. In this study, 44 samples ...

  13. Identification of pathogens for differential diagnosis of fever with jaundice in the Central African Republic: a retrospective assessment, 2008–2010

    OpenAIRE

    Gadia, Christelle Luce Bobossi; Manirakiza, Alexandre; Tekpa, Gaspard; Konamna, Xavier; Vickos, Ulrich; Nakoune, Emmanuel

    2017-01-01

    Background Febrile jaundice results clinically in generalized yellow coloration of the teguments and mucous membranes due to excess plasma bilirubin, accompanied by fever. Two types are found: conjugated and unconjugated bilirubin jaundice. Jaundice is a sign in several diseases due to viruses (viral hepatitis and arbovirus), parasites (malaria) and bacteria (leptospirosis). In the Central African Republic (CAR), only yellow fever is included on the list of diseases for surveillance. The aim ...

  14. [First case of chikungunya fever in Hermosillo, Sonora, Mexico].

    Science.gov (United States)

    Martínez-Medina, Miguel Ángel; Cañedo-Dorame, Ismael Antonio

    2017-01-01

    The Chikungunya is an arbovirus first described during a 1952 outbreak of febrile exantematic disease in southern Tanganyika (now Tanzania). It is a virus within the alphavirus genus of the Togaviridae family, it is usually transmitted to humans by Aedes mosquitoes. Typically, the disease manifests as acute onset of fever and joint pains. This study describes the clinical characteristics the first imported case infected with chikungunya fever (CHIK) in Hermosillo, Sonora, Mexico. We report the case of a 30 years old man seen in our emergency department due to fever, polyarthralgia, rash and headache. This patient has been in Tapachula, Chiapas, a jungle area in southern México, and he returned from a 45 days trip before the onset his symptoms. The chikungunya viral infection (CHIK) was diagnosed by RT-PCR procedure. Paracetamol therapy was administered and his clinical course was self-limited. We concluded that with the increase of mosquito´s habitat by global warming and frequent traveling, CHIK reemerged and showed global distribution recently. This disease must be suspected in patients with compatible clinical symptoms returning from epidemic/endemic areas. CHIK must be diagnosed on the basis of clinical, epidemiological and laboratory criteria.

  15. Fever Management in Parents who Have Children Aged 0-5 Year

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    S. Reshadat

    2012-07-01

    Full Text Available Introduction & Objective: Fever is very common in children and is usually due to self-limiting viral infections. Management of fever is based on culture, community and religion of people all over the world. Parental concerns arise in part because of the belief that fever is a disease rather than a symptom or sign of illness. Misconceptions about childhood fevers heighten parents' concerns leading to inappropriate use of antipyretic drugs or overdosing may cause drug toxicity and frequent use of health care services. This study aimed to identify parental views of fever management in their children aged 0-5 yr.Materials & Methods: In this cross sectional study, 350 parents with children less than 5 years referred to various units of clinics covered by community oriented center of Kermanshah, completed the research questionnaire. Validity and reliability of the questionnaire were determined and the data was analyzed by SPSS Software.Results: Findings showed that the first medical care was sponging (53.1%. Sponging with saltwater was common (47.7% and Over - the - counter medications were (30%. Acetaminophen was the first drug in 90% of the cases. However, many parents express high levels of anxiety so that they seek for self-medication with antibiotic 34% of the cases. Our study showed that correlation between over concern about fever management and parents who had a positive past medical history in their children with P=0.02, parents education (P=0.018 and in employed mothers (P=0.005 was statistically significant.Conclusion: Considerable efforts will be required to educate parents about fever and its management.(Sci J Hamadan Univ Med Sci 2012;19(2:28-33

  16. Crimean-Congo hemorrhagic fever: Risk factors and control measures for the infection abatement

    Science.gov (United States)

    ASLAM, SAADIA; LATIF, MUHAMMAD SHAHZAD; DAUD, MUHAMMAD; RAHMAN, ZIA UR; TABASSUM, BUSHRA; RIAZ, MUHAMMAD SOHAIL; KHAN, ANWAR; TARIQ, MUHAMMAD; HUSNAIN, TAYYAB

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a vector-borne viral disease, widely distributed in different regions of the world. The fever is caused by the CCHF virus (CCHFV), which belongs to the Nairovirus genus and Bunyaviridae family. The virus is clustered in seven genotypes, which are Africa-1, Africa-2, Africa-3, Europe-1, Europe-2, Asia-1 and Asia-2. The virus is highly pathogenic in nature, easily transmissible and has a high case fatality rate of 10–40%. The reservoir and vector of CCHFV are the ticks of the Hyalomma genus. Therefore, the circulation of this virus depends upon the distribution of the ticks. The virus can be transmitted from tick to animal, animal to human and human to human. The major symptoms include headache, high fever, abdominal pain, myalgia, hypotension and flushed face. As the disease progresses, severe symptoms start appearing, which include petechiae, ecchymosis, epistaxis, bleeding gums and emesis. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, antigen detection, serum neutralization and isolation of the virus by cell culture are the diagnostic techniques used for this viral infection. There is no specific antiviral therapy available thus far. However, ribavirin has been approved by the World Health Organization for the treatment of CCHFV infection. Awareness campaigns regarding the risk factors and control measures can aid in reducing the spread of this disease to a greater extent, particularly in developing countries. PMID:26870327

  17. [Investigation of RNA viral genome amplification by multiple displacement amplification technique].

    Science.gov (United States)

    Pang, Zheng; Li, Jian-Dong; Li, Chuan; Liang, Mi-Fang; Li, De-Xin

    2013-06-01

    In order to facilitate the detection of newly emerging or rare viral infectious diseases, a negative-strand RNA virus-severe fever with thrombocytopenia syndrome bunyavirus, and a positive-strand RNA virus-dengue virus, were used to investigate RNA viral genome unspecific amplification by multiple displacement amplification technique from clinical samples. Series of 10-fold diluted purified viral RNA were utilized as analog samples with different pathogen loads, after a series of reactions were sequentially processed, single-strand cDNA, double-strand cDNA, double-strand cDNA treated with ligation without or with supplemental RNA were generated, then a Phi29 DNA polymerase depended isothermal amplification was employed, and finally the target gene copies were detected by real time PCR assays to evaluate the amplification efficiencies of various methods. The results showed that multiple displacement amplification effects of single-strand or double-strand cDNA templates were limited, while the fold increases of double-strand cDNA templates treated with ligation could be up to 6 X 10(3), even 2 X 10(5) when supplemental RNA existed, and better results were obtained when viral RNA loads were lower. A RNA viral genome amplification system using multiple displacement amplification technique was established in this study and effective amplification of RNA viral genome with low load was achieved, which could provide a tool to synthesize adequate viral genome for multiplex pathogens detection.

  18. Yellow Fever

    Science.gov (United States)

    ... Testing Vaccine Information Testing for Vaccine Adverse Events Yellow fever Vaccine Continuing Education Course Yellow Fever Home Prevention Vaccine Vaccine Recommendations Reactions to Yellow Fever Vacine Yellow Fever Vaccine, Pregnancy, & ... Transmission Symptoms, Diagnosis, & Treatment Maps Africa ...

  19. Simultaneous deletion of the 9GL and UK genes from the African swine fever virus Georgia 2007 isolate results in virus attenuation and may be a potential virus vaccine strain

    Science.gov (United States)

    African Swine Fever Virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for the swine industry. The control of African Swine Fever (ASF) has been hampered by the unavailability of vaccines. Successful experi...

  20. Clinical presentation and laboratory findings for the first autochthonous cases of dengue fever in Madeira island, Portugal, October 2012.

    Science.gov (United States)

    Alves, M J; Fernandes, P L; Amaro, F; Osório, H; Luz, T; Parreira, P; Andrade, G; Zé-Zé, L; Zeller, H

    2013-02-07

    An outbreak of dengue fever in Madeira island was reported in 2012. Clinical and laboratory findings of the first two laboratory-confirmed autochthonous cases are reported. Both cases had fever (≥38 °C) and petechial rash. Symptoms also included myalgia, asthenia, nausea, vomiting, anorexia, diffuse abdominal pain, and diarrhoea. The two cases were confirmed by serology and one tested positive for a dengue viral sequence. Dengue virus serotype DEN-1 was identified with probable Central or South American origin.

  1. Yellow fever vaccine-associated neurotropic disease (YEL-AND) - A case report.

    Science.gov (United States)

    Florczak-Wyspiańska, Jolanta; Nawotczyńska, Ewa; Kozubski, Wojciech

    Yellow fever (YF) is a mosquito-borne viral hemorrhagic fever, which is a serious and potentially fatal disease with no specific antiviral treatment that can be effectively prevented by an attenuated vaccine (YEL). Despite the long history of safe and efficacious YF vaccination, sporadic case reports of serious adverse events (SAEs) have been reported, including yellow fever vaccine-associated neurotropic disease (YEL-AND). YEL-AND usually appears within one month of YF vaccination, manifesting as meningoencephalitis, Guillain-Barré syndrome (GBS) or acute disseminated encephalomyelitis (ADEM). We report a case of YEL-AND with meningitis presentation in a 39-year-old Caucasian man without evidence of significant risk factors, which was confirmed by the presence of the YF virus and specific immunoglobulin G (IgG) antibodies in the cerebrospinal fluid (CSF). In conclusion, we should stress the importance of balancing the risk of SAEs associated with the vaccine and the benefits of YF vaccination for each patient individually. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Epidemiological characteristics of Brazilian spotted fever in Minas Gerais State, Brazil, 2000-2008

    Directory of Open Access Journals (Sweden)

    Frederico Figueiredo Amâncio

    2011-10-01

    Full Text Available Brazilian spotted fever is the most common rickettsiosis in Brazil, most prevalent in the States of São Paulo and Minas Gerais. The aim of this study was to describe the epidemiological characteristics of Brazilian spotted fever in Minas Gerais from 2000 to 2008. Of the 132 cases of Brazilian spotted fever, 53 patients died, representing a case-fatality rate of 40.2%. Males predominated, with 78.8% of confirmed cases, and median age was 26.5 years. Absence of rash was associated with increased risk of death (p = 0.005. Greater Metropolitan Belo Horizonte, Rio Doce Valley, and Zona da Mata accounted for 70.6% of the cases, which occurred mainly from May to November. There was an increase in the number of cases, which could suggest an expansion of the disease, but probably resulted from an increase in the health system's diagnostic capacity and sensitivity. Despite this improvement, the case-fatality rate remains high and with no apparent tendency to decrease, thus indicating the need for improved prevention and patient care.

  3. Role of toll like receptors in bacterial and viral diseases – A ...

    African Journals Online (AJOL)

    Avishek Das

    2017-05-20

    May 20, 2017 ... Background: Toll like receptors are key-receptors of the innate immune system, but their role against bacterial and viral infections are yet to be understood. Aim: The present study is aimed to investigate the diversity and frequency distribution of 10 TLR genes among typhoid fever and HIV+ patients. In this ...

  4. Fever

    Directory of Open Access Journals (Sweden)

    Tamas Bartfai

    2010-01-01

    Full Text Available Measurement of body temperature remains one of the most common ways to assess health. An increase in temperature above what is considered to be a normal value is inevitably regarded as a sure sign of disease and referred to with one simple word: fever. In this review, we summarize how research on fever allowed the identification of the exogenous and endogenous molecules and pathways mediating the fever response. We also show how temperature elevation is common to different pathologies and how the molecular components of the fever-generation pathway represent drug targets for antipyretics, such as acetylsalicylic acid, the first “blockbuster drug”. We also show how fever research provided new insights into temperature and energy homeostasis, and into treatment of infection and inflammation.

  5. Transmission of Rift Valley fever virus from European-breed lambs to Culex pipiens mosquitoes.

    Directory of Open Access Journals (Sweden)

    Rianka P M Vloet

    2017-12-01

    Full Text Available Rift Valley fever virus (RVFV is a mosquito-borne bunyavirus of the genus Phlebovirus that is highly pathogenic to ruminants and humans. The disease is currently confined to Africa and the Arabian Peninsula, but globalization and climate change may facilitate introductions of the virus into currently unaffected areas via infected animals or mosquitoes. The consequences of such an introduction will depend on environmental factors, the availability of susceptible ruminants and the capacity of local mosquitoes to transmit the virus. We have previously demonstrated that lambs native to the Netherlands are highly susceptible to RVFV and we here report the vector competence of Culex (Cx. pipiens, the most abundant and widespread mosquito species in the country. Vector competence was first determined after artificial blood feeding of laboratory-reared mosquitoes using the attenuated Clone 13 strain. Subsequently, experiments with wild-type RVFV and mosquitoes hatched from field-collected eggs were performed. Finally, the transmission of RVFV from viremic lambs to mosquitoes was studied.Artificial feeding experiments using Clone 13 demonstrated that indigenous, laboratory-reared Cx. pipiens mosquitoes are susceptible to RVFV and that the virus can be transmitted via their saliva. Experiments with wild-type RVFV and mosquitoes hatched from field-collected eggs confirmed the vector competence of Cx. pipiens mosquitoes from the Netherlands. To subsequently investigate transmission of the virus under more natural conditions, mosquitoes were allowed to feed on RVFV-infected lambs during the viremic period. We found that RVFV is efficiently transmitted from lambs to mosquitoes, although transmission was restricted to peak viremia. Interestingly, in the mosquito-exposed skin samples, replication of RVFV was detected in previously unrecognized target cells.We here report the vector competence of Cx. pipiens mosquitoes from the Netherlands for RVFV. Both

  6. [History of viral hepatitis].

    Science.gov (United States)

    Fonseca, José Carlos Ferraz da

    2010-01-01

    The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives. This article reviews the available scientific information on the history of viral hepatitis. All the information was obtained through extensive bibliographic review, including original and review articles and consultations on the internet. There are reports on outbreaks of jaundice epidemics in China 5,000 years ago and in Babylon more than 2,500 years ago. The catastrophic history of great jaundice epidemics and pandemics is well known and generally associated with major wars. In the American Civil War, 40,000 cases occurred among Union troops. In 1885, an outbreak of catarrhal jaundice affected 191 workers at the Bremen shipyard (Germany) after vaccination against smallpox. In 1942, 28,585 soldiers became infected with hepatitis after inoculation with the yellow fever vaccine. The number of cases of hepatitis during the Second World War was estimated to be 16 million. Only in the twentieth century were the main agents causing viral hepatitis identified. The hepatitis B virus was the first to be discovered. In this paper, through reviewing the history of major epidemics caused by hepatitis viruses and the history of discovery of these agents, singular peculiarities were revealed. Examples of this include the accidental or chance discovery of the hepatitis B and D viruses.

  7. Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers.

    Directory of Open Access Journals (Sweden)

    Trevor V Gale

    2017-09-01

    Full Text Available Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF, PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients.

  8. High IFN-alpha responses associated with depletion of lymphocytes and natural IFN-producing cells during classical swine fever

    NARCIS (Netherlands)

    Summerfield, A.; Alves, M.; Ruggli, N.; Bruin, de M.G.M.; McCullough, K.C.

    2006-01-01

    During the acute phase of the viral hemorrhagic disease, classical swine fever (CSF), a severe hematologic depletion in primary lymphoid organs and depletion of peripheral blood T and B lymphocytes are observed. The onset of these pathologic events is before viremia and independent of leukocyte

  9. [Control, elimination and eradication of viral immuno preventable diseases in Venezuela].

    Science.gov (United States)

    Valero, Nereida; Maldonado, Mery

    2005-09-01

    Vaccination has demonstrated the capacity for the drastic decrease of the prevalence and incidence of several diseases of viral etiology and it has allowed their eradication. Among these human immuno preventable diseases are included poliomyelitis, measles, mumps, chicken pox, rubella, hepatitis A and B, influenza A and yellow fever. In residents, travelers to endemic areas and personal at risk, the vaccines to Japanese and equine encephalitis, rabies and adenovirus can be applied. Venezuela has not escaped from the positive impact in the epidemiology of these illnesses as a consequence of the organization and implementation of big national vaccination campaigns; however, and in spite of these efforts, important outbreaks of measles, yellow fever, chicken pox and hepatitis have occurred in the last few years. The tools to eliminate the majority of these viral diseases exist in Venezuela as well as in other countries, and are readily available, effective and relatively not expensive, but require on the whole of an effort of authorities and communities. The implementation of these strategies should have the support of the World Health Organization and the Panamerican Health Organization. This is a priority for the next few years if our aim is the eradication of these illnesses from Venezuela, the continent and the world.

  10. First international external quality assessment of molecular detection of Crimean-Congo hemorrhagic fever virus.

    Directory of Open Access Journals (Sweden)

    Camille Escadafal

    Full Text Available Crimean-Congo hemorrhagic fever (CCHF is a zoonosis caused by a Nairovirus of the family Bunyaviridae. Infection is transmitted to humans mostly by Hyalomma ticks and also by direct contact with the blood or tissues of infected humans or viremic livestock. Clinical features usually include a rapid progression characterized by hemorrhage, myalgia and fever, with a lethality rate up to 30%. CCHF is one of the most widely distributed viral hemorrhagic fevers and has been reported in Africa, the Middle East and Asia, as well as parts of Europe. There is no approved vaccine or specific treatment against CCHF virus (CCHFV infections. In this context, an accurate diagnosis as well as a reliable surveillance of CCHFV infections is essential. Diagnostic techniques include virus culture, serology and molecular methods, which are now increasingly used. The European Network for the Diagnostics of "Imported" Viral Diseases organized the first international external quality assessment of CCHVF molecular diagnostics in 2011 to assess the efficiency and accurateness of CCHFV molecular methods applied by expert laboratories. A proficiency test panel of 15 samples was distributed to the participants including 10 different CCHFV preparations generated from infected cell cultures, a preparation of plasmid cloned with the nucleoprotein of CCHFV, two CCHFV RNA preparations and two negative controls. Forty-four laboratories worldwide participated in the EQA study and 53 data sets were received. Twenty data sets (38% met all criteria with optimal performance, 10 (19% with acceptable performance, while 23 (43% reported results showing a need for improvement. Differences in performance depended on the method used, the type of strain tested, the concentration of the sample tested and the laboratory performing the test. These results indicate that there is still a need for improving testing conditions and standardizing protocols for the molecular detection of Crimean

  11. Validation of an ELISA for the concurrent detection of total antibodies (IgM and IgG to Rift Valley fever virus

    Directory of Open Access Journals (Sweden)

    Charlotte E. Ellis

    2014-05-01

    Full Text Available Rift Valley fever virus (RVFV infects humans and livestock, causing haemorrhaging andabortions in animals. Three major RVF epizootics have occurred in South Africa since the1950s and the outbreak in 2010 had a mortality rate of 10.7% in humans. Accurate and earlydetection is therefore essential for management of this zoonotic disease. Enzyme-linkedimmunosorbent assays (ELISAs have been developed for the detection of either IgM or IgGantibodies to RVFV in animal sera. In this study, data are presented on the validation of adouble-antigen ELISA for the simultaneous detection of both classes of antibodies to RVFV ina single test. ELISA plates were coated with a recombinant nucleoprotein. The nucleoprotein,conjugated to horseradish peroxidase, was used as the detecting reagent. A total of 534 serafrom sheep and cattle were used in the validation. The sheep sera were collected during a RVFpathogenesis study at the Agricultural Research Council (ARC – Onderstepoort VeterinaryInstitute and the cattle sera were collected during an outbreak of RVF in 2008 at the ARC –Animal Production Institute in Irene, Pretoria. The ELISA had a diagnostic sensitivity of 98.4%and a specificity of 100% when compared to a commercial cELISA. This convenient and fastassay is suitable for use in serological surveys or monitoring immune responses in vaccinatedanimals.

  12. Spatial Heterogeneity of Habitat Suitability for Rift Valley Fever Occurrence in Tanzania: An Ecological Niche Modelling Approach

    Science.gov (United States)

    Sindato, Calvin; Stevens, Kim B.; Karimuribo, Esron D.; Mboera, Leonard E. G.; Paweska, Janusz T.; Pfeiffer, Dirk U.

