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Sample records for hemorrhagic fever virus

  1. Crimean-Congo Hemorrhagic Fever Virus in Bulgaria and Turkey

    Mertens, M.; Schuster, I.; Sas, M. A.; Vatansever, Z.; Hubálek, Zdeněk; Güven, E.; Deniz, A.; Georgiev, G.; Peshev, R.; Groschup, M. H.

    2016-01-01

    Roč. 16, č. 9 (2016), s. 619-623 ISSN 1530-3667 EU Projects: European Commission(XE) 261504 - EDENEXT Institutional support: RVO:68081766 Keywords : Crimean-Congo hemorrhagic fever virus: CCHFV * domestic animals * ELISA * epidemiology Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.045, year: 2016

  2. [Ebola and Marburg hemorrhagic fever viruses: update on filoviruses].

    Leroy, E; Baize, S; Gonzalez, J P

    2011-04-01

    The Ebola and Marburg viruses are the sole members of the Filoviridae family of viruses. They are characterized by a long filamentous form that is unique in the viral world. Filoviruses are among the most virulent pathogens currently known to infect humans. They cause fulminating disease characterized by acute fever followed by generalized hemorrhagic syndrome that is associated with 90% mortality in the most severe forms. Epidemic outbreaks of Marburg and Ebola viruses have taken a heavy toll on human life in Central Africa and devastated large ape populations in Gabon and Republic of Congo. Since their discovery in 1967 (Marburg) and 1976 (Ebola), more than 2,300 cases and 1,670 deaths have been reported. These numbers pale in comparison with the burden caused by malnutrition or other infectious disease scourges in Africa such as malaria, cholera, AIDS, dengue or tuberculosis. However, due to their extremely high lethality, association with multifocal hemorrhaging and specificity to the African continent, these hemorrhagic fever viruses have given rise to great interest on the part not only of the international scientific community but also of the general public because of their perceived potential as biological weapons. Much research has been performed on these viruses and major progress has been made in knowledge of their ecology, epidemiology and physiopathology and in development of vaccine candidates and therapeutic schemes. The purpose of this review is to present the main developments in these particular fields in the last decade.

  3. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    Marko Zivcec

    2016-04-01

    Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

  4. Treating viral hemorrhagic fever.

    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

  5. Marburg hemorrhagic fever associated with multiple genetic lineages of virus

    Bausch, D G; Nichol, S T; Muyembe-Tamfum, J J

    2006-01-01

    Background An outbreak of Marburg hemorrhagic fever was first observed in a gold-mining village in northeastern Democratic Republic of the Congo in October 1998. Methods We investigated the outbreak of Marburg hemorrhagic fever most intensively in May and October 1999. Sporadic cases and short ch...

  6. Animal Models of Tick-Borne Hemorrhagic Fever Viruses

    Heinz Feldmann

    2013-05-01

    Full Text Available Tick-borne hemorrhagic fever viruses (TBHFV are detected throughout the African and Eurasian continents and are an emerging or re-emerging threat to many nations. Due to the largely sporadic incidences of these severe diseases, information on human cases and research activities in general have been limited. In the past decade, however, novel TBHFVs have emerged and areas of endemicity have expanded. Therefore, the development of countermeasures is of utmost importance in combating TBHFV as elimination of vectors and interrupting enzootic cycles is all but impossible and ecologically questionable. As in vivo models are the only way to test efficacy and safety of countermeasures, understanding of the available animal models and the development and refinement of animal models is critical in negating the detrimental impact of TBHFVs on public and animal health.

  7. Vectors of Crimean Congo Hemorrhagic Fever Virus in Iran

    Zakkyeh Telmadarraiy

    2015-10-01

    Full Text Available Background: Ticks are important vectors and reservoirs of Crimean Congo Hemorrhagic Fever (CCHF virus. Human beings may be infected whenever the normal life cycle of the infected ticks on non- human vertebrate hosts is interrupted by the undesirable presence of humans in the cycle. A total of 26 species of Argasid and Ixodid ticks have been recorded in Iran; including nine Hyalomma, two Rhipicephalus, two Dermacentor, five Haemaphysalis, two Boophilus, one Ixodes and two Argas as well as three Ornithodoros species as blood sucking ectoparasites of livestock and poultries. The present paper reviews tick vectors of CCHF virus in Iran, focusing on the role of ticks in different provinces of Iran using reverse transcription polymerase chain reaction (RT-PCR assay.Methods: During ten years study, 1054 tick specimens; including two species of Argasidae and 17 species of Ixodidae were examined for their infection to CCHF virus genome. The output of all studies as well as related publications were discussed in the current paper.Results: The results show that Rhipicephalus sanguineus, Hyalomma marginatum, H. anatolicum, H. asiaticum and H. dromedarii were known as the most frequent species which were positive for CCHF virus.Conclusion: The status of ticks which were positive for CCHF virus revealed that unlike the most common idea that Hyalomma species are the most important vectors of CCHF virus, other ticks including Rhipicephalus,Haemaphysalis and Dermacentor can be reservoir of this virus; thus, considering geographical distribution, type of host and environmental conditions, different tick control measurements should be carried out in areas with high incidence of CCHF disease.

  8. Vectors of Crimean Congo Hemorrhagic Fever Virus in Iran

    Telmadarraiy, Zakkyeh; Chinikar, Sadegh; Vatandoost, Hassan; Faghihi, Faezeh; Hosseini-Chegeni, Asadollah

    2015-01-01

    Background: Ticks are important vectors and reservoirs of Crimean Congo Hemorrhagic Fever (CCHF) virus. Human beings may be infected whenever the normal life cycle of the infected ticks on non-human vertebrate hosts is interrupted by the undesirable presence of humans in the cycle. A total of 26 species of Argasid and Ixodid ticks have been recorded in Iran; including nine Hyalomma, two Rhipicephalus, two Dermacentor, five Haemaphysalis, two Boophilus, one Ixodes and two Argas as well as three Ornithodoros species as blood sucking ectoparasites of livestock and poultries. The present paper reviews tick vectors of CCHF virus in Iran, focusing on the role of ticks in different provinces of Iran using reverse transcription polymerase chain reaction (RT-PCR) assay. Methods: During ten years study, 1054 tick specimens; including two species of Argasidae and 17 species of Ixodidae were examined for their infection to CCHF virus genome. The output of all studies as well as related publications were discussed in the current paper. Results: The results show that Rhipicephalus sanguineus, Hyalomma marginatum, H. anatolicum, H. asiaticum and H. dromedarii were known as the most frequent species which were positive for CCHF virus. Conclusion: The status of ticks which were positive for CCHF virus revealed that unlike the most common idea that Hyalomma species are the most important vectors of CCHF virus, other ticks including Rhipicephalus, Haemaphysalis and Dermacentor can be reservoir of this virus; thus, considering geographical distribution, type of host and environmental conditions, different tick control measurements should be carried out in areas with high incidence of CCHF disease. PMID:26623426

  9. Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions

    Anna Papa

    2017-05-01

    Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is transmitted to humans by bite of infected ticks or by direct contact with blood or tissues of viremic patients or animals. It causes to humans a severe disease with fatality up to 30%. The current knowledge about the vector-host-CCHFV interactions is very limited due to the high-level containment required for CCHFV studies. Among ticks, Hyalomma spp. are considered the most competent virus vectors. CCHFV evades the tick immune response, and following its replication in the lining of the tick's midgut, it is disseminated by the hemolymph in the salivary glands and reproductive organs. The introduction of salivary gland secretions into the host cells is the major route via which CCHFV enters the host. Following an initial amplification at the site of inoculation, the virus is spread to the target organs. Apoptosis is induced via both intrinsic and extrinsic pathways. Genetic factors and immune status of the host may affect the release of cytokines which play a major role in disease progression and outcome. It is expected that the use of new technology of metabolomics, transcriptomics and proteomics will lead to improved understanding of CCHFV-host interactions and identify potential targets for blocking the CCHFV transmission.

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

    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

  11. Crimean Congo Hemorrhagic Fever Virus and Alkhurma (Alkhumra) Virus in Ticks in Djibouti.

    Horton, Katherine C; Fahmy, Nermeen T; Watany, Noha; Zayed, Alia; Mohamed, Abro; Ahmed, Ammar Abdo; Rollin, Pierre E; Dueger, Erica L

    2016-10-01

    Crimean Congo hemorrhagic fever virus and Alkhumra virus, not previously reported in Djibouti, were detected among 141 (infection rate = 15.7 per 100, 95% CI: 13.4-18.1) tick pools from 81 (37%) cattle and 2 (infection rate = 0.2 per 100, 95% CI: 0.0-0.7) tick pools from 2 (1%) cattle, respectively, collected at an abattoir in 2010 and 2011.

  12. 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

    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.

  13. Ebola hemorrhagic Fever.

    Burnett, Mark W

    2014-01-01

    Ebola hemorrhagic fever is an often-fatal disease caused by a virus of the Filoviridae family, genus Ebolavirus. Initial signs and symptoms of the disease are nonspecific, often progressing on to a severe hemorrhagic illness. Special Operations Forces Medical Providers should be aware of this disease, which occurs in sporadic outbreaks throughout Africa. Treatment at the present time is mainly supportive. Special care should be taken to prevent contact with bodily fluids of those infected, which can transmit the virus to caregivers. 2014.

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

    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.

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

    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.

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

    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.

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

    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

  18. Chapare virus, a newly discovered arenavirus isolated from a fatal hemorrhagic fever case in Bolivia.

    Simon Delgado

    2008-04-01

    Full Text Available A small focus of hemorrhagic fever (HF cases occurred near Cochabamba, Bolivia, in December 2003 and January 2004. Specimens were available from only one fatal case, which had a clinical course that included fever, headache, arthralgia, myalgia, and vomiting with subsequent deterioration and multiple hemorrhagic signs. A non-cytopathic virus was isolated from two of the patient serum samples, and identified as an arenavirus by IFA staining with a rabbit polyvalent antiserum raised against South American arenaviruses known to be associated with HF (Guanarito, Machupo, and Sabiá. RT-PCR analysis and subsequent analysis of the complete virus S and L RNA segment sequences identified the virus as a member of the New World Clade B arenaviruses, which includes all the pathogenic South American arenaviruses. The virus was shown to be most closely related to Sabiá virus, but with 26% and 30% nucleotide difference in the S and L segments, and 26%, 28%, 15% and 22% amino acid differences for the L, Z, N, and GP proteins, respectively, indicating the virus represents a newly discovered arenavirus, for which we propose the name Chapare virus. In conclusion, two different arenaviruses, Machupo and Chapare, can be associated with severe HF cases in Bolivia.

  19. First international external quality assessment of molecular detection of Crimean-Congo hemorrhagic fever virus.

    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

  20. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever.

    Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J; Scott, Dana P; Feldmann, Heinz; Ebihara, Hideki

    2016-12-15

    Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

  1. Isolation and whole-genome sequencing of a Crimean-Congo hemorrhagic fever virus strain, Greece.

    Papa, Anna; Papadopoulou, Elpida; Tsioka, Katerina; Kontana, Anastasia; Pappa, Styliani; Melidou, Ageliki; Giadinis, Nektarios D

    2018-03-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) was isolated from a pool of two adult Rhipicephalus bursa ticks removed from a goat in 2015 in Greece. The strain clusters into lineage Europe 2 representing the second available whole-genome sequenced isolate of this lineage. CCHFV IgG antibodies were detected in 8 of 19 goats of the farm. Currently CCHFV is not associated with disease in mammals other than humans. Studies in animal models are needed to investigate the pathogenicity level of lineage Europe 2 and compare it with that of other lineages. Copyright © 2018 Elsevier GmbH. All rights reserved.

  2. 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

    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

  3. Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals.

    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.

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

    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.

  5. Protective role of host aquaporin 6 against Hazara virus, a model for Crimean-Congo hemorrhagic fever virus infection.

    Molinas, Andrea; Mirazimi, Ali; Holm, Angelika; Loitto, Vesa M; Magnusson, Karl-Eric; Vikström, Elena

    2016-04-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is an arthropod-borne pathogen that causes infectious disease with severe hemorrhagic manifestations in vascular system in humans. The proper function of the cells in the vascular system is critically regulated by aquaporins (AQP), water channels that facilitate fluxes of water and small solutes across membranes. With Hazara virus as a model for CCHFV, we investigated the effects of viruses on AQP6 and the impact of AQP6 on virus infectivity in host cells, using transiently expressed GFP-AQP6 cells, immunofluorescent assay for virus detection, epifluorescent imaging of living cells and confocal microscopy. In GFP-AQP6 expressing cells, Hazara virus reduced both the cellular and perinuclear AQP6 distribution and changed the cell area. Infection of human cell with CCHFV strain IbAR 10200 downregulated AQP6 expression at mRNA level. Interestingly, the overexpression of AQP6 in host cells decreased the infectivity of Hazara virus, speaking for a protective role of AQP6. We suggest the possibility for AQP6 being a novel player in the virus-host interactions, which may lead to less severe outcomes of an infection. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention.

    Ziying Han

    2015-10-01

    Full Text Available Hemorrhagic fever viruses, including the filoviruses (Ebola and Marburg and arenaviruses (Lassa and Junín viruses, are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines. Importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. Consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. An important cellular signal implicated previously in EBOV budding is calcium. Indeed, host cell calcium signals are increasingly being recognized to play a role in steps of entry, replication, and transmission for a range of viruses, but if and how filoviruses and arenaviruses mobilize calcium and the precise stage of virus transmission regulated by calcium have not been defined. Here we demonstrate that expression of matrix proteins from both filoviruses and arenaviruses triggers an increase in host cytoplasmic Ca2+ concentration by a mechanism that requires host Orai1 channels. Furthermore, we demonstrate that Orai1 regulates both VLP and infectious filovirus and arenavirus production and spread. Notably, suppression of the protein that triggers Orai activation (Stromal Interaction Molecule 1, STIM1 and genetic inactivation or pharmacological blockade of Orai1 channels inhibits VLP and infectious virus egress. These findings are highly significant as they expand our understanding of host mechanisms that may broadly control enveloped RNA virus budding, and they establish Orai and STIM1 as novel targets for broad-spectrum host-oriented therapeutics to combat these emerging BSL-4 pathogens and potentially other enveloped RNA viruses that bud via similar mechanisms.

  7. Genomic Characterization of Crimean-Congo Hemorrhagic Fever Virus in Hyalomma Tick from Spain, 2014.

    Cajimat, Maria N B; Rodriguez, Sergio E; Schuster, Isolde U E; Swetnam, Daniele M; Ksiazek, Thomas G; Habela, Miguel A; Negredo, Ana Isabel; Estrada-Peña, Agustín; Barrett, Alan D T; Bente, Dennis A

    2017-10-01

    Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne disease caused by CCHF virus (CCHFV). Ticks in the genus Hyalomma are the main vectors and reservoirs of CCHFV. In Spain, CCHFV was first detected in Hyalomma ticks from Cáceres in 2010. Subsequently, two autochthonous CCHF cases were reported in August 2016. In this study, we describe the characterization of the CCHFV genome directly from Hyalomma lusitanicum collected in Cáceres in 2014. Phylogenetic analyses reveal a close relationship with clade III strains from West Africa, with an estimated divergence time of 50 years. The results of this work suggest that CCHFV has been circulating in Spain for some time, and most likely originated from West Africa.

  8. Molecular Assay on Crimean Congo Hemorrhagic Fever Virus in Ticks (Ixodidae) Collected from Kermanshah Province, Western Iran

    Mohammadian, Maria; Chinikar, Sadegh; Telmadarraiy, Zakkyeh; Vatandoost, Hassan; Oshaghi, Mohammad Ali; Hanafi-Bojd, Ahmad Ali; Sedaghat, Mohammad Mehdi; Noroozi, Mehdi; Faghihi, Faezeh; Jalali, Tahmineh; Khakifirouz, Sahar; Shahhosseini, Nariman; Farhadpour, Firoozeh

    2016-01-01

    Background: Crimean-Congo Hemorrhagic Fever (CCHF) is a feverous and hemorrhagic disease endemic in some parts of Iran and caused by an arbovirus related to Bunyaviridae family and Nairovirusgenus. The main virus reservoir in the nature is ticks, however small vertebrates and a wide range of domestic and wild animals are regarded as reservoir hosts. This study was conducted to determine the infection rate of CCHF virus in hard ticks of Sarpole-Zahab County, Kermanshah province, west of Iran. Methods: From total number of 851 collected ticks from 8 villages, 131 ticks were selected randomlyand investigated for detection of CCHF virus using RT-PCR. Results: The virus was found in 3.8% of the tested ticks. Hyalommaanatolicum, H. asiaticum and Rhipicephalus sanguineus species were found to have viral infection, with the highest infection rate (11.11%) in Rh. sanguineus. Conclusion: These findings provide epidemiological evidence for planning control strategies of the disease in the study area. PMID:27308296

  9. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

    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.

  10. Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Kosovo.

    Luka Fajs

    Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is a zoonotic agent that causes severe, life-threatening disease, with a case fatality rate of 10-50%. It is the most widespread tick-borne virus in the world, with cases reported in Africa, Asia and Eastern Europe. CCHFV is a genetically diverse virus. Its genetic diversity is often correlated to its geographical origin. Genetic variability of CCHFV was determined within few endemic areas, however limited data is available for Kosovo. Furthermore, there is little information about the spatiotemporal genetic changes of CCHFV in endemic areas. Kosovo is an important endemic area for CCHFV. Cases were reported each year and the case-fatality rate is significantly higher compared to nearby regions. In this study, we wanted to examine the genetic variability of CCHFV obtained directly from CCHF-confirmed patients, hospitalized in Kosovo from 1991 to 2013. We sequenced partial S segment CCHFV nucleotide sequences from 89 patients. Our results show that several viral variants are present in Kosovo and that the genetic diversity is high in relation to the studied area. We also show that variants are mostly uniformly distributed throughout Kosovo and that limited evolutionary changes have occurred in 22 years. Our results also suggest the presence of a new distinct lineage within the European CCHF phylogenetic clade. Our study provide the largest number of CCHFV nucleotide sequences from patients in 22 year span in one endemic area.

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

    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

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

    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

  13. Hard ticks (Ixodidae and Crimean-Congo hemorrhagic fever virus in south west of Iran.

    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.

  14. [Crimean-Congo hemorrhagic fever].

    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.

  15. Epidemiological survey of Crimean Congo hemorrhagic fever virus in cattle in East Darfur State, Sudan.

    Ibrahim, Alaa M; Adam, Ibrahim A; Osman, Badreldin T; Aradaib, Imadeldin E

    2015-06-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by CCHF virus (CCHFV) of the genus Nairovirus in the family Bunyaviridae. CCHFV causes subclinical infection in domestic livestock and an often fatal hemorrhagic illness in humans, with approximately 30% mortality rates. In the present study, a cross-sectional serosurvey was conducted in a total of 282 randomly selected cattle from five localities in East Darfur State, Sudan. The exposure status to CCHF was determined using enzyme-linked immunosorbent assay (ELISA) for detection of CCHFV-specific IgG antibodies in cattle serum samples. The CCHFV-specific IgG antibodies were detected in 54 out of 282 animals, accounting for a 19.14% prevalence rate. Older cattle (>2 years of age) were approximately five times more likely to be infected with the virus (OR=4.90, CI=1.28-18.98, p-value=0.02). Heavily tick-infested cattle (ticks all over the body) were at 11 times higher at risk compared to tick-free animals (OR=11.11, CI=2.86-43.25, p-value=0.01). Grazing system is another factor affecting CCHF, where cattle grazing on open system were 27 times more at risk compared to other grazing systems (OR=27.22, CI=7.46-99.24, p-value=0.001). There was an association between localities and CCHF cattle (OR=0.24, CI=0.07-0.83, p-value=0.02). This study confirms the exposure of cattle to CCHF in East Darfur and identifies potential risk factors associated with the disease. Further epidemiological studies and improved surveillance are urgently needed to prevent a possible outbreak of CCHF among humans in the Darfur region of Sudan. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Molecular detection of Crimean-Congo hemorrhagic fever virus in ticks, Greece, 2012-2014.

    Papa, Anna; Kontana, Anastasia; Tsioka, Katerina; Chaligiannis, Ilias; Sotiraki, Smaragda

    2017-11-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans mainly through the bite of infected ticks. In Greece, only one clinical case has been observed, in 2008, but the seroprevalence in humans is relatively high (4.2%). To have a first insight into the circulation of CCHFV in Greece, 2000 ticks collected from livestock during 2012-2014 were tested. CCHFV was detected in 36 of the 1290 (2.8%) tick pools (1-5 ticks per pool). Two genetic lineages were identified: Europe 1 and Europe 2. Most Europe 1 sequences were obtained from Rhipicephalus sanguineus sensu lato ticks, while most Europe 2 sequences were recovered from Rhipicephalus bursa ticks. The number of collected Hyalomma marginatum ticks (the principal vector of CCHFV) was low (0.5% of ticks) and all were CCHFV negative. Since it is not known how efficient ticks of the Rhipicephalus genus are as vectors of the virus, laboratory studies will be required to explore the role of Rhipicephalus spp. ticks in CCHFV maintenance and transmission.

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

    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.

  18. Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda

    Towner, Jonathan S.; Sealy, Tara K.; Khristova, Marina L.; Albariño, César G.; Conlan, Sean; Reeder, Serena A.; Quan, Phenix-Lan; Lipkin, W. Ian; Downing, Robert; Tappero, Jordan W.; Okware, Samuel; Lutwama, Julius; Bakamutumaho, Barnabas; Kayiwa, John; Comer, James A.; Rollin, Pierre E.; Ksiazek, Thomas G.; Nichol, Stuart T.

    2008-01-01

    Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA) and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus) distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines. PMID:19023410

  19. Meta-Analysis of High-Throughput Datasets Reveals Cellular Responses Following Hemorrhagic Fever Virus Infection

    Gavin C. Bowick

    2011-05-01

    Full Text Available The continuing use of high-throughput assays to investigate cellular responses to infection is providing a large repository of information. Due to the large number of differentially expressed transcripts, often running into the thousands, the majority of these data have not been thoroughly investigated. Advances in techniques for the downstream analysis of high-throughput datasets are providing additional methods for the generation of additional hypotheses for further investigation. The large number of experimental observations, combined with databases that correlate particular genes and proteins with canonical pathways, functions and diseases, allows for the bioinformatic exploration of functional networks that may be implicated in replication or pathogenesis. Herein, we provide an example of how analysis of published high-throughput datasets of cellular responses to hemorrhagic fever virus infection can generate additional functional data. We describe enrichment of genes involved in metabolism, post-translational modification and cardiac damage; potential roles for specific transcription factors and a conserved involvement of a pathway based around cyclooxygenase-2. We believe that these types of analyses can provide virologists with additional hypotheses for continued investigation.

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

    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.

  1. Molecular epidemiology of Crimean- Congo hemorrhagic fever virus genome isolated from ticks of Hamadan province of Iran

    Tahmasebi, F; Ghiasi, Seyed Mojtaba; Mostafavi, E

    2010-01-01

    BACKGROUND & OBJECTIVES: Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne member of the genus Nairovirus, family Bunyaviridae. CCHFV has been isolated from at least 31 different tick species. The virus is transmitted through the bite of an infected tick, or by direct contact with CCHFV...... to each other. Even though they clustered in the same group with the strain circulating in Iran, they had a closer relationship to the Matin strain. INTERPRETATION & CONCLUSION: Vector control programs should be applied for reducing population density of potential tick vectors in this province. Further...

  2. Crimean-Congo Hemorrhagic Fever

    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.

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

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

    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.

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

    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).

  6. Genetic Diversity of Crimean Congo Hemorrhagic Fever Virus Strains from Iran

    Sadegh Chinikar

    2016-01-01

    Full Text Available Background: Crimean Congo hemorrhagic fever virus (CCHFV is a member of the Bunyaviridae family and Nairovirus genus. It has a negative-sense, single stranded RNA genome approximately 19.2 kb, containing the Small, Medium, and Large segments. CCHFVs are relatively divergent in their genome sequence and grouped in seven distinct clades based on S-segment sequence analysis and six clades based on M-segment sequences. Our aim was to obtain new insights into the molecular epidemiology of CCHFV in Iran.Methods: We analyzed partial and complete nucleotide sequences of the S and M segments derived from 50 Iranian patients. The extracted RNA was amplified using one-step RT-PCR and then sequenced. The sequences were ana­lyzed using Mega5 software.Results: Phylogenetic analysis of partial S segment sequences demonstrated that clade IV-(Asia 1, clade IV-(Asia 2 and clade V-(Europe accounted for 80 %, 4 % and 14 % of the circulating genomic variants of CCHFV in Iran respectively. However, one of the Iranian strains (Iran-Kerman/22 was associated with none of other sequences and formed a new clade (VII. The phylogenetic analysis of complete S-segment nucleotide sequences from selected Ira­nian CCHFV strains complemented with representative strains from GenBank revealed similar topology as partial sequences with eight major clusters. A partial M segment phylogeny positioned the Iranian strains in either associa­tion with clade III (Asia-Africa or clade V (Europe.Conclusion: The phylogenetic analysis revealed subtle links between distant geographic locations, which we pro­pose might originate either from international livestock trade or from long-distance carriage of CCHFV by infected ticks via bird migration.

  7. Crimean-Congo hemorrhagic fever virus in ticks collected from livestock in Albania.

    Papa, Anna; Velo, Enkeleda; Kadiaj, Perparim; Tsioka, Katerina; Kontana, Anastasia; Kota, Majlinda; Bino, Silvia

    2017-10-01

    Albania is a Balkan country endemic for Crimean-Congo hemorrhagic fever (CCHF). It was shown previously that CCHF virus (CCHFV) sequences from Albanian patients cluster into Europe 1 clade. Aim of the present study was to test for CCHFV ticks collected in several regions of Albania, and to determine the genetic lineage(s) of the CCHFV strains in relation with their geographic distribution. A total of 726 ticks (366 Hyalomma marginatum, 349 Rhipicephalus bursa and 11 Rhipicephalus sanguineus) collected from livestock during 2007-2014 were included in the study. Thirty of 215 (13.9%) tick pools were positive for CCHFV. Lineage Europe 1 was detected in H. marginatum ticks collected in the endemic region of Albania, while lineage Europe 2 was detected mainly in R. bursa ticks in various regions of the country. Both genetic lineages were detected in the CCHF endemic area (northeastern Albania), while only Europe 2 lineage was detected in the south of the country. A higher genetic diversity was seen among Europe 2 than Europe 1 Albanian sequences (mean distance 3.7% versus 1%), suggesting a longer evolution of AP92-like strains (Europe 2) in their tick hosts. The present study shows that besides CCHFV lineage Europe 1, lineage Europe 2 is also present in Albania. Combined with results from recent studies, it is concluded that lineage Europe 2 is widely spread in the Balkans and Turkey, and is associated mainly with R. bursa ticks (at least in this region). Its pathogenicity and impact to the public health remain to be elucidated. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Molecular (ticks) and serological (humans) study of Crimean-Congo hemorrhagic fever virus in the Iberian Peninsula, 2013-2015.

    Palomar, Ana M; Portillo, Aránzazu; Santibáñez, Sonia; García-Álvarez, Lara; Muñoz-Sanz, Agustín; Márquez, Francisco J; Romero, Lourdes; Eiros, José M; Oteo, José A

    Crimean-Congo hemorrhagic fever (CCHF) is a viral disease, mainly transmitted through tick bite, of great importance in Public Health. In Spain, Crimean-Congo hemorrhagic fever virus (CCHFV) was detected for the first time in 2010 in Hyalomma lusitanicum ticks collected from deer in Cáceres. The aim of this study was to investigate the presence of CCHFV in ticks from Cáceres, and from other Spanish areas, and to evaluate the presence of antibodies against the virus in individuals exposed to tick bites. A total of 2053 ticks (1333 Hyalomma marginatum, 680 H. lusitanicum and 40 Rhipicephalus bursa) were analyzed using molecular biology techniques (PCR) for CCHFV detection. The determination of specific IgG antibodies against CCHFV in 228 serum samples from humans with regular contact with ticks (at risk of acquiring the infection) was performed by indirect immunofluorescence assay. The CCHFV was not amplified in ticks, nor were antibodies against the virus found in the serum samples analyzed. The absence of the CCHFV in the ticks studied and the lack of antibodies against the virus in individuals exposed to tick bites would seem to suggest a low risk of acquisition of human infection by CCHFV in Spain. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Molecular Assay on Crimean Congo Hemorrhagic Fever Virus in Ticks (Ixodidae Collected from Kermanshah Province, Western Iran

    Maria Mohammadian

    2016-01-01

    Full Text Available Background: Crimean-Congo Hemorrhagic Fever (CCHF is a feverous and hemorrhagic disease endemic in some parts of Iran and caused by an arbovirus related to Bunyaviridae family and Nairovirusgenus. The main virus reser­voir in the nature is ticks, however small vertebrates and a wide range of domestic and wild animals are regarded as reservoir hosts. This study was conducted to determine the infection rate of CCHF virus in hard ticks of Sarpole-Zahab County, Kermanshah province, west of Iran.Methods: From total number of 851 collected ticks from 8 villages, 131 ticks were selected randomlyand investi­gated for detection of CCHF virus using RT-PCR.Results: The virus was found in 3.8% of the tested ticks. Hyalommaanatolicum, H.asiaticum and Rhipicephalus sanguineus species were found to have viral infection, with the highest infection rate (11.11% in Rh. sanguineus.Conclusion: These findings provide epidemiological evidence for planning control strategies of the disease in the study area.

  10. Genistein, a general kinase inhibitor, as a potential antiviral for arenaviral hemorrhagic fever as described in the Pirital virus-Syrian golden hamster model.

    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.

  11. Crimean-Congo Hemorrhagic Fever Virus Suppresses Innate Immune Responses via a Ubiquitin and ISG15 Specific Protease

    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.

  12. Hemorrhagic Fever Caused by a Novel Bunyavirus in China: Pathogenesis and Correlates of Fatal Outcome

    Zhang, Yong-Zhen; He, Yong-Wen; Dai, Yong-An; Xiong, Yanwen; Zheng, Han; Zhou, Dun-Jin; Li, Juan; Sun, Qiangzheng; Luo, Xue-Lian; Cheng, Yu-Li; Qin, Xin-Cheng; Tian, Jun-Hua; Chen, Xiao-Ping; Yu, Bin; Jin, Dong; Guo, Wen-Ping; Li, Wei; Wang, Wen; Peng, Jin-Song; Zhang, Guo-Bin; Zhang, Shaomin; Chen, Xiao-Min; Wang, Yan; Li, Ming-Hui; Li, Zhenjun; Lu, Shan; Ye, Changyun; de Jong, Menno D.; Xu, Jianguo

    2012-01-01

    Background. Hemorrhagic fever-like illness caused by a novel Bunyavirus, Huaiyangshan virus (HYSV, also known as Severe Fever with Thrombocytopenia virus [SFTSV] and Fever, Thrombocytopenia and Leukopenia Syndrome [FTLS]), has recently been described in China. Methods. Patients with

  13. Evidence for widespread infection of African bats with Crimean-Congo hemorrhagic fever-like viruses

    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

  14. Functional analyses of the three simian hemorrhagic fever virus nonstructural protein 1 papain-like proteases.

    Vatter, Heather A; Di, Han; Donaldson, Eric F; Radu, Gertrud U; Maines, Taronna R; Brinton, Margo A

    2014-08-01

    The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural polyprotein 1a is predicted to encode three papain-like proteases (PLP1α, PLP1β, and PLP1γ). Catalytic residues and cleavage sites for each of the SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with each other as well as with those of other arteriviruses, and the predicted catalytic residues were shown to be proximal by homology modeling of the SHFV nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal structures. The functionality of the predicted catalytic Cys residues and cleavage sites was tested by analysis of the autoproteolytic products generated in in vitro transcription/translation reactions done with wild-type or mutant SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy analysis of selected immunoprecipitated cleavage products. The data showed that each of the three SHFV PLP1s is an active protease. Cys63 was identified as the catalytic Cys of SHFV PLP1α and is adjacent to an Ala instead of the canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1γ is able to cleave at both downstream and upstream nsp1 junction sites. Although intermediate precursor polyproteins as well as alternative products generated by each of the SHFV PLP1s cleaving at sites within the N-terminal region of nsp1β were produced in the in vitro reactions, Western blotting of SHFV-infected, MA104 cell lysates with SHFV nsp1 protein-specific antibodies detected only the three mature nsp1 proteins. SHFV is unique among arteriviruses in having three N-terminal papain-like protease 1 (PLP1) domains. Other arteriviruses encode one or two active PLP1s. This is the first functional study of the SHFV PLP1s. Analysis of the products of in vitro autoprocessing of an N-terminal SHFV nonstructural 1a polypeptide fragment showed that each of the three SHFV PLP1s is active, and the predicted catalytic Cys residues and cleavage sites

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

    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.

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

    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.

  17. Biosafety standards for working with Crimean-Congo hemorrhagic fever virus.

    Weidmann, Manfred; Avsic-Zupanc, Tatjana; Bino, Silvia; Bouloy, Michelle; Burt, Felicity; Chinikar, Sadegh; Christova, Iva; Dedushaj, Isuf; El-Sanousi, Ahmed; Elaldi, Nazif; Hewson, Roger; Hufert, Frank T; Humolli, Isme; Jansen van Vuren, Petrus; Koçak Tufan, Zeliha; Korukluoglu, Gülay; Lyssen, Pieter; Mirazimi, Ali; Neyts, Johan; Niedrig, Matthias; Ozkul, Aykut; Papa, Anna; Paweska, Janusz; Sall, Amadou A; Schmaljohn, Connie S; Swanepoel, Robert; Uyar, Yavuz; Weber, Friedemann; Zeller, Herve

    2016-11-01

    In countries from which Crimean-Congo haemorrhagic fever (CCHF) is absent, the causative virus, CCHF virus (CCHFV), is classified as a hazard group 4 agent and handled in containment level (CL)-4. In contrast, most endemic countries out of necessity have had to perform diagnostic tests under biosafety level (BSL)-2 or -3 conditions. In particular, Turkey and several of the Balkan countries have safely processed more than 100 000 samples over many years in BSL-2 laboratories. It is therefore advocated that biosafety requirements for CCHF diagnostic procedures should be revised, to allow the tests required to be performed under enhanced BSL-2 conditions with appropriate biosafety laboratory equipment and personal protective equipment used according to standardized protocols in the countries affected. Downgrading of CCHFV research work from CL-4, BSL-4 to CL-3, BSL-3 should also be considered.

  18. Mice orally immunized with a transgenic plant expressing the glycoprotein of Crimean-Congo hemorrhagic fever virus

    Ghiasi, Seyed Mojtaba; Salmanian, A H; Chinikar, S

    2011-01-01

    in their serum and feces, respectively. The mice in the fed/boosted group showed a significant rise in specific IgG antibodies after a single boost. Our results imply that oral immunization of animals with edible materials from transgenic plants is feasible, and further assessments are under way. In addition......While Crimean-Congo hemorrhagic fever (CCHF) has a high mortality rate in humans, the associated virus (CCHFV) does not induce clinical symptoms in animals, but animals play an important role in disease transmission to humans. Our aim in this study was to examine the immunogenicity of the CCHFV...... glycoprotein when expressed in the root and leaf of transgenic plants via hairy roots and stable transformation of tobacco plants, respectively. After confirmatory analyses of transgenic plant lines and quantification of the expressed glycoprotein, mice were either fed with the transgenic leaves or roots, fed...

  19. Hemorrhagic Fevers - Multiple Languages

    ... dialect) (繁體中文) Expand Section Vaccine Information Statement (VIS) -- Yellow Fever Vaccine: What You Need to Know - English PDF Vaccine Information Statement (VIS) -- Yellow Fever Vaccine: What You Need to Know - 繁體中文 (Chinese, Traditional ( ...

  20. Genetic characterization of Erve virus, a European Nairovirus distantly related to Crimean-Congo hemorrhagic fever virus

    Dilcher, Meik; Koch, Andrea; Hasib, Lekbira; Dobler, Gerhard; Hufert, Frank T.; Weidmann, Manfred

    2012-01-01

    Erve virus (ERVEV) is a European Nairovirus that is suspected to cause severe headache (thunderclap headache) and intracerebral hemorrhage. The mode of transmission to humans (ticks or mosquitoes) is still unknown. Currently, no standardized testing method for ERVEV exists and only a small partial sequence of the polymerase gene is available. Here, we present the first complete genome sequence of ERVEV S, M, and L segments. Phylogenetic comparison of the amino acid sequence of the L-protein (...

  1. Crimean–Congo Hemorrhagic Fever Virus and Borrelia burgdorferi sensu lato in Ticks from Kosovo and Albania

    Sherifi, Kurtesh; Rexhepi, Agim; Berxholi, Kristaq; Mehmedi, Blerta; Gecaj, Rreze M.; Hoxha, Zamira; Joachim, Anja; Duscher, Georg G.

    2018-01-01

    Tick-borne diseases pose a serious threat to human health in South-Eastern Europe, including Kosovo. While Crimean–Congo hemorrhagic fever (CCHF) is a well-known emerging infection in this area, there are no accurate data on Lyme borreliosis and tick-borne encephalitis (TBE). Therefore, we sampled and tested 795 ticks. Ixodes ricinus (n = 218), Dermacentor marginatus (n = 98), and Haemaphysalis spp. (n = 24) were collected from the environment by flagging (all from Kosovo), while Hyalomma marginatum (n = 199 from Kosovo, all from Kosovo) and Rhipicephalus bursa (n = 130, 126 from Albania) could be collected only by removal from animal pasture and domestic ruminants. Ticks were collected in the years 2014/2015 and tested for viral RNA of CCHF and TBE viruses, as well as for DNA of Borrelia burgdorferi sensu lato by real-time PCR. In Kosovo, nine ticks were positive for RNA of Crimean–Congo hemorrhagic fever virus and seven for DNA of B. burgdorferi s. l. None of the ticks tested positive for TBEV. CCHF virus was detected in one H. marginatum male specimen collected while feeding on grazing cattle from the Prizren region and in eight R. bursa specimens (five females and three males collected while feeding on grazing sheep and cattle) from the Prishtina region (Kosovo). B. burgdorferi s. l. was detected in seven questing ticks (four male and one female D. marginatus, two I. ricinus one female and one male) from the Mitrovica region (Kosovo). Our study confirmed that CCHF virus is circulating in Kosovo mainly in H. marginatum and R. bursa in the central areas of the country. B. burgdorferi s. l. was found in its major European host tick, I. ricinus, but also in D. marginatus, in the north of the Kosovo. In order to prevent the spread of these diseases and better control of the tick-borne infections, an improved vector surveillance and testing of ticks for the presence of pathogens needs to be established. PMID:29560357

  2. Crimean–Congo Hemorrhagic Fever Virus and Borrelia burgdorferi sensu lato in Ticks from Kosovo and Albania

    Kurtesh Sherifi

    2018-03-01

    Full Text Available Tick-borne diseases pose a serious threat to human health in South-Eastern Europe, including Kosovo. While Crimean–Congo hemorrhagic fever (CCHF is a well-known emerging infection in this area, there are no accurate data on Lyme borreliosis and tick-borne encephalitis (TBE. Therefore, we sampled and tested 795 ticks. Ixodes ricinus (n = 218, Dermacentor marginatus (n = 98, and Haemaphysalis spp. (n = 24 were collected from the environment by flagging (all from Kosovo, while Hyalomma marginatum (n = 199 from Kosovo, all from Kosovo and Rhipicephalus bursa (n = 130, 126 from Albania could be collected only by removal from animal pasture and domestic ruminants. Ticks were collected in the years 2014/2015 and tested for viral RNA of CCHF and TBE viruses, as well as for DNA of Borrelia burgdorferi sensu lato by real-time PCR. In Kosovo, nine ticks were positive for RNA of Crimean–Congo hemorrhagic fever virus and seven for DNA of B. burgdorferi s. l. None of the ticks tested positive for TBEV. CCHF virus was detected in one H. marginatum male specimen collected while feeding on grazing cattle from the Prizren region and in eight R. bursa specimens (five females and three males collected while feeding on grazing sheep and cattle from the Prishtina region (Kosovo. B. burgdorferi s. l. was detected in seven questing ticks (four male and one female D. marginatus, two I. ricinus one female and one male from the Mitrovica region (Kosovo. Our study confirmed that CCHF virus is circulating in Kosovo mainly in H. marginatum and R. bursa in the central areas of the country. B. burgdorferi s. l. was found in its major European host tick, I. ricinus, but also in D. marginatus, in the north of the Kosovo. In order to prevent the spread of these diseases and better control of the tick-borne infections, an improved vector surveillance and testing of ticks for the presence of pathogens needs to be established.

  3. Crimean-Congo Hemorrhagic Fever Virus and Borrelia burgdorferi sensu lato in Ticks from Kosovo and Albania.

    Sherifi, Kurtesh; Rexhepi, Agim; Berxholi, Kristaq; Mehmedi, Blerta; Gecaj, Rreze M; Hoxha, Zamira; Joachim, Anja; Duscher, Georg G

    2018-01-01

    Tick-borne diseases pose a serious threat to human health in South-Eastern Europe, including Kosovo. While Crimean-Congo hemorrhagic fever (CCHF) is a well-known emerging infection in this area, there are no accurate data on Lyme borreliosis and tick-borne encephalitis (TBE). Therefore, we sampled and tested 795 ticks. Ixodes ricinus ( n  = 218), Dermacentor marginatus ( n  = 98), and Haemaphysalis spp. ( n  = 24) were collected from the environment by flagging (all from Kosovo), while Hyalomma marginatum ( n  = 199 from Kosovo, all from Kosovo) and Rhipicephalus bursa ( n  = 130, 126 from Albania) could be collected only by removal from animal pasture and domestic ruminants. Ticks were collected in the years 2014/2015 and tested for viral RNA of CCHF and TBE viruses, as well as for DNA of Borrelia burgdorferi sensu lato by real-time PCR. In Kosovo, nine ticks were positive for RNA of Crimean-Congo hemorrhagic fever virus and seven for DNA of B. burgdorferi s. l. None of the ticks tested positive for TBEV. CCHF virus was detected in one H. marginatum male specimen collected while feeding on grazing cattle from the Prizren region and in eight R. bursa specimens (five females and three males collected while feeding on grazing sheep and cattle) from the Prishtina region (Kosovo). B. burgdorferi s. l. was detected in seven questing ticks (four male and one female D. marginatus , two I. ricinus one female and one male) from the Mitrovica region (Kosovo). Our study confirmed that CCHF virus is circulating in Kosovo mainly in H. marginatum and R. bursa in the central areas of the country. B. burgdorferi s. l. was found in its major European host tick, I. ricinus , but also in D. marginatus , in the north of the Kosovo. In order to prevent the spread of these diseases and better control of the tick-borne infections, an improved vector surveillance and testing of ticks for the presence of pathogens needs to be established.

  4. Immunological features underlying viral hemorrhagic fevers.

    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.

  5. Inherent dynamics within the Crimean-Congo Hemorrhagic fever virus protease are localized to the same region as substrate interactions

    Eisenmesser, Elan Z.; Capodagli, Glenn; Armstrong, Geoffrey S.; Holliday, Michael; Isern, Nancy G.; Zhang, Fengli; Pegan, Scott D.

    2015-05-01

    Crimean-Congo Hemorrhagic fever virus (CCHFV) is one of several lethal viruses that encodes for a viral ovarian tumor domain (vOTU), which serves to cleave and remove multiple proteins involved in cellular signaling such as ubiquitin (Ub) and interferon stimulated gene produce 15 (ISG15). Such manipulation of the host cell machinery serves to downregulate the host response and, therefore, complete characterization of these proteases is important. While several structures of the CCHFV vOTU protease have been solved, both free and bound to Ub and ISG15, few structural differences have been found and little insight has been gained as to the dynamic plasticity of this protease. Therefore, we have used NMR relaxation experiments to probe the dynamics of CCHV vOTU, both alone and in complex with Ub, thereby discovering a highly dynamic protease that exhibits conformational exchange within the same regions found to engage its Ub substrate. These experiments reveal a structural plasticity around the N-terminal regions of CCHV vOTU, which are unique to vOTUs, and provide a rationale for engaging multiple substrates with the same binding site.

  6. The Non-structural Protein of Crimean-Congo Hemorrhagic Fever Virus Disrupts the Mitochondrial Membrane Potential and Induces Apoptosis*

    Barnwal, Bhaskar; Karlberg, Helen; Mirazimi, Ali; Tan, Yee-Joo

    2016-01-01

    Viruses have developed distinct strategies to overcome the host defense system. Regulation of apoptosis in response to viral infection is important for virus survival and dissemination. Like other viruses, Crimean-Congo hemorrhagic fever virus (CCHFV) is known to regulate apoptosis. This study, for the first time, suggests that the non-structural protein NSs of CCHFV, a member of the genus Nairovirus, induces apoptosis. In this report, we demonstrated the expression of CCHFV NSs, which contains 150 amino acid residues, in CCHFV-infected cells. CCHFV NSs undergoes active degradation during infection. We further demonstrated that ectopic expression of CCHFV NSs induces apoptosis, as reflected by caspase-3/7 activity and cleaved poly(ADP-ribose) polymerase, in different cell lines that support CCHFV replication. Using specific inhibitors, we showed that CCHFV NSs induces apoptosis via both intrinsic and extrinsic pathways. The minimal active region of the CCHFV NSs protein was determined to be 93–140 amino acid residues. Using alanine scanning, we demonstrated that Leu-127 and Leu-135 are the key residues for NSs-induced apoptosis. Interestingly, CCHFV NSs co-localizes in mitochondria and also disrupts the mitochondrial membrane potential. We also demonstrated that Leu-127 and Leu-135 are important residues for disruption of the mitochondrial membrane potential by NSs. Therefore, these results indicate that the C terminus of CCHFV NSs triggers mitochondrial membrane permeabilization, leading to activation of caspases, which, ultimately, leads to apoptosis. Given that multiple factors contribute to apoptosis during CCHFV infection, further studies are needed to define the involvement of CCHFV NSs in regulating apoptosis in infected cells. PMID:26574543

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

    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.

