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Sample records for argentine hemorrhagic fever

  1. Cross-protection in nonhuman primates against Argentine hemorrhagic fever.

    PubMed Central

    Weissenbacher, M C; Coto, C E; Calello, M A; Rondinone, S N; Damonte, E B; Frigerio, M J

    1982-01-01

    The susceptibility of the marmoset Callithrix jacchus to Tacaribe virus infection was investigated to perform cross-protection studies between Junin and Tacaribe viruses. Five marmosets inoculated with Tacaribe virus failed to show any signs of disease, any alterations in erythrocyte, leukocyte, reticulocyte, and platelet counts or any changes in hematocrit or hemoglobin values. No Tacaribe virus could be recovered from blood at any time postinfection. Anti-Tacaribe neutralizing antibodies appeared 3 weeks postinfection. The five Tacaribe-infected marmosets and four noninfected controls were challenged with the pathogenic strain of Junin virus on day 60 post-Tacaribe infection. The former group showed no signs of disease, no viremia, and no challenge virus replication, whereas the control group exhibited the typical symptoms of Argentine hemorrhagic fever, high viremia, and viral titers in organs. Soon after challenge, the Tacaribe-protected marmosets synthesized neutralizing antibodies against Junin virus. These results indicate that the marmoset C. jacchus can be considered an experimental model for protection studies with arenaviruses and that the Tacaribe virus could be considered as a potential vaccine against Junin virus. PMID:6276301

  2. Dengue hemorrhagic fever

    MedlinePlus

    Hemorrhagic dengue; Dengue shock syndrome; Philippine hemorrhagic fever; Thai hemorrhagic fever; Singapore hemorrhagic fever ... Four different dengue viruses are known to cause dengue hemorrhagic fever. Dengue hemorrhagic fever occurs when a person is bitten by ...

  3. Hemorrhagic Fevers

    MedlinePlus

    ... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

  4. Viral Hemorrhagic Fevers

    MedlinePlus

    ... Fever with Renal Syndrome Hendra Virus Disease Kyasanur Forest Disease Lassa Fever Lymphocytic Choriomeningitis (LCM) Marburg Hemorrhagic ... the rodent species carrying several of the New World arenaviruses, live in geographically restricted areas. Therefore, the ...

  5. [Quali-quantitative study of the social variables defining transmission scenarios of Argentine Hemorrhagic Fever in the provinces of Buenos Aires and Santa Fe, 2001-2010].

    PubMed

    Mastrangelo, Andrea; Tagliabue, Paula; Berro, Lorena; De Carolis, Darío; Sinchi, Anabel; Digilio, Clara; Enria, Delia

    2014-08-01

    The aim of this paper was to characterize transmission scenarios of Argentine Hemorrhagic Fever in the post-vaccination period (2001-2010). The study was made up of three phases. The first consisted of a quantitative analysis using the database of the Dr. Julio I. Maiztegui National Institute of Human Viral Diseases [Instituto Nacional de Enfermedades Virales Humanas] regarding the confirmed cases in the period of study (221 cases). Taking into account the transmission site and the known endemic area, cases were grouped into three hypothetical transmission scenarios, identified as: a) classical, b) emerging-reemerging, c) traveling. In the second phase, in order to test these hypotheses, in-depth interviews were carried out from August to September 2011 within an intentionally selected sample of patients distributed proportionally among the three hypotheses. Finally, in the third stage, the data obtained for each hypothetical scenario were grouped into three spatiotemporal scales: the microscale (subject), the mesoscale (locality) and macroscale (region). The results show that new transmission sites are associated with the social dynamics of cereal production and port-bound routes. PMID:25237798

  6. [New transmission scenarios of the Argentine hemorrhagic fever since the introduction of the live attenuated junin virus vaccine (Candid #1): an experience in migrant workers].

    PubMed

    Briggiler, Ana; Sinchi, Anabel; Coronel, Florencia; Sánchez, Zaida; Levis, Silvana; Taylor, Jorge; Enria, Delia

    2015-01-01

    The Argentine hemorrhagic fever (AHF) is a severe acute viral disease caused by the Junin virus of the Arenaviridae family. The AHF endemic area coincides geographically with the largest grain export agro-industrial complex of the country [Argentina]. Since the implementation of vaccination with the Candid #1 vaccine, a significant reduction in incidence was achieved and risk patterns were modified. A previous study allowed characterizing these changes and identifying three transmission scenarios: classic, emergent-reemergent, and traveler. The latter scenario includes seasonal migrant workers who move each year, mainly from the province of Santiago del Estero, the endemic area to work in the detasseling of maize. With the objective of protecting this group of workers, a prevention campaign was initiated which included: capacity building of health personnel in the province, health education, and immunization with the vaccine Candid #1. 3,021 workers were vaccinated. Prior to vaccination, serum samples were taken from a group of 104 volunteers. Tests for neutralizing antibodies specific to the Junin virus were performed and 6 (5.76%) tested positive. The unexpected finding of a high percentage of workers with antibodies suggests the need to evaluate several hypotheses: a) that the result is the product of non-probabilistic sampling; b) that it could be people who fell ill in previous travels, c) or who were vaccinated in previous travels; or d) consider this region as an emerging scenario. PMID:26102120

  7. Simian hemorrhagic fever virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter describes the taxonomic classification of Simian hemorrhagic fever virus (SHFV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biological pro...

  8. Favipiravir (T-705) Inhibits Junín Virus Infection and Reduces Mortality in a Guinea Pig Model of Argentine Hemorrhagic Fever

    PubMed Central

    Gowen, Brian B.; Juelich, Terry L.; Sefing, Eric J.; Brasel, Trevor; Smith, Jennifer K.; Zhang, Lihong; Tigabu, Bersabeh; Hill, Terence E.; Yun, Tatyana; Pietzsch, Colette; Furuta, Yousuke; Freiberg, Alexander N.

    2013-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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. PMID:24386500

  9. Marburg Hemorrhagic Fever (Marburg HF)

    MedlinePlus

    ... The CDC Cancel Submit Search The CDC Marburg hemorrhagic fever (Marburg HF) Note: Javascript is disabled or is ... was first recognized in 1967, when outbreaks of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, ...

  10. Dengue and Dengue Hemorrhagic Fever

    PubMed Central

    Gubler, Duane J.

    1998-01-01

    Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in the waning years of the 20th century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. A major challenge for public health officials in all tropical areas of the world is to devleop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever. PMID:9665979

  11. Viral Hemorrhagic Fever Diagnostics.

    PubMed

    Racsa, Lori D; Kraft, Colleen S; Olinger, Gene G; Hensley, Lisa E

    2016-01-15

    There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. PMID:26354968

  12. Rescue from Cloned cDNAs and In Vivo Characterization of Recombinant Pathogenic Romero and Live-Attenuated Candid #1 Strains of Junin Virus, the Causative Agent of Argentine Hemorrhagic Fever Disease ▿

    PubMed Central

    Emonet, Sebastien F.; Seregin, Alexey V.; Yun, Nadezhda E.; Poussard, Allison L.; Walker, Aida G.; de la Torre, Juan C.; Paessler, Slobodan

    2011-01-01

    The New World arenavirus Junin virus (JUNV) is the causative agent of Argentine hemorrhagic fever (AHF), which is associated with high morbidity and significant mortality. Several pathogenic strains of JUNV have been documented, and a highly attenuated vaccine strain (Candid #1) was generated and used to vaccinate the human population at risk. The identification and functional characterization of viral genetic determinants associated with AHF and Candid #1 attenuation would contribute to the elucidation of the mechanisms contributing to AHF and the development of better vaccines and therapeutics. To this end, we used reverse genetics to rescue the pathogenic Romero and the attenuated Candid #1 strains of JUNV from cloned cDNAs. Both recombinant Candid #1 (rCandid #1) and Romero (rRomero) had the same growth properties and phenotypic features in cultured cells and in vivo as their corresponding parental viruses. Infection with rRomero caused 100% lethality in guinea pigs, whereas rCandid #1 infection was asymptomatic and provided protection against a lethal challenge with Romero. Notably, Romero and Candid #1 trans-acting proteins, L and NP, required for virus RNA replication and gene expression were exchangeable in a minigenome rescue assay. These findings support the feasibility of studies aimed at determining the contribution of each viral gene to JUNV pathogenesis and attenuation. In addition, we rescued Candid #1 viruses with three segments that efficiently expressed foreign genes introduced into their genomes. This finding opens the way for the development of a safe multivalent arenavirus vaccine. PMID:21123388

  13. Pathogenesis of arenavirus hemorrhagic fevers.

    PubMed

    Moraz, Marie-Laurence; Kunz, Stefan

    2011-01-01

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments. PMID:21171877

  14. Crimean-Congo Hemorrhagic Fever (CCHF)

    MedlinePlus

    ... Congo Hemorrhagic Fever (CCHF) [PDF - 2 pages] Virus Ecology Viral Hemorrhagic Fever (VHF) Information for Specific Groups ... Diagnosis Treatment Prevention Outbreak Distribution Map Resources Virus Ecology File Formats Help: How do I view different ...

  15. The Glycoprotein Precursor Gene of Junin Virus Determines the Virulence of the Romero Strain and the Attenuation of the Candid #1 Strain in a Representative Animal Model of Argentine Hemorrhagic Fever

    PubMed Central

    Seregin, Alexey V.; Yun, Nadezhda E.; Miller, Milagros; Aronson, Judith; Smith, Jennifer K.; Walker, Aida G.; Smith, Jeanon N.; Huang, Cheng; Manning, John T.; de la Torre, Juan C.

    2015-01-01

    ABSTRACT The New World arenavirus Junin virus (JUNV) is the causative agent of Argentine hemorrhagic fever (AHF), a potentially deadly disease endemic to central regions of Argentina. The live-attenuated Candid #1 (Can) strain of JUNV is currently used to vaccinate the human population at risk. However, the mechanism of attenuation of this strain is still largely unknown. Therefore, the identification and functional characterization of viral genetic determinants dictating JUNV virulence or attenuation would significantly improve the understanding of the mechanisms underlying AHF and facilitate the development of novel, more effective, and safer vaccines. Here, we utilized a reverse genetics approach to generate recombinant JUNV (rJUNV) strains encoding different gene combinations of the pathogenic Romero (Rom) and attenuated Can strains of JUNV. All strains of rJUNV exhibited in vitro growth kinetics similar to those of their parental counterparts. Analysis of virulence of the rJUNV in a guinea pig model of lethal infection that closely reproduces the features of AHF identified the envelope glycoproteins (GPs) as the major determinants of pathogenesis and attenuation of JUNV. Accordingly, rJUNV strains expressing the full-length GPs of Rom and Can exhibited virulent and attenuated phenotypes, respectively, in guinea pigs. Mutation F427I in the transmembrane region of JUNV envelope glycoprotein GP2 has been shown to attenuate the neurovirulence of JUNV in suckling mice. We document that in the guinea pig model of AHF, mutation F427I in GP2 is also highly attenuating but insufficient to prevent virus dissemination and development of mild clinical and pathological symptoms, indicating that complete attenuation of JUNV requires additional mutations present in Can glycoprotein precursor (GPC). IMPORTANCE Development of antiviral strategies against viral hemorrhagic fevers, including AHF, is one of the top priorities within the Implementation Plan of the U.S. Department

  16. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

    PubMed

    Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Van Wettere, Arnaud J; Jung, Kie-Hoon; Dagley, Ashley; Wandersee, Luci; Downs, Brittney; Smee, Donald F; Furuta, Yousuke; Bray, Mike; Gowen, Brian B

    2016-02-01

    Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin. PMID:26711718

  17. Clinical aspects of Marburg hemorrhagic fever

    PubMed Central

    Mehedi, Masfique; Groseth, Allison; Feldmann, Heinz; Ebihara, Hideki

    2011-01-01

    Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates. Similar to the more widely known Ebola hemorrhagic fever, MHF is characterized by systemic viral replication, immunosuppression and abnormal inflammatory responses. These pathological features of the disease contribute to a number of systemic dysfunctions including hemorrhages, edema, coagulation abnormalities and, ultimately, multiorgan failure and shock, often resulting in death. A detailed understanding of the pathological processes that lead to this devastating disease remains elusive, a fact that contributes to the lack of licensed vaccines or effective therapeutics. This article will review the clinical aspects of MHF and discuss the pathogenesis and possible options for diagnosis, treatment and prevention. PMID:22046196

  18. Infection Control During Filoviral Hemorrhagic Fever Outbreaks

    PubMed Central

    Vanessa, N Raabe; Matthias, Borchert

    2012-01-01

    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. PMID:22529631

  19. Immunological features underlying viral hemorrhagic fevers.

    PubMed

    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. PMID:26163194

  20. Acute Arthritis in Crimean-Congo Hemorrhagic Fever

    PubMed Central

    Ahmeti, Salih; Ajazaj-Berisha, Lindita; Halili, Bahrije; Shala, Anita

    2014-01-01

    Crimean-Congo hemorrhagic fever is a severe viral disease caused by a Nairovirus. An atypical manifestation in the form of acute arthritis was found in a confirmed Crimean-Congo hemorrhagic fever virus Kosova-Hoti strain positive patient. Acute arthritis in Crimean-Congo hemorrhagic fever (CCHF) may be as a result of immune mechanisms or the bleeding disorder underlying CCHF. PMID:24926169

  1. Viruses Causing Hemorrhagic Fever. Safety Laboratory Procedures

    PubMed Central

    Cobo, Fernando

    2016-01-01

    Viral hemorrhagic fevers are diseases caused by viruses which belong to different families, many of them causing severe diseases. These viruses may produce different symptomatology together with a severe multisystem syndrome, and the final result might be the production of hemorrhages in several sites of the body. The majority of them have no other treatment than supportive therapy, although some antiviral drugs can be used in some circumstances. Transmission of VHF has been demonstrated through contact with animal vectors or person-to-person through the contact with body fluids. No risk of transmission has been found during the incubation period, but when the viral load is high the risk of transmission is greatest. Both health care and clinical laboratory workers must safely handle patients and specimens by taking all required precautions during their management. PMID:27014378

  2. Endothelial cells in dengue hemorrhagic fever.

    PubMed

    Srikiatkhachorn, Anon; Kelley, James F

    2014-09-01

    Therapies to prevent or reverse endothelial dysfunction and vascular leak found in dengue hemorrhagic fever (DHF) have not been identified. In this review we summarize dengue viruses and the spectrum of human disease and highlight evidence of endothelial cell dysfunction in DHF based on studies in patients and mouse and tissue culture models. Evidence suggests that both virus antigen and host immune response, can cause endothelial cell dysfunction and weaken endothelial barrier integrity. We suggest possible therapeutic interventions and highlight how therapies targeting altered endothelial function might be evaluated in animal models and in patients with DHF. PMID:25025934

  3. DENGUE FEVER AND DENGUE HEMORRHAGIC FEVER IN ADULTS.

    PubMed

    Tantawichien, Terapong

    2015-01-01

    Dengue fever and dengue hemorrhagic fever are re-emerging diseases that are endemic in the Tropics. The global prevalence of dengue cases has increased in South-East Asia, Africa, the Western Pacific, and the Americas. The increasingly widespread distribution and the rising incidence of dengue virus infections are related to increased distribution of Aedes aegypti, an increasingly urban population, and increasing air travel. Several Southeast Asian countries show that the age of the reported dengue cases has increased from 5-9 years, to older children and young adults. Dengue infection in adolescents and adults has also been recognized as a potential hazard to international travelers returning from endemic areas, especially SoutheastAsia. Dengue is one disease entity with different clinical presentations; often with unpredictable clinical evolutions and outcomes. Bleeding manifestations in adult patients, including petechiae and menorrhagia were also frequently found; however, massive hematemesis may occur in adult patients because of peptic ulcer disease and may not be associated with profound shock as previously reported in children. Although shock and plasma leakage seem to be more prevalent as age decreases, the frequency of internal hemorrhage rises as age increases. Increase in liver enzymes found in both children and adults indicated liver involvement during dengue infections. Pre-existing liver diseases in adults such as chronic hepatitis, alcoholic cirrhosis, and hemoglobinopathies may aggravate the liver impairment in dengue infection. Fulminant hepatitis is a rare but well described problem in adult patients with dengue infection. Currently, no specific therapeutic agent exists for dengue. The early recognition of dengue infection, bleeding tendency, and signs of circulatory collapse would reduce mortality rates in adult patients with dengue infection. PMID:26506734

  4. Epidemiology and Pathogenesis of Bolivian Hemorrhagic Fever

    PubMed Central

    Patterson, Michael; Grant, Ashley; Paessler, Slobodan

    2014-01-01

    The etiologic agent of Bolivian hemorrhagic fever (BHF), Machupo virus (MACV) is reported to have a mortality rate of 25 to 35%. First identified in 1959, BHF was the cause of a localized outbreak in San Joaquin until rodent population controls were implemented in 1964. The rodent Calomys collosus was identified as the primary vector and reservoir for the virus. Multiple animal models were considered during the 1970’s with the most human-like disease identified in Rhesus macaques but minimal characterization of the pathogenesis has been published since. A reemergence of reported BHF cases has been reported in recent years, which necessitates the further study and development of a vaccine to prevent future outbreaks. PMID:24636947

  5. Pulmonary hemorrhage syndrome associated with an autochthonous case of dengue hemorrhagic fever.

    PubMed

    Setlik, Robert F; Ouellette, Daniel; Morgan, Julia; McAllister, C Kenneth; Dorsey, David; Agan, Brian K; Horvath, Lynn; Zimmerman, Michelle K; Purcell, Bret

    2004-07-01

    Dengue fever is a major public health problem worldwide. Dengue hemorrhagic fever, a much rarer form of the disease, occurs when a person previously infected with dengue is re-infected with a different viral serotype. In recent years the infection rates of dengue and both clinical syndromes have increased along the United States-Mexico border. We present the case of a 61-year-old Laotian female who presented with a 1-week history of fever, altered mental status, oral ulceration, and rash. The patient developed diffuse pulmonary hemorrhage and anemia requiring multiple transfusions. She eventually sustained multi-organ system failure and expired. Both the titer data and serologies were consistent with the diagnosis of dengue hemorrhagic fever. We hypothesize that this syndrome was the result of re-infection occurring within the United States. This case is also unusual in that it is the second reported in the literature of pulmonary hemorrhages associated with dengue hemorrhagic fever. PMID:15301127

  6. Hemorrhagic fever with renal syndrome in Montenegro.

    PubMed

    Gledovic, Z B; Jeknic, A S; Grgurevic, A D; Rakocevic, B B; Bozovic, B R; Mugosa, B V

    2008-09-01

    The objective of the study was to analyze the epidemiological features of hemorrhagic fever with renal syndrome (HFRS) in Montenegro. The study included 169 cases of HFRS diagnosed in the period between 1995 and 2005 according to the clinical symptoms and serological confirmation. For the analysis of the demographic characteristics of the cases, as well as of the chronological and topographical features of the disease, a descriptive epidemiological method was employed. The average incidence rate in the observed period was 2.6 per 100,000. In the observed period, 8 people died; the average case fatality rate was 4.8% (range: 0.1-15%). Among the diseased persons, 116 were males and 53 were females; most of the cases were adults. The greatest number of HFRS cases occurred during the summer months. The highest incidence rates were registered in the northeastern, rural part of the country. The most frequent type of hantaviruses in Montenegro were Dobrava-Belgrade and Hantaan, carried by rodent species, i.e., the yellow-neck mouse and the striped-field mouse. It is likely that HFRS in Montenegro will become more common in the near future, unless public health control measures are taken. PMID:18806348

  7. Crimean-Congo hemorrhagic fever in Iran

    PubMed Central

    Keshtkar-Jahromi, Maryam; Sajadi, Mohammad M.; Ansari, Hossein; Mardani, Masoud; Naieni, Kourosh Holakouie

    2014-01-01

    The presence of Crimean-Congo hemorrhagic fever virus (CCHFV) in Iran was first identified in studies of livestock sera and ticks in the 1970s, but the first human infection was not diagnosed until 1999. Since that time, the number of cases of CCHF in Iran has markedly increased. Through January 2012, articles in the published literature have reported a total of 870 confirmed cases, with 126 deaths, for a case fatality rate (CFR) of 17.6%. The disease has been seen in 26 of the country’s 31 provinces, with the greatest number of cases in Sistan and Baluchestan, Isfahan, Fars, Tehran, Khorasan, and Khuzestan provinces. The increase in CCHF in Iran has paralleled that in neighboring Turkey, though the number of cases in Turkey has been much larger, with an overall CFR of around 5%. In this article, we review the features of CCHF in Iran, including its history, epidemiology, animal and tick reservoirs, current surveillance and control programs, diagnostic methods, clinical features and experience with ribavirin therapy, and consider possible explanations for the difference in the CFR of CCHF between Iran and Turkey. The emergence of CCHF in Iran calls for countermeasures at many levels to protect the population, but also provides opportunities for studying the epidemiology, diagnosis and management of the disease. PMID:23872313

  8. Dengue hemorrhagic fever and the kidney.

    PubMed

    Vachvanichsanong, Prayong; Thisyakorn, Usa; Thisyakorn, Chule

    2016-04-01

    Dengue virus infection (DVI)/dengue hemorrhagic fever (DHF) is a common febrile illness with a variety of severities. The mortality rate is high in dengue shock syndrome (DSS), caused by circulatory failure due to plasma leakage resulting in multi-organ failure. However, acute kidney injury (AKI) is rarely reported. In areas of endemic DVI, the prevalence of AKI due to DVI has been reported to be as high as 6.0 % in children with AKI, and 0.9 % in children with DVI who were admitted to a hospital. The mechanism of AKI in DVI is not clear. It may result from (a) direct injury as in other infectious diseases, (b) an indirect mechanism such as via the immune system, since DHF is an immunological disease, or (c) hypotensive DSS, leading in turn to reduced renal blood supply and renal failure. The mortality rates of DF/DHF, DSS and DHF/DSS-related AKI are <1 %, 12-44 %, and >60 %, respectively. Kidney involvement is not actually that rare, but is under-recognized and often only reported when microscopic hematuria, proteinuria, electrolyte imbalance, or even AKI is found. The prevalence of proteinuria and hematuria has been reported as high as 70-80 % in DVI. A correct diagnosis depends on basic investigations of kidney function such as urinalysis, serum creatinine and electrolytes. Although DVI-related renal involvement is treated supportively, it is still important to make an early diagnosis to prevent AKI and its complications, and if AKI does occur, dialysis may be required. Fortunately, in patients who recover, kidney function usually completely recovers as well. PMID:26699788

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

    PubMed

    Khan, Saif; Gupta, N D; Maheshwari, Sandhya

    2013-07-01

    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. PMID:24174736

  10. Crimean-Congo hemorrhagic fever (CCHF) in Southern Kordofan

    PubMed Central

    Taha, Mohamed Ahmed

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a disease that poses a great threat to public health owing to its high mortality rate (30-70%), mode of transmission and geographic distribution. Here, we report on a nine years-old Sudanese boy from Southern Kordofan State who presented with Jaundice, high-grade fever, severe headache, abdominal pain and a history of hematemesis. The diagnosis of CCHF was confirmed based on clinical and serological findings. PMID:27493394

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

    PubMed

    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. PMID:26012219

  12. Clinical Features and Patient Management of Lujo Hemorrhagic Fever

    PubMed Central

    Sewlall, Nivesh H.; Richards, Guy; Duse, Adriano; Swanepoel, Robert; Paweska, Janusz; Blumberg, Lucille; Dinh, Thu Ha; Bausch, Daniel

    2014-01-01

    Background 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. Methods and Findings 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. Conclusions 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

  13. First Crimean-Congo hemorrhagic fever outbreak in India.

    PubMed

    Patel, Atul K; Patel, Ketan K; Mehta, Minesh; Parikh, Tejas M; Toshniwal, Harsh; Patel, Kamlesh

    2011-09-01

    Crimean-Congo hemorrhagic fever (CCHF) has not been reportedly previously from India. Initial clinical features of dengue fever and CCHF are similar and it is very difficult to differentiate and diagnose CCHF. Common clinical features of CCHF include; high grade fever with chills, headache, body ache, myalgia, vomiting, abdominal pain, weakness and bleeding from multiple sites. Laboratory investigations showed cytopenia, raised prothrombin time (PT) and activated partial thromboplastin time (aPTT), raised creatinine phosphokinase (CPK) and lactic dehydrogenase (LDH) as well as altered liver and renal functions. Patients with above symptoms can rapidly progress to bleeding from multiple sites and death compared to dengue fever. It is crucial to recognize CCHF at early stage to institute ribavirin treatment and also to prevent nosocomial spread of disease to health care workers. We are describing first four cases of recent CCHF outbreak in Ahmedabad. PMID:22334974

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

    PubMed Central

    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

  15. Satellite Detection of Ebola River Hemorrhagic Fever Epidemics Trigger Events

    NASA Technical Reports Server (NTRS)

    Tucker, Compton J.; Pinzon, Jorge E.

    2006-01-01

    Ebola hemorrhagic fever, named after the Ebola River in Central Africa, first appeared in June 1976, during an outbreak in Nzara and Maridi, Sudan. In September 1976, a separate outbreak was recognized in Yambuku, Democratic Republic of the Congo (DRC). One fatal case was identified in Tandala, DRC, in June 1977, followed by another outbreak in Nzara, Sudan, in July 1979. Ebola hemorrhagic fever outbreaks results in a very high mortality of patients who contract the disease: from 50 to 80% of infected people perish from this highly virulent disease. Death is gruesome, with those afflicted bleeding to death from massive hemorrhaging of organs and capillaries. The disease was not identified again until the end of 1994, when three outbreaks occurred almost simultaneously in Africa. In October, an outbreak was identified in a chimpanzee community studied by primatologists in Tal, Cote d'lvoire, with one human infection. The following month, multiple cases were reported in northeast Gabon in the gold panning camps of Mekouka, Andock, and Minkebe. Later that same month, the putative index case of the 1995 Kikwit, DRC, outbreak was exposed through an unknown mechanism while working in a charcoal pit. In Gabon, two additional outbreaks were reported in February and JuIy,1996, respectively, in Mayibout II, a village 40 km south of the original outbreak in the gold panning camps, and a logging camp between Ovan and Koumameyong, near Booue. The largest Ebola hemorrhagic fever epidemic occurred in Gulu District, Uganda from August 2000 to January 2001. In December 2001, Ebola reappeared in the Ogooue-lvindo Province, Gabon with extension into Mbomo District, The Republic of the Congo lasting until July 2002. Since 2002 there have been several outbreaks of Ebola hemorrhagic fever in Gabon and adjacent areas of Congo. Of interest is the seasonal context and occasional temporal clustering of Ebola hemorrhagic fever outbreaks. Near simultaneous appearances of Ebola epidemics in

  16. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    DOE PAGESBeta

    Zivcec, Marko; Scholte, Florine; Spiropoulou, Christina; Spengler, Jessica; Bergeron, Éric

    2016-04-21

    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.

  17. Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture.

    PubMed

    Jiang, Hong; Du, Hong; Wang, Li M; Wang, Ping Z; Bai, Xue F

    2016-01-01

    Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed. PMID:26870699

  18. Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture

    PubMed Central

    Jiang, Hong; Du, Hong; Wang, Li M.; Wang, Ping Z.; Bai, Xue F.