    2016-01-01

    Background Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania. Materials and Methods Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values. Principal Findings Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001). Conclusion/Significance The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with

  13. Development and characterization of a Rift Valley fever virus cell-cell fusion assay using alphavirus replicon vectors

    International Nuclear Information System (INIS)

    Filone, Claire Marie; Heise, Mark; Doms, Robert W.; Bertolotti-Ciarlet, Andrea

    2006-01-01

    Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the Bunyaviridae family, is transmitted by mosquitoes and infects both humans and domestic animals, particularly cattle and sheep. Since primary RVFV strains must be handled in BSL-3+ or BSL-4 facilities, a RVFV cell-cell fusion assay will facilitate the investigation of RVFV glycoprotein function under BSL-2 conditions. As for other members of the Bunyaviridae family, RVFV glycoproteins are targeted to the Golgi, where the virus buds, and are not efficiently delivered to the cell surface. However, overexpression of RVFV glycoproteins using an alphavirus replicon vector resulted in the expression of the glycoproteins on the surface of multiple cell types. Brief treatment of RVFV glycoprotein expressing cells with mildly acidic media (pH 6.2 and below) resulted in rapid and efficient syncytia formation, which we quantified by β-galactosidase α-complementation. Fusion was observed with several cell types, suggesting that the receptor(s) for RVFV is widely expressed or that this acid-dependent virus does not require a specific receptor to mediate cell-cell fusion. Fusion occurred over a broad temperature range, as expected for a virus with both mosquito and mammalian hosts. In contrast to cell fusion mediated by the VSV-G glycoprotein, RVFV glycoprotein-dependent cell fusion could be prevented by treating target cells with trypsin, indicating that one or more proteins (or protein-associated carbohydrate) on the host cell surface are needed to support membrane fusion. The cell-cell fusion assay reported here will make it possible to study the membrane fusion activity of RVFV glycoproteins in a high-throughput format and to screen small molecule inhibitors for the ability to block virus-specific membrane fusion

  14. [Viruses and civilization].

    Science.gov (United States)

    Chastel, C

    1999-01-01

    A few million years ago, when primates moved from the east African forest to the savannah, they were already infected with endogenous viruses and occultly transmitted them to the prime Homo species. However it was much later with the building of the first large cities in Mesopotamia that interhuman viral transmission began in earnest. Spreading was further enhanced with the organization of the Egyptian, Greek, Roman, and Arab empires around the Mediterranean. Discovery of the New World in 1492 led to an unprecedented clash of civilizations and the destruction of pre-Columbian Indian civilizations. It also led to a rapid spread of viruses across the Atlantic Ocean with the emergence of yellow fever and appearance of smallpox and measles throughout the world. However the greatest opportunities for worldwide viral development have been created by our present, modern civilization. This fact is illustrated by epidemic outbreaks of human immunodeficiency virus, Venezuela hemorrhagic fever, Rift valley fever virus, and monkey pox virus. Close analysis underscores the major role of human intervention in producing these events.

  15. [Present status of zoonotic hemorrhagic fevers of South America].

    Science.gov (United States)

    Chastel, C

    1993-01-01

    Since 1958, the geographical distribution of Argentine hemorrhagic fever (AHF) has especially extended non only into the province of Buenos Aires but also towards the provinces of Santa Fe and Cordoba, leading to an estimated population at risk of about 1.2 M inhabitants. Recent epidemiological field studies has confirmed the major role of Calomys musculinus and C. laucha rodents in both transmission to man and conservation of Junin virus in nature. However, the human infection may result essentially from contacts with infected C. musculinus. Clinical condition of patients with AHF was greatly improved using AHF convalescent plasma and additional administration of vidarabin may still improve the results of treatment. A live attenuated vaccine, Candid No 1, is presently under evaluation in endemic foci of AHF. On the contrary Bolivian hemorrhagic fever (BHV) appears at present quite silent. A new disease resembling both AHF and BHF, the Venezuelan hemorrhagic fever, appeared in 1989 in the rural areas of central Llanos of Venezuela. The mortality was very high, reaching 23% or more among severely ill patients. The wild small rodents responsible for the disease were identified as Sigmodon alstoni and Zygotontomys brevicauda. Recent extension of agricultural practices and massive immigration may probably explain the recent emergence of this new viral zoonosis.

  16. Febre amarela Yellow fever

    Directory of Open Access Journals (Sweden)

    Pedro Fernando da Costa Vasconcelos

    2003-04-01

    Full Text Available A febre amarela é doenca infecciosa não-contagiosa causada por um arbovírus mantido em ciclos silvestres em que macacos atuam como hospedeiros amplificadores e mosquitos dos gêneros Aedes na África, e Haemagogus e Sabethes na América, são os transmissores. Cerca de 90% dos casos da doença apresentam-se com formas clínicas benignas que evoluem para a cura, enquanto 10% desenvolvem quadros dramáticos com mortalidade em torno de 50%. O problema mostra-se mais grave em África onde ainda há casos urbanos. Nas Américas, no período de 1970-2001, descreveram-se 4.543 casos. Os países que mais diagnosticaram a doença foram o Peru (51,5%, a Bolívia (20,1% e o Brasil (18,7%. Os métodos diagnósticos utilizados incluem a sorologia (IgM, isolamento viral, imunohistoquímica e RT-PCR. A zoonose não pode ser erradicada, mas, a doença humana é prevenível mediante a vacinação com a amostra 17D do vírus amarílico. A OMS recomenda nova vacinação a cada 10 anos. Neste artigo são revistos os principais conceitos da doença e os casos de mortes associados à vacina.Yellow fever is an infectious and non-contagious disease caused by an arbovirus, the yellow fever virus. The agent is maintained in jungle cycles among primates as vertebrate hosts and mosquitoes, especially Aedes in Africa, and Haemagogus and Sabethes in America. Approximately 90% of the infections are mild or asymptomatic, while 10% course to a severe clinical picture with 50% case-fatality rate. Yellow fever is largely distributed in Africa where urban epidemics are still reported. In South America, between 1970-2001, 4,543 cases were reported, mostly from Peru (51.5%, Bolivia (20.1% and Brazil (18.7%. The disease is diagnosed by serology (detection of IgM, virus isolation, immunohistochemistry and RT-PCR. Yellow fever is a zoonosis and cannot be eradicated, but it is preventable in man by using the 17D vaccine. A single dose is enough to protect an individual for at least

  17. Identifying landscape features associated with Rift Valley fever virus transmission, Ferlo region, Senegal, using very high spatial resolution satellite imagery.

    Science.gov (United States)

    Soti, Valérie; Chevalier, Véronique; Maura, Jonathan; Bégué, Agnès; Lelong, Camille; Lancelot, Renaud; Thiongane, Yaya; Tran, Annelise

    2013-03-01

    Dynamics of most of vector-borne diseases are strongly linked to global and local environmental changes. Landscape changes are indicators of human activities or natural processes that are likely to modify the ecology of the diseases. Here, a landscape approach developed at a local scale is proposed for extracting mosquito favourable biotopes, and for testing ecological parameters when identifying risk areas of Rift Valley fever (RVF) transmission. The study was carried out around Barkedji village, Ferlo region, Senegal. In order to test whether pond characteristics may influence the density and the dispersal behaviour of RVF vectors, and thus the spatial variation in RVFV transmission, we used a very high spatial resolution remote sensing image (2.4 m resolution) provided by the Quickbird sensor to produce a detailed land-cover map of the study area. Based on knowledge of vector and disease ecology, seven landscape attributes were defined at the pond level and computed from the land-cover map. Then, the relationships between landscape attributes and RVF serologic incidence rates in small ruminants were analyzed through a beta-binomial regression. Finally, the best statistical model according to the Akaike Information Criterion corrected for small samples (AICC), was used to map areas at risk for RVF. Among the derived landscape variables, the vegetation density index (VDI) computed within a 500 m buffer around ponds was positively correlated with serologic incidence (premote sensing data for identifying environmental risk factors and mapping RVF risk areas at a local scale.

  18. Simulation modelling of population dynamics of mosquito vectors for rift valley Fever virus in a disease epidemic setting.

    Directory of Open Access Journals (Sweden)

    Clement N Mweya

    Full Text Available Rift Valley Fever (RVF is weather dependent arboviral infection of livestock and humans. Population dynamics of mosquito vectors is associated with disease epidemics. In our study, we use daily temperature and rainfall as model inputs to simulate dynamics of mosquito vectors population in relation to disease epidemics.Time-varying distributed delays (TVDD and multi-way functional response equations were implemented to simulate mosquito vectors and hosts developmental stages and to establish interactions between stages and phases of mosquito vectors in relation to vertebrate hosts for infection introduction in compartmental phases. An open-source modelling platforms, Universal Simulator and Qt integrated development environment were used to develop models in C++ programming language. Developed models include source codes for mosquito fecundity, host fecundity, water level, mosquito infection, host infection, interactions, and egg time. Extensible Markup Language (XML files were used as recipes to integrate source codes in Qt creator with Universal Simulator plug-in. We observed that Floodwater Aedines and Culicine population continued to fluctuate with temperature and water level over simulation period while controlled by availability of host for blood feeding. Infection in the system was introduced by floodwater Aedines. Culicines pick infection from infected host once to amplify disease epidemic. Simulated mosquito population show sudden unusual increase between December 1997 and January 1998 a similar period when RVF outbreak occurred in Ngorongoro district.Findings presented here provide new opportunities for weather-driven RVF epidemic simulation modelling. This is an ideal approach for understanding disease transmission dynamics towards epidemics prediction, prevention and control. This approach can be used as an alternative source for generation of calibrated RVF epidemics data in different settings.

  19. Simulation modelling of population dynamics of mosquito vectors for rift valley Fever virus in a disease epidemic setting.

    Science.gov (United States)

    Mweya, Clement N; Holst, Niels; Mboera, Leonard E G; Kimera, Sharadhuli I

    2014-01-01

    Rift Valley Fever (RVF) is weather dependent arboviral infection of livestock and humans. Population dynamics of mosquito vectors is associated with disease epidemics. In our study, we use daily temperature and rainfall as model inputs to simulate dynamics of mosquito vectors population in relation to disease epidemics. Time-varying distributed delays (TVDD) and multi-way functional response equations were implemented to simulate mosquito vectors and hosts developmental stages and to establish interactions between stages and phases of mosquito vectors in relation to vertebrate hosts for infection introduction in compartmental phases. An open-source modelling platforms, Universal Simulator and Qt integrated development environment were used to develop models in C++ programming language. Developed models include source codes for mosquito fecundity, host fecundity, water level, mosquito infection, host infection, interactions, and egg time. Extensible Markup Language (XML) files were used as recipes to integrate source codes in Qt creator with Universal Simulator plug-in. We observed that Floodwater Aedines and Culicine population continued to fluctuate with temperature and water level over simulation period while controlled by availability of host for blood feeding. Infection in the system was introduced by floodwater Aedines. Culicines pick infection from infected host once to amplify disease epidemic. Simulated mosquito population show sudden unusual increase between December 1997 and January 1998 a similar period when RVF outbreak occurred in Ngorongoro district. Findings presented here provide new opportunities for weather-driven RVF epidemic simulation modelling. This is an ideal approach for understanding disease transmission dynamics towards epidemics prediction, prevention and control. This approach can be used as an alternative source for generation of calibrated RVF epidemics data in different settings.

  20. Serological evidence of Rift Valley fever virus circulation in sheep and goats in Zambézia Province, Mozambique.

    Directory of Open Access Journals (Sweden)

    José Fafetine

    Full Text Available Rift Valley fever (RVF is endemic in most parts of Africa and has also been reported to occur in the Arabian Peninsula. It is responsible for significant morbidity and mortality, particularly in livestock, but also in humans. During the last two decades several outbreaks of RVF have been reported in countries in Southern Africa. In contrast to other countries, no clinical disease has been reported in Mozambique during this period. In a serological study conducted in 2007 in five districts of Zambézia Province, Mozambique, of a total of 654 small ruminants sampled (277 sheep and 377 goats, 35.8% of sheep sera and 21.2% of goat sera were positive for RVF virus (RVFV antibodies in a virus neutralization test (VN and in an IgG enzyme-linked immunosorbent assay (ELISA. In 2010, a cross-sectional survey was conducted in 313 sheep and 449 goats in two districts of the same province. This study revealed an overall seropositivity rate of 9.2% in sheep and 11.6% in goat and an increased likelihood of being seropositive in older animals (OR = 7.3; p<0.001 using an IgG ELISA. 29 out of 240 animals assessed for RVF specific IgM by ELISA were positive, suggesting recent exposure to RVFV. However, a longitudinal study carried out between September 2010 and April 2011 in a cohort of 125 of these animals (74 sheep and 51 goats failed to demonstrate seroconversion. The results of the study indicate that RVFV circulates sub-clinically in domestic small ruminants in Zambézia Province.

  1. Seroprevalence of sandfly fever virus infection in military personnel on the western border of Iran

    Directory of Open Access Journals (Sweden)

    Ramin Shiraly

    2017-01-01

    Full Text Available Summary: Military troops deployed to endemic areas are at risk of contracting sandfly fever, an arthropod-borne viral infection. Although typically a self-limited disease, sandfly fever can cause significant morbidity and loss of function among soldiers. We conducted this study to determine the extent of past SFV infection in a group of healthy Iranian military personnel in Ilam province on the western border of Iran. A total of 201 serum samples were tested by indirect immunofluorescence assay (IFA to detect four common sandfly fever virus serotypes. Demographic data were also collected. Overall, 37 samples (18.4% were positive for specific IgG antibodies to sandfly viruses. Sandfly fever Sicilian virus (SFSV and sandfly fever Naples virus (SFNV were the most common serotypes. A positive test was inversely related to nativity (P < 0.01 but was not associated with age (P = 0.163, duration of presence in the border region (P = 0.08 or employment status (P = 0.179.Our findings indicate that past SFV infection is common among military personnel in the western border region of Iran, a Leishmania-endemic region. Therefore, it should be considered in the differential diagnosis of troops presenting with acute febrile illness in similar settings. Keywords: Sandfly fever, Virus, Past infection, Military personnel

  2. Yellow Fever outbreak in Darfur, Sudan in October 2012; the initial outbreak investigation report

    Directory of Open Access Journals (Sweden)

    Mohammed A. Soghaier

    2013-10-01

    Full Text Available Summary: Introduction: Sudan is subject to repeated outbreaks, including Viral Hemorrhagic Fever (VHF, which is considered to be a very serious illness. Yellow Fever (YF outbreaks in Sudan have been reported from the 1940s through 2005. In 2012, a new outbreak of YF occurred in the Darfur region. Objective: To identify the potential for an outbreak, to diagnose the disease and to be able to recognize its cause among the initial reported cases. Methodology: >This is a descriptive and investigative field study that applies standard communicable disease outbreak investigation steps. The study involved clinical, serological, entomological and environmental surveys. Results: The field investigation confirmed the outbreak and identified its cause to be YF. Conclusion: National surveillance systems should be strong enough to detect VHFs in a timely manner. Local health facilities should be prepared to promptly treat the initial cases because the case fatality ratios (CFRs are usually very high among the index cases. Keywords: Yellow Fever, Sudan, Darfur, VHFs, Soghaier

  3. An Outbreak of Ebola Virus Disease in the Lassa Fever Zone.

    Science.gov (United States)

    Goba, Augustine; Khan, S Humarr; Fonnie, Mbalu; Fullah, Mohamed; Moigboi, Alex; Kovoma, Alice; Sinnah, Vandi; Yoko, Nancy; Rogers, Hawa; Safai, Siddiki; Momoh, Mambu; Koroma, Veronica; Kamara, Fatima K; Konowu, Edwin; Yillah, Mohamed; French, Issa; Mustapha, Ibraham; Kanneh, Franklyn; Foday, Momoh; McCarthy, Helena; Kallon, Tiangay; Kallon, Mustupha; Naiebu, Jenneh; Sellu, Josephine; Jalloh, Abdul A; Gbakie, Michael; Kanneh, Lansana; Massaly, James L B; Kargbo, David; Kargbo, Brima; Vandi, Mohamed; Gbetuwa, Momoh; Gevao, Sahr M; Sandi, John D; Jalloh, Simbirie C; Grant, Donald S; Blyden, Sylvia O; Crozier, Ian; Schieffelin, John S; McLellan, Susan L; Jacob, Shevin T; Boisen, Matt L; Hartnett, Jessica N; Cross, Robert W; Branco, Luis M; Andersen, Kristian G; Yozwiak, Nathan L; Gire, Stephen K; Tariyal, Ridhi; Park, Daniel J; Haislip, Allyson M; Bishop, Christopher M; Melnik, Lilia I; Gallaher, William R; Wimley, William C; He, Jing; Shaffer, Jeffrey G; Sullivan, Brian M; Grillo, Sonia; Oman, Scott; Garry, Courtney E; Edwards, Donna R; McCormick, Stephanie J; Elliott, Deborah H; Rouelle, Julie A; Kannadka, Chandrika B; Reyna, Ashley A; Bradley, Benjamin T; Yu, Haini; Yenni, Rachael E; Hastie, Kathryn M; Geisbert, Joan B; Kulakosky, Peter C; Wilson, Russell B; Oldstone, Michael B A; Pitts, Kelly R; Henderson, Lee A; Robinson, James E; Geisbert, Thomas W; Saphire, Erica Ollmann; Happi, Christian T; Asogun, Danny A; Sabeti, Pardis C; Garry, Robert F

    2016-10-15

     Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs.  Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities.  Augustine Goba, director of the KGH Lassa laboratory, diagnosed the first documented case of EVD in Sierra Leone, on 25 May 2014. Thereafter, KGH received and cared for numbers of patients with EVD that quickly overwhelmed the capacity for safe management. Numerous healthcare workers contracted and lost their lives to EVD. The vast majority of subsequent EVD cases in West Africa can be traced back to a single transmission chain that includes this first diagnosed case.  Responding to the challenges of confronting 2 hemorrhagic fever viruses will require continued investments in the development of countermeasures (vaccines, therapeutic agents, and diagnostic assays), infrastructure, and human resources. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Viral diseases of northern ungulates

    Directory of Open Access Journals (Sweden)

    K. Frölich

    2000-03-01

    Full Text Available This paper describes viral diseases reported in northern ungulates and those that are a potential threat to these species. The following diseases are discussed: bovine viral diarrhoea/mucosal disease (BVD/MD, alphaherpesvirus infections, malignant catarrhal fever (MCF, poxvirus infections, parainfluenza type 3 virus infection, Alvsborg disease, foot-and-mouth disease, epizootic haemorrhage disease of deer and bluetongue disease, rabies, respiratory syncytial virus infection, adenovirus infection, hog-cholera, Aujeszky's disease and equine herpesvirus infections. There are no significant differences in antibody prevalence to BVDV among deer in habitats with high, intermediate and low density of cattle. In addition, sequence analysis from the BVDV isolated from roe deer (Capreolus capreolus showed that this strain was unique within BVDV group I. Distinct BVDV strains might circulate in free-ranging roe deer populations in Germany and virus transmission may be independent of domestic livestock. Similar results have been obtained in a serological survey of alpha-herpesviruses in deer in Germany. Malignant catarrhal fever was studied in fallow deer (Cervus dama in Germany: the seroprevalence and positive PCR results detected in sheep originating from the same area as the antibody-positive deer might indicate that sheep are the main reservoir animals. Contagious ecthyma (CE is a common disease in domestic sheep and goats caused by the orf virus. CE has been diagnosed in Rocky Mountain bighorn sheep (Ovis canadensis, mountain goats (Oreamnos americanus, Dall sheep (Ovis dalli, chamois (Rupkapra rupi-capra, muskox {Ovibos moschatus and reindeer (Rangifer tarandus. Most parainfluenza type 3 virus infections are mild or clinically undetectable. Serological surveys in wildlife have been successfully conducted in many species. In 1985, a new disease was identified in Swedish moose (Alces alces, designated as Alvsborg disease. This wasting syndrome probably

  5. Evidence for widespread infection of African bats with Crimean-Congo hemorrhagic fever-like viruses

    Czech Academy of Sciences Publication Activity Database

    Müller, M. A.; Devignot, S.; Lattwein, E.; Corman, V. M.; Maganga, G. D.; Gloza-Rausch, F.; Binger, T.; Vallo, Peter; Emmerich, P.; Cottontail, V. M.; Tschapka, M.; Oppong, S.; Drexler, J. F.; Weber, F.; Leroy, E. M.; Drosten, C.