  8. Dobrava virus carried by the yellow-necked field mouse Apodemus flavicollis, causing hemorrhagic fever with renal syndrome in Romania.

    Panculescu-Gatej, Raluca Ioana; Sirbu, Anca; Dinu, Sorin; Waldstrom, Maria; Heyman, Paul; Murariu, Dimitru; Petrescu, Angela; Szmal, Camelia; Oprisan, Gabriela; Lundkvist, Ake; Ceianu, Cornelia S

    2014-05-01

    Hemorrhagic fever with renal syndrome (HFRS) has been confirmed by serological methods during recent years in Romania. In the present study, focus-reduction neutralization tests (FRNT) confirmed Dobrava hantavirus (DOBV) as the causative agent in some HFRS cases, but could not distinguish between DOBV and Saaremaa virus (SAAV) infections in other cases. DOBV was detected by a DOBV-specific TaqMan assay in sera of nine patients out of 22 tested. Partial sequences of the M genomic segment of DOBV were obtained from sera of three patients and revealed the circulation of two DOBV lineages in Romania. Investigation of rodents trapped in Romania found three DOBV-positive Apodemus flavicollis out of 83 rodents tested. Two different DOBV lineages were also detected in A. flavicollis as determined from partial sequences of the M and S genomic segments. Sequences of DOBV in A. flavicollis were either identical or closely related to the sequences obtained from the HFRS patients. The DOBV strains circulating in Romania clustered in two monophyletic groups, together with strains from Slovenia and the north of Greece. This is the first evidence for the circulation of DOBV in wild rodents and for a DOBV etiology of HFRS in Romania.

  9. Combination of RT-PCR and proteomics for the identification of Crimean-Congo hemorrhagic fever virus in ticks

    Isabel G. Fernández de Mera

    2017-07-01

    Full Text Available Crimean-Congo hemorrhagic fever (CCHF is an emerging tick-borne zoonotic disease caused by the CCHF virus (CCHFV. In this study, an experimental approach combining RT-PCR and proteomics was used for the identification and characterization of CCHFV in 106 ticks from 7 species that were collected from small ruminants in Greece. The methodological approach included an initial screening for CCHFV by RT-PCR followed by proteomics analysis of positive and control negative tick samples. This novel approach allowed the identification of CCHFV-positive ticks and provided additional information to corroborate the RT-PCR findings using a different approach. Two ticks, Dermacentor marginatus and Haemaphysalis parva collected from a goat and a sheep, respectively were positive for CCHFV. The sequences for CCHFV RNA segments S and L were characterized by RT-PCR and proteomics analysis of tick samples, respectively. These results showed the possibility of combining analyses at the RNA and protein levels using RT-PCR and proteomics for the characterization of CCHFV in ticks. The results supported that the CCHFV identified in ticks are genetic variants of the AP92 strain. Although the AP92-like strains probably do not represent a high risk of CCHF to the population, the circulation of genetically diverse CCHFV strains could potentially result in the appearance of novel viral genotypes with increased pathogenicity and fitness.

  10. [Emerging diseases. Crimean-Congo hemorrhagic fever].

    Kuljić-Kapulica, Nada

    2004-01-01

    Recognized for many years in central Asia and Eastern Europe, Crimean-Congo hemorrhagic fever (CCHF) is a severe zoonotic disease which affects people coming into contact with livestock or ticks. The range of the CCHF virus is now known to extend form central Asia to India, Pakistan, Afghanistan, Iran, Iraq, the Middle East, Eastern Europe, and to most of Saharan and sub-Saharan Africa. CCHF virus is a member of the Bunyavirus family, and is classified as a Nairovirus. After an incubation period of approximately 3 to 6 days the abrupt onset of acute febrile illness occurs. The first symptoms are similar to severe influenza and include fever, headache, severe back and abdominal pain. The hemorrhagic fever manifestations occur after several days of illnesses and include petechial rash, ecchymoses, hematemmesis, and melenna. Cases typically present with some form of hepatitis. The mortality rate is 10-50% in different outbreaks with deaths typically occurring during the second week of illness. The genus Hyalomma of ixodid ticks is the most important vector of the CCHF virus. Vertebrates including birds and small animals provide excellent amplifier hosts of both the virus and the tick. The virus can be transmitted to humans by direct contact with infected animals and from person to person. Early diagnosis is possible in special laboratories using antigen detection by imunofluorescence or ELISA tests or molecular methods as PCR and antibody detection. Tick control measures need to be emphasized and utilized to prevent CCHF. This includes spraying camp sites, clothing and danger areas with acaricides or repellent. Strict isolation of patients with CCHF and a focus on barrier nursing would help to prevent nosocomial spread. Presently the vaccine is a dangerous mouse brain-derived version. Future development of a vaccine would help to prevent human infection.

  11. Crimean-Congo hemorrhagic fever virus clades V and VI (Europe 1 and 2 in ticks in Kosovo, 2012.

    Kurtesh Sherifi

    2014-09-01

    Full Text Available Despite being a small country, Kosovo represents one of the few foci of Crimean-Congo hemorrhagic fever (CCHF in Europe. The distribution of Kosovar tick vectors and the evolution of CCHF virus in ticks are both as yet unknown. A better description of the extent and the genetic diversity of CCHFV in ticks from endemic settings is essential, in order to be controlled. We investigated the 2012 distribution of Kosovar ticks alongside the prevalence and the phylogeography of tick-derived CCHFV. Hyalomma marginatum dominated in the endemic municipalities with 90.2% versus 24.3% in the non-endemic regions. Of 1,102 tested ticks, 40 (3.6% were CCHFV-positive, belonging to H. marginatum (29, Rhipicephalus bursa (10, and Ixodes ricinus (1. The virus strains clustered with clade V and VI related sequences. They fell into two lineages: Kosovo I and II. Kosovo I comprised strains recovered exclusively from R. bursa ticks and was closely related to AP92 prototype strain. Kosovo II clustered into Kosovo IIa, including human-derived strains, and IIb including only strains detected in H. marginatum and I. ricinus. Our phylogeographic reconstruction suggests two temporally distinct CCHFV introductions: the most probable location of the most recent common ancestor of Kosovo I lineage was in Greece (63 years ago and that of lineages IIa-b in Turkey (35 years ago. After each CCHFV introduction into Kosovo, subsequent lineage expansions suggest periods of in situ evolution. The study provides the first insight into the genetic variability and the origin of CCHFV in ticks from Kosovo. Our findings indicate the spreading of CCHFV to non-endemic areas, which underlines the importance of further studies in order to monitor and predict future CCHF outbreaks in Kosovo. The AP92-like strains appear to be more widespread than previously thought and may provide a promising target for experimental studies due to their assumed low pathogenicity.

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

    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...

  13. Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever

    Cashman Kathleen A

    2010-10-01

    Full Text Available Abstract Background Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. To date, several potential new vaccine platforms have been explored, but none have progressed toward clinical trials and commercialization. Therefore, the development of a robust vaccine platform that could be generated in sufficient quantities and at a low cost per dose could herald a subcontinent-wide vaccination program. This would move Lassa endemic areas toward the control and reduction of major outbreaks and endemic infections. To this end, we have employed efficient mammalian expression systems to generate a Lassa virus (LASV-like particle (VLP-based modular vaccine platform. Results A mammalian expression system that generated large quantities of LASV VLP in human cells at small scale settings was developed. These VLP contained the major immunological determinants of the virus: glycoprotein complex, nucleoprotein, and Z matrix protein, with known post-translational modifications. The viral proteins packaged into LASV VLP were characterized, including glycosylation profiles of glycoprotein subunits GP1 and GP2, and structural compartmentalization of each polypeptide. The host cell protein component of LASV VLP was also partially analyzed, namely glycoprotein incorporation, though the identity of these proteins remain unknown. All combinations of LASV Z, GPC, and NP proteins that generated VLP did not incorporate host cell ribosomes, a known component of native arenaviral particles, despite detection of small RNA species packaged into pseudoparticles. Although VLP did not contain the same host cell components as the native

  14. Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway.

    Caì, Yíngyún; Postnikova, Elena N; Bernbaum, John G; Yú, Shu Qìng; 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; O'Connor, David H; Goldberg, Tony L; Jahrling, Peter B; Kuhn, Jens H

    2015-01-01

    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 dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin

  15. Vaccine Platforms to Control Arenaviral Hemorrhagic Fevers.

    Carrion, Ricardo; Bredenbeek, Peter; Jiang, Xiaohong; Tretyakova, Irina; Pushko, Peter; Lukashevich, Igor S

    2012-11-20

    Arenaviruses are rodent-borne emerging human pathogens. Diseases caused by these viruses, e.g., Lassa fever (LF) in West Africa and South American hemorrhagic fevers (HFs), are serious public health problems in endemic areas. We have employed replication-competent and replication-deficient strategies to design vaccine candidates potentially targeting different groups "at risk". Our leader LF vaccine candidate, the live reassortant vaccine ML29, is safe and efficacious in all tested animal models including non-human primates. In this study we showed that treatment of fatally infected animals with ML29 two days after Lassa virus (LASV) challenge protected 80% of the treated animals. In endemic areas, where most of the target population is poor and many live far from health care facilities, a single-dose vaccination with ML29 would be ideal solution. Once there is an outbreak, a fast-acting vaccine or post-exposure prophylaxis would be best. The 2(nd) vaccine technology is based on Yellow Fever (YF) 17D vaccine. We designed YF17D-based recombinant viruses expressing LASV glycoproteins (GP) and showed protective efficacy of these recombinants. In the current study we developed a novel technology to clone LASV nucleocapsid within YF17D C gene. Low immunogenicity and stability of foreign inserts must be addressed to design successful LASV/YFV bivalent vaccines to control LF and YF in overlapping endemic areas of West Africa. The 3(rd) platform is based on the new generation of alphavirus replicon virus-like-particle vectors (VLPV). Using this technology we designed VLPV expressing LASV GP with enhanced immunogenicity and bivalent VLPV expressing cross-reactive GP of Junin virus (JUNV) and Machupo virus (MACV), causative agents of Argentinian and Bolivian HF, respectively. A prime-boost regimen required for VLPV immunization might be practical for medical providers, military, lab personnel, and visitors in endemic areas.

  16. Protocols to Assess Coagulation Following In Vitro Infection with Hemorrhagic Fever Viruses

    2016-05-25

    signal standard curves (Figure 1). 4. Analyze qRT-PCR by normalizing TF Ct values to the housekeeping gene (TBP) values. (see Note 6) 3.2 Analysis...likely acceptable. 4. All samples, including standard curve samples, should be run in at least duplicate. 5. To avoid cross contamination between PCR... biosafety cabinet to avoid potentially aerosolizing virus. 8. For this step it is critical to use a wide pipette tip (such as p1000) to avoid

  17. Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance.

    Rasmussen, Angela L; Okumura, Atsushi; Ferris, Martin T; Green, Richard; Feldmann, Friederike; Kelly, Sara M; Scott, Dana P; Safronetz, David; Haddock, Elaine; LaCasse, Rachel; Thomas, Matthew J; Sova, Pavel; Carter, Victoria S; Weiss, Jeffrey M; Miller, Darla R; Shaw, Ginger D; Korth, Marcus J; Heise, Mark T; Baric, Ralph S; de Villena, Fernando Pardo-Manuel; Feldmann, Heinz; Katze, Michael G

    2014-11-21

    Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice from the Collaborative Cross panel of recombinant inbred mice exhibit distinct disease phenotypes after mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, probably mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever. Copyright © 2014, American Association for the Advancement of Science.

  18. Hemodynamics in Korean Hemorrhagic Fever

    Han, Ji Young; Lee, Jung Sang; Koh, Chang Soon; Lee, Mun Ho

    1974-01-01

    The author in an attempt to evaluate hemodynamic changes in the clinical stages of Korean hemorrhagic fever measured plasma volume, cardiac output and effective renal plasma flow utilizing radioisoto as during various phases of the disease. Cardiac output was measured by radiocardiography with external monitoring method using RIHSA. Effective renal plasma flow was obtained from blood clearance curve drawn by external monitoring after radiohippuran injection according to the method described by Razzak et al. The study was carried out in thirty-eight cases of Korean hemorrhagic fever and the following conclusions were obtained. 1) Plasma volume was increased in the patients during the oliguric and hypertensive-diuretic phases, while it was normal in the patients during the normotensive-diuretic phase. 2) Cardiac index was increased in the patients during the oliguric phase and was slightly increased in the patients at the hypertensive diuretic phase. It was normal in the other phases. 3) Total peripheral resistance was increased in the hypertensive patients during diuretic phase, while it was normal in the rest of phases. 4) Effective renal plasma flow was significantly reduced in the patients during the oliguric and diuretic phases as well as at one month after the oliguric onset. There was no significant difference between the oliguric and the early diuretic phases. Renal plasma flow in the group of patients at one month after the oliguric onset was about 45% of the normal, however, it returned to normal level at six months after the onset. 5) Clinical syndrome of relative hypervolemia was observed in some patients during the oliguric phase or hypertensive diuretic phase. Characteristic hemodynamic findings were high cardiac output and normal to relatively increased peripheral resistance these cases. Relatively increased circulating blood volumes due to decreased effective vascular space was suggested for the mechanism of relative hypervolemia. 6) Cardiac

  19. Experimental transmission of Crimean-Congo hemorrhagic fever virus by west African wild ground-feeding birds to Hyalomma marginatum rufipes ticks.

    Zeller, H G; Cornet, J P; Camicas, J L

    1994-06-01

    Hyalomma (H.) marginatum rufipes ticks commonly infest birds and are potential vectors of Crimean-Congo hemorrhagic fever (CCHF) virus in west Africa. An experimental model for investigating the role of birds in the CCHF virus transmission cycle was developed. Following CCHF virus inoculation, antibodies were detected by enzyme-linked immunosorbent assay in one red-beaked hornbill and one glossy starling, but not in two laughing doves and six domestic chickens. None of the birds showed a detectable viremia. Hyalomma marginatum rufipes larvae were placed on three red-beaked hornbills and one glossy starling. These birds were then inoculated with CCHF virus (10(1.5) 50% mouse intracerebral lethal doses). Virus transmission to larvae or nymphs was obtained and seroconversions in birds were recorded. Virus was also detected in 90% of the individually tested nymphs, as well as in adults. The virus was then successfully transmitted by adult ticks to rabbits and the engorged females were allowed to oviposit. Progeny larvae were placed on another group of birds and one of three birds showed seroconversion. The cycle of transmission of virus between ticks and aviremic ground-feeding birds represent a potential reservoir and amplification mechanism of CCHF virus in west Africa.

  20. Crimean–Congo Hemorrhagic Fever Virus and Borrelia burgdorferi sensu lato in Ticks from Kosovo and Albania

    Kurtesh Sherifi; Agim Rexhepi; Kristaq Berxholi; Blerta Mehmedi; Rreze M. Gecaj; Zamira Hoxha; Anja Joachim; Georg G. Duscher

    2018-01-01

    Tick-borne diseases pose a serious threat to human health in South-Eastern Europe, including Kosovo. While Crimean–Congo hemorrhagic fever (CCHF) is a well-known emerging infection in this area, there are no accurate data on Lyme borreliosis and tick-borne encephalitis (TBE). Therefore, we sampled and tested 795 ticks. Ixodes ricinus (n = 218), Dermacentor marginatus (n = 98), and Haemaphysalis spp. (n = 24) were collected from the environment by flagging (all from Kosovo), while Hyalomma mar...

  1. Molecular Diagnostics of Hemorrhagic Fever with Renal Syndrome during a Dobrava Virus Infection Outbreak in the European Part of Russia ▿

    Dzagurova, Tamara K.; Klempa, Boris; Tkachenko, Evgeniy A.; Slyusareva, Galina P.; Morozov, Vyacheslav G.; Auste, Brita; Kruger, Detlev H.

    2009-01-01

    A large outbreak of hemorrhagic fever with renal syndrome (HFRS) occurred in the winter of 2006-2007 in a region southeast of Moscow in Central European Russia. Of the 422 patients with HFRS investigated in this study, 58 patients were found to be infected by Puumala virus, whereas as many as 364 were infected by Dobrava-Belgrade virus (DOBV). Early serum samples from 10 DOBV-infected patients were used for nucleic acid amplification, which was successful for 5 patients. Molecular analyses demonstrated that the causative hantavirus belongs to the DOBV-Aa genetic lineage, which is carried by the striped field mouse (Apodemus agrarius) as the natural reservoir host. Neutralization assays with convalescent-phase sera from these patients confirmed infection by DOBV-Aa; related viruses, such as the Dobrava-Slovenia virus (DOBV-Af) and the Dobrava-Sochi virus (DOBV-Ap), were neutralized at lower efficiencies. The clinical courses of the 205 patients enrolled in the study were found to be mostly mild to moderate; however, an unexpectedly high fraction (27%) of patients exhibited severe illness. One patient died from kidney failure and showed symptoms of generalized subcutaneous hemorrhage. The results provide molecular, serodiagnostic, and clinical evidence that DOBV-Aa is a common pathogen in East Europe that causes large outbreaks of HFRS. PMID:19828747

  2. Hemorrhagic Fever with Renal Syndrome (HFRS)

    ... 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 . ...

  3. Alkhurma Hemorrhagic Fever in Saudi Arabia

    This podcast looks at the epidemiologic characteristics of Alkhurma Hemorrhagic Fever in humans in Najran City, Saudi Arabia. CDC epidemiologist Dr. Adam MacNeil discusses the severity and risk factors for the illness.

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

    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

  5. Reverse transcription PCR-based detection of Crimean-Congo hemorrhagic fever virus isolated from ticks of domestic ruminants in Kurdistan province of Iran.

    Fakoorziba, Mohammad Reza; Golmohammadi, Parvaneh; Moradzadeh, Rahmatollah; Moemenbellah-Fard, Mohammad Djaefar; Azizi, Kourosh; Davari, Behrooz; Alipour, Hamzeh; Ahmadnia, Sara; Chinikar, Sadegh

    2012-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal viral vector-borne zoonosis which has a mortality rate of up to 30% without treatment in humans. CCHF virus is transmitted to humans by ticks, predominantly from the Hyalomma genus. Following the report of two confirmed and one suspected death due to CCHF virus in Kurdistan province of Iran in 2007, this study was undertaken to determine the fauna of hard ticks on domestic ruminants (cattle, sheep, and goats) and their possible infection with CCHF virus using reverse transcription PCR technique. This is the first detection of CCHF virus in ticks from the Kurdistan province of Iran. Overall, 414 ixodid ticks were collected from two districts in this province. They represented four genera from which 10 separate species were identified. The Hyalomma genus was the most abundant tick genus (70%). It was the only genus shown to be infected with the CCHF virus using RT-PCR technique. The number of ticks positive for CCHF virus was 5 out of 90 (5.6%) adult ticks. The three remaining genera (Haemaphysalis, Rhipicephalus, and Dermacentor) were all negative following molecular survey. Four of the five virally-infected ticks were from cattle mainly in the Sanandaj district. We concluded that CCHF virus is present in the Hyalomma ticks on domestic ruminants (cattle) in Kurdistan province of Iran.

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

    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.

  7. Acute gingival bleeding as a complication of dengue hemorrhagic fever

    Saif Khan

    2013-01-01

    Full Text Available Dengue fever is mosquito borne disease caused by dengue virus (DENV of Flaviviridae family. The clinical manifestations range from fever to severe hemorrhage, shock and death. Here, we report a case of 20-year-old male patient undergoing orthodontic treatment presenting with acute gingival bleeding with a history of fever, weakness, backache, retro orbital pain and ecchymosis over his right arm. The hematological investigations revealed anemia, thrombocytopenia and positive dengue non-structural protein-1 antigen and also positive immunoglobulin M and immunoglobulin G antibodies for DENV. Patient was diagnosed as a case of dengue hemorrhagic fever and was immediately referred for appropriate management. This case report emphasizes the importance of taking correct and thorough medical history.

  8. Dengue Hemorrhagic Fever: Epidemiology, Pathogenesis, and Its Transmission Risk Factors

    Aryu Candra

    2010-12-01

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

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

    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.

  10. PATHOGENESIS OF HEMORRHAGIC DUE TO DENGUE VIRUS

    Arief Suseno

    2015-01-01

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

  11. Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever).

    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. Detection, isolation and confirmation of Crimean-Congo hemorrhagic fever virus in human, ticks and animals in Ahmadabad, India, 2010-2011.

    Devendra T Mourya

    Full Text Available BACKGROUND: In January 2011, human cases with hemorrhagic manifestations in the hospital staff were reported from a tertiary care hospital in Ahmadabad, India. This paper reports a detailed epidemiological investigation of nosocomial outbreak from the affected area of Ahmadabad, Gujarat, India. PRINCIPAL FINDINGS: Samples from 3 suspected cases, 83 contacts, Hyalomma ticks and livestock were screened for Crimean-Congo hemorrhagic fever (CCHF virus by qRT-PCR of which samples of two medical professionals (case C and E and the husband of the index case (case D were positive for CCHFV. The sensitivity and specificity of indigenous developed IgM ELISA to screen CCHFV specific antibodies in human serum was 75.0% and 97.5% respectively as compared to commercial kit. About 17.0% domestic animals from Kolat, Ahmadabad were positive for IgG antibodies while only two cattle and a goat showed positivity by qRT-PCR. Surprisingly, 43.0% domestic animals (Buffalo, cattle, sheep and goat showed IgG antibodies in the adjoining village Jivanpara but only one of the buffalo was positive for CCHFV. The Hyalomma anatolicum anatolicum ticks were positive in PCR and virus isolation. CCHFV was isolated from the blood sample of case C, E in Vero E-6 cells and Swiss albino mice. In partial nucleocapsid gene phylogeny from CCHFV positive human samples of the years 2010 and 2011, livestock and ticks showed this virus was similar to Tajikistan (strain TAJ/H08966, which belongs in the Asian/middle east genetic lineage IV. CONCLUSIONS: The likely source of CCHFV was identified as virus infected Hyalomma ticks and livestock at the rural village residence of the primary case (case A. In addition, retrospective sample analysis revealed the existence of CCHFV in Gujarat and Rajasthan states before this outbreak. An indigenous developed IgM ELISA kit will be of great use for screening this virus in India.

  13. Congo crimean hemorrhagic fever in balochistan

    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)

  14. Acute atrial fibrillation during dengue hemorrhagic fever

    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.

  15. Acute atrial fibrillation during dengue hemorrhagic fever

    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.

  16. Early markers of blood coagulation and fibrinolysis activation in Argentine hemorrhagic fever

    Heller, M. V.; Marta, R. F.; Sturk, A.; Maiztegui, J. I.; Hack, C. E.; Cate, J. W.; Molinas, F. C.

    1995-01-01

    Junin virus, an arenaviridae, is the etiological agent of Argentine hemorrhagic fever. In addition to thrombocytopenia, patients present several alterations in both the blood coagulation and the fibrinolytic system, but diffuse intravascular coagulation could not be demonstrated. To investigate

  17. [EBOLA HEMORRHAGIC FEVER: DIAGNOSTICS, ETIOTROPIC AND PATHOGENETIC THERAPY, PREVENTION].

    Zhdanov, K V; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fisun, A Ya

    2015-01-01

    The data on diagnostics, etiotropic and pathogenetic therapy, prevention of Ebola hemorrhagic fever are presented including diagnostic algorithms for different clinical situations. Fundamentals of pathogenetic therapy are described. Various groups of medications used for antiviral therapy of conditions caused by Ebola virus are characterized. Experimental drugs at different stages of clinical studies are considered along with candidate vaccines being developed for the prevention of the disease.

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

    Jency Maria Koshy

    2014-01-01

    Full Text Available Dengue hemorrhagic fever (DHF and Dengue shock syndrome manifest in various forms, ranging from petechial skin hemorrhage to life threatening cerebral, pulmonary, gastrointestinal and genitourinary hemorrhages. However it is very rare to have muscle hematomas in DHF. We report a rare case of spontaneous Iliopsoas hematoma complicating Dengue hemorrhagic fever.

  19. Influence of laboratory animal hosts on the life cycle of Hyalomma marginatum and implications for an in vivo transmission model for Crimean-Congo hemorrhagic fever virus

    Aysen eGargili

    2013-08-01

    Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is one of the most geographically widespread arboviruses and causes a severe hemorrhagic syndrome in humans. The virus circulates in nature in a vertebrate-tick cycle and ticks of the genus Hyalomma are the main vectors and reservoirs. Although the tick vector plays a central role in the maintenance and transmission of CCHFV in nature, comparatively little is known of CCHFV-tick interactions. This is mostly due to the fact that establishing tick colonies is laborious, and working with CCHFV requires a biosafety level 4 laboratory (BSL4 in many countries. Nonetheless, an in vivo transmission model is essential to understand the epidemiology of the transmission cycle of CCHFV. In addition, important parameters such as vectorial capacity of tick species, levels of infection in the host necessary to infect the tick, and aspects of virus transmission by tick bite including the influence of tick saliva, cannot be investigated any other way. Here, we evaluate the influence of different laboratory animal species as hosts supporting the life cycle of Hyalomma marginatum, a two-host tick. Rabbits were considered the host of choice for the maintenance of the uninfected colonies due to high larval attachment rates, shorter larval-nymphal feeding times, higher nymphal molting rates, high egg hatching rates and higher conversion efficiency index. Furthermore, we describe the successful establishment of an in vivo transmission model CCHFV in a BSL4 biocontainment setting using interferon knockout mice. This will give us a new tool to study the transmission and interaction of CCHFV with its tick vector.

  20. Alkhurma Hemorrhagic Fever in Saudi Arabia

    2010-10-28

    This podcast looks at the epidemiologic characteristics of Alkhurma Hemorrhagic Fever in humans in Najran City, Saudi Arabia. CDC epidemiologist Dr. Adam MacNeil discusses the severity and risk factors for the illness.  Created: 10/28/2010 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/17/2010.

  1. Crimean-Congo Hemorrhagic Fever, Sudan, 2008

    This podcast describes the emergence of the first human cases of Crimean-Congo Hemorrhagic Fever in Sudan in 2008. CDC epidemiologist Dr. Stuart Nichol discusses how the disease was found in Sudan and how it spread in a hospital there.

  2. [Clinical picture of hemorrhagic fever with renal syndrome in Croatia].

    Kuzman, Ilija

    2003-01-01

    Among many viral hemorrhagic fevers, only hemorrhagic fever with renal syndrome (HFRS) occurs in Croatia. HFRS is a natural focus zoonosis with sudden onset, characterized by high fever and other clinical symptoms, renal insufficiency and hemorrhages. In Croatia, HFRS is caused by two types of hantaviruses--Puumala (PUU) and Dobrava (DOB). The basic pathologic and patophysiologic disorder in HFRS is capillary damage (vasculitis). Incubation of HFRS has not been precisely determined, it is most frequently around two weeks. The disease onset is usually abrupt. At the beginning, general symptoms include high fever and myalgias, especially in the lumbar region, and abdominal pain, as well as strong headaches, malaise and nausea, and often vomiting or diarrhea. In half of the patients respiratory symptoms occur. Later on, some patients may experience hypotension, oliguria and other signs of renal failure, and apart from petechial, severe hemorrhages may also occur in other organs. During typical clinical presentation of the disease, some characteristic symptoms are clearly distinguished in particular stages of the disease. Therefore, the course of HFRS is usually divided into five distinct stages (febrile, hypotensive, oliguric, polyuric and convalescent). Such a course of the disease is more commonly present in case of DOB virus than PUU virus infection. The febrile stage with sudden onset usually lasts from 3 to 7 days, when thrombocytopenia and hemoconcentration, as well as albuminuria and hematuria are almost always recorded. The hypotensive stage lasts from one to 2 days on an average and is characterized by lower blood pressure and signs of renal failure. The oliguric stage usually starts at the beginning of the second week of the disease, when extensive hemorrhage may occur and urea and creatinine reach their highest values. The oliguric stage is followed by the polyuric stage which can last for up to two weeks, and is characterized by excretion of a large

  3. [Ebola hemorrhagic fever: its extension reflects the African sanitary disaster].

    Bourée, Patrice

    2014-09-01

    Ebola virus, described in 1976 in Zaire, causes severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Epidemics occurred since this time to nowadays in Sudan, Gabon, Congo and currently in Guinea, Liberia, Sierra-Leone, Nigeria and Senegal. Specific treatment and vaccine are not available. So, to prevent the virus transmission with live and dead patients, we must use strict individual and collective measures which are not always understood by local populations and make contact tracing; it is the only way to curb the epidemic.

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

    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. The pathogenesis of Ebola hemorrhagic fever.

    Takada, A; Kawaoka, Y

    2001-10-01

    Ebola virus causes lethal hemorrhagic disease in humans, yet there are still no satisfactory biological explanations to account for its extreme virulence. This review focuses on recent findings relevant to understanding the pathogenesis of Ebola virus infection and developing vaccines and effective therapy. The available data suggest that the envelope glycoprotein and the interaction of some viral proteins with the immune system are likely to play important roles in the extraordinary pathogenicity of this virus. There are also indications that genetically engineered vaccines, including plasmid DNA and viral vectors expressing Ebola virus proteins, and passive transfer of neutralizing antibodies could be feasible options for the control of Ebola virus-associated disease.

  6. Infection control during filoviral hemorrhagic fever outbreaks

    N Raabe Vanessa

    2012-01-01

    Full Text Available Breaking the human-to-human transmission cycle remains the cornerstone of infection control during filoviral (Ebola and Marburg hemorrhagic fever outbreaks. This requires effective identification and isolation of cases, timely contact tracing and monitoring, proper usage of barrier personal protection gear by health workers, and safely conducted burials. Solely implementing these measures is insufficient for infection control; control efforts must be culturally sensitive and conducted in a transparent manner to promote the necessary trust between the community and infection control team in order to succeed. This article provides a review of the literature on infection control during filoviral hemorrhagic fever outbreaks focusing on outbreaks in a developing setting and lessons learned from previous outbreaks. The primary search database used to review the literature was PUBMED, the National Library of Medicine website.

  7. Ebola hemorrhagic fever outbreaks: strategies for effective epidemic management, containment and control

    Matua, Gerald Amandu; Wal, Dirk Mostert Van der; Locsin, Rozzano C.

    2015-01-01

    Ebola hemorrhagic fever, caused by the highly virulent RNA virus of the filoviridae family, has become one of the world's most feared pathogens. The virus induces acute fever and death, often associated with hemorrhagic symptoms in up to 90% of infected patients. The known sub-types of the virus are Zaire, Sudan, Taï Forest, Bundibugyo and Reston Ebola viruses. In the past, outbreaks were limited to the East and Central African tropical belt with the exception of Ebola Reston outbreaks that o...

  8. Crimean-Congo Hemorrhagic Fever, Sudan, 2008

    2010-04-15

    This podcast describes the emergence of the first human cases of Crimean-Congo Hemorrhagic Fever in Sudan in 2008. CDC epidemiologist Dr. Stuart Nichol discusses how the disease was found in Sudan and how it spread in a hospital there.  Created: 4/15/2010 by National Center for Emerging and Zoonotic Infections (proposed).   Date Released: 4/15/2010.

  9. Co-circulation of Crimean-Congo Hemorrhagic Fever virus strains Asia 1 and 2 between the border of Iran and Pakistan.

    Shahhosseini, Nariman; Jafarbekloo, Ahmad; Telmadarraiy, Zakkyeh; Chinikar, Sadegh; Haeri, Ali; Nowotny, Norbert; Groschup, Martin H; Fooks, Anthony R; Faghihi, Faezeh

    2017-11-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a tick-borne viral disease that is transmitted by numerous species of ticks, which serve both as a reservoir and vector of CCHF virus (CCHFV). Molecular and serological tests were undertaken on hard ticks (Ixodidae spp.) and samples from livestock were collected in 2015 from Chabahar County in Southeast Iran. Using RT-PCR, the ticks were tested for the presence of CCHFV. In addition, seven livestock were serologically tested for the presence of IgG antibodies using an ELISA test. IgG antibodies against CCHFV were detected in one of 7 of the livestock that were tested. In total, 49 ticks including five species: Rhipicephalus sanguineus, Hyalomma anatolicum , Hy. asiaticum, Hy. dromedarii and Hy. marginatum with a prevalence of 46.9%, 32.7%, 4.1%, 4.1% and 2.1% respectively were identified. CCHFV was detected in three ticks among 49 collected ticks. The ticks infected with CCHFV belonged to the genus Hyalomma and Rhipicephalus. Phylogenetic analysis demonstrated that two sequences clustered in clade IV (Asia-1) and one sequence was located within clade IV (Asia-2). Most of the animal and human CCHF cases of the country are reported from Sistan and Baluchistan provinces. Regular monitoring programs in the tick population and livestock are needed in the future.

  10. Co-circulation of Crimean-Congo Hemorrhagic Fever virus strains Asia 1 and 2 between the border of Iran and Pakistan

    Nariman Shahhosseini

    2017-11-01

    Full Text Available Crimean-Congo Hemorrhagic Fever (CCHF is a tick-borne viral disease that is transmitted by numerous species of ticks, which serve both as a reservoir and vector of CCHF virus (CCHFV. Molecular and serological tests were undertaken on hard ticks (Ixodidae spp. and samples from livestock were collected in 2015 from Chabahar County in Southeast Iran. Using RT-PCR, the ticks were tested for the presence of CCHFV. In addition, seven livestock were serologically tested for the presence of IgG antibodies using an ELISA test. IgG antibodies against CCHFV were detected in one of 7 of the livestock that were tested. In total, 49 ticks including five species: Rhipicephalus sanguineus, Hyalomma anatolicum, Hy. asiaticum, Hy. dromedarii and Hy. marginatum with a prevalence of 46.9%, 32.7%, 4.1%, 4.1% and 2.1% respectively were identified. CCHFV was detected in three ticks among 49 collected ticks. The ticks infected with CCHFV belonged to the genus Hyalomma and Rhipicephalus. Phylogenetic analysis demonstrated that two sequences clustered in clade IV (Asia-1 and one sequence was located within clade IV (Asia-2. Most of the animal and human CCHF cases of the country are reported from Sistan and Baluchistan provinces. Regular monitoring programs in the tick population and livestock are needed in the future. Keywords: Virology

  11. [Present status of zoonotic hemorrhagic fevers of South America].

    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.

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

    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.

  13. Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome.

    McElroy, Anita K; Erickson, Bobbie R; Flietstra, Timothy D; Rollin, Pierre E; Nichol, Stuart T; Towner, Jonathan S; Spiropoulou, Christina F

    2014-08-15

    Ebola hemorrhagic fever (EHF) outbreaks occur sporadically in Africa and result in high rates of death. The 2000-2001 outbreak of Sudan virus-associated EHF in the Gulu district of Uganda led to 425 cases, of which 216 were laboratory confirmed, making it the largest EHF outbreak on record. Serum specimens from this outbreak had been preserved in liquid nitrogen from the time of collection and were available for analysis. Available samples were tested using a series of multiplex assays to measure the concentrations of 55 biomarkers. The data were analyzed to identify statistically significant associations between the tested biomarkers and hemorrhagic manifestations, viremia, and/or death. Death, hemorrhage, and viremia were independently associated with elevated levels of several chemokines and cytokines. Death and hemorrhage were associated with elevated thrombomodulin and ferritin levels. Hemorrhage was also associated with elevated levels of soluble intracellular adhesion molecule. Viremia was independently associated with elevated levels of tissue factor and tissue plasminogen activator. Finally, samples from nonfatal cases had higher levels of sCD40L. These novel associations provide a better understanding of EHF pathophysiology and a starting point for researching new potential targets for therapeutic interventions. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. Favipiravir (T-705 inhibits Junín virus infection and reduces mortality in a guinea pig model of Argentine hemorrhagic fever.

    Brian B Gowen

    Full Text Available Junín virus (JUNV, the etiologic agent of Argentine hemorrhagic fever (AHF, is classified by the NIAID and CDC as a Category A priority pathogen. Presently, antiviral therapy for AHF is limited to immune plasma, which is readily available only in the endemic regions of Argentina. T-705 (favipiravir is a broadly active small molecule RNA-dependent RNA polymerase inhibitor presently in clinical evaluation for the treatment of influenza. We have previously reported on the in vitro activity of favipiravir against several strains of JUNV and other pathogenic New World arenaviruses.To evaluate the efficacy of favipiravir in vivo, guinea pigs were challenged with the pathogenic Romero strain of JUNV, and then treated twice daily for two weeks with oral or intraperitoneal (i.p. favipiravir (300 mg/kg/day starting 1-2 days post-infection. Although only 20% of animals treated orally with favipiravir survived the lethal challenge dose, those that succumbed survived considerably longer than guinea pigs treated with placebo. Consistent with pharmacokinetic analysis that showed greater plasma levels of favipiravir in animals dosed by i.p. injection, i.p. treatment resulted in a substantially higher level of protection (78% survival. Survival in guinea pigs treated with ribavirin was in the range of 33-40%. Favipiravir treatment resulted in undetectable levels of serum and tissue viral titers and prevented the prominent thrombocytopenia and leucopenia observed in placebo-treated animals during the acute phase of infection.The remarkable protection afforded by i.p. favipiravir intervention beginning 2 days after challenge is the highest ever reported for a small molecule antiviral in the difficult to treat guinea pig JUNV challenge model. These findings support the continued development of favipiravir as a promising antiviral against JUNV and other related arenaviruses.

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

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

    2002-01-01

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

  16. Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever

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

    2002-01-01

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

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

    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.

  18. Phylogenetic characterization of circulating Dengue and Alkhumra Hemorrhagic Fever viruses in western Saudi Arabia and lack of evidence of Zika virus in the region: A retrospective study, 2010-2015.

    Al-Saeed, Moneerah S; El-Kafrawy, Sherif A; Farraj, Suha A; Al-Subhi, Tagreed L; Othman, Norah A; Alsultan, Arwa; Ben Helaby, Huda G; Alshawdari, Mustafa M; Hassan, Ahmed M; Charrel, Remi N; Azhar, Esam I; Hashem, Anwar M

    2017-08-01

    Flaviviruses represent a global public health concern. They consist of ∼70 viruses with almost half of them causing human diseases with unspecified febrile illnesses. Cities in western Saudi Arabia are endemic for viruses (DENV) with sporadic infections due to Alkhumra hemorrhagic fever virus (AHFV). They also represent a major destination for travelers coming for annual religious pilgrimages (Hajj and Umrah) from all over the world. However, whether other flaviviruses are circulating is not known because of the limited number of surveillance studies. Here, we retrospectively screened 690 samples for flaviviruses in samples from patients with unexplained febrile illnesses between 2010 and 2015 in western Saudi Arabia using a pan-flaviviruses RT-PCR assay. Despite Zika virus RNA was not detected, this study confirms circulation and/or sporadic spread of DENV-2, DENV-3, and AHFV, higher prevalence of DENV-2, and a role for visitors from DENV endemic countries in DENV importation into the Kingdom. Further analysis also showed very low genetic diversity of AHFV confirming its slow microevolution. Accordingly, continuous and prospective surveillance for flaviviruses using such assay are warranted in Saudi Arabia which receives millions of Muslims annually to implement effective control measures in light of the global widespread and outbreaks of several flaviviruses. © 2017 Wiley Periodicals, Inc.

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

    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. Ebola hemorrhagic Fever and the current state of vaccine development.

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il

    2014-12-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine.

  1. Hemorrhagic fever with renal syndrome accompanied by panhypopituitarism and central diabetes insipidus: a case report.

    Ahn, Hee Jung; Chung, Jong-Hoon; Kim, Dong-Min; Yoon, Na-Ra; Kim, Choon-Mee

    2018-03-05

    Central diabetes insipidus (DI) was detected in a patient with hemorrhagic fever with renal syndrome (HFRS) who had been molecularly and serologically diagnosed with Hantaan virus infection. We recommend that clinicians differentiate central DI in HFRS patients with a persistent diuretic phase even when pituitary MRI findings are normal.

  2. NNDSS - Table II. Cryptosporidiosis to Dengue Hemorrhagic Fever

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue Hemorrhagic Fever - 2014.In this Table, all conditions with a 5-year average annual national total of more than or...

  3. A Study of Renogram in Korean Hemorrhagic Fever

    Choi, Tae Kyu; Lee, Jung Sang; Koh, Chang Soon; Lee, Mun Ho

    1974-01-01

    The patterns of renogram in patients with Korean hemorrhagic fever were evaluated with clinical course and renal hemodynamic changes in various clinical stages. The renal plasma flow was measured by hippuran blood clearance using 131 I-ortho-iodohippurate and hippuran renogram was analysed means of quantitative and qualitative methods in 26 patients of Korean hemorrhagic fever. The results obtained with this study were as follows;1) During the oliguric phase of Korean hemorrhagic fever, the renogram showed non-functioning (flat) or obstructive pattern. The group of patients with non-functioning pattern of renogram had more severe impairment of renal function and grave prognosis than the group with obstructive pattern of renogram. 2) During the diuretic phase, the renogram showed obstructive or dysfunction ar normal pattern, which was related with the recovery of renal function. Obstruction pattern of renogram was observed till the 2nd week of diuretic phase. Normal pattern of renogram began to appear by the 2nd week of diuretic phase. 3) During the convalescent phase of Korean hemorrhagic fever, 40% of patients showed dysfunction pattern of renogram, and the recovery of abnormal renogram in Korean hemorrhagic fever was more delayed than the recovery of clinical features and laboratory findings. 4) The renogram showed normal pattern 6 months after onset of Korean hemorrhagic fever in all cases. 5) There was significant correlationship between the pattern of renogram and the decrease of renal plasma flow in the patients with Korean hemorrhagic fever. The decrease of renal plasma flow was marked in the patients with non-functioning pattern of renogram and was least in the patients with dysfunction pattern of renogram. All above results suggested that the renogram reflects the effective renal plasma flow and degree of renal impairment, and the renogram may be one of the important indexes which could give us a more precise prognosis in Korean hemorrhagic fever.

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

    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. A Syrian golden hamster model recapitulating ebola hemorrhagic fever.

    Ebihara, Hideki; Zivcec, Marko; Gardner, Donald; Falzarano, Darryl; LaCasse, Rachel; Rosenke, Rebecca; Long, Dan; Haddock, Elaine; Fischer, Elizabeth; Kawaoka, Yoshihiro; Feldmann, Heinz

    2013-01-15

    Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs.

  6. Second International Conference on Crimean-Congo Hemorrhagic Fever.

    Spengler, Jessica R; Bente, Dennis A; Bray, Mike; Burt, Felicity; Hewson, Roger; Korukluoglu, Gülay; Mirazimi, Ali; Weber, Friedemann; Papa, Anna

    2018-02-01

    The Second International Conference on Crimean-Congo Hemorrhagic Fever (CCHF) was held in Thessaloniki, Greece, from September 10-13, 2017, and brought together international public health professionals, clinicians, ecologists, and basic laboratory researchers. Nearly 100 participants, representing 24 countries and the World Health Organization (WHO), were in attendance. Meeting sessions covered the epidemiology of CCHF in humans; ticks and virus-tick interactions; wild and domestic animal hosts; molecular virology; taxonomic classification; pathogenesis and animal models; clinical aspects and diagnosis; clinical management and clinical trials; and disease prevention in humans. The concluding session focused on recent WHO recommendations for public health measures and future research. This report summarizes lectures by the invited speakers and highlights advances in the field. Copyright © 2017. Published by Elsevier B.V.

  7. Dengue fever (image)

    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.

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

    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.

  9. Ebola Hemorrhagic Fever as a Public Health Emergency of International Concern; a Review Article.

    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.

  10. Elevated Dengue Virus Nonstructural Protein 1 Serum Levels and Altered Toll-Like Receptor 4 Expression, Nitric Oxide, and Tumor Necrosis Factor Alpha Production in Dengue Hemorrhagic Fever Patients

    Denise Maciel Carvalho

    2014-01-01

    Full Text Available Background. During dengue virus (DV infection, monocytes produce tumor necrosis factor alpha (TNF-α and nitric oxide (NO which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1 on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1 serum levels and innate immune response (TLR4 expression and TNF-α/NO production of DV infected patients presenting different clinical outcomes. Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA, TNF-α production by peripheral blood mononuclear cells (PBMCs, and TLR4 expression on CD14+ cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF was detected compared to patients with dengue hemorrhagic fever (DHF. Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-α production when compared to DF patients. Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes.

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

    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.

  12. Retinoids, race and the pathogenesis of dengue hemorrhagic fever.

    Mawson, Anthony R

    2013-12-01

    Dengue hemorrhagic fever (DHF) is the most significant mosquito-borne viral disease worldwide in terms of illness, mortality and economic cost, but the pathogenesis of DHF is not well understood and there is no specific treatment or vaccine. Based on evidence of liver involvement, it is proposed that dengue virus and retinoids interact to cause cholestatic liver damage, resulting in the spillage of stored retinoids into the circulation and in an endogenous form of hypervitaminosisis A manifested by the signs and symptoms of the disease, including: fever, severe joint and bone pain, capillary leakage, thrombocytopenia, headache, and gastrointestinal symptoms. While retinoids in low concentration are essential for numerous biological functions, they are prooxidant, cytotoxic, mutagenic and teratogenic in higher concentration, especially when unbound to protein, and an endogenous form of vitamin A intoxication is recognized in cholestasis. The model tentatively explains the observations that 1) repeat infections are more severe than initial dengue virus infections; 2) the incidence of denue has increased dramatically worldwide in recent decades; 3) DHF is less prevalent in people of African ancestry than those of other racial backgrounds; and 4) infants are protected from dengue. The retinoid toxicity hypothesis of DHF predicts the co-existence of low serum concentrations of retinol coupled with high concentrations of retinoic acid and an increased percentage of retinyl esters to total vitamin A. Subject to such tests, it may be possible to treat DHF effectively using drugs that target the metabolism and expression of retinoids. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    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....

  14. Possible sexual transmission of Crimean-Congo hemorrhagic fever

    Natalia Yurievna Pshenichnaya

    2016-04-01

    Full Text Available Three cases of family transmission of laboratory-confirmed Crimean-Congo hemorrhagic fever (CCHF among spouses are reported. These spouses had sexual contact at the end of the incubation period or during the early stage of the mild form of CCHF, without any hemorrhagic symptoms in the first infected spouse. This report demonstrates that sexual contact may represent a real risk of CCHF transmission, even if the patient only experiences mild symptoms.