    2016-01-01

    Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed. PMID:26870699

  19. FATAL RHABDOMYOLYSIS IN DENGUE HEMORRHAGIC FEVER: A CASE REPORT.

    PubMed

    Siriyakorn, Nirada; Insiripong, Somchai

    2015-01-01

    Dengue hemorrhagic fever is caused by dengue virus infection. The classical manifestations consist of fever, thrombocytopenia, and hemoconcentration. However, its unusual complications may be fatal, such as prolong shock, massive bleeding, volume overload, and unusual manifestations, for example, severe rhabdomyolysis. Here we report a case of 17-year old Thai man who was referred to our hospital because of 7-day fever with thrombocytopenia, hemoconcentration and right pleural effusion. The serology tests confirmed to be dengue infection. He developed various complications: severe hepatitis, coagulopathy, and heavy proteinuria; encephalopathy that needed a respiratory ventilator. On day 12 of fever, he had myalgia and passed dark urine. Serum creatinine and serum creatinine phosphokinase (CPK) were found abnormally high. He was diagnosed as severe rhabdomyolysis with acute kidney injury, and immediate hemodialysis was performed. He did not respond to treatment and expired within three hours. Although the mechanism of severe rhabdomyolysis in dengue fever is not clearly known, it may theoretically be proposed such as direct muscle cell injury leading to myositis by dengue virus, myotoxic cytokines which are produced in response to viral infection, dehydration or hypophosphatemia. PMID:26506741

  20. Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs.

    PubMed

    Bell, T M; Bunton, T E; Shaia, C I; Raymond, J W; Honnold, S P; Donnelly, G C; Shamblin, J D; Wilkinson, E R; Cashman, K A

    2016-01-01

    Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development. PMID:26139838

  1. Recent advances in research on Crimean-Congo hemorrhagic fever

    PubMed Central

    Papa, Anna; Mirazimi, Ali; Köksal, Iftihar; Estrada-Pena, Augustin; Feldmann, Heinz

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is an expanding tick-borne hemorrhagic disease with increasing human and animal health impact. Immense knowledge was gained over the past 10 years mainly due to advances in molecular biology, but also driven by an increased global interest in CCHFV as an emerging/re-emerging zoonotic pathogen. In the present article we discuss the advances in research with focus on CCHF ecology, epidemiology, pathogenesis, diagnostics, prophylaxis and treatment. Despite tremendous achievements, future activities have to concentrate on the development of vaccines and antivirals/therapeutics to combat CCHF. Vector studies need to continue for better public and animal health preparedness and response. We conclude with a roadmap for future research priorities. PMID:25453328

  2. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    PubMed Central

    Zivcec, Marko; Scholte, Florine E. M.; Spiropoulou, Christina F.; Spengler, Jessica R.; Bergeron, Éric

    2016-01-01

    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. PMID:27110812

  3. Trigger events: enviroclimatic coupling of Ebola hemorrhagic fever outbreaks

    NASA Technical Reports Server (NTRS)

    Pinzon, Jorge E.; Wilson, James M.; Tucker, Compton J.; Arthur, Ray; Jahrling, Peter B.; Formenty, Pierre

    2004-01-01

    We use spatially continuous satellite data as a correlate of precipitation within tropical Africa and show that the majority of documented Ebola hemorrhagic fever outbreaks were closely associated with sharply drier conditions at the end of the rainy season. We propose that these trigger events may enhance transmission of Ebola virus from its cryptic reservoir to humans. These findings suggest specific directions to help understand the sylvatic cycle of the virus and may provide early warning tools to detect possible future outbreaks of this enigmatic disease.

  4. Acalculous cholecystitis associated with hemorrhagic fever with renal syndrome.

    PubMed

    Nicolas, J B

    2015-10-01

    Hantaviruses are responsible for various types of hemorrhagic fevers depending on the involved subtype. In Europe, Puumala virus is responsible for an epidemic nephropathy. This infection can be complicated by severe abdominal pain. A rarely reported cause of this presenting symptom is acalculous cholecystitis, which must be integrated in the clinicobiological spectrum and should not lead to a surgical sanction. Its presence seems to be correlated with the severity of the disease, whose main pathophysiological phenomenon is plasma leakage induced by a microvascular endothelial dysfunction. We report the case of a young male patient who presented with severe hantavirus infection complicated by acalculous cholecystitis. PMID:25982259

  5. Vaccines for viral hemorrhagic fevers--progress and shortcomings.

    PubMed

    Falzarano, Darryl; Feldmann, Heinz

    2013-06-01

    With a few exceptions, vaccines for viruses that cause hemorrhagic fever remain unavailable or lack well-documented efficacy. In the past decade this has not been due to a lack of the ability to develop vaccine platforms against highly pathogenic viruses, but rather the lack of will/interest to invest in platforms that have the potential to become successful vaccines. The two exceptions to this are vaccines against Dengue virus (DENV) and Rift Valley fever virus (RVFV), which recently have seen significant progress in putting forward new and improved vaccines, respectively. Experimental vaccines for filoviruses and Lassa virus (LASV) do exist but are hindered by a lack of financial interest and only partially or ill-defined correlates/mechanisms of protection that could be assessed in clinical trials. PMID:23773330

  6. Dengue and dengue hemorrhagic fever, Brazil, 1981-2002.

    PubMed

    Siqueira, João Bosco; Martelli, Celina Maria Turchi; Coelho, Giovanini Evelim; Simplicio, Ana Cristina da Rocha; Hatch, Douglas L

    2005-01-01

    In the last 5 years, Brazil has accounted for approximately 70% of reported dengue fever cases in the Americas. We analyzed trends of dengue and dengue hemorrhagic fever (DHF) from the early 1980s to 2002 by using surveillance data from the Brazilian Ministry of Health. Two distinct epidemiologic patterns for dengue were observed: localized epidemics (1986-1993), and endemic and epidemic virus circulation countrywide (1994-2002). Currently, serotypes 1, 2, and 3 cocirculate in 22 of 27 states. Dengue and DHF affected mainly adults; however, an increase in occurrence of DHF among children has been recently detected in northern Brazil, which suggests a shift in the occurrence of severe disease to younger age groups. In 2002, hospitalizations increased, which points out the change in disease severity compared to that seen in the 1990s. We describe the epidemiology of dengue in Brazil, characterizing the changing patterns of it and DHF during the last 20 years. PMID:15705322

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

    PubMed

    Mertens, Marc; Schuster, Isolde; Sas, Miriam A; Vatansever, Zati; Hubalek, Zdenek; Güven, Esin; Deniz, Ahmet; Georgiev, Georgi; Peshev, Raiko; Groschup, Martin H

    2016-09-01

    Infections of humans with the tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) can cause a severe hemorrhagic fever with case fatality rates of up to 80%. Most humans are infected by tick bite, crushing infected ticks by hand or by unprotected contact with blood of viremic mammals. Next to the notified human CCHF cases, the real distribution and the situation in animals in Southeastern Europe are nearly unknown. Since domestic ruminants play a crucial role in the life cycle of the vector ticks and the transmission and amplification of the virus, the antibody prevalence in those animals is a good indicator for the presence of CCHFV in a region. Therefore, the prevalence of CCHFV-specific antibodies was investigated in domestic ruminants of different regions of Bulgaria and Turkey. Sera of 1165 ruminants were tested and a prevalence of up to 90% was identified. The overall prevalence for Bulgaria was 26% and for Turkey 57%. The results highlight the risk of human infections in those regions and the importance of the investigation of the prevalence in animals for identification of risk areas. This article provides a unique overview about published CCHFV antibody prevalence in animals in comparison to human incidences in different areas of Bulgaria and Turkey. Although it will help to complete the understanding of the CCHFV situation in these countries, it also demonstrates the lack of unpublished and published data even in these highly endemic areas. PMID:27467142

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

    PubMed Central

    Warfield, Kelly Lyn; Olinger, Gene Garrard

    2011-01-01

    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. PMID:22253531

  9. Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

    PubMed Central

    Mendenhall, Michelle; Russell, Andrew; Smee, Donald F.; Hall, Jeffery O.; Skirpstunas, Ramona; Furuta, Yousuke; Gowen, Brian B.

    2011-01-01

    Background 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. Methodology/Principal Findings 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 LD50 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. Conclusions/Significance 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

  10. Transmission of epidemic dengue hemorrhagic fever in easternmost Indonesia.

    PubMed

    Sukri, Nono C; Laras, Kanti; Wandra, Toni; Didi, Sukman; Larasati, Ria P; Rachdyatmaka, Josef R; Osok, Stevie; Tjia, Petrus; Saragih, John M; Hartati, Sri; Listyaningsih, Erlin; Porter, Kevin R; Beckett, Charmagne G; Prawira, Ingerani S; Punjabi, Narain; Suparmanto, Sri A; Beecham, H James; Bangs, Michael J; Corwin, Andrew L

    2003-05-01

    In April 2001, a second suspected outbreak of dengue hemorrhagic fever in the easternmost region of Indonesia was investigated in Merauke, a town located in the southeastern corner of Papua, by the Indonesian Ministry of Health and the U.S. Naval Medical Research Unit No. 2. Principal case criteria of hemorrhagic disease provided for a study enrollment of 15 clinically acute and 37 convalescing subjects. Additionally, 32 comparable age/sex controls were selected from neighboring households. Laboratory diagnosis involved three testing methodologies: virus isolation by cell culture, a reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and serologic assays. Antibody (IgM) to dengue virus was detected in 27% of the acute clinical cases, 30% of the convalescing cases, and only 3% of the matched controls. Dengue 3 was the only viral serotype detected from acute serum samples by the RT-PCR. The mean +/- SD age of the acute and convalescing cases was 7.8 +/- 5.4 years. Overall hospital records accounted for 172 suspected outbreak cases, all urban residents of Merauke with no recent travel history outside the area. The estimated outbreak-associated case fatality rate among all suspected dengue cases was 1.2%. A seven-year retrospective review of hospital records in Merauke showed negligible disease reporting involving hemorrhagic disease prior to the outbreak. PMID:12812338

  11. A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques

    PubMed Central

    Vatter, Heather A.; Donaldson, Eric F.; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F.; Lewis, Anne D.; Colgin, Lois M.A.; Axthelm, Michael K.; Pecotte, Jerilyn K.; Baric, Ralph S.; Wong, Scott W.; Brinton, Margo A.

    2014-01-01

    Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages showed a very high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100 PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. PMID:25463617

  12. Pulmonary hemorrhage syndrome associated with dengue fever, High-resolution computed tomography findings: a case report

    PubMed Central

    Marchiori, Edson; Ferreira, José Luiz N; Bittencourt, Carolina N; Neto, César A de Araújo; Zanetti, Gláucia; Mano, Cláudia M; Santos, Alair ASD; Vianna, Alberto D

    2009-01-01

    Dengue hemorrhagic fever is an acute infectious disease caused by dengue virus. We described the high-resolution CT findings in a 70-year-old male with the disease, which was diagnosed by clinical examination and confirmed by serological methods. High-resolution CT demonstrated bilateral areas of consolidation with air bronchogram and ground glass opacities, as well as small bilateral pleural effusions. Dengue hemorrhagic fever should be considered in the differential diagnosis of diffuse pulmonary hemorrhage. PMID:19265524

  13. A retrospective study of acute pancreatitis in patients with hemorrhagic fever with renal syndrome

    PubMed Central

    2013-01-01

    Background Etiological diagnosis is an important part of the diagnosis and treatment of acute pancreatitis. Hantavirus infection is a rare cause of acute pancreatitis, which is easy to ignore. There is a need to analyze clinical features of acute pancreatitis caused by Hantavirus. Methods This is a retrospective study conducted from May 1, 2006 to May 31, 2012 on patients diagnosed with hemorrhagic fever with renal syndrome at our hospital. We reviewed these patients medical records, laboratory results and radiologic examinations to determine the prevalence and summarize clinical features of acute pancreatitis in patients with hemorrhagic fever with renal syndrome. Results A total of 218 patients were diagnosed with hemorrhagic fever with renal syndrome during the 6-year study period. Only 2.8% (6/218) of the total hemorrhagic fever with renal syndrome patients were diagnosed with acute pancreatitis. The first symptom for all six of the patients with acute pancreatitis was fever. All six patients experienced hemorrhage and thrombocytopenia during the disease course, which was different from general acute pancreatitis. In addition, we presented two misdiagnosed clinical cases. Conclusions Acute pancreatitis is not a frequent complication in patients with hemorrhagic fever with renal syndrome. Clinicians should be alerted to the possibility of hemorrhagic fever with renal syndrome when acute pancreatitis patients with epidemiological data have high fever before abdominal pain. PMID:24345089

  14. Dengue hemorrhagic fever in infants: research opportunities ignored.

    PubMed

    Halstead, Scott B; Lan, Nguyen Trong; Myint, Thein Thein; Shwe, Than Nu; Nisalak, Ananda; Kalyanarooj, Siripen; Nimmannitya, Suchitra; Soegijanto, Soegeng; Vaughn, David W; Endy, Timothy P

    2002-12-01

    The age distribution of cases of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in infants under the age of 1 year are reported from Bangkok, Thailand, and for the first time for Ho Chi Minh City, Vietnam; Yangon, Myanmar; and Surabaya, Indonesia. The four dengue viruses were isolated from Thai infants, all of whom were having a primary dengue infection. Progress studying the immunologically distinct infant DHF/DSS has been limited; most contemporary research has centered on DHF/DSS accompanying secondary dengue infections. In designing research results obtained in studies on a congruent animal model, feline infectious peritonitis virus (FIPV) infections of kittens born to FIPV-immune queens should be considered. Research challenges presented by infant DHF/DSS are discussed. PMID:12498666

  15. Animal Models of Tick-Borne Hemorrhagic Fever Viruses

    PubMed Central

    Zivcec, Marko; Safronetz, David; Feldmann, Heinz

    2013-01-01

    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. PMID:25437041

  16. A Syrian Golden Hamster Model Recapitulating Ebola Hemorrhagic Fever

    PubMed Central

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

    2013-01-01

    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. PMID:23045629

  17. A case of brucellosis mimicking Crimean-Congo hemorrhagic fever.

    PubMed

    Metin, Ozge; Teke, Turkan A; Gayretli Aydin, Zeynep G; Kaman, Ayse; Oz, Fatma N; Bayhan, Gulsum I; Tanir, Gonul

    2015-01-01

    Brucellosis is a zoonotic disease caused by Brucella spp. that is transmitted to humans by the ingestion of unpasteurized milk and other dairy products from infected animals or through close contact with secretions. Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by a virus that is transmitted to humans by ixoid tick bites, contact with blood and tissue of infected animals or contact with infected humans. The symptoms of brucellosis are non-specific; it can mimic other diseases. In this paper, we present a case of brucellosis that was initially evaluated as CCHF. We emphasize that brucellosis should be considered in the differential diagnosis of CCHF, especially in endemic countries. PMID:25467988

  18. A predictive model for Dengue Hemorrhagic Fever epidemics.

    PubMed

    Halide, Halmar; Ridd, Peter

    2008-08-01

    A statistical model for predicting monthly Dengue Hemorrhagic Fever (DHF) cases from the city of Makassar is developed and tested. The model uses past and present DHF cases, climate and meteorological observations as inputs. These inputs are selected using a stepwise regression method to predict future DHF cases. The model is tested independently and its skill assessed using two skill measures. Using the selected variables as inputs, the model is capable of predicting a moderately-severe epidemic at lead times of up to six months. The most important input variable in the prediction is the present number of DHF cases followed by the relative humidity three to four months previously. A prediction 1-6 months in advance is sufficient to initiate various activities to combat DHF epidemic. The model is suitable for warning and easily becomes an operational tool due to its simplicity in data requirement and computational effort. PMID:18668414

  19. The global distribution of Crimean-Congo hemorrhagic fever

    PubMed Central

    Messina, Jane P.; Pigott, David M.; Golding, Nick; Duda, Kirsten A.; Brownstein, John S.; Weiss, Daniel J.; Gibson, Harry; Robinson, Timothy P.; Gilbert, Marius; William Wint, G. R.; Nuttall, Patricia A.; Gething, Peter W.; Myers, Monica F.; George, Dylan B.; Hay, Simon I.

    2015-01-01

    Background Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection caused by a virus (CCHFV) from the Bunyaviridae family. Domestic and wild vertebrates are asymptomatic reservoirs for the virus, putting animal handlers, slaughter-house workers and agricultural labourers at highest risk in endemic areas, with secondary transmission possible through contact with infected blood and other bodily fluids. Human infection is characterized by severe symptoms that often result in death. While it is known that CCHFV transmission is limited to Africa, Asia and Europe, definitive global extents and risk patterns within these limits have not been well described. Methods We used an exhaustive database of human CCHF occurrence records and a niche modeling framework to map the global distribution of risk for human CCHF occurrence. Results A greater proportion of shrub or grass land cover was the most important contributor to our model, which predicts highest levels of risk around the Black Sea, Turkey, and some parts of central Asia. Sub-Saharan Africa shows more focalized areas of risk throughout the Sahel and the Cape region. Conclusions These new risk maps provide a valuable starting point for understanding the zoonotic niche of CCHF, its extent and the risk it poses to humans. PMID:26142451

  20. The first epidemic of dengue hemorrhagic fever in French Guiana.

    PubMed

    Reynes, J M; Laurent, A; Deubel, V; Telliam, E; Moreau, J P

    1994-11-01

    From July 1991 to October 1992, an outbreak of dengue spread into the main urban areas of French Guiana, where 90% of the country's 114,808 inhabitants live. In mid-July 1991 dengue-2 virus was identified as being responsible for most cases, while dengue-1 virus was rarely isolated and circulated at a low level. The number of dengue cases during this period was unknown because there was no clinically based dengue surveillance system. The only available data were for the number of suspected cases as indicated by the number of patients for whom blood samples were submitted to a laboratory for dengue diagnosis. Eight hundred forty-seven of the 2,948 suspected cases were diagnosed in the laboratory as dengue cases. Six fatal cases were reported. This outbreak was marked by the appearance of the first clinical cases of dengue hemorrhagic fever (DHF) in French Guiana. Forty cases met the World Health Organization definition of clinical DHF: 32 were grade II, seven were grade III, and one was grade IV and fatal. Eighteen cases were confirmed in the laboratory and 12 were probable; there was no proof of the dengue etiology for the remaining patients. PMID:7985746

  1. Ebola Hemorrhagic Fever and the Current State of Vaccine Development

    PubMed Central

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

    2014-01-01

    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. PMID:25562048

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

    PubMed

    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. PMID:25562048

  3. Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

    PubMed Central

    Guo, Xiling; Zhang, Li; Zhang, Wenshuai; Chi, Ying; Zeng, Xiaoyan; Li, Xian; Qi, Xian; Jin, Qiu; Zhang, Xiao; Huang, Mingming; Wang, Hua; Chen, Yin; Bao, Changjun; Hu, Jianli; Liang, Shuyi; Bao, Lin; Wu, Tao

    2013-01-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly discovered member of the Bunyaviridae family, is the causative agent of an emerging hemorrhagic fever, SFTS, in China. Currently, there are no vaccines or effective therapies against SFTS. In this study, a combinatorial human antibody library was constructed from the peripheral lymphocytes of 5 patients who had recovered from SFTS. The library was screened against purified virions for the production of single-chain variable-region fragments (ScFv). Of the 6 positive clones, one clone (monoclonal antibody [MAb] 4-5) showed neutralizing activity against SFTSV infection in Vero cells. MAb 4-5 was found to effectively neutralize all of the clinical isolates of SFTSV tested, which were isolated from patients in China from 2010 to 2012. MAb 4-5 was found to bind a linear epitope in the ectodomain of glycoprotein Gn. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism. These data suggest that MAb 4-5 can be used as a promising candidate molecule for immunotherapy against SFTSV infection. PMID:23863504

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

    PubMed Central

    Resman Rus, Katarina; Fajs, Luka; Korva, Miša; Avšič-Županc, Tatjana

    2016-01-01

    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. PMID:27348219

  5. Vectors of Crimean Congo Hemorrhagic Fever Virus in Iran

    PubMed Central

    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

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

    PubMed

    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

  7. Inhibitors of cellular kinases with broad-spectrum antiviral activity for hemorrhagic fever viruses.

    PubMed

    Mohr, Emma L; McMullan, Laura K; Lo, Michael K; Spengler, Jessica R; Bergeron, Éric; Albariño, César G; Shrivastava-Ranjan, Punya; Chiang, Cheng-Feng; Nichol, Stuart T; Spiropoulou, Christina F; Flint, Mike

    2015-08-01

    Host cell kinases are important for the replication of a number of hemorrhagic fever viruses. We tested a panel of kinase inhibitors for their ability to block the replication of multiple hemorrhagic fever viruses. OSU-03012 inhibited the replication of Lassa, Ebola, Marburg and Nipah viruses, whereas BIBX 1382 dihydrochloride inhibited Lassa, Ebola and Marburg viruses. BIBX 1382 blocked both Lassa and Ebola virus glycoprotein-dependent cell entry. These compounds may be used as tools to understand conserved virus-host interactions, and implicate host cell kinases that may be targets for broad spectrum therapeutic intervention. PMID:25986249

  8. An Unusual Case of Crimean Congo Hemorrhagic Fever: Prolonged Bleeding with Successful Recovery.

    PubMed

    Hussain, Qurban; Shaikh, Bilal Hussain; Bhutto, Ali Raza; Sohaib, Muneebah

    2016-02-01

    Crimean Congo Hemorrhagic Fever (CCHF) is a tick-borne viral disease with a major reservoir in both domestic and wild animals. In Pakistan, it is endemic largely in rural areas and most cases occur in spring and autumn. Recently, cases are being reported throughout the year, including winter months, with some even from urban areas. Death from CCHF is most likely to occur during the hemorrhagic phase. We report a case presenting from an urban locality in December. Clinical presentation was characterized by a prolonged hemorrhagic phase and a delayed normalization of platelet counts. PMID:26876406

  9. Alkhurma hemorrhagic fever in travelers returning from Egypt, 2010.

    PubMed

    Carletti, Fabrizio; Castilletti, Concetta; Di Caro, Antonino; Capobianchi, Maria R; Nisii, Carla; Suter, Fredy; Rizzi, Marco; Tebaldi, Alessandra; Goglio, Antonio; Passerini Tosi, Cristiana; Ippolito, Giuseppe

    2010-12-01

    Two travelers returning to Italy from southern Egypt were hospitalized with a fever of unknown origin. Test results showed infection with Alkhurma virus. The geographic distribution of this virus could be broader than previously thought. PMID:21122237

  10. Alkhurma Hemorrhagic Fever in Travelers Returning from Egypt, 2010

    PubMed Central

    Carletti, Fabrizio; Castilletti, Concetta; Di Caro, Antonino; Capobianchi, Maria R.; Nisii, Carla; Suter, Fredy; Rizzi, Marco; Tebaldi, Alessandra; Goglio, Antonio; Tosi, Cristiana Passerini

    2010-01-01

    Two travelers returning to Italy from southern Egypt were hospitalized with a fever of unknown origin. Test results showed infection with Alkhurma virus. The geographic distribution of this virus could be broader than previously thought. PMID:21122237

  11. Genetic Detection and Isolation of Crimean-Congo hemorrhagic fever virus, Kosovo, Yugoslavia

    PubMed Central

    Boźović, Bojana; Pavlidou, Vassiliki; Papadimitriou, Evangelia; Pelemis, Mijomir; Antoniadis, Aantonis

    2002-01-01

    Crimean-Congo hemorrhagic fever virus (C-CHFV) strains were isolated from a fatal case and the attending physician in Kosovo, Yugoslavia. Early, rapid diagnosis of the disease was achieved by reverse transcription-polymerase chain reaction. The physician was successfully treated with oral ribavirin. These cases yielded the first genetically studied C-CHFV human isolates in the Balkans. PMID:12141973

  12. Crimean-Congo Hemorrhagic Fever Virus in Ticks from Migratory Birds, Morocco1

    PubMed Central

    Palomar, Ana M.; Portillo, Aránzazu; Santibáñez, Paula; Mazuelas, David; Arizaga, Juan; Crespo, Ariñe; Gutiérrez, Óscar; Cuadrado, Juan Francisco

    2013-01-01

    Crimean-Congo hemorrhagic fever virus was detected in ticks removed from migratory birds in Morocco. This finding demonstrates the circulation of this virus in northwestern Africa and supports the hypothesis that the virus can be introduced into Europe by infected ticks transported from Africa by migratory birds. PMID:23347801

  13. Guineafowl, ticks and Crimean-Congo hemorrhagic fever in Turkey: the perfect storm?

    PubMed

    Sekercioğlu, Cağan Hakkı

    2013-01-01

    To control ticks carrying the emerging Crimean-Congo hemorrhagic fever (CCHF) in Turkey the government is introducing thousands of exotic helmeted guineafowl (Numida meleagris). However, not only do these birds eat negligible numbers of ticks, but they are also excellent nurseries for the young of Hyalomma marginatum ticks, the best vectors of CCHF. PMID:23206535

  14. Hemorrhagic Fever with Renal Syndrome, Zibo City, China, 2006–2014

    PubMed Central

    Wang, Ling; Wang, Tao; Cui, Feng; Zhai, Shen-Yong; Zhang, Ling; Yang, Shu-Xia; Wang, Zhi-Qiang

    2016-01-01

    Analysis of hemorrhagic fever with renal syndrome cases in Zibo City, China, during 2006–2014 showed that it occurred year-round. Peaks in spring and fall/winter were caused by Hantaan and Seoul viruses, respectively. Rodent hosts were the striped field mouse for Hantaan virus and the brown rat and house mouse for Seoul virus. PMID:26812444

  15. Hemorrhagic Fever with Renal Syndrome, Zibo City, China, 2006-2014.

    PubMed

    Wang, Ling; Wang, Tao; Cui, Feng; Zhai, Shen-Yong; Zhang, Ling; Yang, Shu-Xia; Wang, Zhi-Qiang; Yu, Xue-Jie

    2016-02-01

    Analysis of hemorrhagic fever with renal syndrome cases in Zibo City, China, during 2006-2014 showed that it occurred year-round. Peaks in spring and fall/winter were caused by Hantaan and Seoul viruses, respectively. Rodent hosts were the striped field mouse for Hantaan virus and the brown rat and house mouse for Seoul virus. PMID:26812444

  16. Role of Migratory Birds in Spreading Crimean-Congo Hemorrhagic Fever, Turkey

    PubMed Central

    Eroglu, Cafer; Erciyas-Yavuz, Kiraz; Hokelek, Murat; Acici, Mustafa; Yilmaz, Hava

    2014-01-01

    We investigated migratory birds’ role in spreading Crimean-Congo hemorrhagic fever virus (CCHFV) through attached ticks. We detected CCHFV RNA in ticks on migratory birds in Turkey. Two isolates showed similarity with CCHFV genotype 4, suggesting a role for ticks in CCHFV epidemics in Turkey and spread of CCHFV by birds. PMID:25062428

  17. Viral Hemorrhagic Fever Cases in the Country of Georgia: Acute Febrile Illness Surveillance Study Results

    PubMed Central

    Kuchuloria, Tinatin; Imnadze, Paata; Chokheli, Maiko; Tsertsvadze, Tengiz; Endeladze, Marina; Mshvidobadze, Ketevan; Clark, Danielle V.; Bautista, Christian T.; Fadeel, Moustafa Abdel; Pimentel, Guillermo; House, Brent; Hepburn, Matthew J.; Wölfel, Silke; Wölfel, Roman; Rivard, Robert G.

    2014-01-01

    Minimal information is available on the incidence of Crimean–Congo hemorrhagic fever (CCHF) virus and hantavirus infections in Georgia. From 2008 to 2011, 537 patients with fever ≥ 38°C for ≥ 48 hours without a diagnosis were enrolled into a sentinel surveillance study to investigate the incidence of nine pathogens, including CCHF virus and hantavirus. Of 14 patients with a hemorrhagic fever syndrome, 3 patients tested positive for CCHF virus immunoglobulin M (IgM) antibodies. Two of the patients enrolled in the study had acute renal failure. These 2 of 537 enrolled patients were the only patients in the study positive for hantavirus IgM antibodies. These results suggest that CCHF virus and hantavirus are contributing causes of acute febrile syndromes of infectious origin in Georgia. These findings support introduction of critical diagnostic approaches and confirm the need for additional surveillance in Georgia. PMID:24891463

  18. [Emergence of dengue hemorrhagic fever in the Americas. Reemergence of dengue].