    2016-01-01

    Roč. 6, č. 26637 (2016), č. článku 26637. ISSN 2045-2322 EU Projects: European Commission(XE) 278976 - ANTIGONE; European Commission(XE) 260427 - CCH Fever Institutional support: RVO:68081766 Keywords : sheep disease virus * family Bunyaviridae * serological relationships * antibody-response * migratory birds * rapid detection * viral load * ticks * nairovirus * genus Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 4.259, year: 2016

  6. Uncovering of Classical Swine Fever Virus adaptive response to vaccination by Next Generation Sequencing

    DEFF Research Database (Denmark)

    Fahnøe, Ulrik; Orton, Richard; Höper, Dirk

    Next Generation Sequencing (NGS) has rapidly become the preferred technology in nucleotide sequencing, and can be applied to unravel molecular adaptation of RNA viruses such as Classical Swine Fever Virus (CSFV). However, the detection of low frequency variants within viral populations by NGS...... is affected by errors introduced during sample preparation and sequencing, and so far no definitive solution to this problem has been presented....

  7. DEFEAT OF THE CARDIOVASCULAR SYSTEM IN VIRAL INFECTIONS

    Directory of Open Access Journals (Sweden)

    E. V. Sharipova

    2017-01-01

    Full Text Available Article is devoted to studying of the submitted epidemiological, clinical, tool, laboratory data on pathology of cardiovascular system at various viral infections. The review is based on results of domestic and foreign researches. At viral infections damage of heart and his carrying-out system perhaps as during the sharp period of a disease, and the period of a convalescence or at the chronic course of virus process. The greatest cardiothrogenism is possessed by enteroviruses, which affect the myocardium in 5–15% of cases. Much attention is paid to herpesviruses, widespread, persistently persistent in the body, as one of the reasons for the development of dilated cardiomyopathy, coronary vasculitis, early atherosclerosis, cardiac rhythm disturbance. Other infections that may affect the cardiovascular system include influenza viruses, adenovirus, poliovirus, Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, hepatitis, mumps, rubella, herpes simplex, varicella, arbovirus, respiratory-syntial virus, yellow fever virus et al. Complications from cardiovascular system can come to light at various age.

  8. Identifying Areas Suitable for the Occurrence of Rift Valley Fever in North Africa: Implications for Surveillance.

    Science.gov (United States)

    Arsevska, E; Hellal, J; Mejri, S; Hammami, S; Marianneau, P; Calavas, D; Hénaux, V

    2016-12-01

    Rift Valley fever (RVF) is a vector-borne zoonotic disease that has caused widespread outbreaks throughout Africa and the Arabian Peninsula, with serious consequences for livestock-based economies and public health. Although there have never been any reports of RVF in Morocco, Algeria, Tunisia and Libya, it is a priority disease in the Maghreb, due to the threat of introduction of the virus through transboundary livestock movements or infected mosquito vectors. However, the implementation of surveillance activities and early warning contingency plans requires better knowledge of the epidemiological situation. We conducted a multicriteria decision analysis, integrating host distribution with a combination of important ecological factors that drive mosquito abundance, to identify hotspots and suitable time periods for RVF enzootic circulation (i.e. stable transmission at a low to moderate level for an extended period of time) and an RVF epizootic event (i.e. a sudden occurrence of a large number of infected animals over a large geographic area) in the Maghreb. We also modelled vector species distribution using available information on vector presence and habitat preference. We found that the northern regions of the Maghreb were moderately suitable for RVF enzootics, but highly suitable for RVF epizootics. The vector species distribution model identified these regions as the most favourable mosquito habitats. Due to the low density of animal hosts and arid conditions, the desert region showed low RVF suitability, except in oases. However, the presence of competent vectors in putative unsuitable areas underlines the need for further assessments of mosquito habitat preference. This study produced monthly RVF suitability maps useful for animal health managers and veterinary services involved in designing risk-based surveillance programmes. The suitability maps can be further enhanced using existing country-specific sources of information and by incorporating knowledge

  9. Virus del dengue: estructura y ciclo viral Dengue virus: structure and viral cycle

    Directory of Open Access Journals (Sweden)

    Myriam L Velandia

    2011-03-01

    viral cycle has begun to be described and this knowledge will impact the rational design of new antiviral drugs. Patients suffering dengue can have an undifferentiated fever or in the severe cases, show an aberrant immunological activation process that lead to soluble inflammatory mediators secretion, affecting tissue function, mainly endothelium. This organ dysfunction is associated with plasma leakage and coagulatory imbalance. Despite it has been recently described some host factors associated with severity of infection, it remains unknown some aspects of viral biology or the role of DENV proteins in disease pathogenesis. This article pretends to make an updated revision about DENV structure, cell viral cycle and introduce some concepts about dengue immunopathogenesis.

  10. Rat bite fever without fever.

    Science.gov (United States)

    Stehle, P; Dubuis, O; So, A; Dudler, J

    2003-09-01

    Rat bite fever is a rarely reported acute febrile bacterial illness caused by Streptobacillus moniliformis or Spirillum minus following a rat bite. It is classically characterised by abrupt onset of fever with rigors, myalgias, headache, and the appearance of a generalised maculopapular petechial skin rash. Polyarthritis complicates the course of the disease in up to 50% of infected patients, and numerous hurdles can make the diagnosis particularly difficult in the absence of fever or rash, as in the present case. A high degree of awareness is necessary to make the correct diagnosis in such cases. Diagnosis has important prognostic implications as the disease is potentially lethal, but easily treatable.

  11. Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever).

    Science.gov (United States)

    1986-07-23

    fever , chills, nausea, headache and muscle ache in July 1985. One day after admission he developed petechial haemorrhage over his body and limbs and in...ftOA179 565 NENORNAGIC FEVER WI TH RENAL SYNDOMNE (KOREAN HEMORRHAIC FEVER )(U) KOREN UNIV SEOUL COLL OF MEDICINE N N LEE 23 JUL " DAD7-94-G-4616...34,, , " S , S S .S =. 5 5 . S S S * B M Lfl IC) uIeuCc FVM WITH RENAL SYNDR~OME (KOREAN EMORRHAGIC FEVER ) ANNUAL AND FINAL REPORT S HO WANG LIZB N.D. 5

  12. Surveillance for yellow Fever virus in non-human primates in southern Brazil, 2001-2011: a tool for prioritizing human populations for vaccination.

    OpenAIRE

    Marco A B Almeida; Jader da C Cardoso; Edmilson Dos Santos; Daltro F da Fonseca; Laura L Cruz; Fernando J C Faraco; Marilina A Bercini; Kátia C Vettorello; Mariana A Porto; Renate Mohrdieck; Tani M S Ranieri; Maria T Schermann; Alethéa F Sperb; Francisco Z Paz; Zenaida M A Nunes

    2014-01-01

    Author Summary Yellow fever (YF) is a viral hemorrhagic disease that affects humans as well as several species of non-human primates, especially New World monkeys found in South America. Yellow fever virus (YFV) is maintained in a natural cycle involving tree-hole breeding mosquitoes and non-human primates hosts. Because YF is often fatal in susceptible New World monkey populations, sudden die-offs of New World monkeys or epizootics can signal YFV circulation in an environment where humans ma...

  13. Chikungunya fever. Rheumatic manifestations of an emerging disease in Europe.

    Science.gov (United States)

    Horcada, M Loreto; Díaz-Calderón, Carlos; Garrido, Laura

    2015-01-01

    Chikungunya fever is a viral disease caused by an alphavirus belonging to the Togaviridae family, transmitted by several species of Aedes mosquitoes: Aedes aegypti and Aedes albopictus (A. albopictus). It is endemic in Africa and Asia with recurrent outbreaks. It is an emerging disease and cases in Europe transmitted by A. albopictus have been established in Mediterranean areas. The first autochthonous cases detected on the Caribbean islands suppose a serious threat of spreading disease to America, which so far has been disease free. Clinical symptoms begin abruptly with fever, skin rash and polyarthritis. Although mortality is low, a high percentage of patients develop a chronic phase defined by persistent arthritis for months or even years. A severe immune response is responsible for joint inflammation. The absence of specific treatment and lack of vaccine requires detailed studies about its immunopathogenesis in order to determine the most appropriate target. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. An inactivated cell-culture vaccine against yellow fever.

    Science.gov (United States)

    Monath, Thomas P; Fowler, Elizabeth; Johnson, Casey T; Balser, John; Morin, Merribeth J; Sisti, Maggie; Trent, Dennis W

    2011-04-07

    Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed. In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42. The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; Pvaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine. A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.).

  15. Prevalence of undifferentiated fever in adults of Rawalpindi having primary dengue fever

    International Nuclear Information System (INIS)

    Zafar, H.; Hayyat, A.; Akhtar, N.

    2013-01-01

    The objectives of the study were to highlight early subclinical presentation of dengue viral infection (DVI) as an undifferentiated febrile illness. The descriptive cross-sectional study was carried out at Microbiology Department, Rawalpindi Medical College from March to September 2009. Stratified random sampling was used to select subjects from various urban and rural areas of Rawalpindi, and Serum IgG anti-dengue antibodies were detected by using 3rd generation enzyme-linked immunosorbent assay (ELISA). Out of the total 240 subjects, 69 (28.75%) were found to be positive for anti-dengue IgG antibodies. Of the positive cases, 41 (59.4%) - comprising 31 (44.9%) urban residents - and 10 (14.4%) rural residents presented with a previous history of undifferentiated fever (p<0.05). It was concluded that primary DVI can present as subclinical form in healthy population residing in rural and urban areas of Rawalpindi, which is an alarming situation indicating the spread of disease in the study area. (author)

  16. Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals.

    Directory of Open Access Journals (Sweden)

    Jessica R Spengler

    2016-01-01

    Full Text Available Crimean-Congo hemorrhagic fever (CCHF is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. This review highlights the role of livestock in the maintenance and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology.

  17. Interim Report on Multiple Sequence Alignments and TaqMan Signature Mapping to Phylogenetic Trees

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, S; Jaing, C

    2012-03-27

    The goal of this project is to develop forensic genotyping assays for select agent viruses, addressing a significant capability gap for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the Taqman signature development for South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.

  18. Analysis of classical swine fever virus RNA replication determinants using replicons

    DEFF Research Database (Denmark)

    Risager, Peter Christian; Fahnøe, Ulrik; Gullberg, Maria

    2013-01-01

    Self-replicating RNAs (replicons), with or without reporter gene sequences, derived from the genome of the Paderborn strain of classical swine fever virus (CSFV) have been produced. The full-length viral cDNA, propagated within a bacterial artificial chromosome (BAC), was modified by targeted...... recombination within E. coli. RNA transcripts were produced in vitro and introduced into cells by electroporation. The translation and replication of the replicon RNAs could be followed by the accumulation of luciferase (from Renilla reniformis or Gaussia princeps) protein expression (where appropriate......), as well as by detection of the CSFV NS3 protein production within the cells. Inclusion of the viral E2 coding region within the replicon was advantageous for the replication efficiency. Production of chimeric RNAs, substituting the NS2 and NS3 coding regions (as a unit) from the Paderborn strain...

  19. T Cells and Pathogenesis of Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome

    OpenAIRE

    Francis A. Ennis; Masanori Terajima

    2011-01-01

    We previously hypothesized that increased capillary permeability observed in both hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) may be caused by hantavirus-specific cytotoxic T cells attacking endothelial cells presenting viral antigens on their surface based on clinical observations and in vitro experiments. In HCPS, hantavirus-specific T cell responses positively correlated with disease severity. In HFRS, in one report, contrary to HCPS, T cell ...

  20. Renal Artery Embolization of Perirenal Hematoma in Hemorrhagic Fever with Renal Syndrome: A Case Report

    International Nuclear Information System (INIS)

    Choi, Hee Seok; Lee, Yong Seok; Lim, Ji Hyon; Kim, Kyung Soo; Yoon, Yup; Hwang, Jae Cheol

    2007-01-01

    Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease characterized by fever, hemorrhage and renal failure. Among the various hemorrhagic complications of HFRS, spontaneous rupture of the kidney and perirenal hematoma are very rare findings. We report here on a case of HFRS complicated by massive perirenal hematoma, and this was treated with transcatheter arterial embolization. Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease caused by hantavirus. HFRS is clinically characterized by fever, renal failure and hemorrhage in organs such as lung, kidney, spleen and the pituitary gland. Renal medullary hemorrhage is a well-known complication in the kidney, but spontaneous rupture of the kidney and perirenal hematoma in HFRS is rare, and patients showing continuous bleeding and massive perirenal hematoma have often been surgically treated. We report here on a case of HFRS complicated by massive perirenal hematoma, and the patient was treated with transcatheter arterial embolization. In summary, spontaneous rupture of the kidney and perirenal hematoma is a rare complication of HFRS. We report here on a case of HFRS that caused massive perirenal hematoma, and this was treated with superselective renal artery embolization

  1. Renal Artery Embolization of Perirenal Hematoma in Hemorrhagic Fever with Renal Syndrome: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hee Seok; Lee, Yong Seok; Lim, Ji Hyon; Kim, Kyung Soo; Yoon, Yup [Dongguk University College of Medicine, Goyang (Korea, Republic of); Hwang, Jae Cheol [Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of)

    2007-08-15

    Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease characterized by fever, hemorrhage and renal failure. Among the various hemorrhagic complications of HFRS, spontaneous rupture of the kidney and perirenal hematoma are very rare findings. We report here on a case of HFRS complicated by massive perirenal hematoma, and this was treated with transcatheter arterial embolization. Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease caused by hantavirus. HFRS is clinically characterized by fever, renal failure and hemorrhage in organs such as lung, kidney, spleen and the pituitary gland. Renal medullary hemorrhage is a well-known complication in the kidney, but spontaneous rupture of the kidney and perirenal hematoma in HFRS is rare, and patients showing continuous bleeding and massive perirenal hematoma have often been surgically treated. We report here on a case of HFRS complicated by massive perirenal hematoma, and the patient was treated with transcatheter arterial embolization. In summary, spontaneous rupture of the kidney and perirenal hematoma is a rare complication of HFRS. We report here on a case of HFRS that caused massive perirenal hematoma, and this was treated with superselective renal artery embolization.

  2. Rab5 Enhances Classical Swine Fever Virus Proliferation and Interacts with Viral NS4B Protein to Facilitate Formation of NS4B Related Complex

    Directory of Open Access Journals (Sweden)

    Jihui Lin

    2017-08-01

    Full Text Available Classical swine fever virus (CSFV is a fatal pig pestivirus and causes serious financial losses to the pig industry. CSFV NS4B protein is one of the most important viral replicase proteins. Rab5, a member of the small Rab GTPase family, is involved in infection and replication of numerous viruses including hepatitis C virus and dengue virus. Until now, the effects of Rab5 on the proliferation of CSFV are poorly defined. In the present study, we showed that Rab5 could enhance CSFV proliferation by utilizing lentivirus-mediated constitutive overexpression and eukaryotic plasmid transient overexpression approaches. On the other hand, lentivirus-mediated short hairpin RNA knockdown of Rab5 dramatically inhibited virus production. Co-immunoprecipitation, glutathione S-transferase pulldown and laser confocal microscopy assays further confirmed the interaction between Rab5 and CSFV NS4B protein. In addition, intracellular distribution of NS4B-Red presented many granular fluorescent signals (GFS in CSFV infected PK-15 cells. Inhibition of basal Rab5 function with Rab5 dominant negative mutant Rab5S34N resulted in disruption of the GFS. These results indicate that Rab5 plays a critical role in facilitating the formation of the NS4B related complexes. Furthermore, it was observed that NS4B co-localized with viral NS3 and NS5A proteins in the cytoplasm, suggesting that NS3 and NS5A might be components of the NS4B related complex. Taken together, these results demonstrate that Rab5 positively modulates CSFV propagation and interacts with NS4B protein to facilitate the NS4B related complexes formation.

  3. Preliminary mapping of non-conserved epitopes on envelope glycoprotein E2 of bovine viral diarrhea virus type 1 and 2

    NARCIS (Netherlands)

    Jelsma, H.; Loeffen, W.L.A.; Beuningen, van A.R.; Rijn, van P.A.

    2013-01-01

    Bovine viral diarrhea virus (BVDV) belongs together with Classical swine fever virus (CSFV) and Border disease virus (BDV) to the genus Pestivirus in the Flaviviridae family. BVDV has been subdivided into two different species, BVDV1 and BVDV2 based on phylogenetic analysis. Subsequent

  4. Investigation of an isolated case of human Crimean–Congo hemorrhagic fever in Central Uganda, 2015

    Directory of Open Access Journals (Sweden)

    Stephen Balinandi

    2018-03-01

    Full Text Available Background: Crimean–Congo hemorrhagic fever (CCHF is the most geographically widespread tick-borne viral infection. Outbreaks of CCHF in sub-Saharan Africa are largely undetected and thus under-reported. On November 9, 2015, the National Viral Hemorrhagic Fever Laboratory at the Uganda Virus Research Institute received an alert for a suspect VHF case in a 33-year-old male who presented with VHF compatible signs and symptoms at Mengo Hospital in Kampala. Methods: A blood sample from the suspect patient was tested by RT-PCR for CCHF and found positive. Serological testing on sequential blood specimens collected from this patient showed increasing anti-CCHFV IgM antibody titers, confirming recent infection. Repeat sampling of the confirmed case post recovery showed high titers for anti-CCHFV-specific IgG. An epidemiological outbreak investigation was initiated following the initial RT-PCR positive detection to identify any additional suspect cases. Results: Only a single acute case of CCHF was detected from this outbreak. No additional acute CCHF cases were identified following field investigations. Environmental investigations collected 53 tick samples, with only 1, a Boophilus decoloratus, having detectable CCHFV RNA by RT-PCR. Full-length genomic sequencing on a viral isolate from the index human case showed the virus to be related to the DRC (Africa 2 lineage. Conclusions: This is the fourth confirmed CCHF outbreak in Uganda within 2 years after more than 50 years of no reported human CCHF cases in this country. Our investigations reaffirm the endemicity of CCHFV in Uganda, and show that exposure to ticks poses a significant risk for human infection. These findings also reflect the importance of having an established national VHF surveillance system and diagnostic capacity in a developing country like Uganda, in order to identify the first cases of VHF outbreaks and rapidly respond to reduce secondary cases. Additional efforts should focus on

  5. Phylogenetic analysis in a recent controlled outbreak of Crimean-Congo haemorrhagic fever in the south of Iran, December 2008

    DEFF Research Database (Denmark)

    Chinikar, S; Ghiasi, Seyed Mojtaba; Mojtaba Ghiasi, S

    2010-01-01

    Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with a high mortality rate in humans. The CCHF virus is transmitted to humans through the bite of Ixodid ticks or contact with blood or tissues of CCHF patients or infected livestock. In December 2008, a re-emerging outbreak...... of CCHF occurred in the southern part of Iran. Five people were hospitalised with sudden fever and haemorrhaging, and CCHF was confirmed by RT-PCR and serological assays. One of the cases had a fulminant course and died. Livestock was identified as the source of infection; all animals in the incriminated...

  6. Identification of New Protein Interactions between Dengue Fever Virus and Its Hosts, Human and Mosquito

    Science.gov (United States)

    Mairiang, Dumrong; Zhang, Huamei; Sodja, Ann; Murali, Thilakam; Suriyaphol, Prapat; Malasit, Prida; Limjindaporn, Thawornchai; Finley, Russell L.