  15. Ebola Virus and Marburg Virus

    Ebola virus and Marburg virus Overview Ebola virus and Marburg virus are related viruses that cause hemorrhagic fevers — illnesses marked by severe bleeding (hemorrhage), organ failure and, in many ...

  16. Evaluation of patients with Crimean-Congo hemorrhagic fever in ...

    Background: Crimean-Congo hemorrhagic fever (CCHF), which is associated with a high mortality rate in the Black Sea region of Turkey, has received increasing attention. Objective: In this study, the epidemiological features, clinical and laboratory findings, treatments, and outcomes of patients diagnosed with CCHF ...

  17. Crimean-Congo Hemorrhagic Fever, Kazakhstan, 2009–2010

    Knust, Barbara; Medetov, Zhumagul B.; Kyraubayev, Kakimzhan B.; Bumburidi, Yekaterina; Erickson, Bobbie Rae; MacNeil, Adam; Bayserkin, Baurzhan S.; Ospanov, Kenes S.

    2012-01-01

    We evaluated Crimean-Congo hemorrhagic fever (CCHF) surveillance data from southern Kazakhstan during 2009–2010 and found both spatial and temporal association between reported tick bites and CCHF cases. Public health measures should center on preventing tick bites, increasing awareness of CCHF signs and symptoms, and adopting hospital infection control practices. PMID:22469505

  18. Brucellosis in Patients with Crimean-Congo Hemorrhagic Fever

    Fazilet Duygu

    2017-12-01

    Full Text Available Background: Crimean-Congo hemorrhagic fever (CCHF is a fatal zoonotic viral disease caused by infection with a tick-borne virus of the genus Nairovirus. In this study, we investigated the incidence of brucellosis in patients diag­nosed with CCHF.Methods: Overall, 169 patients hospitalized with an initial diagnosis of CCHF were included in 2011 in To­kat/ Turkey. Immunoglobulin M (IgM antibodies and/or PCR results were used in the laboratory diagnosis of CCHF, while plate and standard tube agglutination (STA tests were used to diagnose brucellosis.Results: Overall, 120 patients (79% with positive PCR tests were diagnosed with CCHF. Five (4.16% were also diag­nosed with brucellosis based on the positive plate and STA test results. Four patients (2.36% had negative CCHF PCR and positive STA test results.Conclusion: Brucellosis and CCHF can mimic each other and that all patients with CCHF or brucellosis should be screened for both conditions.

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

    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.

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

    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.

  1. Epidemiologic characteristics and military implications of hemorrhagic fever with renal syndrome in croatia.

    Mulić, Rosanda; Ropac, Darko

    2002-10-01

    To analyze epidemiologic characteristics of hemorrhagic fever with renal syndrome in Croatia, including military implications of the disease and measures for its prevention. We analyzed data from obligatory infectious disease reports and notification of deaths due to infectious diseases, data on the hemorrhagic fever with renal syndrome epidemics in Croatia, and data collected by survey of the population, serological findings, and studies of wild rodents serving as reservoirs of the infection. During the 1987-2001 period, 235 cases of hemorrhagic fever with renal syndrome were recorded in Croatia, with 147 (62.6%) of them among Croatian Army soldiers. Mortality rate was up to 15.4% (mean 2.2%) (5/235). The highest number of cases was recorded in months of June and July, ie, during the warm season characterized by increased activity of both the animals acting as infection reservoirs and humans as hosts. The known natural foci of hemorrhagic fever with renal syndrome have been Plitvice and Slunj areas, Velika and Mala Kapela mountains, Zagreb area (Velika Gorica and Jastrebarsko), west Slavonia, Novska area, and Dinara Mountain. The disease has not been recorded in the littoral area and Adriatic islands. The identified causative agents include Dobrava and Puumala viruses of the genus Hantavirus, whereas rodents Clethrionomys glareolus, Apodemus flavicollis, Apodemus agrarius, and Apodemus sylvaticus serve as the main reservoirs of the infection. Typical biotopes of the infection in Croatia are deciduous woods. The measures of prevention in Croatia include pest control, disinfection, hygienic waste disposal, preventing rodent access to food and water, proper choice of camping sites, and health education. Hemorrhagic fever with renal syndrome occurs predominantly in soldiers, in a sporadic or epidemic form. Because of the course of disease and potentially lethal outcome, the disease has a considerable impact on the field task performance and combat readiness of

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

    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. EPIDEMIOLOGY, CLINICAL AND LABORATORY FEATURES OF CRIMEAN-CONGO HEMORRHAGIC FEVER IN GEORGIA.

    Vashakidze, E; Mikadze, I

    2015-10-01

    Crimean-Congo hemorrhagic fever virus transmitted to humans by Hyalomma ticks or by direct contact with the blood of infected humans or domestic animals. The most common clinical signs of CCHF are fever, nausea, headache, diarrhea, myalgia, petechial rash, and bleeding. CCHF is a severe disease in humans with a fatality rate up to 15-85%. This study was undertaken to determine the predictors of fatality among patients with CCHF based on epidemiological, clinical, and laboratory findings. 34 patients were enrolled in the study, aged 4 to 77; 17 - male and 17 female. 3 of them were fatal cases. All of them were from Shua Kartli: Khashuri, Gori and Kaspi districts, involved in farming/handling livestock and the history of tick bite was present in most of patients. Evaluation of the epidemiological characteristics of this cases showed that the female to male ratio was nearly similar. The disease is common in the rural areas of the region, mostly in the actively working age group and almost all patients were farmers. The results of our study show that the most cardinal clinical and laboratory features of Crimean-Congo hemorrhagic fever are - acute beginning of disease, high fever, intoxication and hemorrhagic symptoms, thrombocytopenia, high level of aminotransferases and creatine. Predictors of fatality are: an altered mental status, in early stage of disease dramatic decreased thrombocytes count and significantly high level of aspartate aminotransferase, also longer the mean prothrombin time and INR.

  4. Is the epidemiology of alkhurma hemorrhagic fever changing?: A three-year overview in Saudi Arabia.

    Ziad A Memish

    Full Text Available BACKGROUND: The epidemiology of Alkhurma hemorrhagic fever disease is yet to be fully understood since the virus was isolated in 1994 in the Kingdom of Saudi Arabia. SETTING: Preventive Medicine department, Ministry of Health, Kingdom of Saudi Arabia. DESIGN: Retrospective analysis of all laboratory confirmed cases of Alkhurma hemorrhagic fever disease collected through active and passive surveillance from 1(st-January 2009 to December, 31, 2011. RESULTS: Alkhurma hemorrhagic fever (AHFV disease increased from 59 cases in 2009 to 93 cases in 2011. Cases are being discovered outside of the region where it was initially diagnosed in Saudi Arabia. About a third of cases had no direct contact with animals or its products. Almost all cases had gastro-intestinal symptoms. Case fatality rate was less than 1%. CONCLUSIONS: Findings in this study showed the mode of transmission of AHFV virus may not be limited to direct contact with animals or its products. Gastro-intestinal symptoms were not previously documented. Observed low case fatality rate contradicted earlier reports. Close monitoring of the epidemiology of AHFV is recommended to aid appropriate diagnosis. Housewives are advised to wear gloves when handling animals and animal products as a preventive measure.

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

    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.

  6. GEOSPATIAL ANALYSIS OF URBAN LAND USE PATTERN ANALYSIS FOR HEMORRHAGIC FEVER RISK – A REVIEW

    L. N. Izzah

    2016-09-01

    Full Text Available Human modification of the natural environment continues to create habitats in which vectors of a wide variety of human and animal pathogens (such as Plasmodium, Aedes aegypti, Arenavirus etc. thrive if unabated with an enormous potential to negatively affect public health. Typical examples of these modifications include impoundments, dams, irrigation systems, landfills and so on that provide enabled environment for the transmission of Hemorrhagic fever such as malaria, dengue, avian flu, Lassa fever etc. Furthermore, contemporary urban dwelling pattern appears to be associated with the prevalence of Hemorrhagic diseases in recent years. These observations are not peculiar to the developing world, as urban expansion also contributes significantly to mosquito and other vectors habitats. This habitats offer breeding ground to some vector virus populations. The key to disease control is developing an understanding of the contribution of human landscape modification to vector-borne pathogen transmission and how a balance may be achieved between human development, public health, and responsible urban land use. A comprehensive review of urban land use Pattern Analysis for Hemorrhagic fever risk has been conducted in this paper. The study found that most of the available literatures dwell more on the impact of urban land use on malaria and dengue fevers; however, studies are yet to be found discussing the implications of urban land use on the risk of Ebola, Lassa and other non-mosquito borne VHFs. A relational model for investigating the influence of urban land use change pattern on the risk of Hemorrhagic fever has been proposed in this study.

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

    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

  8. Crimean-Congo hemorrhagic fever: Risk factors and control measures for the infection abatement

    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

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

    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

  10. Manual of Hemorrhagic Fever with Renal Syndrome

    1989-04-01

    added to form 2,000 ml solution. (3) Fresh guinea pig serum (GPS), which may be stored at -80’ C. (4) Dithiothreitol solution (DTT), 3 mg/ml, which...named Seoul virus, has been serol gically identified in Africa, North and South America, India, te Ihighlands of New Guinea , 3 Y/ j5 HFRS several...kalium and protein free and essentially natrium-free, is recommended. If parenteral alimentation is necessary, the usual treatment is to infuse

  11. Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9).

    Weber, David J; Rutala, William A; Fischer, William A; Kanamori, Hajime; Sickbert-Bennett, Emily E

    2016-05-02

    Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

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

    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.

  13. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    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.

    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. Spatiotemporal Analysis of the Ebola Hemorrhagic Fever in West Africa in 2014

    Xu, M.; Cao, C. X.; Guo, H. F.

    2017-09-01

    Ebola hemorrhagic fever (EHF) is an acute hemorrhagic diseases caused by the Ebola virus, which is highly contagious. This paper aimed to explore the possible gathering area of EHF cases in West Africa in 2014, and identify endemic areas and their tendency by means of time-space analysis. We mapped distribution of EHF incidences and explored statistically significant space, time and space-time disease clusters. We utilized hotspot analysis to find the spatial clustering pattern on the basis of the actual outbreak cases. spatial-temporal cluster analysis is used to analyze the spatial or temporal distribution of agglomeration disease, examine whether its distribution is statistically significant. Local clusters were investigated using Kulldorff's scan statistic approach. The result reveals that the epidemic mainly gathered in the western part of Africa near north Atlantic with obvious regional distribution. For the current epidemic, we have found areas in high incidence of EVD by means of spatial cluster analysis.

  16. Molecular detection of Crimean-Congo Hemorrhagic Fever (CCHF Virus in tick species collected from livestock in Marvdasht, Fars province during 2012-2013

    F Farhadpour

    2015-03-01

    Conclusion: Due to confirming the cycle of the virus, it can be mentioned that CCHF has recently emerged as an important public health problem in this region and systematic performance monitoring and control programs to reduce the livestock population, distribution, inform and educate high-risk occupations of vectors is required.

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

    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

  18. [Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines and chemotherapeutic agents].

    Kiselev, O I; Vasin, A V; Shevyryova, M P; Deeva, E G; Sivak, K V; Egorov, V V; Tsvetkov, V B; Egorov, A Yu; Romanovskaya-Romanko, E A; Stepanova, L A; Komissarov, A B; Tsybalova, L M; Ignatjev, G M

    2015-01-01

    Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic outbreak caused by Ebola virus Zaire since 1976 as regards its extremely large scale and rapid spread in the population. Experiments to study the agent have continued for more than 20 years. The EHF virus has a relatively simple genome with seven genes and additional reading frame resulting from RNA editing. While being of a relatively low genetic capacity, the virus can be ranked as a standard for pathogenicity with the ability to evade the host immune response in uttermost perfection. The EHF virus has similarities with retroviruses, but belongs to (-)RNA viruses of a nonretroviral origin. Genetic elements of the virus, NIRV, were detected in animal and human genomes. EHF virus glycoprotein (GP) is a class I fusion protein and shows more similarities than distinctions in tertiary structure with SIV and HIV gp41 proteins and even influenza virus hemagglutinin. EHF is an unusual infectious disease, and studying the molecular basis of its pathogenesis may contribute to new findings in therapy of severe conditions leading to a fatal outcome.

  19. Potential Analysis of Promoting the Dengue Hemorrhagic Fever Prevention Through Youtube

    Mara Ipa

    2014-11-01

    Full Text Available Background: Deal with health promotion efforts in terms of disease control using media or social networking is an innovative breakthrough in a region having a broad range of territory, such as Indonesia and others countries alike. The use of social media /video platforms such as youtube, vimeo, veoh in health promotion has been significantly increased. This study aims to determine the potential availability of information about dengue hemorrhagic fever (DHF on YouTube social media and social media potential of as a medium for dissemination of knowledge of health promotion. Methods: This study used a social media site or website which is the most popular video hosting sites in the world, ‘YouTube’, with the keyword of ‘dengue hemorrhagic fever’. The selected video directly associated with DHF, videos in English that were included in this study using Latin letters in the description of the video; with duration less than or equal to 5 minutes. 76 videos analyzed with content analysis methods. Results:Showed that 76 videos divided into categories of prevention, control, transmission, treatment, dengue fever treatment, and other categories. Other information classification categories explain the severity of dengue virus infection, dengue vector (morphology, bionomics, intrinsic phase dengue virus and some research conducted as dengue vaccine discovery efforts. Conclusion: The availability of information about dengue on YouTube social media is still very deficient. Recommendation: YouTube has the potential of social media as a medium for disseminating health promotion information about dengue.

  20. Ebola hemorrhagic fever outbreaks: strategies for effective epidemic management, containment and control.

    Matua, Gerald Amandu; Van der Wal, Dirk Mostert; Locsin, Rozzano C

    2015-01-01

    Ebola hemorrhagic fever, caused by the highly virulent RNA virus of the filoviridae family, has become one of the world's most feared pathogens. The virus induces acute fever and death, often associated with hemorrhagic symptoms in up to 90% of infected patients. The known sub-types of the virus are Zaire, Sudan, Taï Forest, Bundibugyo and Reston Ebola viruses. In the past, outbreaks were limited to the East and Central African tropical belt with the exception of Ebola Reston outbreaks that occurred in animal facilities in the Philippines, USA and Italy. The on-going outbreak in West Africa that is causing numerous deaths and severe socio-economic challenges has resulted in widespread anxiety globally. This panic may be attributed to the intense media interest, the rapid spread of the virus to other countries like United States and Spain, and moreover, to the absence of an approved treatment or vaccine. Informed by this widespread fear and anxiety, we analyzed the commonly used strategies to manage and control Ebola outbreaks and proposed new approaches that could improve epidemic management and control during future outbreaks. We based our recommendations on epidemic management practices employed during recent outbreaks in East, Central and West Africa, and synthesis of peer-reviewed publications as well as published "field" information from individuals and organizations recently involved in the management of Ebola epidemics. The current epidemic management approaches are largely "reactive", with containment efforts aimed at halting spread of existing outbreaks. We recommend that for better outcomes, in addition to "reactive" interventions, "pre-emptive" strategies also need to be instituted. We conclude that emphasizing both "reactive" and "pre-emptive" strategies is more likely to lead to better epidemic preparedness and response at individual, community, institutional, and government levels, resulting in timely containment of future Ebola outbreaks. Copyright

  1. Guillain-Barre syndrome associated with hemorrhagic fever with renal syndrome in China: a case report.

    Jiao, Jie; Wu, Lei; Yin, Jianyuan; Quan, Xiaojiao; Chen, Wei; Hu, Jie

    2018-03-27

    We describe a case of Guillain-Barre syndrome (GBS) associated with hemorrhagic fever with renal syndrome. To our knowledge, only five cases of GBS associated with Hantavirus infection have been reported so far. A 62-year-old man presented intermittent fever, chill and oliguria. According to remarkable leukocytosis, atypical lymphocytes, thrombocytopenia and former dwelling in hemorrhagic fever-endemic area, he was suspected as hemorrhagic fever with renal syndromeand certified with positive Hantavirus IgG. Later, the patient had symmetrical flaccid paralysis of all extremities. Electromyography showed peripheral nerve injury (mainly in axon). The patient was diagnosed as having acute motor sensory axonal neuropathy (AMSAN). After immunoglobulin infusion, patient showed progressive recovery and was transferred 3 weeks after his first admission to a rehabilitation center. Our case was the 6th reported case of GBS associated with hemorrhagic fever with renal syndrome. Moreover, we for the first time classified the subtype of GBS (AMSAN) based on the electrophysiology characteristics. GBS should be suspected in patients who are already diagnosed as hemorrhagic fever with renal syndrome when delayed symmetrical limb paralysis occurs. Until recent now, GBS was only reported in hemorrhagic fever patients in Europe and Asia, which termed as hemorrhagic fever with renal syndrome.

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

    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...

  3. Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

    Zhi-Hai Chen

    Full Text Available Hemorrhagic fevers (HF caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF, 34 with Hemorrhagic Fever with Renal Syndrome (HFRS, one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC, higher levels of creations kinase (CK and alanine aminotransferase (ALT, while HFRS patients presented with an elevation of blood urea nitrogen (BUN and creatinine (CREA. These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

  4. Effective oral favipiravir (T-705 therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic Fever.

    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

  5. Question about the Clinical Characteristics of Crimean Hemorrhagic Fever

    A.I. Bogdanova

    2016-11-01

    Full Text Available Background. The research was organized in order to analyze features of the main clinical symptoms in patients with Crimean hemorrhagic fever (CHF. Materials and methods. In furtherance of this goal 37 patients with the diagnosis of moderate CHF were exa­mined; they were treated at BPHF Nichoga Regional Clinical Hospital of Infectious Diseases during 2005–2016. Results. The main complaints were general weakness (100 %, diffuse headache (91 %, loss of appetite (76 %, arthralgias (80 %, giddiness (32 %, nausea (52 %, vomiting (46 %, myalgia (65 % and arthralgia (78 %. Hemorrhagic syndrome manifested with petechial rash (79 %, post-injection (32.2 % and traumatic (7.5 % hematomas, blee­ding gums (52.3 %. Among cavity bleedings the examined patients had nasal (14.3 %, gastrointestinal (15.7 %, and microhematuria (18.3 %. There was no impairment of respiratory and cardiovascular systems. In 78 % of cases the symptoms of CNS dysfunction like retardation, bradyphrasia, rapid debilitating symptom and in several cases (8.1 % a sleep disorder were noted. Conclusions. Thus, the clinical picture of the main symptoms of CHF testifies the existence of HS as a main pathogenetic factor of illness which influences the disease course and finally defines the forecast of the disease.

  6. Deteksi Penyakit Dengue Hemorrhagic Fever dengan Pendekatan One Class Classification

    Zida Ziyan Azkiya

    2017-10-01

    Full Text Available Two class classification problem maps input into two target classes. In certain cases, training data is available only in the form of a single class, as in the case of Dengue Hemorrhagic Fever (DHF patients, where only data of positive patients is available. In this paper, we report our experiment in building a classification model for detecting DHF infection using One Class Classification (OCC approach. Data from this study is sourced from laboratory tests of patients with dengue fever. The OCC methods compared are One-Class Support Vector Machine and One-Class K-Means. The result shows SVM method obtained precision value = 1.0, recall = 0.993, f-1 score = 0.997, and accuracy of 99.7% while the K-Means method obtained precision value = 0.901, recall = 0.973, f- 1 score = 0.936, and accuracy of 93.3%. This indicates that the SVM method is slightly superior to K-Means for One-Class Classification of DHF patients.

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

    Guzman, María G; Kouri, Gustavo

    2003-05-01

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

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

    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

  9. Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein

    Bertagnoli, Stéphane; Gelfi, Jacqueline; Le Gall, Ghislaine; Boilletot, Eric; Vautherot, Jean-François; Rasschaert, Denis; Laurent, Sylvie; Petit, Frédérique; Boucraut-Baralon, Corine; Milon, Alain

    1996-01-01

    Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma vir...

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

    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...

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

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

    2017-10-01

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

  12. Enzootic transmission of yellow fever virus, Venezuela.

    Auguste, Albert J; Lemey, Philippe; Bergren, Nicholas A; Giambalvo, Dileyvic; Moncada, Maria; Morón, Dulce; Hernandez, Rosa; Navarro, Juan-Carlos; Weaver, Scott C

    2015-01-01

    Phylogenetic analysis of yellow fever virus (YFV) strains isolated from Venezuela strongly supports YFV maintenance in situ in Venezuela, with evidence of regionally independent evolution within the country. However, there is considerable YFV movement from Brazil to Venezuela and between Trinidad and Venezuela.

  13. Novel Molecular Beacon Probe-Based Real-Time RT-PCR Assay for Diagnosis of Crimean-Congo Hemorrhagic Fever Encountered in India

    Aman Kamboj

    2014-01-01

    Full Text Available Crimean-Congo hemorrhagic fever (CCHF is an emerging zoonotic disease in India and requires immediate detection of infection both for preventing further transmission and for controlling the infection. The present study describes development, optimization, and evaluation of a novel molecular beacon-based real-time RT-PCR assay for rapid, sensitive, and specific diagnosis of Crimean-Congo hemorrhagic fever virus (CCHFV. The developed assay was found to be a better alternative to the reported TaqMan assay for routine diagnosis of CCHF.

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

    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. Becoming an International Scientist in South Korea: Ho Wang Lee’s Research Activity about Epidemic Hemorrhagic Fever

    Miyoung SHIN

    2017-04-01

    Full Text Available In the 1960-70s, South Korea was still in the position of a science latecomer. Although the scientific research environment in South Korea at that time was insufficient, there was a scientist who achieved outcomes that could be recognized internationally while acting in South Korea. He was Ho Wang Lee(1928~ who found Hantann Virus that causes epidemic hemorrhagic fever for the first time in the world. It became a clue to identify causative viruses of hemorrhagic diseases that were scattered here and there throughout the world. In addition, these outcomes put Ho Wang Lee on the global center of research into epidemic hemorrhagic fever. This paper examines how a Korean scientist who was in the periphery of virology could go into the central area of virology. Also this article shows the process through which the virus found by Ho Wang Lee was registered with the international academia and he proceeded with follow-up research based on this progress to reach the level at which he generalized epidemic hemorrhagic fever related studies throughout the world. While he was conducting the studies, experimental methods that he had never experienced encountered him as new difficulties. He tried to solve the new difficulties faced in his changed status through devices of cooperation and connection. Ho Wang Lee’s growth as a researcher can be seen as well as a view of a researcher that grew from a regional level to an international level and could advance from the area of non-mainstream into the mainstream. This analytic tool is meaningful in that it can be another method of examining the growth process of scientists in South Korea or developing countries.

  16. Investigation of an isolated case of human Crimean–Congo hemorrhagic fever in Central Uganda, 2015

    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

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

    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.

  18. Spatial analysis of hemorrhagic fever with renal syndrome in China

    Yang Hong

    2006-04-01

    Full Text Available Abstract Background Hemorrhagic fever with renal syndrome (HFRS is endemic in many provinces with high incidence in mainland China, although integrated intervention measures including rodent control, environment management and vaccination have been implemented for over ten years. In this study, we conducted a geographic information system (GIS-based spatial analysis on distribution of HFRS cases for the whole country with an objective to inform priority areas for public health planning and resource allocation. Methods Annualized average incidence at a county level was calculated using HFRS cases reported during 1994–1998 in mainland China. GIS-based spatial analyses were conducted to detect spatial autocorrelation and clusters of HFRS incidence at the county level throughout the country. Results Spatial distribution of HFRS cases in mainland China from 1994 to 1998 was mapped at county level in the aspects of crude incidence, excess hazard and spatial smoothed incidence. The spatial distribution of HFRS cases was nonrandom and clustered with a Moran's I = 0.5044 (p = 0.001. Spatial cluster analyses suggested that 26 and 39 areas were at increased risks of HFRS (p Conclusion The application of GIS, together with spatial statistical techniques, provide a means to quantify explicit HFRS risks and to further identify environmental factors responsible for the increasing disease risks. We demonstrate a new perspective of integrating such spatial analysis tools into the epidemiologic study and risk assessment of HFRS.

  19. Hepatitis in Patients with Crimean –Congo Hemorrhagic Fever

    Batool Sharifi-Mood

    2014-04-01

    Full Text Available Background: Crimean–Congo hemorrhagic fever (CCHF is a viral disease and causing approximately 30% fatality rate. Recent studies have been reported that hepatitis in CCHF patients is with high mortality. The aim of this study was to determine the prevalence of hepatitis in the CCHF cases and also detect the mortality rate among patients with hepatitis. Materials and Methods: The present study was conducted in patients with CCHF who were hospitalized in Boo-Ali hospital in Zahedan between Oct 2009 to Feb 2012. Liver function tests including aminotransferase enzymes and prothrombin time and mortality rate were evaluated. Results: Among 53 patients with CCHF, hepatitis was seen in 19 patients (45%. Nine patients died (21%. All dead patients had a serum aminotransaminase level ≥10 times the upper normal limit. Conclusion: Our study showed that hepatitis is prevalent in CCHF patients and a serum aminotransaminase level ≥5 times the upper normal limit (UNL is a risk factor for severe disease and high mortality.

  20. Clinical manifestation and pathophysiology of Crimean-Congo hemorrhagic fever on human

    Siavash Hamzehpour

    2017-10-01

    Full Text Available The Crimean-Congo hemorrhagic fever is a febrile and acute viral disease, and it is sporadic and epidemic in human societies, although it is special for animals (1. The disease was first identified in the Crimean Peninsula in the years 1945-1944 and was called the Crimean Hemorrhagic Fever. In 1956, the epidemic of the disease in the Congo also occurred, and due to the similarity of the disease agent, the combination of names of these two regions was used for naming the disease (2. The cause of this disease is a single-stranded viraemia virus from the genus Neurovirus and the Bunyaviridae family (3. One of the ways to transmit the disease is tick bites, and the hyaloma ticks are the most important constituent of the Crimean-Congo fever vein and the reservoir. In addition to transmitting the disease to vertebrates, due to a vertical and horizontal transmission, they transmit it to the next generation (4. Also, human contact with meat, blood and contaminated secretions of livestock in a livestock eradication period causes the transmission of the disease (5. Human to human transmission, which is more often seen as a hospital infection, is also a means of transmitting the disease (6. The incubation period after a tick bite is 1 to 3 days and a maximum of 9 days, and is slightly longer after contact with contaminated blood or tissue about 5-6 days, and finally 14 days (7. In the early stages of the disease, symptoms are sudden which include severe headaches, fever, chills, muscle pain, especially the back and leg muscles, neck stiffness, dizziness, reddening of the eyes, fear of light, nausea, vomiting and diarrhea. Then, a severe generalized muscle pain appears, mostly at the back and hamstring, and the patient complains of back pain and epigastric pain (8. In the examination of patients, facial flushing and chest thigtness, hyperemia of throat mucusand petechialsare common symptoms which draw attention. Hemorrhagic phenomena include melena

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

    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.

  2. Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

    Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

    1996-08-01

    Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

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

    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 ...

  4. Ebola haemorrhagic fever virus: pathogenesis, immune responses, potential prevention.

    Marcinkiewicz, Janusz; Bryniarski, Krzysztof; Nazimek, Katarzyna

    2014-01-01

    Ebola zoonotic RNA filovirus represents human most virulent and lethal pathogens, which induces acute hemorrhagic fever and death within few days in a range of 60-90% of symptomatic individuals. Last outbreak in 2014 in West Africa caused panic that Ebola epidemic can be spread to other continents. Number of deaths in late December reached almost 8,000 individuals out of more than 20,000 symptomatic patients. It seems that only a coordinated international response could counteract the further spread of Ebola. Major innate immunity mechanisms against Ebola are associated with the production of interferons, that are inhibited by viral proteins. Activation of host NK cells was recognized as a leading immune function responsible for recovery of infected people. Uncontrolled cell infection by Ebola leads to an impairment of immunity with cytokine storm, coagulopathy, systemic bleeding, multi-organ failure and death. Tested prevention strategies to induce antiviral immunity include: i. recombinant virus formulations (vaccines); ii. cocktail of monoclonal antibodies (serotherapy); iii. alternative RNA-interference-based antiviral methods. Maintaining the highest standards of aseptic and antiseptic precautions is equally important. Present brief review summarizes a current knowledge concerning pathogenesis of Ebola hemorrhagic disease and the virus interaction with the immune system and discusses recent advances in prevention of Ebola infection by vaccination and serotherapy.

  5. A Study on Plasma Renin Activity in Korean Hemorrhagic Fever

    Kim, Suhng Gwon; Cho, Bo Yun; Lee, Jung Sang; Koh, Won Soon; Lee, Mun Ho; Kim, Won Dong; Yun, Hong Jin

    1976-01-01

    To evaluate the possible pathophysiologic role of renin in acute renal failure observed in Korean hemorrhagic fever (KHF), the author measured the basal plasma renin activity (PRA) and the stimulated PRA by radioimmunoassay for angiotensin I in 15 normal controls and 42 KHF patients who are admitted in Seoul National University Hospital and Nation Army Hospital from Jan. 1975 to Jan. 1976. The results obtained were as follows:The mean basal PRA in normal control group was 2.9±2.16 ng/ml/hr in the patients during the oliguric phase of KHF, the mean basal PRA was 4.7±2.13 ng/ml/hr, and there was statistically significant increase compared to the normal control. In the patients during the diuretic phase of KHF, the mean basal PRA was 3.4±2.09 ng/ml/hr, and there was statistically significant decrease compared to the oliguric phase of KHF. In normal control group, the mean basal PRA was 2.9±2.16 ng/ml/hr. And the PRA 1 hour after the administration of Lasix 40 mg intravenously (stimulated PRA) was 5.3±2.20 ng/ml/hr and there was statistically significant increase compared to basal level. In oliguric phase of KHF, the mean basal PRA was 4.6±2.01 ng/ml/hr. And stimulated PRA was 4.4±2.34 ng/ml/hr and there was no significant changes. In diuretic phase of KHF, the mean basal PR was 3.3±1.86 ng/ml/hr. And stimulated PRA was 5.2±2.58 ng/ml/hr and there was statistically significant increase compared to basal level. There were statistically no significant correlations between basal PRA and stimulated PRA and serum creatinine. BUN, urine volume and peritoneal dialysis.

  6. The Co- Infection of Crime Congo Hemorrhagic Fever and Brucellosis: A Case Report

    A Saghafipour

    2012-07-01

    Full Text Available

    Background and Objectives: Crimean-Congo Hemorrhagic fever (CCHF is a viral disease transmitted to ruminants or human by the bite of mature tick vectors. It can be transmitted through contact with the infectious blood or viraemic tissues during slaughter and hospital contacts. 80% of the cases are sub clinical and the rest of them are presenting with an acute febrile and occasionally hemorrhagic disease. The mortality rate of the fulminate form of the disease is equal to 20% to 50%. The hemorrhage is usually in the form of hematoma, melena, nose, conjunctiva, uterine or subcutaneous bleeding. CCHF complications are: encephalitis, optic neuropathy, hepatitis, renal failure and myocardial necrosis.

     

    Case Report: In this article, we’ve discussed a CCHF patient who presented with high fever, myalgia, headache, nausea, vomiting, abdominal pain, diffuse cutaneous and gingival hemorrhage during the course of the disease while the patient was hospitalized. Profound jaundice, petechia and global ecchymosis were considerable. Lab data showed at the beginning of hospitalization that the number of liver enzymes was increased up to 8-10 times. The number of placates were lower than 150000 ml. Moreover, during the first three days there was a decrease in the number of white blood cells and PTT was abnormal. (AST was higher than 100 units per litre. The results of serologic examination of IgM- ELISA virus for CCHF on day 5 and IgG-ELISA on day 10–which were carried out in pasture Institute-were reported to be positive. According to the patient’s history and clinical symptoms, he was also suspicious for Brucellosis and the lab data demonstrated that he is also infected with Brucella. (Wright=1.320, 2ME=1.160 (The patient was a 22 year old man, sheep farmer, residing in the GhalehKamkar area of Qom City.

     

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

    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.

  8. Dengue hemorrhagic fever complicated with acute liver failure: a case report.

    Dalugama, Chamara; Gawarammana, Indika Bandara

    2017-12-08

    Dengue is a common arboviral infection with a clinically diverse spectrum of presentations. Although hepatic dysfunction is commonly identified in patients will dengue illness, acute liver failure is rare. The etiopathogenesis of hepatic dysfunction is multifactorial and related to direct viral invasion of hepatocytes, immunological factors and hypoxia particularly in cases of shock in dengue hemorrhagic fever. Ideal management of dengue-related hepatic dysfunction and acute liver failure is still debated. We report a 53-year-old Sri Lankan Sinhalese male with serologically confirmed dengue fever presenting with evidence of plasma leakage developing acute liver failure evidenced by deranged liver functions, coagulopathy and altered sensorium. In addition to the 'standard care', the patient was managed with intravenous N-acetyl cysteine and blood transfusions even in the absence of bleeding or dropping packed cell volume (PCV), targeting a higher PCV in anticipation of better oxygenation at tissue level. He made a full recovery with no sequential infections. N-acetyl cysteine and packed cell transfusion aiming at a higher PCV to maintain adequate tissue perfusion during shock may be beneficial in acute liver failure due to dengue virus. Large randomized trials should be carried out to establish the efficacy of these treatment strategies to support these observations and change the current practice.

  9. [Clinical presentation of different severities of hemorrhagic fever with renal syndrome: how to recognise it].

    Lausević, Mirjana; Lausević, Zeljko; Stojimirović, Biljana

    2012-07-01

    Besides viral serotype, HLA haplotype and cytokine genes polymorphism are associated with clinical presentation of hemorrhagic fever with renal syndrome. Since these analyses are unavailable in routine clinical practice, the aim of this study was to assess clinical, laboratory and radiographic findings associated with clinical presentation of disease severity. A total of 30 patients (27 men and 3 women), average age 40 +/- 14.9 years, treated for hemorrhagic fever with renal syndrome from January 1, 1999 to December 31, 2009 in Clinical Center of Serbia, were included in the study. Nine patients (30%) had mild, 14 (46.7%) moderate and 7 (23.3%) severe form of the disease; 24 (800%) recovered, 6 (20%) died in the acute phase of the illness, and 19 patients (63.3%) required hemodialysis. The average titer of antiviral antibodies in patients infected with Belgrade serotype virus were significantly higher in those with severe clinical presentation. Hypotension, anuria, macrohaematuria, pulmonary infiltration, pleural effusion, hepatomegalia and positive meningeal signs were more frequent in the patients with severe form of the disease. Statistically significant differences between groups with mild, moderate and severe clinical picture were found in serum total protein, albumin, calcium, glutamate pyruvate and glutamate oxaloacetate transaminase on admittance; serum creatinine and phosphorus concentration on day 14 and day 21; serum sodium and calciums on day 14; hemoglobine concentration on day 21. A statistically significant correlation was found between clinical presentation of the disease severity and platelet count, white blood cell count, hemoglobine concentration, serum calcium and serum transaminases on admittance. Multivariate analysis identified variables' combinations associated with clinical presentation of the disease. Our study confirmed that we can distinguish patients who will manifest different severities of the disease on the basis of careful

  10. Crimean Congo hemorrhagic fever among the one-humped camel (Camelus dromedaries) in Central Sudan.

    Suliman, Hajer M; Adam, Ibrahim A; Saeed, Shamseldin I; Abdelaziz, Sanaa A; Haroun, Eltahir M; Aradaib, Imadeldin E

    2017-08-03

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonotic disease caused by Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus in the family Bunyaviridae. CCHF is typically asymptomatic in animals but can be highly fatal in humans approaching case fatality rate of approximately 30%. In the present investigation, a cross sectional study was conducted to determine the prevalence of CCHF and to identify the potential risk factors associated with CCHFV seropositivity among the one-humped camel (Camelus dromedaries) in Central Sudan. A total of 361 camels selected randomly from six localities were employed in the study. Sera sampled were tested for the presence of CCHFV-specific immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assay (ELISA). CCHFV seropositivity was recorded in 77 out of 361 animals accounting for a prevalence rate of 21.3%. Age (OR = 3.6, CI = 1.72-7.79, p-value = 0.026); locality (OR = 5.85, CI = 1.81-18.83, p- value = 0.003), tick number (OR = 4.6, CI = 1.37-9.81, P-value 0.04); tick control (OR = 2.2, CI, 1.11-4.35, P-value = 0.023) and breed (OR = 6.60, CI = 2.38-18.36, P-value = 0.001) were recorded as potential risk factors for contracting CCHF. The prevalence of CCHF is significantly high among camels in Khartoum State, Sudan. Age, breed, locality and tick control are considered as potential risk factors for contracting CCHF. This study would be expected to reduce the impact on the livelihood of pastoral communities and ultimately avoid disease spread in human.

  11. Clinical presentation of different severities of hemorrhagic fever with renal syndrome: How to recognize it

    Laušević Mirjana

    2012-01-01

    Full Text Available Background/Aim. Besides viral serotype, HLA haplotype and cytokine genes polymorphism are associated with clinical presentation of hemorrhagic fever with renal syndrome. Since these analyses are unavailable in routine clinical practice, the aim of this study was to assess clinical, laboratory and radiographic findings associated with clinical presentation of disease severity. Methods. A total of 30 patients (27 men and 3 women, average age 40 ± 14.9 years, treated for hemorrhagic fever with renal syndrome from January 1, 1999 to December 31, 2009 in Clinical Center of Serbia, were included in the study. Nine patients (30% had mild, 14 (46.7% moderate and 7 (23.3% severe form of the disease; 24 (80% recovered, 6 (20% died in the acute phase of the illness, and 19 patients (63.3% required hemodialysis. Results. The average titer of antiviral antibodies in patients infected with Belgrade serotype virus were significantly higher in those with severe clinical presentation. Hypotension, anuria, macrohaematuria, pulmonary infiltration, pleural effusion, hepatomegalia and positive meningeal signs were more frequent in the patients with severe form of the disease. Statistically significant differences between groups with mild, moderate and severe clinical picture were found in serum total protein, albumin, calcium, glutamate pyruvate and glutamate oxaloacetate transaminase on admittance; serum creatinine and phosphorus concentration on day 14 and day 21; serum sodium and calciums on day 14; hemoglobine concentration on day 21. A statistically significant correlation was found between clinical presentation of the disease severity and platelet count, white blood cell count, hemoglobine concentration, serum calcium and serum transaminases on admittance. Multivariate analysis identified variables` combinations associated with clinical presentation of the disease. Conclusion. Our study confirmed that we can distinguish patients who will manifest different

  12. Renal Artery Embolization of Perirenal Hematoma in Hemorrhagic Fever with Renal Syndrome: A Case Report

    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.

  13. Renal Artery Embolization of Perirenal Hematoma in Hemorrhagic Fever with Renal Syndrome: A Case Report

    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

  14. Acute viral hemorrhage disease: A summary on new viruses

    Somsri Wiwanitkit

    2015-10-01

    Full Text Available Acute hemorrhagic disease is an important problem in medicine that can be seen in many countries, especially those in tropical world. There are many causes of acute hemorrhagic disease and the viral infection seems to be the common cause. The well-known infection is dengue, however, there are many new identified viruses that can cause acute hemorrhagic diseases. In this specific short review, the authors present and discuss on those new virus diseases that present as “acute hemorrhagic fever”.

  15. Capacity building permitting comprehensive monitoring of a severe case of Lassa hemorrhagic fever in Sierra Leone with a positive outcome: Case Report

    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. 20 Years Spatial-Temporal Analysis of Dengue Fever and Hemorrhagic Fever in Mexico.

    Hernández-Gaytán, Sendy Isarel; Díaz-Vásquez, Francisco Javier; Duran-Arenas, Luis Gerardo; López Cervantes, Malaquías; Rothenberg, Stephen J

    2017-10-01

    Dengue Fever (DF) is a human vector-borne disease and a major public health problem worldwide. In Mexico, DF and Dengue Hemorrhagic Fever (DHF) cases have increased in recent years. The aim of this study was to identify variations in the spatial distribution of DF and DHF cases over time using space-time statistical analysis and geographic information systems. Official data of DF and DHF cases were obtained in 32 states from 1995-2015. Space-time scan statistics were used to determine the space-time clusters of DF and DHF cases nationwide, and a geographic information system was used to display the location of clusters. A total of 885,748 DF cases was registered of which 13.4% (n = 119,174) correspond to DHF in the 32 states from 1995-2015. The most likely cluster of DF (relative risk = 25.5) contained the states of Jalisco, Colima, and Nayarit, on the Pacific coast in 2009, and the most likely cluster of DHF (relative risk = 8.5) was in the states of Chiapas, Tabasco, Campeche, Oaxaca, Veracruz, Quintana Roo, Yucatán, Puebla, Morelos, and Guerrero principally on the Gulf coast over 2006-2015. The geographic distribution of DF and DHF cases has increased in recent years and cases are significantly clustered in two coastal areas (Pacific and Gulf of Mexico). This provides the basis for further investigation of risk factors as well as interventions in specific areas. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

  17. Consensus report: Preventive measures for Crimean-Congo Hemorrhagic Fever during Eid-al-Adha festival.

    Leblebicioglu, Hakan; Sunbul, Mustafa; Memish, Ziad A; Al-Tawfiq, Jaffar A; Bodur, Hurrem; Ozkul, Aykut; Gucukoglu, Ali; Chinikar, Sadegh; Hasan, Zahra

    2015-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is endemic in Eurasian countries such as, Turkey, Pakistan, Afghanistan and Iran. CCHF virus is spread by the Hyalomma tick, which is found mainly on cattle and sheep. Muslim countries, in which these animals are sacrificed during Eid-Al-Adha, are among the countries where CCHF is endemic, and it has been observed that CCHF is associated with practices surrounding the Eid-ad-Adha festival. The dates for Eid-Al-Adha drift 10 days earlier in each year according to Georgian calendar. In previous years Eid-al-Adha occurred in autumn-winter months however in the next 10-15 years it will be take place in the summer months when CCHF is more prevalent. This may lead to a rise in the number of cases due to increased dissemination of CCHF virus with uncontrolled animal movements in and between countries. This consensus report focuses on the variable practices regarding animal handling in different regions and possible preventative measures to reduce the incidence of CCHF. Environmental hygiene and personal protection are essential parts of prevention. There is a need for international collaborative preparedness and response plans for prevention and management of CCHF during Eid-Al-Adha in countries where the disease is prevalent. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Dengue Hemorrhagic Fever at 60 Years: Early Evolution of Concepts of Causation and Treatment.

    Halstead, Scott B; Cohen, Sanford N

    2015-09-01

    During the decade of the 1960s, the epidemiology of a new dengue disease, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), was described by collaborative research performed by Thai scientists from many institutions and by workers at the U.S. Army's SEATO Medical Research Laboratory in Bangkok, Thailand. Careful clinical and physiological studies provided the initial description of DSS. DSS cases were caused by each of the four dengue viruses (DENV) and not chikungunya (CHIK) virus or DENV 5 and 6, were associated with a secondary-type dengue antibody response in children over the age of 1 year, were associated with a primary antibody response in infants less than 1 year old whose mothers had neutralizing antibodies to all four DENV, were associated more frequently with secondary DENV 2 infections than those due to DENV 1 and 3, and were more common in females than males over the age of 3 years. Robust laboratory methods for growth and recovery of DENV in tissue cultures were introduced. In addition, life-saving principles of fluid and plasma protein resuscitation of hypovolemia were described. Most epidemiological observations made during the decade of the 1960s have been confirmed in the succeeding 45 years. Much contemporary research on pathogenesis fails to address the two distinct immunological antecedents of DHF/DSS. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Thyroid Hormones and Thyroid Function status in each clinical phase of Korean Hemorrhagic Fever

    Shin, Young Tae; Jeon, Byung Sook; Yoon, Sung Yeul; Lee, Houn Young; Kim, Sam Yong; Ro, Heung Kyu

    1983-01-01

    Fifteen cases of Korean hemorrhagic fever who were admitted Chungnam National University Hospital from October 1981 to December 1981 were analysed on the evaluation of metabolic changes of the thyroid hormones, and thyroid function status in each clinical phase. 1) Serum T 3 , T 4 concentration, FT 4 I and T 4 /TBG ratio were significantly lower (p 4 , TSH and TBG concentration were within normal range in all phase of KHF. Thus in Korean hemorrhagic fever, euthyroidism is probably maintained by normal or elevated serum FT 4 . 2) T 4 /T 3 and rT 3 /T 3 ratio (p 4 to T 3 in oliguric and early diuretic phase.

  20. Changes of Pituitary Hormones after Injection of Naloxone in the Hypotensive Phase of Korean Hemorrhagic Fever

    Lim, Sang Moo; Cho, Bo Youn; Lee, Hong Gyu; Lee, Jung Sang; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Byung Tae [Hallym Medical College, Seoul (Korea, Republic of)

    1986-09-15

    The opiate antagonist, naloxone, was injected for the reversal of hypotension due to Korean hemorrhagic fever, and the authors observed changes in pituitary hormones. In the hypotensive phase of the Korean hemorrhagic fever, the beta-endorphin was high, and normalized gradually in the diuretic and convalescent period. The naloxone raised the pulse rate and the blood pressure within 30 minutes without change in the central venous pressure. Around 30 minuted after the injection of the naloxone, the beta-endorphin, ACTH and cortisol rose. The prolactin fell down 60 minutes after the naloxone injection.

  1. Detection of viral hemorrhagic septicemia virus

    Winton, James; Kurath, Gael; Batts, William

    2007-01-01

    Viral hemorrhagic septicemia virus (VHSV) is considered to be one of the most important viral pathogens of finfish and is listed as reportable by many nations and international organizations (Office International des Epizooties 2006). Prior to 1988, VHSV was thought to be limited to Europe (Wolf 1988; Smail 1999). Subsequently, it was shown that the virus is endemic among many marine and anadromous fish species in both the Pacific and Atlantic Oceans (Meyers and Winton 1995; Skall et al. 2005). Genetic analysis reveals that isolates of VHSV can be divided into four genotypes that generally correlate with geographic location with the North American isolates generally falling into VHSV Genotype IV (Snow et al. 2004). In 2005-2006, reports from the Great Lakes region indicated that wild fish had experienced disease or, in some cases, very large die-offs from VHSV (Elsayed et al. 2006, Lumsden et al. 2007). The new strain from the Great Lakes, now identified as VHSV Genotype IVb, appears most closely related to isolates of VHSV from mortalities that occurred during 2000-2004 in rivers and near-shore areas of New Brunswick and Nova Scotia, Canada (Gagne et al. 2007). The type IVb isolate found in the Great Lakes region is the only strain outside of Europe that has been associated with significant mortality in freshwater species.