    PubMed

    Guzmán Tirado, M G; Kourí Flores, G; Bravo González, J R

    1999-01-01

    Dengue is at present the most important human arbovirosis. It is the main cause of hospitalization and death among children from southeast Asia. Two fifth of the world population live in dengue risk areas. In 1997, over 100 countries reported epidemic and more than 50,000,000 cases and 25,000 deaths were estomated. Nowadays, the Americas is passing through the same situation Asia faced years ago. In 1997, 27 countries reported cases of dengue, and in 14 of them cases of dengue hemorrhagic fever were documented. In all, 387,459 cases of classic dengue and 11,645 of dengue hemorrhagic fever were registered. During the last 2 decades dengue has increased significantly in our region with ups and downs in the annual incidence since 1981. It should be remarked that every 3 or 4 years there is a cyclic decrease and a further increase of the incidence, though it trends to rise. As regards dengue hemorrhagic fever, the situation is not more favorable. The Cuban epidemic that appeared in 1981 was completely untimely in the region. In 1989, 8 years later, the second important dengue hemorrhagic fever epidemic emerged in Venezuela, and from that moment on there has been an increasing tendency of this clinical form of the disease. The factors of the emergence and reemergence are present and rise year after year. The neoliberal policies and the consequent privatization of the health services in most of the countries allow us to watch a gloomy future in relation to the development of dengue and its severe form, the dengue hemorrhagic fever/dengue shock syndrome. PMID:10887549

  19. Viral hemorrhagic fevers of animals caused by DNA viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we outline serious diseases of food and fiber animals that cause damaging economic effect on products all over the world. The only vector-borne DNA virus is included here, such as African swine fever virus, and the herpes viruses discussed have a complex epidemiology characterized by outbreak...

  20. Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

    PubMed Central

    Rudd, Penny A.; Wilson, Jane; Gardner, Joy; Larcher, Thibaut; Babarit, Candice; Le, Thuy T.; Anraku, Itaru; Kumagai, Yutaro; Loo, Yueh-Ming; Gale, Michael; Akira, Shizuo; Khromykh, Alexander A.

    2012-01-01

    Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7−/−) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7−/− mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7−/− mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome. PMID:22761364

  1. Interferon response factors 3 and 7 protect against Chikungunya virus hemorrhagic fever and shock.

    PubMed

    Rudd, Penny A; Wilson, Jane; Gardner, Joy; Larcher, Thibaut; Babarit, Candice; Le, Thuy T; Anraku, Itaru; Kumagai, Yutaro; Loo, Yueh-Ming; Gale, Michael; Akira, Shizuo; Khromykh, Alexander A; Suhrbier, Andreas

    2012-09-01

    Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7(-/-)) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7(-/-) mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7(-/-) mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome. PMID:22761364

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

    PubMed

    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. PMID:26483375

  3. 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

    SciTech Connect

    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.

  4. First report of sylvatic DENV-2-associated dengue hemorrhagic fever in West Africa.

    PubMed

    Franco, Leticia; Palacios, Gustavo; Martinez, José Antonio; Vázquez, Ana; Savji, Nazir; De Ory, Fernando; Sanchez-Seco, María Paz; Martín, Dolores; Lipkin, W Ian; Tenorio, Antonio

    2011-08-01

    Dengue virus (DENV) circulates in human and sylvatic cycles. Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses. Although sylvatic dengue cycles occur in West African countries and Malaysia, only a few cases of mild human disease caused by sylvatic strains and one single case of dengue hemorrhagic fever in Malaysia have been reported. Here we report a case of dengue hemorrhagic fever (DHF) with thrombocytopenia (13000/µl), a raised hematocrit (32% above baseline) and mucosal bleeding in a 27-year-old male returning to Spain in November 2009 after visiting his home country Guinea Bissau. Sylvatic DENV-2 West African lineage was isolated from blood and sera. This is the first case of DHF associated with sylvatic DENV-2 in Africa and the second case worldwide of DHF caused by a sylvatic strain. PMID:21829739

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

    PubMed

    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. PMID:26512362

  6. First International External Quality Assessment of Molecular Detection of Crimean-Congo Hemorrhagic Fever Virus

    PubMed Central

    Escadafal, Camille; Ölschläger, Stephan; Avšič-Županc, Tatjana; Papa, Anna; Vanhomwegen, Jessica; Wölfel, Roman; Mirazimi, Ali; Teichmann, Anette; Donoso-Mantke, Oliver; Niedrig, Matthias

    2012-01-01

    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

  7. A Novel Rhabdovirus Associated with Acute Hemorrhagic Fever in Central Africa

    PubMed Central

    Slikas, Elizabeth; Steffen, Imke; Muyembe, Jean-Jacques; Sittler, Taylor; Veeraraghavan, Narayanan; Ruby, J. Graham; Wang, Chunlin; Makuwa, Maria; Mulembakani, Prime; Tesh, Robert B.; Mazet, Jonna; Rimoin, Anne W.; Taylor, Travis; Schneider, Bradley S.; Simmons, Graham; Delwart, Eric; Wolfe, Nathan D.; Chiu, Charles Y.; Leroy, Eric M.

    2012-01-01

    Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09×106 RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ∼140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1∶1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa. PMID:23028323

  8. Changing epidemiology of dengue hemorrhagic fever in Thailand.

    PubMed

    Chareonsook, O; Foy, H M; Teeraratkul, A; Silarug, N

    1999-02-01

    Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) are reportable diseases, the third most common causes for hospitalization of children in Thailand. Data collected from the Ministry of Public Health were analysed for trends. Rates of DHF increased in Thailand until 1987 when the largest epidemic ever, 325/100000 population, was recorded. Whereas the disease used to be confined to large cities, the rate is now higher in rural (102.2 per 100000) than urban areas (95.4 per 100000 in 1997). The age of highest incidence has increased, and the age group most severely affected is now those 5-9 years old (679/100000 in 1997). The case fatality rate has decreased with improved treatment and is now only 0.28%. PMID:10098800

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

    PubMed

    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. PMID:22482712

  10. Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome

    PubMed Central

    2013-01-01

    Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis. PMID:24305068

  11. Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome.

    PubMed

    Tsai, Jih-Jin; Chokephaibulkit, Kulkanya; Chen, Po-Chih; Liu, Li-Teh; Hsiao, Hui-Mien; Lo, Yu-Chih; Perng, Guey Chuen

    2013-01-01

    Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis. PMID:24305068

  12. Gene expression in primate liver during viral hemorrhagic fever

    PubMed Central

    Djavani, Mahmoud; Crasta, Oswald R; Zhang, Yan; Zapata, Juan Carlos; Sobral, Bruno; Lechner, Melissa G; Bryant, Joseph; Davis, Harry; Salvato, Maria S

    2009-01-01

    Background Rhesus macaques infected with lymphocytic choriomeningitis virus (LCMV) provide a model for human Lassa fever. Disease begins with flu-like symptoms and progresses rapidly with fatal consequences. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al J. Virol. 2007) showing distinct pre-viremic and viremic stages that discriminated virulent from benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. Results Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a broader effect on liver cell function than did infection with non-virulent LCMV-Armstrong. During the first few days after infection, LCMV altered expression of genes associated with energy production, including fatty acid and glucose metabolism. The transcriptome profile resembled that of an organism in starvation: mRNA for acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis was reduced while genes for enzymes in gluconeogenesis were up-regulated. Expression was also altered for genes associated with complement and coagulation cascades, and with signaling pathways involving STAT1 and TGF-β. Conclusion Most of the 4500 differentially expressed transcripts represented a general response to both virulent and mild infections. However, approximately 250 of these transcripts had significantly different expression in virulent infections as compared to mild infections, with approximately 30 of these being differentially regulated during the pre-viremic stage of infection. The genes that are expressed early and differently in mild and virulent disease are potential biomarkers for prognosis and triage of acute viral disease. PMID:19216742

  13. Serosurvey of Crimean-Congo hemorrhagic fever virus in domestic animals, Gujarat, India, 2013.

    PubMed

    Mourya, Devendra T; Yadav, Pragya D; Shete, Anita; Majumdar, Triparna D; Kanani, Amit; Kapadia, Dhirendra; Chandra, Vartika; Kachhiapatel, Anantdevesh J; Joshi, Pravinchandra T; Upadhyay, Kamalesh J; Dave, Paresh; Raval, Dinkar

    2014-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease that causes a fatal hemorrhagic illness in humans. This disease is asymptomatic in animals. CCHF was first confirmed in a nosocomial outbreak in 2011 in Gujarat State. Another notifiable outbreak occurred in July, 2013, in Karyana Village, Amreli district, Gujarat State. Anti-CCHF virus (CCHFV) immunoglobulin G (IgG) antibodies were detected in domestic animals from the adjoining villages of the affected area, indicating a considerable amount of positivity against domestic animals. The present serosurvey was carried out to determine the prevalence of CCHFV among bovine, sheep, and goat populations from 15 districts of Gujarat State, India. A total of 1226 serum samples from domestic animals were screened for IgG antibodies using a CCHF animal IgG enzyme-linked immunosorbent assay (ELISA) kit from the Centers for Disease Control and Prevention. Antibodies were detected in all the 15 districts surveyed; with positivity of 12.09%, 41.21%, and 33.62% in bovine, sheep, and goat respectively. This necessitates the surveillance of CCHFV IgG antibodies in animals and hemorrhagic fever cases in human. PMID:25229708

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

    PubMed Central

    Spengler, Jessica R.; Bergeron, Éric; Rollin, Pierre E.

    2016-01-01

    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. PMID:26741652

  15. Imaging of hemorrhagic fever with renal syndrome: a potential bioterrorism agent of military significance.

    PubMed

    Bui-Mansfield, Liem T; Cressler, Dana K

    2011-11-01

    Hemorrhagic fever with renal syndrome (HFRS) is a potentially fatal infectious disease with worldwide distribution. Its etiologic agents are viruses of the genus Hantavirus of the virus family Bunyaviridae. Hypothetical ease of production and distribution of these agents, with their propensity to incapacitate victims and overwhelm health care resources, lend themselves as significant potential biological agents of terrorism. HFRS has protean clinical manifestations, which may mimic upper respiratory tract infection, nephrolithiasis, and Hantavirus pulmonary syndrome and may delay proper treatment. Sequelae of HFRS, such as hemorrhage, acute renal failure, retroperitoneal edema, pancreatitis, pulmonary edema, and neurologic symptoms, can be detected by different imaging modalities. Medical providers caring for HFRS patients must be aware of its radiologic features, which may help to confirm its clinical diagnosis. In this article, the authors review the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and complications of HFRS. PMID:22165665

  16. Relationship between total thiol status and thrombocytopenia in patients with Crimean-Congo hemorrhagic fever.

    PubMed

    Guner, Rahmet; Tasyaran, Mehmet A; Keske, Siran; Hasanoglu, Imran; Kalem, Ayse Kaya; Yapar, Derya; Gulen, Tugba Arslan; Neselioglu, Salim; Isikoglu, Semra; Erel, Ozcan

    2012-11-01

    The objective of this study was to investigate the relationship between serum total thiol level and total oxidant status (TOS) and thrombocytopenia among patients with Crimean-Congo hemorrhagic fever (CCHF). Eighty-three subjects and 56 controls were enrolled in the study. Thiol levels were measured with the DTNB method and TOS was measured with the Erel's method among subjects and controls. Thiol levels were lower in subjects than controls and TOS levels were higher in subjects than controls. There was a significant correlation between total thiol levels and platelet counts (r = 0.84, p < 0.0001) among subjects. Further investigations are needed into the link between total thiol level and TOS and the pathogenesis of hemorrhage in CCHF. PMID:23413704

  17. Co-Circulation of Multiple Hemorrhagic Fever Diseases with Distinct Clinical Characteristics in Dandong, China

    PubMed Central

    Wang, Wen; Zhao, Yong-Xiang; Zhang, Jing-Shan; He, Jin-Rong; Li, Ming-Hui; Zhao, Xue-Hua; Liu, De-Wei; Fu, Xiao-Kang; Tian, Di; Li, Xing-Wang; Xu, Jianguo; Plyusnin, Alexander; Holmes, Edward C.; Zhang, Yong-Zhen

    2014-01-01

    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. PMID:24587107

  18. [Characterization of the natural foci of Congo-Crimean hemorrhagic fever on the territory of Ukraine].

    PubMed

    Kovalenko, I S; Khaĭtovich, A B; Kir'iakova, L S

    2006-01-01

    The natural foci of the Congo-Crimean hemorrhagic fever (CCHF) in Ukraine were characterized by their geographical factors. The circulation of CCHF virus was found to occur mainly in forest and forest-steppe zones irrespective of the location of administrative regions. The territories found to be most favorable for the prolonged existence of the focus of CCHF were those having high humidity. The possibility of using geoinformation technologies for the correction of the boundaries of natural foci, the evaluation of the influence of geographical factors on the circulation of the virus was shown. PMID:17163141

  19. Fatal outcome of coinfection of Crimean-Congo hemorrhagic fever and malaria.

    PubMed

    Christova, Iva; Petrov, Andrei; Papa, Anna; Vutchev, Dimitar; Kalvatchev, Nikolay; Vatev, Nikolay; Stoycheva, Mariana

    2015-01-01

    Here, we report a case of a Bulgarian patient with imported falciparum malaria that manifested 6 days after his arrival in Bulgaria, which was complicated by bloody diarrhea 2 days later. Blood smear revealed high parasitemia, with annular forms and gametocytes of Plasmodium falciparum. In addition, RNA of the Crimean-Congo hemorrhagic fever (CCHF) virus was detected in the blood sample by real-time reverse transcription (RT)-PCR and nested RT-PCR. The obtained sequence was found to be clustered within the Europe 1 lineage close to the other Bulgarian strains. Notably, the two infectious diseases may appear with many similar symptoms that are difficult to distinguish. PMID:25420643

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

    PubMed Central

    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

  1. Short report: Diagnostic testing for hemorrhagic fevers in Pakistan: 2007-2013.

    PubMed

    Hasan, Zahra; Atkinson, Barry; Jamil, Bushra; Samreen, Azra; Altaf, Lamia; Hewson, Roger

    2014-12-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) and dengue virus (DENV) are endemic to Pakistan. Patients presenting with symptoms of fever, bleeding, and rash cannot be distinguished without appropriate testing. We report data on 354 samples tested for CCHFV at The Aga Khan University Hospital in Pakistan between 2007 and 2013. All samples were tested for the presence of CCHFV RNA. Some samples were also tested for DENV RNA, NS-1 antigen, and/or reactive immunoglobulin M antibodies. Of 354 clinical specimens screened for CCHFV, 52 specimens were positive, with 24 cases in 2013 alone. Most cases were from Sindh and Baluchistan, which border other CCHFV-endemic regions: Iran and Afghanistan. Among CCHFV-negative samples, 168 samples were tested for DENV, and 36% of these samples were found to be DENV-positive. Rapid differentiation of CCHFV and DENV can prevent nosocomial transmission and result in time and cost savings for patients and healthcare workers. PMID:25311694

  2. Hemorrhagic Fever Occurs After Intravenous, But Not After Intragastric, Inoculation of Rhesus Macaques With Lymphocytic Choriomeningitis Virus

    PubMed Central

    Lukashevich, Igor S.; Djavani, Mahmoud; Rodas, Juan D.; Zapata, Juan C.; Usborne, Amy; Emerson, Carol; Mitchen, Jacque; Jahrling, Peter B.; Salvato, Maria S.

    2008-01-01

    Arenaviruses can cause hemorrhagic fever and death in primates and guinea pigs, but these viruses are not highly pathogenic for most rodent carriers. In the United States, arenaviruses precipitated outbreaks of hepatitis in captive monkeys, and they present an emerging health threat in the tropical areas of Africa and South America. We describe infection of rhesus macaques with the prototype arenavirus, lymphocytic choriome-ningitis virus (LCMV), using the WE strain that has been known to cause both encephalopathy and multifocal hemorrhage. Five macaques were inoculated: two by the intravenous (i.v.) and three by the intragastric (i.g.) route. Whereas the two i.v.-inoculated monkeys developed signs and lesions consistent with fatal hemorrhagic fever, the i.g.-inoculated monkeys had an attenuated infection with no disease. Pathological signs of the primate i.v. infection differ significantly from guinea pig arenavirus infections and make this a superior model for human viral hemorrhagic disease. PMID:11992578

  3. Genetic analysis and epidemiology of Crimean Congo hemorrhagic fever viruses in Baluchistan province of Pakistan

    PubMed Central

    2013-01-01

    Background Pakistan is considered as an endemic country for Crimean-Congo Hemorrhagic fever with numerous outbreaks and sporadic cases reported during the past two decades. Majority of cases are reported from Baluchistan province with subsequent transmissions to non-endemic regions mainly through infected animals directly or via infested ticks. We hereby describe the molecular investigations of CCHF cases reported during 2008 in Quetta city of Baluchistan province. Methods Serum Samples from 44 patients, with clinical signs of hemorrhagic fever attending a tertiary care hospital in Quetta city, were collected and tested for CCHF virus antigen and genomic RNA, using capture IgM EIA kit and standard RT-PCR assay, respectively. The partial S-gene fragments were directly sequenced to get information related to the prevailing CCHFV genotypes and their molecular epidemiology in Pakistan. Results Out of the total forty four, sixteen (36%) samples were found positive for CCHF IgM. Similarly, viral RNA was detected in six (16%) samples. Phylogenetic analysis revealed that all study viruses belong to genotype Asia-1 with closest similarity (99-100%) to the previously reported strains from Pakistan, Afghanistan and Iran. Conclusion We conclude that CCHF virus remains endemic within Baluchistan and its neighboring regions of Afghanistan warranting a need of incessant surveillance activities. PMID:23641865

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

    PubMed Central

    Müller, Marcel A.; Devignot, Stéphanie; Lattwein, Erik; Corman, Victor Max; Maganga, Gaël D.; Gloza-Rausch, Florian; Binger, Tabea; Vallo, Peter; Emmerich, Petra; Cottontail, Veronika M.; Tschapka, Marco; Oppong, Samuel; Drexler, Jan Felix; Weber, Friedemann; Leroy, Eric M.; Drosten, Christian

    2016-01-01

    Crimean Congo hemorrhagic fever virus (CCHFV) is a highly virulent tick-borne pathogen that causes hemorrhagic fever in humans. The geographic range of human CCHF cases largely reflects the presence of ticks. However, highly similar CCHFV lineages occur in geographically distant regions. Tick-infested migratory birds have been suggested, but not confirmed, to contribute to the dispersal. Bats have recently been shown to carry nairoviruses distinct from CCHFV. In order to assess the presence of CCHFV in a wide range of bat species over a wide geographic range, we analyzed 1,135 sera from 16 different bat species collected in Congo, Gabon, Ghana, Germany, and Panama. Using a CCHFV glycoprotein-based indirect immunofluorescence test (IIFT), we identified reactive antibodies in 10.0% (114/1,135) of tested bats, pertaining to 12/16 tested species. Depending on the species, 3.6%–42.9% of cave-dwelling bats and 0.6%–7.1% of foliage-living bats were seropositive (two-tailed t-test, p = 0.0447 cave versus foliage). 11/30 IIFT-reactive sera from 10 different African bat species had neutralizing activity in a virus-like particle assay. Neutralization of full CCHFV was confirmed in 5 of 7 sera. Widespread infection of cave-dwelling bats may indicate a role for bats in the life cycle and geographic dispersal of CCHFV. PMID:27217069

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

    PubMed

    Müller, Marcel A; Devignot, Stéphanie; Lattwein, Erik; Corman, Victor Max; Maganga, Gaël D; Gloza-Rausch, Florian; Binger, Tabea; Vallo, Peter; Emmerich, Petra; Cottontail, Veronika M; Tschapka, Marco; Oppong, Samuel; Drexler, Jan Felix; Weber, Friedemann; Leroy, Eric M; Drosten, Christian

    2016-01-01

    Crimean Congo hemorrhagic fever virus (CCHFV) is a highly virulent tick-borne pathogen that causes hemorrhagic fever in humans. The geographic range of human CCHF cases largely reflects the presence of ticks. However, highly similar CCHFV lineages occur in geographically distant regions. Tick-infested migratory birds have been suggested, but not confirmed, to contribute to the dispersal. Bats have recently been shown to carry nairoviruses distinct from CCHFV. In order to assess the presence of CCHFV in a wide range of bat species over a wide geographic range, we analyzed 1,135 sera from 16 different bat species collected in Congo, Gabon, Ghana, Germany, and Panama. Using a CCHFV glycoprotein-based indirect immunofluorescence test (IIFT), we identified reactive antibodies in 10.0% (114/1,135) of tested bats, pertaining to 12/16 tested species. Depending on the species, 3.6%-42.9% of cave-dwelling bats and 0.6%-7.1% of foliage-living bats were seropositive (two-tailed t-test, p = 0.0447 cave versus foliage). 11/30 IIFT-reactive sera from 10 different African bat species had neutralizing activity in a virus-like particle assay. Neutralization of full CCHFV was confirmed in 5 of 7 sera. Widespread infection of cave-dwelling bats may indicate a role for bats in the life cycle and geographic dispersal of CCHFV. PMID:27217069

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

    PubMed

    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. PMID:22558378

  7. Stampidine prevents mortality in an experimental mouse model of viral hemorrhagic fever caused by lassa virus

    PubMed Central

    Uckun, Fatih M; Petkevich, Alexander S; Vassilev, Alexei O; Tibbles, Heather E; Titov, Leonid

    2004-01-01

    Background The potential use of microorganisms as agents of biological warfare (BW) is a growing concern. Lassa virus, a member of the Arenavirus class of Hemorrhagic fever (HF) viruses has emerged as a worldwide concern among public health officials. The purpose of the present study was to further elucidate the antiviral activity spectrum of stampidine, a novel nucleoside analog with potent anti-viral activity against the immunodeficiency viruses HIV-1, HIV-2, and FIV, by examining its effects on survival of mice challenged with Lassa virus. Methods We examined the therapeutic effect of Stampidine in CBA mice inoculated with intracerebral injections of the Josiah strain of Lassa virus. Mice were treated either with vehicle or nontoxic doses of stampidine administered intraperitoneally 24 hours prior to, 1 hour prior to, and 24 hours, 48 hours, 72 hours, and 96 hours after virus inoculation. Results The probability of survival following the Lassa challenge was significantly improved for stampidine treated mice (Kaplan Meier, Chi-squared = 11.7, df = 2, Log-Rank p-value = 0.003). Conclusion Therefore, stampidine shows clinical potential as a new agent for treatment of viral hemorrhagic fevers caused by Lassa virus. PMID:14720304

  8. Comparative Pathogenesis of Alkhumra Hemorrhagic Fever and Kyasanur Forest Disease Viruses in a Mouse Model

    PubMed Central

    Sawatsky, Bevan; McAuley, Alexander J.; Holbrook, Michael R.; Bente, Dennis A.

    2014-01-01

    Kyasanur Forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (AHFV) are genetically closely-related, tick-borne flaviviruses that cause severe, often fatal disease in humans. Flaviviruses in the tick-borne encephalitis (TBE) complex typically cause neurological disease in humans whereas patients infected with KFDV and AHFV predominately present with hemorrhagic fever. A small animal model for KFDV and AHFV to study the pathogenesis and evaluate countermeasures has been lacking mostly due to the need of a high biocontainment laboratory to work with the viruses. To evaluate the utility of an existing mouse model for tick-borne flavivirus pathogenesis, we performed serial sacrifice studies in BALB/c mice infected with either KFDV strain P9605 or AHFV strain Zaki-1. Strikingly, infection with KFDV was completely lethal in mice, while AHFV caused no clinical signs of disease and no animals succumbed to infection. KFDV and high levels of pro-inflammatory cytokines were detected in the brain at later time points, but no virus was found in visceral organs; conversely, AHFV Zaki-1 and elevated levels of cytokines were found in the visceral organs at earlier time points, but were not detected in the brain. While infection with either virus caused a generalized leukopenia, only AHFV Zaki-1 induced hematologic abnormalities in infected animals. Our data suggest that KFDV P9605 may have lost its ability to cause hemorrhagic disease as the result of multiple passages in suckling mouse brains. However, likely by virtue of fewer mouse passages, AHFV Zaki-1 has retained the ability to replicate in visceral organs, cause hematologic abnormalities, and induce pro-inflammatory cytokines without causing overt disease. Given these striking differences, the use of inbred mice and the virus passage history need to be carefully considered in the interpretation of animal studies using these viruses. PMID:24922308

  9. Divergent Simian Arteriviruses Cause Simian Hemorrhagic Fever of Differing Severities in Macaques

    PubMed Central

    Moncla, Louise H.; Weiler, Andrea M.; Charlier, Olivia; Rojas, Oscar; Byrum, Russell; Ragland, Dan R.; Cohen, Melanie; Sanford, Hannah B.; Qin, Jing

    2016-01-01

    ABSTRACT Simian hemorrhagic fever (SHF) is a highly lethal disease in captive macaques. Three distinct arteriviruses are known etiological agents of past SHF epizootics, but only one, simian hemorrhagic fever virus (SHFV), has been isolated in cell culture. The natural reservoir(s) of the three viruses have yet to be identified, but African nonhuman primates are suspected. Eleven additional divergent simian arteriviruses have been detected recently in diverse and apparently healthy African cercopithecid monkeys. Here, we report the successful isolation in MARC-145 cell culture of one of these viruses, Kibale red colobus virus 1 (KRCV-1), from serum of a naturally infected red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) sampled in Kibale National Park, Uganda. Intramuscular (i.m.) injection of KRCV-1 into four cynomolgus macaques (Macaca fascicularis) resulted in a self-limiting nonlethal disease characterized by depressive behavioral changes, disturbance in coagulation parameters, and liver enzyme elevations. In contrast, i.m. injection of SHFV resulted in typical lethal SHF characterized by mild fever, lethargy, lymphoid depletion, lymphoid and hepatocellular necrosis, low platelet counts, increased liver enzyme concentrations, coagulation abnormalities, and increasing viral loads. As hypothesized based on the genetic and presumed antigenic distance between KRCV-1 and SHFV, all four macaques that had survived KRCV-1 injection died of SHF after subsequent SHFV injection, indicating a lack of protective heterotypic immunity. Our data indicate that SHF is a disease of macaques that in all likelihood can be caused by a number of distinct simian arteriviruses, although with different severity depending on the specific arterivirus involved. Consequently, we recommend that current screening procedures for SHFV in primate-holding facilities be modified to detect all known simian arteriviruses. PMID:26908578

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

    PubMed Central

    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

  11. Cross-sectional Serosurvey of Crimean-Congo Hemorrhagic Fever Virus IgG in Livestock, India, 2013-2014.

    PubMed

    Mourya, Devendra T; Yadav, Pragya D; Shete, Anita M; Sathe, Padmakar S; Sarkale, Prasad C; Pattnaik, Bramhadev; Sharma, Gaurav; Upadhyay, Kamlesh J; Gosavi, Surekha; Patil, Deepak Y; Chaubal, Gouri Y; Majumdar, Triparna D; Katoch, Vishwa M

    2015-10-01

    We conducted a cross-sectional serosurvey of Crimean-Congo hemorrhagic fever (CCHF) among livestock in 22 states and 1 union territory of India. A total of 5,636 samples from bovines, sheep, and goats were screened for CCHF virus IgG. IgG was detected in 354 samples, indicating that this virus is widespread in this country. PMID:26402332

  12. Cross-sectional Serosurvey of Crimean-Congo Hemorrhagic Fever Virus IgG in Livestock, India, 2013–2014

    PubMed Central

    Yadav, Pragya D.; Shete, Anita M.; Sathe, Padmakar S.; Sarkale, Prasad C.; Pattnaik, Bramhadev; Sharma, Gaurav; Upadhyay, Kamlesh J.; Gosavi, Surekha; Patil, Deepak Y.; Chaubal, Gouri Y.; Majumdar, Triparna D.; Katoch, Vishwa M.