    2013-01-01

    The four divergent serotypes of dengue virus are the causative agents of dengue fever, dengue hemorrhagic fever and dengue shock syndrome. About two-fifths of the world's population live in areas where dengue is prevalent, and thousands of deaths are caused by the viruses every year. Dengue virus is transmitted from one person to another primarily by the yellow fever mosquito, Aedes aegypti. Recent studies have begun to define how the dengue viral proteins interact with host proteins to mediate viral replication and pathogenesis. A combined analysis of these studies, however, suggests that many virus-host protein interactions remain to be identified, especially for the mosquito host. In this study, we used high-throughput yeast two-hybrid screening to identify mosquito and human proteins that physically interact with dengue proteins. We tested each identified host protein against the proteins from all four serotypes of dengue to identify interactions that are conserved across serotypes. We further confirmed many of the interactions using co-affinity purification assays. As in other large-scale screens, we identified some previously detected interactions and many new ones, moving us closer to a complete host – dengue protein interactome. To help summarize and prioritize the data for further study, we combined our interactions with other published data and identified a subset of the host-dengue interactions that are now supported by multiple forms of evidence. These data should be useful for understanding the interplay between dengue and its hosts and may provide candidates for drug targets and vector control strategies. PMID:23326450

  7. Identification of new protein interactions between dengue fever virus and its hosts, human and mosquito.

    Science.gov (United States)

    Mairiang, Dumrong; Zhang, Huamei; Sodja, Ann; Murali, Thilakam; Suriyaphol, Prapat; Malasit, Prida; Limjindaporn, Thawornchai; Finley, Russell L

    2013-01-01

    The four divergent serotypes of dengue virus are the causative agents of dengue fever, dengue hemorrhagic fever and dengue shock syndrome. About two-fifths of the world's population live in areas where dengue is prevalent, and thousands of deaths are caused by the viruses every year. Dengue virus is transmitted from one person to another primarily by the yellow fever mosquito, Aedes aegypti. Recent studies have begun to define how the dengue viral proteins interact with host proteins to mediate viral replication and pathogenesis. A combined analysis of these studies, however, suggests that many virus-host protein interactions remain to be identified, especially for the mosquito host. In this study, we used high-throughput yeast two-hybrid screening to identify mosquito and human proteins that physically interact with dengue proteins. We tested each identified host protein against the proteins from all four serotypes of dengue to identify interactions that are conserved across serotypes. We further confirmed many of the interactions using co-affinity purification assays. As in other large-scale screens, we identified some previously detected interactions and many new ones, moving us closer to a complete host - dengue protein interactome. To help summarize and prioritize the data for further study, we combined our interactions with other published data and identified a subset of the host-dengue interactions that are now supported by multiple forms of evidence. These data should be useful for understanding the interplay between dengue and its hosts and may provide candidates for drug targets and vector control strategies.

  8. Identification of new protein interactions between dengue fever virus and its hosts, human and mosquito.

    Directory of Open Access Journals (Sweden)

    Dumrong Mairiang

    Full Text Available The four divergent serotypes of dengue virus are the causative agents of dengue fever, dengue hemorrhagic fever and dengue shock syndrome. About two-fifths of the world's population live in areas where dengue is prevalent, and thousands of deaths are caused by the viruses every year. Dengue virus is transmitted from one person to another primarily by the yellow fever mosquito, Aedes aegypti. Recent studies have begun to define how the dengue viral proteins interact with host proteins to mediate viral replication and pathogenesis. A combined analysis of these studies, however, suggests that many virus-host protein interactions remain to be identified, especially for the mosquito host. In this study, we used high-throughput yeast two-hybrid screening to identify mosquito and human proteins that physically interact with dengue proteins. We tested each identified host protein against the proteins from all four serotypes of dengue to identify interactions that are conserved across serotypes. We further confirmed many of the interactions using co-affinity purification assays. As in other large-scale screens, we identified some previously detected interactions and many new ones, moving us closer to a complete host - dengue protein interactome. To help summarize and prioritize the data for further study, we combined our interactions with other published data and identified a subset of the host-dengue interactions that are now supported by multiple forms of evidence. These data should be useful for understanding the interplay between dengue and its hosts and may provide candidates for drug targets and vector control strategies.

  9. Complete Genomes of Classical Swine Fever Virus Cloned into Bacterial Artificial Chromosomes

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Reimann, I.; Uttenthal, Åse

    Complete genome amplification of viral RNA provides a new tool for the generation of modified pestiviruses. We have used our full-genome amplification strategy for generation of amplicons representing complete genomes of classical swine fever virus. The amplicons were cloned directly into a stabl...... single-copy bacterial artificial chromosome (BAC) generating full-length pestivirus DNAs from which infectious RNA transcripts could be also derived. Our strategy allows construction of stable infectious BAC DNAs from a single full-length PCR product....

  10. A novel indirect ELISA for diagnosis of dengue fever

    Directory of Open Access Journals (Sweden)

    Rohan Narayan

    2016-01-01

    Full Text Available Background & objectives: Dengue fever (DF is associated with significant morbidity and mortality in the tropical and sub-tropical regions of the world. Since there are no effective antiviral drugs for treatment, clinicians often rely on the accurate diagnosis of dengue fever to begin supportive therapy at early stages of the illness. The objective of this study was to develop an in-house dengue virus serotype 2 (DENV-2 non-structural protein- 5 (NS5 based indirect ELISA. Methods: DENV-2 was raised in Vero cells and the viral proteins were separated and subsequently the NS5 protein was eluted. Serum samples from primary and secondary dengue fever patients; and acute and convalescent samples from Japanese encephalitis (JE and West Nile virus (WNV cases were used to validate the ELISA. Results: The assay was found to be 100 per cent specific in detecting DENV-2 specific antibodies from patient′s serum. However, in terms of sensitivity, the assay could detect IgM antibodies only from 90 per cent of the primary dengue samples. The IgM/IgG ratio of the primary and secondary samples was 7.24 and 0.64, respectively. Interpretation & conclusions: The results indicate that the DENV-2 NS5 ELISA is dengue group specific and can be used to differentiate dengue infection from other circulating Flavivirus infections. This NS5 ELISA can also be used to distinguish between primary and secondary dengue fever on the basis of IgM/IgG ratios. Further studies with larger sample sizes and different DENV serotypes are required to validate the ELISA.

  11. [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.

  12. The influence of current and future climate on the spatial distribution of coccidioidomycosis in the southwestern United States

    Science.gov (United States)

    Gorris, M. E.; Hoffman, F. M.; Zender, C. S.; Treseder, K. K.; Randerson, J. T.

    2017-12-01

    Coccidioidomycosis, otherwise known as valley fever, is an infectious fungal disease currently endemic to the southwestern U.S. The magnitude, spatial distribution, and seasonality of valley fever incidence is shaped by variations in regional climate. As such, climate change may cause new communities to become at risk for contracting this disease. Humans contract valley fever by inhaling fungal spores of the genus Coccidioides. Coccidioides grow in the soil as a mycelium, and when stressed, autolyze into spores 2-5 µm in length. Spores can become airborne from any natural or anthropogenic soil disturbance, which can be exacerbated by dry soil conditions. Understanding the relationship between climate and valley fever incidence is critical for future disease risk management. We explored several multivariate techniques to create a predictive model of county-level valley fever incidence throughout the southwestern U.S., including Arizona, California, New Mexico, Nevada, and Utah. We incorporated surface air temperature, precipitation, soil moisture, surface dust concentrations, leaf area index, and the amount of agricultural land, all of which influence valley fever incidence. A log-linear regression model that incorporated surface air temperature, soil moisture, surface dust concentration, and the amount of agricultural land explained 34% of the county-level variance in annual average valley fever incidence. We used this model to predict valley fever incidence for the Representative Concentration Pathway 8.5 using simulation output from the Community Earth System Model. In our analysis, we describe how regional hotspots of valley fever incidence may shift with sustained warming and drying in the southwestern U.S. Our predictive model of valley fever incidence may help mitigate future health impacts of valley fever by informing health officials and policy makers of the climate conditions suitable for disease outbreak.

  13. Effective oral favipiravir (T-705 therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic Fever.

    Directory of Open Access Journals (Sweden)

    Michelle Mendenhall

    2011-10-01

    Full Text Available Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed.Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV to further preclinical development of T-705 (Favipiravir, a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD(50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity.Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based on challenge with highly pathogenic arenaviruses

  14. Crimean-Congo Hemorrhagic Fever Virus Suppresses Innate Immune Responses via a Ubiquitin and ISG15 Specific Protease

    Directory of Open Access Journals (Sweden)

    Florine E.M. Scholte

    2017-09-01

    Full Text Available Antiviral responses are regulated by conjugation of ubiquitin (Ub and interferon-stimulated gene 15 (ISG15 to proteins. Certain classes of viruses encode Ub- or ISG15-specific proteases belonging to the ovarian tumor (OTU superfamily. Their activity is thought to suppress cellular immune responses, but studies demonstrating the function of viral OTU proteases during infection are lacking. Crimean-Congo hemorrhagic fever virus (CCHFV, family Nairoviridae is a highly pathogenic human virus that encodes an OTU with both deubiquitinase and deISGylase activity as part of the viral RNA polymerase. We investigated CCHFV OTU function by inactivating protease catalytic activity or by selectively disrupting its deubiquitinase and deISGylase activity using reverse genetics. CCHFV OTU inactivation blocked viral replication independently of its RNA polymerase activity, while deubiquitinase activity proved critical for suppressing the interferon responses. Our findings provide insights into viral OTU functions and support the development of therapeutics and vaccines.

  15. Capacity building permitting comprehensive monitoring of a severe case of Lassa hemorrhagic fever in Sierra Leone with a positive outcome: Case Report

    Directory of Open Access Journals (Sweden)

    Fonnie Mbalu

    2011-06-01

    Full Text Available Abstract Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory characterisation of serological, biochemical and molecular aspects of the disease imported by infected individuals from Western Africa to the United States, Canada, Europe, Japan and Israel. Our report presents the first comprehensive real time diagnosis and characterization of a severe, hemorrhagic Lassa fever case in a Sierra Leonean individual admitted to the Kenema Government Hospital Lassa Fever Ward. Fever, malaise, unresponsiveness to anti-malarial and antibiotic drugs, followed by worsening symptoms and onset of haemorrhaging prompted medical officials to suspect Lassa fever. A recombinant Lassa virus protein based diagnostic was employed in diagnosing Lassa fever upon admission. This patient experienced a severe case of Lassa hemorrhagic fever with dysregulation of overall homeostasis, significant liver and renal system involvement, the interplay of pro- and anti-inflammatory cytokines during the course of hospitalization and an eventual successful outcome. These studies provide new insights into the pathophysiology and management of this viral illness and outline the improved infrastructure, research and real-time diagnostic capabilities within LASV endemic areas.

  16. 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.

  17. Fever

    Science.gov (United States)

    ... also cause fevers. Some examples are: Arthritis or connective tissue illnesses such as rheumatoid arthritis and systemic lupus erythematosus Ulcerative colitis and Crohn disease Vasculitis or periarteritis nodosa The first symptom of a cancer may be a fever. This is particularly true ...

  18. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Florian Douam

    2017-08-01

    Full Text Available Yellow fever virus (YFV is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β signaling and type II interferon (IFN-γ signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ integrates into this antiviral system. Here, we report that while wild-type (WT and IFN-λ receptor knockout (λR−/− mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR−/− mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB. α/βR−/− λR−/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.

  19. Association of Mean Platelet Volume with Severity, Serology & Treatment Outcome in Dengue Fever: Prognostic Utility.

    Science.gov (United States)

    Sharma, Kritika; Yadav, Ajay

    2015-11-01

    Dengue is the most rapidly spreading mosquito-borne viral disease in the world. Dengue fever (DF) with its severe manifestations such as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) has emerged as a major public health problem of international concern. Thrombocytopenia and bleeding are common complications of dengue fever, hence besides platelet counts, there is a need to assess the role of mean platelet volume. Studying association of mean platelet volume (MPV) with severity, serology & treatment outcome to assess its prognostic utility, which can be of great help in limiting morbidity & mortality associated with dengue fever. The present study was conducted in Central Pathology Lab of SMS Medical College & Hospital, Jaipur, Rajasthan from the period of March 2013 till October 2013. Blood samples were collected from 200 patients with NS 1 Antigen positivity experiencing febrile illness, clinically consistent with dengue infection. Evaluation of platelet counts, MPV, IgM and IgG antibodies was done in all these cases. Categorical data were presented as numbers (percent) and were compared among groups using Chi-square test. Groups compared for demographic data were presented as mean and standard deviation and were compared using student t-test, ANOVA and Post-Hoc Test, Tukey Test using SPSS, version 20 for Windows. A total of 200 Dengue fever cases were studied. Out of which, 68% cases were of DF, 23% DHF & 9% DSS i.e. classical dengue fever was most common presentation. Maximum (44%) cases were in age group of 15-24 years. Fever was the presenting complaint in all cases (100%). 98% cases of dengue had thrombocytopenia. MPV showed no significant correlation with severity, serology & treatment outcome, thus excluding its role in dengue cases. Mean platelet volume is not important as prognostic parameter in dengue fever.

  20. A Systematic Scoping Study of the Socio-Economic Impact of Rift Valley Fever: Research Gaps and Needs.

    Science.gov (United States)

    Peyre, M; Chevalier, V; Abdo-Salem, S; Velthuis, A; Antoine-Moussiaux, N; Thiry, E; Roger, F

    2015-08-01

    Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants. RVF virus has been reported in most African countries, as well as in the Arabic Peninsula. This paper reviews the different types of socio-economic impact induced by RVF disease and the attempts to evaluate them. Of the 52 papers selected for this review, 13 types of socio-economic impact were identified according to the sector impacted, the level and temporal scale of the impact. RVF has a dramatic impact on producers and livestock industries, affecting public and animal health, food security and the livelihood of the pastoralist communities. RVF also has an impact on international trade and other agro-industries. The risk of introducing RVF into disease-free countries via the importation of an infected animal or mosquito is real, and the consequent restriction of access to export markets may induce dramatic economic consequences for national and local economies. Despite the important threat of RVF, few studies have been conducted to assess the socio-economic impact of the disease. The 17 studies identified for quantitative analysis in this review relied only on partial cost analysis, with limited reference to mid- and long-term impact, public health or risk mitigation measures. However, the estimated impacts were high (ranging from $5 to $470 million USD losses). To reduce the impact of RVF, early detection and rapid response should be implemented. Comprehensive disease impact studies are required to provide decision-makers with science-based information on the best intervention measure to implement ensuring efficient resource allocation. Through the analysis of RVF socio-economic impact, this scoping study proposes insights into the mechanisms underpinning its often-underestimated importance. This study highlights the need for comparative socio-economic studies to help decision-makers with their choices related to RVF disease management. © 2014 The Authors

  1. The sero-epidemiology of Rift Valley fever in people in the Lake Victoria Basin of western Kenya.

    Directory of Open Access Journals (Sweden)

    Elizabeth Anne Jessie Cook

    2017-07-01

    Full Text Available Rift Valley fever virus (RVFV is a zoonotic arbovirus affecting livestock and people. This study was conducted in western Kenya where RVFV outbreaks have not previously been reported. The aims were to document the seroprevalence and risk factors for RVFV antibodies in a community-based sample from western Kenya and compare this with slaughterhouse workers in the same region who are considered a high-risk group for RVFV exposure. The study was conducted in western Kenya between July 2010 and November 2012. Individuals were recruited from randomly selected homesteads and a census of slaughterhouses. Structured questionnaire tools were used to collect information on demographic data, health, and risk factors for zoonotic disease exposure. Indirect ELISA on serum samples determined seropositivity to RVFV. Risk factor analysis for RVFV seropositivity was conducted using multi-level logistic regression. A total of 1861 individuals were sampled in 384 homesteads. The seroprevalence of RVFV in the community was 0.8% (95% CI 0.5-1.3. The variables significantly associated with RVFV seropositivity in the community were increasing age (OR 1.2; 95% CI 1.1-1.4, p<0.001, and slaughtering cattle at the homestead (OR 3.3; 95% CI 1.0-10.5, p = 0.047. A total of 553 slaughterhouse workers were sampled in 84 ruminant slaughterhouses. The seroprevalence of RVFV in slaughterhouse workers was 2.5% (95% CI 1.5-4.2. Being the slaughterman, the person who cuts the animal's throat (OR 3.5; 95% CI 1.0-12.1, p = 0.047, was significantly associated with RVFV seropositivity. This study investigated and compared the epidemiology of RVFV between community members and slaughterhouse workers in western Kenya. The data demonstrate that slaughtering animals is a risk factor for RVFV seropositivity and that slaughterhouse workers are a high-risk group for RVFV seropositivity in this environment. These risk factors have been previously reported in other studies providing further

  2. The sero-epidemiology of Rift Valley fever in people in the Lake Victoria Basin of western Kenya.

    Science.gov (United States)

    Cook, Elizabeth Anne Jessie; Grossi-Soyster, Elysse Noel; de Glanville, William Anson; Thomas, Lian Francesca; Kariuki, Samuel; Bronsvoort, Barend Mark de Clare; Wamae, Claire Njeri; LaBeaud, Angelle Desiree; Fèvre, Eric Maurice

    2017-07-01

    Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting livestock and people. This study was conducted in western Kenya where RVFV outbreaks have not previously been reported. The aims were to document the seroprevalence and risk factors for RVFV antibodies in a community-based sample from western Kenya and compare this with slaughterhouse workers in the same region who are considered a high-risk group for RVFV exposure. The study was conducted in western Kenya between July 2010 and November 2012. Individuals were recruited from randomly selected homesteads and a census of slaughterhouses. Structured questionnaire tools were used to collect information on demographic data, health, and risk factors for zoonotic disease exposure. Indirect ELISA on serum samples determined seropositivity to RVFV. Risk factor analysis for RVFV seropositivity was conducted using multi-level logistic regression. A total of 1861 individuals were sampled in 384 homesteads. The seroprevalence of RVFV in the community was 0.8% (95% CI 0.5-1.3). The variables significantly associated with RVFV seropositivity in the community were increasing age (OR 1.2; 95% CI 1.1-1.4, p<0.001), and slaughtering cattle at the homestead (OR 3.3; 95% CI 1.0-10.5, p = 0.047). A total of 553 slaughterhouse workers were sampled in 84 ruminant slaughterhouses. The seroprevalence of RVFV in slaughterhouse workers was 2.5% (95% CI 1.5-4.2). Being the slaughterman, the person who cuts the animal's throat (OR 3.5; 95% CI 1.0-12.1, p = 0.047), was significantly associated with RVFV seropositivity. This study investigated and compared the epidemiology of RVFV between community members and slaughterhouse workers in western Kenya. The data demonstrate that slaughtering animals is a risk factor for RVFV seropositivity and that slaughterhouse workers are a high-risk group for RVFV seropositivity in this environment. These risk factors have been previously reported in other studies providing further evidence for RVFV

  3. 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.

  4. Evaluation of Viral Meningoencephalitis Cases

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    Handan Ilhan

    2012-08-01

    Full Text Available AIM: To evaluate retrospectively adult cases of viral encephalitis. METHOD: Fifteen patients described viral encephalitis hospitalized between the years 2006-2011 follow-up and treatment at the infectious diseases clinic were analyzed retrospectively. RESULTS: Most of the patients (%60 had applied in the spring. Fever (87%, confusion (73%, neck stiffness (73%, headache (73%, nausea-vomiting (33%, loss of consciousness (33%, amnesia (33%, agitation (20%, convulsion (%20, focal neurological signs (13%, Brudzinski-sign (13% were most frequently encountered findings. Electroencephalography test was applied to 13 of 14 patients, and pathological findings compatible with encephalitis have been found. Radiological imaging methods such as CT and MRI were performed in 9 of the 14 patients, and findings consistent with encephalitis were reported. All of initial cerebrospinal fluid (CSF samples were abnormal. The domination of the first examples was lymphocytes in 14 patients; only one patient had an increase in neutrophilic cells have been found. CSF protein level was high in nine patients, and low glucose level was detected in two patients. Herpes simplex virus polymerized chain reaction (PCR analyze was performed to fourteen patients CSF. Only two of them (14% were found positive. One of the patients sample selectively examined was found to be Parvovirus B19 (+, the other patient urine sample Jacobs-creutzfeld virus PCR was found to be positively. Empiric acyclovir therapy was given to all patients. Neuropsychiatric squeal developed at the one patient. CONCLUSION: The cases in the forefront of change in mental status viral meningoencephalitis should be considered and empirical treatment with acyclovir should be started. [TAF Prev Med Bull 2012; 11(4.000: 447-452

  5. 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.

  6. Malignant Catarrhal Fever: Understanding Molecular Diagnostics in Context of Epidemiology

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    Hong Li

    2011-10-01

    Full Text Available Malignant catarrhal fever (MCF is a frequently fatal disease, primarily of ruminants, caused by a group of gammaherpesviruses. Due to complexities of pathogenesis and epidemiology in various species, which are either clinically-susceptible or reservoir hosts, veterinary clinicians face significant challenges in laboratory diagnostics. The recent development of specific assays for viral DNA and antibodies has expanded and improved the inventory of laboratory tests and opened new opportunities for use of MCF diagnostics. Issues related to understanding and implementing appropriate assays for specific diagnostic needs must be addressed in order to take advantage of molecular diagnostics in the laboratory.