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

    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.

  3. Hemorrhagic fever with renal syndrome: clinical, pathogenetic and therapeutic aspects

    Vera F. Pavelkina

    2017-09-01

    Full Text Available Introduction: The republic of Mordovia (RM is an active natural focus of hemorrhagic fever with renal syndrome (HFRS. The incidence of HFRS ranges from 10 to 40 cases per 100 000 people, i.e. exceeds the average Russian rate. The relevance of HFRS is determined by the involvement of many organs and systems in the pathological process. The intoxication syndrome (IS takes a leading place in the pathogenesis of the disease. The development of IS is associated with both the phenomenon of viremia, and the accumulation of endogenous toxins in the body. Despite the large number of recommendations, the problem of IS correction is not completely solved. Antiviral drugs are not applicable in connection with a short period of viremia. Therefore, the basis of treatment is pathogenetic therapy. The purpose of research is to study the clinical, epidemiological and therapeutic aspects of the medium degree HFRS. Materials and Methods: In the course of the study, the patients of two groups were examined: the first group (comparison group, 35 patients received basal therapy; the second group (primary group, 25 patients received a dropwise preparation of remaxol (400 ml for 7 days intravenously. The control group consisted of 30 healthy people of a similar age group. The clinical features of the disease in the Republic of Mordovia, as well as objective indicators were observed. Urea, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, medium-weight molecules (MWM, circulating immune complexes (CIC, total, effective concentration and binding capacity of albumin (TCA, ECA, BCA, and toxicity index (TI were studied. Results: The infection was mainly in rural areas (78.3 %. Despite the c yclicity of the course, there was no clearly defined period of oliguria in the HFRS clinic (in 22 %, polyuria in 27 % of cases. Hepatomegaly is combined with a change in functional liver samples. The pathological changes indicate the presence of IS, which

  4. The International Conference on Hemorrhagic Fever with Renal Syndrome (1st) Held in Seoul, Korea on 4-6 May 1989

    1990-05-01

    suggest that the body is important for a maker of 1lFRS-virus infection. 69 PROSPECTIVE STUDY ON PANHYPOPITUITARISM AS A SEQUELA OF HEMORRHAGIC FEVER...necrosis is a characteristic and common autopsy finding. Contrary to this, only 14 cases of clinical panhypopituitarism have been reported. Recently we...confirmed six patients with panhypopituitarism by high resolution sella computed tomo-,raphy(CT) and combined anterior pituitary stimulation lest(CAPS I

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

    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

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

    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...

  7. Differential Regulation of PAI-1 in Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever With Renal Syndrome

    Bellomo, Carla; Korva, Miša; Papa, Anna; Mäkelä, Satu; Mustonen, Jukka; Avšič-Županc, Tatjana; Vaheri, Antti; Martinez, Valeria P; Strandin, Tomas

    2018-01-01

    Abstract We analyzed the levels of circulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)–1 in acute hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). The levels of tPA commonly increased in both diseases, whereas PAI-1 correlated with disease severity in HCPS but not in HFRS.

  8. Yellow fever virus: genetic and phenotypic diversity and implications for detection, prevention and therapy.

    Beasley, David W C; McAuley, Alexander J; Bente, Dennis A

    2015-03-01

    Yellow fever virus (YFV) is the prototypical hemorrhagic fever virus, yet our understanding of its phenotypic diversity and any molecular basis for observed differences in disease severity and epidemiology is lacking, when compared to other arthropod-borne and haemorrhagic fever viruses. This is, in part, due to the availability of safe and effective vaccines resulting in basic YFV research taking a back seat to those viruses for which no effective vaccine occurs. However, regular outbreaks occur in endemic areas, and the spread of the virus to new, previously unaffected, areas is possible. Analysis of isolates from endemic areas reveals a strong geographic association for major genotypes, and recent epidemics have demonstrated the emergence of novel sequence variants. This review aims to outline the current understanding of YFV genetic and phenotypic diversity and its sources, as well as the available animal models for characterizing these differences in vivo. The consequences of genetic diversity for detection and diagnosis of yellow fever and development of new vaccines and therapeutics are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Pharmacotherapy of Ebola hemorrhagic fever: a brief review of current status and future perspectives.

    Olszanecki, Rafał; Gawlik, Grzegorz

    2014-01-01

    The 2014 outbreak clearly showed that Ebola viruses (EBOV) remain a substantial threat for public health. The mainstay of management of patients with Ebola disease is isolation of patients and use of strict barrier nursing procedures; the present treatment strategies are mainly symptomatic and supportive (fluid resuscitation, antypyretics, antidiarrheal drugs). Currently, there is no approved therapy for Ebola hemorrhagic fever (EHF), however several advanced treatment options were tested in animal models (on non-human primates or rodents). They include use of both symptomatic (e.g. use of tissue factor inhibitors - rhNAPc2, rhAPC - to abolish coagulopathy) and specific antiviral approaches: e.g. monoclonal anti EBOV antibodies (ZMapp, MB-003), phosphorodiamidate morpholino oligomers (PMOs), liposomes containing siRNA (LNP-siRNA:TKM-Ebola) and small molecule inhibitors (e.g. BCX4430, favipiravir). The scope of this article is to briefly review the most promising therapeutics for EHF, based on the data coming from rare clinical reports, studies on animals and results from in vitro models.

  10. Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses

    Abraham, Jonathan; Corbett, Kevin D.; Farzan, Michael; Choe, Hyeryun; Harrison, Stephen C. (Harvard-Med)

    2010-08-18

    New World hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. The GP1 subunit of the surface glycoprotein mediates cell attachment through transferrin receptor 1 (TfR1). We report the structure of Machupo virus (MACV) GP1 bound with human TfR1. Atomic details of the GP1-TfR1 interface clarify the importance of TfR1 residues implicated in New World arenavirus host specificity. Analysis of sequence variation among New World arenavirus GP1s and their host-species receptors, in light of the molecular structure, indicates determinants of viral zoonotic transmission. Infectivities of pseudoviruses in cells expressing mutated TfR1 confirm that contacts at the tip of the TfR1 apical domain determine the capacity of human TfR1 to mediate infection by particular New World arenaviruses. We propose that New World arenaviruses that are pathogenic to humans fortuitously acquired affinity for human TfR1 during adaptation to TfR1 of their natural hosts.

  11. T Cells and Pathogenesis of Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome

    Francis A. Ennis

    2011-07-01

    Full Text Available 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 responses negatively correlated with disease severity, but in another report the number of regulatory T cells, which are thought to suppress T cell responses, negatively correlated with disease severity. In rat experiments, in which hantavirus causes persistent infection, depletion of regulatory T cells helped infected rats clear virus without inducing immunopathology. These seemingly contradictory findings may suggest delicate balance in T cell responses between protection and immunopathogenesis. Both too strong and too weak T cell responses may lead to severe disease. It is important to clarify the role of T cells in these diseases for better treatment (whether to suppress T cell functions and protection (vaccine design which may need to take into account viral factors and the influence of HLA on T cell responses.

  12. An Outbreak of Ebola Virus Disease in the Lassa Fever Zone.

    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.

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

    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.

  14. Spatial analysis of hemorrhagic fever with renal syndrome in Zibo City, China, 2009-2012.

    Feng Cui

    Full Text Available BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS is highly endemic in mainland China, where human cases account for 90% of the total global cases. Zibo City is one of the most serious affected areas in Shandong Province China with the HFRS incidence increasing sharply from 2009 to 2012. However, the hotspots of HFRS in Zibo remained unclear. Thus, a spatial analysis was conducted with the aim to explore the spatial, spatial-temporal and seasonal patterns of HFRS in Zibo from 2009 to 2012, and to provide guidance for formulating regional prevention and control strategies. METHODS: The study was based on the reported cases of HFRS from the National Notifiable Disease Surveillance System. Annualized incidence maps and seasonal incidence maps were produced to analyze the spatial and seasonal distribution of HFRS in Zibo City. Then spatial scan statistics and space-time scan statistics were conducted to identify clusters of HFRS. RESULTS: There were 200 cases reported in Zibo City during the 4-year study period. One most likely cluster and one secondary cluster for high incidence of HFRS were identified by the space-time analysis. And the most likely cluster was found to exist at Yiyuan County in October to December 2012. The human infections in the fall and winter reflected a seasonal characteristic pattern of Hantaan virus (HTNV transmission. The secondary cluster was detected at the center of Zibo in May to June 2009, presenting a seasonal characteristic of Seoul virus (SEOV transmission. CONCLUSION: To control and prevent HFRS in Zibo city, the comprehensive preventive strategy should be implemented in the southern areas of Zibo in autumn and in the northern areas of Zibo in spring.

  15. Mean Platelet Volume and Neutrophil-to-Lymphocyte Ratio in Patients with Crimean–Congo Hemorrhagic Fever

    Derya Koçer

    2015-01-01

    Full Text Available Objectives: Crimean–Congo hemorrhagic fever (CCHF is a tick-borne zoonotic infection caused by Crimean Congo hemorrhagic fever virus (CCHFV. The aim of the present study was to investigate the association between blood neutrophil-to-lymphocyte ratio (NLR and mean platelet volume (MPV which are simple markers of subclinical inflammation and CCHF. We also investigated the relationship of these markers with coagulation parameters.Methods: Thirty-one suspected CCHF patients, who submitted to Training and Research Hospital, Kayseri, Turkey between 2009 and 2013, were evaluated retrospectively. Among thirty-one patients, nineteen were laboratory confirmed CCHF patients diagnosed by RT-PCR or CCHFV-specific IgM positivity. Alanine aminotransferase (ALT, aspartate aminotransferase (AST, lactate dehydrogenase (LDH, creatinin phosphokinase (CK, coagulation parameters, white blood cell counts (WBCs, and platelet counts of patient group were compared with twenty-five healthy individuals.Results: MPV, AST, ALT, LDH, CK and coagulation parameters were significantly higher in patients with CCHF than the controls, whereas WBCs, neutrophil, lymphocyte, hemoglobin, platelet counts and NLR were significantly lower (p<0.05. We found no significant correlation between MPV, NLR and coagulation parameters.Conclusions: Our study demonstrates that MPV and NLR may be beneficial markers in the diagnosis of CCHF. But these parameters should not be considered stand-alone tests for this use owing to nonspecificity with other diseases.

  16. Phylogeny of Yellow Fever Virus, Uganda, 2016.

    Hughes, Holly R; Kayiwa, John; Mossel, Eric C; Lutwama, Julius; Staples, J Erin; Lambert, Amy J

    2018-08-17

    In April 2016, a yellow fever outbreak was detected in Uganda. Removal of contaminating ribosomal RNA in a clinical sample improved the sensitivity of next-generation sequencing. Molecular analyses determined the Uganda yellow fever outbreak was distinct from the concurrent yellow fever outbreak in Angola, improving our understanding of yellow fever epidemiology.

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

    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.

  18. 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

    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...

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

    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.

  20. Report of the first case of Crimean Congo hemorrhagic fever in Qazvin Province (2016

    AR. Nikoonejad

    2016-12-01

    Full Text Available Crimean Congo hemorrhagic fever is a potentially fatal disease that is reported from Asia, Africa and Europe. In May, 2016 a 42 year-old female is admitted to Buali-Sina hospital with epistaxis and within a few hours got loss of consciousness and shock. The patient was put on supportive care and oral Ribavirin. From the sixth admission day, the general condition of the patient improved and on the eleventh day she was discharged without an important sequela. Consequently, it is necessary to consider this disease in the differential diagnosis of all patients presented with fever and acute bleeding diathesis.

  1. Molecular characterization of African swine fever virus in apparently ...

    African swine fever (ASF) is a highly lethal and economically significant disease of domestic pigs in Uganda where outbreaks regularly occur. There is neither a vaccine nor treatment available for ASF control. Twenty two African swine fever virus (ASFV) genotypes (I - XXII) have been identified based on partial sequencing ...

  2. Close Relationship of Ruminant Pestiviruses and Classical Swine Fever Virus

    Postel, Alexander; Schmeiser, Stefanie; Oguzoglu, Tuba Cigdem; Indenbirken, Daniela; Alawi, Malik; Fischer, Nicole; Grundhoff, Adam

    2015-01-01

    To determine why serum from small ruminants infected with ruminant pestiviruses reacted positively to classical swine fever virus (CSFV)–specific diagnostic tests, we analyzed 2 pestiviruses from Turkey. They differed genetically and antigenically from known Pestivirus species and were closely related to CSFV. Cross-reactions would interfere with classical swine fever diagnosis in pigs. PMID:25811683

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

    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.

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

    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.

  5. [A case of brucellosis and Crimean-Congo hemorrhagic fever coinfection in an endemic area].

    Karakeçili, Faruk; Çıkman, Aytekin; Akın, Hicran; Gülhan, Barış; Özçiçek, Adalet

    2016-04-01

    Brucellosis, a zoonotic disease which is especially seen in developing countries is still an important public health problem worldwide. Crimean-Congo hemorrhagic fever (CCHF) is another zoonotic disease that transmits to humans by infected tick bites as well as exposure to blood or tissue from infected animals. Both of the diseases are common among persons who live in rural areas and deal with animal husbandry. Since brucellosis usually presents with non-specific clinical symptoms and may easily be confused with many other diseases, the diagnosis of those infections could be delayed or misdiagnosed. In this report, a case of coinfection of brucellosis and CCHF has been presented to emphasize the possibility of association of these infections. A 70-year-old female patient with a history of dealing with animal husbandry in a rural area admitted to our hospital with the complaints of fever, malaise, generalized body and joint pains, and headache. Her complaints had progressed within the past two days. She also reported nausea, vomiting, abdominal pain and bloody diarrhea. She denied any history of tick bites. Her physical examination was significant for the presence of 38.8°C fever, increased bowel sounds and splenomegaly. Laboratory analysis revealed leukopenia, thrombocytopenia and high levels of liver enzymes. The patient was admitted to our service with the prediagnosis of CCHF. Serum sample was sent to the Department of Microbiology Reference Laboratory at Public Health Agency of Turkey for CCHF testing. During patient's hospitalization in service, more detailed history was confronted and it was learned that she had fatigue, loss of appetite, sweating, joint pain, and intermittent fever complaints were continuing within a month and received various antibiotic treatments. The tests for brucellosis were conducted and positive results for Brucella Rose Bengal test, tube agglutination (1/160 titers) and immune capture test with Coombs (1/320 titers) were determined

  6. A crimean - congo hemorrhagic fever outbreak in northern balochistan

    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)

  7. Forecasting dengue hemorrhagic fever cases using ARIMA model: a case study in Asahan district

    Siregar, Fazidah A.; Makmur, Tri; Saprin, S.

    2018-01-01

    Time series analysis had been increasingly used to forecast the number of dengue hemorrhagic fever in many studies. Since no vaccine exist and poor public health infrastructure, predicting the occurrence of dengue hemorrhagic fever (DHF) is crucial. This study was conducted to determine trend and forecasting the occurrence of DHF in Asahan district, North Sumatera Province. Monthly reported dengue cases for the years 2012-2016 were obtained from the district health offices. A time series analysis was conducted by Autoregressive integrated moving average (ARIMA) modeling to forecast the occurrence of DHF. The results demonstrated that the reported DHF cases showed a seasonal variation. The SARIMA (1,0,0)(0,1,1)12 model was the best model and adequate for the data. The SARIMA model for DHF is necessary and could applied to predict the incidence of DHF in Asahan district and assist with design public health maesures to prevent and control the diseases.

  8. STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES

    Atkins, Elisha; Huang, Wei Cheng

    1958-01-01

    A substance with pyrogenic properties appears in the blood streams of rabbits made febrile by the intravenous inoculation of the PR8 strain of influenza A and Newcastle disease viruses (NDV). By means of a technique involving passive transfer of sera from animals given virus to recipient rabbits, the titer of circulating pyrogen was found to be closely correlated with the course of fever produced by virus. Certain properties of the pyrogen are described which differentiate it from the originally injected virus and suggest that the induced pyrogen is of endogenous origin. These properties resemble those of endogenous pyrogens occurring in other forms of experimental fever. The source of virus-induced pyrogen is unknown. In vitro incubation of virus with various constituents of the circulation did not result in the appearance of endogenous pyrogen. Granulocytopenia induced by HN2 failed to influence either fever or the production of endogenous pyrogen in rabbits injected with NDV. Similarly, the intraperitoneal inoculation of NDV into prepared exudates did not modify the febrile response. These findings do not lend support to the possibility that the polymorphonuclear leukocyte is a significant source of endogenous pyrogen in virus-induced fever. It is concluded that the liberation of an endogenous pyrogen from some as yet undefined source is an essential step in the pathogenesis of fever caused by the influenza group of viruses. PMID:13513908

  9. PLASMA LEAKAGE PROFILES OF DENGUE HEMORRHAGIC FEVER PATIENTS IN RSUD DR. SOETOMO, SURABAYA, EAST JAVA, INDONESIA JANUARY – JUNE 2014

    Ferdian Rizaliansyah

    2017-04-01

    Full Text Available Plasma leakage is one crucial point of dengue hemorrhagic fever (DHF that differentiates it from dengue fever (DF. DHF has to meet 4 criteria which are 2 – 7 days of acute fever, hemorrhagic manifestation, thrombocytopenia (≤100.000 cells/mm3 and evidence of plasma leakage. Plasma leakage consists of increasing hematocrit ≥20%, hypoalbuminemia or evidence of pleural effusion or ascites. Often doctors only base their DHF diagnosis on the presence of thrombocytopenia. This study analyzed the presence of plasma leakage between adult and pediatric patients with a DHF diagnosis in RSUD Dr. Soetomo in order to make the diagnosis and healthcare services better in the future. This was a retrospective study which used medical records of DHF patients admitted from January to June 2014. 78 cases were included, 24 adult patients (31% and 54 pediatric patients (69%. 29/78 (37% patients had no evidence of plasma leakage. No adult patients had ascites whereas 11/54 (20% pediatric patients presented with ascites. No adult patients had pleural effusion whereas 25/54 (53% pediatric patients did. Most adult patients that had serum albumin checked had normal albumin levels (12/14 [86%] while only 14/28 (52% pediatric patients had normal albumin level. 5/22 (23% adult patients versus 32/53 (60% pediatric patients showed hematocrit increments ≥20%. Patients admitted with dengue virus infection may currently be often misclassified as DHF because there are no plasma leakage manifestation in some patients.. There are significant differences in plasma leakage manifestations between adult and pediatric patients which poses a theory that pediatric patients are more susceptible to have plasma leakage manifestations than adult patients.

  10. T Cells and Pathogenesis of Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome

    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 ...

  11. Treatment model of dengue hemorrhagic fever infection in human body

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  12. Clinical and epidemiological features of hemorrhagic fever with renal syndrome course in Perm region

    M. V. Ivanova

    2011-01-01

    Full Text Available The results of retrospective analysis of hemorrhagic fever with renal syndrome (HFRS incidence in the Perm region for 1995–2009 are shown in the article. There are highly active natural foci of infection on the territory of the region, mainly in the subzone of mixed coniferous-deciduous forests. Factors supporting the morbidity are high numbers of small mammals, in particular, the bank vole, with a large circulation of the HFRS virus and active population visit of natural foci in summer-autumn period. Analysis of clinical features of HFRS in 338 patients living in the Perm region, revealed some peculiarities of its course. Among surveyed contingent men (72,4% prevailed. Most of the patients (80,4% were of working age (16 to 60 years. More frequently mild and moderate forms (92,8% of HFRS were observed. A typical picture of the disease with the development of all specific syndromes occurred mainly in patients with severe and moderate forms. Mild cases occurred blurry in the absence of pathognomonic symptoms. Notable was the frequent lesion of liver, with the development of acute anicteric hepatitis (51,2%. Among the complications dominated: pneumonia (4,7% and acute renal  ailure (4,4%. Manifestations of DIC syndrome with recurrent bleeding were registered in 0,6% of patients, toxic shock – at 0,3%. Case fatality rate was 0,6%.

  13. African Swine Fever Virus Biology and Vaccine Approaches.

    Revilla, Yolanda; Pérez-Núñez, Daniel; Richt, Juergen A

    2018-01-01

    African swine fever (ASF) is an acute and often fatal disease affecting domestic pigs and wild boar, with severe economic consequences for affected countries. ASF is endemic in sub-Saharan Africa and the island of Sardinia, Italy. Since 2007, the virus emerged in the republic of Georgia, and since then spread throughout the Caucasus region and Russia. Outbreaks have also been reported in Belarus, Ukraine, Lithuania, Latvia, Estonia, Romania, Moldova, Czech Republic, and Poland, threatening neighboring West European countries. The causative agent, the African swine fever virus (ASFV), is a large, enveloped, double-stranded DNA virus that enters the cell by macropinocytosis and a clathrin-dependent mechanism. African Swine Fever Virus is able to interfere with various cellular signaling pathways resulting in immunomodulation, thus making the development of an efficacious vaccine very challenging. Inactivated preparations of African Swine Fever Virus do not confer protection, and the role of antibodies in protection remains unclear. The use of live-attenuated vaccines, although rendering suitable levels of protection, presents difficulties due to safety and side effects in the vaccinated animals. Several African Swine Fever Virus proteins have been reported to induce neutralizing antibodies in immunized pigs, and vaccination strategies based on DNA vaccines and recombinant proteins have also been explored, however, without being very successful. The complexity of the virus particle and the ability of the virus to modulate host immune responses are most likely the reason for this failure. Furthermore, no permanent cell lines able to sustain productive virus infection by both virulent and naturally attenuated African Swine Fever Virus strains exist so far, thus impairing basic research and the commercial production of attenuated vaccine candidates. © 2018 Elsevier Inc. All rights reserved.

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

    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

  15. WEB Services Implementation on The Report of Dengue Hemorrhagic Fever (DHF At Health Office Karanganyar

    Ragil Saputra

    2013-06-01

    Full Text Available Abstract— Dengue Hemorrhagic Fever (DHF is one of the infectious diseases that frequently leads to Extraordinary Situation. The management of report is conducted by Health Community Center which subsequently gives report to Health Office. A problem arising from the report management is the fact that the report is conducted manually, therefore, the data is less valid and is not processed as quickly as possible. The quick and accurate data report system enables to lessen the risk of Dengue Hemorrhagic Fever. Due to this fact, it is undeniable necessary to provide an integrated inter-system of Dengue Fever report. This system includes an inter-system between one Health Community Center to another and to the system in Health Office. The integration of inter-system report is able to be conducted by the use of web service technology. Therefore, this research focuses on the development of Web Service based integrated system on the report of Dengue Fever. Data exchange is conducted in XML form by the application of SOAP and WSDL technologies. Library NuSOAP is necessary to provide class soapClient and soapServer. In other words, it functions as the listener whose functions are to receive and to respond at the access demand toward web service. The result is web service based report system which has dual functions since the system has functions to be either server or client. Keywords— web service, integration, SOAP, DHF.

  16. [EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

    Zhdanov, K W; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fusin, A Ya

    2015-01-01

    The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

  17. Typing of viral hemorrhagic septicemia virus by monoclonal antibodies

    Ito, Takafumi; Kurita, Jun; Sano, Motohiko

    2012-01-01

    Seven mAbs with specific reaction patterns against each of the four genotypes and eight subtypes of viral hemorrhagic septicemia virus (VHSV) were produced, aiming to establish an immunoassay for typing VHSV isolates according to their genotype. Among the mAbs, VHS-1.24 reacted with all genotypes...

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

    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.

  19. Dengue hemorrhagic fever and typhoid fever association based on spatial standpoint using scan statistics in DKI Jakarta

    Hervind, Widyaningsih, Y.

    2017-07-01

    Concurrent infection with multiple infectious agents may occur in one patient, it appears frequently in dengue hemorrhagic fever (DHF) and typhoid fever. This paper depicted association between DHF and typhoid based on spatial point of view. Since paucity of data regarding dengue and typhoid co-infection, data that be used are the number of patients of those diseases in every district (kecamatan) in Jakarta in 2014 and 2015 obtained from Jakarta surveillance website. Poisson spatial scan statistics is used to detect DHF and typhoid hotspots area district in Jakarta separately. After obtain the hotspot, Fisher's exact test is applied to validate association between those two diseases' hotspot. The result exhibit hotspots of DHF and typhoid are located around central Jakarta. The further analysis used Poisson space-time scan statistics to reveal the hotspot in term of spatial and time. DHF and typhoid fever more likely occurr from January until May in the area which is relatively similar with pure spatial result. Preventive action could be done especially in the hotspot areas and it is required further study to observe the causes based on characteristics of the hotspot area.

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

    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 ...

  1. Ribavirin: an effective treatment of crimean-congo hemorrhagic fever

    Sheikh, A.S.

    2004-01-01

    Objective: To determine the efficiency of Ribavirin, an anti-viral drug, in patients diagnosed to have CCHF. Patients and Methods: A total of 94 cases were included in the study on high index of suspicion of CCHF. The major criteria of admission were a short history of high-grade fever associated with bleeding from more than one site, i.e., haematemesis, epistaxis etc. the mean age was 34.71 plus minus 12.81 years. All the suspected cases were kept in isolation unit of the hospital and barrier nursing was advised. Results: All the 94 cases were sent to CDC, Atlanta, USA for confirmation and 39 (41.4%) were confirmed to have CCHF. Symptomatic treatment like platelet concentration transfusions, fresh-blood transfusions and antipyretics were given to all cases. Oral Ribavirin was given only to the confirmed cases. It was started in a dose of 2 gm initially, followed by 1 gm 6 hourly for 4 days and then 500 mg 8 hours for 6 days. After a mean period of 2.30 plus minus 0.69 days to treatment with Ribavirin, the clinical as well as the laboratory parameters started improving and returned to normal level after 10 -day course of treatment. Mild anemia and thrombocytosis were seen as adverse effects in some of the patients. Conclusion: For treatment of this fatal disease, we recommended use of oral Ribavirin in all patients diagnosed to have CCHF in the above-mentioned doses, on the basis of our study results.(author)

  2. Spatiotemporal trends and climatic factors of hemorrhagic fever with renal syndrome epidemic in Shandong Province, China.

    Li-Qun Fang

    Full Text Available BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS is a rodent-borne disease caused by Hantaviruses. It is endemic in all 31 provinces, autonomous regions, and metropolitan areas in mainland China where human cases account for 90% of the total global cases. Shandong Province is among the most serious endemic areas. HFRS cases in Shandong Province were first reported in Yutai County in 1968. Since then, the disease has spread across the province, and as of 2005, all 111 counties were reported to have local human infections. However, causes underlying such rapid spread and wide distribution remain less well understood. METHODS AND FINDINGS: Here we report a spatiotemporal analysis of human HFRS cases in Shandong using data spanning 1973 to 2005. Seasonal incidence maps and velocity vector maps were produced to analyze the spread of HFRS over time in Shandong Province, and a panel data analysis was conducted to explore the association between HFRS incidence and climatic factors. Results show a rapid spread of HFRS from its epicenter in Rizhao, Linyi, Weifang Regions in southern Shandong to north, east, and west parts of the province. Based on seasonal shifts of epidemics, three epidemic phases were identified over the 33-year period. The first phase occurred between 1973 and 1982 during which the foci of HFRS was located in the south Shandong and the epidemic peak occurred in the fall and winter, presenting a seasonal characteristic of Hantaan virus (HTNV transmission. The second phase between 1983 and 1985 was characterized by northward and westward spread of HFRS foci, and increases in incidence of HFRS in both fall-winter and spring seasons. The human infections in the spring reflected a characteristic pattern of Seoul virus (SEOV transmission. The third phase between 1986 and 2005 was characterized by the northeast spread of the HFRS foci until it covered all counties, and the HFRS incidence in the fall-winter season decreased while it

  3. Serum Cytokine Profiles Differentiating Hemorrhagic Fever with Renal Syndrome and Hantavirus Pulmonary Syndrome

    Svetlana F. Khaiboullina

    2017-05-01

    Full Text Available Hantavirus infection is an acute zoonosis that clinically manifests in two primary forms, hemorrhagic fever with renal syndrome (HFRS and hantavirus pulmonary syndrome (HPS. HFRS is endemic in Europe and Russia, where the mild form of the disease is prevalent in the Tatarstan region. HPS is endemic in Argentina, as well as other countries of North and South American. HFRS and HPS are usually acquired via the upper respiratory tract by inhalation of virus-contaminated aerosol. Although the pathogenesis of HFRS and HPS remains largely unknown, postmortem tissue studies have identified endothelial cells as the primary target of infection. Importantly, cell damage due to virus replication, or subsequent tissue repair, has not been documented. Since no single factor has been identified that explains the complexity of HFRS or HPS pathogenesis, it has been suggested that a cytokine storm may play a crucial role in the manifestation of both diseases. In order to identify potential serological markers that distinguish HFRS and HPS, serum samples collected during early and late phases of the disease were analyzed for 48 analytes using multiplex magnetic bead-based assays. Overall, serum cytokine profiles associated with HPS revealed a more pro-inflammatory milieu as compared to HFRS. Furthermore, HPS was strictly characterized by the upregulation of cytokine levels, in contrast to HFRS where cases were distinguished by a dichotomy in serum cytokine levels. The severe form of hantavirus zoonosis, HPS, was characterized by the upregulation of a higher number of cytokines than HFRS (40 vs 21. In general, our analysis indicates that, although HPS and HFRS share many characteristic features, there are distinct cytokine profiles for these diseases. These profiles suggest a strong activation of an innate immune and inflammatory responses are associated with HPS, relative to HFRS, as well as a robust activation of Th1-type immune responses. Finally, the results

  4. Seroprevalence of yellow fever virus in selected health facilities in Western Kenya from 2010 to 2012.

    Kwallah, Allan ole; Inoue, Shingo; Thairu-Muigai, Anne Wangari; Kuttoh, Nancy; Morita, Kouichi; Mwau, Matilu

    2015-01-01

    Yellow fever (YF), which is caused by a mosquito-borne virus, is an important viral hemorrhagic fever endemic in equatorial Africa and South America. Yellow fever virus (YFV) is the prototype of the family Flaviviridae and genus Flavivirus. The aim of this study was to determine the seroprevalence of YFV in selected health facilities in Western Kenya during the period 2010-2012. A total of 469 serum samples from febrile patients were tested for YFV antibodies using in-house IgM-capture ELISA, in-house indirect IgG ELISA, and 50% focus reduction neutralization test (FRNT50). The present study did not identify any IgM ELISA-positive cases, indicating absence of recent YFV infection in the area. Twenty-eight samples (6%) tested positive for YFV IgG, because of either YFV vaccination or past exposure to various flaviviruses including YFV. Five cases were confirmed by FRNT50; of these, 4 were either vaccination or natural infection during the YF outbreak in 1992-1993 or another period and 1 case was confirmed as a West Nile virus infection. Domestication and routine performance of arboviral differential diagnosis will help to address the phenomenon of pyrexia of unknown origin, contribute to arboviral research in developing countries, and enhance regular surveillance.

  5. Anterior pituitary lobe atrophy as late complication of hemorrhagic fever with renal syndrome

    Jovanović Dragan

    2009-01-01

    Full Text Available Introduction. Hemorrhagic fever with renal syndrome (HFRS is acute infective multisystemic disease followed by febrility, hemorrhages and acute renal insufficiency. Bleeding in the anterior pituitary lobe leading to tissue necrosis occurs in acute stage of severe clinical forms of HFRS, while atrophy of the anterior pituitary lobe with diminution of the gland function occurs after recovery stage. Case report. We presented a patient with the development of chronic renal insufficiency and hypopituitarism as complication that had been diagnosed six years after Hantavirus infection. Magnetic resonance of the pituitary gland revealed atrophy and empty sella turcica. Conclusion. Regarding frequency of this viral infection and its endemic character in some parts of our country partial and/or complete loss of pituitary function should be considered during the late stage of HFRS.

  6. On the mathematical analysis of Ebola hemorrhagic fever: deathly infection disease in West African countries.

    Atangana, Abdon; Goufo, Emile Franc Doungmo

    2014-01-01

    For a given West African country, we constructed a model describing the spread of the deathly disease called Ebola hemorrhagic fever. The model was first constructed using the classical derivative and then converted to the generalized version using the beta-derivative. We studied in detail the endemic equilibrium points and provided the Eigen values associated using the Jacobian method. We furthered our investigation by solving the model numerically using an iteration method. The simulations were done in terms of time and beta. The study showed that, for small portion of infected individuals, the whole country could die out in a very short period of time in case there is not good prevention.

  7. [Actual vitamin and main foodstuffs consumption by recovered patients suffered from hemorrhagic fever with renal syndrome].

    Kasanova, G M; Tutel'ian, A V

    2011-01-01

    Actual consumption of vitamins A, E, beta-carotene, ascorbic acid, thiamin, pyridoxine and main foodstuffs by recovered patients suffered from hemorrhagic fever with renal syndrome has been given. Frequency analysis of foodstuffs consumption was used to study actual nourishment of recovered patients. Surplus consumption of fat mainly due to the use of saturated fatty acids, deficiency of poly unsaturated fatty acids, surplus sugar consumption and predominance of proteins of animal origin over proteins of vegetable origin in ration has been revealed. Deficiency of water soluble vitamins equals to 41,6-78,7% of all examined patients, deficiency of fat water soluble vitamins is lower (21,4-38,3%).

  8. A Nonfatal Case of Dobrava Hantavirus Hemorrhagic Fever with Renal Syndrome Combined with Hantavirus Cardiopulmonary Syndrome

    Shemsedin Dreshaj

    2018-01-01

    Full Text Available Among hantaviruses (HTNV, 22 are known as pathogenic for humans. HTNV can cause two clinical entities: hemorrhagic fever with renal syndrome (HFRS and hantavirus pulmonary syndrome or hantavirus cardiopulmonary syndrome (HCPS. In most countries of Eastern Europe as well as in Kosovo, HTNV infection is presented mainly as HFRS. Here, we report a 20-year-old man with HFRS and HCPS caused by Dobrava hantavirus strain, successfully treated in Intensive Care Unit of Infectious Diseases Clinic, University Clinical Center of Kosovo. In HFRS endemic areas, patients with acute respiratory distress syndrome need to be evaluated for Dobrava hantavirus strain as a possible causative agent.

  9. Functional analysis of replication determinantsin classical swine fever virus

    Hadsbjerg, Johanne

    and animal pathogens should facilitate finding new approaches for efficient disease control. The principal aim of this thesis is to characterise determinants involved in the replication of classical swine fever virus (CSFV). Classical swine fever is a highly contagious virus disease of domestic pigs and wild...... in cell culture. Knowledge of these sequence variations and putative long-range interactions will provide valuable insights into mechanisms underlying virustranslation and replication. In manuscript 3, a selection marker has been inserted into a CSFV-based replicon making it suitable for screening...

  10. A comparison of clinical diagnosis and serological diagnosis in an epidemic of Crimean-Congo Hemorrhagic Fever

    Nadeem, M.; Ali, N.; Anwar, M.

    2003-01-01

    Crimean Congo Hemorrhagic Fever (CCHF) is the life-threatening disease caused by Nairovirus of genus Bunya virus caused by tick bite of Hayalomma species or by direct contact of the blood/sera of the patient and animals suffering from this disease. Epidemics have been occurring in Balochistan province of Pakistan and neighboring Afghanistan and Iran from time to time with this mortality. Aim: In the absence of facilities for detection of serological markers of CCHF (IgM Et IgG antibodies and PCR for viral RNA), a study was designed to diagnose and treat cases of CCHF reporting to a specialist unit hospital situated at Quetta, Pakistan. The aim was to compare the clinical features, complications and outcome of both groups of patients: one detecting the disease clinically only and the other depending upon serological tests for the diagnosis. Methods: Thirty-four patients having fever of less than two weeks of duration with features of bleeding from the skin and various orifices were included in this study from June 2001 to September 2001 after hospitalization. Index case and some of the consecutive cases were subjected to detection of serological markers. Rest of the cases were diagnosed on clinical ground and baseline laboratory investigations only. Difference in both the group was noted carefully. All the patients were given Ribavirin and blood products as and when required. Results: Statistically there was no obvious difference in clinical manifestations (fever, body aches, purpuric spots, ecchymosis, epistaxis, gum bleed etc. ) and laboratory findings (blood picture, serum ALT, serum urea and electrolytes, PT, APTT, etc). There was also no difference in mortality of the two groups studied. Conclusion: In an on ongoing outbreak of CCHF, history, clinical findings and supportive baseline, laboratory investigations may be sufficient for early detection and treatment of CCHF cases. However for documentation of start of epidemic, serological markers should be done

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

    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

  12. Propagation of classical swine fever virus in vitro circumventing heparan sulfate-adaptation.

    Eymann-Häni, Rita; Leifer, Immanuel; McCullough, Kenneth C; Summerfield, Artur; Ruggli, Nicolas

    2011-09-01

    Amplification of natural virus isolates in permanent cell lines can result in adaptation, in particular enhanced binding to heparan sulfate (HS)-containing glycosaminoglycans present on most vertebrate cells. This has been reported for several viruses, including the pestivirus classical swine fever virus (CSFV), the causative agent of a highly contagious hemorrhagic disease in pigs. Propagation of CSFV in cell culture is essential in virus diagnostics and research. Adaptation of CSFV to HS-binding has been related to amino acid changes in the viral E(rns) glycoprotein, resulting in viruses with altered replication characteristics in vitro and in vivo. Consequently, a compound blocking the HS-containing structures on cell surfaces was employed to monitor conversion from HS-independency to HS-dependency. It was shown that the porcine PEDSV.15 cell line permitted propagation of CSFV within a limited number of passages without adaptation to HS-binding. The selection of HS-dependent CSFV mutants was also prevented by propagation of the virus in the presence of DSTP 27. The importance of these findings can be seen from the altered ratio of cell-associated to secreted virus upon acquisition of enhanced HS-binding affinity, a phenotype proposed previously to be related to virulence in the natural host. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

    Friis, Martin Barfred; Rasmussen, Thomas Bruun; Belsham, Graham

    2012-01-01

    Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, cDNAs corresponding to the wild type (wt) or mutant forms of the IRES of CSFV strain Paderborn were...... in vitro and electroporated into porcine PK15 cells. Rescued mutant viruses were obtained from RNAs that contained mutations within domain IIIf which retained more than 75% of wt translation efficiency. Sequencing of cDNA generated from these rescued viruses verified the maintenance of the introduced...... changes within the IRES. The growth characteristics of each rescued mutant virus were compared to that of the wt virus. It was shown that viable mutant viruses with reduced translation initiation efficiency can be designed and generated and that viruses containing mutations within domain IIIf of the IRES...

  14. Mild Clinical Course of Severe Fever with Thrombocytopenia Syndrome Virus Infection in an Elderly Japanese Patient

    Yuko Ohagi

    2014-01-01

    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging infectious and hemorrhagic disease recently described in China and western Japan. A 71-year-old healthy Japanese woman noticed a tick biting her after harvesting in an orchard and removed it herself. She developed diarrhea, anorexia, and chills eight days later. Because these symptoms continued, she visited a primary care physician 6 days after the onset. Laboratory data revealed thrombocytopenia, leukocytopenia, and elevated liver enzymes. She was then referred to our hospital. Although not completely fulfilling the diagnostic criteria used in a retrospective study in Japan, SFTS was suspected, and we detected SFTS virus in the patient’s blood using RT-PCR. However, she recovered without intensive treatment and severe complications 13 days after the onset. In this report, we present a mild clinical course of SFTS virus infection in Japan in detail.

  15. Ebola hemorrhagic fever under scope, view of knowledge, attitude and practice from rural Sudan in 2015.

    Mohamed, Mohamed M G; Shwaib, Hussam M; Fahim, Monica M; Ahmed, Elhamy A; Omer, Mawadda K; Monier, Islam A; Balla, Siham A

    Ebola hemorrhagic fever (EHF) is an emerging threat to public health. The last epidemic in West Africa had a great effect on the affected communities. Timely and effective interventions were necessary in addition to community participation to control the epidemic. The knowledge, attitude and practices of vulnerable communities remain unknown, particularly in Sudan. The aim of this study was to explore the knowledge, attitude and practices of rural residents in Sudan regarding Ebola hemorrhagic fever. We conducted a cross sectional, community-based large-scale study in Al Gaziera state in rural Sudan in eight localities. In total, 1500 random adult participants were selected. The participants were assessed by a predesigned pretested questionnaire regarding their knowledge, attitude and practices regarding Ebola. Their sources of information were determined, and we assessed demographic factors as predictors of knowledge. We found poor knowledge, a fair attitude and suboptimal practices among the participants. The main sources of information were the press and media. Education was the only predictor of knowledge regarding Ebola. A lack of knowledge and suboptimal preventive practices mandates orientation and education programs to raise public awareness. Health care providers are advised to engage more in educating the community. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  16. Clinical symptoms and laboratory findings supporting early diagnosis of Crimean-Congo hemorrhagic fever in Iran.

    Mostafavi, Ehsan; Pourhossein, Behzad; Chinikar, Sadegh

    2014-07-01

    Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease, which is usually transmitted to humans by tick bites or contact with blood or other infected tissues of livestock. Patients suffering from CCHF demonstrate an extensive spectrum of clinical symptoms. As it can take considerable time from suspecting the disease in hospital until reaching a definitive diagnosis in the laboratory, understanding the clinical symptoms and laboratory findings of CCHF patients is of paramount importance for clinicians. The data were collected from patients who were referred to the Laboratory of Arboviruses and Viral Hemorrhagic Fevers at the Pasteur institute of Iran with a primary diagnosis of CCHF between 1999 and 2012 and were assessed by molecular and serologic tests. Referred patients were divided into two groups: patients with a CCHF positive result and patients with a CCHF negative result. The laboratory and clinical findings of these two groups were then compared. Two-thousand five hundred thirty-six probable cases of CCHF were referred to the laboratory, of which 871 cases (34.3%) were confirmed to be CCHF. Contact with infected humans and animals increased the CCHF infection risk (P important role in patient survival and the application of the findings of this study can prove helpful as a key for early diagnosis. © 2014 Wiley Periodicals, Inc.

  17. Duplex ultrasonography in the hemorrhagic fever with renal syndrome; Correlation with laboratory findings

    Han, Chun Hee; Cho, K. S.; Auh, Y. h.; Park, C. S.; Park, S. K.; Kim, S. B.

    1994-01-01

    Assuming that the duplex Doppler sonography might be useful in predicting the disease evolution of hemorrhagic fever with renal syndrome, we compared the resistive index (RI) with the clinical and laboratory findings in 18 patients. We underwent 30 duplex Doppler examinations in 18 patients: one examination in nine, two examinations in six, and three examinations in three patients. Duplex Dopper waveforms were obtained from the main, segmental,interlobar, and arcuate arteries of both kidneys, and the RI was calculated for each study. In oliguric phase, the mean RI was high (average, 0.94), and the serum BUN(averate, 92.3mg/dl) and creatinine(average, 10.4mg/dl) levels were elevated. In diuretic phase the mean RI was normalized (average, 0.7), and the serum BUN(average, 31.1mg/dl)and serum creatinine (average, 2.9mg/dl) levels were low. There was statistically significant correlation between the mean RI and the serum levels of BUN and creatinine and 24 hour urine output (P<0.001). We conclude that the mean RI is a useful indicator in predicting the disease evolution in patients with hemorrhagic fever with renal syndrome

  18. Clinical and immunological characteristics of hemorrhagic fever with renal syndrome in women of different age groups

    Kutdusova A.M.

    2012-09-01

    Full Text Available Objective: To evaluate the clinical and immunological features of the hemorrhagic fever with renal syndrome in women of different age groups. Materials and methods: Clinical and laboratory characteristics of hemorrhagic fever with renal syndrome in 148 women aged 17 to 65 years old have been investigated. Patients have been divided into two groups: group I included 101 patients with normal menstrual rhythm, group II included 47 female patients with menopause. In 57 women (36 from group I, 21 — from group II the content of CD3+, CD4+, CD8+, CD16+, CD19+ — sub-populations of peripheral blood lymphocytes has been determined. Results: In compared groups significant differences in structure and frequency of complications of the disease have been revealed. Unidirectional tendency to increase significantly reduced absolute rates of investigated lymphocyte subpopulations in dynamics of the disease has been identified. It also has been stated that by the time of early convalescence in case of severe form of HFRS the indices did not reach the standard level. In an older group of women deeper damage and long-term recovery of immune system have been marked. Conclusion: According to the results of clinical and immunological studies the research work has revealed that in young women the response of the immune system to HFRS has developed faster and stronger than that in patients during the menopause period.