    2015-01-01

    We conducted a cross-sectional serosurvey of Crimean-Congo hemorrhagic fever (CCHF) among livestock in 22 states and 1 union territory of India. A total of 5,636 samples from bovines, sheep, and goats were screened for CCHF virus IgG. IgG was detected in 354 samples, indicating that this virus is widespread in this country. PMID:26402332

  13. Notes from the field: Increase in reported Crimean-Congo hemorrhagic fever cases--country of Georgia, 2014.

    PubMed

    Mamuchishvili, Nana; Salyer, Stephanie J; Stauffer, Kendra; Geleishvili, Marika; Zakhashvili, Khatuna; Morgan, Juliette

    2015-03-01

    During January-September 2014, Georgia's National Centers for Disease Control and Public Health (NCDC) detected 22 cases of Crimean-Congo hemorrhagic fever (CCHF) in the country. CCHF is caused by infection with a tickborne virus of the Bunyaviridae family. Transmission occurs from the bite of an infected tick or from crushing an infected tick with bare skin. Secondary transmission can result from contact with blood or tissues of infected animals and humans. CCHF initially manifests as a nonspecific febrile illness that progresses to a hemorrhagic phase, marked by rapidly developing symptoms leading to multiorgan failure, shock, and death in severe cases. The clinical severity, transmissibility, and infectiousness of CCHF are responsible for its categorization as a viral hemorrhagic fever high-priority bioterrorism agent. PMID:25742385

  14. Characteristics and Risk Factors for Fatality in Patients with Dengue Hemorrhagic Fever, Taiwan, 2014.

    PubMed

    Wei, Hsin-Yi; Shu, Pei-Yun; Hung, Min-Nan

    2016-08-01

    An unprecedented dengue outbreak involving more than 15,000 infections, including 136 dengue hemorrhagic fever (DHF) cases and 20 fatalities, occurred in Taiwan in 2014. The median age of the DHF cases was 71 years (range: 4-92 years) and most of them (N = 100, 73.5%) had comorbidities, of which the majority were hypertension (56%) and diabetes mellitus (DM; 27%). Only approximately half of the DHF cases (59/136) were classified as severe dengue, based on the 2009 WHO-revised dengue classification. The fatality rate for this DHF outbreak was 14.7%. DM (odds ratio [OR] = 3.60, 95% confidence interval [CI] = 1.22-10.63) and presentation with severe plasma leakage (OR = 6.42, 95% CI = 1.76-23.63) were independent risk factors for fatality. PMID:27273649

  15. Analysis of the Spatiotemporal Characteristics of Hemorrhagic Fever with Renal Syndrome in Hubei Province, China

    NASA Astrophysics Data System (ADS)

    Fan, H.; Ge, L.; Song, L.; Zhao, Q.

    2015-07-01

    Hemorrhagic fever with renal syndrome(HFRS) is a worldwide fulminant infectious disease. Since the first HFRS cases in Hubei Province were reported in 1957, the disease has spread across the province and Hubei has become one of seriously affected areas in China. However, the epidemic characteristics of HFRS are still not entirely clear. Therefore, a systematic investigation of spatial and temporal distribution pattern of HFRS system is needed. In order to facilitate better prevention and control of HFRS in Hubei Province, in this paper, a GIS spatiotemporal analysis and modeling tool was developed to analyze the spatiotemporal dynamics of the HFRS epidemic, as well as providinga comprehensive examination the dynamic pattern of HFRS in Hubei over the past 30 years (1980-2009), to determine spatiotemporal change trends and the causes of HFRS. This paper describes the experiments and their results.

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

    PubMed Central

    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 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. PMID:26812146

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

    PubMed

    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. PMID

  18. Bayesian Phylogeography of Crimean-Congo Hemorrhagic Fever Virus in Europe

    PubMed Central

    Zehender, Gianguglielmo; Ebranati, Erika; Shkjezi, Renata; Papa, Anna; Luzzago, Camilla; Gabanelli, Elena; Lo Presti, Alessandra; Lai, Alessia; Rezza, Giovanni; Galli, Massimo; Bino, Silvia; Ciccozzi, Massimo

    2013-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a zoonosis mainly transmitted by ticks that causes severe hemorrhagic fever and has a mortality rate of 5-60%. The first outbreak of CCHF occurred in the Crimean peninsula in 1944-45 and it has recently emerged in the Balkans and eastern Mediterranean. In order to reconstruct the origin and pathway of the worldwide dispersion of the virus at global and regional (eastern European) level, we investigated the phylogeography of the infection by analysing 121 publicly available CCHFV S gene sequences including two recently characterised Albanian isolates. The spatial and temporal phylogeny was reconstructed using a Bayesian Markov chain Monte Carlo approach, which estimated a mean evolutionary rate of 2.96 x 10-4 (95%HPD=1.6 and 4.7 x 10-4) substitutions/site/year for the analysed fragment. All of the isolates segregated into seven highly significant clades that correspond to the known geographical clades: in particular the two new isolates from northern Albania clustered significantly within the Europe 1 clade. Our phylogeographical reconstruction suggests that the global CCHFV clades originated about one thousand years ago from a common ancestor probably located in Africa. The virus then spread to Asia in the XV century and entered Europe on at least two occasions: the first in the early 1800s, when a still circulating but less or non-pathogenic virus emerged in Greece and Turkey, and the second in the early 1900s, when a pathogenic CCHFV strain began to spread in eastern Europe. The most probable location for the origin of this European clade 1 was Russia, but Turkey played a central role in spreading the virus throughout Europe. Given the close proximity of the infected areas, our data suggest that the movement of wild and domestic ungulates from endemic areas was probably the main cause of the dissemination of the virus in eastern Europe. PMID:24223988

  19. Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population, livestock and ticks in Kosovo.

    PubMed

    Fajs, Luka; Humolli, Isme; Saksida, Ana; Knap, Nataša; Jelovšek, Mateja; Korva, Miša; Dedushaj, Isuf; Avšič-Županc, Tatjana

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is an acute, tick borne disease often associated with hemorrhagic presentations and high case fatality rate. Kosovo is a highly endemic area for CCHF, with a significant case fatality rate. The aim of our study was to determine the prevalence of CCHF in Kosovo. We tested 1105 serum samples from healthy population in both endemic and non-endemic areas in the country. Our results revealed a seroprevalence of 4.0% (range 0-9.3%) which is comparable to the seroprevalence in other countries. We show that seroprevalence is correlated to the disease incidence in each studied municipality. We also tested 401 animal sera (353 cow, 30 sheep, 10 goat and 8 chicken) in four endemic municipalities in Kosovo. We detected specific antibodies in all animals except in chicken. Seroprevalence in cows is comparable to other endemic areas and correlates to the seroprevalence in humans. No CCHF RNA could be detected in 105 tick samples obtained in 2012 and 2013. Sequencing of CCHFV positive ticks from 2001 revealed that the virus is most closely related to viral strains that were detected in CCHF patients from Kosovo. Results suggest that mild CCHF cases are most probably underdiagnosed and consequently that the burden of disease is higher than reported. Our study provides key information for CCHF surveillance and raises awareness for possible imported cases in CCHF non-endemic countries. PMID:25393542

  20. Knowledge Levels Regarding Crimean-Congo Hemorrhagic Fever Among Emergency Healthcare Workers in an Endemic Region

    PubMed Central

    Yolcu, Sadiye; Kader, Cigdem; Kayipmaz, Afsin Emre; Ozbay, Sedat; Erbay, Ayse

    2014-01-01

    Background In this study, we aimed to determine knowledge levels regarding Crimean-Congo hemorrhagic fever (CCHF) among emergency healthcare workers (HCWs) in an endemic region. Methods A questionnaire form consisting of questions about CCHF was applied to the participants. Results The mean age was 29.6 ± 6.5 years (range 19 - 45). Fifty-four (49.5%) participants were physicians, 39 (35.8%) were nurses and 16 (14.7%) were paramedics. All of the participants were aware of CCHF, and 48 (44%) of them had previously followed CCHF patients. Rates of the use of protective equipment (masks and gloves) during interventions for patients who were admitted to the emergency service with active hemorrhage were 100% among paramedics, 76.9% among nurses and 61.1% among physicians (P = 0.003). Among 86 (78.9%) HCWs who believed that their knowledge regarding CCHF was adequate, 62 (56.9%) declared that they would prefer not to care for patients with CCHF (P = 0.608). Conclusions The use of techniques to prevent transmission of this disease, including gloves, face masks, face visors and box coats, should be explained to emergency room HCWs, and encouragement should be provided for using these techniques. PMID:24734146

  1. Prevalence of Crimean-Congo Hemorrhagic Fever Virus in Healthy Population, Livestock and Ticks in Kosovo

    PubMed Central

    Fajs, Luka; Humolli, Isme; Saksida, Ana; Knap, Nataša; Jelovšek, Mateja; Korva, Miša; Dedushaj, Isuf; Avšič-Županc, Tatjana

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is an acute, tick borne disease often associated with hemorrhagic presentations and high case fatality rate. Kosovo is a highly endemic area for CCHF, with a significant case fatality rate. The aim of our study was to determine the prevalence of CCHF in Kosovo. We tested 1105 serum samples from healthy population in both endemic and non-endemic areas in the country. Our results revealed a seroprevalence of 4.0% (range 0–9.3%) which is comparable to the seroprevalence in other countries. We show that seroprevalence is correlated to the disease incidence in each studied municipality. We also tested 401 animal sera (353 cow, 30 sheep, 10 goat and 8 chicken) in four endemic municipalities in Kosovo. We detected specific antibodies in all animals except in chicken. Seroprevalence in cows is comparable to other endemic areas and correlates to the seroprevalence in humans. No CCHF RNA could be detected in 105 tick samples obtained in 2012 and 2013. Sequencing of CCHFV positive ticks from 2001 revealed that the virus is most closely related to viral strains that were detected in CCHF patients from Kosovo. Results suggest that mild CCHF cases are most probably underdiagnosed and consequently that the burden of disease is higher than reported. Our study provides key information for CCHF surveillance and raises awareness for possible imported cases in CCHF non-endemic countries. PMID:25393542

  2. Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever

    PubMed Central

    Guler, Nil; Eroglu, Cafer; Yilmaz, Hava; Karadag, Adil; Alacam, Hasan; Sunbul, Mustafa; Fletcher, Tom E.; Leblebicioglu, Hakan

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended. PMID:27304063

  3. Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever.

    PubMed

    Guler, Nil; Eroglu, Cafer; Yilmaz, Hava; Karadag, Adil; Alacam, Hasan; Sunbul, Mustafa; Fletcher, Tom E; Leblebicioglu, Hakan

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended. PMID:27304063

  4. Dengue hemorrhagic fever in infants: a study of clinical and cytokine profiles.

    PubMed

    Nguyen, Thanh Hung; Lei, Huan-Yao; Nguyen, Trong Lan; Lin, Yee-Shin; Huang, Kao-Jean; Le, Bich Lien; Lin, Chiou-Feng; Yeh, Trai-Ming; Do, Quang Ha; Vu, Thi Que Huong; Chen, Lien-Cheng; Huang, Jyh-Hsiung; Lam, Thi My; Liu, Ching-Chuan; Halstead, Scott B

    2004-01-15

    A prospective study of clinical and cytokine profiles of 107 infants with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) was conducted. Fever, petechiae on the skin, and hepatomegaly were the most common clinical findings associated with DHF/DSS in infants. DSS occurred in 20.5% of the patients. Hemoconcentration and thrombocytopenia were observed in 91.5% and 92.5% of the patients, respectively. Serologic testing revealed that almost all of the patients (95.3%) had primary dengue virus infections. These data demonstrate that clinical and laboratory findings of DHF/DSS in infants are compatible with the World Health Organization's clinical diagnostic criteria for pediatric DHF. The present study is the first to report evidence of production of cytokines in infants with DHF/DSS and to describe the difference between the cytokine profile of infants with primary dengue virus infections and children with secondary infections. Overproduction of both proinflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) and anti-inflammatory cytokines (interleukin-10 and -6) may play a role in the pathogenesis of DHF/DSS in infants. PMID:14722886

  5. Mitogen therapy for biological warfare/terrorist attacks and viral hemorrhagic fever control.

    PubMed

    Wimer, Bruce M

    2002-02-01

    Ken Alibek was for 17 years a leader in Biopreparat, the Soviet Union's top secret agency involved in developing and stockpiling the most lethal bacteria, viruses, and toxins in the history of mankind before he defected with his family to the United States in 1992. Very contrite when he discovered he had been misled to believe that his efforts had been essential to the survival of his homeland, Alibek has become active sounding an alarm about, among other things, thousands of unemployed Russian scientists who have been seeking survival by selling their destructive expertise to rouge states and bioterrorists. Working full time in devising protective measures that might help control the damaging effects of terrorist attacks, Alibek has placed strong emphasis on stimulating nonspecific immunities of victims mainly with interleukins and other cytokines. A more productive alternative would be giving mitogens such as PHA and PWM to reinforce vaccine and antibiotic actions, at the same time stimulating protective immune, myelopoietic, and lymphopoietic responses. A key objective would be to find an effective management for the dreaded viral hemorrhagic fevers. Using Ebola infection as an experimental model, Yang et al. have shown that PHA can block both the viral secretions that inhibit neutrophil immune responses and the viral transmembrane glycoprotein that facilitates damage of the human endothelial cells responsible for the lethal hemorrhagic manifestations. Normal serum glycoproteins have in the past been clearly shown to inhibit the functions of PHA, thereby increasing dosage requirements. Extrapolation of this interaction with serum glycoproteins suggests that PHA given intravenously in adequate dosage should readily be able to block the deleterious Ebola virus glycoprotein effects. Data in an extensive classification of the hemorrhagic fever viruses recently presented by Barry make it possible to predict that mitogen therapy should be effective for virtually all

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

    PubMed

    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. PMID:25898993

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

    PubMed Central

    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

  8. Hospital-Based Surveillance for Viral Hemorrhagic Fevers and Hepatitides in Ghana

    PubMed Central

    Bonney, Joseph Humphrey Kofi; Osei-Kwasi, Mubarak; Adiku, Theophilus Korku; Barnor, Jacob Samson; Amesiya, Robert; Kubio, Chrysantus; Ahadzie, Lawson; Ölschläger, Stephan; Lelke, Michaela; Becker-Ziaja, Beate; Pahlmann, Meike; Günther, Stephan

    2013-01-01

    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. PMID:24069490

  9. [The Alkhurma virus (family Flaviviridae, genus Flavivirus): an emerging pathogen responsible for hemorrhage fever in the Middle East].

    PubMed

    Charrel, R N; de Lamballerie, X

    2003-01-01

    To date tick-borne flaviviruses causing hemorrhagic fevers in humans have been isolated in Siberia (Omsk hemorrhagic fever virus), India (Kyasanur Forest disease virus), and Saudi Arabia (Akhurma virus). Because of their potential use as biological weapons for bioterrorism, these 3 viruses require level 4 biosafety handling facilities and have been listed as hypervirulent pathogens by the Center for Disease Control and Prevention. Alkhurma virus was isolated in 1995 from patients with hemorrhagic fever in Saudi Arabia. Current evidence suggests that transmission to humans can occur either transcutaneously either by contamination of a skin wound with the blood of an infected vertebrate or bites of an infected tick or orally by drinking unpasteurized contaminated milk. To date a total of 24 symptomatic human cases have been recorded with a mortality rate at 25% (6/24). Pauci-symptomatic or asymptomatic cases are likely but epidemiologic data are currently unavailable. The complete coding sequence of the prototype strain of Alkhurma virus was determined and published in 2001 based on international research project involving investigators from France, Great Britain, and Saudi Arabia. Phylogenetic studies demonstrate that closest known relative of Alkhurma virus is Kyasanur Forest disease virus and that both viruses share a common ancestor. Genetic analysis of several human strains sequentially isolated over a 5-year period showed a very low diversity. This finding has important potential implications for diagnosis and vaccination. PMID:14579470

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

    PubMed

    Kara, Soner S; Kara, Duygu; Fettah, Ali

    2016-01-01

    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 in the study. Both infectious causes, such as

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

    PubMed

    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. PMID:26183413

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

    PubMed

    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. PMID:26085471

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

    SciTech Connect

    Abraham, Jonathan; Corbett, Kevin D.; Farzan, Michael; Choe, Hyeryun; Harrison, Stephen C.

    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.

  14. Spatiotemporal Heterogeneity Analysis of Hemorrhagic Fever with Renal Syndrome in China Using Geographically Weighted Regression Models

    PubMed Central

    Li, Shujuan; Ren, Hongyan; Hu, Wensheng; Lu, Liang; Xu, Xinliang; Zhuang, Dafang; Liu, Qiyong

    2014-01-01

    Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in China. The identification of the spatiotemporal pattern of HFRS will provide a foundation for the effective control of the disease. Based on the incidence of HFRS, as well as environmental factors, and social-economic factors of China from 2005–2012, this paper identified the spatiotemporal characteristics of HFRS distribution and the factors that impact this distribution. The results indicate that the spatial distribution of HFRS had a significant, positive spatial correlation. The spatiotemporal heterogeneity was affected by the temperature, precipitation, humidity, NDVI of January, NDVI of August for the previous year, land use, and elevation in 2005–2009. However, these factors did not explain the spatiotemporal heterogeneity of HFRS incidences in 2010–2012. Spatiotemporal heterogeneity of provincial HFRS incidences and its relation to environmental factors would provide valuable information for hygiene authorities to design and implement effective measures for the prevention and control of HFRS in China. PMID:25429681

  15. A New Transferrin Receptor Aptamer Inhibits New World Hemorrhagic Fever Mammarenavirus Entry.

    PubMed

    Maier, Keith E; Jangra, Rohit K; Shieh, Kevin R; Cureton, David K; Xiao, Hui; Snapp, Erik L; Whelan, Sean P; Chandran, Kartik; Levy, Matthew

    2016-01-01

    Pathogenic New World hemorrhagic fever mammarenaviruses (NWM) utilize Glycoprotein 1 (GP1) to target the apical domain of the human transferrin receptor (hTfR) for facilitating cell entry. However, the conservation between their GP1s is low. Considering this and the slow evolutionary progression of mammals compared to viruses, therapeutic targeting of hTfR provides an attractive avenue for cross-strain inhibition and diminishing the likelihood of escape mutants. Aptamers present unique advantages for the development of inhibitors to vial entry, including ease of synthesis, lack of immunogenicity, and potentially cold-chain breaking solutions to diseases endemic to South America. Here, recognizing that in vivo competition with the natural ligand, transferrin (Tf), likely drove the evolution of GP1 to recognize the apical domain, we performed competitive in vitro selections against hTfR-expressing cells with supplemented Tf. The resultant minimized aptamer, Waz, binds the apical domain of the receptor and inhibits infection of human cells by recombinant NWM in culture (EC50 ~400 nmol/l). Aptamer multimerization further enhanced inhibition >10-fold (EC50 ~30 nmol/l). Together, our results highlight the ability to use a competitor to bias the outcome of a selection and demonstrate how avidity effects can be leveraged to enhance both aptamer binding and the potency of viral inhibition. PMID:27219515

  16. Sero-epidemiological survey of Crimean-Congo hemorrhagic fever virus in Tunisia

    PubMed Central

    Wasfi, Fares; Dowall, Stuart; Ghabbari, Tayssir; Bosworth, Andrew; Chakroun, Mohamed; Varghese, Anitha; Tiouiri, Hanene; Ben Jemaa, Mounir; Znazen, Abir; Hewson, Roger; Zhioua, Elyes; Letaief, Amel

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease associated with a high case fatality rate and transmitted mainly by Hyalomma marginatum. The geographical distribution of H. marginatum covers most of the Western Mediterranean basin. We aimed to investigate whether CCHF virus (CCHFv) is circulating in Tunisia. Samples from unexplained acute febrile patients (n = 181) and a high risk group of humans, mainly slaughter workers (n = 38), were collected in the summer of 2014 and analyzed for exposure to CCHFv using serological tests and real-time RT-PCR. Ticks were collected from Northern and Southern Tunisia during May–June 2014 and examined for the presence of CCHFv by real-time RT-PCR. Of the 181 febrile patients, 5 showed only high titers of IgM suggesting a recent exposure to CCHFv. Among 38 slaughter workers, 2 had IgG anti-CCHFv responses yielding a seroprevalence of 5.2%. No CCHFv was detected in ticks and sera. Our results provide evidence of human exposure to CCHFv in Tunisia. PMID:26956221

  17. Molecular Diagnosis of Hemorrhagic Fever with Renal Syndrome Caused by Puumala Virus

    PubMed Central

    Lagerqvist, Nina; Hagström, Åsa; Lundahl, Malin; Nilsson, Elin; Juremalm, Mikael; Larsson, Inger; Alm, Erik; Bucht, Göran; Ahlm, Clas

    2016-01-01

    Rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus pulmonary syndrome (HPS; also called hantavirus cardiopulmonary syndrome [HCPS]) in the Americas. Puumala virus (PUUV) is the most common causative agent of HFRS in Europe. Current routine diagnostic methods are based on serological analyses and can yield inconclusive results. Hantavirus-infected patients are viremic during the early phase of disease; therefore, detection of viral RNA genomes can be a valuable complement to existing serological methods. However, the high genomic sequence diversity of PUUV has hampered the development of molecular diagnostics, and currently no real-time reverse transcription-quantitative (RT)-PCR assay is available for routine diagnosis of HFRS. Here, we present a novel PUUV RT-PCR assay. The assay was validated for routine diagnosis of HFRS on samples collected in Sweden during the winter season from 2013 to 2014. The assay allowed detection of PUUV RNA in 98.7% of confirmed clinical HFRS samples collected within 8 days after symptomatic onset. In summary, this study shows that real-time RT-PCR can be a reliable alternative to serological tests during the early phase of HFRS. PMID:26962084

  18. Molecular Diagnosis of Hemorrhagic Fever with Renal Syndrome Caused by Puumala Virus.

    PubMed

    Lagerqvist, Nina; Hagström, Åsa; Lundahl, Malin; Nilsson, Elin; Juremalm, Mikael; Larsson, Inger; Alm, Erik; Bucht, Göran; Ahlm, Clas; Klingström, Jonas

    2016-05-01

    Rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus pulmonary syndrome (HPS; also called hantavirus cardiopulmonary syndrome [HCPS]) in the Americas. Puumala virus (PUUV) is the most common causative agent of HFRS in Europe. Current routine diagnostic methods are based on serological analyses and can yield inconclusive results. Hantavirus-infected patients are viremic during the early phase of disease; therefore, detection of viral RNA genomes can be a valuable complement to existing serological methods. However, the high genomic sequence diversity of PUUV has hampered the development of molecular diagnostics, and currently no real-time reverse transcription-quantitative (RT)-PCR assay is available for routine diagnosis of HFRS. Here, we present a novel PUUV RT-PCR assay. The assay was validated for routine diagnosis of HFRS on samples collected in Sweden during the winter season from 2013 to 2014. The assay allowed detection of PUUV RNA in 98.7% of confirmed clinical HFRS samples collected within 8 days after symptomatic onset. In summary, this study shows that real-time RT-PCR can be a reliable alternative to serological tests during the early phase of HFRS. PMID:26962084

  19. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

    PubMed Central

    Shao, Junjie; Liang, Yuying; Ly, Hinh

    2015-01-01

    Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV) to highly virulent hemorrhagic fever (HF) causing viruses such as Lassa (LASV), Junin (JUNV), Machupo (MACV), Lujo (LUJV), Sabia (SABV), Guanarito (GTOV), and Chapare (CHPV), for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens. PMID:26011826

  20. Hemorrhagic Fever with Renal Syndrome Caused by 2 Lineages of Dobrava Hantavirus, Russia1

    PubMed Central

    Klempa, Boris; Tkachenko, Evgeniy A.; Dzagurova, Tamara K.; Yunicheva, Yulia V.; Morozov, Vyacheslav G.; Okulova, Natalia M.; Slyusareva, Galina P.; Smirnov, Aleksey

    2008-01-01

    Dobrava-Belgrade virus (DOBV) is a European hantavirus that causes hemorrhagic fever with renal syndrome (HFRS); case-fatality rates in Balkan countries are as high as 12%. To determine causative agents, we examined 126 cases of DOBV-associated HFRS in central and southern European Russia. In central Russia (Lipetsk, Voronezh, Orel regions), outbreaks were caused by a DOBV variant (DOBV-Aa) carried by Apodemus agrarius. In southern Russia (Sochi district), where HFRS is endemic, HFRS cases were caused by a new DOBV variant (DOBV-Ap), found in A. ponticus, a novel hantavirus natural host. Both viruses, DOBV-Aa/Lipetsk and DOBV-Ap/Sochi, were isolated through Vero E6 cells, genetically characterized, and used for serotyping of the HFRS patients’ serum. The clinical severity of HFRS caused by DOBV-Aa resembles that of HFRS caused by Puumala virus (mild to moderate); clinical severity of disease caused by DOBV-Ap infections is more often moderate to severe. PMID:18394280

  1. Hemorrhagic fever with renal syndrome caused by 2 lineages of Dobrava hantavirus, Russia.

    PubMed

    Klempa, Boris; Tkachenko, Evgeniy A; Dzagurova, Tamara K; Yunicheva, Yulia V; Morozov, Vyacheslav G; Okulova, Natalia M; Slyusareva, Galina P; Smirnov, Aleksey; Kruger, Detlev H

    2008-04-01

    Dobrava-Belgrade virus (DOBV) is a European hantavirus that causes hemorrhagic fever with renal syndrome (HFRS); case-fatality rates in Balkan countries are as high as 12%. To determine causative agents, we examined 126 cases of DOBV-associated HFRS in central and southern European Russia. In central Russia (Lipetsk, Voronezh, Orel regions), outbreaks were caused by a DOBV variant (DOBV-Aa) carried by Apodemus agrarius. In southern Russia (Sochi district), where HFRS is endemic, HFRS cases were caused by a new DOBV variant (DOBV-Ap), found in A. ponticus, a novel hantavirus natural host. Both viruses, DOBV-Aa/Lipetsk and DOBV-Ap/Sochi, were isolated through Vero E6 cells, genetically characterized, and used for serotyping of the HFRS patients' serum. The clinical severity of HFRS caused by DOBV-Aa resembles that of HFRS caused by Puumala virus (mild to moderate); clinical severity of disease caused by DOBV-Ap infections is more often moderate to severe. PMID:18394280

  2. The climatic factors influencing the occurrence of dengue hemorrhagic fever in Thailand.

    PubMed

    Thammapalo, Suwich; Chongsuwiwatwong, Virasakdi; McNeil, Don; Geater, Alan

    2005-01-01

    The aim of this study was to determine the independent effects of climatic factors: rainfall, temperature and relative humidity, on the occurrence of dengue hemorrhagic fever (DHF) in Thailand after adjustment for cyclical pattern. Data regarding monthly DHF reported cases by province, monthly rainfall, rain-days, average daily maximum temperature, average daily minimum temperature and average relative humidity, and mid-year province population from 1978 to 1997 (240 months) in 73 provinces were collected from various governmental departments. The general equation: Incidence of DHF = constant + trends + cyclic effects + climatic factors + noise was used as the statistical model. Out of 73 provinces examined, an increase in temperature was associated with a rise in the incidence of DHF in 9 provinces, whereas increased rainfall was associated with a decreased incidence of DHF in 7 provinces. Analysis by region shows that DHF incidence was negatively associated with extra rainfall in the southern region, but was positively associated with elevated temperatures in the central and northern regions. Variability in incidence was explained mostly (14.7% to 75.3%) by trend and cyclic change and much less (0.2% to 3.6%) by independent climatic factors. PMID:15906666