  7. Evaluation of positive Rift Valley fever virus formalin-fixed paraffin embedded samples as a source of sequence data for retrospective phylogenetic analysis.

    Science.gov (United States)

    Mubemba, B; Thompson, P N; Odendaal, L; Coetzee, P; Venter, E H

    2017-05-01

    Rift Valley fever (RVF), caused by an arthropod borne Phlebovirus in the family Bunyaviridae, is a haemorrhagic disease that affects ruminants and humans. Due to the zoonotic nature of the virus, a biosafety level 3 laboratory is required for isolation of the virus. Fresh and frozen samples are the preferred sample type for isolation and acquisition of sequence data. However, these samples are scarce in addition to posing a health risk to laboratory personnel. Archived formalin-fixed, paraffin-embedded (FFPE) tissue samples are safe and readily available, however FFPE derived RNA is in most cases degraded and cross-linked in peptide bonds and it is unknown whether the sample type would be suitable as reference material for retrospective phylogenetic studies. A RT-PCR assay targeting a 490 nt portion of the structural G N glycoprotein encoding gene of the RVFV M-segment was applied to total RNA extracted from archived RVFV positive FFPE samples. Several attempts to obtain target amplicons were unsuccessful. FFPE samples were then analysed using next generation sequencing (NGS), i.e. Truseq ® (Illumina) and sequenced on the Miseq ® genome analyser (Illumina). Using reference mapping, gapped virus sequence data of varying degrees of shallow depth was aligned to a reference sequence. However, the NGS did not yield long enough contigs that consistently covered the same genome regions in all samples to allow phylogenetic analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. MP-12 virus containing the clone 13 deletion in the NSs gene prevents lethal disease when administered after Rift Valley fever virus infection in hamsters.

    Science.gov (United States)

    Gowen, Brian B; Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Nishiyama, Shoko; Wandersee, Luci; Scharton, Dionna; Jung, Kie-Hoon; Ikegami, Tetsuro

    2015-01-01

    Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) causes a range of illnesses that include retinitis, fulminant hepatitis, neurologic disease, and hemorrhagic fever. In hospitalized individuals, case fatality rates can be as high as 10-20%. There are no vaccines or antivirals approved for human use to prevent or treat severe RVFV infections. We previously tested the efficacy of the MP-12 vaccine strain and related variants with NSs truncations as a post-exposure prophylaxis in mice infected with wild-type pathogenic RVFV strain ZH501. Post-exposure efficacy of the rMP12-C13type, a recombinant MP-12 vaccine virus which encodes an in-frame truncation removing 69% of the NSs protein, resulted in 30% survival when administering the virus within 30 min of subcutaneous ZH501 challenge in mice, while the parental MP-12 virus conferred no protection by post-exposure vaccination. Here, we demonstrate uniform protection of hamsters by post-exposure vaccination with rMP12-C13type administered 6 h post-ZH501 infection while no efficacy was observed with the parental MP-12 virus. Notably, both the MP-12 and rMP12-C13type viruses were highly effective (100% protection) when administered 21 days prior to challenge. In a subsequent study delaying vaccination until 8, 12, and 24 h post-RVFV exposure, we observed 80, 70, and 30% survival, respectively. Our findings indicate that the rapid protective innate immune response elicited by rMP12-C13type may be due to the truncated NSs protein, suggesting that the resulting functional inactivation of NSs plays an important role in the observed post-exposure efficacy. Taken together, the data demonstrate that post-exposure vaccination with rMP12-C13type is effective in limiting ZH501 replication and associated disease in standard pre-exposure vaccination and post-challenge treatment models of RVFV infection, and suggest an extended post-exposure prophylaxis window beyond that initially observed in mice.

  9. Valley Fever

    Science.gov (United States)

    ... Coccidioides. The fungi live in the soil of dry areas like the southwestern U.S. You get it ... that expose them to soil dust. These include construction workers, agricultural workers, and military forces doing field ...

  10. AEGY-28 Cell Line of Aedes aegypti (Diptera Culicidae is Infection Refractory to Dengue 2 and Yellow Fever Virus

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    Nadia Y. Castañeda

    2007-07-01

    Full Text Available Mosquito cell derived cultures are useful tools for arbovirus isolation, identification or characterization. For studying dengue (DENV and yellow fever viruses (YFV Aedes albopictus C6/36 or Aedes pseudoscutellaris AP-61 cell lines, are normally used. The Aedes aegypti AEGY-28 cell line was obtained from embryonic tissues and characterized previously by one of us. In order to evaluate its susceptibility to two Flavivirus, AEGY- 28 cells were inoculated with different multiplicity of infection (MOI with type 2 DENV (COL-789, MOI: 1 and 5 and YFV clinical isolates (V-341, MOI 0,02 then processed at different times post infection (p.i.. Immunostai ning and fluorometric cell-ELISA were carried out to identify and quantify viral antigens. C6/36 and Vero cells were used as positive controls. Unexpectedly, immunoreactivity was not found in inoculated AEGY-28 cells, even in higher MOI or late times p.i., therefore antigen quantification using fluorometric cell-ELISA were not  plausible. Reverse transcriptase PCR with specific primers did not detect viral RNA in AEGY-28 inoculated cells. We can conclude that Aedes aegypti AEGY-28 cell line is not susceptible to dengue and yellow fever Flavivirus, a finding possibly related with the lacking of specific molecules at the plasma membrane or absence of cell machinery necessary for viral replication.

  11. Large-scale chromatin immunoprecipitation with promoter sequence microarray analysis of the interaction of the NSs protein of Rift Valley fever virus with regulatory DNA regions of the host genome.

    Science.gov (United States)

    Benferhat, Rima; Josse, Thibaut; Albaud, Benoit; Gentien, David; Mansuroglu, Zeyni; Marcato, Vasco; Souès, Sylvie; Le Bonniec, Bernard; Bouloy, Michèle; Bonnefoy, Eliette

    2012-10-01

    Rift Valley fever virus (RVFV) is a highly pathogenic Phlebovirus that infects humans and ruminants. Initially confined to Africa, RVFV has spread outside Africa and presently represents a high risk to other geographic regions. It is responsible for high fatality rates in sheep and cattle. In humans, RVFV can induce hepatitis, encephalitis, retinitis, or fatal hemorrhagic fever. The nonstructural NSs protein that is the major virulence factor is found in the nuclei of infected cells where it associates with cellular transcription factors and cofactors. In previous work, we have shown that NSs interacts with the promoter region of the beta interferon gene abnormally maintaining the promoter in a repressed state. In this work, we performed a genome-wide analysis of the interactions between NSs and the host genome using a genome-wide chromatin immunoprecipitation combined with promoter sequence microarray, the ChIP-on-chip technique. Several cellular promoter regions were identified as significantly interacting with NSs, and the establishment of NSs interactions with these regions was often found linked to deregulation of expression of the corresponding genes. Among annotated NSs-interacting genes were present not only genes regulating innate immunity and inflammation but also genes regulating cellular pathways that have not yet been identified as targeted by RVFV. Several of these pathways, such as cell adhesion, axonal guidance, development, and coagulation were closely related to RVFV-induced disorders. In particular, we show in this work that NSs targeted and modified the expression of genes coding for coagulation factors, demonstrating for the first time that this hemorrhagic virus impairs the host coagulation cascade at the transcriptional level.

  12. A Q fever case mimicking crimean-congo haemorrhagic fever

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    O Karabay

    2011-01-01

    Full Text Available Coxiella burnetii is the bacterium that causes Q fever. Human infection is mainly transmitted from cattle, goats and sheep. The disease is usually self-limited. Pneumonia and hepatitis are the most common clinical manifestations. In this study, we present a case of Q fever from the western part of Turkey mimicking Crimean-Congo haemorrhagic fever (CCHF in terms of clinical and laboratory findings.

  13. [Feeding pattern of Rift Valley Fever virus vectors in Senegal. Implications in the disease epidemiology].

    Science.gov (United States)

    Ba, Y; Diallo, D; Dia, I; Diallo, M

    2006-10-01

    During the rainy season 2003, an entomological survey was undertaken in the Sahelian bioclimatic zone of the Ferlo area in northern Senegal, in order to evaluate the degree of interaction between Rift valley fever (RVF) virus vectors and domestic animals and to determine the role of natural vertebrate hosts in the transmission and maintenance cycle. The study of vector-host contact was carried out under bed net traps using man, cow, sheep, chicken as bait whereas the RVFV vectors-vertebrate host interactions were studied through the analysis by an ELISA technique of the origin of the blood meals from naturally engorged females collected by aspiration. Blood meals sources were determined using a set of eight antibodies. Overall, the different known RVFV vectors (Culex poicilipes, Aedes vexans and Aedes ochraceus) were opportunistic although the bovine-baited net was, as far the more effective trap with 53.6% of collected mosquitoes. It was followed by the sheep-baited net (16.7%), man-baited net (12.6%) and chicken-baited net (11.6%). The more effectiveness of the bovine-baited net confirms the degree of implication of this host in RVF epidemiology. The study of vector-hosts interactions in nature showed that among the 1,112 mosquito blood meals tested, 701 were identified of which 693 were from Aedes vexans. The percentage of non-reacting blood meal was 36.7% whereas 16.9 % of the blood meals were taken at least on two vertebrate hosts. Overall, 53.2% of the blood meals from Ae. vexans were taken on equine, 18.6% on bovines, 7.1% on sheep and 0.6% on human. No blood meal was taken on rodent. The greatest diversity was observed in August. These host feedings patterns show that although equine is known to play a minor role in RVF epidemiology a thorough attention should be made to this host with regard to the percentage of blood meals taken in this host. The low percentage of blood meals taken on human could probably explain the low human infection rate observed up

  14. Certain peculiarities of the prevalence of typhoid fever under conditions of the environmental pollution

    Energy Technology Data Exchange (ETDEWEB)

    Toichuev, R. M.; Mamytova, M. [Institute of Medical Problems of the Southern Branch, Osh(Kyrgyzstan)

    2012-09-15

    ; morbidity rates were 0.1 cases per 100000 adult population and 0.3 cases per 100000 child population. A total of 86 patients with TF were recorded in Jalal-Abad Province. Of them, 31 patients were children under 14. Morbidity rates were as follows: 8.3 and 9.2, respectively, i.e. 10 times higher as compared to the other provinces of the Republic. To detect the causes of TF we studied the prevalence of the disease considering the location of water sources. The incidence of TF among the residents of the Mayluusuu Valley, the water of which is polluted with radionicles, was 124.7 (adult population) and 251.6 (child population) in 2010 and 130.9 and 162.5, respectively, in 2011. Moreover, starting from 2006 typhoid fever cases have been reported in the winter and spring times among the residents of the Mayluusuu Valley. In 2010, 52 (73.23%) out of the total of 71 patients with TF admitted to the hospitals in Jalal-Abad Province were the residents of the Mayluusuu Valley, as compared to 64 (74.45%) out of the total 86 patients reported in 2011. Thus, the higher TF morbidity rate in the south of the Kyrgyz Republic is due to poor sanitation in the region (the Mayluusuu Valley), i.e. this radionuclide-polluted area remains one of the typhoid fever 'hot-spots'. (author)

  15. BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.

    Science.gov (United States)

    Taylor, Raymond; Kotian, Pravin; Warren, Travis; Panchal, Rekha; Bavari, Sina; Julander, Justin; Dobo, Sylvia; Rose, Angela; El-Kattan, Yahya; Taubenheim, Brian; Babu, Yarlagadda; Sheridan, William P

    2016-01-01

    The adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.

  16. Case definition for Ebola and Marburg haemorrhagic fevers: a complex challenge for epidemiologists and clinicians.

    Science.gov (United States)

    Pittalis, Silvia; Fusco, Francesco Maria; Lanini, Simone; Nisii, Carla; Puro, Vincenzo; Lauria, Francesco Nicola; Ippolito, Giuseppe

    2009-10-01

    Viral haemorrhagic fevers (VHFs) represent a challenge for public health because of their epidemic potential, and their possible use as bioterrorism agents poses particular concern. In 1999 the World Health Organization (WHO) proposed a case definition for VHFs, subsequently adopted by other international institutions with the aim of early detection of initial cases/outbreaks in western countries. We applied this case definition to reports of Ebola and Marburg virus infections to estimate its sensitivity to detect cases of the disease. We analyzed clinical descriptions of 795 reported cases of Ebola haemorrhagic fever: only 58.5% of patients met the proposed case definition. A similar figure was obtained reviewing 169 cases of Marburg diseases, of which only 64.5% were in accordance with the case definition. In conclusion, the WHO case definition for hemorrhagic fevers is too specific and has poor sensitivity both for case finding during Ebola or Marburg outbreaks, and for early detection of suspected cases in western countries. It can lead to a hazardous number of false negatives and its use should be discouraged for early detection of cases.

  17. Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus.

    Science.gov (United States)

    Hakobyan, Astghik; Galindo, Inmaculada; Nañez, Almudena; Arabyan, Erik; Karalyan, Zaven; Chistov, Alexey A; Streshnev, Philipp P; Korshun, Vladimir A; Alonso, Covadonga; Zakaryan, Hovakim

    2018-01-01

    Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl)uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no effective vaccine is available. Both compounds displayed a potent, dose-dependent inhibitory effect on ASFV infection in Vero cells. The major antiviral effect was observed when aUY11 and cm1UY11 were added at early stages of infection and maintained during the complete viral cycle. Furthermore, virucidal assay revealed a significant extracellular anti-ASFV activity for both compounds. We also found decrease in the synthesis of early and late viral proteins in Vero cells treated with cm1UY11. Finally, the inhibitory effect of aUY11 and cm1UY11 on ASFV infection in porcine alveolar macrophages was confirmed. Overall, our study has identified novel anti-ASFV compounds with potential for future therapeutic developments.

  18. [Surveillance data on typhoid fever and paratyphoid fever in 2015, China].

    Science.gov (United States)

    Liu, F F; Zhao, S L; Chen, Q; Chang, Z R; Zhang, J; Zheng, Y M; Luo, L; Ran, L; Liao, Q H

    2017-06-10

    Objective: Through analyzing the surveillance data on typhoid fever and paratyphoid fever in 2015 to understand the related epidemiological features and most possible clustering areas of high incidence. Methods: Individual data was collected from the passive surveillance program and analyzed by descriptive statistic method. Characteristics on seasonal, regional and distribution of the diseases were described. Spatial-temporal clustering characteristics were estimated, under the retrospective space-time method. Results: A total of 8 850 typhoid fever cases were reported from the surveillance system, with incidence rate as 0.65/100 000. The number of paratyphoid fever cases was 2 794, with incidence rate as 0.21/100 000. Both cases of typhoid fever and paratyphoid fever occurred all year round, with high epidemic season from May to October. Most cases involved farmers (39.68 % ), children (15.89 % ) and students (12.01 % ). Children under 5 years showed the highest incidence rate. Retrospective space-time analysis for provinces with high incidence rates would include Yunnan, Guangxi, Guizhou, Hunan and Guangdong, indicating the first and second class clusters were mainly distributed near the bordering adjacent districts and counties among the provinces. Conclusion: In 2015, the prevalence rates of typhoid fever and paratyphoid fever were low, however with regional high prevalence areas. Cross regional transmission existed among provinces with high incidence rates which might be responsible for the clusters to appear in these areas.

  19. Yellow fever

    Science.gov (United States)

    ... to thrive. Blood tests can confirm the diagnosis. Treatment There is no specific treatment for yellow fever. ... SJ, Endy TP, Rothman AL, Barrett AD. Flaviviruses (dengue, yellow fever, Japanese encephalitis, West Nile encephalitis, St. ...

  20. Statistical modeling of the abundance of vectors of West African Rift Valley fever in Barkédji, Senegal.

    Directory of Open Access Journals (Sweden)

    Cheikh Talla

    Full Text Available Rift Valley fever is an emerging mosquito-borne disease that represents a threat to human and animal health. The exophilic and exophagic behavior of the two main vector in West Africa (Aedes vexans and Culex poicilipes, adverse events post-vaccination, and lack of treatment, render ineffective the disease control. Therefore it is essential to develop an information system that facilitates decision-making and the implementation of adaptation strategies. In East Africa, RVF outbreaks are linked with abnormally high rainfall, and can be predicted up to 5 months in advance by modeling approaches using climatic and environmental parameters. However, the application of these models in West Africa remains unsatisfactory due to a lack of data for animal and human cases and differences in the dynamics of the disease emergence and the vector species involved in transmission. Models have been proposed for West Africa but they were restricted to rainfall impact analysis without a spatial dimension. In this study, we developed a mixed Bayesian statistical model to evaluate the effects of climatic and ecological determinants on the spatiotemporal dynamics of the two main vectors. Adult mosquito abundance data were generated from July to December every fortnight in 2005-2006 at 79 sites, including temporary ponds, bare soils, shrubby savannah, wooded savannah, steppes, and villages in the Barkédji area. The results demonstrate the importance of environmental factors and weather conditions for predicting mosquito abundance. The rainfall and minimum temperature were positively correlated with the abundance of Cx. poicilipes, whereas the maximum temperature had negative effects. The rainfall was negatively correlated with the abundance of Ae. vexans. After combining land cover classes, weather conditions, and vector abundance, our model was used to predict the areas and periods with the highest risks of vector pressure. This information could support decision

  1. Yellow fever vaccine: an effective vaccine for travelers.

    Science.gov (United States)

    Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj

    2014-01-01

    Yellow fever (YF) is an acute viral communicable disease transmitted by an arbovirus of the Flavivirus genus. It is primarily a zoonotic disease, especially the monkeys. Worldwide, an estimated 200,000 cases of yellow fever occurred each year, and the case-fatality rate is ~15%. Forty-five endemic countries in Africa and Latin America, with a population of close to 1 billion, are at risk. Up to 50% of severely affected persons from YF die without treatment. During 2009, 55 cases and 18 deaths were reported from Brazil, Colombia, and Peru. Brazil reported the maximum number of cases and death, i.e., 42 cases with 11 deaths. From January 2010 to March 2011, outbreaks of YF were reported to the WHO by Cameroon, Democratic Republic of Congo, Cote d'Ivoire, Guinea, Sierra Leone, Senegal, and Uganda. Cases were also reported in three northern districts of Abim, Agago, and Kitugun near the border with South Sudan. YF usually causes fever, muscle pain with prominent backache, headache, shivers, loss of appetite, and nausea or vomiting. Most patients improve, and their symptoms disappear after 3 to 4 d. Half of the patients who enter the toxic phase die within 10-14 d, while the rest recover without significant organ damage. Vaccination has been the single most important measure for preventing YF. The 17D-204 YF vaccine is a freeze-dried, live attenuated, highly effective vaccine. It is available in single-dose or multi-dose vials and should be stored at 2-8 °C. It is reconstituted with normal saline and should be used within 1 h of reconstitution. The 0.5 mL dose is delivered subcutaneously. Revaccination is recommended every 10 y for people at continued risk of exposure to yellow fever virus (YFV). This vaccine is available worldwide. Travelers, especially to Africa or Latin America from Asia, must have a certificate documenting YF vaccination, which is required by certain countries for entry under the International Health Regulations (IHR) of the WHO.

  2. Population genetics of two key mosquito vectors of Rift Valley Fever virus reveals new insights into the changing disease outbreak patterns in Kenya.