  19. Meeting report: First International Conference on Crimean-Congo hemorrhagic fever.

    Papa, Anna; Weber, Friedemann; Hewson, Roger; Weidmann, Manfred; Koksal, Iftihar; Korukluoglu, Gulay; Mirazimi, Ali

    2015-08-01

    Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tick-borne disease of humans, occurring from western China to the Balkans in Eurasia and south throughout the length of Africa. Its incidence has increased over the past decade, particularly in Turkey and Iran, and the disease has also emerged in India. Research has been hindered by limited laboratory capacity in many regions where the disease is prevalent, indicating the need for collaboration between investigators in endemic countries and those with greater scientific resources. In an effort to increase such collaboration, the First International Conference on Crimean-Congo hemorrhagic fever was held in Thessaloniki, Greece, from February 13 to 14, 2015. This meeting followed the conclusion of an EU-supported Collaborative Project under the Health Cooperation Work Programme of the 7th Framework Programme (Grant agreement No. 260427). It is expected to be the first in a series of meetings that will bring together researchers from around the world to exchange knowledge and experience on various aspects of CCHF. This report summarizes major presentations by the invited speakers at the First International Conference on CCHF. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Occurrence of hemorrhagic fever with renal syndrome in military unit stationed in the combat zone

    Ćirić Slaviša

    2003-01-01

    Full Text Available Since it has been recognized as a separate disease during the Korean war hemorrhagic fever with renal syndrome (HFRS has often been discovered among the members of different armies in various countries, military personnel being the highest risk group for the disease. In the period from March to May 1999 we treated 6 soldiers coming from the military formation stationed at Kosovo and Metohia. The reaction of indirect hemagglutination test proved the presence of antibodies against Hantavira in each of them. They were infected during the stay in a dugout in the area with great population of field rodents. Only one patient was slightly ill, on the admission to the hospitalall. The others had severe clinical and laboratory findings: several days lasting fever, strong abdominal pain, as well as the pain in the loins dyspeptical discomfort, manifold increased blood urea nitrogen and serum creatinine values, thrombocytopenia, etc. Oliguria occurred in 4 patients. Hemorrhagic manifestations were slight (epistaxis, petechial rash conjunctival injection, or absent. Because of the aggravation of the acute renal failure, hemodialysis was performed in 3 patients, while other 3 underwent conservative treatment. Two of the patients had severe anemia because of which transfusions of erythrocytes and plasma were performed. Complications occurred in 2 patients (convulsive crises and lung infections. All patients recovered completely.

  1. [Manifestations of hemorrhagic fever with renal syndrome in a military unit stationed in a combat zone].

    Cirić, Slavisa; Denić, Vesna; Mitrović, Vekoslav; Mitrović-Perisić, Natasa; Denić, Nebojsa; Cirić, Slobodan

    2003-01-01

    Since it has been recognized as a separate disease during the Korean war, hemorrhagic fever with renal syndrome (HFRS) has often been discovered among the members of different armies in various countries, military personnel being the highest risk group for the disease. In the period from March to May 1999 we treated 6 soldiers coming from the military formation stationed at Kosovo and Metohia. The reaction of indirect hemagglutination test proved the presence of antibodies against Hantavira in each of them. They were infected during the stay in a dugout in the area with great population of field rodents. Only one patient was slightly ill, on the admission to the hospital. The others had severe clinical and laboratory findings: several days lasting fever, strong abdominal pain, as well as the pain in the loins, dyspeptical discomfort, manifold increased blood urea nitrogen and serum creatinine values, thrombocytopenia, etc. Oliguria occurred in 4 patients. Hemorrhagic manifestations were slight (epistaxis, petechial rash, conjunctival injection), or absent. Because of the aggravation of the acute renal failure, hemodialysis was performed in 3 patients, while other 3 underwent conservative treatment. Two of the patients had severe anemia because of which transfusions of erythrocytes and plasma were performed. Complications occurred in 2 patients (convulsive crises and lung infections). All patients recovered completely.

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

    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 ...

  3. [Electron microscopic study on the petechial hemorrhagic spots in patients with epidemic hemorrhage fever (EHF)].

    Wang, S Q; Feng, M; Yang, L

    1994-12-01

    EHF viral particles were found in the squamous epithelial cells and capillary endothelial cells of the petechial spots located at the mucous membrane of the soft palate in cases of early stage of severe type EHF by transmission electron microscopy. The viral particles are round or oval in shape, about 100 nm in diameter with a lipid bilayer envelope from which spikes are protruding. The virions matured by budding through the intracytoplasmic membranes into the smooth surfaced vesicles. The morphological characteristics of the virion coincided with the viral particles of Family Bunyaviridae. It was the first time to demonstrate that the squamous epithelial cells of the soft palate is one of the target cells in EHF virus infection and to describe the subcellular morphological evidence of the petechial spots at the soft palate by EM.

  4. African Swine Fever Virus, Siberia, Russia, 2017.

    Kolbasov, Denis; Titov, Ilya; Tsybanov, Sodnom; Gogin, Andrey; Malogolovkin, Alexander

    2018-04-01

    African swine fever (ASF) is arguably the most dangerous and emerging swine disease worldwide. ASF is a serious problem for the swine industry. The first case of ASF in Russia was reported in 2007. We report an outbreak of ASF in Siberia, Russia, in 2017.

  5. A case of Crimean-Congo hemorrhagic fever complicated with acute pancreatitis.

    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.

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

    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

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

    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. Identification of New Protein Interactions between Dengue Fever Virus and Its Hosts, Human and Mosquito

    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

  9. Identification of new protein interactions between dengue fever virus and its hosts, human and mosquito.

    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.

  10. Identification of new protein interactions between dengue fever virus and its hosts, human and mosquito.

    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.

  11. Lassa hemorrhagic fever in a late term pregnancy from northern sierra leone with a positive maternal outcome: case report

    Bangura James J

    2011-08-01

    Full Text Available Abstract Lassa fever (LF is a devastating viral disease prevalent in West Africa. Efforts to take on this public health crisis have been hindered by lack of infrastructure and rapid field deployable diagnosis in areas where the disease is prevalent. Recent capacity building at the Kenema Government Hospital Lassa Fever Ward (KGH LFW in Sierra Leone has lead to a major turning point in the diagnosis, treatment and study of LF. Herein we present the first comprehensive rapid diagnosis and real time characterization of an acute hemorrhagic LF case at KGH LFW. This case report focuses on a third trimester pregnant Sierra Leonean woman from the historically non-endemic Northern district of Tonkolili who survived the illness despite fetal demise. Employed in this study were newly developed recombinant LASV Antigen Rapid Test cassettes and dipstick lateral flow immunoassays (LFI that enabled the diagnosis of LF within twenty minutes of sample collection. Deregulation of overall homeostasis, significant hepatic and renal system involvement, and immunity profiles were extensively characterized during the course of hospitalization. Rapid diagnosis, prompt treatment with a full course of intravenous (IV ribavirin, IV fluids management, and real time monitoring of clinical parameters resulted in a positive maternal outcome despite admission to the LFW seven days post onset of symptoms, fetal demise, and a natural still birth delivery. These studies solidify the growing rapid diagnostic, treatment, and surveillance capabilities at the KGH LF Laboratory, and the potential to significantly improve the current high mortality rate caused by LF. As a result of the growing capacity, we were also able to isolate Lassa virus (LASV RNA from the patient and perform Sanger sequencing where we found significant genetic divergence from commonly circulating Sierra Leonean strains, showing potential for the discovery of a newly emerged LASV strain with expanded geographic

  12. Acute Cholecystitis as a Cause of Fever in Aneurysmal Subarachnoid Hemorrhage

    Na Rae Yang

    2017-05-01

    Full Text Available Background Fever is a very common complication that has been related to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH. The incidence of acalculous cholecystitis is reportedly 0.5%–5% in critically ill patients, and cerebrovascular disease is a risk factor for acute cholecystitis (AC. However, abdominal evaluations are not typically performed for febrile patients who have recently undergone aSAH surgeries. In this study, we discuss our experiences with febrile aSAH patients who were eventually diagnosed with AC. Methods We retrospectively reviewed 192 consecutive patients who underwent aSAH from January 2009 to December 2012. We evaluated their characteristics, vital signs, laboratory findings, radiologic images, and pathological data from hospitalization. We defined fever as a body temperature of >38.3°C, according to the Society of Critical Care Medicine guidelines. We categorized the causes of fever and compared them between patients with and without AC. Results Of the 192 enrolled patients, two had a history of cholecystectomy, and eight (4.2% were eventually diagnosed with AC. Among them, six patients had undergone laparoscopic cholecystectomy. In their pathological findings, two patients showed findings consistent with coexistent chronic cholecystitis, and two showed necrotic changes to the gall bladder. Patients with AC tended to have higher white blood cell counts, aspartame aminotransferase levels, and C-reactive protein levels than patients with fevers from other causes. Predictors of AC in the aSAH group were diabetes mellitus (odds ratio [OR], 8.758; P = 0.033 and the initial consecutive fasting time (OR, 1.325; P = 0.024. Conclusions AC may cause fever in patients with aSAH. When patients with aSAH have a fever, diabetes mellitus and a long fasting time, AC should be suspected. A high degree of suspicion and a thorough abdominal examination of febrile aSAH patients allow for prompt diagnosis and treatment of this

  13. Various clinical conditions can mimic Crimean-Congo hemorrhagic fever in pediatric patients in endemic regions

    Soner S. Kara

    2016-09-01

    Full Text Available Summary: Crimean-Congo hemorrhagic fever (CCHF is a tick-borne disease with high mortality. Many disorders can mimic CCHF. It is important to recognize the condition and to perform differential diagnosis in endemic countries. Twenty-one children aged 18 years or less with a preliminary diagnosis of CCHF were retrospectively evaluated. Real-time PCR and a confirmatory indirect immunofluorescence assay for negative results were performed. The diagnoses determined that 9 patients had (42.9% CCHF; 7 patients had (33.3% viral upper respiratory tract infections (URTI; 2 patients had (9.5% brucellosis; 1 patients had (4.7% periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA syndrome episode; 1 patient had (4.7% cerebral palsy, diabetes insipidus, acute gastroenteritis, and hypernatremic dehydration; and 1 patient had (4.7% cellulitis after a tick bite. The mean age of patients with CCHF was greater than that of the other patients (116.1 ± 53.6 vs. 94.1 ± 52.1 months, p = 0.02. Seventeen (81% of the children included had a history of tick bites, 2 (9.5% had a history of contact with a patient with CCHF, and 2 (9.5% had no exposure, but were living in an endemic region. Three patients had an underlying disorder: cerebral palsy and diabetes insipidus, epilepsy, or PFAPA. All of the children experienced fever. Other frequent symptoms were malaise, diarrhea, vomiting, and abdominal pain, but none of these differed statistically between the patient groups. CCHF patients had a longer mean duration of symptoms (10.56 ± 1.42 vs. 6.75 ± 3.62 days, p = 0.008 and a longer mean length of hospitalization (8.00 ± 2.08 vs. 3.58 ± 1.56 days, p < 0.001 than the other patients. At laboratory examination, patients with CCHF had statistically significant lower leukocyte and platelet counts, more prolonged coagulation parameters, and greater AST, ALT, LDH, and CK levels than the other patients. No mortality or complications occurred

  14. Molecular-genetic risk assessement of determining angiotensin-converting enzyme hyperactivity in hemorrhagic fever with renal syndrome

    Ildar R. Minniakhmetov

    2012-09-01

    Full Text Available The present study was designed to investigate changes in angiotensin-converting enzyme (ACE blood activity and angiotensin II type 1 receptor gene polymorphism as a possible disease predictor in hemorrhagic fever with renal syndrome (HFRS. Four hundred and nine patients (346 males and 63 females with HFRS serologic confirmation were enrolled in the study. Their age ranged from 15 to 65 years. ACE blood activity was assessed kinetically using the Bühlmann (Switzerland kit. Peripheral blood genomic DNA was isolated by a phenol-chloroform extraction. The genotyping of DNA loci was done using a polymerase chain reaction of DNA synthesis. Statistically, ACE blood activity was significantly higher throughout the entire HFRS course with diverse severity apart from the feverish phase of moderate-to-severe uncomplicated disease forms. *A1166 and *C1166 alleles, *A1166/*A1166 and *C1166/*C1166 genotypes of angiotensin II type 1 receptor gene were not associated with HFRS severity. The results of this study indicate that high ACE activity has not adaptive characteristics due to abnormalities in angiotensin II reception. It is an adequate metabolic response of the body to endotheliotropic virus activity.

  15. Low adiposity during early infancy is associated with a low risk for developing dengue hemorrhagic fever: a preliminary model.

    Daniel H Libraty

    Full Text Available Dengue virus (DENV infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF. DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection.

  16. Low adiposity during early infancy is associated with a low risk for developing dengue hemorrhagic fever: a preliminary model.

    Libraty, Daniel H; Zhang, Lei; Woda, Marcia; Giaya, Kris; Kathivu, Chido Loveness; Acosta, Luz P; Tallo, Veronica; Segubre-Mercado, Edelwisa; Bautista, Analisa; Obcena, AnaMae; Brion, Job D; Capeding, Rosario Z

    2014-01-01

    Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection.

  17. Plasma oxidative stress and total thiol levels in Crimean-Congo hemorrhagic fever.

    Karadag-Oncel, Eda; Erel, Ozcan; Ozsurekci, Yasemin; Caglayik, Dilek Yagci; Kaya, Ali; Gozel, Mustafa Gokhan; Icagasioglu, Fusun Dilara; Engin, Aynur; Korukluoglu, Gulay; Uyar, Yavuz; Elaldi, Nazif; Ceyhan, Mehmet

    2014-01-01

    In this study, we investigated the pro- and antioxidant status of patients with a pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) in terms of their role in its pathogenesis. During the study period, 34 children and 41 adults were diagnosed with CCHF. The control group consisted of healthy age- and gender-matched children and adults. Serum levels of the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and plasma total thiol (TTL) were evaluated and compared between groups. The difference in mean TAC values between CCHF patients and healthy controls was not statistically significant (P > 0.05). Mean TOS, OSI, and TTL values were significantly lower in CCHF patients than in healthy controls (P 0.05). Our results suggest that TTL may play a more important role in CCHF pathogenesis than the other parameters investigated. The mean TOS and OSI values were higher in the control group than in CCHF patients.

  18. Spatial cluster analysis of human cases of Crimean Congo hemorrhagic fever reported in Pakistan.

    Abbas, Tariq; Younus, Muhammad; Muhammad, Sayyad Aun

    2015-01-01

    Crimean Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonotic disease that has been reported in almost all geographic regions in Pakistan. The aim of this study was to identify spatial clusters of human cases of CCHF reported in country. Kulldorff's spatial scan statisitc, Anselin's Local Moran's I and Getis Ord Gi* tests were applied on data (i.e. number of laboratory confirmed cases reported from each district during year 2013). The analyses revealed a large multi-district cluster of high CCHF incidence in the uplands of Balochistan province near it border with Afghanistan. The cluster comprised the following districts: Qilla Abdullah; Qilla Saifullah; Loralai, Quetta, Sibi, Chagai, and Mastung. Another cluster was detected in Punjab and included Rawalpindi district and a part of Islamabad. We provide empirical evidence of spatial clustering of human CCHF cases in the country. The districts in the clusters should be given priority in surveillance, control programs, and further research.

  19. Potential impacts of climate variability on dengue hemorrhagic fever in Honduras, 2010.

    Zambrano, L I; Sevilla, C; Reyes-García, S Z; Sierra, M; Kafati, R; Rodriguez-Morales, A J; Mattar, S

    2012-12-01

    Climate change and variability are affecting human health and disease direct or indirectly through many mechanisms. Dengue is one of those diseases that is strongly influenced by climate variability; however its study in Central America has been poorly approached. In this study, we assessed potential associations between macroclimatic and microclimatic variation and dengue hemorrhagic fever (DHF) cases in the main hospital of Honduras during 2010. In this year, 3,353 cases of DHF were reported in the Hospital Escuela, Tegucigalpa. Climatic periods marked a difference of 158% in the mean incidence of cases, from El Niño weeks (-99% of cases below the mean incidence) to La Niña months (+59% of cases above it) (pHonduras. However, it is necessary to extend these studies in this and other countries in the Central America region, because these models can be applied for surveillance as well as for prediction of dengue.

  20. Interleukin-10 as a Marker of Disease Progression in Dengue Hemorrhagic Fever

    Tauseef, A.; Akmal, A.; Umar, N.; Sabir, S.; Sajjad, S.; Zulfiqar, S.

    2016-01-01

    Objective: To evaluate the plasma interleukin-10 (IL-10) levels in patients suffering from dengue hemorrhagic fever between 4 to 7 days of onset of disease and 24 hours after the first sample, to find out the association of plasma IL-10 levels with the outcome. Study Design: Analytical study. Place and Duration of Study: All major hospitals of Lahore, Pakistan, from August to November 2012. Methodology: Participants included 50 registered patients of dengue hemorrhagic fever (DHF) aged between 15 - 50 years. Plasma IL-10 concentrations were measured on above stated day. Outcome was described as recovery and shock. Platelet count and hematocrit percentages were also recorded. Statistical analyses were done using SPSS version 19. A p-value 0.05 was considered significant. Results: Plasma IL-10 levels were found to be raised in DHF patients and were associated with fatal outcome (p=0.004). In recovered DHF patients, plasma IL-10 levels decreased after 24 hours (mean 26.54 ± 16.03 pg/ml) as compared to admission time (mean 74.39 ± 61.69 pg/ml) but in case of DHF patients suffering from shock, plasma IL-10 was found to be higher after 24 hours (mean 87.69 ± 7.77 pg/ml) as compared to levels at admission time (mean 42.56 ± 28.09 pg/ml). ROC curve analysis revealed a change (30 units pg/ml) of plasma IL-10 concentration, within 24 hours of admission, raised from the base line to be 105 times more critical for shock in DHF patients (100 percentage sensitivity and 71.4 percentage specificity, p < 0.001). Conclusion: Elevated plasma IL-10 is a potential predictor of disease severity and fatal outcome in DHF patients. (author)

  1. Factors Associated with Marburg Hemorrhagic Fever: Analysis of Patient Data from Uige, Angola

    Roddy, Paul; Thomas, Sara L.; Jeffs, Benjamin; Folo, Pascoal Nascimento; Palma, Pedro Pablo; Henrique, Bengi Moco; Villa, Luis; Machado, Fernando Paixao Damiao; Bernal, Oscar; Jones, Steven M.; Strong, James E.; Feldmann, Heinz; Borchert, Matthias

    2012-01-01

    Background Reliable on-site polymerase chain reaction (PCR) testing for Marburg hemorrhagic fever (MHF) is not always available. Therefore, clinicians triage patients on the basis of presenting symptoms and contact history. Using patient data collected in Uige, Angola, in 2005, we assessed the sensitivity and specificity of these factors to evaluate the validity of World Health Organization (WHO)–recommended case definitions for MHF. Methods Multivariable logistic regression was used to identify independent predictors of PCR confirmation of MHF. A data-derived algorithm was developed to obtain new MHF case definitions with improved sensitivity and specificity. Results A MHF case definition comprising (1) an epidemiological link or (2) the combination of myalgia or arthralgia and any hemorrhage could potentially serve as an alternative to current case definitions. Our data-derived case definitions maintained the sensitivity and improved the specificity of current WHO-recommended case definitions. Conclusions Continued efforts to improve clinical documentation during filovirus outbreaks would aid in the refinement of case definitions and facilitate outbreak control. PMID:20441515

  2. IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever

    Lilian Karem Flores-Mendoza

    2017-01-01

    Full Text Available Background. Cytokines play important roles in the physiopathology of dengue infection; therefore, the suppressors of cytokine signaling (socs that control the type and timing of cytokine functions could be involved in the origin of immune alterations in dengue. Objective. To explore the association of cytokine and socs levels with disease severity in dengue patients. Methods. Blood samples of 48 patients with confirmed dengue infection were analyzed. Amounts of interleukins IL-2, IL-4, IL-6, and IL-10, interferon- (IFN- γ, and tumor necrosis factor- (TNF- α were quantified by flow cytometry, and the relative expression of socs1 and socs3 mRNA was quantified by real-time RT-PCR. Results. Increased levels of IL-10 and socs3 and lower expression of socs1 were found in patients with dengue hemorrhagic fever (DHF with respect to those with dengue fever (DF (p199.8-fold, socs1 (134 pg/ml have the highest sensitivity and specificity to discriminate between DF and DHF. Conclusion. Simultaneous changes in IL-10 and socs1/socs3 could be used as prognostic biomarkers of dengue severity.

  3. Data mining for dengue hemorrhagic fever (DHF) prediction with naive Bayes method

    Arafiyah, Ria; Hermin, Fariani

    2018-01-01

    Handling of infectious diseases is determined by the accuracy and speed of diagnosis. Government through the Regulation of the Minister of Health of the Republic of Indonesia No. 82 of 2014 on the Control of Communicable Diseases establishes Dengue Hemorrhagic Fever (DHF) has made DHF prevention a national priority. Various attempts were made to overcome this misdiagnosis. The treatment and diagnosis of DHF using ANFIS has result an application program that can decide whether a patient has dengue fever or not [1]. An expert system of dengue prevention by using ANFIS has predict the weather and the number of sufferers [2]. The large number of data on DHF often cannot affect a person in making decisions. The use of data mining method, able to build data base support in decision makers diagnose DHF disease [3]. This study predicts DHF with the method of Naive Bayes. Parameter of The input variable is the patient’s medical data (temperature, spotting, bleeding, and tornuine test) and the output variable suffers from DBD or not while the system output is diagnosis of the patient suffering from DHF or not. Result of model test by using tools of Orange 3.4.5 obtained level of precision model is 77,3%.

  4. Ongoing spillover of Hantaan and Gou hantaviruses from rodents is associated with hemorrhagic fever with renal syndrome (HFRS in China.

    Wen Wang

    Full Text Available BACKGROUND: Longquan City, Zhejiang province, China, has been seriously affected by hemorrhagic fever with renal syndrome (HFRS since the first cases were registered in 1974. To understand the epidemiology and emergence of HFRS in Longquan, which may be indicative of large parts of rural China, we studied long-term incidence patterns and performed a molecular epidemiological investigation of the causative hantaviruses in human and rodent populations. METHOD/PRINCIPAL FINDINGS: During 1974-2011, 1866 cases of HFRS were recorded in Longquan, including 20 deaths. In 2011, the incidence of HFRS remained high, with 19.61 cases/100,000 population, despite the onset of vaccination in 1997. During 1974-1998, HFRS cases in Longquan occurred mainly in winter, while in the past decade the peak of HFRS has shifted to the spring. Notably, the concurrent prevalence of rodent-borne hantaviruses in the region was also high. Phylogenetic analyses of viral sequences recovered from rodents in Longquan revealed the presence of novel genetic variants of Gou virus (GOUV in Rattus sp. rats and Hantaan virus (HTNV in the stripe field mice, respectively. Strikingly, viral sequences sampled from infected humans were very closely related to those from rodents. CONCLUSIONS/SIGNIFICANCE: HFRS represents an important public health problem in Longquan even after years of preventive measures. Our data suggest that continual spillover of the novel genetic variant of GOUV and the new genetic lineage of HTNV are responsible for the high prevalence of HFRS in humans. In addition, this is the first report of GOUV associated with human HFRS cases, and our data suggest that GOUV is now the major cause of HFRS in this region.

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

    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. Dengue fever: a Wikipedia clinical review

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

    2014-01-01

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

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

    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, ...

  8. Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

    Friis, Martin Barfred; Rasmussen, Thomas Bruun; Belsham, Graham J.

    Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, the nucleotides 47 to 427, including the IRES region of the wt CSFV strain Paderborn, were amplified...... and inserted, under T7 promoter control, into mono- and dicistronic plasmids containing the reporter genes rLuc and fLuc. Mutant fragments of the IRES sequence were generated by overlap PCR and inserted into the reporter plasmids. To evaluate IRES functionality, translation of the rLUC was placed under...... viruses were obtained after one cell culture passage from constructs with more than 75 % translation efficiency compared to the wildtype IRES. cDNA was generated from these clones and sequenced to verify the maintenance of the changes in the IRES. These results show that full-length viable mutant viruses...

  9. Public Knowledge and Attitude toward Crimean Congo Hemorrhagic Fever in Tokat Turkey

    R Yilmaz

    2009-12-01

    Full Text Available "nBackground: The World health Organization (WHO declares Crimean Congo hemorrhagic fe­ver (CCHF endemic in Turkey. Despite the magnitude of problem, no documented evi­dence exists in Turkey, which reveals the aware­ness and practices of the country's adult popula­tion regarding CCHF, its spread, symptoms, treatment, and preven­tion. This study was conducted to assess the level of knowledge, attitudes, and practices regarding CCHF in people visit­ing terti­ary care hospital in Tokat, Turkey."nMethods: This questionnaire based cross-sectional survey was conducted among patients' rela­tives or guardians who ad­mitted pediatric outpatient clinics during May-July 2008. The question­naire was composed of 25 questions."nResults: A total of 1034 respondents participated in the survey. Sufficient knowledge about CCHF was not found in 28.9% of the sample. Literate individuals were relatively better informed about CCHF as compared to the illiterate peo­ple. Television and radio were con­sidered as the most important and useful source of information on the disease."nConclusion: We have found insufficient knowledge on CCHF in our population. It is thought to have no chance of suc­cess against a fatal disease such as CCHF, which has serious consequences, without the contribution of commu­nity. It is clear that there are important tasks for health, agri­culture, and media sectors to improve public knowledge and awareness about CCHF. "n Keywords: Crimean Congo hemorrhagic fever, Public knowledge, Survey, Turkey

  10. Ribavirin for Crimean-Congo hemorrhagic fever: systematic review and meta-analysis

    G Gail

    2010-07-01

    Full Text Available Abstract Background Crimean-Congo hemorrhagic fever epidemics often occur in areas where health services are limited, and result in high case fatality rates. Besides intensive care, ribavirin is often recommended. A solid evidence base for the use of this drug will help justify assuring access to the drug in areas where epidemics are common. Methods We carried out a systematic review of observational and experimental studies of people with suspected or confirmed Crimean-Congo hemorrhagic fever that included comparisons between patients given ribavirin and those not. We extracted data on mortality, hospital stay, and adverse events. Risk of bias was assessed using a standard checklist, and data were presented in meta-analytical graphs, stratified by study design, and GRADE tables presented. The risk of bias was summarised using the GRADE method. Results 21 unique studies, including one randomised controlled trial of ribavirin, were included. Quality of the evidence was very low, with a Down and Black median score of 4 (maximum possible 33. Ribavirin treatment was not shown to be superior to no ribavirin treatment for mortality rate in a single RCT (RR: 1.13, 95%CI: 0.29 to 4.32, 136 participants, GRADE=low quality evidence; but ribavirin was associated with reduced mortality by 44% when compared to no ribavirin treatment in the pooled observational studies (RR: 0.56, 95%CI: 0.35 to 0.90, 955 participants; GRADE=very low quality evidence. Adverse events were more common with the ribavirin patients, but no severe adverse events were reported. No difference in length of hospital stay was reported. Conclusions No clear message of benefit is available from the current data on ribavirin as observational data are heavily confounded, and the one trial carried out has limited power. However, ribavirin could potentially have benefits in this condition and these results clearly indicate a pragmatic, randomised controlled trial in the context of good quality

  11. Molecular analysis of yellow fever virus 17DD vaccine strain

    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.

  12. Sensitive and specific detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)—Specific IgM and IgG antibodies in human sera using recombinant CCHFV nucleoprotein as antigen in μ-capture and IgG immune complex (IC) ELISA tests

    Emmerich, Petra; Mika, Angela; von Possel, Ronald; Rackow, Anne; Liu, Yang; Schmitz, Herbert; Sherifi, Kurtesh; Halili, Barie; Jakupi, Xhevat; Berisha, Lindita; Ahmeti, Salih

    2018-01-01

    As the most widespread tick-borne arbovirus causing infections in numerous countries in Asia, Africa and Europe, Crimean-Congo Hemorrhagic Fever Virus (CCHFV, family Nairoviridae) was included in the WHO priority list of emerging pathogens needing urgent Research & Development attention. To ensure preparedness for potential future outbreak scenarios, reliable diagnostic tools for identification of acute cases as well as for performance of seroprevalence studies are necessary. Here, the CCHFV ortholog of the major bunyavirus antigen, the nucleoprotein (NP), was recombinantly expressed in E.coli, purified and directly labeled with horseradish peroxidase (HRP). Employing this antigen, two serological tests, a μ-capture ELISA for the detection of CCHFV-specific IgM antibodies (BLACKBOX CCHFV IgM) and an IgG immune complex (IC) ELISA for the detection of CCHFV-specific IgG antibodies (BLACKBOX CCHFV IgG), were developed. Test performance was evaluated and compared with both in-house gold standard testing by IgM/IgG indirect immunofluorescence (IIF) and commercially available ELISA tests (VectoCrimean-CHF-IgM/IgG, Vector-Best, Russia) using a serum panel comprising paired samples collected in Kosovo during the years 2013–2016 from 15 patients with an acute, RT-PCR-confirmed CCHFV infection, and 12 follow-up sera of the same patients collected approximately one year after having overcome the infection. Reliably detecting IgM antibodies in all acute phase sera collected later than day 4 after onset of symptoms, both IgM ELISAs displayed excellent diagnostic and analytical sensitivity (100%, 95% confidence interval (CI): 85.2%–100.0%). While both IgG ELISAs readily detected the high IgG titers present in convalescent patients approximately one year after having overcome the infection (sensitivity 100%, 95% CI: 73.5%–100.0%), the newly developed BLACKBOX CCHFV IgG ELISA was superior to the commercial IgG ELISA in detecting the rising IgG titers during the acute phase

  13. Fatal dengue hemorrhagic fever in adults: emphasizing the evolutionary pre-fatal clinical and laboratory manifestations.

    Ing-Kit Lee

    Full Text Available BACKGROUND: A better description of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF is important in alerting clinicians of severe dengue and improving management. METHODS AND FINDINGS: Of 309 adults with DHF, 10 fatal patients and 299 survivors (controls were retrospectively analyzed. Regarding causes of fatality, massive gastrointestinal (GI bleeding was found in 4 patients, dengue shock syndrome (DSS alone in 2; DSS/subarachnoid hemorrhage, Klebsiella pneumoniae meningitis/bacteremia, ventilator associated pneumonia, and massive GI bleeding/Enterococcus faecalis bacteremia each in one. Fatal patients were found to have significantly higher frequencies of early altered consciousness (≤24 h after hospitalization, hypothermia, GI bleeding/massive GI bleeding, DSS, concurrent bacteremia with/without shock, pulmonary edema, renal/hepatic failure, and subarachnoid hemorrhage. Among those experienced early altered consciousness, massive GI bleeding alone/with uremia/with E. faecalis bacteremia, and K. pneumoniae meningitis/bacteremia were each found in one patient. Significantly higher proportion of bandemia from initial (arrival laboratory data in fatal patients as compared to controls, and higher proportion of pre-fatal leukocytosis and lower pre-fatal platelet count as compared to initial laboratory data of fatal patients were found. Massive GI bleeding (33.3% and bacteremia (25% were the major causes of pre-fatal leukocytosis in the deceased patients; 33.3% of the patients with pre-fatal profound thrombocytopenia (<20,000/µL, and 50% of the patients with pre-fatal prothrombin time (PT prolongation experienced massive GI bleeding. CONCLUSIONS: Our report highlights causes of fatality other than DSS in patients with severe dengue, and suggested hypothermia, leukocytosis and bandemia may be warning signs of severe dengue. Clinicians should be alert to the potential development of massive GI bleeding

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

    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.

  15. What Does the Future Hold for Yellow Fever Virus? (I

    Raphaëlle Klitting

    2018-06-01

    Full Text Available The recent resurgence of yellow fever virus (YFV activity in the tropical regions of Africa and South America has sparked renewed interest in this infamous arboviral disease. Yellow fever virus had been a human plague for centuries prior to the identification of its urban transmission vector, the Aedes (Stegomyia aegypti (Linnaeus mosquito species, and the development of an efficient live-attenuated vaccine, the YF-17D strain. The combination of vector-control measures and vaccination campaigns drastically reduced YFV incidence in humans on many occasions, but the virus never ceased to circulate in the forest, through its sylvatic invertebrate vector(s and vertebrate host(s. Outbreaks recently reported in Central Africa (2015–2016 and Brazil (since late 2016, reached considerable proportions in terms of spatial distribution and total numbers of cases, with multiple exports, including to China. In turn, questions about the likeliness of occurrence of large urban YFV outbreaks in the Americas or of a successful import of YFV to Asia are currently resurfacing. This two-part review describes the current state of knowledge and gaps regarding the molecular biology and transmission dynamics of YFV, along with an overview of the tools that can be used to manage the disease at individual, local and global levels.

  16. Surveillance for yellow Fever virus in non-human primates in southern Brazil, 2001-2011: a tool for prioritizing human populations for vaccination.

    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...

  17. Host preferences support the prominent role of Hyalomma ticks in the ecology of Crimean-Congo hemorrhagic fever.

    Jessica R Spengler

    2018-02-01

    Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is a tick-borne zoonotic agent that is maintained in nature in an enzootic vertebrate-tick-vertebrate cycle. Hyalomma genus ticks have been implicated as the main CCHFV vector and are key in maintaining silent endemic foci. However, what contributes to their central role in CCHFV ecology is unclear. To assess the significance of host preferences of ticks in CCHFV ecology, we performed comparative analyses of hosts exploited by 133 species of ticks; these species represent 5 genera with reported geographical distribution over the range of CCHFV. We found that the composition of vertebrate hosts on which Hyalomma spp. feed is different than for other tick genera. Immatures of the genus Hyalomma feed preferentially on species of the orders Rodentia, Lagomorpha, and the class Aves, while adults concentrate mainly on the family Bovidae. With the exception of Aves, these hosts include the majority of the vertebrates consistently reported to be viremic upon CCHFV infection. While other tick genera also feed on these hosts, Hyalomma spp. almost completely concentrate their populations on them. Hyalomma spp. feed on less phylogenetically diverse hosts than any other tick genus, implying that this network of hosts has a low resilience. Indeed, removing the most prominent hosts quickly collapsed the network of parasitic interactions. These results support the intermittent activity of CCHFV foci: likely, populations of infected Hyalomma spp. ticks exceed the threshold of contact with humans only when these critical hosts reach adequate population density, accounting for the sporadic occurence of clinical tick-transmitted cases. Our data describe the association of vertebrate host preferences with the role of Hyalomma spp. ticks in maintaining endemic CCHFV foci, and highlight the importance of host-tick dynamics in pathogen ecology.

  18. Elevated soluble CD163 plasma levels are associated with disease severity in patients with hemorrhagic fever with renal syndrome.

    Junning Wang

    Full Text Available Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS. Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163. The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS.Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry.The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001. The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001. A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets.sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further.

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

    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.

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

    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.

  1. Evaluation of knowledge about protection against Crimean-Congo hemorrhagic fever.

    Gungormus, Z; Kiyak, E

    2011-05-01

    This study was conducted in order to evaluate individuals' knowledge about protection against Crimean Congo hemorrhagic fever (CCHF). This descriptive study was carried out among 478 persons, to whom a Family Health Center located within boundaries of Erzurum Metropolitan Municipality, provides health service. A questionnaire form developed by the researchers was used for collecting data. Seventy-one point eight percent of individuals who participated in the study stated they had knowledge about CCHF, 25.9% stated that region was risky in terms of being bitten by ticks, 61.3% stated they could recognize ticks and 56.1% stated that not all tick bites cause the disease. Seventy-seven point eight percent stated CCHF is a virulent disease, 33.1% stated it can be transmitted from human to human and 30.3% stated it can be transmitted from animals to humans. In terms of protection from tick bites, 45, 15.3 and 11.3% of individuals stated wearing clothes to cover the whole body, carefully inspecting the body, and not touching ticks with bare hands, respectively, were good methods. Ninety-two point one percent stated it is necessary to go to a healthcare organization immediately in case of tick bite, whereas 18% of individuals stated it is necessary to remove the tick with tweezers or forceps. The results of this study show most individuals are not well informed about methods for protecting against CCHF, for removing ticks and what precautions to take to protect against tick bites.

  2. YouTube videos as a source of medical information during the Ebola hemorrhagic fever epidemic.

    Nagpal, Sajan Jiv Singh; Karimianpour, Ahmadreza; Mukhija, Dhruvika; Mohan, Diwakar; Brateanu, Andrei

    2015-01-01

    The content and quality of medical information available on video sharing websites such as YouTube is not known. We analyzed the source and quality of medical information about Ebola hemorrhagic fever (EHF) disseminated on YouTube and the video characteristics that influence viewer behavior. An inquiry for the search term 'Ebola' was made on YouTube. The first 100 results were arranged in decreasing order of "relevance" using the default YouTube algorithm. Videos 1-50 and 51-100 were allocated to a high relevance (HR), and a low relevance (LR) video group, respectively. Multivariable logistic regression models were used to assess the predictors of a video being included in the HR vs. LR groups. Fourteen videos were excluded because they were parodies, songs or stand-up comedies (n = 11), not in English (n = 2) or a remaining part of a previous video (n = 1). Two scales, the video information and quality and index and the medical information and content index (MICI) assessed the overall quality, and the medical content of the videos, respectively. There were no videos from hospitals or academic medical centers. Videos in the HR group had a higher median number of views (186,705 vs. 43,796, p YouTube videos presenting clinical symptoms of infectious diseases during epidemics are more likely to be included in the HR group and influence viewers behavior.

  3. Rapid molecular assays for the detection of yellow fever virus in low-resource settings.

    Escadafal, Camille; Faye, Oumar; Sall, Amadou Alpha; Faye, Ousmane; Weidmann, Manfred; Strohmeier, Oliver; von Stetten, Felix; Drexler, Josef; Eberhard, Michael; Niedrig, Matthias; Patel, Pranav

    2014-03-01

    Yellow fever (YF) is an acute viral hemorrhagic disease transmitted by Aedes mosquitoes. The causative agent, the yellow fever virus (YFV), is found in tropical and subtropical areas of South America and Africa. Although a vaccine is available since the 1930s, YF still causes thousands of deaths and several outbreaks have recently occurred in Africa. Therefore, rapid and reliable diagnostic methods easy to perform in low-resources settings could have a major impact on early detection of outbreaks and implementation of appropriate response strategies such as vaccination and/or vector control. The aim of this study was to develop a YFV nucleic acid detection method applicable in outbreak investigations and surveillance studies in low-resource and field settings. The method should be simple, robust, rapid and reliable. Therefore, we adopted an isothermal approach and developed a recombinase polymerase amplification (RPA) assay which can be performed with a small portable instrument and easy-to-use lyophilized reagents. The assay was developed in three different formats (real-time with or without microfluidic semi-automated system and lateral-flow assay) to evaluate their application for different purposes. Analytical specificity and sensitivity were evaluated with a wide panel of viruses and serial dilutions of YFV RNA. Mosquito pools and spiked human plasma samples were also tested for assay validation. Finally, real-time RPA in portable format was tested under field conditions in Senegal. The assay was able to detect 20 different YFV strains and demonstrated no cross-reactions with closely related viruses. The RPA assay proved to be a robust, portable method with a low detection limit (<21 genome equivalent copies per reaction) and rapid processing time (<20 min). Results from real-time RPA field testing were comparable to results obtained in the laboratory, thus confirming our method is suitable for YFV detection in low-resource settings.

  4. Rapid molecular assays for the detection of yellow fever virus in low-resource settings.

    Camille Escadafal

    2014-03-01

    Full Text Available BACKGROUND: Yellow fever (YF is an acute viral hemorrhagic disease transmitted by Aedes mosquitoes. The causative agent, the yellow fever virus (YFV, is found in tropical and subtropical areas of South America and Africa. Although a vaccine is available since the 1930s, YF still causes thousands of deaths and several outbreaks have recently occurred in Africa. Therefore, rapid and reliable diagnostic methods easy to perform in low-resources settings could have a major impact on early detection of outbreaks and implementation of appropriate response strategies such as vaccination and/or vector control. METHODOLOGY: The aim of this study was to develop a YFV nucleic acid detection method applicable in outbreak investigations and surveillance studies in low-resource and field settings. The method should be simple, robust, rapid and reliable. Therefore, we adopted an isothermal approach and developed a recombinase polymerase amplification (RPA assay which can be performed with a small portable instrument and easy-to-use lyophilized reagents. The assay was developed in three different formats (real-time with or without microfluidic semi-automated system and lateral-flow assay to evaluate their application for different purposes. Analytical specificity and sensitivity were evaluated with a wide panel of viruses and serial dilutions of YFV RNA. Mosquito pools and spiked human plasma samples were also tested for assay validation. Finally, real-time RPA in portable format was tested under field conditions in Senegal. CONCLUSION/SIGNIFICANCE: The assay was able to detect 20 different YFV strains and demonstrated no cross-reactions with closely related viruses. The RPA assay proved to be a robust, portable method with a low detection limit (<21 genome equivalent copies per reaction and rapid processing time (<20 min. Results from real-time RPA field testing were comparable to results obtained in the laboratory, thus confirming our method is suitable for

  5. Immunofluorescence Plaque Assay for African Swine Fever Virus

    Tessler, J.; Hess, W. R.; Pan, I. C.; Trautman, R.

    1974-01-01

    Suitably diluted cell culture adapted African swine fever virus preparations were inoculated on VERO cell monolayers and grown on coverslips. Gum tragacanth was used as an overlay. After three days incubation at 37°C the infected cultures were fixed with acetone and stained with fluorescent antibody conjugate. Fluorescing plaques consisted of 20-30 infected cells. Three statistical criteria for a quantitatively reliable assay were met: the Poisson distribution for plaque counts, linearity of the relationship between the concentration of virus and the plaque count and reproducibility of replicate titrations. The method is suitable for counts up to at least 70 plaques per 5 cm2 coverslip and computed titers are reproducible within 0.16 log units with a total of 300 plaques enumerated. PMID:4279763

  6. Bovine viral diarrhea virus 1b fetal infection with extensive hemorrhages

    Bovine viral diarrhea virus (BVDV) subtype 1b was isolated from tissues of a term bovine fetus with hemorrhages in multiple tissues. At autopsy, multiple petechial hemorrhages were observed at gross examination throughout the body and placenta. Lung, kidney, thymus, and liver fresh tissues were exam...

  7. No evidence of African swine fever virus replication in hard ticks

    Carvalho Ferreira, de H.C.; Zúquete, S.T.; Wijnveld, M.; Weesendorp, E.; Jongejan, F.; Stegeman, J.A.; Loeffen, W.L.A.

    2014-01-01

    African swine fever (ASF) is caused by African swine fever virus (ASFV), a tick-borne DNA virus. Soft ticks of the genus Ornithodoros are the only biological vectors of ASFV recognized so far. Although other hard ticks have been tested for vector competence, two commonly found tick species in

  8. No evidence of African swine fever virus replication in hard ticks

    de Carvalho Ferreira, Helena C; Tudela Zúquete, Sara; Wijnveld, Michiel; Weesendorp, Eefke; Jongejan, Frans; Stegeman, Arjan; Loeffen, Willie L A

    African swine fever (ASF) is caused by African swine fever virus (ASFV), a tick-borne DNA virus. Soft ticks of the genus Ornithodoros are the only biological vectors of ASFV recognized so far. Although other hard ticks have been tested for vector competence, two commonly found tick species in

  9. The phylogeny of yellow fever virus 17D vaccines.

    Stock, Nina K; Boschetti, Nicola; Herzog, Christian; Appelhans, Marc S; Niedrig, Matthias

    2012-02-01

    In recent years the safety of the yellow fever live vaccine 17D came under scrutiny. The focus was on serious adverse events after vaccinations that resemble a wild type infection with yellow fever and whose reasons are still not known. Also the exact mechanism of attenuation of the vaccine remains unknown to this day. In this context, the standards of safety and surveillance in vaccine production and administration have been discussed. Therein embodied was the demand for improved documentation of the derivation of the seed virus used for yellow fever vaccine production. So far, there was just a historical genealogy available that is based on source area and passage level. However, there is a need for a documentation based on molecular information to get better insights into the mechanisms of pathology. In this work we sequenced the whole genome of different passages of the YFV-17D strain used by Crucell Switzerland AG for vaccine production. Using all other publically available 17D full genome sequences we compared the sequence variance of all vaccine strains and oppose a phylogenetic tree based on full genome sequences to the historical genealogy. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    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.

  11. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat; Jokinen, Jenny; Lukashevich, Igor S.; Pushko, Peter

    2014-01-01

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. - Highlights: • The iDNA ® platform combines advantages of DNA and live attenuated vaccines. • Yellow fever (YF) 17D vaccine was launched from iDNA plasmid in vitro and in vivo. • Safety of iDNA-generated 17D virus was confirmed in AG129 mice. • BALB/c mice seroconverted after a single-dose vaccination with iDNA. • YF virus-neutralizing response was elicited in iDNA-vaccinated mice

  12. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Jokinen, Jenny; Lukashevich, Igor S. [Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville, KY (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States)

    2014-11-15

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. - Highlights: • The iDNA{sup ®} platform combines advantages of DNA and live attenuated vaccines. • Yellow fever (YF) 17D vaccine was launched from iDNA plasmid in vitro and in vivo. • Safety of iDNA-generated 17D virus was confirmed in AG129 mice. • BALB/c mice seroconverted after a single-dose vaccination with iDNA. • YF virus-neutralizing response was elicited in iDNA-vaccinated mice.

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

    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

  14. 77 FR 68783 - Prospective Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

    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...

  15. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice.

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat; Jokinen, Jenny; Lukashevich, Igor S; Pushko, Peter

    2014-11-01

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model.

    Carlson, Jolene; O'Donnell, Vivian; Alfano, Marialexia; Velazquez Salinas, Lauro; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Higgs, Stephen; Borca, Manuel V

    2016-10-22

    African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4) virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus) is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi) showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi). This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN)-γ responses, or specific cytokine profiles) and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  17. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

    Jolene Carlson

    2016-10-01

    Full Text Available African swine fever (ASF is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV. There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4 virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi. This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN-γ responses, or specific cytokine profiles and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  18. Prevalence of African swine fever virus and classical swine fever virus antibodies in pigs in Benue State, Nigeria.

    Asambe, A; Sackey, A K B; Tekdek, L B

    2018-03-01

    This study investigated the prevalence of African swine fever virus (ASFV) and classical swine fever virus (CSFV) antibodies in pigs in Benue State, Nigeria. Serum samples were collected from a total of 460 pigs, including 416 from 74 piggeries and 44 from Makurdi slaughter slab. The samples were analysed using indirect enzyme-linked immunosorbent assay (ELISA) test kit to detect the presence of ASFV antibodies, while competitive ELISA test kit was used to detect antibodies to CSFV. Our findings showed a total ASF prevalence of 13 (2.8%), while prevalences of 7 (1.7%) and 6 (13.6%) were observed in piggeries and in Makurdi slaughter slab, respectively. However, no CSFV antibody sera were detected in this study. Relatively higher ASFV antibody-positive pigs were detected in the slaughter slab than in piggeries. The difference in prevalence of ASF between the two locations was significantly associated (p = 0.017). These findings suggest the presence of ASFV antibody-positive pig in Benue State, Nigeria. Continuous surveillance and monitoring of these diseases among pigs in Nigeria to prevent any fulminating outbreak are recommended.