  3. Dengue hemorrhagic fever epidemiology in Thailand: description and forecasting of epidemics.

    PubMed

    Barbazan, Philippe; Yoksan, Sutee; Gonzalez, Jean-Paul

    2002-06-01

    Despite the use of a variety of control strategies, dengue hemorrhagic fever (DHF) control is a major and permanent challenge for public health services in Thailand and in Southeast Asia. In order to improve the efficiency of DHF control in Thailand, these activities have to concentrate on areas and populations at higher risk, which implies early identification of higher incidence periods. A retrospective study of spatial and temporal variations of DHF incidence in all 73 provinces of Thailand (1983-1995) allowed discrimination between seasonal (endemic) transmission dependent on climatic variations and vector density and non-seasonal (epidemic) transmission, mainly due to the occurrence of a new virus serotype in a population with low immunity. To identify epidemic months, which appear significantly clustered, a significant deviation from the monthly average incidence was defined. The occurrence of two consecutive epidemic months in a given area has a high probability (P = 0.66) of being followed by a cluster of 2-18 epidemic months (average: 7.7 months). This observation is proposed as a warning of epidemic outbreak enabling an early launch of control activities. As an example, when this method is retrospectively applied to the studied period, 11,388 province months (73 provinces x 156 months), 579 epidemic outbreaks (5.1% of the total) are identified. Control activities can thus be improved through early management and prevention of the 308,636 supplementary cases occurring during epidemics (37.0% of the total recorded). PMID:12067829

  4. Possible drivers of Crimean-Congo hemorrhagic fever virus transmission in Kosova.

    PubMed

    Jameson, Lisa J; Ramadani, Naser; Medlock, Jolyon M

    2012-09-01

    Crimean-Congo hemorrhagic fever (CCHF) has long been a disease of concern in Kosova; however, little is known about the enzootic cycles of the virus in this country. Since the first documented case in 1954, sporadic cases and occasional outbreaks have been recorded with cases more consistently reported following the conflict in 1999. CCHF virus exists in enzootic cycles between wild animal species and ticks. The infection rates within ticks and hence the exposure to humans is determined by both the biology and seasonal dynamics of ticks, and the population dynamics and structure of the wild animals. These, in turn, are affected by complex interactions between climatic variables, changes in agricultural practices, land management, and wild animal density. If we are to understand the spatial and temporal occurrence of human disease, we must understand the ecology of the virus in nature. This article discusses the possible ecological, societal, political, and economic drivers that may impact the enzootic cycle of the virus and contribute to an increase in virus amplification and/or human exposure to infected ticks in Kosova. PMID:22217174

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

    PubMed

    Fajs, Luka; Jakupi, Xhevat; Ahmeti, Salih; Humolli, Isme; Dedushaj, Isuf; Avšič-Županc, Tatjana

    2014-01-01

    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. PMID:24416468

  6. Molecular Epidemiology of Crimean-Congo Hemorrhagic Fever Virus in Kosovo

    PubMed Central

    Fajs, Luka; Jakupi, Xhevat; Ahmeti, Salih; Humolli, Isme; Dedushaj, Isuf; Avšič-Županc, Tatjana

    2014-01-01

    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. PMID:24416468

  7. Community-based approach for prevention and control of dengue hemorrhagic fever in Kanchanaburi Province, Thailand.

    PubMed

    Therawiwat, Manirat; Fungladda, Wijitr; Kaewkungwal, Jaranit; Imamee, Nirat; Steckler, Allan

    2005-11-01

    An action research design was conducted in two villages of Mueang District, Kanchanaburi Province to assess the effectiveness of a community-based approach program. Knowledge, perceived susceptibility, self-efficacy, and regular larval survey behavior were measured for program outputs. Container Index (CI), House Index (HI), and Breteau Index (BI) were used to confirm program outcomes. Key community stakeholders in the experimental village were identified and empowered through active learning in the village. Monthly meetings with the key stakeholders were used to share experiences learned, to reflect on the program outputs and outcomes as well as to plan for the next cycle of program activities. The program was quite successful. Knowledge, perception, self-efficacy, and larval survey practices in the experimental group were significantly higher than before the experiment, and higher than the comparison group. CI, HI, and BI were decreased sharply to better than the national target. Community status as community leaders was the best predictor for larval survey behavior at the first survey. Participating in the study program activities was the best predictor at the end of the program. The results from this study suggest that the dengue hemorrhagic fever (DHF) prevention and control program at the sub-district health level should be more proactive and emphasized at the village level. Monitoring the disease control program outputs and outcomes should be performed regularly during monthly meetings. Finally, local health officers need to be empowered for these matters. PMID:16610646

  8. The LANL hemorrhagic fever virus database, a new platform for analyzing biothreat viruses.

    PubMed

    Kuiken, Carla; Thurmond, Jim; Dimitrijevic, Mira; Yoon, Hyejin

    2012-01-01

    Hemorrhagic fever viruses (HFVs) are a diverse set of over 80 viral species, found in 10 different genera comprising five different families: arena-, bunya-, flavi-, filo- and togaviridae. All these viruses are highly variable and evolve rapidly, making them elusive targets for the immune system and for vaccine and drug design. About 55,000 HFV sequences exist in the public domain today. A central website that provides annotated sequences and analysis tools will be helpful to HFV researchers worldwide. The HFV sequence database collects and stores sequence data and provides a user-friendly search interface and a large number of sequence analysis tools, following the model of the highly regarded and widely used Los Alamos HIV database [Kuiken, C., B. Korber, and R.W. Shafer, HIV sequence databases. AIDS Rev, 2003. 5: p. 52-61]. The database uses an algorithm that aligns each sequence to a species-wide reference sequence. The NCBI RefSeq database [Sayers et al. (2011) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res., 39, D38-D51.] is used for this; if a reference sequence is not available, a Blast search finds the best candidate. Using this method, sequences in each genus can be retrieved pre-aligned. The HFV website can be accessed via http://hfv.lanl.gov. PMID:22064861

  9. A novel AP92-like Crimean-Congo hemorrhagic fever virus strain, Greece.

    PubMed

    Papa, Anna; Chaligiannis, Ilias; Kontana, Natasa; Sourba, Tatiana; Tsioka, Katerina; Tsatsaris, Andreas; Sotiraki, Smaragda

    2014-09-01

    Ticks were collected from various regions of northern Greece and tested for the presence of Crimean-Congo hemorrhagic fever virus (CCHFV) RNA. Human and animal sera were collected in the regions where CCHFV-positive ticks were detected, and they were tested for the presence of IgG antibodies against the virus. A CCHFV strain was detected in Rhipicephalus bursa ticks collected from sheep in Kastoria regional unit, differing by 9.7% at the nucleotide level from the AP92 strain, which was isolated in 1975 in another region of Greece. Up to date, CCHF cases have not been reported in these regions. The human seroprevalence in the area was estimated at 6%, while IgG-positive sheep was detected in two of the four neighboring farms tested. The circulation of this specific CCHFV lineage in Greece, especially in a region where the seroprevalence is high, together with the lack of human CCHF cases, suggests a probable antigenic, but non- or low-pathogenic character of this lineage. Further studies on these strains will increase our knowledge about the role of AP92-like strains in the CCHF epidemiology, which might be useful for drug and vaccine design. PMID:24953797

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

    PubMed Central

    Cohen, Sanford N.

    2015-01-01

    SUMMARY 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. PMID:26085471

  11. A Three-Component Biomarker Panel for Prediction of Dengue Hemorrhagic Fever

    PubMed Central

    Brasier, Allan R.; Ju, Hyunsu; Garcia, Josefina; Spratt, Heidi M.; Victor, Sundar S.; Forshey, Brett M.; Halsey, Eric S.; Comach, Guillermo; Sierra, Gloria; Blair, Patrick J.; Rocha, Claudio; Morrison, Amy C.; Scott, Thomas W.; Bazan, Isabel; Kochel, Tadeusz J.; the Venezuelan Dengue Fever Working Group

    2012-01-01

    Dengue virus infections are a major cause of morbidity in tropical countries. Early detection of dengue hemorrhagic fever (DHF) may help identify individuals that would benefit from intensive therapy. Predictive modeling was performed using 11 laboratory values of 51 individuals (38 DF and 13 DHF) obtained on initial presentation using logistic regression. We produced a robust model with an area under the curve of 0.9615 that retained IL-10 levels, platelets, and lymphocytes as the major predictive features. A classification and regression tree was developed on these features that were 86% accurate on cross-validation. The IL-10 levels and platelet counts were also identified as the most informative features associated with DHF using a Random Forest classifier. In the presence of polymerase chain reaction-proven acute dengue infections, we suggest a complete blood count and rapid measurement of IL-10 can assist in the triage of potential DHF cases for close follow-up or clinical intervention improving clinical outcome. PMID:22302872

  12. Epidemiologic Features and Risk Factors of Crimean–Congo Hemorrhagic Fever in Samsun Province, Turkey

    PubMed Central

    Sisman, Aziz

    2013-01-01

    Background Crimean–Congo hemorrhagic fever (CCHF) is a tick-borne infectious disease that has a considerable mortality risk and is a challenge for the population of endemic rural areas and health care workers. This study investigated the epidemiologic features and main risk factors of CCHF in Samsun Province, Turkey, using CCHF cases diagnosed from 2007 to 2011 recorded by the Samsun Provincial Health Directorate. Methods In the study area, 126 cases were evaluated statistically and spatially. Minitab 16 software was used for statistical analysis of the data, and ArcGIS 9.3 software was used for spatial analysis. Results Among those who received a diagnosis of CCHF, 69 (54.7%) were male, 57 (45.3%) were female, 114 (90.5%) were discharged, and 12 (9.5%) died. A total of 112 of the 126 (88.9%) cases occurred at an altitude higher than 600 m. In addition, 84.1% of cases were reported during May through July, which are the busiest months for those working in the agriculture and animal husbandry sectors. Conclusions CCHF causes severe disease and has a high mortality rate (about 10% in Turkey). Early diagnosis of CCHF can be improved by periodic education of people at high risk, ie, men and women working in agriculture and animal husbandry in rural areas and those working in health care. PMID:23208513

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

    PubMed Central

    Golden, Joseph W.; Hammerbeck, Christopher D.; Mucker, Eric M.; Brocato, Rebecca L.

    2015-01-01

    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. PMID:26266264

  14. Epidemiology and phylogenetic analysis of crimean-congo hemorrhagic fever viruses in xinjiang, china.

    PubMed

    Sun, Surong; Dai, Xiang; Aishan, Muhetaer; Wang, Xinhui; Meng, Weiwei; Feng, Conghui; Zhang, Fuchun; Hang, Changshou; Hu, Zhihong; Zhang, Yujiang

    2009-08-01

    In 2004 and 2005, an epidemiological survey of Crimean-Congo hemorrhagic fever virus (CCHFV) was conducted in Xinjiang, China. A total of 5,629 serum samples of human and livestock were collected and tested for the CCHFV antibody, and 17,319 ticks were collected for viral identification. Reverse passive hemagglutination inhibition assays showed that the average prevalence of CCHFV antibody was 1.7% for the humans and 12.7% for the livestock. A relatively high antibody prevalence, ranging from 19.1% to 23.4%, was found in the livestock of the northwest, southwest, and northeast parts of the Tarim Basin. When the ticks were pooled to inoculate suckling mice, followed by reverse transcription-PCR (RT-PCR) to detect CCHFV RNA, the average RT-PCR-positive rates for Hyalomma asiaticum kozlovi and H. asiaticum asiaticum were 12.9% and 2.6%, respectively. A significant correlation was found between the antibody prevalence in the livestock and the CCHFV prevalence in H. asiaticum of the same geographic region. No CCHFV RNA was detected in Dermacentor nivenus, Rhipicephalus turanius, or Rhipicephalus sanguineus. A total of 27 partial S segments of CCHFVs were sequenced and used for phylogeny analysis. All but one Chinese isolate grouped into the Asia 1 clade, which contains the strains from Xinjiang and Uzbekistan, while the other strain, Fub90009, grouped with strains from the Middle East. PMID:19553586

  15. Analysis of simian hemorrhagic fever virus (SHFV) subgenomic RNAs, junction sequences, and 5' leader.

    PubMed

    Zeng, L; Godeny, E K; Methven, S L; Brinton, M A

    1995-03-10

    Full-length simian hemorrhagic fever virus (SHFV) genome RNA (about 15 kb in length) and six subgenomic RNAs, ranging in size from 0.65 to 4.7 kb, were detected by Northern blot hybridization in MA104 cytoplasmic extracts with a 3' genomic antisense probe. The 5' regions of the two smallest subgenomic RNAs (RNAs 6 and 7) were cloned and sequenced. Sequence analysis indicated that these two RNAs contained a common 5' leader sequence joined to the subgenomic RNA bodies via a highly conserved junction sequence; the junction sequence of RNA 7 was 5'-TTAACC-3', while that of RNA 6 was 5'-TCAACC-3'. The complete 5' leader sequence (208 nt) was obtained from genomic RNA. The genomic 5' junction sequence is identical to that of RNA 7. Northern blot hybridization with an antisense 5' leader probe confirmed the presence of the complete leader sequence in all six species of subgenomic RNA. In its virion morphology, genome size, gene order, and replication strategy, SHFV is most similar to viruses such as equine arteritis virus, lactate dehydrogenase-elevating virus, and Lelystad virus/porcine respiratory and reproductive syndrome virus. PMID:7886957

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

    PubMed

    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. PMID:25694097

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

    PubMed

    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. PMID:26299853

  18. Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo

    PubMed Central

    Borchert, Matthias; Grein, Thomas; Roth, Cathy; Swanepoel, Robert; Libande, Modeste L.; Talarmin, Antoine; Bertherat, Eric; Muyembe-Tamfum, Jean-Jacques; Tugume, Ben; Colebunders, Robert; Kondé, Kader M.; Pirard, Patricia; Olinda, Loku L.; Rodier, Guénaël R.; Campbell, Patricia; Tomori, Oyewale; Ksiazek, Thomas G.; Rollin, Pierre E.

    2003-01-01

    We conducted two antibody surveys to assess risk factors for Marburg hemorrhagic fever in an area of confirmed Marburg virus transmission in the Democratic Republic of the Congo. Questionnaires were administered and serum samples tested for Marburg-specific antibodies by enzyme-linked immunosorbent assay. Fifteen (2%) of 912 participants in a general village cross-sectional antibody survey were positive for Marburg immunoglobulin G antibody. Thirteen (87%) of these 15 were men who worked in the local gold mines. Working as a miner (odds ratio [OR] 13.9, 95% confidence interval [CI] 3.1 to 62.1) and receiving injections (OR 7.4, 95% CI 1.6 to 33.2) were associated with a positive antibody result. All 103 participants in a targeted antibody survey of healthcare workers were antibody negative. Primary transmission of Marburg virus to humans likely occurred via exposure to a still unidentified reservoir in the local mines. Secondary transmission appears to be less common with Marburg virus than with Ebola virus, the other known filovirus. PMID:14720391

  19. The impact of Crimean-Congo hemorrhagic fever virus on public health.

    PubMed

    Mertens, Marc; Schmidt, Katja; Ozkul, Aykut; Groschup, Martin H

    2013-05-01

    Climatic, environmental and economic changes, as well as the steadily increasing global trade and personal mobility provide ample opportunities for emerging pathogens with zoonotic potential to spread to previously unaffected countries. Crimean-Congo hemorrhagic fever virus (CCHFV) is considered to be one of the major emerging disease threats spreading to and within the European Union following an expanding distribution of its main vector, ticks of the genus Hyalomma. Every year more than 1000 human CCHF cases are reported from countries of southeastern Europe and Turkey. CCHFV can cause high case fatality rates and can be transmitted from human to human. There are no vaccine prophylaxis and therapeutic interventions available at present. Several EU-funded research projects focus currently on CCHFV which highlights the awareness for this problem at the European level. As public health deals with questions of prevention on a population level rather than healing and health on an individual level, the analysis of existing data plays a fundamental role to minimize its epidemic potential, by reducing infection risks, and to manage disease outbreaks. This review gives a summary of the current knowledge and data with focus at the interface between public health and CCHFV. Based on this knowledge, guidelines for the risk classification of a region and for outbreak prevention are given. This review will assist decision makers and public health authorities in understanding risk scenarios and in deciding on effective countermeasures, as well as human and veterinary scientists by highlighting existing gaps in knowledge. PMID:23458713

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

    PubMed

    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

  1. Temporal trends of dengue fever/dengue hemorrhagic fever in Bangkok, Thailand from 1981 to 2000: an age-period-cohort analysis.

    PubMed

    Kongsomboon, K; Singhasivanon, P; Kaewkungwal, J; Nimmannitya, S; Mammen, M P; Nisalak, A; Sawanpanyalert, P

    2004-12-01

    The aim of this study was to examine the effects of age, time period, and birth cohorts with dengue fever/dengue hemorrhagic fever (DF/DHF) in Bangkok, Thailand over the period 1981-2000. The age group at greatest risk for DF/DHF was 5-9 years old. The period effect shows a remittent pattern, with significant increases in 1986-1990 and 1996-2000. The birth cohort group showed a significant decreasing trend from the 1961-1965 group to the 1991-1995 group (R2 = 0.7620) with a decreasing rate of 0.1. We concluded that the temporal trend of DF/DHF is decreasing; especially for DHF. PMID:15916090

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

    PubMed

    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

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

    PubMed Central

    Han, Ziying; Madara, Jonathan J.; Herbert, Andrew; Prugar, Laura I.; Ruthel, Gordon; Lu, Jianhong; Liu, Yuliang; Liu, Wenbo; Liu, Xiaohong; Wrobel, Jay E.; Reitz, Allen B.; Dye, John M.; Harty, Ronald N.; Freedman, Bruce D.

    2015-01-01

    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. PMID:26513362

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

    PubMed

    Han, Ziying; Madara, Jonathan J; Herbert, Andrew; Prugar, Laura I; Ruthel, Gordon; Lu, Jianhong; Liu, Yuliang; Liu, Wenbo; Liu, Xiaohong; Wrobel, Jay E; Reitz, Allen B; Dye, John M; Harty, Ronald N; Freedman, Bruce D

    2015-10-01

    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. PMID:26513362

  5. The impact of the vaccination program for hemorrhagic fever with renal syndrome in Hu County, China.

    PubMed

    Xiao, Dan; Wu, Kejian; Tan, Xin; Yan, Tiecheng; Li, Haitao; Yan, Yongping

    2014-02-01

    The incidence of hemorrhagic fever with renal syndrome (HFRS) in Hu County ranked third of all counties in China in 2010. Although this county has provided a HFRS vaccination program freely since 1994, the impact of HFRS remains quite substantial. In order to continue the vaccination program effectively and control HFRS, a detailed understanding of the effect of the vaccination program should be undertaken. The Cochran-Armitage trend test was employed to examine the temporal trends of HFRS incidences, mortality rate and vaccination compliance. Temporal cluster analysis was performed to detect time periods of high HFRS risk. Cross correlation analysis was conducted to detect the correlation between HFRS incidence and vaccination compliance. Wavelet analysis was employed to detect the shift of the periodicity of HFRS. Between 1971 and 2011, the HFRS incidence and mortality rate ranged from 9.53/100,000 to 300.57/100,000 and 0 to 24.91/100,000, respectively, with a fluctuating but distinctly declining trend (incidence: Z=-34.38, P<0.01; mortality rate: Z=-23.44, P<0.01). The vaccination compliance ranged from 4.55% to 83.67%, with a distinctly increasing trend (Z=1621.70, P<0.01). The most likely temporal cluster of the HFRS epidemic was between 1983 and 1988 (RR=3.44, P<0.01) or 1979-1988 (RR=3.18, P<0.01) with different maximum temporal cluster size. There was a negative correlation between HFRS incidence and vaccination compliance when the lagged year was 1 and 2 (cross correlation coefficient=-0.51 and -0.55). The periodicity of HFRS epidemic was prolonged from about 5 years during 1976-1988 to 15 years after 1988, especially after the start of HFRS vaccination in 1994. In conclusion, the increase in vaccination compliance may play an important role in HFRS control and prevention in Hu County, China. PMID:24252696

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

    PubMed Central

    Chinikar, Sadegh; Bouzari, Saeid; Shokrgozar, Mohammad Ali; Mostafavi, Ehsan; Jalali, Tahmineh; Khakifirouz, Sahar; Nowotny, Norbert; Fooks, Anthony R.; Shah-Hosseini, Nariman

    2016-01-01

    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. PMID:27308271

  7. Assessing changes in vascular permeability in a hamster model of viral hemorrhagic fever

    PubMed Central

    2010-01-01

    Background A number of RNA viruses cause viral hemorrhagic fever (VHF), in which proinflammatory mediators released from infected cells induce increased permeability of the endothelial lining of blood vessels, leading to loss of plasma volume, hypotension, multi-organ failure, shock and death. The optimal treatment of VHF should therefore include both the use of antiviral drugs to inhibit viral replication and measures to prevent or correct changes in vascular function. Although rodent models have been used to evaluate treatments for increased vascular permeability (VP) in bacterial sepsis, such studies have not been performed for VHF. Results Here, we use an established model of Pichinde virus infection of hamsters to demonstrate how changes in VP can be detected by intravenous infusion of Evans blue dye (EBD), and compare those measurements to changes in hematocrit, serum albumin concentration and serum levels of proinflammatory mediators. We show that EBD injected into sick animals in the late stage of infection is rapidly sequestered in the viscera, while in healthy animals it remains within the plasma, causing the skin to turn a marked blue color. This test could be used in live animals to detect increased VP and to assess the ability of antiviral drugs and vasoactive compounds to prevent its onset. Finally, we describe a multiplexed assay to measure levels of serum factors during the course of Pichinde arenavirus infection and demonstrate that viremia and subsequent increase in white blood cell counts precede the elaboration of inflammatory mediators, which is followed by increased VP and death. Conclusions This level of model characterization is essential to the evaluation of novel interventions designed to control the effects of virus-induced hypercytokinemia on host vascular function in VHF, which could lead to improved survival. PMID:20846417

  8. A comparison of dengue hemorrhagic fever control interventions in northeastern Thailand.

    PubMed

    Chaikoolvatana, Anun; Chanruang, Suparat; Pothaled, Prakongsil

    2008-07-01

    This study compared the effectiveness of the currently available interventions of dengue vector and dengue hemorrhagic fever (DHF) control used in northeastern Thailand, an area with a high incidence of the disease. Also, the basic knowledge of dengue vector and DHF control of a group of 568 participants from local communities was measured. These communities were divided into two groups that had no reported cases in the previous year (non-DHF) and a group that had reported cases (DHF). Three current interventions of dengue vector and DHF control were assessed: insecticide fogging, 1% w/w temephos sand granules, and a combination of these two. Assessment included numbers of DHF cases, vector indices [house index (HI), container index (CI), and Breteau index (BI)], and cost. A multiple choice questionnaire was used to measure participants' basic knowledge desirable for knowledge retention. Data was statistically analyzed by the use of means, standard deviations, percentages, ANOVA repeated measure, and logistic regression. The results showed 1% w/w temephos sand granules as the most effective intervention of dengue vector and DHF control and there was a statistically significant difference between the control measures (p =0.001). Most participants had either a very low or very high level of knowledge and basic knowledge was statistically significantly associated with vector index (BI) (p = 0.008). Participants stated that they mainly gained knowledge about dengue vector and DHF control from public health workers followed by television and public media. Overall, the findings of this study illustrated the importance of public health workers and communities in health issues at the local level and the need to assess the benefits of current interventions and combinations of current and new interventions of dengue vector and control. PMID:19058598

  9. The geographic distribution of cases of Crimean-Congo hemorrhagic fever: Kastamonu, Turkey.

    PubMed

    Aker, Servet; Akıncı, Halil; Kılıçoğlu, Cem; Leblebicioglu, Hakan

    2015-09-01

    The purpose of this study was to analyze the epidemiological characteristics of cases diagnosed with Crimean-Congo Hemorrhagic Fever (CCHF) with the help of Geographic Information Systems (GIS) and to establish an epidemiological risk map. Data for 434 cases diagnosed with CCHF between 01.01.2004 and 31.12.2013 were subjected to statistical analysis SPSS 13.0 software. A digital map of Kastamonu was transferred onto ArcGIS 10.0 software in order to establish a risk map for CCHF. The highest cumulative incidence of CCHF is 41.29/10,000, and in people living at altitudes of 1001-1200 meters. ROC analysis of altitudes above sea level of residences with CCHF cases revealed an area under the curve of 74.5% (95% CI: 0.72-0.76, p<0.05). At a cut-off point of 836.5 meters, sensitivity was 0.74 and specificity 0.76. Cumulative incidence of CCHF was significantly positively correlated with number of animals per head (r=0.76) and area of agricultural land per head (r=0.59) (p<0.05). No significant correlation was determined between cumulative incidence and forested area percentages. This study reveals that both men and women living at more than 836.5 meters above sea level and working in agriculture and animal husbandry are at risk of CCHF between May and July. Detailed examination of the ecology of vector ticks is now needed in order to fully determine the epidemiology of the disease. PMID:26139033

  10. Serological assays based on recombinant viral proteins for the diagnosis of arenavirus hemorrhagic fevers.

    PubMed

    Fukushi, Shuetsu; Tani, Hideki; Yoshikawa, Tomoki; Saijo, Masayuki; Morikawa, Shigeru

    2012-10-01

    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. PMID:23202455

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

    PubMed

    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) (p<0.01). Linear regression showed significantly higher dengue incidence with lower values of Oceanic Niño Index (p=0.0097), higher rain probability (p=0.0149), accumulated rain (p=0.0443) and higher relative humidity (p=0.0292). At a multiple linear regression model using those variables, ONI values shown to be the most important and significant factor found to be associated with the monthly occurrence of DHF cases (r²=0.649; βstandardized=-0.836; p=0.01). As has been shown herein, climate variability is an important element influencing the dengue epidemiology in Honduras. 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. PMID:23202593

  12. Systems Pharmacology Uncovers the Multiple Mechanisms of Xijiao Dihuang Decoction for the Treatment of Viral Hemorrhagic Fever

    PubMed Central

    Liu, Jianling; Pei, Tianli; Mu, Jiexin; Zheng, Chunli; Chen, Xuetong; Huang, Chao; Fu, Yingxue; Liang, Zongsuo; Wang, Yonghua

    2016-01-01

    Background. Viral hemorrhagic fevers (VHF) are a group of systemic diseases characterized by fever and bleeding, which have posed a formidable potential threat to public health with high morbidity and mortality. Traditional Chinese Medicine (TCM) formulas have been acknowledged with striking effects in treatment of hemorrhagic fever syndromes in China's history. Nevertheless, their accurate mechanisms of action are still confusing. Objective. To systematically dissect the mechanisms of action of Chinese medicinal formula Xijiao Dihuang (XJDH) decoction as an effective treatment for VHF. Methods. In this study, a systems pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, drug targeting, network, and pathway analysis was developed. Results. 23 active compounds of XJDH were obtained and 118 VHF-related targets were identified to have interactions with them. Moreover, systematic analysis of drug-target network and the integrated VHF pathway indicate that XJDH probably acts through multiple mechanisms to benefit VHF patients, which can be classified as boosting immune system, restraining inflammatory responses, repairing the vascular system, and blocking virus spread. Conclusions. The integrated systems pharmacology method provides precise probe to illuminate the molecular mechanisms of XJDH for VHF, which will also facilitate the application of traditional medicine in modern medicine. PMID:27239215

  13. Systems Pharmacology Uncovers the Multiple Mechanisms of Xijiao Dihuang Decoction for the Treatment of Viral Hemorrhagic Fever.