    Directory of Open Access Journals (Sweden)

    David P Tchouassi

    2014-12-01

    Full Text Available Rift Valley fever (RVF outbreaks in Kenya have increased in frequency and range to include northeastern Kenya where viruses are increasingly being isolated from known (Aedes mcintoshi and newly-associated (Ae. ochraceus vectors. The factors contributing to these changing outbreak patterns are unclear and the population genetic structure of key vectors and/or specific virus-vector associations, in particular, are under-studied. By conducting mitochondrial and nuclear DNA analyses on >220 Kenyan specimens of Ae. mcintoshi and Ae. ochraceus, we uncovered high levels of vector complexity which may partly explain the disease outbreak pattern. Results indicate that Ae. mcintoshi consists of a species complex with one of the member species being unique to the newly-established RVF outbreak-prone northeastern region of Kenya, whereas Ae. ochraceus is a homogeneous population that appears to be undergoing expansion. Characterization of specimens from a RVF-prone site in Senegal, where Ae. ochraceus is a primary vector, revealed direct genetic links between the two Ae. ochraceus populations from both countries. Our data strongly suggest that unlike Ae. mcintoshi, Ae. ochraceus appears to be a relatively recent, single 'introduction' into Kenya. These results, together with increasing isolations from this vector, indicate that Ae. ochraceus will likely be of greater epidemiological importance in future RVF outbreaks in Kenya. Furthermore, the overall vector complexity calls into question the feasibility of mosquito population control approaches reliant on genetic modification.

  3. Population Genetics of Two Key Mosquito Vectors of Rift Valley Fever Virus Reveals New Insights into the Changing Disease Outbreak Patterns in Kenya

    Science.gov (United States)

    Tchouassi, David P.; Bastos, Armanda D. S.; Sole, Catherine L.; Diallo, Mawlouth; Lutomiah, Joel; Mutisya, James; Mulwa, Francis; Borgemeister, Christian; Sang, Rosemary; Torto, Baldwyn

    2014-01-01

    Rift Valley fever (RVF) outbreaks in Kenya have increased in frequency and range to include northeastern Kenya where viruses are increasingly being isolated from known (Aedes mcintoshi) and newly-associated (Ae. ochraceus) vectors. The factors contributing to these changing outbreak patterns are unclear and the population genetic structure of key vectors and/or specific virus-vector associations, in particular, are under-studied. By conducting mitochondrial and nuclear DNA analyses on >220 Kenyan specimens of Ae. mcintoshi and Ae. ochraceus, we uncovered high levels of vector complexity which may partly explain the disease outbreak pattern. Results indicate that Ae. mcintoshi consists of a species complex with one of the member species being unique to the newly-established RVF outbreak-prone northeastern region of Kenya, whereas Ae. ochraceus is a homogeneous population that appears to be undergoing expansion. Characterization of specimens from a RVF-prone site in Senegal, where Ae. ochraceus is a primary vector, revealed direct genetic links between the two Ae. ochraceus populations from both countries. Our data strongly suggest that unlike Ae. mcintoshi, Ae. ochraceus appears to be a relatively recent, single 'introduction' into Kenya. These results, together with increasing isolations from this vector, indicate that Ae. ochraceus will likely be of greater epidemiological importance in future RVF outbreaks in Kenya. Furthermore, the overall vector complexity calls into question the feasibility of mosquito population control approaches reliant on genetic modification. PMID:25474018

  4. Genome analysis of yellow fever virus of the ongoing outbreak in Brazil reveals polymorphisms

    Directory of Open Access Journals (Sweden)

    Myrna C Bonaldo

    Full Text Available The current yellow fever outbreak in Brazil is the most severe one in the country in recent times. It has rapidly spread to areas where YF virus (YFV activity has not been observed for more than 70 years and vaccine coverage is almost null. Here, we sequenced the whole YFV genome of two naturally infected howler-monkeys (Alouatta clamitans obtained from the Municipality of Domingos Martins, state of Espírito Santo, Brazil. These two ongoing-outbreak genome sequences are identical. They clustered in the 1E sub-clade (South America genotype I along with the Brazilian and Venezuelan strains recently characterised from infections in humans and non-human primates that have been described in the last 20 years. However, we detected eight unique amino acid changes in the viral proteins, including the structural capsid protein (one change, and the components of the viral replicase complex, the NS3 (two changes and NS5 (five changes proteins, that could impact the capacity of viral infection in vertebrate and/or invertebrate hosts and spreading of the ongoing outbreak.

  5. Typhoid fever

    Science.gov (United States)

    Typhoid fever is an infection that causes diarrhea and a rash . It is most commonly caused due to ... in their stools for years, spreading the disease. Typhoid fever is common in developing countries. Most cases in ...

  6. A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

    Science.gov (United States)

    2013-09-12

    performance liquid chroma- tography to greater than 95% purity (Bio-synthesis, Inc., Lewisville, TX). Lyophilized peptides were initially resuspended in...lesser extent RVFV-6sc, were found to precipitate Gc (Figure 5); however, in the presence of the non- ionic detergent Triton-X, which will solubilize...Viral membrane fusion. Nat Struct Mol Biol 15: 690–698. 12. Allison SL, Schalich J, Stiasny K, Mandl CW, Kunz C, et al. (1995) Oligomeric rearrangement

  7. Fever in Infants and Children

    Science.gov (United States)

    ... or higher that is unresponsive to fever-reducing medicine?YesNoDoes your child have a low-grade fever (up to 101°) ... fever, give your child a nonaspirin fever-reducing medicine. Call your child’s doctor after 24 hours if the fever continues ...

  8. 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.

  9. Integrated Analysis of Environment, Cattle and Human Serological Data: Risks and Mechanisms of Transmission of Rift Valley Fever in Madagascar.

    Science.gov (United States)

    Olive, Marie-Marie; Chevalier, Véronique; Grosbois, Vladimir; Tran, Annelise; Andriamandimby, Soa-Fy; Durand, Benoit; Ravalohery, Jean-Pierre; Andriamamonjy, Seta; Rakotomanana, Fanjasoa; Rogier, Christophe; Heraud, Jean-Michel

    2016-07-01

    Rift Valley fever (RVF) is a vector-borne disease affecting ruminants and humans. Madagascar was heavily affected by RVF in 2008-2009, with evidence of a large and heterogeneous spread of the disease. The identification of at-risk environments is essential to optimize the available resources by targeting RVF surveillance in Madagascar. Herein, the objectives of our study were: (i) to identify the environmental factors and areas favorable to RVF transmission to both cattle and human and (ii) to identify human behaviors favoring human infections in Malagasy contexts. First, we characterized the environments of Malagasy communes using a Multiple Factor Analysis (MFA). Then, we analyzed cattle and human serological data collected at national level using Generalized Linear Mixed Models, with the individual serological status (cattle or human) as the response, and MFA factors, as well as other potential risk factors (cattle density, human behavior) as explanatory variables. Cattle and human seroprevalence rates were positively associated to humid environments (p<0.001). Areas with high cattle density were at risk (p<0.01; OR = 2.6). Furthermore, our analysis showed that frequent contact with raw milk contributed to explain human infection (OR = 1.6). Finally, our study highlighted the eastern-coast, western and north-western parts as high-risk areas for RVF transmission in cattle. Our integrated approach analyzing environmental, cattle and human datasets allow us to bring new insight on RVF transmission patterns in Madagascar. The association between cattle seroprevalence, humid environments and high cattle density suggests that concomitant vectorial and direct transmissions are critical to maintain RVF enzootic transmission. Additionally, in the at-risk humid environment of the western, north-western and the eastern-coast areas, suitable to Culex and Anopheles mosquitoes, vectorial transmission probably occurs in both cattle and human. The relative contribution of

  10. Integrated Analysis of Environment, Cattle and Human Serological Data: Risks and Mechanisms of Transmission of Rift Valley Fever in Madagascar.

    Directory of Open Access Journals (Sweden)

    Marie-Marie Olive

    2016-07-01

    Full Text Available Rift Valley fever (RVF is a vector-borne disease affecting ruminants and humans. Madagascar was heavily affected by RVF in 2008-2009, with evidence of a large and heterogeneous spread of the disease. The identification of at-risk environments is essential to optimize the available resources by targeting RVF surveillance in Madagascar. Herein, the objectives of our study were: (i to identify the environmental factors and areas favorable to RVF transmission to both cattle and human and (ii to identify human behaviors favoring human infections in Malagasy contexts.First, we characterized the environments of Malagasy communes using a Multiple Factor Analysis (MFA. Then, we analyzed cattle and human serological data collected at national level using Generalized Linear Mixed Models, with the individual serological status (cattle or human as the response, and MFA factors, as well as other potential risk factors (cattle density, human behavior as explanatory variables. Cattle and human seroprevalence rates were positively associated to humid environments (p<0.001. Areas with high cattle density were at risk (p<0.01; OR = 2.6. Furthermore, our analysis showed that frequent contact with raw milk contributed to explain human infection (OR = 1.6. Finally, our study highlighted the eastern-coast, western and north-western parts as high-risk areas for RVF transmission in cattle.Our integrated approach analyzing environmental, cattle and human datasets allow us to bring new insight on RVF transmission patterns in Madagascar. The association between cattle seroprevalence, humid environments and high cattle density suggests that concomitant vectorial and direct transmissions are critical to maintain RVF enzootic transmission. Additionally, in the at-risk humid environment of the western, north-western and the eastern-coast areas, suitable to Culex and Anopheles mosquitoes, vectorial transmission probably occurs in both cattle and human. The relative contribution

  11. Predicting the mosquito species and vertebrate species involved in the theoretical transmission of Rift Valley fever virus in the United States.

    Directory of Open Access Journals (Sweden)

    Andrew J Golnar

    2014-09-01

    Full Text Available Rift Valley fever virus (RVFV is a mosquito-borne virus in the family Bunyaviridiae that has spread throughout continental Africa to Madagascar and the Arabian Peninsula. The establishment of RVFV in North America would have serious consequences for human and animal health in addition to a significant economic impact on the livestock industry. Published and unpublished data on RVFV vector competence, vertebrate host competence, and mosquito feeding patterns from the United States were combined to quantitatively implicate mosquito vectors and vertebrate hosts that may be important to RVFV transmission in the United States. A viremia-vector competence relationship based on published mosquito transmission studies was used to calculate a vertebrate host competence index which was then combined with mosquito blood feeding patterns to approximate the vector and vertebrate amplification fraction, defined as the relative contribution of the mosquito or vertebrate host to pathogen transmission. Results implicate several Aedes spp. mosquitoes and vertebrates in the order Artiodactyla as important hosts for RVFV transmission in the U.S. Moreover, this study identifies critical gaps in knowledge which would be necessary to complete a comprehensive analysis identifying the different contributions of mosquitoes and vertebrates to potential RVFV transmission in the U.S. Future research should focus on (1 the dose-dependent relationship between viremic exposure and the subsequent infectiousness of key mosquito species, (2 evaluation of vertebrate host competence for RVFV among North American mammal species, with particular emphasis on the order Artiodactyla, and (3 identification of areas with a high risk for RVFV introduction so data on local vector and host populations can help generate geographically appropriate amplification fraction estimates.

  12. Predicting the mosquito species and vertebrate species involved in the theoretical transmission of Rift Valley fever virus in the United States.

    Science.gov (United States)

    Golnar, Andrew J; Turell, Michael J; LaBeaud, A Desiree; Kading, Rebekah C; Hamer, Gabriel L

    2014-09-01

    Rift Valley fever virus (RVFV) is a mosquito-borne virus in the family Bunyaviridiae that has spread throughout continental Africa to Madagascar and the Arabian Peninsula. The establishment of RVFV in North America would have serious consequences for human and animal health in addition to a significant economic impact on the livestock industry. Published and unpublished data on RVFV vector competence, vertebrate host competence, and mosquito feeding patterns from the United States were combined to quantitatively implicate mosquito vectors and vertebrate hosts that may be important to RVFV transmission in the United States. A viremia-vector competence relationship based on published mosquito transmission studies was used to calculate a vertebrate host competence index which was then combined with mosquito blood feeding patterns to approximate the vector and vertebrate amplification fraction, defined as the relative contribution of the mosquito or vertebrate host to pathogen transmission. Results implicate several Aedes spp. mosquitoes and vertebrates in the order Artiodactyla as important hosts for RVFV transmission in the U.S. Moreover, this study identifies critical gaps in knowledge which would be necessary to complete a comprehensive analysis identifying the different contributions of mosquitoes and vertebrates to potential RVFV transmission in the U.S. Future research should focus on (1) the dose-dependent relationship between viremic exposure and the subsequent infectiousness of key mosquito species, (2) evaluation of vertebrate host competence for RVFV among North American mammal species, with particular emphasis on the order Artiodactyla, and (3) identification of areas with a high risk for RVFV introduction so data on local vector and host populations can help generate geographically appropriate amplification fraction estimates.

  13. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    Science.gov (United States)

    Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

  14. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    Directory of Open Access Journals (Sweden)

    Andrea Marzi

    Full Text Available Ebola virus (EBOV is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF. Single monoclonal antibodies (MAbs specific for Zaire ebolavirus (ZEBOV have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226 with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

  15. [An imported dengue Fever case in Turkey and review of the literature].

    Science.gov (United States)

    Uyar, Yavuz; Aktaş, Eray; Yağcı Çağlayık, Dilek; Ergönül, Onder; Yüce, Ayşe

    2013-01-01

    Dengue fever is an acute viral disease that can affect all age groups in tropical and subtropical countries. The predominant vectors are the mosquitoes namely Aedes aegypti and A.albopictus. Although there have been no case reports in Turkey due to DF, there is seroepidemiological evidence indicating the presence of Dengue virus (DENV) in Turkey. In this case report we presented an imported dengue fever case. The patient was 40 years old, previously healthy male, Switzerland citizen. He had immigrated from Dubai to India two weeks ago and after one week from immigration he attended to a hospital in India because of high fever. The NS1 antigen test (Bio-Rad Laboratories, USA) was found positive and the patient was followed-up with diagnosis of dengue fever in India. During his visit to Turkey, he attended to the hospital for a routine control and his analysis revealed thrombocytopenia (PLT: 48.000/µl), leukopenia (white blood cell: 2800/µL) and elevated liver enzymes (AST: 76 U/L, ALT: 83 U/L). Fever was not detected in follow-up. The patient had petechial rash on his lower extremities. white blood cell and PLT count increased to 4100/µl and 93.000/µl, respectively. Liver function tests revealed a decrease in AST (63 U/L) and ALT (78 U/L) on the third day. The PLT count increased to 150.000/ml. Since the patient had no fever and had normal physical and laboratory findings, he was discharged from the hospital. For the confirmation of dengue fever diagnosis the serum sample was sent to National Public Health Center, Virology Reference and Research Laboratory where IgM and IgG antibodies against DENV types 1-4 were investigated by indirect immunofluorescence method (Euroimmun, Germany). The serum sample yielded positive result at the dilutions of 1/1000 for IgM and 1/10.000 for IgG. The last dilution of type 3 DENV IgM and IgG were determined high density of fluorescein, thus the serotype was identified as "DENV type 3". Travel-related diseases become important

  16. RNA Encapsidation and Packaging in the Phleboviruses

    Directory of Open Access Journals (Sweden)

    Katherine E. Hornak

    2016-07-01

    Full Text Available The Bunyaviridae represents the largest family of segmented RNA viruses, which infect a staggering diversity of plants, animals, and insects. Within the family Bunyaviridae, the Phlebovirus genus includes several important human and animal pathogens, including Rift Valley fever virus (RVFV, severe fever with thrombocytopenia syndrome virus (SFTSV, Uukuniemi virus (UUKV, and the sandfly fever viruses. The phleboviruses have small tripartite RNA genomes that encode a repertoire of 5–7 proteins. These few proteins accomplish the daunting task of recognizing and specifically packaging a tri-segment complement of viral genomic RNA in the midst of an abundance of host components. The critical nucleation events that eventually lead to virion production begin early on in the host cytoplasm as the first strands of nascent viral RNA (vRNA are synthesized. The interaction between the vRNA and the viral nucleocapsid (N protein effectively protects and masks the RNA from the host, and also forms the ribonucleoprotein (RNP architecture that mediates downstream interactions and drives virion formation. Although the mechanism by which all three genomic counterparts are selectively co-packaged is not completely understood, we are beginning to understand the hierarchy of interactions that begins with N-RNA packaging and culminates in RNP packaging into new virus particles. In this review we focus on recent progress that highlights the molecular basis of RNA genome packaging in the phleboviruses.

  17. 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

  18. Rocky Mountain spotted fever

    Science.gov (United States)

    ... spotted fever on the foot Rocky Mountain spotted fever, petechial rash Antibodies Deer and dog tick References McElligott SC, Kihiczak GG, Schwartz RA. Rocky Mountain spotted fever and other rickettsial infections. In: Lebwohl MG, Heymann ...

  19. The interferon response circuit in antiviral host defense.

    Science.gov (United States)

    Haller, O; Weber, F

    2009-01-01

    Viruses have learned to multiply in the face of a powerful innate and adaptive immune response of the host. They have evolved multiple strategies to evade the interferon (IFN) system which would otherwise limit virus growth at an early stage of infection. IFNs induce the synthesis of a range of antiviral proteins which serve as cell-autonomous intrinsic restriction factors. For example, the dynamin-like MxA GTPase inhibits the multiplication of influenza and bunyaviruses (such as La Crosse virus, Hantaan virus, Rift Valley Fever virus, and Crimean-Congo hemorrhagic fever virus) by binding and sequestering the nucleocapsid protein into large perinuclear complexes. To overcome such intracellular restrictions, virulent viruses either inhibit IFN synthesis, bind and inactivate secreted IFN molecules, block IFN-activated signaling, or disturb the action of IFN-induced antiviral proteins. Many viruses produce specialized proteins to disarm the danger signal or express virulence genes that target members of the IFN regulatory factor family (IRFs) or components of the JAK-STAT signaling pathway. An alternative evasion strategy is based on extreme viral replication speed which out-competes the IFN response. The identification of viral proteins with IFN antagonistic functions has great implications for disease prevention and therapy. Virus mutants lacking IFN antagonistic properties represent safe yet highly immunogenic candidate vaccines. Furthermore, novel drugs intercepting viral IFN-antagonists could be used to disarm the viral intruders.

  20. Hematological and biochemical indicators for the early diagnosis of dengue viral infection

    International Nuclear Information System (INIS)

    Butt, N.; Abbasi, A.; Sheikh, Q.H.

    2008-01-01

    To determine the haematological and biochemical indicators for the early diagnosis of dengue viral infection. Patients presenting with a fever of less than 2 weeks duration, generalized morbiliform rash and bleeding manifestations were included. Clinical history was recorded and patients were placed on fluid and haematological support. Diagnosis was established by Polymerase Chain Reaction (PCR) for dengue virus or detection of dengue virus specific IgM and IgG. One hundred and four patients met the inclusion criteria during the study period. Sixty six patients had clinical and haematological features suggestive of grade I Dengue Hemorrhagic Fever (DHF); 34 patients had grade II DHF and 4 had grade III DHF out of whom 3 progressed to grade IV DHF. All the patients presented with fever followed by generalized morbiliform rash (81.73%), vomiting (79.8%), abdominal pain (65.38%), backache (62.5%), depression (60.6%) and mucosal bleeding manifestations (34.6%). Clinically, conjunctival infection was present in 93 patients (89.4%), hepatomegaly 59 (56.7%), lymphadenopathy in 17 (16.3%), splenomegaly in 13 (12.5%), pleural effusion in 11 (10.5%) and ascites in 8 (7.6%). Common laboratory findings were thrombocytopenia in 100% patients, leucopenia in 55 (52.8%), raised hematocrit in 52 (50%), and elevated aminotransferases, gamma GT in 100 (96%) patients. The overall mortality was 2.88%. In this series clinical history and examination supported by the triad of thrombocytopenia, raised hematocrit and elevated liver enzymes was sufficient for the early diagnosis of dengue hemorrhagic fever without waiting for dengue serology. (author)

  1. New approaches for the standardization and validation of a real-time qPCR assay using TaqMan probes for quantification of yellow fever virus on clinical samples with high quality parameters.

    Science.gov (United States)

    Fernandes-Monteiro, Alice G; Trindade, Gisela F; Yamamura, Anna M Y; Moreira, Otacilio C; de Paula, Vanessa S; Duarte, Ana Cláudia M; Britto, Constança; Lima, Sheila Maria B

    2015-01-01

    The development and production of viral vaccines, in general, involve several steps that need the monitoring of viral load throughout the entire process. Applying a 2-step quantitative reverse transcription real time PCR assay (RT-qPCR), viral load can be measured and monitored in a few hours. In this context, the development, standardization and validation of a RT-qPCR test to quickly and efficiently quantify yellow fever virus (YFV) in all stages of vaccine production are extremely important. To serve this purpose we used a plasmid construction containing the NS5 region from 17DD YFV to generate the standard curve and to evaluate parameters such as linearity, precision and specificity against other flavivirus. Furthermore, we defined the limits of detection as 25 copies/reaction, and quantification as 100 copies/reaction for the test. To ensure the quality of the method, reference controls were established in order to avoid false negative results. The qRT-PCR technique based on the use of TaqMan probes herein standardized proved to be effective for determining yellow fever viral load both in vivo and in vitro, thus becoming a very important tool to assure the quality control for vaccine production and evaluation of viremia after vaccination or YF disease.