  19. Spatiotemporal transmission dynamics of hemorrhagic fever with renal syndrome in China, 2005-2012.

    Wen-Yi Zhang

    2014-11-01

    Full Text Available Hemorrhagic fever with renal syndrome (HFRS is a rodent-borne disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem with 90% of the total reported cases in the world. This study describes the spatiotemporal dynamics of HFRS cases in China and identifies the regions, time, and populations at highest risk, which could help the planning and implementation of key preventative measures.Data on all reported HFRS cases at the county level from January 2005 to December 2012 were collected from Chinese Center for Disease Control and Prevention. Geographic Information System-based spatiotemporal analyses including Local Indicators of Spatial Association and Kulldorff's space-time scan statistic were performed to detect local high-risk space-time clusters of HFRS in China. In addition, cases from high-risk and low-risk counties were compared to identify significant demographic differences.A total of 100,868 cases were reported during 2005-2012 in mainland China. There were significant variations in the spatiotemporal dynamics of HFRS. HFRS cases occurred most frequently in June, November, and December. There was a significant positive spatial autocorrelation of HFRS incidence during the study periods, with Moran's I values ranging from 0.46 to 0.56 (P<0.05. Several distinct HFRS cluster areas were identified, mainly concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties.This study identified significant space-time clusters of HFRS in China during 2005-2012 indicating that preventative strategies for HFRS should be particularly focused on the northeastern, central, and eastern of China to achieve the most cost-effective outcomes.

  20. Serum levels of inflammatory and regulatory cytokines in patients with hemorrhagic fever with renal syndrome

    Avšič-Županc Tatjana

    2011-05-01

    Full Text Available Abstract Background Hantaviruses are the causative agents of two zoonotic diseases: hemorrhagic fever with renal syndrome (HFRS and hantavirus cardiopulmonary syndrome (HCPS. The pathogenesis of HFRS is poorly understood. However, it has been suggested that immune mechanisms, including cytokines, might have an important role in HFRS pathogenesis. Thus, the aim of our study was to investigate cytokine profiles in serum samples of HFRS patients from Slovenia and explore a possible correlation between cytokine levels and disease severity. Methods Acute-phase serum samples from 52 patients, diagnosed with DOBV infection, and 61 patients, diagnosed with PUUV infection, were included in this study. Patients were divided into two groups - severe or mild - based on disease severity. Levels of IL-10, IL-12, INF-γ and TNF-α were measured in the serum samples with commercial ELISA tests. Results Increased levels of IL-10, INF-γ, and TNF-α were found in almost all the serum samples tested. On average, higher concentrations were detected in patients infected with DOBV than PUUV. Furthermore, significantly higher levels of IL-10 (P = 0.001 and TNF-α (P = 0.003 were found in patients with a more severe clinical course of disease. The same association between IL-10 (P P = 0.021, and the severity of the disease was observed also when only patients infected with DOBV were considered. No differences in cytokine concentrations according to disease severity were observed in patients infected with PUUV. Concentrations of serum IL-12 in HFRS patients were in the normal range, however, higher levels were detected in patients infected with PUUV than in patients infected with DOBV. Conclusions We suggest that imbalance in production of proinflammatory and regulatory cytokines might be in part responsible for a more severe course of HFRS.

  1. The untranslated regions of classic swine fever virus RNA trigger apoptosis.

    Wei-Li Hsu

    Full Text Available Classical swine fever virus (CSFV causes a broad range of disease in pigs, from acute symptoms including high fever and hemorrhages, to chronic disease or unapparent infection, depending on the virus strain. CSFV belongs to the genus Pestivirus of the family Flaviviridae. It carries a single-stranded positive-sense RNA genome. An internal ribosomal entry site (IRES in the 5' untranslated region (UTR drives the translation of a single open reading frame encoding a 3898 amino acid long polypeptide chain. The open reading frame is followed by a 3' UTR comprising four highly structured stem-loops. In the present study, a synthetic RNA composed of the 5' and 3' UTRs of the CSFV genome devoid of any viral coding sequence and separated by a luciferase gene cassette (designated 5'UTR-Luc-3'UTR triggered apoptotic cell death as early as 4 h post-transfection. The apoptosis was measured by DNA laddering analysis, TUNEL assay, annexin-V binding determined by flow cytometry, and by analysis of caspase activation. Contrasting with this, only trace DNA laddering was observed in cells transfected with the individual 5' or 3' UTR RNA; even when the 5' UTR and 3' UTR were co-transfected as separate RNA molecules, DNA laddering did not reach the level induced by the chimeric 5'UTR-Luc-3'UTR RNA. Interestingly, RNA composed of the 5'UTR and of stem-loop I of the 3'UTR triggered much stronger apoptosis than the 5' or 3'UTR alone. These results indicate that the 5' and 3' UTRs act together in cis induce apoptosis. We furthered obtained evidence that the UTR-mediated apoptosis required double-stranded RNA and involved translation shutoff possibly through activation of PKR.

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

    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.

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

    Suhail Sufi M

    2011-08-01

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

  4. Vector competence of Culicoides sonorensis (Diptera: Ceratopogonidae) to epizootic hemorrhagic disease virus serotype 7

    Background: Culicoides sonorensis (Diptera: Ceratopogonidae) is a vector of epizootic hemorrhagic disease virus (EHDV) serotypes 1 and 2 in North America, where these viruses are well-known pathogens of white-tailed deer (WTD) and other wild ruminants. Although historically rare, reports of clinica...

  5. Genetic characterization of epizootic hemorrhagic disease virus strains isolated from cattle in Israel

    Epizootic hemorrhagic disease virus (EHDV), an Orbivirus not previously reported in Israel, was isolated from Israeli cattle during a “bluetongue like” disease outbreak in 2006. To ascertain the origin of this new virus, three isolates from the outbreak were fully sequenced and compared with availab...

  6. Transmission of yellow fever vaccine virus through breast-feeding - Brazil, 2009.

    2010-02-12

    In April, 2009, the state health department of Rio Grande do Sul, Brazil, was notified by the Cachoeira do Sul municipal health department of a case of meningoencephalitis requiring hospitalization in an infant whose mother recently had received yellow fever vaccine during a postpartum visit. The Field Epidemiology Training Program of the Secretariat of Surveillance in Health of the Brazilian Ministry of Health assisted state and municipal health departments with an investigation. This report summarizes the results of that investigation, which determined that the infant acquired yellow fever vaccine virus through breast-feeding. The mother reported 2 days of headache, malaise, and low fever occurring 5 days after receipt of yellow fever vaccine. The infant, who was exclusively breast-fed, was hospitalized at age 23 days with seizures requiring continuous infusion of intravenous anticonvulsants. The infant received antimicrobial and antiviral treatment for meningoencephalitis. The presence of 17DD yellow fever virus was detected by reverse transcription--polymerase chain reaction (RT-PCR) in the infant's cerebrospinal fluid (CSF); yellow fever--specific immunoglobulin M (IgM) antibodies also were present in serum and CSF. The infant recovered completely, was discharged after 24 days of hospitalization, and has had normal neurodevelopment and growth through age 6 months. The findings in this report provide documentation that yellow fever vaccine virus can be transmitted via breast-feeding. Administration of yellow fever vaccine to breast-feeding women should be avoided except in situations where exposure to yellow fever viruses cannot be avoided or postponed.

  7. Functional requirements of the yellow fever virus capsid protein.

    Patkar, Chinmay G; Jones, Christopher T; Chang, Yu-hsuan; Warrier, Ranjit; Kuhn, Richard J

    2007-06-01

    Although it is known that the flavivirus capsid protein is essential for genome packaging and formation of infectious particles, the minimal requirements of the dimeric capsid protein for virus assembly/disassembly have not been characterized. By use of a trans-packaging system that involved packaging a yellow fever virus (YFV) replicon into pseudo-infectious particles by supplying the YFV structural proteins using a Sindbis virus helper construct, the functional elements within the YFV capsid protein (YFC) were characterized. Various N- and C-terminal truncations, internal deletions, and point mutations of YFC were analyzed for their ability to package the YFV replicon. Consistent with previous reports on the tick-borne encephalitis virus capsid protein, YFC demonstrates remarkable functional flexibility. Nearly 40 residues of YFC could be removed from the N terminus while the ability to package replicon RNA was retained. Additionally, YFC containing a deletion of approximately 27 residues of the C terminus, including a complete deletion of C-terminal helix 4, was functional. Internal deletions encompassing the internal hydrophobic sequence in YFC were, in general, tolerated to a lesser extent. Site-directed mutagenesis of helix 4 residues predicted to be involved in intermonomeric interactions were also analyzed, and although single mutations did not affect packaging, a YFC with the double mutation of leucine 81 and valine 88 was nonfunctional. The effects of mutations in YFC on the viability of YFV infection were also analyzed, and these results were similar to those obtained using the replicon packaging system, thus underscoring the flexibility of YFC with respect to the requirements for its functioning.

  8. [Western area surge for controlling Ebola hemorrhagic fever outbreak in Sierra Leone and evaluation of its effect].

    Chen, Yong; Wu, Dan; Zhang, Wenyi; Chen, Zeliang; Chang, Guohui; Tian, Shuguang; Yang, Ruifu; Liu, Chao

    2015-10-01

    To investigate the Western Area Surge (WAS) program in the Ebola outbreak of Sierra Leone, and to analyze its implementing effect. The subject of this study was 3,813 laboratory confirmed Ebola hemorrhagic fever (EHF) cases reported in Sierra Leone from November 19, 2014 through January 27, 2015, a period before and after the implementation of the WAS program. To analyze and make conclusions according to the working experience of China Mobile Laboratory Reponses Team in the fight of Ebola outbreak, using WHO published EHF case definition to make diagnosis and compare the number of bed numbers, confirmed EHF cases, samples tested, and positive rates before and after implementation of WAS program. From the implementation of WAS program on 17th December 2014 to half a month later, the total numbers of Ebola holding and treatment centers increased from 640 to 960, six additional laboratories were established. On January, 2015, another two laboratories from America and The Netherlands were established. The numbers of samples tested one month before and after WAS program were 7,891 and 9,783, respectively, with an increase of 24.0 percent, while the positive rate of Ebola virus decreased from 22.2% (1,752/7,891) to 11.0% (1,077/9,783). The positive rate of blood samples decreased from 39.6% (248/626) in the month before WAS program to 27.4% (131/478) (χ2=17.93, P<0.001) in the mother after WAS program, the positive rate of blood samples 22.7% (103/454) to 10% (62/609) (χ2=31.03, P<0.001), accordingly. After 3 weeks of WAS program, in addition to Western Area, another four hotspots in Sierra Leone had also reported a significant decrease of the numbers of confirmed EVD cases. Forty-two days after implementation of WAS program, the daily number of laboratory confirmed EHF cases decreased from 63 to 10. WAS program played a vital role in controlling the EHF outbreak rapidly in Sierra Leone. It could also provide guidance for the control similar large infectious diseases

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

    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.

  10. Temporal trend and climate factors of hemorrhagic fever with renal syndrome epidemic in Shenyang City, China

    Liu Xiaodong

    2011-12-01

    Full Text Available Abstract Background Hemorrhagic fever with renal syndrome (HFRS is an important infectious disease caused by different species of hantaviruses. As a rodent-borne disease with a seasonal distribution, external environmental factors including climate factors may play a significant role in its transmission. The city of Shenyang is one of the most seriously endemic areas for HFRS. Here, we characterized the dynamic temporal trend of HFRS, and identified climate-related risk factors and their roles in HFRS transmission in Shenyang, China. Methods The annual and monthly cumulative numbers of HFRS cases from 2004 to 2009 were calculated and plotted to show the annual and seasonal fluctuation in Shenyang. Cross-correlation and autocorrelation analyses were performed to detect the lagged effect of climate factors on HFRS transmission and the autocorrelation of monthly HFRS cases. Principal component analysis was constructed by using climate data from 2004 to 2009 to extract principal components of climate factors to reduce co-linearity. The extracted principal components and autocorrelation terms of monthly HFRS cases were added into a multiple regression model called principal components regression model (PCR to quantify the relationship between climate factors, autocorrelation terms and transmission of HFRS. The PCR model was compared to a general multiple regression model conducted only with climate factors as independent variables. Results A distinctly declining temporal trend of annual HFRS incidence was identified. HFRS cases were reported every month, and the two peak periods occurred in spring (March to May and winter (November to January, during which, nearly 75% of the HFRS cases were reported. Three principal components were extracted with a cumulative contribution rate of 86.06%. Component 1 represented MinRH0, MT1, RH1, and MWV1; component 2 represented RH2, MaxT3, and MAP3; and component 3 represented MaxT2, MAP2, and MWV2. The PCR model

  11. Phylogeny of the Viral Hemorrhagic Septicemia Virus in European Aquaculture.

    Michael Cieslak

    Full Text Available One of the most valuable aquaculture fish in Europe is the rainbow trout, Oncorhynchus mykiss, but the profitability of trout production is threatened by a highly lethal infectious disease, viral hemorrhagic septicemia (VHS, caused by the VHS virus (VHSV. For the past few decades, the subgenogroup Ia of VHSV has been the main cause of VHS outbreaks in European freshwater-farmed rainbow trout. Little is currently known, however, about the phylogenetic radiation of this Ia lineage into subordinate Ia clades and their subsequent geographical spread routes. We investigated this topic using the largest Ia-isolate dataset ever compiled, comprising 651 complete G gene sequences: 209 GenBank Ia isolates and 442 Ia isolates from this study. The sequences come from 11 European countries and cover the period 1971-2015. Based on this dataset, we documented the extensive spread of the Ia population and the strong mixing of Ia isolates, assumed to be the result of the Europe-wide trout trade. For example, the Ia lineage underwent a radiation into nine Ia clades, most of which are difficult to allocate to a specific geographic distribution. Furthermore, we found indications for two rapid, large-scale population growth events, and identified three polytomies among the Ia clades, both of which possibly indicate a rapid radiation. However, only about 4% of Ia haplotypes (out of 398 occur in more than one European country. This apparently conflicting finding regarding the Europe-wide spread and mixing of Ia isolates can be explained by the high mutation rate of VHSV. Accordingly, the mean period of occurrence of a single Ia haplotype was less than a full year, and we found a substitution rate of up to 7.813 × 10-4 nucleotides per site per year. Finally, we documented significant differences between Germany and Denmark regarding their VHS epidemiology, apparently due to those countries' individual handling of VHS.

  12. Third wave of African swine fever infection in Armenia: Virus demonstrates the reduction of pathogenicity

    Sargsyan, M. A.; Voskanyan, H. E.; Karalova, E. M.; Hakobyan, L. H.; Karalyan, Z. A.

    2018-01-01

    Aim: First cases of clinically uncommon African swine fever (ASF), caused by virus genotype II are described in this article. These cases occurred in Armenia, Tavush region, Dilijan municipality in 2011. The aim of this study was to identify and describe the new pathogenic forms of ASF in Armenia. Materials and Methods: The isolation and identification of ASF virus (ASFV) were carried out using conventional techniques. Clinical signs of infection were recorded daily. Gross anatomical pathology characteristics were observed during routine postmortem examinations. Blood and serum were obtained by puncture of the jugular vein using a vacutainer system. Results: The presence of ASFV DNA in the spleens was confirmed by polymerase chain reaction. Sequenced sections of p72 showed phylogenetic identity to genotype 2. The pathology exhibits unusual manifestations of the main disease. The unusual form of ASF demonstrates characteristics of a subacute form of the disease, with the possibility of conversion to a chronic form. Decreased lethality, low level of hemorrhages, and absence of severe pancytopenia in smears from spleen, lymph nodes, and blood are common features of the new form of ASF. Unlike severe thrombocytopenia in the typical ASF, the unusual form exhibited moderate or minor decrease of this feature. Despite a moderate decrease in hemadsorption titers, the unusual pattern of the disease was characterized by viremia and the presence of the virus in the visceral organs, including the brain. Conclusion: Our data allow assuming that new nosological form of ASF (genotype II) may present as a transitional form of the disease with the possibility of chronization. PMID:29479149

  13. Third wave of African swine fever infection in Armenia: Virus demonstrates the reduction of pathogenicity

    M. A. Sargsyan

    2018-01-01

    Full Text Available Aim: First cases of clinically uncommon African swine fever (ASF, caused by virus genotype II are described in this article. These cases occurred in Armenia, Tavush region, Dilijan municipality in 2011. The aim of this study was to identify and describe the new pathogenic forms of ASF in Armenia. Materials and Methods: The isolation and identification of ASF virus (ASFV were carried out using conventional techniques. Clinical signs of infection were recorded daily. Gross anatomical pathology characteristics were observed during routine postmortem examinations. Blood and serum were obtained by puncture of the jugular vein using a vacutainer system. Results: The presence of ASFV DNA in the spleens was confirmed by polymerase chain reaction. Sequenced sections of p72 showed phylogenetic identity to genotype 2. The pathology exhibits unusual manifestations of the main disease. The unusual form of ASF demonstrates characteristics of a subacute form of the disease, with the possibility of conversion to a chronic form. Decreased lethality, low level of hemorrhages, and absence of severe pancytopenia in smears from spleen, lymph nodes, and blood are common features of the new form of ASF. Unlike severe thrombocytopenia in the typical ASF, the unusual form exhibited moderate or minor decrease of this feature. Despite a moderate decrease in hemadsorption titers, the unusual pattern of the disease was characterized by viremia and the presence of the virus in the visceral organs, including the brain. Conclusion: Our data allow assuming that new nosological form of ASF (genotype II may present as a transitional form of the disease with the possibility of chronization.

  14. Yellow Fever Virus Vaccine–associated Deaths in Young Women 1

    Seligman, Stephen J.

    2011-01-01

    Yellow fever vaccine–associated viscerotropic disease is a rare sequela of live-attenuated virus vaccine. Elderly persons and persons who have had thymectomies have increased susceptibility. A review of published and other data suggested a higher than expected number of deaths from yellow fever vaccine–associated viscerotropic disease among women 19–34 years of age without known immunodeficiency.

  15. Lineage-Specific Real-Time RT-PCR for Yellow Fever Virus Outbreak Surveillance, Brazil.

    Fischer, Carlo; Torres, Maria C; Patel, Pranav; Moreira-Soto, Andres; Gould, Ernest A; Charrel, Rémi N; de Lamballerie, Xavier; Nogueira, Rita Maria Ribeiro; Sequeira, Patricia C; Rodrigues, Cintia D S; Kümmerer, Beate M; Drosten, Christian; Landt, Olfert; Bispo de Filippis, Ana Maria; Drexler, Jan Felix

    2017-11-01

    The current yellow fever outbreak in Brazil prompted widespread yellow fever virus (YFV) vaccination campaigns, imposing a responsibility to distinguish between vaccine- and wild-type YFV-associated disease. We developed novel multiplex real-time reverse transcription PCRs that differentiate between vaccine and American wild-type YFV. We validated these highly specific and sensitive assays in an outbreak setting.

  16. Lineage-Specific Real-Time RT-PCR for Yellow Fever Virus Outbreak Surveillance, Brazil

    Fischer, Carlo; Torres, Maria C.; Patel, Pranav; Moreira-Soto, Andres; Gould, Ernest A.; Charrel, Rémi N.; de Lamballerie, Xavier; Nogueira, Rita Maria Ribeiro; Sequeira, Patricia C.; Rodrigues, Cintia D.S.; Kümmerer, Beate M.; Drosten, Christian; Landt, Olfert; Bispo de Filippis, Ana Maria; Drexler, Jan Felix

    2017-01-01

    The current yellow fever outbreak in Brazil prompted widespread yellow fever virus (YFV) vaccination campaigns, imposing a responsibility to distinguish between vaccine- and wild-type YFV-associated disease. We developed novel multiplex real-time reverse transcription PCRs that differentiate between vaccine and American wild-type YFV. We validated these highly specific and sensitive assays in an outbreak setting.

  17. A DNA vaccine against yellow fever virus: development and evaluation.

    Milton Maciel

    2015-04-01

    Full Text Available Attenuated yellow fever (YF virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE, aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.

  18. A DNA vaccine against yellow fever virus: development and evaluation.

    Maciel, Milton; Cruz, Fábia da Silva Pereira; Cordeiro, Marli Tenório; da Motta, Márcia Archer; Cassemiro, Klécia Marília Soares de Melo; Maia, Rita de Cássia Carvalho; de Figueiredo, Regina Célia Bressan Queiroz; Galler, Ricardo; Freire, Marcos da Silva; August, Joseph Thomas; Marques, Ernesto T A; Dhalia, Rafael

    2015-04-01

    Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.

  19. A DNA Vaccine against Yellow Fever Virus: Development and Evaluation

    Maciel, Milton; Cruz, Fábia da Silva Pereira; Cordeiro, Marli Tenório; da Motta, Márcia Archer; Cassemiro, Klécia Marília Soares de Melo; Maia, Rita de Cássia Carvalho; de Figueiredo, Regina Célia Bressan Queiroz; Galler, Ricardo; Freire, Marcos da Silva; August, Joseph Thomas; Marques, Ernesto T. A.; Dhalia, Rafael

    2015-01-01

    Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies. PMID:25875109

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

    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.

  1. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

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

    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.

  3. Virulence determinants within the E2 glycoprotein of Classical Swine Fever Virus

    Johnston, Camille Melissa; Fahnøe, Ulrik; Lohse, Louise

    Classical Swine Fever is a highly contagious disease of pigs caused by Classical Swine Fever Virus (CSFV), a member of the pestivirus genus within the family Flaviviridae. The E2 glycoprotein of CSFV has been shown to be an important factor for the virulence of the virus. In a recent study, we have......Kos (with the SL motif). The results indicate that the E2 residues 763-64 play an important role in CSFV virulence....

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

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

    2013-01-01

    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 e...

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

    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.

  6. An evaluation of modified case definitions for the detection of dengue hemorrhagic fever. Puerto Rico Association of Epidemiologists.

    Rigau-Pérez, J G; Bonilla, G L

    1999-12-01

    The case definition for dengue hemorrhagic fever (DHF) requires fever, platelets plasma leakage evidenced by hemoconcentration > or = 20%, pleural or abdominal effusions, hypoproteinemia or hypoalbuminemia. We evaluated the specificity and yield of modified DHF case definitions and the recently proposed World Health Organization criteria for a provisional diagnosis of DHF, using a data base of laboratory-positive and laboratory-negative reports of hospitalizations for suspected dengue in Puerto Rico, 1994 to 1996. By design, all modifications had 100% sensitivity. More liberal criteria for plasma leakage were examined: 1) adding as evidence a single hematocrit > or = 50% (specificity 97.4%); 2) accepting hemoconcentration > or = 10% (specificity 90.1%); and 3) accepting either hematocrit > or = 50% or hemoconcentration > or = 10% (specificity 88.8%). The new DHF cases identified by these definitions (and percent laboratory positive) were 25 (100.0%), 95 (90.5%), and 107 (91.6%), respectively. In contrast, the provisional diagnosis of DHF (fever and hemorrhage, and one or more of platelets or = 20%, or at least a rising hematocrit [redefined quantitatively as a 5% or greater relative change]) showed a specificity of 66.8%, and identified 318 new DHF cases, of which 282 (88.7%) were laboratory-positive. Very small changes in the criteria may result in a large number of new cases. The modification that accepted either hematocrit > or = 50% or hemoconcentration > or = 10% had acceptable specificity, while doubling the detection of DHF-compatible, laboratory-positive severe cases, but "provisional diagnosis" showed even lower specificity, and may produce inflated DHF incidence figures. Modified case definitions should be prospectively evaluated with patients in a health-care facility before they are recommended for widespread use.

  7. Role Of Adhesion Molecules Vcam-1 And Ve-Cadherin In Endothelium Dysfunction Development At Hemorrhagic Fever With Renal Syndrome

    А.А. Baygildina

    2009-12-01

    Full Text Available The research goal is to determine the changes in concentration of both sVCAM-1 and VE-cadherin in blood serum of patients suffered from hemorrhagic fever with renal syndrome (HFRS. 87 patients aged 15-65 were examined. Concentrations of both sVCAM-1 and VE- cadherin in blood serum by means of "Bender MedSystems" (Austria ELISA test were determined. It was shown that in both medium severe and severe forms of HFRS statistically the significant rise of sVCAM-1 concentration in blood with high indices in oliguric period took place. Complicated form was characterized by high indices of sVCAM-1 level in fever period, extremely decreasing in concentration in oliguric period and tendency to normalizing in clinical convalescence period. VE-cadherin level in blood was predominantly lower than control in all the observed groups with the exception of fever period in group with medium severe disease form. Negative correlation of normal intensity between adhesion molecules levels in blood was revealed. In conclusion it is necessary to point out that high VCAM-1 expression by endotheliocytes evidences the development of an adhesion form of endothelial dysfunction, low VE-cadherin production in a base for development of angiogenic form of endothelial dysfunction and changes in expression of these adhesion molecules that have adaptive metabolic response to macroorganism of HFRS pathogenic action

  8. T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models.

    Watson, Alan M; Klimstra, William B

    2017-04-11

    The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus.

  9. T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models

    Watson, Alan M.; Klimstra, William B.

    2017-01-01

    The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus. PMID:28398253

  10. Seroprevalence of sandfly fever virus infection in military personnel on the western border of Iran

    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

  11. Dengue virus receptor

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

    2011-01-01

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

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

    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

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

    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

  14. Differences in Mortality and Clinical Manifestations of Dengue Hemorrhagic Fever in Taiwan in Different Years: A Comparison for Cases in 2014 and 2015 Epidemics.

    Chang, Ko; Huang, Chung-Hao; Lee, Ing-Kit; Lu, Po-Liang; Lin, Chun-Yu; Chen, Tun-Chieh; Lai, Ping-Chang; Hsieh, Hsiao-Cheng; Yu, Hsin-Liang; Hung, Chih-Hsing; Wu, Meng-Chieh; Chin, Yi-Ying; Huang, Chun-Chi; Wu, Deng-Chyang; Chen, Yen-Hsu

    2017-08-01

    People in southern Taiwan experienced two major dengue outbreaks in 2014 and 2015. The mortality and clinical features were very different between these 2 years. Dengue virus serotype 1 (DENV-1) caused epidemic outbreak in 2014 and DENV-2 was predominant in 2015. The characteristics of dengue hemorrhagic fever (DHF) cases in the 2 years was analyzed. We conducted a retrospective chart review to analyze the clinical and laboratory features of 206 adult patients with DHF in southern Taiwan in 2014 and 2015. The mortality rate of DHF cases in 2015 was higher than that of cases in 2014 (38.7% versus 12.4%, P mortality cases, diabetes, chronic renal failure, proton-pump inhibitors using, platelet transfusion, and Charlson comorbidity index score (Charlson score) were also higher in 2015. Multivariate analysis for the mortality cases revealed that the risk factors were Charlson score ≥ 5 ( P = 0.02, odds ratio [OR] = 4.07, 95% confidence interval [CI] = 1.244-13.307), severe hepatitis ( P mortality and more complications, such as gastrointestinal bleeding, severe hepatitis, and myocarditis, than in 2014 in southern Taiwan. In the 2-year DHF case series, Charlson score ≥ 5, severe hepatitis, and acute renal failure were independent significant variables for mortality.

  15. Some clinical and laboratory parameters of hemorrhagic fever with renal failure syndrome against the background correction of hyperhomocysteinemia

    G. R. Syrtlanova

    2013-01-01

    Full Text Available The aim of the research was to curry out correction of hyperhomocysteinemia in patients with hemorrhagic fever with renal failure syndrome (HFRS and evaluate some clinical and laboratory parameters. The results of examining 91 men patients with HFRS at the age of 18 till 50 years old are presented. The vitamin complex «Angiovit» was used for hyperhomocysteinemia correction. The correction of hyperhomocysteinemia using the vitamin complex in all the three considered forms (mid, severs, complicated there are statistically significant decreases of homocysteine, the duration of oliguric stage and the concentration of creatinine in oliguric and diuretic stages in patients with HFRS compared with the group of patients having the generally basically therapy.

  16. A Different Approach to Assess Oxidative Stress in Dengue Hemorrhagic Fever Patients Through The Calculation of Oxidative Stress Index

    Edi Hartoyo

    2017-09-01

    Full Text Available The objectives of this study were to determine the involvement of Oxidative Stress (OS in the pathogenesis of dengue hemorrhagic fever (DHF through the analysis of oxidative stress Index (OSI. The levels of malondialdehyde (MDA, superoxide dismutase (SOD and catalase (CAT activity, and OSI were measured in 61 child dengue patients and (aged 6 months–18 years with three different stages of DHF, i.e stage I, II, and III. The results show that the levels of MDA, SOD and CAT activity, and OSI significantly different between the group. The all parameters that investigated in this present study seems higher MDA level and OSI in the higher grade of DHF, except for SOD and CAT activity. From this result, it can be concluded that oxidative stress pathways might be involved in the pathomechanism of DHF and OSI might be used as a biomarker for OS and the severity in DHF patients.

  17. Differentiation of strains of yellow fever virus in γ-irradiated mice

    Fitzgeorge, R.; Bradish, C.J.

    1980-01-01

    The mouse sensitized by optimal, sub-lethal γ-irradiation has been used for the differentiation of strains of yellow fever virus and for the resolution of their immunogenicity and pathogenicity as distinct characteristics. For different strains of yellow fever virus, the patterns of antibody-synthesis, regulatory immunity (pre-challenge) and protective immunity (post-challenge) are differentially sensitive to γ-irradiation. These critical differentiations of strains of yellow fever virus in γ-irradiated mice have been compared with those shown in normal athymic and immature mice in order to elucidate the range of quantifiable in vivo characteristics and the course of the virus-host interaction. This is discussed as a basis for the comparisons of the responses of model and principal hosts to vaccines and pathogens. (author)

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

    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

  19. Production of Potent Fully Human Polyclonal Antibodies Against Zaire Ebola Virus in Transchromosomal Cattle

    2016-07-01

    both humans and non-human primates (NHP) causing severe hemorrhagic fevers with symptoms of disease including sudden onset of fever , chills, headache...and anorexia followed by sore throat, vomiting, diarrhea, hemorrhaging, and the appearance of a petechial rash1-3. Filoviruses are categorized as...hemorrhagic fever . Clinics in laboratory medicine 30, 161-177 (2010). 6. Parren, P.W., et al., Pre- and postexposure prophylaxis of Ebola virus

  20. Fever

    ... 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 ...

  1. Fever

    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.

  2. Immunization of Pigs by DNA Prime and Recombinant Vaccinia Virus Boost To Identify and Rank African Swine Fever Virus Immunogenic and Protective Proteins.

    Jancovich, James K; Chapman, Dave; Hansen, Debra T; Robida, Mark D; Loskutov, Andrey; Craciunescu, Felicia; Borovkov, Alex; Kibler, Karen; Goatley, Lynnette; King, Katherine; Netherton, Christopher L; Taylor, Geraldine; Jacobs, Bertram; Sykes, Kathryn; Dixon, Linda K

    2018-04-15

    African swine fever virus (ASFV) causes an acute hemorrhagic fever in domestic pigs, with high socioeconomic impact. No vaccine is available, limiting options for control. Although live attenuated ASFV can induce up to 100% protection against lethal challenge, little is known of the antigens which induce this protective response. To identify additional ASFV immunogenic and potentially protective antigens, we cloned 47 viral genes in individual plasmids for gene vaccination and in recombinant vaccinia viruses. These antigens were selected to include proteins with different functions and timing of expression. Pools of up to 22 antigens were delivered by DNA prime and recombinant vaccinia virus boost to groups of pigs. Responses of immune lymphocytes from pigs to individual recombinant proteins and to ASFV were measured by interferon gamma enzyme-linked immunosorbent spot (ELISpot) assays to identify a subset of the antigens that consistently induced the highest responses. All 47 antigens were then delivered to pigs by DNA prime and recombinant vaccinia virus boost, and pigs were challenged with a lethal dose of ASFV isolate Georgia 2007/1. Although pigs developed clinical and pathological signs consistent with acute ASFV, viral genome levels were significantly reduced in blood and several lymph tissues in those pigs immunized with vectors expressing ASFV antigens compared with the levels in control pigs. IMPORTANCE The lack of a vaccine limits the options to control African swine fever. Advances have been made in the development of genetically modified live attenuated ASFV that can induce protection against challenge. However, there may be safety issues relating to the use of these in the field. There is little information about ASFV antigens that can induce a protective immune response against challenge. We carried out a large screen of 30% of ASFV antigens by delivering individual genes in different pools to pigs by DNA immunization prime and recombinant vaccinia

  3. Crimean-Congo hemorrhagic fever in pregnancy: A systematic review and case series from Russia, Kazakhstan and Turkey.

    Pshenichnaya, Natalia Yurievna; Leblebicioglu, Hakan; Bozkurt, Ilkay; Sannikova, Irina Viktorovna; Abuova, Gulzhan Narkenovna; Zhuravlev, Andrey Sergeevich; Barut, Sener; Shermetova, Mutabar Bekovna; Fletcher, Tom E

    2017-05-01

    Crimean-Congo hemorrhagic fever (CCHF) is acute viral infection and a major emerging infectious diseases threat, affecting a large geographical area. There is no proven antiviral therapy and it has a case fatality rate of 4-30%. The natural history of disease and outcomes of CCHF in pregnant women is poorly understood. To systematically review the characteristics of CCHF in pregnancy, and report a case series of 8 CCHF cases in pregnant women from Russia, Kazakhstan and Turkey. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. PubMed, SCOPUS, Science Citation Index (SCI) were searched for reports published between January 1960 and June 2016. Two independent reviewers selected and reviewed studies and extracted data. Thirty-four cases of CCHF in pregnancy were identified, and combined with the case series data, 42 cases were analyzed. The majority of cases originated in Turkey (14), Iran (10) and Russia (6). There was a maternal mortality of 14/41(34%) and fetal/neonatal mortality of in 24/41 cases (58.5%). Hemorrhage was associated with maternal (p=0.009) and fetal/neonatal death (p<0.0001). There was nosocomial transmission to 38 cases from 6/37 index pregnant cases. Cases of CCHF in pregnancy are rare, but associated with high rates of maternal and fetal mortality, and nosocomial transmission. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Rift Valley Fever.

    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.

  5. Remarkable sequence similarity between the dinoflagellate-infecting marine girus and the terrestrial pathogen African swine fever virus

    Claverie Jean-Michel

    2009-10-01

    Full Text Available Abstract Heterocapsa circularisquama DNA virus (HcDNAV; previously designated as HcV is a giant virus (girus with a ~356-kbp double-stranded DNA (dsDNA genome. HcDNAV lytically infects the bivalve-killing marine dinoflagellate H. circularisquama, and currently represents the sole DNA virus isolated from dinoflagellates, one of the most abundant protists in marine ecosystems. Its morphological features, genome type, and host range previously suggested that HcDNAV might be a member of the family Phycodnaviridae of Nucleo-Cytoplasmic Large DNA Viruses (NCLDVs, though no supporting sequence data was available. NCLDVs currently include two families found in aquatic environments (Phycodnaviridae, Mimiviridae, one mostly infecting terrestrial animals (Poxviridae, another isolated from fish, amphibians and insects (Iridoviridae, and the last one (Asfarviridae exclusively represented by the animal pathogen African swine fever virus (ASFV, the agent of a fatal hemorrhagic disease in domestic swine. In this study, we determined the complete sequence of the type B DNA polymerase (PolB gene of HcDNAV. The viral PolB was transcribed at least from 6 h post inoculation (hpi, suggesting its crucial function for viral replication. Most unexpectedly, the HcDNAV PolB sequence was found to be closely related to the PolB sequence of ASFV. In addition, the amino acid sequence of HcDNAV PolB showed a rare amino acid substitution within a motif containing highly conserved motif: YSDTDS was found in HcDNAV PolB instead of YGDTDS in most dsDNA viruses. Together with the previous observation of ASFV-like sequences in the Sorcerer II Global Ocean Sampling metagenomic datasets, our results further reinforce the ideas that the terrestrial ASFV has its evolutionary origin in marine environments.

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

    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.

  7. Horizontal transmissible protection against myxomatosis and rabbit hemorrhagic disease by using a recombinant myxoma virus.

    Bárcena, J; Morales, M; Vázquez, B; Boga, J A; Parra, F; Lucientes, J; Pagès-Manté, A; Sánchez-Vizcaíno, J M; Blasco, R; Torres, J M

    2000-02-01

    We have developed a new strategy for immunization of wild rabbit populations against myxomatosis and rabbit hemorrhagic disease (RHD) that uses recombinant viruses based on a naturally attenuated field strain of myxoma virus (MV). The recombinant viruses expressed the RHDV major capsid protein (VP60) including a linear epitope tag from the transmissible gastroenteritis virus (TGEV) nucleoprotein. Following inoculation, the recombinant viruses induced specific antibody responses against MV, RHDV, and the TGEV tag. Immunization of wild rabbits by the subcutaneous and oral routes conferred protection against virulent RHDV and MV challenges. The recombinant viruses showed a limited horizontal transmission capacity, either by direct contact or in a flea-mediated process, promoting immunization of contact uninoculated animals.

  8. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

    2011-02-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

    2010-01-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

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

    2018-01-12

    Jan 12, 2018 ... Engineering a wild fast-growing Mycoplasma bacterium to generate a novel vaccine for contagious caprine ... Engineering vaccines against hemorrhagic septicemia in ruminants ... Solutions. Careers · Contact Us · Site map.

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

    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.

  12. Detection of yellow fever virus genomes from four imported cases in China.

    Cui, Shujuan; Pan, Yang; Lyu, Yanning; Liang, Zhichao; Li, Jie; Sun, Yulan; Dou, Xiangfeng; Tian, Lili; Huo, Da; Chen, Lijuan; Li, Xinyu; Wang, Quanyi

    2017-07-01

    Yellow fever virus (YFV), as the first proven human-pathogenic virus, is still a major public health problem with a dramatic upsurge in recent years. This is a report on four imported cases of yellow fever virus into China identified by whole genome sequencing. Phylogenetic analysis was performed and the results showed that these four viruses were highly homologous with Angola 71 strains (AY968064). In addition, effective mutations of amino acids were not observed in the E protein domain of four viruses, thus confirming the effectiveness of the YFV-17D vaccine (X03700). Although there is low risk of local transmission in most part of China, the increasing public health risk of YF caused by international exchange should not be ignored. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. 20 YEARS OF PROGRESS IN DENGUE HEMORRHAGIC FEVER AND OTHER ARBOVIRAL DISEASES RESEARCH

    Sumarmo Poorwo Soedarmo

    2012-09-01

    Full Text Available Throughout the 20 year history of U.S. Naval Medical Research Unit No. 2 Detachment (NAMRU, many viruses and viral diseases have been studied. The greatest emphasis has been in the field of arboviruses, specifically dengue virus, chikungunya virus, and Japanese B encephalitis virus. The initial focus of the work was to define the extent of the threat posed by these viruses. Studies were conducted to determine antibody prevalence, and to determine the etiologies of infectious febrile disease in hospitalized patients. Later the work advanced into more specific areas, especially the entomologic and clinical components of these viruses. Little was known of the incidence or kind of arbovirus infections in Indonesia when NAMRU was established. Previous serological studies had used the cross reactive haemagglutination assay. Green et al. in 1973 provided convincing serological evidence of infections with chikungunya virus and group B arboviruses by using the specific virus neutralization assay. These results demonstrated the need for further studies to isolate the causative agent, to describe the epidemiology, and to investigate the clinical features of the associated disease.

  14. Genotyping of African swine fever virus (ASFV) isolates associated ...

    Four of these viruses were isolated directly from serum samples. All the viruses were classified within the domesticpig cycle-associated p72 and p54 genotype IX which also includes viruses responsible for ASF outbreaks in Kenya in 2006 and 2007 and Uganda in 2003. To define virus relationships at higher resolution, ...

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

    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.

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

    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.

  17. CRISPR-Cas9, a tool to efficiently increase the development of recombinant African swine fever viruses

    African swine fever is a contagious and often lethal disease for domestic pigs with a significant economic impact on the swine industry. The etiological agent, African swine fever virus (ASFV), is a highly structurally complex double stranded DNA virus. No effective vaccines or antiviral treatment ...

  18. [Clinical and epidemiologic characteristics of hemorrhagic fever with renal syndrome in patients treated at the Dr. Fran Mihaljević Clinic for Infectious Diseases in Zagreb].

    Puljiz, Ivan; Kuzman, Ilija; Turcinov, Drago; Markotić, Alemka; Celjuska, Elvira

    2003-01-01

    The aim of the study was to examine and analyze the main epidemiologic and clinical data of 94 patients with hemorrhagic fever with renal syndrome (HFRS) hospitalized at the University Hospital for Infectious Diseases in Zagreb during the HFRS outbreak in Croatia in 2002. A total of 110 patients with clinical diagnosis HFRS were treated at the University Hospital for Infectious Diseases in Zagreb. In 110 of HFRS suspected patients, the clinical diagnosis was verified serologically in 94 patients and they were included in the retrospective study. In 93 patients the diagnosis was confirmed by enzyme-linked immunosorbent assay (ELISA), and in one patient by indirect immunofluorescence assay (IFA). Results were analyzed by the use of descriptive statistics. Puumala (PUU) virus infection was verified in 80 (85.1%), Dobrava (DOB) infection in 8 (8.5%) and cross-reactive antibodies to both PUU and DOB viruses in 5 (5.3%) HFRS patients. In one patient who was confirmed by IFA the hantavirus serotype causing HFRS could not be determined. The localities of the presumed HFRS patient exposure to hantaviruses were mostly in the Zagreb area. Most patients were aged 21-50 (83.0%) and male (76.6%). The majority of HFRS cases occurred between May and August (75.5%). A high proportion of HFRS cases were found in the general population from Zagreb and its surroundings (78.7%). The majority of patients were hospitalized in the febrile stage of the disease (70.2%). The main symptoms were: fever (100%), headache (88.3%) and backache (87.2%). Oliguria was recorded in 56.4% and, anuria in 7.5% of patients, however, only three (3.2%) patients required hemodialysis. Six patients developed hemorrhagic manifestations, especially petechiae on the skin and mucosa. One patient in the convalescent stage had subarachnoidal bleeding. Six patients had pathologic electroencephalogram (EEG) findings and two developed epileptic seizures. Lumbar puncture was performed in 12 patients without inflammatory

  19. Knowledge regarding Ebola Hemorrhagic Fever among private dental practitioners in Tricity, India: A cross-sectional questionnaire study.

    Gupta, Nidhi; Mehta, Nishant; Gupta, Preety; Arora, Vikram; Setia, Priyanka

    2015-01-01

    Ebola viral fever, a highly contagious haemorrhagic disease has today become a major public health concern in the developing countries worldwide. The purpose of this study was to assess knowledge among dental practitioners regarding Ebola Haemorrhagic Fever (Ebola HF) in Tricity, (Chandigarh, Panchkula and Mohali). A total of 500 private dental practitioners were randomly approached to participate in this cross-sectional survey. A self-structured, closed ended questionnaire was administered to each participant to record demographic and professional characteristics followed by their knowledge regarding Ebola HF. Knowledge section included questions related to communicability; symptomatology and diagnostics; at-risk individuals; prevention and treatment; and, virus characteristics of Ebola HF. The results were expressed in percentages. Multivariable linear regression analysis was carried out to assess the association of participants's demographic and professional characteristics with the knowledge scores. Statistically significant difference was seen when mean knowledge scores were compared based on the locality and qualification of the participants (P < 0.05). Dental practitioners from urban areas with higher qualification had better knowledge yet there were notable deficiencies regarding the virus characteristics, diagnostics, elimination and treatment.

  20. DETECTION OF CLASSICAL SWINE FEVER VIRUS BY RT-PCR IN WEST BENGAL, INDIA

    Sumit Chowdhury

    2016-12-01

    Full Text Available Classical swine fever is a deadly disease of swine, caused by a RNA virus. The present study has identified presence of the classical swine fever virus (CSFV in pigs of West Bengal by one step reverse transcriptase PCR (RT-PCR performed using 5’ NTR specific primers. Internal organs from clinically affected pigs were examined from three districts of West Bengal. RT-PCT has identified presence of CSFV in all the tissues examined confirming presence of CSFV in different parts of the state.

  1. [Epizootology of hemorrhagic fever with renal syndrome in the Central Chernozem Region].

    Balakirev, A E; Bashkirtsev, V N; Sedova, N S; Okulova, N M; Trankvilevskiĭ, D V; Sikora, I V; Frolova, S M; Luz'ianov, E N; Shinkorenko, N N; Sapel'nikov, A F; Tkachenko, E A

    2006-01-01

    A total of 5149 small mammals belonging to 16 species were collected from the Lipetsk, Voronezh, and Belgorod regions (40 administrative districts) in 2003-2004 and examined by ELISA and IFA to detect hantavirus antigen and antibodies in the lung tissues. Hantavirus circulation was revealed in 13 species, the highest hantavirus activity being detected in field (Apodemus agrarius) and small wood (A. (S) uralensis) mice (Dobrava-Belgrad virus), bank (Clethrionomis glareolus) (Puumala virus) and common (Microtus arvalis) (Tula virus) voles. These species were frequently found to have their untypical hantaviruses, which was most commonly observed in small wood mice. It is suggested that the small wood mouse is likely to take a certain part in maintaining the circulation of Dobrava-Belgrad virus.

  2. Control of Ebola hemorrhagic fever: vaccine development and our Ebola project in Sierra Leone.

    Watanabe, Tokiko; Kawaoka, Yoshihiro

    2016-01-01

    Since December 2013, West Africa has experienced the worst Ebola virus outbreak in recorded history. Of the 28,639 cases reported to the World Health Organization as of March 2016, nearly half (14,124) occurred in Sierra Leone. With a case fatality rate of approximately 40%, this outbreak has claimed the lives of 11,316 individuals. No FDA-approved vaccines or drugs are available to prevent or treat Ebola virus infection. Experimental vaccines and therapies are being developed; however, their safety and efficacy are still being evaluated. Therefore, there is an urgent need to develop control measures to prevent or limit future Ebola virus outbreaks.Previously, we developed a replication-defective Ebola virus that lacks the coding region for the essential viral transcription activator VP30 (Ebola ΔVP30 virus). Here, we evaluated the vaccine efficacy of Ebola ΔVP30 virus in a non-human primate model and describe our collaborative Ebola project in Sierra Leone.