    PubMed

    Liu, Jianling; Pei, Tianli; Mu, Jiexin; Zheng, Chunli; Chen, Xuetong; Huang, Chao; Fu, Yingxue; Liang, Zongsuo; Wang, Yonghua

    2016-01-01

    Background. Viral hemorrhagic fevers (VHF) are a group of systemic diseases characterized by fever and bleeding, which have posed a formidable potential threat to public health with high morbidity and mortality. Traditional Chinese Medicine (TCM) formulas have been acknowledged with striking effects in treatment of hemorrhagic fever syndromes in China's history. Nevertheless, their accurate mechanisms of action are still confusing. Objective. To systematically dissect the mechanisms of action of Chinese medicinal formula Xijiao Dihuang (XJDH) decoction as an effective treatment for VHF. Methods. In this study, a systems pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, drug targeting, network, and pathway analysis was developed. Results. 23 active compounds of XJDH were obtained and 118 VHF-related targets were identified to have interactions with them. Moreover, systematic analysis of drug-target network and the integrated VHF pathway indicate that XJDH probably acts through multiple mechanisms to benefit VHF patients, which can be classified as boosting immune system, restraining inflammatory responses, repairing the vascular system, and blocking virus spread. Conclusions. The integrated systems pharmacology method provides precise probe to illuminate the molecular mechanisms of XJDH for VHF, which will also facilitate the application of traditional medicine in modern medicine. PMID:27239215

  14. Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

    PubMed Central

    Golden, Joseph W.; Maes, Piet; Kwilas, Steven A.; Ballantyne, John

    2016-01-01

    ABSTRACT Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT50), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. IMPORTANCE Arenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can mitigate the severity of disease caused by arenaviruses, particularly species found in South America. Because of variations in potency of the human-derived product, limited availability, and safety concerns, this treatment option has essentially been abandoned. Accordingly, despite this approach being an effective postinfection treatment option, research on novel approaches to produce potent polyclonal antibody-based therapies have been deficient. Here we show that DNA-based vaccine technology can be used to make potently neutralizing antibodies in rabbits that exclusively target the glycoproteins of several human-pathogenic arenaviruses found in South America, including JUNV, MACV, GTOV, and SABV. These antibodies protected guinea pigs from lethal disease when given post-virus challenge. We also generated a purified antibody cocktail with antibodies targeting three arenaviruses and demonstrated protective efficacy against all three targets. Our findings demonstrate that use of the DNA vaccine technology could be used to produce candidate antiarenavirus neutralizing antibody-based products. PMID:26792737

  15. [Discovery, clinical and etiological characteristic of hemorrhagic fever with renal syndrome in the subtropical zone of Krasnodar region].

    PubMed

    Dzagurova, T K; Tkachenko, E A; Iunicheva, Iu V; Morozov, V G; Briukhanov, A F; Bashkirtsev, V N; Sedova, N S; Klempa, B; Kruger, D

    2008-01-01

    Twenty-six patients with hemorrhagic fever with renal syndrome (HFRS) were revealed as a result of serological examination of 582 patients with fever living around Sochi town. Etiologic role of Dobrava virus subtype as the cause of HFRS was assessed by immunofluorescent and ELISA assays, and neutralization test. The principal host of this virus and source of infection for humans is Caucasian forest mouse Apodemus ponticus. HFRS morbidity was sporadic and not dependent from patients' occupation and season. Comparative analysis of clinical and laboratory data from HFRS cases caused by DOB/Sochi and DOB/Lipetsk subspecies, as well as Puumala virus showed higher proportion of severe forms of disease in patients with HFRS from Sochi. PMID:18376466

  16. Dengue fever (image)

    MedlinePlus

    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.

  17. Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.

    PubMed

    Bente, Dennis A; Forrester, Naomi L; Watts, Douglas M; McAuley, Alexander J; Whitehouse, Chris A; Bray, Mike

    2013-10-01

    Crimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review

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

    PubMed

    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 < 0.001), more 'likes' (1119 vs. 224, p < 0.001), channel subscriptions (208 vs. 32, p < 0.001), and 'shares' (519 vs. 98, p < 0.001). Multivariable logistic regression showed that only the 'clinical symptoms' component of the MICI scale was associated with a higher likelihood of a video being included in the HR vs. LR group.(OR 1.86, 95 % CI 1.06-3.28, p = 0.03). YouTube videos presenting clinical symptoms of infectious diseases during epidemics are more likely to be included in the HR group and influence viewers behavior. PMID:26322263

  19. Changes in Plasma Adiponectin Concentrations in Patients With Hemorrhagic Fever With Renal Syndrome

    PubMed Central

    Du, Hong; Bai, Xuefan; Lian, Jianqi; Li, Jing; Zhang, Ying; Wang, Pingzhong; Jiang, Hong

    2016-01-01

    Abstract The objective is to observe the changes in plasma adiponectin (APN) and its predictive capacity for disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS). One hundred and five patients who were treated at our center between October 2011 and December 2012 were randomly enrolled in this study. The patients were divided into a mild-type group, a moderate-type group, a severe-type group, and a critical-type group according to the HFRS criteria for clinical classification. Ninety-three plasma samples from the patients in the acute stage and 78 samples from the patients in the convalescent stage were obtained, and 28 samples from healthy subjects were obtained as controls. The concentrations of APN were detected using the enzyme-linked immunosorbent assay. The levels of white blood cells, platelets, hematocrit, albumin, blood urea nitrogen, serum creatinine, and uric acid in the samples were routinely tested. The levels of APN among the different types were compared; the correlation between APN and the laboratory parameters was analyzed. The predictive effectiveness for prognosis of APN and the laboratory parameters as mentioned above were evaluated using the receiver operating characteristic curve analysis. The levels of APN in the mild- and moderate-type patients in the acute stage were significantly higher than the severe-type and control (P < 0.05) and decreased with the severity of the disease, while there were no obvious difference among severe-, critical-type and control groups. The levels of APN in patients in the convalescent stage were higher than the control group (P < 0.05), and the APN levels of the critical-type group were higher compared with the mild-type groups (P < 0.05). Adiponectin was negatively correlated with white blood cells and hematocrit and positively correlated with platelets, albumin, and uric acid (P < 0.001). Adiponectin showed no statistical significance for predicting prognosis, with the

  20. Treatment of a patient with severe hemorrhagic fever accompanied by infection with methicillinresistant Staphylococcus aureus, Acinetobacter baumannii, aspergillus and mucor: a case report.

    PubMed

    Zhang, Di; Wang, Xue; Lv, Jing; Dong, Yalin

    2015-12-01

    A 40-year-old Korean man developed hemorrhagic fever in Xi'an, which is one of the main endemic areas for this illness in China. According to the local epidemiological situation, his condition could have been due to hantavirus infection, but this was not confirmed. He presented with the typical symptoms of hemorrhagic fever and rapidly progressed to a severe multisystem illness. The clinical situation deteriorated rapidly after admission, and he became coinfected with methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, aspergillus, and mucor. The patient was successfully treated with appropriate fluid infusion, hemodynamic support, continuous renal replacement therapy, liver protectants, and antibacterials. This case indicates that the choice of antimicrobials and the required dose are crucial issues, and that the vaccination campaign for hemorrhagic fever in Xi'an needs greater attention. PMID:26521926

  1. Thrombocytopenia associated with dengue hemorrhagic fever responds to intravenous administration of anti-D (Rh(0)-D) immune globulin.

    PubMed

    de Castro, Reynaldo Angelo C; de Castro, Jo-Anne A; Barez, Marie Yvette C; Frias, Melchor V; Dixit, Jitendra; Genereux, Maurice

    2007-04-01

    Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue hemorrhagic fever (DHF). An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF (see Saito et al., 2004, Clin Exp Immunol 138: 299-303; Mitrakul, 1979, Am J Trop Med Hyg 26: 975-984; and Boonpucknavig, 1979, Am J Trop Med Hyg 28: 881-884). The interim data of two randomized placebo controlled trials in patients (N = 47) meeting WHO criteria for dengue hemorrhagic fever (DHF) with severe thrombocytopenia (platelets < or = 50,000/mm(3)) reveal that the increase in platelet count with anti-D immune globulin (WinRho SDF), 50 microg/kg (250 IU/kg) intravenously is more brisk than the placebo group. The mean maximum platelet count of the anti-D-treated group at 48 hours was 91,500/mm(3) compared with 69,333/mm(3) in the placebo group. 75% of the anti-D-treated group demonstrated an increase of platelet counts > or = 20,000 compared with only 58% in the placebo group. These data suggest that treatment of severe thrombocytopenia accompanying DHF with anti-D may be a useful and safe therapeutic option. PMID:17426181

  2. Dengue and dengue hemorrhagic fever epidemics in Brazil: what research is needed based on trends, surveillance, and control experiences?

    PubMed

    Teixeira, Maria da Glória; Costa, Maria da Conceição Nascimento; Barreto, Maurício Lima; Mota, Eduardo

    2005-01-01

    Dengue epidemics account annually for several million cases and deaths worldwide. The high endemic level of dengue fever and its hemorrhagic form correlates to extensive domiciliary infestation by Aedes aegypti and multiple viral serotype human infection. This study analyzed serial case reports registered in Brazil since 1981, describing incidence evolutionary patterns and spatial distribution. Epidemic waves followed the introduction of every serotype (DEN 1 to 3), and reduction in susceptible individuals possibly accounted for decreasing case frequency. An incremental expansion of affected areas and increasing occurrence of dengue fever and its hemorrhagic form with high case fatality were noted in recent years. In contrast, efforts based solely on chemical vector control have been insufficient. Moreover, some evidence demonstrates that educational measures do not permanently modify population habits. Thus, as long as a vaccine is not available, further dengue control depends on potential results from basic interdisciplinary research and intervention evaluation studies, integrating environmental changes, community participation and education, epidemiological and virological surveillance, and strategic technological innovations aimed to stop transmission. PMID:16158135

  3. Clusters of spatial, temporal, and space-time distribution of hemorrhagic fever with renal syndrome in Liaoning Province, Northeastern China

    PubMed Central

    2011-01-01

    Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by Hantavirus, with characteristics of fever, hemorrhage, kidney damage, and hypotension. HFRS is recognized as a notifiable public health problem in China, and Liaoning Province is one of the most seriously affected areas with the most cases in China. It is necessary to investigate the spatial, temporal, and space-time distribution of confirmed cases of HFRS in Liaoning Province, China for future research into risk factors. Methods A cartogram map was constructed; spatial autocorrelation analysis and spatial, temporal, and space-time cluster analysis were conducted in Liaoning Province, China over the period 1988-2001. Results When the number of permutation test was set to 999, Moran's I was 0.3854, and was significant at significance level of 0.001. Spatial cluster analysis identified one most likely cluster and four secondary likely clusters. Temporal cluster analysis identified 1998-2001 as the most likely cluster. Space-time cluster analysis identified one most likely cluster and two secondary likely clusters. Conclusions Spatial, temporal, and space-time scan statistics may be useful in supervising the occurrence of HFRS in Liaoning Province, China. The result of this study can not only assist health departments to develop a better prevention strategy but also potentially increase the public health intervention's effectiveness. PMID:21867563

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

    PubMed Central

    Kamboj, Aman; Pateriya, Atul Kumar; Mishra, Anamika; Ranaware, Pradip; Kulkarni, Diwakar D.; Raut, Ashwin Ashok

    2014-01-01

    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. PMID:24877102

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

    PubMed

    Grove, Jessica N; Branco, Luis M; Boisen, Matt L; Muncy, Ivana J; Henderson, Lee A; Schieffellin, John S; Robinson, James E; Bangura, James J; Fonnie, Mbalu; Schoepp, Randal J; Hensley, Lisa E; Seisay, Alhassan; Fair, Joseph N; Garry, Robert F

    2011-01-01

    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. PMID:21689444

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

    PubMed Central

    2011-01-01

    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. PMID:21689444

  7. Rapid Detection and Quantification of RNA of Ebola and Marburg Viruses, Lassa Virus, Crimean-Congo Hemorrhagic Fever Virus, Rift Valley Fever Virus, Dengue Virus, and Yellow Fever Virus by Real-Time Reverse Transcription-PCR

    PubMed Central

    Drosten, Christian; Göttig, Stephan; Schilling, Stefan; Asper, Marcel; Panning, Marcus; Schmitz, Herbert; Günther, Stephan

    2002-01-01

    Viral hemorrhagic fevers (VHFs) are acute infections with high case fatality rates. Important VHF agents are Ebola and Marburg viruses (MBGV/EBOV), Lassa virus (LASV), Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), dengue virus (DENV), and yellow fever virus (YFV). VHFs are clinically difficult to diagnose and to distinguish; a rapid and reliable laboratory diagnosis is required in suspected cases. We have established six one-step, real-time reverse transcription-PCR assays for these pathogens based on the Superscript reverse transcriptase-Platinum Taq polymerase enzyme mixture. Novel primers and/or 5′-nuclease detection probes were designed for RVFV, DENV, YFV, and CCHFV by using the latest DNA database entries. PCR products were detected in real time on a LightCycler instrument by using 5′-nuclease technology (RVFV, DENV, and YFV) or SybrGreen dye intercalation (MBGV/EBOV, LASV, and CCHFV). The inhibitory effect of SybrGreen on reverse transcription was overcome by initial immobilization of the dye in the reaction capillaries. Universal cycling conditions for SybrGreen and 5′-nuclease probe detection were established. Thus, up to three assays could be performed in parallel, facilitating rapid testing for several pathogens. All assays were thoroughly optimized and validated in terms of analytical sensitivity by using in vitro-transcribed RNA. The ≥95% detection limits as determined by probit regression analysis ranged from 1,545 to 2,835 viral genome equivalents/ml of serum (8.6 to 16 RNA copies per assay). The suitability of the assays was exemplified by detection and quantification of viral RNA in serum samples of VHF patients. PMID:12089242

  8. Fever

    MedlinePlus

    A fever is a body temperature that is higher than normal. It is not an illness. It is part of your body's defense against infection. Most bacteria ... cause infections do well at the body's normal temperature (98.6 F). A slight fever can make ...

  9. Assessment of Recombination in the S-segment Genome of Crimean-Congo Hemorrhagic Fever Virus in Iran

    PubMed Central

    Chinikar, Sadegh; Shah-Hosseini, Nariman; Bouzari, Saeid; Shokrgozar, Mohammad Ali; Mostafavi, Ehsan; Jalali, Tahmineh; Khakifirouz, Sahar; Groschup, Martin H; Niedrig, Matthias

    2016-01-01

    Background: Crimean-Congo Hemorrhagic Fever Virus (CCHFV) belongs to genus Nairovirus and family Bunyaviridae. The main aim of this study was to investigate the extent of recombination in S-segment genome of CCHFV in Iran. Methods: Samples were isolated from Iranian patients and those available in GenBank, and analyzed by phylogenetic and bootscan methods. Results: Through comparison of the phylogenetic trees based on full length sequences and partial fragments in the S-segment genome of CCHFV, genetic switch was evident, due to recombination event. Moreover, evidence of multiple recombination events was detected in query isolates when bootscan analysis was used by SimPlot software. Conclusion: Switch of different genomic regions between different strains by recombination could contribute to CCHFV diversification and evolution. The occurrence of recombination in CCHFV has a critical impact on epidemiological investigations and vaccine design. PMID:27047968

  10. Effects of Humidity Variation on the Hantavirus Infection and Hemorrhagic Fever with Renal Syndrome Occurrence in Subtropical China.

    PubMed

    Xiao, Hong; Huang, Ru; Gao, Li-Dong; Huang, Cun-Rui; Lin, Xiao-Ling; Li, Na; Liu, Hai-Ning; Tong, Shi-Lu; Tian, Huai-Yu

    2016-02-01

    Infection rates of rodents have a significant influence on the transmission of hemorrhagic fever with renal syndrome (HFRS). In this study, four cities and two counties with high HFRS incidence in eastern Hunan Province in China were studied, and surveillance data of rodents, as well as HFRS cases and related environmental variables from 2007 to 2010, were collected. Results indicate that the distribution and infection rates of rodents are closely associated with environmental conditions. Hantavirus infections in rodents were positively correlated with temperature vegetation dryness index and negatively correlated with elevation. The predictive risk maps based on multivariate regression model revealed that the annual variation of infection risks is small, whereas monthly variation is large and corresponded well to the seasonal variation of human HFRS incidence. The identification of risk factors and risk prediction provides decision support for rodent surveillance and the prevention and control of HFRS. PMID:26711521

  11. Fever

    PubMed Central

    Conti, Bruno

    2010-01-01

    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. PMID:20305990

  12. Recovery of Recombinant Crimean Congo Hemorrhagic Fever Virus Reveals a Function for Non-structural Glycoproteins Cleavage by Furin

    PubMed Central

    Bergeron, Éric; Zivcec, Marko; Chakrabarti, Ayan K.; Nichol, Stuart T.; Albariño, César G.; Spiropoulou, Christina F.

    2015-01-01

    Crimean Congo hemorrhagic fever virus (CCHFV) is a negative-strand RNA virus of the family Bunyaviridae (genus: Nairovirus). In humans, CCHFV causes fever, hemorrhage, severe thrombocytopenia, and high fatality. A major impediment in precisely determining the basis of CCHFV’s high pathogenicity has been the lack of methodology to produce recombinant CCHFV. We developed a reverse genetics system based on transfecting plasmids into BSR-T7/5 and Huh7 cells. In our system, bacteriophage T7 RNA polymerase produced complementary RNA copies of the viral S, M, and L segments that were encapsidated with the support, in trans, of CCHFV nucleoprotein and L polymerase. The system was optimized to systematically recover high yields of infectious CCHFV. Additionally, we tested the ability of the system to produce specifically designed CCHFV mutants. The M segment encodes a polyprotein that is processed by host proprotein convertases (PCs), including the site-1 protease (S1P) and furin-like PCs. S1P and furin cleavages are necessary for producing the non-structural glycoprotein GP38, while S1P cleavage yields structural Gn. We studied the role of furin cleavage by rescuing a recombinant CCHFV encoding a virus glycoprotein precursor lacking a functional furin cleavage motif (RSKR mutated to ASKA). The ASKA mutation blocked glycoprotein precursor’s maturation to GP38, and Gn precursor’s maturation to Gn was slightly diminished. Furin cleavage was not essential for replication, as blocking furin cleavage resulted only in transient reduction of CCHFV titers, suggesting that either GP38 and/or decreased Gn maturation accounted for the reduced virion production. Our data demonstrate that nairoviruses can be produced by reverse genetics, and the utility of our system uncovered a function for furin cleavage. This viral rescue system could be further used to study the CCHFV replication cycle and facilitate the development of efficacious vaccines to counter this biological and public

  13. Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system.

    PubMed

    Suda, Yuto; Fukushi, Shuetsu; Tani, Hideki; Murakami, Shin; Saijo, Masayuki; Horimoto, Taisuke; Shimojima, Masayuki

    2016-06-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV. PMID:26935918

  14. Vascular Leakage in Dengue Hemorrhagic Fever Is Associated with Dengue Infected Monocytes, Monocyte Activation/Exhaustion, and Cytokines Production

    PubMed Central

    Chunhakan, Sirichan; Butthep, Punnee; Yoksan, Sutee; Tangnararatchakit, Kanchana; Chuansumrit, Ampaiwan

    2015-01-01

    The vascular leakage was shown by the increment of hematocrit (Hct), dengue viral infected monocyte, monocyte status, and cytokines production in patients infected with dengue virus. Dengue viral antigens were demonstrated in monocytes (CD14+) from peripheral blood mononuclear cells. The increased levels of Hct, interleukin- (IL-) 10, and tumor necrosis factor-alpha (TNF-α) were detected in dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) patients as compared with other febrile illnesses (OFIs). The highest levels of Hct and IL-10 were detected in DSS patients as compared with other groups (P < 0.05) especially on one day before and after defervescence. The unstimulated and lipopolysaccharide- (LPS-) stimulated monocytes from DSS patients showed the significantly decreased of intracellular IL-1β and TNF-α. In addition, the lowest level of mean fluorescence intensity (MFI) of CD11b expression on monocytes surface in DSS patients was also demonstrated. Furthermore, the negative correlations between IL-10 levels and intracellular IL-1β and MFI of CD11b expression in unstimulated and LPS-stimulated monocytes were also detected. Nevertheless, not only were the relationships between the prominent IL-10 and the suppression of intracellular monocyte secretion, namely, IL-1β, TNF-α, demonstrated but also the effect of vascular leakage was observed. PMID:25722892

  15. Fever

    MedlinePlus

    ... of charts. A fever is defined as a temperature 1° or more above the normal 98.6°. Minor infections may cause mild or short-term temperature elevations. Temperatures of 103° and above are considered ...

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

    PubMed

    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). PMID:26381398

  17. Interventions to control virus transmission during an outbreak of Ebola hemorrhagic fever: experience from Kikwit, Democratic Republic of the Congo, 1995.

    PubMed

    Kerstiëns, B; Matthys, F

    1999-02-01

    On 6 May 1995, the Médecins sans Frontières (MSF) coordinator in Kinshasa, Democratic Republic of the Congo (DRC), received a request for assistance for what was believed to be a concurrent outbreak of bacillary dysentery and viral hemorrhagic fever (suspected Ebola hemorrhagic fever [EHF]) in the town of Kikwit, DRC. On 11 May, the MSF intervention team assessed Kikwit General Hospital. This initial assessment revealed a nonfunctional isolation ward for suspected EHF cases; a lack of water and electricity; no waste disposal system; and no protective gear for medical staff. The priorities set by MSF were to establish a functional isolation ward to deal with EHF and to distribute protective supplies to individuals who were involved with patient care. Before the intervention, 67 health workers contracted EHF; after the initiation of control measures, just 3 cases were reported among health staff and none among Red Cross volunteers involved in body burial. PMID:9988193

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

    PubMed Central

    2011-01-01

    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 distribution

  19. Lassa hemorrhagic fever in a late term pregnancy from northern Sierra Leone with a positive maternal outcome: case report.

    PubMed

    Branco, Luis M; Boisen, Matt L; Andersen, Kristian G; Grove, Jessica N; Moses, Lina M; Muncy, Ivana J; Henderson, Lee A; Schieffellin, John S; Robinson, James E; Bangura, James J; Grant, Donald S; Raabe, Vanessa N; Fonnie, Mbalu; Zaitsev, Eleina M; Sabeti, Pardis C; Garry, Robert F

    2011-01-01

    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 distribution

  20. Genetic characterization of the M RNA segment of a Balkan Crimean-Congo hemorrhagic fever virus strain.

    PubMed

    Papa, Anna; Papadimitriou, E; Boźović, B; Antoniadis, A

    2005-03-01

    Crimean-Congo hemorrhagic fever (CCHF) virus causes one of the most severe diseases in humans, with a mortality rate of up to 30%. It is transmitted to humans by the bite of hard ticks or by contact with blood or tissues from human patients or infected livestock. Balkan Peninsula is an endemic region of the disease, and sporadic cases or even outbreaks are observed every year. The M RNA segment encodes for the glycoprotein precursor of two surface glycoproteins Gn and Gc. Up to now complete M RNA CCHF virus sequences have been published from strains isolated in Nigeria, China, Pakistan, Tajikistan, and Russia. In the present study, the genetic characterization of the complete nucleotide sequence of the M RNA segment of a Balkan CCHF virus strain, Kosovo/9553/2001, isolated in summer of 2001 from a human fatal case in Kosovo is reported. This is the first published complete M nucleotide sequence of a CCHF virus strain isolated in Balkans. It was found that the Balkan strain is similar to the Russian strain, both strains differing from all other completely sequenced CCHF virus strains by approximately 22% at the nucleotide level forming an independent clade in the phylogenetic tree. PMID:15648072

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

    PubMed Central

    Lu, Bo; Sun, Qinghua; Tang, Wenge; Liu, Xiaobo; Yang, Weizhong; Xu, Xinyi; Liu, Qiyong

    2015-01-01

    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. PMID:26193359

  2. Tofla virus: A newly identified Nairovirus of the Crimean-Congo hemorrhagic fever group isolated from ticks in Japan

    PubMed Central

    Shimada, Satoshi; Aoki, Kotaro; Nabeshima, Takeshi; Fuxun, Yu; Kurosaki, Yohei; Shiogama, Kazuya; Onouchi, Takanori; Sakaguchi, Miako; Fuchigami, Takeshi; Ono, Hokuto; Nishi, Kodai; Posadas-Herrera, Guillermo; Uchida, Leo; Takamatsu, Yuki; Yasuda, Jiro; Tsutsumi, Yutaka; Fujita, Hiromi; Morita, Kouichi; Hayasaka, Daisuke

    2016-01-01

    Ixodid ticks transmit several important viral pathogens. We isolated a new virus (Tofla virus: TFLV) from Heamaphysalis flava and Heamaphysalis formsensis in Japan. The full-genome sequences revealed that TFLV belonged to the genus Nairovirus, family Bunyaviridae. Phylogenetic analyses and neutralization tests suggested that TFLV is closely related to the Hazara virus and that it is classified into the Crimean-Congo hemorrhagic fever group. TFLV caused lethal infection in IFNAR KO mice. The TFLV-infected mice exhibited a gastrointestinal disorder, and positron emission tomography-computed tomography images showed a significant uptake of 18F-fluorodeoxyglucose in the intestinal tract. TFLV was able to infect and propagate in cultured cells of African green monkey-derived Vero E6 cells and human-derived SK-N-SH, T98-G and HEK-293 cells. Although TFLV infections in humans and animals are currently unknown, our findings may provide clues to understand the potential infectivity and to develop of pre-emptive countermeasures against this new tick-borne Nairovirus. PMID:26863911

  3. Comparative analysis of immune responses to Russian spring-summer encephalitis and Omsk hemorrhagic fever viruses in mouse models

    PubMed Central

    Tigabu, Bersabeh; Juelich, Terry; Holbrook, Michael R.

    2010-01-01

    Omsk hemorrhagic fever virus (OHFV) and Russian spring-summer encephalitis virus (RSSEV) are tick-borne flaviviruses that have close homology but different pathology and disease outcomes. Previously, we reported that C57BL/6 and BALB/c mice were excellent models to study the pathology and clinical signs of human RSSEV and OHFV infection. In the study described here, we found that RSSEV infection induced robust release of proinflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) and chemokines (MCP-1, MIP-1β, RANTES and KC) in the brain at 9 and 11dpi, together with moderate to low Th1 and Th2 cytokines. In contrast, OHFV infection stimulated an early and prominent induction of IL-1α, TNF-α, IL-12p70, MCP-1, MIP-1α and MIP-1β in the spleen of infected mice. Collectively our data suggest that a differential host response to infection may lead to the alternate disease outcomes seen following OHFV or RSSEV infection. PMID:20875909

  4. Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing.

    PubMed

    Kim, Won-Keun; Kim, Jeong-Ah; Song, Dong Hyun; Lee, Daesang; Kim, Yong Chul; Lee, Sook-Young; Lee, Seung-Ho; No, Jin Sun; Kim, Ji Hye; Kho, Jeong Hoon; Gu, Se Hun; Jeong, Seong Tae; Wiley, Michael; Kim, Heung-Chul; Klein, Terry A; Palacios, Gustavo; Song, Jin-Won

    2016-01-01

    Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses. PMID:27221218

  5. Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing

    PubMed Central

    Kim, Won-Keun; Kim, Jeong-Ah; Song, Dong Hyun; Lee, Daesang; Kim, Yong Chul; Lee, Sook-Young; Lee, Seung-Ho; No, Jin Sun; Kim, Ji Hye; Kho, Jeong Hoon; Gu, Se Hun; Jeong, Seong Tae; Wiley, Michael; Kim, Heung-Chul; Klein, Terry A.; Palacios, Gustavo; Song, Jin-Won

    2016-01-01

    Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses. PMID:27221218

  6. Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17.