  2. Valley-dependent band structure and valley polarization in periodically modulated graphene

    Science.gov (United States)

    Lu, Wei-Tao

    2016-08-01

    The valley-dependent energy band and transport property of graphene under a periodic magnetic-strained field are studied, where the time-reversal symmetry is broken and the valley degeneracy is lifted. The considered superlattice is composed of two different barriers, providing more degrees of freedom for engineering the electronic structure. The electrons near the K and K' valleys are dominated by different effective superlattices. It is found that the energy bands for both valleys are symmetric with respect to ky=-(AM+ξ AS) /4 under the symmetric superlattices. More finite-energy Dirac points, more prominent collimation behavior, and new crossing points are found for K' valley. The degenerate miniband near the K valley splits into two subminibands and produces a new band gap under the asymmetric superlattices. The velocity for the K' valley is greatly renormalized compared with the K valley, and so we can achieve a finite velocity for the K valley while the velocity for the K' valley is zero. Especially, the miniband and band gap could be manipulated independently, leading to an increase of the conductance. The characteristics of the band structure are reflected in the transmission spectra. The Dirac points and the crossing points appear as pronounced peaks in transmission. A remarkable valley polarization is obtained which is robust to the disorder and can be controlled by the strain, the period, and the voltage.

  3. Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence.

    Science.gov (United States)

    Terasaki, Kaori; Ramirez, Sydney I; Makino, Shinji

    2016-10-01

    Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice

  4. Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues.

    Directory of Open Access Journals (Sweden)

    Alec J Hirsch

    2017-03-01

    Full Text Available Zika virus (ZIKV, an emerging flavivirus, has recently spread explosively through the Western hemisphere. In addition to symptoms including fever, rash, arthralgia, and conjunctivitis, ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus. We report herein the results of ZIKV infection of adult rhesus macaques. Following subcutaneous infection, animals developed transient plasma viremia and viruria from 1-7 days post infection (dpi that was accompanied by the development of a rash, fever and conjunctivitis. Animals produced a robust adaptive immune response to ZIKV, although systemic cytokine response was minimal. At 7 dpi, virus was detected in peripheral nervous tissue, multiple lymphoid tissues, joints, and the uterus of the necropsied animals. Notably, viral RNA persisted in neuronal, lymphoid and joint/muscle tissues and the male and female reproductive tissues through 28 to 35 dpi. The tropism and persistence of ZIKV in the peripheral nerves and reproductive tract may provide a mechanism of subsequent neuropathogenesis and sexual transmission.

  5. Yellow fever: epidemiology and prevention.

    Science.gov (United States)

    Barnett, Elizabeth D

    2007-03-15

    Yellow fever continues to occur in regions of Africa and South America, despite the availability of effective vaccines. Recently, some cases of severe neurologic disease and multiorgan system disease have been described in individuals who received yellow fever vaccine. These events have focused attention on the need to define criteria for judicious use of yellow fever vaccine and to describe the spectrum of adverse events that may be associated with yellow fever vaccine. Describing host factors that would increase risk of these events and identifying potential treatment modalities for yellow fever and yellow fever vaccine-associated adverse events are subjects of intense investigation.

  6. A case of Crimean-Congo hemorrhagic fever complicated with acute pancreatitis.

    Science.gov (United States)

    Bastug, Aliye; Kayaaslan, Bircan; But, Ayse; Aslaner, Halide; Sertcelik, Ahmet; Akinci, Esragul; Onguru, Pinar; Yetkin, Meltem Arzu; Bodur, Hurrem

    2014-11-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease characterized by nonspecific symptoms like fever, myalgia, severe headache, nausea, vomiting, diarrhea, and abdominal pain. It can result in various complications during the course of the disease due to the diffuse endothelial injury involved in the pathogenesis of CCHF. Here we present a patient with CCHF complicated by acute pancreatitis, including pleural and intra-abdominal effusions. A 70-year-old patient was referred to our hospital from an endemic area with the suspicion of CCHF. The physical examination of the patient revealed high fever (38°C), somnolence, and petechial eruption. The diagnosis of case was confirmed with positive reverse transcriptase polymerase chain reaction (RT-PCR). The viral load of the patient was 4×10(9) copies/mL. On the fifth day of admission, upper abdominal pain, scleral ichter, and abdominal distention developed. The patient had abdominal tenderness with guarding. The laboratory tests revealed an amylase level of 1740 U/L (28-100), lipase level of 583 U/L (13-60), and total bilirubin level of 3.75 mg/dL (<0.3). The diagnosis of acute pancreatitis was confirmed with radiological findings. Until now, atypical presentations of CCHF have been reported in some case reports, but not acute pancreatitis. To the best of our knowledge, this is the first case of acute pancreatitis in the literature seen in the course of CCHF.

  7. Comparison of sampling techniques for Rift Valley Fever virus potential vectors, Aedes aegypti and Culex pipiens complex, in Ngorongoro District in northern Tanzania.

    Science.gov (United States)

    Mweya, Clement N; Kimera, Sharadhuli I; Karimuribo, Esron D; Mboera, Leonard E G

    2013-07-01

    We investigated mosquito sampling techniques with two types of traps and attractants at different time for trapping potential vectors for Rift Valley Fever virus. The study was conducted in six villages in Ngorongoro district in Tanzania from September to October 2012. A total of 1814 mosquitoes were collected, of which 738 were collected by CDC light traps and 1076 by Mosquito Magnet trapping technique. Of the collected mosquitoes, 12.46% (N = 226) were Aedes aegypti and 87.54% (N = 1588) were Culex pipiens complex. More mosquitoes were collected outdoors using Mosquito Magnets baited with octenol attractant, 36.38% (N =660) followed by indoor trapping using CDC light traps without attractant, 29.60% (N = 537). Most of Ae. aegypti mosquitoes were collected outdoor using Mosquito Magnets, 95% (N = 214) whereas Cx. pipiens complex were trapped both indoor using CDC light traps without attractant and outdoors using both CDC light traps baited with carbon dioxide (CO2) sachets and Mosquito Magnets. Analysis on the differences in abundance of mosquitoes trapped by different techniques using Generalized Linear Models was statistically significance at p-value < 0.05 for both species. Three hours mosquito collections show differing patterns in activity, most Ae. aegypti species were collected primarily during the first and last quarters of the day. Cx pipiens complex was active throughout the night, early evening and early morning then decreased markedly during the day time. The results presented in this paper emphasize the possibility of using Mosquito Magnets in order to efficiently capture these potential RVF vectors.

  8. Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg haemorrhagic fever on an airplane: results of a European expert consultation.

    Science.gov (United States)

    Gilsdorf, Andreas; Morgan, Dilys; Leitmeyer, Katrin

    2012-11-21

    Travel from countries where viral haemorrhagic fevers (VHF) are endemic has increased significantly over the past decades. In several reported VHF events on airplanes, passenger trace back was initiated but the scale of the trace back differed considerably. The absence of guidance documents to help the decision on necessity and scale of the trace back contributed to this variation.This article outlines the recommendations of an expert panel on Lassa fever, Ebola and Marburg haemorrhagic fever to the wider scientific community in order to advise the relevant stakeholders in the decision and scale of a possible passenger trace back. The evidence was collected through review of published literature and through the views of an expert panel. The guidance was agreed by consensus. Only a few events of VHF cases during air travel are reported in literature, with no documented infection in followed up contacts, so that no evidence of transmission of VHF during air travel exists to date. Based on this and the expert opinion, it was recommended that passenger trace back was undertaken only if: the index case had symptoms during the flight; the flight was within 21 days after detection of the event; and for Lassa fever if exposure of body fluid has been reported. The trace back should only be done after confirmation of the index case. Passengers and crew with direct contact, seat neighbours (+/- 1 seat), crew and cleaning personal of the section of the index case should be included in the trace back. No evidence has been found for the transmission of VHF in airplanes. This information should be taken into account, when a trace back decision has to be taken, because such a measure produces an enormous work load. The procedure suggested by the expert group can guide decisions made in future events, where a patient with suspected VHF infection travelled on a plane. However, the actual decision on start and scale of a trace back always lies in the hands of the responsible people

  9. Yellow Fever outbreak in Darfur, Sudan in October 2012; the initial outbreak investigation report.

    Science.gov (United States)

    Soghaier, Mohammed A; Hagar, Ahmed; Abbas, Mohammed A; Elmangory, Mutasim M; Eltahir, Khalid M; Sall, Amadou A

    2013-10-01

    Sudan is subject to repeated outbreaks, including Viral Hemorrhagic Fever (VHF), which is considered to be a very serious illness. Yellow Fever (YF) outbreaks in Sudan have been reported from the 1940s through 2005. In 2012, a new outbreak of YF occurred in the Darfur region. To identify the potential for an outbreak, to diagnose the disease and to be able to recognize its cause among the initial reported cases. >This is a descriptive and investigative field study that applies standard communicable disease outbreak investigation steps. The study involved clinical, serological, entomological and environmental surveys. The field investigation confirmed the outbreak and identified its cause to be YF. National surveillance systems should be strong enough to detect VHFs in a timely manner. Local health facilities should be prepared to promptly treat the initial cases because the case fatality ratios (CFRs) are usually very high among the index cases. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  10. Ebola Hemorrhagic Fever as a Public Health Emergency of International Concern; a Review Article.

    Science.gov (United States)

    Safari, Saeed; Baratloo, Alireza; Rouhipour, Alaleh; Ghelichkhani, Parisa; Yousefifard, Mahmood

    2015-01-01

    Ebola hemorrhagic fever (EHF) was first reported in 1976 with two concurrent outbreaks of acute viral hemorrhagic fever centered in Yambuku (near the Ebola river), Democratic Republic of Congo, and in Nzara, Sudan. The current outbreak of the Ebola virus was started by reporting the first case in March 2014 in the forest regions of southeastern Guinea. Due to infection rates raising over 13,000% within a 6-month period, Ebola is now considered as a global public health emergency and on August 8(th), 2014 the World Health Organization (WHO) declared the epidemic to be a Public Health Emergency of International Concern. With more than 5000 involved cases and nearly 3000 deaths, this event has turned into the largest and most dangerous Ebola virus outbreak in the world. Based on the above-mentioned, the present article aimed to review the virologic characteristics, transmission, clinical manifestation, diagnosis, treatment, and prevention of Ebola virus disease.

  11. Q fever in Greenland

    DEFF Research Database (Denmark)

    Koch, Anders; Svendsen, Claus Bo; Christensen, Jens Jorgen

    2010-01-01

    We report a patient with Q fever endocarditis in a settlement in eastern Greenland (Isortoq, Ammassalik area). Likely animal sources include sled dogs and seals. Q fever may be underdiagnosed in Arctic areas but may also represent an emerging infection.......We report a patient with Q fever endocarditis in a settlement in eastern Greenland (Isortoq, Ammassalik area). Likely animal sources include sled dogs and seals. Q fever may be underdiagnosed in Arctic areas but may also represent an emerging infection....

  12. Molecular diagnostics for lassa fever at Irrua specialist teaching hospital, Nigeria: lessons learnt from two years of laboratory operation.

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    Danny A Asogun

    Full Text Available BACKGROUND: Lassa fever is a viral hemorrhagic fever endemic in West Africa. However, none of the hospitals in the endemic areas of Nigeria has the capacity to perform Lassa virus diagnostics. Case identification and management solely relies on non-specific clinical criteria. The Irrua Specialist Teaching Hospital (ISTH in the central senatorial district of Edo State struggled with this challenge for many years. METHODOLOGY/PRINCIPAL FINDINGS: A laboratory for molecular diagnosis of Lassa fever, complying with basic standards of diagnostic PCR facilities, was established at ISTH in 2008. During 2009 through 2010, samples of 1,650 suspected cases were processed, of which 198 (12% tested positive by Lassa virus RT-PCR. No remarkable demographic differences were observed between PCR-positive and negative patients. The case fatality rate for Lassa fever was 31%. Nearly two thirds of confirmed cases attended the emergency departments of ISTH. The time window for therapeutic intervention was extremely short, as 50% of the fatal cases died within 2 days of hospitalization--often before ribavirin treatment could be commenced. Fatal Lassa fever cases were older (p = 0.005, had lower body temperature (p<0.0001, and had higher creatinine (p<0.0001 and blood urea levels (p<0.0001 than survivors. Lassa fever incidence in the hospital followed a seasonal pattern with a peak between November and March. Lassa virus sequences obtained from the patients originating from Edo State formed--within lineage II--a separate clade that could be further subdivided into three clusters. CONCLUSIONS/SIGNIFICANCE: Lassa fever case management was improved at a tertiary health institution in Nigeria through establishment of a laboratory for routine diagnostics of Lassa virus. Data collected in two years of operation demonstrate that Lassa fever is a serious public health problem in Edo State and reveal new insights into the disease in hospitalized patients.

  13. The yellow fever 17D virus as a platform for new live attenuated vaccines.

    Science.gov (United States)

    Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

    2014-01-01

    The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

  14. Mapping of zones potentially occupied by Aedes vexans and Culex poicilipes mosquitoes, the main vectors of Rift Valley fever in Senegal

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    Yves M. Tourre

    2008-11-01

    Full Text Available A necessary condition for Rift Valley fever (RVF emergence is the presence of Aedes (Aedimorphus vexans and Culex (Culex poicilipes mosquitoes carrying the arbovirus and responsible for the infection. This paper presents a detailed mapping in the Sahelian region of Senegal of zones potentially occupied by these mosquitoes (ZPOMs whose population density is directly linked to ecozones in the vicinity of small ponds. The vectors habitats and breeding sites have been characterized through an integrated approach combining remote sensing technology, geographical information systems, geographical positioning systems and field observations for proper geo-referencing. From five SPOT-5 images (~10 m spatial resolution with appropriate channels, a meridional composite transect of 290 x 60 km was first constructed at the height of the summer monsoon. Subsequent ZPOMs covered major ecozones from north to south with different hydrological environments and different patterns pond distributions. It was found that an overall area of 12,817 ha ± 10% (about 0.8% of the transect is occupied by ponds with an average ZPOM 17 times larger than this (212,813 ha ± 10% or about 14% of the transect. By comparing the very humid year of 2003 with 2006 which had just below normal rainfall, the ZPOMs inter-annual variability was analyzed in a sandy-clayey ecozone with an important hydrofossil riverbed within the Ferlo region of Senegal. Very probably contributing to an increased abundance of vectors by the end of August 2003, it was shown that the aggregate pond area was already about 22 times larger than in August 2006, corresponding to an approximately five times larger total ZPOM. The results show the importance of pin-pointing small ponds (sizes down to 0.1 ha and their geographical distribution in order to assess animal exposure to the RVF vectors.

  15. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

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    Joseph W. Golden

    2015-01-01

    Full Text Available Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs.

  16. Mechanisms of fever production and lysis: lessons from experimental LPS fever.

    Science.gov (United States)

    Roth, Joachim; Blatteis, Clark M

    2014-10-01

    Fever is a cardinal symptom of infectious or inflammatory insults, but it can also arise from noninfectious causes. The fever-inducing agent that has been used most frequently in experimental studies designed to characterize the physiological, immunological and neuroendocrine processes and to identify the neuronal circuits that underlie the manifestation of the febrile response is lipopolysaccharide (LPS). Our knowledge of the mechanisms of fever production and lysis is largely based on this model. Fever is usually initiated in the periphery of the challenged host by the immediate activation of the innate immune system by LPS, specifically of the complement (C) cascade and Toll-like receptors. The first results in the immediate generation of the C component C5a and the subsequent rapid production of prostaglandin E2 (PGE2). The second, occurring after some delay, induces the further production of PGE2 by induction of its synthesizing enzymes and transcription and translation of proinflammatory cytokines. The Kupffer cells (Kc) of the liver seem to be essential for these initial processes. The subsequent transfer of the pyrogenic message from the periphery to the brain is achieved by neuronal and humoral mechanisms. These pathways subserve the genesis of early (neuronal signals) and late (humoral signals) phases of the characteristically biphasic febrile response to LPS. During the course of fever, counterinflammatory factors, "endogenous antipyretics," are elaborated peripherally and centrally to limit fever in strength and duration. The multiple interacting pro- and antipyretic signals and their mechanistic effects that underlie endotoxic fever are the subjects of this review.

  17. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

    Science.gov (United States)

    Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

    2017-08-15

    Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR -/- ) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR -/- ) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR -/- λR -/- mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity. IMPORTANCE YFV-17D is a live attenuated flavivirus vaccine strain recognized as one of the most effective vaccines ever developed. However, the host and viral determinants governing YFV-17D attenuation and its potent immunogenicity are still unknown. Here, we analyzed the

  18. Discriminating fever behavior in house flies.

    Directory of Open Access Journals (Sweden)

    Robert D Anderson

    Full Text Available Fever has generally been shown to benefit infected hosts. However, fever temperatures also carry costs. While endotherms are able to limit fever costs physiologically, the means by which behavioral thermoregulators constrain these costs are less understood. Here we investigated the behavioral fever response of house flies (Musca domestica L. challenged with different doses of the fungal entomopathogen, Beauveria bassiana. Infected flies invoked a behavioral fever selecting the hottest temperature early in the day and then moving to cooler temperatures as the day progressed. In addition, flies infected with a higher dose of fungus exhibited more intense fever responses. These variable patterns of fever are consistent with the observation that higher fever temperatures had greater impact on fungal growth. The results demonstrate the capacity of insects to modulate the degree and duration of the fever response depending on the severity of the pathogen challenge and in so doing, balance the costs and benefits of fever.

  19. Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy

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    Eliana C.A. Benites

    2014-07-01

    Full Text Available OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc and University Hospital (HU, Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland, and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta for detection of influenza virus (H1N1, B, rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test. RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3% was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%, respiratory syncytial virus AB (8.7%, and coronavirus (6.8%. Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7 were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.

  20. Early intranuclear replication of African swine fever virus genome modifies the landscape of the host cell nucleus.

    Science.gov (United States)

    Simões, Margarida; Martins, Carlos; Ferreira, Fernando

    2015-12-02

    Although African swine fever virus (ASFV) replicates in viral cytoplasmic factories, the presence of viral DNA within the host cell nucleus has been previously reported to be essential for productive infection. Herein, we described, for the first time, the intranuclear distribution patterns of viral DNA replication events, preceding those that occur in the cytoplasmic compartment. Using BrdU pulse-labelling experiments, newly synthesized ASFV genomes were exclusively detected inside the host cell nucleus at the early phase of infection, both in swine monocyte-derived macrophages (MDMs) and Vero cells. From 8hpi onwards, BrdU labelling was only observed in ASFV cytoplasmic factories. Our results also show that ASFV specifically activates the Ataxia Telangiectasia Mutated Rad-3 related (ATR) pathway in ASFV-infected swine MDMs from the early phase of infection, most probably because ASFV genome is recognized as foreign DNA. Morphological changes of promyelocytic leukaemia nuclear bodies (PML-NBs), nuclear speckles and Cajal bodies were also found in ASFV-infected swine MDMs, strongly suggesting the viral modulation of cellular antiviral responses and cellular transcription, respectively. As described for other viral infections, the nuclear reorganization that takes place during ASFV infection may also provide an environment that favours its intranuclear replication events. Altogether, our results contribute for a better understanding of ASFV replication strategies, starting with an essential intranuclear DNA replication phase which induces host nucleus changes towards a successful viral infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

    Science.gov (United States)

    Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

    2016-02-01

    Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs.