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

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

    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.

  5. VECTOR RESISTANCE STATUS OF DENGUE HEMORRHAGIC FEVER (Aedes aegypti IN THE SIDOREJO DISTRICT SALATIGA CITY AGAINST TEMEPHOS (ORGANOPHOSPHATES

    Ary Oktsari Yanti S

    2014-06-01

    Full Text Available One of the efforts to control the incidence of Dengue Hemorrhagic Fever (DHF is contrled thedengue vector larvae using larvasida. The most widely larvasida used to control larvae Ae.aegypti is temephos. In Indonesia 1% temephos (abate 1SG has been used since 1976, and since1980 has been used for the eradication program ofAe. aegypti larvae. The purpose of this studyis to determine the resistance status of vectors of dengue hemorrhagic fever (Ae. aegypti ofendemic, sporadic, and potentially in Sub District Sidorejo Salatiga City to temephos(organofosfat. This research was conducted using experimental research design (TrueExperiment, posttcst design with control groups (posttest-only Control Group Design. Thepopulation of the research were larvae of Ae. aegypti collected from the study area. Samples testlarvae were used of Ae. aegypti third and early fourth instars larvae which were maintenance ofthe first generation. The result showed that the mortality percentages of Ae. aegypti larvaeof endemic, sporadic and potential administratives against temephos using WHO standardconcentration (0,625; 0,125; 0,025 mg/1 indicates the mortality of Ae. aegypti larvae by 100%Based on the status resistance criteria, Ae. aegypti larvae from endemic, sporadic, and potentialadministratives of Sidorejo Sub-District, Salatiga City is still susceptible to temephos.Keywords : Status of resistance, Aedes aegypti. TemephosSalah satu upaya menurunkan Demam Berdarah Dengue (DBD adalah melaluipengcndalian jentik vektor DBD dengan larvasida. Larvasida yang digunakan untukmengcndalikan jentik Ae. aegypti adalah temephos. Temephos 1% (abate ISG sudah programdi Indonesia sejak 1976, scjak 1980 telah digunakan secara massal untuk programpemberantasan jentik Ae. aegypti. Tujuan penelitian ini adalah untuk mengetahui status resistensivektor demam berdarah dengue Ae. aegypti di kclurahan endemis, sporadis, dan potensialKecamatan Sidorejo Kota Salatiga terhadap temephos

  6. RELATIONSHIP BETWEEN KNOWLEDGE OF VECTOR WITH HOUSEHOLD INSECTICIDE USAGE BEHAVIOR IN DENGUE HEMORRHAGIC FEVER ENDEMIC AREAS IN BALI PROVINCE

    Diana Andriyani Pratamawati

    2014-06-01

    Full Text Available Bali Province has a case fatality rate (CFR of Dengue Hemorrhagic Fever (DHF 56.16 per100,000 populations in 2011. Data of Riskesdas 2010 showed that anti mosquito (householdinsecticides was the most widely used by people to prevent vector borne diseases. This studyaimed to describe behavior by using household insecticides to prevent DHF and determinewhether this behavior was based on dengue vector knowledge. This research was a descriptivestudy using survey methods. Unit analysis was households in DHF endemic area in DenpasarCity, Gianyar and Badung Regency which had highest dengue cases until August 2011. Resultsshowed that 54.5% of the 88 respondents has high level in dengue vector knowledge. Mostrespondents (59.1% has good category in household insecticide usage behavior. Kendall taucorrelation test (t showed no significant relation between knowledge of dengue vectors withhousehold insecticide usage behavior for dengue vector control (t = 0,076, p value= 0,479.Keywords: Knowledge, Vector, Dengue Hemorrhagic Fever, HouseholdInsecticides Provinsi Bali memiliki case fatality rate (CFR Demam Berdarah Dengue (DBD 56,16 per100.000 penduduk pada tahun 2011. Data Riskesdas 2010 menunjukkan bahwa obat antinyamuk (insektisida rumah tangga merupakan cara yang paling banyak digunakan olehmasyarakat untuk mencegah penyakit tular vektor. Studi ini bertujuan untuk mendeskripsikanperilaku dalam menggunakan insektisida rumah tangga untuk mencegah DBDserta mengetahuiapakah perilaku ini didasari oleh pengetahuanmengenai vektor DBD. Penelitian ini merupakanstudi deskriptif dengan menggunakan metode survei. Unit analisis adalah rumah tangga didaerah endemis DBD di Kota Denpasar, Kabupaten Gianyar, dan Kabupaten Badung yangmemiliki kasus DBD tertinggi hingga bulan Agustus tahun 2011. Hasil penelitianmenunjukkan bahwa 54,5% dari 88 responden memiliki tingkat pengetahuan yang tinggitentang vektor DBD. Sebagian besar responden (59,1% memiliki perilaku

  7. Dengue Hemorrhagic Fever Tranmission Risk Level on Three Local Health Center in Three Endemic District in South Sulawesi Province, Indonesia

    Dicky Andiarsa

    2017-12-01

    Full Text Available Abstrak. Penelitian ini bertujuan untuk menentukan tingkat risiko penularan DBD di wilayah endemis DBD di Kabupaten Bone, Kota Palopo dan Kota Makassar Provinsi Sulawesi Selatan. Penelitian dilaksanakan Bulan Mei-Juni 2015 pada rumah tangga secara sistematik sampling sebanyak 100 rumah pada setiap wilayah kerja puskesmas endemis DBD tertinggi di Kab. Bone (Watampone, Kota Palopo (Wara dan Kota Makassar (Mangasa Provinsi Sulawesi Selatan. Data dianalisis untuk menunjukkan indikator surveilans larva (HI, CI, dan BI dan density figure. Data disajikan dengan jumlah larva berdasarkan jenis kontainer, persentase dan distribusi kontainer. Nilai ABJ ketiga puskesmas termasuk rendah Watampone: 53%, Wara: 54%, Mangasa: 68%. Persentase CI (angka container larva tertinggi adalah Puskesmas Watampone (17, 78%, selanjutnya Wara (17,71% dan Mangasa (15,47%. Berdasarkan perhitungan HI, CI dan BI, density figure dari ketiga kabupaten pada kategori sedang hingga tinggi dan Maya index menunjukkan tingkat risiko penularan DBD sedang. Hasil menunjukkan bahwa Density figure pada kontainer rumah tangga yang diperiksa sedang hingga tinggi. Kampanye pencegahan DBD yang kuat, deteksi kasus dari rumah ke rumah dan upaya persuasif yang mengedukasi mengenai hal ini penting dilakukan untuk meningkatkan kesadaran masyarakat agar ikut berpartisipasi dan lebih waspada terhadap DBD.Kata Kunci: DBD, larva, Aedes aegypti, kontainer, Maya IndeksAbstract. The aim of this research is to determine of transmission risk level of Dengue Hemorrhagic Fever (DHF endemic area in District of Bone, Municipal of Palopo, and Municipal of Makassar, South Sulawesi province. Study held in May-June 2015 to 100 households by systematically sampling method in three highest local healthcare center work area in each endemic in District of Bone (Watampone, Municipal of Palopo (Wara, and Municipal of Makassar (Mangasa, South Sulawesi Province. Data analyzed to show the indicators of DHF surveillance (House

  8. Zika Virus, a Cause of Fever in Central Java, Indonesia

    1981-01-01

    considered with the isolation of ZIKA Lee, V. H. & Moore, D. L. (1972). Vectors of the virus from a variety of other Aedes of the subgenus 1969 yellow...a vector of the virus . 46, 669-673. Marchette, N. J., Garcia, R. & Rudnick, A. (1969). Acknowledgements Isolation of Zika virus from Aedes aegypti mos...hemagglutination test for the diagnosis of human Twelve isolations of Zika virus from Aedes leptospirosis. Journal of Clinical Microbiology

  9. Increased Levels of VEGF-A and HIF-1α in Turkish Children with Crimean-Congo Hemorrhagic Fever

    Murat Sefikogullari

    2017-04-01

    Full Text Available Background: Crimean-Congo Hemorrhagic Fever (CCHF is a disease characterized by serious course, including acute viral fever, ecchymosis, thrombocytopenia, liver dysfunction and high rate of mortality. Hypoxia Inducible Factor-1α (HIF-1α and Vascular Endothelial Growth Factor-A (VEGF-A play an important role both in the inflamma­tory process and plasma leakage. The aim of this study was to define HIF-1α and VEGF-A serum levels obtained from CCHF patients and control group and to investigate whether these factors were correlated with the pathogenesis of this disease.Methods: Thirty cases younger than 17 yr confirmed by RT-PCR and/or ELISA for CCHF were included in this study. Thirty age and sex matched healthy peoples were enrolled as controls. Blood samples collected from the pa­tient and control groups. Serum levels of HIF-1α and VEGF-A were measured with ELISA.Results: Levels of HIF-1α and VEGF-A were statistically significantly increased in CCHF patients compared to the control group (P< 0.05.  A significant positive correlation was found between the levels of HIF-1α and VEGF-A in the patient group (P< 0.01. The levels of ALT, AST, CK, aPTT, WBC and Thrombocyte count were significantly higher in the patients than in the control group (P< 0.001. A positive correlation was found among the levels of AST and CK from biochemical parame­ters and VEGF and HIF-1α in the patient group (P< 0.05Conclusion: HIF-1α and VEGF-A might play an important role in CCHF pathogenesis.

  10. 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.

    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.

  11. Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

    Nougairede, Antoine; Klitting, Raphaelle; Aubry, Fabien; Gilles, Magali; Touret, Franck; De Lamballerie, Xavier

    2018-01-01

    Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. Here we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared diff...

  12. Uncovering of Classical Swine Fever Virus adaptive response to vaccination by Next Generation Sequencing

    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....

  13. Serological reactions in Rhesus monkeys inoculated with the 17D strain of yellow fever virus.

    GROOT, H

    1962-01-01

    Haemagglutination-inhibition tests, which depend on the appearance of haemagglutination-inhibiting antibodies in the serum in virus infections, are in common use in the study of arthropod-borne diseases. This paper contains the results of an investigation into the appearance and pattern of haemagglutination-inhibiting antibodies in the serum of rhesus monkeys inoculated intracerebrally with the 17D strain of yellow fever virus during the testing of seed lots of yellow fever vaccine. These antibodies appeared on the tenth day after inoculation, and were still demonstrable four years later. In all of the eight monkeys tested complement-fixing and neutralizing antibodies against yellow fever antigens also developed, and in six out of the eight heterologous antigens developed.

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

    2005-04-01

    disease. Death has been observed in 33.9% of cases. Hepatorenal failure, shock, and severe anemia were all factors associated with death.^’" U.S...Allpahuayo virus; a newly recognized arenavirus (Arenaviridae) from arboreal rice rats [Oecomys bicolorand Oecomys parico(a) in northeastern Peru . Virology

  15. Antibodies against Severe Fever with Thrombocytopenia Syndrome Virus in Healthy Persons, China, 2013

    Zhang, Lei; Sun, Jimin; Yan, Jie; Lv, Huakun; Chai, Chengliang; Sun, Yi; Shao, Bin; Jiang, Jianmin; Chen, Zhiping

    2014-01-01

    In June 2013, a subclinical infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Zhejiang Province, China, prompting seroprevalence studies in 6 districts within the province. Of 986 healthy persons tested, 71 had IgG antibodies against SFTSV. This finding suggests that most natural infections with SFTSV are mild or subclinical. PMID:25061813

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

    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...

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

    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

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

    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

  19. Antibodies against severe fever with Thrombocytopenia syndrome Virus in healthy persons, China, 2013

    Zhang Lei, Lei; Sun, J.; Yan, J.; Huakun, L.; Chai, C.Y.; Sun, Y.; Shao, B.; Jiang, J.D.; Chen, Z.; Kortekaas, J.A.; Zhang, Y.

    2014-01-01

    In June 2013, a subclinical infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Zhejiang Province, China, prompting seroprevalence studies in 6 districts within the province. Of 986 healthy persons tested, 71 had IgG antibodies against SFTSV. This finding

  20. Comparison of Two Hybrid Models for Forecasting the Incidence of Hemorrhagic Fever with Renal Syndrome in Jiangsu Province, China.

    Wei Wu

    Full Text Available Cases of hemorrhagic fever with renal syndrome (HFRS are widely distributed in eastern Asia, especially in China, Russia, and Korea. It is proved to be a difficult task to eliminate HFRS completely because of the diverse animal reservoirs and effects of global warming. Reliable forecasting is useful for the prevention and control of HFRS.Two hybrid models, one composed of nonlinear autoregressive neural network (NARNN and autoregressive integrated moving average (ARIMA the other composed of generalized regression neural network (GRNN and ARIMA were constructed to predict the incidence of HFRS in the future one year. Performances of the two hybrid models were compared with ARIMA model.The ARIMA, ARIMA-NARNN ARIMA-GRNN model fitted and predicted the seasonal fluctuation well. Among the three models, the mean square error (MSE, mean absolute error (MAE and mean absolute percentage error (MAPE of ARIMA-NARNN hybrid model was the lowest both in modeling stage and forecasting stage. As for the ARIMA-GRNN hybrid model, the MSE, MAE and MAPE of modeling performance and the MSE and MAE of forecasting performance were less than the ARIMA model, but the MAPE of forecasting performance did not improve.Developing and applying the ARIMA-NARNN hybrid model is an effective method to make us better understand the epidemic characteristics of HFRS and could be helpful to the prevention and control of HFRS.

  1. Effects of Climate and Rodent Factors on Hemorrhagic Fever with Renal Syndrome in Chongqing, China, 1997-2008.

    Yuntao Bai

    Full Text Available China has the highest global incidence of hemorrhagic fever with renal syndrome (HFRS, constituting 90% of the cases in the world. Chongqing, located in the Three Gorges Reservoir Region, has been experiencing differences in the occurrence of HFRS from 1997 to 2008. The current study was designed to explore the effects of climate and rodent factors on the transmission of HFRS in Chongqing. Data on monthly HFRS cases, rodent strains, and climatic factors were collected from 1997 to 2008. Spatio-temporal analysis indicated that most HFRS cases were clustered in central Chongqing and that the incidence of HFRS decreased from 1997 to 2008. Poisson regression models showed that temperature (with lagged months of 0 and 5 and rainfall (with 2 lagged months were key climatic factors contributing to the transmission of HFRS. A zero-inflated negative binomial model revealed that rodent density was also significantly associated with the occurrence of HFRS in the Changshou district. The monthly trend in HFRS incidence was positively associated with rodent density and rainfall and negatively associated with temperature. Possible mechanisms are proposed through which construction of the dam influenced the incidence of HFRS in Chongqing. The findings of this study may contribute to the development of early warning systems for the control and prevention of HFRS in the Three Gorges Reservoir Region.

  2. The spatial analysis on hemorrhagic fever with renal syndrome in Jiangsu province, China based on geographic information system.

    Bao, Changjun; Liu, Wanwan; Zhu, Yefei; Liu, Wendong; Hu, Jianli; Liang, Qi; Cheng, Yuejia; Wu, Ying; Yu, Rongbin; Zhou, Minghao; Shen, Hongbing; Chen, Feng; Tang, Fenyang; Peng, Zhihang

    2014-01-01

    Hemorrhagic fever with renal syndrome (HFRS) is endemic in mainland China, accounting for 90% of total reported cases worldwide, and Jiangsu is one of the most severely affected provinces. In this study, the authors conducted GIS-based spatial analyses in order to determine the spatial distribution of the HFRS cases, identify key areas and explore risk factors for public health planning and resource allocation. Interpolation maps by inverse distance weighting were produced to detect the spatial distribution of HFRS cases in Jiangsu from 2001 to 2011. Spatio-temporal clustering was applied to identify clusters at the county level. Spatial correlation analysis was conducted to detect influencing factors of HFRS in Jiangsu. HFRS cases in Jiangsu from 2001 to 2011 were mapped and the results suggested that cases in Jiangsu were not distributed randomly. Cases were mainly distributed in northeastern and southwestern Jiangsu, especially in Dafeng and Sihong counties. It was notable that prior to this study, Sihong county had rarely been reported as a high-risk area of HFRS. With the maximum spatial size of 50% of the total population and the maximum temporal size of 50% of the total population, spatio-temporal clustering showed that there was one most likely cluster (LLR = 624.52, Phighways, railways, rivers and lakes. The application of GIS together with spatial interpolation, spatio-temporal clustering and spatial correlation analysis can effectively identify high-risk areas and factors influencing HFRS incidence to lay a foundation for researching its pathogenesis.

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

    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.

  4. Case report: probable transmission of vaccine strain of yellow fever virus to an infant via breast milk

    Kuhn, Susan; Twele-Montecinos, Loreto; MacDonald, Judy; Webster, Patricia; Law, Barbara

    2011-01-01

    The 17D yellow fever vaccine is a live-virus vaccine that has been in use since the 1940s. The incidence of encephalitis after yellow fever vaccination among young infants is much higher than among children older than nine months of age. Until recently, avoidance of vaccination by breastfeeding women who have received yellow fever vaccine had been based on theoretical grounds only. We report the probable transmission of vaccine strain of yellow fever virus from a mother to her infant through ...

  5. Herpes Simplex Encephalitis Complicated by Cerebral Hemorrhage during Acyclovir Therapy.

    Harada, Yukinori; Hara, Yuuta

    2017-01-01

    Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE.

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

    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.

  7. Oral receptivity of Aedes aegypti from Cape Verde for yellow fever, dengue, and chikungunya viruses.

    Vazeille, Marie; Yébakima, André; Lourenço-de-Oliveira, Ricardo; Andriamahefazafy, Barrysson; Correira, Artur; Rodrigues, Julio Monteiro; Veiga, Antonio; Moreira, Antonio; Leparc-Goffart, Isabelle; Grandadam, Marc; Failloux, Anna-Bella

    2013-01-01

    At the end of 2009, 21,313 cases of dengue-3 virus (DENV-3) were reported in the islands of Cape Verde, an archipelago located in the Atlantic Ocean 570 km from the coast of western Africa. It was the first dengue outbreak ever reported in Cape Verde. Mosquitoes collected in July 2010 in the city of Praia, on the island of Santiago, were identified morphologically as Aedes aegypti formosus. Using experimental oral infections, we found that this vector showed a moderate ability to transmit the epidemic dengue-3 virus, but was highly susceptible to chikungunya and yellow fever viruses.

  8. Crimean-Congo haemorrhagic fever virus infection in birds: field investigations in Senegal.

    Zeller, H G; Cornet, J P; Camicas, J L

    1994-01-01

    In Senegal, wild ground-feeding birds are frequently infested with immature ticks. In two areas where numerous Crimean-Congo haemorrhagic fever (CCHF) virus isolations were obtained from Hyalomma marginatum rufipes adult ticks collected on ungulates, 175 birds were captured and sera collected. CCHF antibodies were detected by ELISA in 6/22 red-beaked hornbills (Tockus erythrorhynchus), 2/11 glossy starlings (Lamprotornis sp.) and 1/3 guinea fowls. The virus was isolated from H. m. rufipes nymphs collected on a hornbill. The role of wild ground-feeding birds in CCHF virus ecology in West Africa is discussed.

  9. Reconstructing the highly virulent Classical Swine Fever Virus strain Koslov

    Fahnøe, Ulrik; Pedersen, Anders Gorm; Nielsen, Jens

    -prone nature of the RNA-dependent RNA polymerase resulting in the majority of circulating forms being non-functional. However, since any infectious virus particle should necessarily be the offspring of a functional virus, we hypothesized that it should be possible to synthesize a highly virulent form...

  10. Awareness among butchers regarding crimean congo hemorrhagic fever in rawalpindi cantt

    Khaleeq, T.A.; Rahman, M.U.; Tariq, N.A.; Mashhadi, S.F.; Jamil, R.

    2016-01-01

    To study the awareness of butchers regarding Crimean-Congo Haemorrhagic fever (CCHF) in relation to their education level. Study Design: Cross sectional survey. Place and Duration of Study: Conducted from January to March 2015 in Qasaiee Chowk and Tench Bhatta markets of ward 5 of Rawalpindi cantt. Material and Methods: Sample size was calculated using G-Power sample size calculator at 95 percent confidence level with an effect size of 0.38. Ward 5 of Rawalpindi cantt was chosen through lottery method and all available professional butchers in the markets were interviewed with informed consent. A pre-tested 14 items closed ended questionnaire was used and interview was conducted by a well briefed team of medical students. Data was analyzed using SPSS version 20.0. Results: Results showed that only 14 (9.33 percent) butchers knew the name of CCHF. Out of these 10 (71.4 percent) had some form of formal education. All 14 of these had heard about CCHF from television proving it to be an important medium of information. However none of the 150 respondents took any preventive measure against CCHF. Conclusion: Our study concluded that the level of awareness regarding CCHF in butchers is very low and no preventive measures are taken by them. Also the level of education has a significant effect on the awareness. (author)

  11. Effectiveness of Mosquito Trap with Sugar Fermented Attractant to the Vector of Dengue Hemorrhagic Fever

    Endang Puji Astuti

    2011-06-01

    Full Text Available Aedes aegypti is the main vector of dengue fever that is still become health problem in the world. Various control efforts has been done at several areas through chemically or naturally control. Developing mosquitoes trapping tool is an alternative method to control mosquitoes besides insecticides utilization. This laboratorium research utilize sugar fermented process to yield CO2 as one of attractan to mosquito. Production of ethanol and CO2 can be yielded from anaerob sugar fermentation proccess (without O2 by khamir Saccharomyces cerevisiae activities. The trapped mosquitoes was observed up to 48 hours exposure, the highest average of mosquito trapped is on solution treatment with yeast 1 gram (43.2% and 40 gr sugar (48.4%. The highest effectivity of trapping tool both inside or outside was on the 14th day. There were declained amount of trapped mosquitos on 16th and 18th days. This laboratorium research has described that trapping tool with sugar fermented solution were effective to control population of dengue vector.

  12. In vitro infection of salmonid epidermal tissues by infectious hematopoietic necrosis virus and viral hemorrhagic septicemia virus

    Yamamoto, T.; Batts, W.N.; Winton, J.R.

    1992-01-01

    The ability of two rhabdoviruses, infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV), to infect fish skin was investigated by in vitro infection of excised tissues. Virus replication was determined by plaque assay of homogenized tissue extracts, and the virus antigen was detected by immunohistology of tissue sections. Gill, fin, and ventral abdominal skin tissues of rainbow trout Oncorhynchus mykiss that had been infected in vitro with a virulent strain of IHNV (193–110) produced substantial increases in virus titer within 24 h. Titers continued to increase up until day 3 of incubation; by this time, virus had increased 1,000-fold or more. This increase in IHNV titer occurred in epidermal tissues of fingerlings and of older fish. In another experiment, IHNV replicated in excised rainbow trout tissues whether the fish had been subject to prior infection with a virulent strain of IHNV (Western Regional Aquaculture Consortium isolate) or whether the fish had been infected previously with an attenuated strain of the virus (Nan Scott Lake, with 100 passes in culture). A virulent strain of VHSV (23/75) replicated effectively in excised gill tissues and epidermal tissues of rainbow trout and chinook salmon O. tshawytscha; however, the avirulent North American strain of VHSV (Makah) replicated poorly or not at all.

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

    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.

  14. Dengue fever: a Wikipedia clinical review.

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

    2014-01-01

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

  15. Review of Dengue hemorrhagic fever fatal cases seen among adults: a retrospective study.

    Sing-Sin Sam

    Full Text Available BACKGROUND: Dengue is a mosquito-borne viral disease endemic in many countries in the tropics and sub-tropics. The disease affects mainly children, but in recent years it is becoming more of an adult disease. Malaysia experienced a large dengue outbreak in 2006 to 2007, involving mostly adults, with a high number of deaths. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a retrospective study to examine dengue death cases in our hospital from June 2006 to October 2007 with a view to determine if there have been changes in the presentation of severe to fatal dengue. Nine of ten fatal cases involved adult females with a median age of 32 years. All had secondary dengue infection. The mean duration of illness prior to hospitalization was 4.7 days and deaths occurred at an average of 2.4 days post-admission. Gastrointestinal pain, vomiting, diarrhea, intravascular leakages and bleeding occurred in the majority of cases. DSS complicated with severe bleeding, multi-organ failure and coagulopathy were the primary causes of deaths. Seven patients presented with thrombocytopenia and hypoalbuminemia, five of which had hemoconcentration and increased ALT and AST indicative of liver damage. Co-morbidities particularly diabetes mellitus was common in our cohort. Prominent unusual presentations included acute renal failure, acute respiratory distress syndrome, myocarditis with pericarditis, and hemorrhages over the brain and heart. CONCLUSIONS: In our cohort, dengue fatalities are seen primarily in adult females with secondary dengue infection. The majority of the patients presented with common clinical and laboratory warning signs of severe dengue. Underlying co-morbidities may contribute to the rapid clinical deterioration in severe dengue. The uncommon presentations of dengue are likely a reflection of the changing demographics where adults are now more likely to contract dengue in dengue endemic regions.

  16. Public Knowledge and Attitude toward Crimean Congo Hemorrhagic Fever in Tokat Turkey

    R Yilmaz

    2009-12-01

    Full Text Available Background: The World health Organization (WHO declares Crimean Congo hemorrhagic fe­ver (CCHF endemic in Turkey. Despite the magnitude of problem, no documented evi­dence exists in Turkey, which reveals the aware­ness and practices of the country's adult popula­tion regarding CCHF, its spread, symptoms, treatment, and preven­tion. This study was conducted to assess the level of knowledge, attitudes, and practices regarding CCHF in people visit­ing terti­ary care hospital in Tokat, Turkey.Methods: This questionnaire based cross-sectional survey was conducted among patients' rela­tives or guardians who ad­mitted pediatric outpatient clinics during May-July 2008. The question­naire was composed of 25 questions.Results: A total of 1034 respondents participated in the survey. Sufficient knowledge about CCHF was not found in 28.9% of the sample. Literate individuals were relatively better informed about CCHF as compared to the illiterate peo­ple. Television and radio were con­sidered as the most important and useful source of information on the disease.Conclusion: We have found insufficient knowledge on CCHF in our population. It is thought to have no chance of suc­cess against a fatal disease such as CCHF, which has serious consequences, without the contribution of commu­nity. It is clear that there are important tasks for health, agri­culture, and media sectors to improve public knowledge and awareness about CCHF.

  17. Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections

    Müller Marcel A

    2005-02-01

    Full Text Available Abstract Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

  18. Investigations into yellow fever virus and other arboviruses in the northern regions of Kenya.

    Henderson, B E; Metselaar, D; Kirya, G B; Timms, G L

    1970-01-01

    Previous studies having shown an appreciable level of yellow fever immunity to exist in northern Kenya, further epidemiological and serological surveys were carried out there in 1968 in an attempt to define more clearly the distribution of yellow fever and to locate possible vector and reservoir hosts of the disease; these surveys also provided information on a number of other arboviruses.Altogether 436 sera from 5 areas in northern Kenya were screened by haemagglutination-inhibition tests with 8 antigens, and 107 of these sera by neutralization tests for Group-B arboviruses. Small numbers of yellow-fever-immune adults were found in Ileret, Garissa, Loglogo and Mikona. At Marsabit high proportions of immune adults and children were found among the Burgi tribe. As the Burgi are permanent agricultural workers on Marsabit Mountain, an entomological investigation was made, over 15 000 mosquitos being collected. From these, 13 strains of Pongola virus, 1 strain of Semliki Forest virus and an unidentified virus were isolated, but no yellow fever strains. Aedes africanus and Aedes simpsoni were not found at Marsabit; small numbers of Aedes aegypti were collected biting man. The vector potential of other mosquitos collected (particularly Mansonia africana, which is present throughout the year) is discussed.

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

    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

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

    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

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

    2015-03-26

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

  2. Experimental Infection of Ornithodoros erraticus sensu stricto with Two Portuguese African Swine Fever Virus Strains. Study of Factors Involved in the Dynamics of Infection in Ticks.

    Rita Ribeiro

    Full Text Available African swine fever (ASF is a frequently devastating hemorrhagic disease of domestic pigs and wild boar and Ornithodoros erraticus sensu stricto argasid ticks are the only biological vectors of African swine fever virus (ASFV known to occur in Europe. Recently this disease emerged in Eastern Europe and Russian Federation, showing a huge potential for a rapid spread between countries. There is some risk of re-emergence of ASF in the countries where these ticks exist, that can contribute for the persistence of infection and compromise control measures. In this study we aimed to identify factors that determine the probability of infection and its dynamics in the tick vector Ornithodoros erraticus sensu stricto, with two Portuguese strains of ASFV. Our results suggest that these ticks have a high likelihood of excreting the two haemadsorbing ASF viruses of different host origins and that, in field surveys, the analysis of adults and 5th nymphal stage can provide the best chance of detecting virus infection. The results also indicate that infection of pigs with highly virulent ASF viruses will promote higher rates of infection and a higher likelihood for virus excretion by ticks. Nevertheless, there is also a risk, although lower, that ticks can become infected on pigs that have overcome the acute phase of infection, which was simulated in our study by membrane feeding ticks with low titres of virus. We believe these results can be valuable in designing and interpreting the results of ASF control programmes, and future work can also be undertaken as our dataset is released under open access, to perform studies in risk assessment for ASFV persistence in a region where O. erraticus sensu stricto ticks are present.

  3. The spatial analysis on hemorrhagic fever with renal syndrome in Jiangsu province, China based on geographic information system.

    Changjun Bao

    Full Text Available Hemorrhagic fever with renal syndrome (HFRS is endemic in mainland China, accounting for 90% of total reported cases worldwide, and Jiangsu is one of the most severely affected provinces. In this study, the authors conducted GIS-based spatial analyses in order to determine the spatial distribution of the HFRS cases, identify key areas and explore risk factors for public health planning and resource allocation.Interpolation maps by inverse distance weighting were produced to detect the spatial distribution of HFRS cases in Jiangsu from 2001 to 2011. Spatio-temporal clustering was applied to identify clusters at the county level. Spatial correlation analysis was conducted to detect influencing factors of HFRS in Jiangsu.HFRS cases in Jiangsu from 2001 to 2011 were mapped and the results suggested that cases in Jiangsu were not distributed randomly. Cases were mainly distributed in northeastern and southwestern Jiangsu, especially in Dafeng and Sihong counties. It was notable that prior to this study, Sihong county had rarely been reported as a high-risk area of HFRS. With the maximum spatial size of 50% of the total population and the maximum temporal size of 50% of the total population, spatio-temporal clustering showed that there was one most likely cluster (LLR = 624.52, P<0.0001, RR = 8.19 and one second-most likely cluster (LLR = 553.97, P<0.0001, RR = 8.25, and both of these clusters appeared from 2001 to 2004. Spatial correlation analysis showed that the incidence of HFRS in Jiangsu was influenced by distances to highways, railways, rivers and lakes.The application of GIS together with spatial interpolation, spatio-temporal clustering and spatial correlation analysis can effectively identify high-risk areas and factors influencing HFRS incidence to lay a foundation for researching its pathogenesis.

  4. [The warning model and influence of climatic changes on hemorrhagic fever with renal syndrome in Changsha city].

    Xiao, Hong; Tian, Huai-yu; Zhang, Xi-xing; Zhao, Jian; Zhu, Pei-juan; Liu, Ru-chun; Chen, Tian-mu; Dai, Xiang-yu; Lin, Xiao-ling

    2011-10-01

    To realize the influence of climatic changes on the transmission of hemorrhagic fever with renal syndrome (HFRS), and to explore the adoption of climatic factors in warning HFRS. A total of 2171 cases of HFRS and the synchronous climatic data in Changsha from 2000 to 2009 were collected to a climate-based forecasting model for HFRS transmission. The Cochran-Armitage trend test was employed to explore the variation trend of the annual incidence of HFRS. Cross-correlations analysis was then adopted to assess the time-lag period between the climatic factors, including monthly average temperature, relative humidity, rainfall and Multivariate Elño-Southern Oscillation Index (MEI) and the monthly HFRS cases. Finally the time-series Poisson regression model was constructed to analyze the influence of different climatic factors on the HFRS transmission. The annual incidence of HFRS in Changsha between 2000 - 2009 was 13.09/100 000 (755 cases), 9.92/100 000 (578 cases), 5.02/100 000 (294 cases), 2.55/100 000 (150 cases), 1.13/100 000 (67 cases), 1.16/100 000 (70 cases), 0.95/100 000 (58 cases), 1.40/100 000 (87 cases), 0.75/100 000 (47 cases) and 1.02/100 000 (65 cases), respectively. The incidence showed a decline during these years (Z = -5.78, P Climate factors significantly influence the incidence of HFRS. If the influence of variable-autocorrelation, seasonality, and long-term trend were controlled, the accuracy of forecasting by the time-series Poisson regression model in Changsha would be comparatively high, and we could forecast the incidence of HFRS in advance.

  5. Increased serum ferritin levels in patients with Crimean-Congo hemorrhagic fever: can it be a new severity criterion?

    Barut, Sener; Dincer, Fatma; Sahin, Idris; Ozyurt, Huseyin; Akkus, Mehmet; Erkorkmaz, Unal

    2010-01-01

    Serum ferritin is one of the markers indicating hemophagocytosis that may have a role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). This study was designed to determine any correlation between serum ferritin and routine diagnostic laboratory markers of CCHF, and to investigate the relationship between serum ferritin levels and disease severity. Sixty-six patients with CCHF admitted to the hospital during the spring and summer months of 2006 and 2007 were included in the study. Serum ferritin levels were measured in sera obtained during the initial days of hospitalization. Data from 53 patients showing decreasing platelet counts over the first three days were used for further analysis and these patients were divided into two groups according to disease severity: group A included severe cases with lowest platelet counts 20x10(9)/l. Forty patients (60.6%) were male (mean age 43+/-17 years). Three patients died, thus the fatality rate was 4.5%. Fifty-one patients (77.3%) had abnormal serum ferritin levels, with levels above 500 ng/ml in 62.1%. There was a significant negative correlation between ferritin levels and concordant platelet counts (p or =1862ng/ml had a sensitivity of 87.5% and a specificity of 83.8% in differentiating severe cases from mild ones. Increased serum ferritin levels may suggest a significant role of hemophagocytosis in the pathogenesis of CCHF and may be a useful marker for diagnosis, disease activity, and prognosis. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Rift valley fever virus lacking the NSs and NSm genes is highly attenuated, confers protective immunity from virulent virus challenge, and allows for differential identification of infected and vaccinated animals.

    Bird, Brian H; Albariño, César G; Hartman, Amy L; Erickson, Bobbie Rae; Ksiazek, Thomas G; Nichol, Stuart T

    2008-03-01

    Rift Valley fever (RVF) virus is a mosquito-borne human and veterinary pathogen associated with large outbreaks of severe disease throughout Africa and more recently the Arabian peninsula. Infection of livestock can result in sweeping "abortion storms" and high mortality among young animals. Human infection results in self-limiting febrile disease that in approximately 1 to 2% of patients progresses to more serious complications including hepatitis, encephalitis, and retinitis or a hemorrhagic syndrome with high fatality. The virus S segment-encoded NSs and the M segment-encoded NSm proteins are important virulence factors. The development of safe, effective vaccines and tools to screen and evaluate antiviral compounds is critical for future control strategies. Here, we report the successful reverse genetics generation of multiple recombinant enhanced green fluorescent protein-tagged RVF viruses containing either the full-length, complete virus genome or precise deletions of the NSs gene alone or the NSs/NSm genes in combination, thus creating attenuating deletions on multiple virus genome segments. These viruses were highly attenuated, with no detectable viremia or clinical illness observed with high challenge dosages (1.0 x 10(4) PFU) in the rat lethal disease model. A single-dose immunization regimen induced robust anti-RVF virus immunoglobulin G antibodies (titer, approximately 1:6,400) by day 26 postvaccination. All vaccinated animals that were subsequently challenged with a high dose of virulent RVF virus survived infection and could be serologically differentiated from naïve, experimentally infected animals by the lack of NSs antibodies. These rationally designed marker RVF vaccine viruses will be useful tools for in vitro screening of therapeutic compounds and will provide a basis for further development of RVF virus marker vaccines for use in endemic regions or following the natural or intentional introduction of the virus into previously unaffected areas.

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

    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...

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

    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

  9. Humoral immune responses of dengue fever patients using epitope-specific serotype-2 virus-like particle antigens.

    Wayne D Crill

    Full Text Available Dengue virus (DENV is a serious mosquito-borne pathogen causing significant global disease burden, either as classic dengue fever (DF or in its most severe manifestation dengue hemorrhagic fever (DHF. Nearly half of the world's population is at risk of dengue disease and there are estimated to be millions of infections annually; a situation which will continue to worsen with increasing expansion of the mosquito vectors and epidemic DF/DHF. Currently there are no available licensed vaccines or antivirals for dengue, although significant effort has been directed toward the development of safe and efficacious dengue vaccines for over 30 years. Promising vaccine candidates are in development and testing phases, but a better understanding of immune responses to DENV infection and vaccination is needed. Humoral immune responses to DENV infection are complex and may exacerbate pathogenicity, yet are essential for immune protection. In this report, we develop DENV-2 envelope (E protein epitope-specific antigens and measure immunoglobulin responses to three distinct epitopes in DENV-2 infected human serum samples. Immunoglobulin responses to DENV-2 infection exhibited significant levels of individual variation. Antibody populations targeting broadly cross-reactive epitopes centered on the fusion peptide in structural domain II were large, highly variable, and greater in primary than in secondary DENV-2 infected sera. E protein domain III cross-reactive immunoglobulin populations were similarly variable and much larger in IgM than in IgG. DENV-2 specific domain III IgG formed a very small proportion of the antibody response yet was significantly correlated with DENV-2 neutralization, suggesting that the highly protective IgG recognizing this epitope in murine studies plays a role in humans as well. This report begins to tease apart complex humoral immune responses to DENV infection and is thus important for improving our understanding of dengue disease

  10. Therapeutics of Ebola hemorrhagic fever: whole-genome transcriptional analysis of successful disease mitigation.

    Yen, Judy Y; Garamszegi, Sara; Geisbert, Joan B; Rubins, Kathleen H; Geisbert, Thomas W; Honko, Anna; Xia, Yu; Connor, John H; Hensley, Lisa E

    2011-11-01

    The mechanisms of Ebola (EBOV) pathogenesis are only partially understood, but the dysregulation of normal host immune responses (including destruction of lymphocytes, increases in circulating cytokine levels, and development of coagulation abnormalities) is thought to play a major role. Accumulating evidence suggests that much of the observed pathology is not the direct result of virus-induced structural damage but rather is due to the release of soluble immune mediators from EBOV-infected cells. It is therefore essential to understand how the candidate therapeutic may be interrupting the disease process and/or targeting the infectious agent. To identify genetic signatures that are correlates of protection, we used a DNA microarray-based approach to compare the host genome-wide responses of EBOV-infected nonhuman primates (NHPs) responding to candidate therapeutics. We observed that, although the overall circulating immune response was similar in the presence and absence of coagulation inhibitors, surviving NHPs clustered together. Noticeable differences in coagulation-associated genes appeared to correlate with survival, which revealed a subset of distinctly differentially expressed genes, including chemokine ligand 8 (CCL8/MCP-2), that may provide possible targets for early-stage diagnostics or future therapeutics. These analyses will assist us in understanding the pathogenic mechanisms of EBOV infection and in identifying improved therapeutic strategies.

  11. Proteomic analysis of swine serum following highly virulent classical swine fever virus infection

    Guo Huan-cheng

    2011-03-01

    Full Text Available Abstract Background Classical swine fever virus (CSFV belongs to the genus Pestivirus within the family Flaviviridae. Virulent strains of classical swine fever virus (CSFV cause severe disease in pigs characterized by immunosuppression, thrombocytopenia and disseminated intravascular coagulation, which causes significant economic losses to the pig industry worldwide. Methods To reveal proteomic changes in swine serum during the acute stage of lethal CSFV infection, 5 of 10 pigs were inoculated with the virulent CSFV Shimen strain, the remainder serving as uninfected controls. A serum sample was taken at 3 days post-infection from each swine, at a stage when there were no clinical symptoms other than increased rectal temperatures (≥40°C. The samples were treated to remove serum albumin and immunoglobulin (IgG, and then subjected to two-dimension differential gel electrophoresis. Results Quantitative intensity analysis revealed 17 protein spots showing at least 1.5-fold quantitative alteration in expression. Ten spots were successfully identified by MALDI-TOF MS or LTQ MS. Expression of 4 proteins was increased and 6 decreased in CSFV-infected pigs. Functions of these proteins included blood coagulation, anti-inflammatory activity and angiogenesis. Conclusion These proteins with altered expression may have important implications in the pathogenesis of classical swine fever and provide a clue for identification of biomarkers for classical swine fever early diagnosis.

  12. Surge of Dengue Virus Infection and Chikungunya Fever in Bali in 2010: The Burden of Mosquito-Borne Infectious Diseases in a Tourist Destination

    Yoshikawa, Minako Jen; Kusriastuti, Rita

    2013-01-01

    Labor flow and travelers are important factors contributing to the spread of Dengue virus infection and chikungunya fever. Bali Province of Indonesia, a popular resort and tourist destination, has these factors and suffers from mosquito-borne infectious diseases. Using area study approach, a series of fieldwork was conducted in Bali to obtain up-to-date primary disease data, to learn more about public health measures, and to interview health officers, hotel personnel, and other resource persons. The national data including information on two other provinces were obtained for comparison. The health ministry reported 5,810 and 11,697 cases of dengue hemorrhagic fever in Bali in 2009 and 2010, respectively. Moreover, two densely populated tourist areas and one district have shown a particularly high incidence and sharp increases in 2010. Cases of chikungunya fever reported in Bali more than doubled in 2010 from the previous year. Our findings suggest that Bali can benefit from a significant reduction in vector populations and dissemination of disease preventive knowledge among both local residents and foreign visitors. This will require a concerted and trans-border approach, which may prove difficult in the province. PMID:23874141

  13. Screening for Viral Hemorrhagic Septicemia Virus in Marine Fish along the Norwegian Coastal Line

    Sandlund, Nina; Gjerset, Britt; Bergh, Øivind

    2014-01-01

    Viral hemorrhagic septicemia virus (VHSV) infects a wide range of marine fish species. To study the occurrence of VHSV in wild marine fish populations in Norwegian coastal waters and fjord systems a total of 1927 fish from 39 different species were sampled through 5 research cruises conducted......, and to our knowledge the first detection of VHSV in silvery pout. However, low prevalence of VHSV genotype Ib in Atlantic herring and other wild marine fish are well known in other parts of Europe. Earlier there have been a few reports of disease outbreaks in farmed rainbow trout with VHSV of genotype Ib...

  14. Oral infection of Aedes aegypti with yellow fever virus: geographic variation and genetic considerations.

    Tabachnick, W J; Wallis, G P; Aitken, T H; Miller, B R; Amato, G D; Lorenz, L; Powell, J R; Beaty, B J

    1985-11-01

    Twenty-eight populations representing a worldwide distribution of Aedes aegypti were tested for their ability to become orally infected with yellow fever virus (YFV). Populations had been analyzed for genetic variations at 11 isozyme loci and assigned to one of 8 genetic geographic groups of Ae. aegypti. Infection rates suggest that populations showing isozyme genetic relatedness also demonstrate similarity to oral infection rates with YFV. The findings support the hypothesis that genetic variation exists for oral susceptibility to YFV in Ae. aegypti.

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

    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

  16. Efficient, trans-complementing packaging systems for chimeric, pseudoinfectious dengue 2/yellow fever viruses

    Shustov, Alexandr V.; Frolov, Ilya

    2010-01-01

    In our previous studies, we have stated to build a new strategy for developing defective, pseudoinfectious flaviviruses (PIVs) and applying them as a new type of vaccine candidates. PIVs combined the efficiency of live vaccines with the safety of inactivated or subunit vaccines. The results of the present work demonstrate further development of chimeric PIVs encoding dengue virus 2 (DEN2V) glycoproteins and yellow fever virus (YFV)-derived replicative machinery as potential vaccine candidates. The newly designed PIVs have synergistically functioning mutations in the prM and NS2A proteins, which abolish processing of the latter proteins and make the defective viruses capable of producing either only noninfectious, immature and/or subviral DEN2V particles. The PIV genomes can be packaged to high titers into infectious virions in vitro using the NS1-deficient YFV helper RNAs, and both PIVs and helpers can then be passaged as two-component genome viruses at an escalating scale.

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

    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.

  18. Screening test for neutralizing antibodies against yellow fever virus, based on a flavivirus pseudotype.

    Séverine Mercier-Delarue

    Full Text Available Given the possibility of yellow fever virus reintroduction in epidemiologically receptive geographic areas, the risk of vaccine supply disruption is a serious issue. New strategies to reduce the doses of injected vaccines should be evaluated very carefully in terms of immunogenicity. The plaque reduction test for the determination of neutralizing antibodies (PRNT is particularly time-consuming and requires the use of a confinement laboratory. We have developed a new test based on the use of a non-infectious pseudovirus (WN/YF17D. The presence of a reporter gene allows sensitive determination of neutralizing antibodies by flow cytometry. This WN/YF17D test was as sensitive as PRNT for the follow-up of yellow fever vaccinees. Both tests lacked specificity with sera from patients hospitalized for acute Dengue virus infection. Conversely, both assays were strictly negative in adults never exposed to flavivirus infection or vaccination, and in patients sampled some time after acute Dengue infection. This WN/YF17D test will be particularly useful for large epidemiological studies and for screening for neutralizing antibodies against yellow fever virus.

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

    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

  20. Studies on the pathogenesis of fever with influenzal viruses. I. The appearance of an endogenous pyrogen in the blood following intravenous injection of virus.