    PubMed

    Pagliari, Carla; Simões Quaresma, Juarez Antônio; Kanashiro-Galo, Luciane; de Carvalho, Leda Viegas; Vitoria, Webster Oliveira; da Silva, Wellington Luiz Ferreira; Penny, Ricardo; Vasconcelos, Barbara Cristina Baldez; da Costa Vasconcelos, Pedro Fernando; Duarte, Maria Irma Seixas

    2016-02-01

    Acute kidney injury is an unusual complication during dengue infection. The objective of this study was to better identify the characteristics of glomerular changes focusing on in situ immune cells and cytokines. An immunohistochemical assay was performed on 20 kidney specimens from fatal human cases of dengue hemorrhagic fever (DHF). It was observed a lymphomononuclear infiltrate, neutrophils and nuclear fragmentation in the glomeruli, hydropic degeneration, nuclear retraction, eosinophilic tubules and intense acute congestion. Sickle erythrocytes were frequent in glomeruli and inflammatory infiltrate. The glomeruli presented endothelial swelling and mesangial proliferation. Lymphocytes CD4+ predominated over CD8+ T cells, B cells and natural killer cells. There were also an expressive number of macrophagic CD68+ cells. S100, Foxp3 and CD123 cells were not identified. Cells expressing IL17 and IL18+ cytokines predominated in the renal tissues, while IL4, IL6, IL10, IL13, TNF-alpha and IFN-gamma were rarely visualized. The high number of cells expressing IL17 and IL18+ could reflect the acute inflammatory response and possibly contribute to the local lesion. CD8+ T cells could play a role in the cytotoxic response. DHF is a multifactorial disease of capillary leakage associated with a "Tsunami of cytokines expression". The large numbers of cells expressing IL17 seems to play a role favoring the increased permeability. PMID:26741825

  7. Surveillance for an emerging disease: dengue hemorrhagic fever in Puerto Rico, 1988-1997. Puerto Rico Association of Epidemiologists.

    PubMed

    Rigau-Pérez, J G

    1999-12-01

    Surveillance for emerging diseases is critically dependent on four factors: reporting methods, case definition, laboratory diagnosis, and knowledge of the disease among health-care professionals. The dengue hemorrhagic fever (DHF) surveillance system in Puerto Rico collects patient data from three sources: dengue case investigation (DCI) forms sent with diagnostic samples, clinical reports from hospital infection control nurses (ICNs), and hospital records. Recruitment of ICN reporting produced a marked increase in notifications (67 to 294). Hospital records of possible DHF cases showed that tests for ascertaining diagnosis (e.g., blood in stool, serum albumin) were frequently not performed. DCI and ICN reports underestimated severity. After hospital record review, the ratio of total DHF cases to cases detected by surveillance was approximately 3:1, whether using clinical criteria or using clinical and dengue laboratory diagnosis. An important determinant for the low sensitivity (28.4%) and high specificity (96.5%) of the surveillance system was the World Health Organization (WHO) clinical definition for DHF. In spite of such limitations, DHF surveillance data in Puerto Rico provide abundant, reliable information for monitoring disease trends. These methods may be applied to other situations to define the characteristics and incidence trends of emerging infections. PMID:10730300

  8. Viremia and antibody response of small African and laboratory animals to Crimean-Congo hemorrhagic fever virus infection.

    PubMed

    Shepherd, A J; Leman, P A; Swanepoel, R

    1989-05-01

    Eleven species of small African wild mammals, laboratory rabbits, guinea pigs, and Syrian hamsters were infected with Crimean-Congo hemorrhagic fever (CCHF) virus. Low-titered viremia followed by development of antibody was observed in scrub hares (Lepus saxatilis), Cape ground squirrels (Xerus inauris), red veld rats (Aethomys chrysophilus), white tailed rats (Mystromys albicaudatus), bushveld gerbils (Tatera leucogaster), striped mice (Rhabdomys pumilio), and guinea pigs. The maximum viremic titer in 4 scrub hares was 10(1.7-4.2) 50% mouse lethal doses/ml. Viremia was detected in 1/17 infected laboratory rabbits. Antibody response was only detected in South African hedgehogs (Atelerix frontalis), highveld gerbils (T. brantsii), Namaqua gerbils (Desmodillus auricularis), 2 species of multimammate mouse (Mastomys natalensis and M. coucha), and Syrian hamsters. The results of the study indicate that a proportion of infected scrub hares develop CCHF viremia of an intensity shown in the Soviet Union to be sufficient for infection of feeding immature ixodid ticks, but that South African hedgehogs and wild rodents are unlikely to be of importance as maintenance hosts of the virus in southern Africa. PMID:2499205

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

    SciTech Connect

    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.

  10. Geo-spatial Hotspots of Hemorrhagic Fever with Renal Syndrome and Genetic Characterization of Seoul Variants in Beijing, China

    PubMed Central

    Zuo, Shu-Qing; Fang, Li-Qun; Zhan, Lin; Zhang, Pan-He; Jiang, Jia-Fu; Wang, Li-Ping; Ma, Jia-Qi; Wang, Bing-Cai; Wang, Ri-Min; Wu, Xiao-Ming; Yang, Hong; Cao, Zhi-Wei; Cao, Wu-Chun

    2011-01-01

    Background Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, and has extended from rural areas to cities recently. Beijing metropolis is a novel affected region, where the HFRS incidence seems to be diverse from place to place. Methodology/Principal Findings The spatial scan analysis based on geographical information system (GIS) identified three geo-spatial “hotspots” of HFRS in Beijing when the passive surveillance data from 2004 to 2006 were used. The Relative Risk (RR) of the three “hotspots” was 5.45, 3.57 and 3.30, respectively. The Phylogenetic analysis based on entire coding region sequence of S segment and partial L segment sequence of Seoul virus (SEOV) revealed that the SEOV strains circulating in Beijing could be classified into at least three lineages regardless of their host origins. Two potential recombination events that happened in lineage #1 were detected and supported by comparative phylogenetic analysis. The SEOV strains in different lineages and strains with distinct special amino acid substitutions for N protein were partially associated with different spatial clustered areas of HFRS. Conclusion/Significance Hotspots of HFRS were found in Beijing, a novel endemic region, where intervention should be enhanced. Our data suggested that the genetic variation and recombination of SEOV strains was related to the high risk areas of HFRS, which merited further investigation. PMID:21264354

  11. Tofla virus: A newly identified Nairovirus of the Crimean-Congo hemorrhagic fever group isolated from ticks in Japan.

    PubMed

    Shimada, Satoshi; Aoki, Kotaro; Nabeshima, Takeshi; Fuxun, Yu; Kurosaki, Yohei; Shiogama, Kazuya; Onouchi, Takanori; Sakaguchi, Miako; Fuchigami, Takeshi; Ono, Hokuto; Nishi, Kodai; Posadas-Herrera, Guillermo; Uchida, Leo; Takamatsu, Yuki; Yasuda, Jiro; Tsutsumi, Yutaka; Fujita, Hiromi; Morita, Kouichi; Hayasaka, Daisuke

    2016-01-01

    Ixodid ticks transmit several important viral pathogens. We isolated a new virus (Tofla virus: TFLV) from Heamaphysalis flava and Heamaphysalis formsensis in Japan. The full-genome sequences revealed that TFLV belonged to the genus Nairovirus, family Bunyaviridae. Phylogenetic analyses and neutralization tests suggested that TFLV is closely related to the Hazara virus and that it is classified into the Crimean-Congo hemorrhagic fever group. TFLV caused lethal infection in IFNAR KO mice. The TFLV-infected mice exhibited a gastrointestinal disorder, and positron emission tomography-computed tomography images showed a significant uptake of (18)F-fluorodeoxyglucose in the intestinal tract. TFLV was able to infect and propagate in cultured cells of African green monkey-derived Vero E6 cells and human-derived SK-N-SH, T98-G and HEK-293 cells. Although TFLV infections in humans and animals are currently unknown, our findings may provide clues to understand the potential infectivity and to develop of pre-emptive countermeasures against this new tick-borne Nairovirus. PMID:26863911

  12. Structural Characterization of the Crimean-Congo Hemorrhagic Fever Virus Gn Tail Provides Insight into Virus Assembly*

    PubMed Central

    Estrada, D. Fernando; De Guzman, Roberto N.

    2011-01-01

    The RNA virus that causes the Crimean Congo Hemorrhagic Fever (CCHF) is a tick-borne pathogen of the Nairovirus genus, family Bunyaviridae. Unlike many zoonotic viruses that are only passed between animals and humans, the CCHF virus can also be transmitted from human to human with an overall mortality rate approaching 30%. Currently, there are no atomic structures for any CCHF virus proteins or for any Nairovirus proteins. A critical component of the virus is the envelope Gn glycoprotein, which contains a C-terminal cytoplasmic tail. In other Bunyaviridae viruses, the Gn tail has been implicated in host-pathogen interaction and viral assembly. Here we report the NMR structure of the CCHF virus Gn cytoplasmic tail, residues 729–805. The structure contains a pair of tightly arranged dual ββα zinc fingers similar to those found in the Hantavirus genus, with which it shares about 12% sequence identity. Unlike Hantavirus zinc fingers, however, the CCHF virus zinc fingers bind viral RNA and contain contiguous clusters of conserved surface electrostatics. Our results provide insight into a likely role of the CCHF virus Gn zinc fingers in Nairovirus assembly. PMID:21507948

  13. Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles

    PubMed Central

    Zivcec, Marko; Metcalfe, Maureen G.; Albariño, César G.; Guerrero, Lisa W.; Pegan, Scott D.; Spiropoulou, Christina F.; Bergeron, Éric

    2015-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is an often lethal, acute inflammatory illness that affects a large geographic area. The disease is caused by infection with CCHF virus (CCHFV), a nairovirus from the Bunyaviridae family. Basic research on CCHFV has been severely hampered by biosafety requirements and lack of available strains and molecular tools. We report the development of a CCHF transcription- and entry-competent virus-like particle (tecVLP) system that can be used to study cell entry and viral transcription/replication over a broad dynamic range (~4 orders of magnitude). The tecVLPs are morphologically similar to authentic CCHFV. Incubation of immortalized and primary human cells with tecVLPs results in a strong reporter signal that is sensitive to treatment with neutralizing monoclonal antibodies and by small molecule inhibitors of CCHFV. We used glycoproteins and minigenomes from divergent CCHFV strains to generate tecVLPs, and in doing so, we identified a monoclonal antibody that can prevent cell entry of tecVLPs containing glycoproteins from 3 pathogenic CCHFV strains. In addition, our data suggest that different glycoprotein moieties confer different cellular entry efficiencies, and that glycoproteins from the commonly used strain IbAr10200 have up to 100-fold lower ability to enter primary human cells compared to glycoproteins from pathogenic CCHFV strains. PMID:26625182

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

    PubMed

    Bai, Yuntao; Xu, Zhiguang; Lu, Bo; Sun, Qinghua; Tang, Wenge; Liu, Xiaobo; Yang, Weizhong; Xu, Xinyi; Liu, Qiyong

    2015-01-01

    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. PMID:26193359

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

    PubMed Central

    2010-01-01

    microscopy analysis demonstrated that LASV VLP appeared structurally similar to native virions, with pleiomorphic distribution in size and shape. LASV VLP that displayed GPC or GPC+NP were immunogenic in mice, and generated a significant IgG response to individual viral proteins over the course of three immunizations, in the absence of adjuvants. Furthermore, sera from convalescent Lassa fever patients recognized VLP in ELISA format, thus affirming the presence of native epitopes displayed by the recombinant pseudoparticles. Conclusions These results established that modular LASV VLP can be generated displaying high levels of immunogenic viral proteins, and that small laboratory scale mammalian expression systems are capable of producing multi-milligram quantities of pseudoparticles. These VLP are structurally and morphologically similar to native LASV virions, but lack replicative functions, and thus can be safely generated in low biosafety level settings. LASV VLP were immunogenic in mice in the absence of adjuvants, with mature IgG responses developing within a few weeks after the first immunization. These studies highlight the relevance of a VLP platform for designing an optimal vaccine candidate against Lassa hemorrhagic fever, and warrant further investigation in lethal challenge animal models to establish their protective potential. PMID:20961433

  16. Genovariation Study of Hantavirus in Main Endemic Areas of Hemorrhagic Fever with Renal Syndrome in Hebei Province, China

    PubMed Central

    Li, Qi; Cai, Yanan; Wei, Yamei; Han, Xu; Han, Zhanying; Zhang, Yanbo; Qi, Shunxiang; Xu, Yonggang

    2016-01-01

    Background Hemorrhagic fever with renal syndrome (HFRS) is an important infectious disease in Hebei Province. At present, cases from the northeast regions of the province account for >80% of the total incidences. However, studies that examine the region-specific genetic variations of the Hantavirus (HV), the causative pathogen for HFRS, have been lacking. Methods Rodents were collected in northeast Hebei Province from 2004 to 2013, and the HV strains used in this study were isolated in 1993. Lung tissues were isolated from the rodents and HV antigen was detected by indirect immunofluorescence. The M1 and M2 fragments of HV M region were amplified by reverse transcription polymerase chain reaction (RT-PCR), cloned into pMDl9-T vector, sequenced and compared with representative standard stains for homology and phylogenetic analysis. Result A total of 21 samples of HV antigen-positive were collected. Real-time PCR analysis revealed that the 19 rodent lungs and two HV strains were positive for the SEO virus. 11 samples were chosen to sequence, and they shared 95.8%–99.8% in nucleotide homology, and 83.6%–99.2% when compared to the standard strains of SEO virus. Phylogenetic analysis demonstrated that all strains were grouped into the same S3 subtype. Conclusion SEO was the major epidemic genotype of HV in the main HFRS endemic areas in Hebei Province, and S3 was the major subtype. There was minor genetic variation in HV over short term periods, while long term variations were higher. PMID:27442527

  17. Crimean-Congo Hemorrhagic Fever Virus Entry into Host Cells Occurs through the Multivesicular Body and Requires ESCRT Regulators

    PubMed Central

    Shtanko, Olena; Nikitina, Raisa A.; Altuntas, Cengiz Z.; Chepurnov, Alexander A.; Davey, Robert A.

    2014-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne bunyavirus causing outbreaks of severe disease in humans, with a fatality rate approaching 30%. There are no widely accepted therapeutics available to prevent or treat the disease. CCHFV enters host cells through clathrin-mediated endocytosis and is subsequently transported to an acidified compartment where the fusion of virus envelope with cellular membranes takes place. To better understand the uptake pathway, we sought to identify host factors controlling CCHFV transport through the cell. We demonstrate that after passing through early endosomes in a Rab5-dependent manner, CCHFV is delivered to multivesicular bodies (MVBs). Virus particles localized to MVBs approximately 1 hour after infection and affected the distribution of the organelle within cells. Interestingly, blocking Rab7 activity had no effect on association of the virus with MVBs. Productive virus infection depended on phosphatidylinositol 3-kinase (PI3K) activity, which meditates the formation of functional MVBs. Silencing Tsg101, Vps24, Vps4B, or Alix/Aip1, components of the endosomal sorting complex required for transport (ESCRT) pathway controlling MVB biogenesis, inhibited infection of wild-type virus as well as a novel pseudotyped vesicular stomatitis virus (VSV) bearing CCHFV glycoprotein, supporting a role for the MVB pathway in CCHFV entry. We further demonstrate that blocking transport out of MVBs still allowed virus entry while preventing vesicular acidification, required for membrane fusion, trapped virions in the MVBs. These findings suggest that MVBs are necessary for infection and are the sites of virus-endosome membrane fusion. PMID:25233119

  18. Crimean-Congo Hemorrhagic Fever in the One-Humped Camel (Camelus dromedarius) in East and Northeast of Iran

    PubMed Central

    Champour, Mohsen; Chinikar, Sadegh; Mohammadi, Gholamreza; Razmi, Gholamreza; Mostafavi, Ehsan; Shah-Hosseini, Nariman; Khakifirouz, Sahar; Jalali, Tahmineh

    2016-01-01

    Background: This comprehensive study was conducted on multi-purpose one-humped camel (Camelus dromedarius) sera and ticks to assess the epidemiological aspects of the Crimean-Congo hemorrhagic fever virus (CCHFV) in northeast Iran. Methods: From May 2012 to January 2013, eleven cities were randomly selected in the Khorasan Provinces of Iran as “clusters,” and at least 14 one-humped camels were sampled from each area. Reverse transcriptase polymerase chain reaction was used for the detection of the CCHFV genome in ticks. Sera were analyzed using specific enzyme-linked immunosorbent assay tests. Results: Four hundred and eighty ixodid ticks were collected, and the genome of the CCHFV was detected in 49 (10.2%) out of 480 ticks. The CCHFV genome was detected in two out of four tick species, and in tick samples from three cities in Khorassan-e-Jonoobi. All three provinces, and six out of eleven cities, were CCHFV-specific IgG-positive. In total, nine (5.3%) out of 170 one-humped camels were IgG-positive. The highest rate of IgG-positive samples was found in Nehbandan (16.67%). Conclusion: Continued surveillance and strictly enforced importation and quarantine practices should be implemented to prevent human exposure and the on-going dispersal of infected ticks and livestock in these regions. It is recommended that acaricides be used to prevent CCHF transmission to humans, and to reduce the tick population. In addition, care should be taken by abattoirs workers and people who work with one-humped camels. PMID:27308275

  19. Relationship of plasma cell-free DNA level with mortality and prognosis in patients with Crimean-Congo hemorrhagic fever.

    PubMed

    Bakir, Mehmet; Engin, Aynur; Kuskucu, Mert Ahmet; Bakir, Sevtap; Gündag, Omür; Midilli, Kenan

    2016-07-01

    Crimean-Congo hemorrhagic fever (CCHF) is a viral infection. Circulating plasma cell-free DNA (pcf-DNA) is a novel marker indicating cellular damage. So far, the role of pcf-DNA did not investigate in CCHF patients. In the current study, pcf-DNA levels were investigated in CCHF patients with different clinical severity grades to explore the relationship between circulating pcf-DNA level, virus load, and disease severity. Seventy-two patients were categorized as mild, intermediate, and severe based on severity grading scores. The pcf-DNA level was obtained from all participants on admission and from the survivors on the day of the discharge. The controls consisted of 31 healthy. Although the pcf-DNA level at admission was higher in patients than in the controls, the difference was not statistically significant (P = 0.291). However, at admission and in the convalescent period, the difference between pcf-DNA levels in mild, intermediate, and severe patient groups was significant. The pcf-DNA level in severe patients was higher than in the others. Furthermore, compared to survivors, non-survivors had higher pcf-DNA levels at admission (P = 0.001). A direct relationship was found between the pcf-DNA level and the viral load on the day of discharge in surviving patients. ROC curve analysis identified a pcf-DNA level of 0.42 as the optimal cut-off for prediction of mortality. The positive predictive value, negative predictive value, specificity, and sensitivity for predicting mortality was 100%, 72%, 100%, and 79%, respectively. In summary, our findings revealed that pcf-DNA levels may be used as a biomarker in predicting CHHF prognosis. J. Med. Virol. 88:1152-1158, 2016. © 2015 Wiley Periodicals, Inc. PMID:26680021

  20. Crimean-Congo Hemorrhagic Fever Virus Clades V and VI (Europe 1 and 2) in Ticks in Kosovo, 2012

    PubMed Central

    Muji, Skender; Robaj, Avni; Ahmeti, Salih; Jakupi, Xhevat; Emmerich, Petra; Krüger, Andreas

    2014-01-01

    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. PMID:25255381

  1. The Spatial Analysis on Hemorrhagic Fever with Renal Syndrome in Jiangsu Province, China Based on Geographic Information System

    PubMed Central

    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

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:25207806

  2. Increasing incidence of hemorrhagic fever with renal syndrome could be associated with livestock husbandry in Changchun, Northeastern China

    PubMed Central

    2014-01-01

    Background Since the end of the 1990s, the incidence of hemorrhagic fever with renal syndrome (HFRS) has been increasing dramatically in Changchun, northeastern China. However, it is unknown which, and how, underlying risk factors have been involved in the reemergence of the disease. Methods Data on HFRS cases at the county scale were collected from 1998 to 2012. Data on livestock husbandry including the numbers of large animals (cattle, horses, donkeys and mules), sheep, and deer, and on climatic and land cover variables were also collected. Epidemiological features, including the spatial, temporal and human patterns of disease were characterized. The potential factors related to spatial heterogeneity and temporal trends were analyzed using standard and time-series Poisson regression analysis, respectively. Results Annual incidence varied among the 10 counties. Shuangyang County in southeastern Changchun had the highest number of cases (1,525 cases; 35.9% of all cases), but its population only accounted for 5.6% of the total population. Based on seasonal pattern in HFRS incidence, two epidemic phases were identified. One was a single epidemic peak at the end of each year from 1988 to 1997 and the other consisted of dual epidemic peaks at both the end and the beginning of each year from 1998 to the end of the study period. HFRS incidence was higher in males compared to females, and most of the HFRS cases occurred in peasant populations. The results of the Poisson regression analysis indicated that the spatial distribution and the increasing incidence of HFRS were significantly associated with livestock husbandry and climate factors, particularly with deer cultivation. Conclusions Our results indicate that the re-emergence of HFRS in Changchun has been accompanied by changing seasonal patterns over the past 25 years. Integrated measures focusing on areas related to local livestock husbandry could be helpful for the prevention and control of HFRS. PMID:24894341

  3. Fine Epitope Mapping of the Central Immunodominant Region of Nucleoprotein from Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

    PubMed Central

    Liu, Dongliang; Li, Yang; Zhao, Jing; Deng, Fei; Duan, Xiaomei; Kou, Chun; Wu, Ting; Li, Yijie; Wang, Yongxing; Ma, Ji; Yang, Jianhua; Hu, Zhihong; Zhang, Fuchun; Zhang, Yujiang; Sun, Surong

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF), a severe viral disease known to have occurred in over 30 countries and distinct regions, is caused by the tick-borne CCHF virus (CCHFV). Nucleocapsid protein (NP), which is encoded by the S gene, is the primary antigen detectable in infected cells. The goal of the present study was to map the minimal motifs of B-cell epitopes (BCEs) on NP. Five precise BCEs (E1, 247FDEAKK252; E2a, 254VEAL257; E2b, 258NGYLNKH264; E3, 267EVDKA271; and E4, 274DSMITN279) identified through the use of rabbit antiserum, and one BCE (E5, 258NGYL261) recognized using a mouse monoclonal antibody, were confirmed to be within the central region of NP and were partially represented among the predicted epitopes. Notably, the five BCEs identified using the rabbit sera were able to react with positive serum mixtures from five sheep which had been infected naturally with CCHFV. The multiple sequence alignment (MSA) revealed high conservation of the identified BCEs among ten CCHFV strains from different areas. Interestingly, the identified BCEs with only one residue variation can apparently be recognized by the positive sera of sheep naturally infected with CCHFV. Computer-generated three-dimensional structural models indicated that all the antigenic motifs are located on the surface of the NP stalk domain. This report represents the first identification and mapping of the minimal BCEs of CCHFV-NP along with an analysis of their primary and structural properties. Our identification of the minimal linear BCEs of CCHFV-NP may provide fundamental data for developing rapid diagnostic reagents and illuminating the pathogenic mechanism of CCHFV. PMID:25365026

  4. Seroprevalence of Crimean-Congo Hemorrhagic Fever Virus in Erzincan Province, Turkey, Relationship with Geographic Features and Risk Factors.

    PubMed

    Cikman, Aytekin; Aydin, Merve; Gulhan, Baris; Karakecili, Faruk; Kesik, Ozan Arif; Ozcicek, Adalet; Akin, Hicran; Kara, Murat

    2016-03-01

    To determine the seroprevalence and risk factors associated with Crimean-Congo hemorrhagic fever virus (CCHFV) in residents of Erzincan, Turkey. Although CCHFV is endemic in Erzincan, this is the first study to evaluate its seroprevalence in this region. This study included a total of 372 subjects, 174 of whom had been exposed to or bitten by ticks, 145 of whom worked with livestock, and 53 of whom resided in the city and did not have exposure to livestock. Data on CCHFV IgG and IgM antibodies were extracted from serum samples collected from all subjects using an ELISA. All samples were tested for CCHFV IgG and CCHFV IgM. Only IgM-positive samples were processed for detection of viral RNA through RT-PCR. Using seropositive cases only, we performed spatial analyses to evaluate correlations between seroprevalence and geographic location (i.e., proximity to rivers, altitude, and slope angle of land). In this study, 14.0% (52/322) of the total subjects were positive for CCHFV IgG. Seven of the individuals were positive both for CCHFV IgG and CCHFV IgM. Of these seven, only one sample tested positive for CCHFV RNA. Individuals who worked with livestock in the rural areas and had a history of tick exposure were statistically more likely to test positive for CCHFV IgG than individuals from the city and not exposed to ticks (p < 0.05). Seroprevalence was affected by geographic characteristics, including distance to rivers, altitude, and slope angle of land. We observed a high seroprevalence of CCHFV in Erzincan, which is similar to that observed in other endemic regions of Turkey. CCHFV seroprevalence rates are found to be quite high in the people who live in the sloping fields at certain heights and where there are a lot of rivers and streams. PMID:26808904

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

    PubMed

    Sherifi, Kurtesh; Cadar, Daniel; Muji, Skender; Robaj, Avni; Ahmeti, Salih; Jakupi, Xhevat; Emmerich, Petra; Krüger, Andreas

    2014-09-01

    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. PMID:25255381

  6. Dengue hemorrhagic fever

    MedlinePlus

    ... a severe, potentially deadly infection spread by some mosquitos. Causes Four different dengue viruses are known to ... occurs when a person is bitten by a mosquito that is infected with the virus. The mosquito ...

  7. Viral Hemorrhagic Fevers

    MedlinePlus

    ... Related Links About VSPB (Viral Special Pathogens Branch) File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  8. A novel mu-capture enzyme-linked immunosorbent assay based on recombinant proteins for sensitive and specific diagnosis of hemorrhagic fever with renal syndrome.

    PubMed Central

    Zöller, L G; Yang, S; Gött, P; Bautz, E K; Darai, G

    1993-01-01

    Hantavirus nucleocapsid protein has recently been identified as a major antigen inducing an early and long-lasting humoral immune response in patients with hemorrhagic fever with renal syndrome. A mu-capture enzyme-linked immunosorbent assay utilizing recombinant nucleocapsid proteins of Hantavirus strains Hantaan 76-118 (Hantaan serotype) and CG 18-20 (Puumala serotype) as diagnostic antigens and specific monoclonal antibodies as the detection system has been developed. Histidine-tailed recombinant proteins were expressed in Escherichia coli and purified in a single step by affinity chromatography on a nickel-chelate resin. The assay was evaluated with a panel of sera from patients with hemorrhagic fever with renal syndrome originating from various geographic regions. The overall sensitivity of the mu-capture enzyme-linked immunosorbent assay (both recombinant antigens) was 100%, and its specificity was also found to be 100%. Immunoglobulin M antibodies were detected as early as on day 3, and maximum titers were obtained between days 8 and 25 after onset of the disease. The assay was regularly found to be positive within 3 to 4 months but in some cases up to 2 years after the acute phase of the disease. Images PMID:8099085

  9. A Specific Interaction of Small Molecule Entry Inhibitors with the Envelope Glycoprotein Complex of the Junín Hemorrhagic Fever Arenavirus*

    PubMed Central

    Thomas, Celestine J.; Casquilho-Gray, Hedi E.; York, Joanne; DeCamp, Dianne L.; Dai, Dongcheng; Petrilli, Erin B.; Boger, Dale L.; Slayden, Richard A.; Amberg, Sean M.; Sprang, Stephen R.; Nunberg, Jack H.