  2. Molecular analysis of yellow fever virus 17DD vaccine strain

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    Paulo R. Post

    1991-06-01

    Full Text Available The Oswaldo Cruz Foundation produces most of the yellow fever (YF vaccine prepared world wide. As part of a broader approach to determine the genetic variability in YF l7D seeds and vaccines and its relevance to viral attenuation the 17DD virus was purifed directly from chick embryo homogenates which is the source of virus used for vaccination of millions of people in Brazil and other countries for half a century. Neutralization and hemagglutination tests showed that the purified virus is similar to the original stock. Furthermore, radioimmune precipitation of 35S-methionine-labeled viral proteins using mouse hyperimmune ascitic fluid revealed identical patterns for the purified 17DD virus and the YF l7D-204 strain except for the 17DD E protein which migrated slower on SDS-PAGE. This difference is likely to be due to N-linked glycosylation. Finally, comparison by northern blot nybridization of virion RNAs of purified 17DD with two other strains of YF virus only fenome-sized molecules for all three viruses. These observations suggest that vaccine phenotype is primarily associated with the accumulation of mutations.

  3. Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.

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    Elena Sandalova

    Full Text Available Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR, proliferation (Ki-67/Bcl-2(low and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV. CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-gamma during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response.

  4. 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.

  5. Severe Crimean-Congo haemorrhagic fever presented with massive retroperitoneal haemorrhage that recovered without antiviral treatment

    DEFF Research Database (Denmark)

    Gharabaghi, Mehrnaz Asadi; Chinikar, Sadegh; Ghiasi, Seyyed Mojtaba

    2011-01-01

    Crimean-Congo haemorrhagic fever (CCHF) is a tickborne viral zoonosis with up to 50% mortality in humans caused by CCHF virus belonging to the genus Nairovirus, family Bunyaviridae. The geographical distribution of CCHF cases corresponds closely with the distribution of principle tick vectors...... that is species of Hyaloma. The disease presents with non-specific febrile symptoms, but progress to a serious haemorrhagic syndrome that, soon after, a full blown multi organ failure may develop with prominent features of liver damage and bleeding diathesis. The authors present a case of a 39-year-old man...

  6. Rift Valley fever virus-infected mosquito ova and associated pathology: possible implications for endemic maintenance

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    Romoser WS

    2011-09-01

    Full Text Available William S Romoser1, Marco Neira Oviedo1, Kriangkrai Lerdthusnee2, Lisa A Patrican3, Michael J Turell4, David J Dohm4, Kenneth J Linthicum5, Charles L Bailey61Department of Biomedical Sciences, College of Osteopathic Medicine, Tropical Disease Institute, Ohio University, Athens, Ohio, USA; 2Department of Entomology, Faculty of Agriculture, Kasetsart University, Bangkok, Thailand; 3Infectious Disease Division, National Center for Medical Intelligence, Fort Detrick, Frederick, Maryland, USA; 4Department of Vector Assessment, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA; 5Center for Medical, Agricultural, and Veterinary Entomology, United States Department of Agriculture – Agricultural Research Service, Gainesville, Florida, USA; 6National Center for Biodefense and Infectious Disease, School of Systems Biology, College of Science, George Mason University, Manassas, Virginia, USABackground: Endemic/enzootic maintenance mechanisms like vertical transmission (pathogen passage from infected adults to their offspring are central in the epidemiology of zoonotic pathogens. In Kenya, Rift Valley fever virus (RVFV may be maintained by vertical transmission in ground-pool mosquitoes such as Aedes mcintoshi. RVFV can cause serious morbidity and mortality in humans and livestock. Past epidemics/epizootics have occurred in sub-Saharan Africa but, since the late 1970s, RVFV has also appeared in North Africa and the Middle East. Preliminary results revealed RVFV-infected eggs in Ae. mcintoshi after virus injection into the hemocoel after the first of two blood meals, justifying further study.Methods: Mosquitoes were collected from an artificially flooded water-catching depression along a stream in Kenya, shipped live to the USA, and studied using an immunocytochemical method for RVFV-antigen localization in mosquito sections.Results and conclusion: After virus injection into the

  7. Oropouche Fever: A Review.

    Science.gov (United States)

    Sakkas, Hercules; Bozidis, Petros; Franks, Ashley; Papadopoulou, Chrissanthy

    2018-04-04

    Oropouche fever is an emerging zoonotic disease caused by Oropouche virus (OROV), an arthropod transmitted Orthobunyavirus circulating in South and Central America. During the last 60 years, more than 30 epidemics and over half a million clinical cases attributed to OROV infection have been reported in Brazil, Peru, Panama, Trinidad and Tobago. OROV fever is considered the second most frequent arboviral febrile disease in Brazil after dengue fever. OROV is transmitted through both urban and sylvatic transmission cycles, with the primary vector in the urban cycle being the anthropophilic biting midge Culicoides paraensis . Currently, there is no evidence of direct human-to-human OROV transmission. OROV fever is usually either undiagnosed due to its mild, self-limited manifestations or misdiagnosed because its clinical characteristics are similar to dengue, chikungunya, Zika and yellow fever, including malaria as well. At present, there is no specific antiviral treatment, and in the absence of a vaccine for effective prophylaxis of human populations in endemic areas, the disease prevention relies solely on vector control strategies and personal protection measures. OROV fever is considered to have the potential to spread across the American continent and under favorable climatic conditions may expand its geographic distribution to other continents. In view of OROV's emergence, increased interest for formerly neglected tropical diseases and within the One Health concept, the existing knowledge and gaps of knowledge on OROV fever are reviewed.

  8. Haemorrhagic Fevers, Viral

    Science.gov (United States)

    ... plan 2015: West Africa Ebola outbreak Health worker Ebola infections in Guinea, Liberia and Sierra Leone Infection prevention and control guidance for care of Ebola patients Publications, technical guidance on Ebola Related topics ...

  9. Travelers' Health: Typhoid and Paratyphoid Fever

    Science.gov (United States)

    ... days should raise suspicion of typhoid or paratyphoid fever. Typhoid fever is a nationally notifiable disease. TREATMENT Specific ... typhoid-fever Table 3-21. Vaccines to prevent typhoid fever VACCINA- TION AGE (y) DOSE, MODE OF ADMINISTRA- ...

  10. Serological evaluation of Crimean-Congo hemorrhagic fever in humans with high-risk professions living in enzootic regions of Isfahan province of Iran and genetic analysis of circulating strains

    DEFF Research Database (Denmark)

    Chinikar, Sadegh; Ghiasi, Seyed Mojtaba; Naddaf, Saeed

    2012-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease that is asymptomatic in infected livestock, but causes a serious threat to humans with a mortality rate up to 50%. Although the CCHF virus (CCHFV) is often transmitted by ticks, livestock-to-human and human-to-human transmission a...

  11. Hard ticks (Ixodidae and Crimean-Congo hemorrhagic fever virus in south west of Iran.

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    Narges Sharifinia

    2015-03-01

    Full Text Available Ticks are vectors of some important arthropod-borne diseases in both fields of veterinary and medicine, such as Lyme, tularemia, Rocky Mountain spotted fever, and some types of encephalitis as well as Crimean Congo hemorrhagic fever (CCHF. Iran is known as one of the main foci of CCHF in west of Asia. This study was conducted in DarrehShahr County because of the development of animal husbandry in this area to detect the fauna and viral infection of the hard ticks of livestock. A cross-sectional survey was conducted during 2011-2012 with random sampling in four villages. A sample of ticks was subjected to RT-PCR method for detection of viral infection. During the study period, 592 Ixodidae ticks were collected and identified as seven species of Hyalomma asiaticum, Hy. marginatum, Hy. anatolicum, Hy. dromedarii, Hy. detritum, Rhipicephalus bursa and Rh. sanguineus. More than 20% of these ticks were examined to detect the genome of CCHF virus while 6.6% were positive. All species of Hyalomma were found to be positive. A high rate of livestock was found to be infected with hard ticks, which can act as the vectors of the CCHF disease. Regarding infection of all five Hyalomma species captured in this area, this genus should be considered as the main vector of CCHF. Planning control program can be performed based on the obtained data on seasonal activity of Ixodidae to prevent animal infestation as well as to reduce the risk of CCHF transmission.

  12. Management of a Lassa fever outbreak, Rhineland-Palatinate, Germany, 2016.

    Science.gov (United States)

    Ehlkes, Lutz; George, Maja; Samosny, Gerhard; Burckhardt, Florian; Vogt, Manfred; Bent, Stefan; Jahn, Klaus; Zanger, Philipp

    2017-09-01

    Due to rapid diagnosis and isolation of imported cases, community outbreaks of viral haemorrhagic fevers (VHF) are considered unlikely in industrialised countries. In March 2016, the first documented locally acquired case of Lassa fever (LF) outside Africa occurred, demonstrating the disease's potential as a cross-border health threat. We describe the management surrounding this case of LF in Rhineland-Palatinate - the German federal state where secondary transmission occurred. Twelve days after having been exposed to the corpse of a LF case imported from Togo, a symptomatic undertaker tested positive for Lassa virus RNA. Potential contacts were traced, categorised based on exposure risk, and monitored. Overall, we identified 21 contact persons with legal residency in Rhineland-Palatinate: seven related to the index case, 13 to the secondary case, and one related to both. The secondary case received treatment and recovered. Five contacts were quarantined and one was temporarily banned from work. No further transmission occurred. Based on the experience gained during the outbreak and a review of national and international guidelines, we conclude that exposure risk attributable to corpses may currently be underestimated, and we present suggestions that may help to improve the anti-epidemic response to imported VHF cases in industrialised countries.

  13. Genistein, a general kinase inhibitor, as a potential antiviral for arenaviral hemorrhagic fever as described in the Pirital virus-Syrian golden hamster model.

    Science.gov (United States)

    Vela, Eric M; Knostman, Katherine A; Mott, Jason M; Warren, Richard L; Garver, Jennifer N; Vela, Lela Johnson; Stammen, Rachelle L

    2010-09-01

    Arenaviruses are rodent-borne negative strand RNA viruses and infection of these viruses in humans may result in disease and hemorrhagic fever. To date, supportive care, ribavirin, and in some cases immune plasma remain the foremost treatment options for arenaviral hemorrhagic fever. Research with the hemorrhagic fever causing-arenaviruses usually requires a Biosafety level (BSL)-4 environment; however, surrogate animal model systems have been developed to preliminarily study and screen various vaccines and antivirals. The Syrian golden hamster-Pirital virus (PIRV) surrogate model of hemorrhagic fever provides an opportunity to test new antivirals in an ABSL-3 setting. Thus, we challenged hamsters, implanted with telemetry, with PIRV and observed viremia and tissue viral titers, and changes in core body temperature, hematology, clinical chemistry, and coagulation parameters. Physical signs of disease of the PIRV-infected hamsters included weight loss, lethargy, petechial rashes, epistaxis, ocular orbital and rectal hemorrhage, and visible signs of neurologic disorders. However, treating animals with genistein, a plant derived isoflavone and general kinase inhibitor, resulted in increased survival rates and led to an improved clinical profile. In all, the results from this study demonstrate the potential of a general kinase inhibitor genistein as an antiviral against arenaviral hemorrhagic fever. 2010 Elsevier B.V. All rights reserved.

  14. NNDSS - Table II. Salmonellosis (excluding typhoid fever and paratyphoid fever) to Shigellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Salmonellosis (excluding typhoid fever and paratyphoid fever) to Shigellosis - 2018. In this Table, provisional cases of selected notifiable...

  15. Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

    Science.gov (United States)

    Assunção-Miranda, I; Cruz-Oliveira, C; Neris, R L S; Figueiredo, C M; Pereira, L P S; Rodrigues, D; Araujo, D F F; Da Poian, A T; Bozza, M T

    2016-03-01

    To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. Heme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. These results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV. © 2016 The Society for Applied Microbiology.

  16. A crimean - congo hemorrhagic fever outbreak in northern balochistan

    International Nuclear Information System (INIS)

    Nadeem, M.; Ali, N.

    2007-01-01

    To describe the clinical characteristics, epidemiology, predictors of fatal outcome (PFO), and management effects of Crimean-Congo haemorrhagic fever (CCHF) patients during an outbreak in Northern Balochistan. Patients presenting with a fever of less than 2 weeks duration and bleeding manifestations were included. Clinical history was recorded and patients were placed on oral ribavirin, and hematological support. Diagnosis was established by PCR for CCHF or detection of CCHF specific IgM and IgG. Eighty-four patients were received, 34 (40.5%) were suspected of suffering from classical CCHF. All 34 (100%) patients presented with a history of fever and bleeding (epistaxis, gum bleeding, melena or haematuria). Mean platelet count was 30 x 109/L and mean ALT (alanine transferase) was 288 U/L. Among fatal cases, the mean platelet count was 18.4 x 10 9/L and ALT was 781 units/L. PCR for CCHF viral RNA performed on 10 patients was positive in 3 (30%) patients. CCHF specific IgM and IgG was positive in 17.6% (6/34). Four patients were brought in moribund condition and expired before treatment could be started, 4 patients expired during treatment and 76.5% (26/34) were cured. The overall mortality was 23.5% (8/34). Main predictors of fatal outcome were ALT z 150 units/L, activated partial thromboplastin time(aPT) z 60 seconds, prothrombin time (PT) z 34 seconds, aspartate transferase (AST) z 200 units/L, platelets o 20 x 109/L, and fibrinogen o 110 mg/dL. In this series of CCHF occurring in Northern parts of Balochistan, gastrointestinal tract bleeding was the worst prognostic factor associated with fatal outcome. Providing education to healthcare workers and at risk populations, hematological support, antiviral drugs, and barrier nursing may help reduce mortality. (author)

  17. Re-emergence of Rift Valley fever virus in Barkedji (Senegal, West Africa) in 2002-2003: identification of new vectors and epidemiological implications.

    Science.gov (United States)

    Ba, Y; Sall, A A; Diallo, D; Mondo, M; Girault, L; Dia, I; Diallo, M

    2012-09-01

    The Rift Valley fever virus (RVFV) is a threat that must not be neglected, as the consequences of RVFV are dramatic, both for human and animal health. This virus is a zoonotic virus that already has demonstrated a real capacity for re-emerging after long periods of silence, as observed in Barkedji (Senegal, West Africa) in 2002. In this article we present the 2nd emergence in Barkedji after the 1st manifestation in 1993, and for the 1st time the circulation of RVFV during 2 consecutive years among mosquito populations in Senegal. As part of the entomological surveillance program undertaken since 1990 to detect circulation of the RVFV in Barkedji, 108,336 mosquitoes belonging to 34 species and 5 genera were collected in 2002-2003. Aedes vexans and Culex poicilipes, previously known to be vectors of RVFV in Senegal, comprised 88.7% of the total collection. In 2002, Ae. vexans was the most abundant mosquito, followed by Cx. poicilipes; the opposite situation was observed in 2003. In 2002, 29 and 10 RVFV isolates were obtained from Cx. poicilipes (minimum infection rate [MIR] = 0.13%) and Ae. vexans (MIR = 0.02%) pools, respectively and the MIR for the 2 species were significantly different (chi2 = 34.65; df = 1, P < 0.001). In 2003, 7 RVFV strains were isolated from Cx. poicilipes (3, MIR = 0.03), Mansonia africana (2, MIR = 0.08), Ae. fowleri (1), and Ma. uniformis (1, MIR = 0.05). The 3 latter species were found to be associated with RVFV for the 1st time in Senegal. A significant decrease in MIR was observed from 2002 to 2003 (chi2 6.28; df = 1, P = 0.01) for Cx. poicilipes, the only species involved in the transmission during the 2 sampling years.

  18. Rift Valley Fever Vaccine Virus Clone 13 Is Able to Cross the Ovine Placental Barrier Associated with Foetal Infections, Malformations, and Stillbirths.

    Directory of Open Access Journals (Sweden)

    Birgit Makoschey

    2016-03-01

    Full Text Available Rift Valley fever virus (RVFV is a mosquito-borne pathogen that affects domesticated ruminants and occasionally humans. Classical RVF vaccines are based on formalin-inactivated virus or the live-attenuated Smithburn strain. The inactivated vaccine is highly safe but requires multiple administrations and yearly re-vaccinations. Although the Smithburn vaccine provides solid protection after a single vaccination, this vaccine is not safe for pregnant animals. An alternative live-attenuated vaccine, named Clone 13, carries a large natural deletion in the NSs gene which encodes the major virulence factor of the virus. The Clone 13 vaccine was previously shown to be safe for young lambs and calves. Moreover, a study in pregnant ewes suggested that the vaccine could also be applied safely during gestation. To anticipate on a possible future incursion of RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and pregnant ewes. In line with the guidelines from the World Organisation for Animal health (Office International des Epizooties, OIE and regulations of the European Pharmacopeia (EP, these studies were performed with an overdose. Our studies with lambs showed that Clone 13 dissemination within vaccinated animals is very limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in-contact sentinels and did not revert to virulence upon animal-to-animal passage. Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13 virus is able to spread to the fetus, resulting in malformations and stillbirths. Altogether, our results suggest that Clone 13 can be applied safely in lambs, but that caution should be taken when Clone 13 is used in pregnant animals, particularly during the first trimester of gestation.

  19. Safety and immunogenicity of Onderstepoort Biological Products’ Rift Valley fever Clone 13 vaccine in sheep and goats under field conditions in Senegal

    Directory of Open Access Journals (Sweden)

    Modou M. Lo

    2015-05-01

    Full Text Available This blinded field safety study was conducted in Senegal to assess safety and immunogenicity of administration of the registered dose of Rift Valley fever virus (RVFV Clone 13 vaccine (Onderstepoort Biological Products to sheep and goats of West African breeds under natural conditions. A total of 267 small ruminants (220 sheep, 47 goats were included; half received RVFV Clone 13 vaccine at the recommended dose and half received the diluent (as placebo only. The study was performed on three commercial farms in the northern and eastern region of Senegal in accordance with veterinary good clinical practices. The animals were observed daily for 3 days after vaccination, and then weekly for 1 year. In both sheep and goats vaccinated against RVFV seroconversion rates above 70% were recorded. No seroconversion related to RVFV was observed in placebo-treated animals. No statistically significant differences were determined between placebo and vaccinated groups for mean rectal temperatures for the first 3 days after administration (p > 0.05. No abnormal clinical signs related to treatment were noted, and only one slight injection site reaction was observed in one vaccinated animal for 2 days after vaccination. Out of 176 births assessed over 1 year (93 from the vaccinated group, 83 from the placebo group, 9 were abnormal in the placebo group and 3 in the vaccinated group (p > 0.05. The frequency of adverse events was similar in the placebo and vaccinated groups. RVFV Clone 13 vaccine administered according to the manufacturer’s instructions was safe and well tolerated in West African breeds of sheep and goats, including animals of approximately 6 months of age and pregnant females, under field conditions in Senegal. Antibody levels persisted up to 1 year after vaccination.

  20. Rift Valley Fever Vaccine Virus Clone 13 Is Able to Cross the Ovine Placental Barrier Associated with Foetal Infections, Malformations, and Stillbirths

    Science.gov (United States)

    Makoschey, Birgit; van Kilsdonk, Emma; Hubers, Willem R.; Vrijenhoek, Mieke P.; Smit, Marianne; Wichgers Schreur, Paul J.; Kortekaas, Jeroen; Moulin, Véronique

    2016-01-01

    Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants and occasionally humans. Classical RVF vaccines are based on formalin-inactivated virus or the live-attenuated Smithburn strain. The inactivated vaccine is highly safe but requires multiple administrations and yearly re-vaccinations. Although the Smithburn vaccine provides solid protection after a single vaccination, this vaccine is not safe for pregnant animals. An alternative live-attenuated vaccine, named Clone 13, carries a large natural deletion in the NSs gene which encodes the major virulence factor of the virus. The Clone 13 vaccine was previously shown to be safe for young lambs and calves. Moreover, a study in pregnant ewes suggested that the vaccine could also be applied safely during gestation. To anticipate on a possible future incursion of RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and pregnant ewes. In line with the guidelines from the World Organisation for Animal health (Office International des Epizooties, OIE) and regulations of the European Pharmacopeia (EP), these studies were performed with an overdose. Our studies with lambs showed that Clone 13 dissemination within vaccinated animals is very limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in-contact sentinels and did not revert to virulence upon animal-to-animal passage. Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13 virus is able to spread to the fetus, resulting in malformations and stillbirths. Altogether, our results suggest that Clone 13 can be applied safely in lambs, but that caution should be taken when Clone 13 is used in pregnant animals, particularly during the first trimester of gestation. PMID:27031621