    ATKINS, E; HUANG, W C

    1958-03-01

    A substance with pyrogenic properties appears in the blood streams of rabbits made febrile by the intravenous inoculation of the PR8 strain of influenza A and Newcastle disease viruses (NDV). By means of a technique involving passive transfer of sera from animals given virus to recipient rabbits, the titer of circulating pyrogen was found to be closely correlated with the course of fever produced by virus. Certain properties of the pyrogen are described which differentiate it from the originally injected virus and suggest that the induced pyrogen is of endogenous origin. These properties resemble those of endogenous pyrogens occurring in other forms of experimental fever. The source of virus-induced pyrogen is unknown. In vitro incubation of virus with various constituents of the circulation did not result in the appearance of endogenous pyrogen. Granulocytopenia induced by HN(2) failed to influence either fever or the production of endogenous pyrogen in rabbits injected with NDV. Similarly, the intraperitoneal inoculation of NDV into prepared exudates did not modify the febrile response. These findings do not lend support to the possibility that the polymorphonuclear leukocyte is a significant source of endogenous pyrogen in virus-induced fever. It is concluded that the liberation of an endogenous pyrogen from some as yet undefined source is an essential step in the pathogenesis of fever caused by the influenza group of viruses.

  1. Filgrastim as a Rescue Therapy for Persistent Neutropenia in a Case of Dengue Hemorrhagic Fever with Acute Respiratory Distress Syndrome and Myocarditis

    Desh Deepak

    2011-01-01

    Full Text Available Pathogenesis of dengue involves suppression of immune system leading to development of characteristic presentation of haematological picture of thrombocytopenia and leucopenia. Sometimes, this suppression in immune response is responsible for deterioration in clinical status of the patient in spite of all specific and supportive therapy. Certain drugs like steroids are used for rescue therapy in conditions like sepsis. We present a novel use of filgrastim as a rescue therapy in a patient with dengue hemorrhagic fever (DHF with acute respiratory distress syndrome (ARDS, myocarditis, and febrile neutropenia and not responding to standard management.

  2. Dengue virus markers of virulence and pathogenicity

    Rico-Hesse, Rebeca

    2009-01-01

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

  3. Climate Change and the Arboviruses: Lessons from the Evolution of the Dengue and Yellow Fever Viruses.

    Tabachnick, Walter J

    2016-09-29

    The impact of anticipated changes in global climate on the arboviruses and the diseases they cause poses a significant challenge for public health. The past evolution of the dengue and yellow fever viruses provides clues about the influence of changes in climate on their future evolution. The evolution of both viruses has been influenced by virus interactions involving the mosquito species and the primate hosts involved in virus transmission, and by their domestic and sylvatic cycles. Information is needed on how viral genes in general influence phenotypic variance for important viral functions. Changes in global climate will alter the interactions of mosquito species with their primate hosts and with the viruses in domestic cycles, and greater attention should be paid to the sylvatic cycles. There is great danger for the evolution of novel viruses, such as new serotypes, that could compromise vaccination programs and jeopardize public health. It is essential to understand (a) both sylvatic and domestic cycles and (b) the role of virus genetic and environmental variances in shaping virus phenotypic variance to more fully assess the impact of global climate change.

  4. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    Daddario-DiCaprio, Kathleen M; Geisbert, Thomas W; Geisbert, Joan B; Stroeher, Ute; Hensley, Lisa E; Grolla, Allen; Fritz, Elizabeth A; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M

    2006-01-01

    Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic fever, including a recent highly publicized outbreak in Angola that produced severe disease and significant mortality in infected patients...

  5. Detection and Circulation of a Novel Rabbit Hemorrhagic Disease Virus in Australia

    Mahar, Jackie E.; Read, Andrew J.; Gu, Xingnian; Urakova, Nadya; Mourant, Roslyn; Piper, Melissa; Haboury, Stéphanie; Holmes, Edward C.; Strive, Tanja

    2018-01-01

    The highly virulent rabbit hemorrhagic disease virus (RHDV) has been widely used in Australia and New Zealand since the mid-1990s to control wild rabbits, an invasive vertebrate pest in these countries. In January 2014, an exotic RHDV was detected in Australia, and 8 additional outbreaks were reported in both domestic and wild rabbits in the 15 months following its detection. Full-length genomic analysis revealed that this virus is a recombinant containing an RHDVa capsid gene and nonstructural genes most closely related to nonpathogenic rabbit caliciviruses. Nationwide monitoring efforts need to be expanded to assess if the increasing number of different RHDV variants circulating in the Australian environment will affect biological control of rabbits. At the same time, updated vaccines and vaccination protocols are urgently needed to protect pet and farmed rabbits from these novel rabbit caliciviruses. PMID:29260677

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

    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.

  7. A Space-Time Study of Hemorrhagic Fever with Renal Syndrome (HFRS and Its Climatic Associations in Heilongjiang Province, China

    Junyu He

    2017-08-01

    Full Text Available Background: Hemorrhagic fever with renal syndrome (HFRS is highly endemic in China, especially in Heilongjiang province (90% of all reported HFRS cases worldwide occur in China. The dynamic identification of high HFRS incidence spatiotemporal regions and the quantitative assessment of HFRS associations with climate change in Heilongjiang province can provide valuable guidance for HFRS monitoring, preventing and control. Yet, so far there exist very few and of limited scope quantitative studies of the spatiotemporal HFRS spread and its climatic associations in Heilongjiang province. Making up for this lack of quantitative studies is the reason for the development of the present work.Method: To address this need, the well-known Bayesian maximum entropy (BME method of space-time modeling and mapping together with its recently proposed variant, the projected BME (P-BME method, were employed in this work to perform a composite space-time analysis and mapping of HFRS incidence in Heilongjiang province during the years 2005–2013. Also, using multivariate El Niño-Southern Oscillation index as a proxy, we proposed a combination of Hilbert-Huang transform and wavelet analysis to study the “HFRS incidence-climate change” associations.Results: The main results of this work were two-fold: (1 three core areas were identified with high HFRS incidences that were spatially distributed and exhibited distinct biomodal temporal patterns in the eastern, western, and southern parts of Heilongjiang province; and (2 there exists a considerable association between HFRS incidence and climate change, particularly, an ~6 months period coherency was clearly detected.Conclusions: The combination of modern space-time modeling and mapping techniques (P-BME theory, Hilbert-Huang spectrum analysis, and wavelet analysis used in this work led to valuable quantitative findings concerning the spatiotemporal spread of HFRS incidence in Heilongjiang province and its association

  8. Yellow Fever Vaccine: What You Need to Know

    ... How can I prevent yellow fever? Yellow fever vaccine Yellow fever vaccine can prevent yellow fever. Yellow fever vaccine ... such as those containing DEET. 3 Yellow fever vaccine Yellow fever vaccine is a live, weakened virus. It is ...

  9. Modeled Forecasts of Dengue Fever in San Juan, PR Using NASA Satellite Enhanced Weather Forecasts

    Morin, Cory; Quattrochi, Dale; Zavodsky, Bradley; Case, Jonathan

    2015-01-01

    Dengue virus is transmitted between humans and mosquitoes of the genus Aedes and causes approximately 96 million cases of disease (dengue fever) each year (Bhatet al. 2013). Symptoms of dengue fever include fever, headache, nausea, vomiting, and eye, muscle and joint pain (CDC). More sever manifestations such as abdominal pain, bleeding from nose and gums, vomiting of blood, and clammy skin occur in rare cases of dengue hemorrhagic fever (CDC). Dengue fever occurs throughout tropical and sub-tropical regions worldwide, however, the geographical range and size of epidemics is increasing. Weather and climate are drivers of dengue virus transmission dynamics (Morin et al. 2013) by affecting mosquito proliferation and the virus extrinsic incubation period (i.e. required time for the virus to replicate and disseminate within the mosquito before it can retransmit the virus).

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

    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

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

    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.

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

    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.

  13. The yellow fever 17D virus as a platform for new live attenuated vaccines.

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

    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.

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

    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.

  16. Ebola Virus Inactivation by Detergents Is Annulled in Serum

    van Kampen, Jeroen J. A.; Tintu, Andrei; Russcher, Henk; Fraaij, Pieter L. A.; Reusken, Chantal B. E. M.; Rijken, Mikel; van Hellemond, Jaap J.; van Genderen, Perry J. J.; Koelewijn, Rob; de Jong, Menno D.; Haddock, Elaine; Fischer, Robert J.; Munster, Vincent J.; Koopmans, Marion P. G.

    2017-01-01

    Treatment of blood samples from hemorrhagic fever virus (HFV)-infected patients with 0.1% detergents has been recommended for virus inactivation and subsequent safe laboratory testing. However, data on virus inactivation by this procedure are lacking. Here we show the effect of this procedure on

  17. Successful topical respiratory tract immunization of primates against Ebola virus.

    Bukreyev, Alexander; Rollin, Pierre E; Tate, Mallory K; Yang, Lijuan; Zaki, Sherif R; Shieh, Wun-Ju; Murphy, Brian R; Collins, Peter L; Sanchez, Anthony

    2007-06-01

    Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys--in which HPIV3 infection is mild and asymptomatic--and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.

  18. Alteration of a second putative fusion peptide of structural glycoprotein E2 of Classical Swine Fever Virus alters virus replication and virulence in swine

    E2, the major envelope glycoprotein of Classical Swine Fever Virus (CSFV), is involved in several critical virus functions including cell attachment, host range susceptibility, and virulence in natural hosts. Functional structural analysis of E2 based on Wimley-White interfacial hydrophobicity dis...

  19. Confirmation and phylogenetic analysis of rabbit hemorrhagic disease virus in free-living rabbits from the Netherlands

    van de Bildt, M. W. G.; van Bolhuis, G. H.; van Zijderveld, F.; van Riel, D.; Drees, J. M.; Osterhaus, A. D. M. E.; Kuiken, T.

    2006-01-01

    The number of free-living European rabbits (Oryctolagus cuniculus) in the Netherlands has declined dramatically in recent years. Although rabbit hemorrhagic disease virus (RHDV) infection has been implicated as a possible cause of this decline, the definitive diagnosis has not been reported. We

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

    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.

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

    Luis Valdés

    1999-07-01

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

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

    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....

  3. Attenuation of Recombinant Yellow Fever 17D Viruses Expressing Foreign Protein Epitopes at the Surface

    Bonaldo, Myrna C.; Garratt, Richard C.; Marchevsky, Renato S.; Coutinho, Evandro S. F.; Jabor, Alfredo V.; Almeida, Luís F. C.; Yamamura, Anna M. Y.; Duarte, Adriana S.; Oliveira, Prisciliana J.; Lizeu, Jackeline O. P.; Camacho, Luiz A. B.; Freire, Marcos S.; Galler, Ricardo

    2005-01-01

    The yellow fever (YF) 17D vaccine is a live attenuated virus. Three-dimensional (3D) homology modeling of the E protein structure from YF 17D virus and its comparison with that from tick-borne encephalitis virus revealed that it is possible to accommodate inserts of different sizes and amino acid compositions in the flavivirus E protein fg loop. This is consistent with the 3D structures of both the dimeric and trimeric forms in which the fg loop lies exposed to solvents. We demonstrate here that YF 17D viruses bearing foreign humoral (17D/8) and T-cell (17D/13) epitopes, which vary in sequence and length, displayed growth restriction. It is hypothesized that interference with the dimer-trimer transition and with the formation of a ring of such trimers in order to allow fusion compromises the capability of the E protein to induce fusion of viral and endosomal membranes, and a slower rate of fusion may delay the extent of virus production. This would account for the lower levels of replication in cultured cells and of viremia in monkeys, as well as for the more attenuated phenotype of the recombinant viruses in monkeys. Testing of both recombinant viruses (17D/8 and 17D/13) for monkey neurovirulence also suggests that insertion at the 17D E protein fg loop does not compromise the attenuated phenotype of YF 17D virus, further confirming the potential use of this site for the development of new live attenuated 17D virus-based vaccines. PMID:15956601

  4. Inhibition of Interferon Induction and Action by the Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus

    Holzer, Barbara; Bakshi, Siddharth; Bridgen, Anne; Baron, Michael D.

    2011-01-01

    The Nairoviruses are an important group of tick-borne viruses that includes pathogens of man (Crimean Congo hemorrhagic fever virus) and livestock animals (Dugbe virus, Nairobi sheep disease virus (NSDV)). NSDV is found in large parts of East Africa and the Indian subcontinent (where it is known as Ganjam virus). We have investigated the ability of NSDV to antagonise the induction and actions of interferon. Both pathogenic and apathogenic isolates could actively inhibit the induction of type ...

  5. Fever versus Fever: the role of host and vector susceptibility and interspecific competition in shaping the current and future distributions of the sylvatic cycles of dengue virus and yellow fever virus

    Hanley, Kathryn A.; Monath, Thomas P.; Weaver, Scott C.; Rossi, Shannan L.; Richman, Rebecca L.; Vasilakis, Nikos

    2013-01-01

    Two different species of flaviviruses, dengue virus (DENV) and yellow fever virus (YFV), that originated in sylvatic cycles maintained in non-human primates and forest-dwelling mosquitoes have emerged repeatedly into sustained human-to-human transmission by Aedes aegypti mosquitoes. Sylvatic cycles of both viruses remain active, and where the two viruses overlap in West Africa they utilize similar suites of monkeys and Aedes mosquitoes. These extensive similarities render the differences in the biogeography and epidemiology of the two viruses all the more striking. First, the sylvatic cycle of YFV originated in Africa and was introduced into the New World, probably as a result of the slave trade, but is absent in Asia; in contrast, sylvatic DENV likely originated in Asia and has spread to Africa but not to the New World. Second, while sylvatic YFV can emerge into extensive urban outbreaks in humans, these invariably die out, whereas four different types of DENV have established human transmission cycles that are ecologically and evolutionarily distinct from their sylvatic ancestors. Finally, transmission of YFV among humans has been documented only in Africa and the Americas, whereas DENV is transmitted among humans across most of the range of competent Aedes vectors, which in the last decade has included every continent save Antarctica. This review summarizes current understanding of sylvatic transmission cycles of YFV and DENV, considers possible explanations for their disjunct distributions, and speculates on the potential consequences of future establishment of a sylvatic cycle of DENV in the Americas. PMID:23523817

  6. Vector competence of Culicoides sonorensis (Diptera: Ceratopogonidae to epizootic hemorrhagic disease virus serotype 7

    Ruder Mark G

    2012-10-01

    Full Text Available Abstract Background Culicoides sonorensis (Diptera: Ceratopogonidae is a vector of epizootic hemorrhagic disease virus (EHDV serotypes 1 and 2 in North America, where these viruses are well-known pathogens of white-tailed deer (WTD and other wild ruminants. Although historically rare, reports of clinical EHDV infection in cattle have increased in some parts of the world over the past decade. In 2006, an EHDV-7 epizootic in cattle resulted in economic loss for the Israeli dairy industry. White-tailed deer are susceptible to EHDV-7 infection and disease; however, this serotype is exotic to the US and the susceptibility of C. sonorensis to this cattle-virulent EHDV is not known. The objective of the study was to determine if C. sonorensis is susceptible to EHDV-7 infection and is a competent vector. Methods To evaluate the susceptibility of C. sonorensis, midges were fed on EHDV-7 infected WTD, held at 22 ± 1°C, and processed individually for virus isolation and titration on 4–16 days post feeding (dpf. Midges with a virus titer of ≥102.7 median tissue culture infective doses (TCID50/midge were considered potentially competent. To determine if infected C. sonorensis were capable of transmitting EHDV-7 to a host, a susceptible WTD was then fed on by a group of 14–16 dpf midges. Results From 4–16 dpf, 45% (156/350 of midges that fed on WTD with high titer viremia (>107 TCID50/ml were virus isolation-positive, and starting from 10–16 dpf, 32% (35/109 of these virus isolation-positive midges were potentially competent (≥102.7 TCID50/midge. Midges that fed on infected deer transmitted the virus to a susceptible WTD at 14–16 dpf. The WTD developed viremia and severe clinical disease. Conclusion This study demonstrates that C. sonorensis is susceptible to EHDV-7 infection and can transmit the virus to susceptible WTD, thus, C. sonorensis should be considered a potential vector of EHDV-7. Together with previous work, this study demonstrates

  7. Vector competence of Culicoides sonorensis (Diptera: Ceratopogonidae) to epizootic hemorrhagic disease virus serotype 7.

    Ruder, Mark G; Howerth, Elizabeth W; Stallknecht, David E; Allison, Andrew B; Carter, Deborah L; Drolet, Barbara S; Klement, Eyal; Mead, Daniel G

    2012-10-17

    Culicoides sonorensis (Diptera: Ceratopogonidae) is a vector of epizootic hemorrhagic disease virus (EHDV) serotypes 1 and 2 in North America, where these viruses are well-known pathogens of white-tailed deer (WTD) and other wild ruminants. Although historically rare, reports of clinical EHDV infection in cattle have increased in some parts of the world over the past decade. In 2006, an EHDV-7 epizootic in cattle resulted in economic loss for the Israeli dairy industry. White-tailed deer are susceptible to EHDV-7 infection and disease; however, this serotype is exotic to the US and the susceptibility of C. sonorensis to this cattle-virulent EHDV is not known. The objective of the study was to determine if C. sonorensis is susceptible to EHDV-7 infection and is a competent vector. To evaluate the susceptibility of C. sonorensis, midges were fed on EHDV-7 infected WTD, held at 22 ± 1°C, and processed individually for virus isolation and titration on 4-16 days post feeding (dpf). Midges with a virus titer of ≥ 10(2.7) median tissue culture infective doses (TCID(50))/midge were considered potentially competent. To determine if infected C. sonorensis were capable of transmitting EHDV-7 to a host, a susceptible WTD was then fed on by a group of 14-16 dpf midges. From 4-16 dpf, 45% (156/350) of midges that fed on WTD with high titer viremia (>10(7) TCID(50)/ml) were virus isolation-positive, and starting from 10-16 dpf, 32% (35/109) of these virus isolation-positive midges were potentially competent (≥ 10(2.7) TCID(50)/midge). Midges that fed on infected deer transmitted the virus to a susceptible WTD at 14-16 dpf. The WTD developed viremia and severe clinical disease. This study demonstrates that C. sonorensis is susceptible to EHDV-7 infection and can transmit the virus to susceptible WTD, thus, C. sonorensis should be considered a potential vector of EHDV-7. Together with previous work, this study demonstrates that North America has a susceptible ruminant and

  8. Production of neutralizing antisera against viral hemorrhagic septicemia (VHS) virus by intravenous injections of rabbits

    Olesen, Niels Jørgen; Lorenzen, Niels; LaPatra, S.E.

    1999-01-01

    Rabbit antisera against viral hemorrhagic septicemia virus (VHSV) produced by two immunization procedures were compared for neutralization and immunochemical properties against homologous and heterologous strains. The VHSV isolate used as the immunogen was a member of a serogroup not neutralized...... by previously available antisera. The results from this study suggested that frequent intravenous (IV) injections of rabbits with viral antigens were superior to adjuvant-mediated, combined subcutaneous and intraperitoneal (SC/IP) injections for the production of neutralizing antisera. All IV injected rabbits...... produced high neutralization titers against the homologous VHSV isolate but not against an isolate from a different serogroup. The SC/IP injected rabbits had no significant neutralization titers against either the homologous VHSV strain or two isolates of a heterologous VHSV strain. Sera from all injected...

  9. Comparison of two Next Generation sequencing platforms for full genome sequencing of Classical Swine Fever Virus

    Fahnøe, Ulrik; Pedersen, Anders Gorm; Höper, Dirk

    2013-01-01

    to the consensus sequence. Additionally, we got an average sequence depth for the genome of 4000 for the Iontorrent PGM and 400 for the FLX platform making the mapping suitable for single nucleotide variant (SNV) detection. The analysis revealed a single non-silent SNV A10665G leading to the amino acid change D......Next Generation Sequencing (NGS) is becoming more adopted into viral research and will be the preferred technology in the years to come. We have recently sequenced several strains of Classical Swine Fever Virus (CSFV) by NGS on both Genome Sequencer FLX (GS FLX) and Iontorrent PGM platforms...

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

    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 ...

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

    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.

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

    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.

  13. Complete Genomes of Classical Swine Fever Virus Cloned into Bacterial Artificial Chromosomes

    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....

  14. Estimation of the transmission dynamics of African swine fever virus within a swine house

    Nielsen, J. P.; Larsen, T. S.; Hisham Beshara Halasa, Tariq

    2017-01-01

    The spread of African swine fever virus (ASFV) threatens to reach further parts of Europe. In countries with a large swine production, an outbreak of ASF may result in devastating economic consequences for the swine industry. Simulation models can assist decision makers setting up contingency plans......·00 (95% CI 0-1). Furthermore, we simulated the spread of ASFV within a pig house using a modified SEIR-model to establish the time from infection of one animal until ASFV is detected in the herd. Based on a chosen detection limit of 2·55% equivalent to 10 dead pigs out of 360, the disease would...

  15. Caffeic acid, a coffee-related organic acid, inhibits infection by severe fever with thrombocytopenia syndrome virus in vitro.

    Ogawa, Motohiko; Shirasago, Yoshitaka; Ando, Shuji; Shimojima, Masayuki; Saijo, Masayuki; Fukasawa, Masayoshi

    2018-04-05

    Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) causes tick-borne hemorrhagic fever in East Asia. The disease is characterized by high morbidity and mortality. Here, we evaluated the effects of caffeic acid (CA), a coffee-related organic acid with antiviral effects, against SFTSV infection. CA dose-dependently inhibited SFTSV infection in permissive human hepatoma Huh7.5.1-8 cells when SFTSV was added into the culture medium with CA. However, quinic acid (QA), another coffee-related organic acid, did not inhibit SFTSV infection. The 50% inhibitory concentration (IC 50 ) of CA against SFTSV was 0.048 mM, whereas its 50% cytotoxic concentration was 7.6 mM. The selectivity index (SI) was 158. Pre-incubation of SFTSV with CA for 4 h resulted in a greater inhibition of SFTSV infection (IC 50  = 0.019 mM; SI = 400). The pre-incubation substantially decreased viral attachment to the cells. CA treatment of the SFTSV-infected cells also inhibited the infection, albeit less effectively. CA activity after cell infection with SFTSV was more pronounced at a low multiplicity of infection (MOI) of 0.01 per cell (IC 50  = 0.18 mM) than at a high MOI of 1 per cell (IC 50  > 1 mM). Thus, CA inhibited virus spread by acting directly on the virus rather than on the infected cells. In conclusion, CA acted on SFTSV and inhibited viral infection and spread, mainly by inhibiting the binding of SFTSV to the cells. We therefore demonstrated CA to be a potential anti-SFTSV drug for preventing and treating SFTS. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Studies on the pathogenesis of fever with influenzal viruses. II. The effects of endogenous pyrogen in normal and virus-tolerant recipients.

    ATKINS, E; HUANG, W C

    1958-03-01

    Observations have been made on the fever-inducing properties of an endogenous pyrogen found in the circulation of rabbits after the intravenous inoculation of Newcastle disease virus (NDV). When endogenous pyrogen was given to a normal recipient, a biphasic fever was produced which simulated that seen with bacterial endotoxins. With the use of a technique of serial passive transfer, it has been shown that the "double-humped" response results from two separate actions of the injected pyrogen. The first of these appears to be a direct stimulation of the thermoregulatory centers. The second involves the release of further endogenous pyrogen in the normal recipient to cause, in turn, the second fever peak. Since the injection of endogenous pyrogen did not produce a significant change in the number of circulating leukocytes, it is inferred that this substance is different from either bacterial or tissue polysaccharides. In rabbits rendered tolerant by a previous injection of virus the second fever peak failed to appear and the response to endogenous pyrogen was monophasic. Evidence indicates that the absence of a second fever peak in the tolerant recipient was not due to rise in temperature on the preceding day of virus injection or to the development of either serum inhibitors or tolerance to virus itself. It is postulated that prior mobilization of endogenous pyrogen by virus may have modified the ability of the tolerant recipient to liberate further amounts of this substance in response to an injection of endogenous pyrogen.

  17. Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits.

    Bertó-Moran, Alejandro; Pacios, Isabel; Serrano, Emmanuel; Moreno, Sacramento; Rouco, Carlos

    2013-01-01

    The interaction among several parasites in European rabbits (Oryctolagus cuniculus) is crucial to host fitness and to the epidemiology of myxomatosis and rabbit hemorrhagic disease. These diseases have caused significant reductions in rabbit populations on the Iberian Peninsula. Most studies have focused on the epidemiology and pathogenesis of these viruses individually, and little is known about interactions between these viruses and other parasites. Taking advantage of an experimental restocking program in Spain, the effects of coccidian and nematode infections on the probability of having detectable antibody to myxoma and rabbit hemorrhagic disease viruses were tested in European wild rabbits. For 14 mo, we monitored rabbit abundance and parasite loads (coccidia and nematodes) in three reintroduced rabbit populations. While coccidian and nematode loads explained seasonal antibody prevalences to myxoma virus, the pattern was less clear for rabbit hemorrhagic disease. Contrary to expectations, prevalence of antibody to myxoma virus was inversely proportional to coccidian load, while nematode load seemed to play a minor role. These results have implications for viral disease epidemiology and for disease management intended to increase rabbit populations in areas where they are important for ecosystem conservation.

  18. Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells.

    Yu Cong

    2016-05-01

    Full Text Available Humans infected with yellow fever virus (YFV, a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM and dendritic cells (MoDC from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease.

  19. Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults.

    Miyaji, Karina Takesaki; Avelino-Silva, Vivian Iida; Simões, Marisol; Freire, Marcos da Silva; Medeiros, Carlos Roberto de; Braga, Patrícia Emilia; Neves, Maria Angélica Acalá; Lopes, Marta Heloisa; Kallas, Esper Georges; Sartori, Ana Marli Christovam

    2017-04-03

    The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged  60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. previously vaccinated healthy persons aged  18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. 46 persons aged  60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.

  20. Approaches and Perspectives for Development of African Swine Fever Virus Vaccines

    Marisa Arias

    2017-10-01

    Full Text Available African swine fever (ASF is a complex disease of swine, caused by a large DNA virus belonging to the family Asfarviridae. The disease shows variable clinical signs, with high case fatality rates, up to 100%, in the acute forms. ASF is currently present in Africa and Europe where it circulates in different scenarios causing a high socio-economic impact. In most affected regions, control has not been effective in part due to lack of a vaccine. The availability of an effective and safe ASFV vaccines would support and enforce control–eradication strategies. Therefore, work leading to the rational development of protective ASF vaccines is a high priority. Several factors have hindered vaccine development, including the complexity of the ASF virus particle and the large number of proteins encoded by its genome. Many of these virus proteins inhibit the host’s immune system thus facilitating virus replication and persistence. We review previous work aimed at understanding ASFV–host interactions, including mechanisms of protective immunity, and approaches for vaccine development. These include live attenuated vaccines, and “subunit” vaccines, based on DNA, proteins, or virus vectors. In the shorter to medium term, live attenuated vaccines are the most promising and best positioned candidates. Gaps and future research directions are evaluated.

  1. Serum neutralization as a differential serological test for classical swine fever virus and other pestivirus infections

    Paredes J.C.M.

    1999-01-01

    Full Text Available Serum neutralization tests (SN were performed against classical swine fever virus (CSFV, bovine viral diarrhea virus (BVDV and border disease virus (BDV on samples of swine serum collected for screening of antibodies to CSFV, in order to determine the SN value as a differential serological test. Ninety-nine sera out of a sample of 16,664 were positive for antibodies to pestiviruses in an ELISA test which did not distinguish antibodies to different pestiviruses. When submitted to SN, 81 sera were positive for CSFV antibodies only. In 17 sera, crossreactive antibodies to either CSFV, BVDV or BDV were detected. In most of these sera (13 out of 17 the differences between SN titres against the three viruses were not sufficient to estimate which was the most likely antibody-inducing virus. It was concluded that, for the SN to be useful in such differentiation, it is essential to examine a sample which must include a representative number of sera from the same farm where suspect animals were detected. When isolated serum samples are examined, such as those obtained with the sampling strategy adopted here, the SN may give rise to inconclusive results.

  2. CRISPR-Cas9, a tool to efficiently increase the development of recombinant African swine fever viruses.

    Borca, Manuel V; Holinka, Lauren G; Berggren, Keith A; Gladue, Douglas P

    2018-02-16

    African swine fever virus (ASFV) causes a highly contagious disease called African swine fever. This disease is often lethal for domestic pigs, causing extensive losses for the swine industry. ASFV is a large and complex double stranded DNA virus. Currently there is no commercially available treatment or vaccine to prevent this devastating disease. Development of recombinant ASFV for producing live-attenuated vaccines or studying the involvement of specific genes in virus virulence has relied on the relatively rare event of homologous recombination in primary swine macrophages, causing difficulty to purify the recombinant virus from the wild-type parental ASFV. Here we present the use of the CRISPR-Cas9 gene editing system as a more robust and efficient system to produce recombinant ASFVs. Using CRISPR-Cas9 a recombinant virus was efficiently developed by deleting the non-essential gene 8-DR from the genome of the highly virulent field strain Georgia07 using swine macrophages as cell substrate.

  3. Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens.

    Lokhandwala, Shehnaz; Waghela, Suryakant D; Bray, Jocelyn; Martin, Cameron L; Sangewar, Neha; Charendoff, Chloe; Shetti, Rashmi; Ashley, Clay; Chen, Chang-Hsin; Berghman, Luc R; Mwangi, Duncan; Dominowski, Paul J; Foss, Dennis L; Rai, Sharath; Vora, Shaunak; Gabbert, Lindsay; Burrage, Thomas G; Brake, David; Neilan, John; Mwangi, Waithaka

    2016-11-01

    The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ + ) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Sequence adaptations during growth of rescued classical swine fever viruses in cell culture and within infected pigs

    Hadsbjerg, Johanne; Friis, Martin Barfred; Fahnøe, Ulrik

    2016-01-01

    RNA could be detected. However, the animals inoculated with these mutant viruses seroconverted against CSFV. Thus, these mutant viruses were highly attenuated in vivo. All 4 rescued viruses were also passaged up to 20 times in cell culture. Using full genome sequencing, the same two adaptations within......Classical swine fever virus (CSFV) causes an economically important disease of swine. Four different viruses were rescued from full-length cloned cDNAs derived from the Paderborn strain of CSFV. Three of these viruses had been modified by mutagenesis (with 7 or 8 nt changes) within stem 2...... each of four independent virus populations were observed that restored the coding sequence to that of the parental field strain. These adaptations occurred with different kinetics. The combination of reverse genetics and in depth, full genome sequencing provides a powerful approach to analyse virus...

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

    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.

  6. [Birds, mosquitoes and West Nile virus: little risk of West Nile fever in the Netherlands].

    Duijster, Janneke W; Stroo, C J Arjan; Braks, Marieta A H

    2016-01-01

    Due to increased incidence of West Nile fever (WNF) in Europe and the rapid spread of West Nile virus (WNV) in the US, it is commonly thought that it will only be a matter of time before WNV reaches the Netherlands. However, assessing whether WNV is really a threat to the Dutch population is challenging, due to the numerous factors affecting transmission of the virus. Some of these factors are known to limit the risk of WNF in the Netherlands. This risk is determined by the interaction between the pathogen (WNV), the vectors (Culex mosquitoes), the reservoirs (birds) and the exposure of humans to infected mosquitoes. In this paper, we discuss the factors influencing introduction, establishment and spread of WNV in the Netherlands. The probability that each of these three phases will occur in the Netherlands is currently relatively small, as is the risk of WNF infection in humans in the Netherlands.

  7. Ensayo preclínico de la vacuna candid #1 producida en Argentina contra la Fiebre Hemorrágica Argentina Preclinical assay of Candid #1 vaccine against Argentine Hemorrhagic Fever made in Argentina

    Ana M. Ambrosio

    2005-08-01

    Full Text Available Se comparó en cobayos la seguridad, inmunogenicidad y eficacia protectora de un lote de vacuna Candid #1(C#1 fabricada en Estados Unidos de América (EE.UU. y distintos lotes de la misma vacuna fabricados en Argentina (Arg. El lote TSI 5-1-92 (EE.UU. y los lotes Exp Nº 3, 7A y 8A (Arg fueron inoculados (0.5 ml, IM en cobayos de 250-400 g. Para cada ensayo diez animales recibieron solución fisiológica y sirvieron como control. Todos fueron desafiados con la cepa patógena P23790 de virus Junin. Se registró: a temperatura rectal, b peso corporal, c presencia de anticuerpos neutralizantes (AcNT pre y post-vacunación, d respuesta al desafío. Todos los animales vacunados desarrollaron AcNT anti virus Junin (rango = 40- 81920 y sobrevivieron al desafío. En cada grupo control 8/10 animales murieron (día 23.3 ± 5.4 post-desafío. Los cobayos resultaron idénticamente protegidos de una descarga letal de virus Junin por la vacuna importada y los diferentes lotes de C#1 producidos en Argentina.Candid #1 vaccine against Argentine Hemorrhagic Fever produced in USA versus lots of the same vaccine made in Argentina were compared in guinea pigs regarding safety, immunogenicity and protective efficacy against a challenge with pathogenic Junin virus. Lots Nº Exp 3, 7A and 8A of Argentine origin as well as lot TSI 5-1-92 from USA were inoculated in guinea pigs of 250-400 g in two consecutive assays. Ten animals inoculated with saline performed as normal controls in each experiment. Parameters studied were: a temperature; b body weight; c neutralizing antibodies to Junin virus; d response to viral challenge. Animals gained weight and remained normothermic up to the challenge. Guinea pigs that received Candid #1 from any manufacturer elicited neutralizing antibodies to Junin virus (titles from 40 to 81920 and survived to challenge whilst 8/10 animals died in each control group. Data presented demonstrated that Candid #1 vaccines from USA or Argentine

  8. Development of a membrane adsorber based capture step for the purification of yellow fever virus.

    Pato, Tânia P; Souza, Marta Cristina O; Silva, Andréa N M R; Pereira, Renata C; Silva, Marlon V; Caride, Elena; Gaspar, Luciane P; Freire, Marcos S; Castilho, Leda R

    2014-05-19

    Yellow fever (YF) is an endemic disease in some tropical areas of South America and Africa that presents lethality rate between 20 and 50%. There is no specific treatment and to control this disease a highly effective live-attenuated egg based vaccine is widely used for travelers and residents of areas where YF is endemic. However, recent reports of rare, sometimes fatal, adverse events post-vaccination have raised concerns. In order to increase safety records, alternative strategies should be considered, such as developing a new inactivated vaccine using a cell culture based technology, capable of meeting the demands in cases of epidemic. With this goal, the production of YF virus in Vero cells grown on microcarriers and its subsequent purification by chromatographic techniques was studied. In this work we investigate the capture step of the purification process of the YF virus. At first, virus stability was studied over a wide pH range, showing best results for the alkaline region. Considering this result and the pI of the envelope protein previously determined in silico, a strong anion exchanger was considered most suitable. Due to the easy scalability, simplicity to handle, absence of diffusional limitations and suitability for virus handling of membrane adsorbers, a Q membrane was evaluated. The amount of antigen adsorbed onto the membrane was investigated within the pH range for virus stability, and the best pH for virus adsorption was considered to be 8.5. Finally, studies on gradient and step elution allowed to determine the most adequate salt concentration for washing (0.15M) and virus elution (0.30 M). Under these operating conditions, it was shown that this capture step is quite efficient, showing high product recovery (93.2±30.3%) and efficient DNA clearance (0.9±0.3 ng/dose). Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Antigenic variants of yellow fever virus with an altered neurovirulence phenotype in mice.

    Ryman, K D; Xie, H; Ledger, T N; Campbell, G A; Barrett, A D

    1997-04-14

    The live-attenuated yellow fever (YF) vaccine virus, strain 17D-204, has long been known to consist of a heterologous population of virions. Gould et al. (J. Gen. Virol. 70, 1889-1894 (1989)) previously demonstrated that variant viruses exhibiting a YF wild-type-specific envelope (E) protein epitope are present at low frequency in the vaccine pool and were able to isolate representative virus variants with and without this epitope, designated 17D(+wt) and 17D(-wt), respectively. These variants were employed here in an investigation of YF virus pathogenesis in the mouse model. Both the 17D-204 parent and the 17D(+wt) variant viruses were lethal for adult outbred mice by the intracerebral route of inoculation. However, the 17D(-wt) variant was significantly attenuated (18% mortality rate) and replicated to much lower titer in the brains of infected mice. A single amino acid substitution in the envelope (E) protein at E-240 (Ala-->Val) was identified as responsible for the restricted replication of the 17D(-wt) variant in vivo. The 17D(+wt) variant has an additional second-site mutation, believed to encode a reversion to the neurovirulence phenotype of the 17D-204 parent virus. The amino acid substitution in the E protein at E-173 (Thr-->Ile) of the 17D(+wt) variant which results in the appearance of the wild-type-specific epitope or nucleotide changes in the 5' and 3' noncoding regions of the virus are proposed as a candidates.

  10. Antigenic profile of African horse sickness virus serotype 4 VP5 and identification of a neutralizing epitope shared with bluetongue virus and epizootic hemorrhagic disease virus

    Martinez-Torrecuadrada, J.L.; Langeveld, J.P.M.; Venteo, A.

    1999-01-01

    African horse sickness virus (AHSV) causes a fatal disease in horses. The virus capsid is composed of a double protein layer, the outermost of which is formed by two proteins: VP2 and VP5. VP2 is known to determine the serotype of the virus and to contain the neutralizing epitopes. The biological...... in a plaque reduction assay were generated. To dissect the antigenic structure of AHSV VP5, the protein was cloned in Escherichia coil using the pET3 system. The immunoreactivity of both MAbs, and horse and rabbit polyclonal antisera, with 17 overlapping fragments from VP5 was analyzed. The most....... Neutralizing epitopes were defined at positions 85-92 (PDPLSPGE) for MAb 10AE12 and at 179-185 (EEDLRTR) for MAb 10AC6. Epitope 10AE12 is highly conserved between the different orbiviruses. MAb 10AE12 was able to recognize bluetongue virus VP5 and epizootic hemorrhagic disease virus VP5 by several techniques...

  11. 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.

    Chinikar, Sadegh; Ghiasi, Seyed M; Naddaf, Saeed; Piazak, Norair; Moradi, Maryam; Razavi, Mohammad R; Afzali, Neda; Haeri, Ali; Mostafavizadeh, Kamyar; Ataei, Behrouz; Khalilifard-Brojeni, Mohammad; Husseini, Sayed M; Bouloy, Michele

    2012-09-01

    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 also occurs. In the current study, we focused on CCHF in the province of Isfahan, located in the center of Iran and deemed to be the second most infected province. Human and livestock sera and resident ticks in the livestock are collected from different regions of the province and analyzed with specific IgG ELISA and RT-PCR tests. Overall, 12% and 12.7% of studied human and livestock populations were IgG positive, respectively. The genome of CCHFV was detected in 9% of ticks resident in livestock involved in this survey. The CCHFV isolates from infected ticks were genetically examined. Nucleotide sequence of the S-segment revealed that the different isolates were closely related to each other, with nucleotide sequence identities higher than 98%. Phylogenetic analysis demonstrated that a variant isolate clustered with the Iraq strain. This high proportion of IgG-positive sera and nearly high proportion of infected ticks increases the risk of CCHF outbreaks in the province and probably posits a great danger to other provinces.

  12. Visualization of the African swine fever virus infection in living cells by incorporation into the virus particle of green fluorescent protein-p54 membrane protein chimera

    Hernaez, Bruno; Escribano, Jose M.; Alonso, Covadonga

    2006-01-01

    Many stages of African swine fever virus infection have not yet been studied in detail. To track the behavior of African swine fever virus (ASFV) in the infected cells in real time, we produced an infectious recombinant ASFV (B54GFP-2) that expresses and incorporates into the virus particle a chimera of the p54 envelope protein fused to the enhanced green fluorescent protein (EGFP). The incorporation of the fusion protein into the virus particle was confirmed immunologically and it was determined that p54-EGFP was fully functional by confirmation that the recombinant virus made normal-sized plaques and presented similar growth curves to the wild-type virus. The tagged virus was visualized as individual fluorescent particles during the first stages of infection and allowed to visualize the infection progression in living cells through the viral life cycle by confocal microscopy. In this work, diverse potential applications of B54GFP-2 to study different aspects of ASFV infection are shown. By using this recombinant virus it was possible to determine the trajectory and speed of intracellular virus movement. Additionally, we have been able to visualize for first time the ASFV factory formation dynamics and the cytophatic effect of the virus in live infected cells. Finally, we have analyzed virus progression along the infection cycle and infected cell death as time-lapse animations

  13. A recombinase polymerase amplification assay for rapid detection of Crimean-Congo Haemorrhagic fever Virus infection.

    Laura C Bonney

    2017-10-01

    Full Text Available Crimean-Congo Haemorrhagic fever Virus (CCHFV is a rapidly emerging vector-borne pathogen and the cause of a virulent haemorrhagic fever affecting large parts of Europe, Africa, the Middle East and Asia.An isothermal recombinase polymerase amplification (RPA assay was successfully developed for molecular detection of CCHFV. The assay showed rapid (under 10 minutes detection of viral extracts/synthetic virus RNA of all 7 S-segment clades of CCHFV, with high target specificity. The assay was shown to tolerate the presence of inhibitors in crude preparations of mock field samples, indicating that this assay may be suitable for use in the field with minimal sample preparation. The CCHFV RPA was successfully used to screen and detect CCHFV positives from a panel of clinical samples from Tajikistan.The assay is a rapid, isothermal, simple-to-perform molecular diagnostic, which can be performed on a light, portable real-time detection device. It is ideally placed therefore for use as a field-diagnostic or in-low resource laboratories, for monitoring of CCHF outbreaks at the point-of-need, such as in remote rural regions in affected countries.

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

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

    2008-03-01

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

  15. Disinfection of foot-and-mouth disease and African swine fever viruses with citric acid and sodium hypochlorite on birch wood carriers

    Transboundary animal disease viruses such as foot-and-mouth disease virus (FMDV) and African swine fever virus (ASFV) are highly contagious and cause severe morbidity and mortality in livestock. Proper disinfection during an outbreak can help prevent virus spread and will shorten the time for contam...

  16. A flow cytometry-based assay for quantifying non-plaque forming strains of yellow fever virus.

    Erika Hammarlund

    Full Text Available Primary clinical isolates of yellow fever virus can be difficult to quantitate by standard in vitro methods because they may not form discernable plaques or induce a measurable cytopathic effect (CPE on cell monolayers. In our hands, the Dakar strain of yellow fever virus (YFV-Dakar could not be measured by plaque assay (PA, focus-forming assay (FFA, or by measurement of CPE. For these reasons, we developed a YFV-specific monoclonal antibody (3A8.B6 and used it to optimize a highly sensitive flow cytometry-based tissue culture limiting dilution assay (TC-LDA to measure levels of infectious virus. The TC-LDA was performed by incubating serial dilutions of virus in replicate wells of C6/36 cells and stained intracellularly for virus with MAb 3A8.B6. Using this approach, we could reproducibly quantitate YFV-Dakar in tissue culture supernatants as well as from the serum of viremic rhesus macaques experimentally infected with YFV-Dakar. Moreover, the TC-LDA approach was >10-fold more sensitive than standard plaque assay for quantitating typical plaque-forming strains of YFV including YFV-17D and YFV-FNV (French neurotropic vaccine. Together, these results indicate that the TC-LDA technique is effective for quantitating both plaque-forming and non-plaque-forming strains of yellow fever virus, and this methodology may be readily adapted for the study and quantitation of other non-plaque-forming viruses.

  17. The Temporal Program of Peripheral Blood Gene Expression in the Response of Nonhuman Primates to Ebola Hemorrhagic Fever

    2007-08-28

    the family Filoviridae. The EBOV genus consists of four distinct species: Ivory Coast Ebola virus, Reston Ebola virus, Sudan Ebola virus, and Zaire...S, Liu CL, Belcher CE, Botstein D, Staudt LM, Brown PO, Relman DA: Stereotyped and specific gene expression programs in human innate immune responses

  18. Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles

    Bárcena, Juan; Guerra, Beatriz; Angulo, Iván; González, Julia; Valcárcel, Félix; Mata, Carlos P.; Castón, José R.; Blanco, Esther; Alejo, Alí

    2015-01-01

    International audience; In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particl...

  19. Restoration of glycoprotein Erns dimerization via pseudoreversion partially restores virulence of classical swine fever virus.

    Tucakov, Anna Katharina; Yavuz, Sabine; Schürmann, Eva-Maria; Mischler, Manjula; Klingebeil, Anne; Meyers, Gregor

    2018-01-01

    The classical swine fever virus (CSFV) represents one of the most important pathogens of swine. The CSFV glycoprotein E rns is an essential structural protein and an important virulence factor. The latter is dependent on the RNase activity of this envelope protein and, most likely, its secretion from the infected cell. A further important feature with regard to its function as a virulence factor is the formation of disulfide-linked E rns homodimers that are found in virus-infected cells and virions. Mutant CSFV lacking cysteine (Cys) 171, the residue responsible for intermolecular disulfide bond formation, were found to be attenuated in pigs (Tews BA, Schürmann EM, Meyers G. J Virol 2009;83:4823-4834). In the course of an animal experiment with such a dimerization-negative CSFV mutant, viruses were reisolated from pigs that contained a mutation of serine (Ser) 209 to Cys. This mutation restored the ability to form disulphide-linked E rns homodimers. In transient expression studies E rns mutants carrying the S209C change were found to form homodimers with about wt efficiency. Also the secretion level of the mutated proteins was equivalent to that of wt E rns . Virus mutants containing the Cys171Ser/Ser209Cys configuration exhibited wt growth rates and increased virulence when compared with the Cys171Ser mutant. These results provide further support for the connection between CSFV virulence and E rns dimerization.

  20. Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles.

    Bárcena, Juan; Guerra, Beatriz; Angulo, Iván; González, Julia; Valcárcel, Félix; Mata, Carlos P; Castón, José R; Blanco, Esther; Alejo, Alí

    2015-09-24

    In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particles (VLPs). Our results further confirmed the differential antigenic properties exhibited by RHDV and RHDV2, highlighting the need of using RHDV2-specific diagnostic assays to monitor the spread of this new virus.