    2011-01-01

    Arenaviruses are responsible for acute hemorrhagic fevers worldwide and are recognized to pose significant threats to public health and biodefense. Small molecule compounds have recently been discovered that inhibit arenavirus entry and protect against lethal infection in animal models. These chemically distinct inhibitors act on the tripartite envelope glycoprotein (GPC) through its unusual stable signal peptide subunit to stabilize the complex against pH-induced activation of membrane fusion in the endosome. Here, we report the production and characterization of the intact transmembrane GPC complex of Junín arenavirus and its interaction with these inhibitors. The solubilized GPC is antigenically indistinguishable from the native protein and forms a homogeneous trimer in solution. When reconstituted into a lipid bilayer, the purified complex interacts specifically with its cell-surface receptor transferrin receptor-1. We show that small molecule entry inhibitors specific to New World or Old World arenaviruses bind to the membrane-associated GPC complex in accordance with their respective species selectivities and with dissociation constants comparable with concentrations that inhibit GPC-mediated membrane fusion. Furthermore, competitive binding studies reveal that these chemically distinct inhibitors share a common binding pocket on GPC. In conjunction with previous genetic studies, these findings identify the pH-sensing interface of GPC as a highly vulnerable target for antiviral intervention. This work expands our mechanistic understanding of arenavirus entry and provides a foundation to guide the development of small molecule compounds for the treatment of arenavirus hemorrhagic fevers. PMID:21159779

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

    SciTech Connect

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

    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.

  11. Climate and climate change and infectious disease risk in Thailand: A spatial study of dengue hemorrhagic fever using GIS and remotely-sensed imagery

    NASA Astrophysics Data System (ADS)

    Kuzera, Kristopher

    The scientific community has widely accepted that climate plays a key role in the sustainability and transmission of many infectious diseases. Global climate change can potentially trigger the spread of disease into new regions and increase the intensity of disease in regions where it is endemic. This study explores the association between monthly conditions of climate change to changes in disease risk, emphasizing the potential spread of dengue fever due to climate change in Thailand. This study also develops techniques new to GIS and remote sensing that generate surfaces of daily minimum temperature toward identifying areas at greater transmission risk. Dengue fever expansion due to global warming is a serious concern for Thailand where warming temperatures may increase the size of the habitat of the disease-spreading vector, Aedes aegypti, particularly during cooler months when transmission is limited by environmental conditions. In this study, first, the association between past dengue hemorrhagic fever (DHF) and climate in Thailand is determined. Second, evidence of recent climate change is related to changes in DHF rates. Third, daily minimum temperature is derived from remote sensing toward identifying the spatial and temporal limitations of potential transmission risk. The results indicate that minimum temperature has recently experienced a rapid increase, particularly in the winter months when transmission is low. This is associated with a recent rise in winter DHF cases. As increasing minimum temperatures in these regions are anticipated to continue, we can expect dengue transmission rates to also increase throughout the year.

  12. Evaluation of serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha in patients with Crimean-Congo hemorrhagic fever.

    PubMed

    Ergonul, Onder; Tuncbilek, Semra; Baykam, Nurcan; Celikbas, Aysel; Dokuzoguz, Basak

    2006-04-01

    We investigated the role played by cytokines in the mortality of patients with Crimean-Congo hemorrhagic fever (CCHF). Serum levels of several cytokines were measured in 3 patients with fatal CCHF and in 27 patients with nonfatal CCHF. Levels of interleukin (IL)-6 (P< or = .001) and tumor necrosis factor (TNF)-alpha (P = .004) were significantly higher in patients with fatal CCHF than in patients with nonfatal CCHF, whereas levels of IL-10 were not significantly different between the 2 groups (P = .937). Disseminated intravascular coagulation (DIC) scores were also higher in the patients with fatal CCHF (P = .023). Levels of IL-6 and TNF-alpha were positively correlated with DIC scores, whereas levels of IL-10 were negatively correlated with DIC scores. In conclusion, these findings demonstrate that proinflammatory cytokines play a major role in the mortality of patients with CCHF. PMID:16518755

  13. A hantavirus causing hemorrhagic fever with renal syndrome requires gC1qR/p32 for efficient cell binding and infection

    SciTech Connect

    Choi, Yun; Kwon, Young-Chan; Kim, Soo-In; Park, Jung-Min; Lee, Kyung-Hee; Ahn, Byung-Yoon

    2008-11-25

    Hantaan virus (HTNV) is a pathogenic hantavirus that causes hemorrhagic fever with renal syndrome (HFRS). HTNV infection is mediated by {alpha}v{beta}3 integrin. We used protein blots of Vero E6 cell homogenates to demonstrate that radiolabeled HTNV virions bind to gC1qR/p32, the acidic 32-kDa protein known as the receptor for the globular head domain of complement C1q. RNAi-mediated suppression of gC1qR/p32 markedly reduced HTNV binding and infection in human lung epithelial A549 cells. Conversely, transient expression of either simian or human gC1qR/p32 rendered non-permissive CHO cells susceptible to HTNV infection. These results suggest an important role for gC1qR/p32 in HTNV infection and pathogenesis.

  14. Drought, epidemic disease, and the fall of classic period cultures in Mesoamerica (AD 750-950). Hemorrhagic fevers as a cause of massive population loss.

    PubMed

    Acuna-Soto, Rodolfo; Stahle, David W; Therrell, Matthew D; Gomez Chavez, Sergio; Cleaveland, Malcolm K

    2005-01-01

    The classical period in Mexico (AD 250-750) was an era of splendor. The city of Teotihuacan was one of the largest and most sophisticated human conglomerates of the pre-industrial world. The Mayan civilization in southeastern Mexico and the Yucatan peninsula reached an impressive degree of development at the same time. This time of prosperity came to an end during the Terminal Classic Period (AD 750-950) a time of massive population loss throughout Mesoamerica. A second episode of massive depopulation in the same area was experienced during the sixteenth century when, in less than one century, between 80% and 90% of the entire indigenous population was lost. The 16th century depopulation of Mexico constitutes one of the worst demographic catastrophes in human history. Although newly imported European and African diseases caused high mortality among the native population, the major 16th century population losses were caused by a series of epidemics of a hemorrhagic fever called Cocoliztli, a highly lethal disease unknown to both Aztec and European physicians during the colonial era. The cocoliztli epidemics occurred during the 16th century megadrought, when severe drought extended at times from central Mexico to the boreal forest of Canada, and from the Pacific to the Atlantic coast. The collapse of the cultures of the Classic Period seems also to have occurred during a time of severe drought. Tree ring and lake sediment records indicate that some of the most severe and prolonged droughts to impact North America-Mesoamerica in the past 1000-4000 years occurred between AD 650 and 1000, particularly during the 8th and 9th centuries, a period of time that coincides with the Terminal Classic Period. Based on the similarities of the climatic (severe drought) and demographic (massive population loss) events in Mesoamerica during the sixteenth century, we propose that drought-associated epidemics of hemorrhagic fever may have contributed to the massive population loss

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

    PubMed Central

    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

  16. Dengue Fever

    Technology Transfer Automated Retrieval System (TEKTRAN)

    “Dengue Fever” will be included in “Health Information for International Travel, 2007-2008” which will be published by the U.S. Centers for Disease Control and Prevention. Dengue and dengue hemorrhagic fever are viral diseases transmitted by Aedes mosquitoes. The disease is found in tropical and s...

  17. Epidemiological Survey of Crimean-Congo Hemorrhagic Fever (CCHF), a Fatal Infectious Disease in Khuzestan Province, Southwest Iran, During 1999 - 2015

    PubMed Central

    Sharififard, Mona; Alavi, Sayed Mohammad; Salmanzadeh, Shokrollah; Safdari, Farhad; Kamali, Amin

    2016-01-01

    Background Crimean-Congo hemorrhagic fever (CCHF) is an arboviral zoonotic disease transmitted to humans mainly through the bite of blood-sucking Ixodidae ticks and also via contact with the blood and tissues of infected livestock. Objectives This study is a retrospective descriptive survey based on data collected from the health center of Khuzestan province, Iran, during 1999 - 2015. Patients and Methods Patients with symptoms of severe headache, high fever, and bleeding were evaluated. Laboratory tests and serological or molecular assays were used to detect probable and confirmed cases, respectively. The epidemiological parameters of this study were analyzed on the basis of probable cases. Results A total of 42 patients were diagnosed as probable cases, and 17 of these (42.5%) were confirmed serologically. Two peaks of the disease occurred in Khuzestan province, in 2003 and 2010, with seven cases each of those years, leading to the deaths of five and two patients, respectively. Men and women comprised 57.1% and 42.9% of the patients, respectively. Of all probable cases, 64.3% were from urban areas and 35.7% were from rural areas. The age groups of 10 - 19 and 20 - 29 years, with a frequency of 26.2% in each group, were exposed to the most infections. Farmers and housewives were the highest at-risk occupational groups with a frequency of 28.6% and 26%, respectively. Fever, bleeding, and thrombocytopenia were reported in 95% of the patients, and the case-fatality ratio was calculated to be 28.6% (12 of 42 cases). Conclusions Continuous training is necessary to improve the knowledge and awareness of the highest-risk groups with regard to the transmission modes, prevention, symptoms, and treatment of this disease. PMID:27540454

  18. Characterization of dengue virus infections in a sample of patients suggests unique clinical, immunological, and virological profiles that impact on the diagnosis of dengue and dengue hemorrhagic fever.

    PubMed

    Senaratne, Thamarasi; Wimalaratne, Harith; Alahakoon, D G S; Gunawardane, Nirmali; Carr, Jillian; Noordeen, Faseeha

    2016-10-01

    Dengue virus (DENV) infections are increasing with respect to incidence and severity in the Central Province of Sri Lanka. The objective of this study was to define the clinical, immunological, and virological profiles of patients admitted to the General Hospital, Kandy with clinically apparent dengue. Demographic, clinical, hematological parameters, liver enzymes (ALT and AST), and blood samples were collected from 292 patients with fever <5 days post onset and fulfilling the WHO criteria for the diagnosis of dengue fever/dengue hemorrhagic fever (DF/DHF). Samples were analyzed for, anti-DENV IgM, IgG, and DENV nucleic acid. Myalgia was the commonest complaint by 65% of the patients. Packed cell volume was >45% in 27% of the patients while 42.12% had reduced platelets and 62.67% had reduced white blood cell counts. In contrast to other studies, positive tourniquet test (PTT) and petechiae were not major indicators of DENV infection or severity of the disease. Clinical profiles were significantly different between DF and DHF/DSS and showed many similarities to that reported elsewhere. Altogether, 43 patients (14.73%) were viremic as detected by RT-PCR; 181 patients (62%) were positive for anti-DENV IgM, and 245 (84%) patients were positive for anti-DENV IgG. In combination, anti-DENV IgM and RT-PCR assays detected 224 (77.5%) of DENV infected cases, thus improving the DENV diagnosis rate. Hence, the diagnostic utility of PTT, anti-DENV IgM/IgG serology, or RT-PCR used alone in the early phase of illness is low in Sri Lanka but the diagnostic value can be improved by a combination of serology and RT-PCR. J. Med. Virol. 88:1703-1710, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990973

  19. Association DENV1 and DENV2 infection with high serum levels of soluble thrombomodulin and VEGF in patients with dengue fever and dengue hemorrhagic fever

    PubMed Central

    del Moral-Hernández, Oscar; Martínez-Hernández, Norma E; Mosso-Pani, Manuel A; Hernández-Sotelo, Daniel; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; Antonio-Vejar, Verónica; Leyva-Vázquez, Marco Antonio

    2014-01-01

    Infection by dengue virus (DENV) can be asymptomatic or manifest in two clinically differentiated forms: dengue fever (DF) and denguehemorrhagic fever (DHF). The principal pathophysiological characteristic of DHF is the increase in vascular permeability and the loss of plasma caused by the malfunction of the vascular endothelium that induces the release of chemical mediators. However, so far there is nothing that allows for the identification the patients that are at risk of developing the more severe form of the illness. The objective of this study was to investigate the relationship between the serum levels of soluble thrombomodulin (sTM) and VEGF with the severity of dengue and the viral serotype. 231 serum samples were analyzed, 70 DF, 80 DHF and 81 control group, all were residents of Guerrero state in Mexico. The infection by dengue virus as well and the levels of sTM and VEGF were determined using the ELISA sandwich, while the serotype was determined by real time RT-PCR. Our results show that the concentrations of sTM correlate with the degree of severity of the disease given that they are significantly higher (p<0.001) in the DHF group (median = 10.2 ng/mL) than in the DF group (median = 7.2 ng/mL), and these in turn higher than those of the control group (median = 3.3 ng/mL). The concentration of sTM was significantly higher (p=0.0002) in the patients infected with DENV2. For the VEGF, the highest levels were found in DF (median = 291.3 pg/mL) and did not correlate with the severity of the disease. In conclusion, our results indicate that sTM is a good marker for the severity of the infection by DENV, better than VEGF, and with higher sensibility and specificity. PMID:24600491

  20. [Hemorrhagic form of dengue fever observed at the Infectious Diseases Department CHU Yalgado Ouédraogo, Burkina Faso].

    PubMed

    Mamoudou, Savadogo; Boushab, Boushab Mohamed

    2016-01-01

    Dengue is a re-emerging arboviral disease in tropical countries. Haemorrhagic form may be associated with circulatory failure and produce hypovolemic shock, which is often fatal. We report a series of three cases of hemorrhagic dengue observed at the Infectious Diseases Department CHU Yalgado Ouédraogo, Ouagadougou, in order to describe its epidemiological, clinical, and evolutive characteristics. Our study included young females who had an onset age of between 35 years and 45 years, residing in the city of Ouagadougou. Despite multiple concentrated platelets transfusions and symptomatic treatment, we mourned a death. The development of antivirals and of new vaccines is a silver lining to prevent dengue lethality. PMID:27303584

  1. Crimean-Congo Hemorrhagic Fever Knowledge, Attitudes, Practices, Risk Factors, and Seroprevalence in Rural Georgian Villages with Known Transmission in 2014

    PubMed Central

    Greiner, Ashley L.; Mamuchishvili, Nana; Kakutia, Natia; Stauffer, Kendra; Geleishvili, Marika; Chitadze, Nazibrola; Chikviladze, Tamar; Zakhashvili, Khatuna; Morgan, Juliette; Salyer, Stephanie J.

    2016-01-01

    In 2014 the highest annual case count of Crimean-Congo hemorrhagic fever (CCHF) was detected in Georgia since surveillance began in 2009. CCHF is a high-fatality hemorrhagic syndrome transmitted by infected ticks and animal blood. In response to this immediate public health threat, we assessed CCHF risk factors, seroprevalence, and CCHF-related knowledge, attitudes, and practices in the 12 rural villages reporting a 2014 CCHF case, to inform CCHF prevention and control measures. Households were randomly selected for interviewing and serum sample collection. Data were weighted by non-response and gender; percentages reflect weighting. Among 618 respondents, median age was 54.8 years (IQR: 26.5, range: 18.6–101.4); 215 (48.8%) were male. Most (91.5%) participants reported ≥1 CCHF high-risk activity. Of 389 participants with tick exposure, 286 (46.7%) participants handled ticks bare-handed; 65/216 (29.7%) knew the risk. Of 605 respondents, 355 (57.9%) reported animal blood exposure; 32/281 (12.7%) knew the risk. Of 612 responding, 184 (28.8%) knew protective measures against CCHF and tick exposures, but only 54.3% employed the measures. Of 435 serum samples collected, 12 were anti-CCHF IgG positive, indicating a weighted 3.0% seroprevalence. Most (66.7%) seropositive subjects reported tick exposure. In these villages, CCHF risk factors are prevalent, while CCHF-related knowledge and preventive practices are limited; these findings are critical to informing public health interventions to effectively control and prevent ongoing CCHF transmission. Additionally, CCHF seroprevalence is higher than previously detected (0.03%), highlighting the importance of this disease in the South Caucuses and in supporting ongoing regional investigations. PMID:27336731

  2. An isolated epizootic of hemorrhagic-like fever in cats caused by a novel and highly virulent strain of feline calicivirus.

    PubMed

    Pedersen, N C; Elliott, J B; Glasgow, A; Poland, A; Keel, K

    2000-05-11

    An isolated epizootic of a highly fatal feline calicivirus (FCV) infection, manifested in its severest form by a systemic hemorrhagic-like fever, occurred over a 1-month period among six cats owned by two different employees and a client of a private veterinary practice. The infection may have started with an unowned shelter kitten that was hospitalized during this same period for a severe atypical upper respiratory infection. The causative agent was isolated from blood and nasal swabs from two cats; the electron microscopic appearance was typical for FCV and capsid gene sequencing showed it to be genetically similar to other less pathogenic field strains. An identical disease syndrome was recreated in laboratory cats through oral inoculation with tissue culture grown virus. During the course of transmission studies in experimental cats, the agent was inadvertently spread by caretakers to an adjoining room containing a group of four normal adult cats. One of the four older cats was found dead and a second was moribund within 48-72h in spite of symptomatic treatment; lesions in these animals were similar to those of the field cats but with the added feature of severe pancreatitis. The mortality in field cats, deliberately infected laboratory cats, and inadvertently infected laboratory cats ranged from 33-50%. This new isolate of calicivirus, named FCV-Ari, was neutralized at negligible to low titer by antiserum against the universal FCV-F9 vaccine strain. Cats orally immunized with FCV-F9, and then challenge-exposed shortly thereafter with FCV-Ari, developed a milder self-limiting form of disease, indicating partial protection. However, all of the field cats, including the three that died, had been previously immunized with parenteral FCV-F9 vaccine. FCV-Ari caused a disease that was reminiscent of Rabbit Hemorrhagic Disease, a highly fatal calicivirus infection of older rabbits. PMID:10781727

  3. Crimean-Congo Hemorrhagic Fever Knowledge, Attitudes, Practices, Risk Factors, and Seroprevalence in Rural Georgian Villages with Known Transmission in 2014.

    PubMed

    Greiner, Ashley L; Mamuchishvili, Nana; Kakutia, Natia; Stauffer, Kendra; Geleishvili, Marika; Chitadze, Nazibrola; Chikviladze, Tamar; Zakhashvili, Khatuna; Morgan, Juliette; Salyer, Stephanie J

    2016-01-01

    In 2014 the highest annual case count of Crimean-Congo hemorrhagic fever (CCHF) was detected in Georgia since surveillance began in 2009. CCHF is a high-fatality hemorrhagic syndrome transmitted by infected ticks and animal blood. In response to this immediate public health threat, we assessed CCHF risk factors, seroprevalence, and CCHF-related knowledge, attitudes, and practices in the 12 rural villages reporting a 2014 CCHF case, to inform CCHF prevention and control measures. Households were randomly selected for interviewing and serum sample collection. Data were weighted by non-response and gender; percentages reflect weighting. Among 618 respondents, median age was 54.8 years (IQR: 26.5, range: 18.6-101.4); 215 (48.8%) were male. Most (91.5%) participants reported ≥1 CCHF high-risk activity. Of 389 participants with tick exposure, 286 (46.7%) participants handled ticks bare-handed; 65/216 (29.7%) knew the risk. Of 605 respondents, 355 (57.9%) reported animal blood exposure; 32/281 (12.7%) knew the risk. Of 612 responding, 184 (28.8%) knew protective measures against CCHF and tick exposures, but only 54.3% employed the measures. Of 435 serum samples collected, 12 were anti-CCHF IgG positive, indicating a weighted 3.0% seroprevalence. Most (66.7%) seropositive subjects reported tick exposure. In these villages, CCHF risk factors are prevalent, while CCHF-related knowledge and preventive practices are limited; these findings are critical to informing public health interventions to effectively control and prevent ongoing CCHF transmission. Additionally, CCHF seroprevalence is higher than previously detected (0.03%), highlighting the importance of this disease in the South Caucuses and in supporting ongoing regional investigations. PMID:27336731

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

    PubMed Central

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

    2015-01-01

    Background: Ebola viral fever, a highly contagious haemorrhagic disease has today become a major public health concern in the developing countries worldwide. Aim: The purpose of this study was to assess knowledge among dental practitioners regarding Ebola Haemorrhagic Fever (Ebola HF) in Tricity, (Chandigarh, Panchkula and Mohali). Materials and Methods: 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. Results: 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). Conclusion: Dental practitioners from urban areas with higher qualification had better knowledge yet there were notable deficiencies regarding the virus characteristics, diagnostics, elimination and treatment. PMID:25838631

  5. Multiple Circulating Infections Can Mimic the Early Stages of Viral Hemorrhagic Fevers and Possible Human Exposure to Filoviruses in Sierra Leone Prior to the 2014 Outbreak

    PubMed Central

    Boisen, Matthew L.; Schieffelin, John S.; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B.; Shaffer, Jeffrey G.; Hastie, Kathryn M.; Hartnett, Jessica N.; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K.; Andersen, Kristian G.; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W.; Geisbert, Joan B.; Pitts, Kelly R.; Geisbert, Thomas W.; Kulakoski, Peter; Wilson, Russell B.; Henderson, Lee; Sabeti, Pardis C.; Grant, Donald S.; Garry, Robert F.; Saphire, Erica O.; Khan, Sheik Humarr

    2015-01-01

    Abstract Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction–based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak. PMID:25531344

  6. Multiple circulating infections can mimic the early stages of viral hemorrhagic fevers and possible human exposure to filoviruses in Sierra Leone prior to the 2014 outbreak.

    PubMed

    Boisen, Matthew L; Schieffelin, John S; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B; Shaffer, Jeffrey G; Hastie, Kathryn M; Hartnett, Jessica N; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K; Andersen, Kristian G; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W; Geisbert, Joan B; Pitts, Kelly R; Geisbert, Thomas W; Kulakoski, Peter; Wilson, Russell B; Henderson, Lee; Sabeti, Pardis C; Grant, Donald S; Garry, Robert F; Saphire, Erica O; Branco, Luis M; Khan, Sheik Humarr

    2015-02-01

    Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction-based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak. PMID:25531344

  7. Time-Specific Ecologic Niche Models Forecast the Risk of Hemorrhagic Fever with Renal Syndrome in Dongting Lake District, China, 2005–2010

    PubMed Central

    Lin, Xiao-Ling; Li, Xiu-Jun; Ma, Gui-Hua; Huang, Ru; Yang, Hui-Suo; Tian, Huaiyu; Xiao, Hong

    2014-01-01

    Background Hemorrhagic fever with renal syndrome (HFRS), a rodent-borne infectious disease, is one of the most serious public health threats in China. Increasing our understanding of the spatial and temporal patterns of HFRS infections could guide local prevention and control strategies. Methodology/Principal Findings We employed statistical models to analyze HFRS case data together with environmental data from the Dongting Lake district during 2005–2010. Specifically, time-specific ecologic niche models (ENMs) were used to quantify and identify risk factors associated with HFRS transmission as well as forecast seasonal variation in risk across geographic areas. Results showed that the Maximum Entropy model provided the best predictive ability (AUC = 0.755). Time-specific Maximum Entropy models showed that the potential risk areas of HFRS significantly varied across seasons. High-risk areas were mainly found in the southeastern and southwestern areas of the Dongting Lake district. Our findings based on models focused on the spring and winter seasons showed particularly good performance. The potential risk areas were smaller in March, May and August compared with those identified for June, July and October to December. Both normalized difference vegetation index (NDVI) and land use types were found to be the dominant risk factors. Conclusions/Significance Our findings indicate that time-specific ENMs provide a useful tool to forecast the spatial and temporal risk of HFRS. PMID:25184252

  8. Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever

    PubMed Central

    Chanthick, Chanettee; Kanlaya, Rattiyaporn; Kiatbumrung, Rattanaporn; Pattanakitsakul, Sa-nga; Thongboonkerd, Visith

    2016-01-01

    Vascular leakage is a life-threatening complication of dengue virus (DENV) infection. Previously, association between “paracellular” endothelial hyperpermeability and plasma leakage had been extensively investigated. However, whether “transcellular” endothelial leakage is involved in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) remained unknown. We thus investigated effects of DENV (serotype 2) infection on transcellular transport of albumin, the main oncotic plasma protein, through human endothelial cell monolayer by Western blotting, immunofluorescence staining, fluorescence imaging, and fluorometry. The data showed that Alexa488-conjugated bovine serum albumin (Alexa488-BSA) was detectable inside DENV2-infected cells and its level was progressively increased during 48-h post-infection. While paracellular transport could be excluded using FITC-conjugated dextran, Alexa488-BSA was progressively increased and decreased in lower and upper chambers of Transwell, respectively. Pretreatment with nystatin, an inhibitor of caveolae-dependent endocytic pathway, significantly decreased albumin internalization into the DENV2-infected cells, whereas inhibitors of other endocytic pathways showed no significant effects. Co-localization of the internalized Alexa488-BSA and caveolin-1 was also observed. Our findings indicate that DENV infection enhances caveolae-mediated albumin transcytosis through human endothelial cells that may ultimately induce plasma leakage from intravascular compartment. Further elucidation of this model in vivo may lead to effective prevention and better therapeutic outcome of DHF/DSS. PMID:27546060

  9. Crimean-Congo Hemorrhagic Fever Virus Gn Bioinformatic Analysis and Construction of a Recombinant Bacmid in Order to Express Gn by Baculovirus Expression System

    PubMed Central

    Rahpeyma, Mehdi; Fotouhi, Fatemeh; Makvandi, Manouchehr; Ghadiri, Ata; Samarbaf-Zadeh, Alireza

    2015-01-01

    Background Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the nairovirus, a genus in the Bunyaviridae family, which causes a life threatening disease in human. Currently, there is no vaccine against CCHFV and detailed structural analysis of CCHFV proteins remains undefined. The CCHFV M RNA segment encodes two viral surface glycoproteins known as Gn and Gc. Viral glycoproteins can be considered as key targets for vaccine development. Objectives The current study aimed to investigate structural bioinformatics of CCHFV Gn protein and design a construct to make a recombinant bacmid to express by baculovirus system. Materials and Methods To express the Gn protein in insect cells that can be used as antigen in animal model vaccine studies. Bioinformatic analysis of CCHFV Gn protein was performed and designed a construct and cloned into pFastBacHTb vector and a recombinant Gn-bacmid was generated by Bac to Bac system. Results Primary, secondary, and 3D structure of CCHFV Gn were obtained and PCR reaction with M13 forward and reverse primers confirmed the generation of recombinant bacmid DNA harboring Gn coding region under polyhedron promoter. Conclusions Characterization of the detailed structure of CCHFV Gn by bioinformatics software provides the basis for development of new experiments and construction of a recombinant bacmid harboring CCHFV Gn, which is valuable for designing a recombinant vaccine against deadly pathogens like CCHFV. PMID:26862379

  10. Puumala Hantavirus-Induced Hemorrhagic Fever with Renal Syndrome Must Be Considered across the Borders of Nephrology to Avoid Unnecessary Diagnostic Procedures

    PubMed Central

    Kitterer, Daniel; Segerer, Stephan; Alscher, M. Dominik; Braun, Niko; Latus, Joerg

    2015-01-01

    Background Nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome, is caused by Puumala virus and is characterized by acute kidney injury and thrombocytopenia. Methods A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed. Results Of the 456 investigated patients, 335 had received inpatient treatment. At time of admission to hospital, 72% of the patients had still an AKI and thrombocytopenia was present in 64% of the patients. The 335 patients were treated in 29 different hospitals and 6 of which had nephrology departments. 10 out of 335 patients received treatment in university hospitals and 63% of patients admitted themselves to hospital. Initially, the patients were admitted to 12 different clinical departments (29% of the patients were referred to a nephrology department) and during the course of the disease, 8% of the patients were transferred to another department in the same hospital and 3% were transferred to a nephrology department at another hospital. Regarding diagnostic procedures, in 28% of the inpatients computed tomography to exclude pulmonary embolism or due to severe gastrointestinal symptoms, lumbar puncture to exclude meningitis, magnetic resonance tomography of the brain owing to suspected stroke because of visual disorders, gastroscopy, or colonoscopy due to gastrointestinal symptoms was performed at time of admission to hospital. Conclusions NE must be considered by physicians across the borders of nephrology to avoid unnecessary diagnostic procedures especially in areas where NE is endemic. PMID:26650941