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Sample records for argentine hemorrhagic fever

  1. Argentine hemorrhagic fever: a primate model.

    PubMed

    Weissenbacher, M C; Calello, M A; Colillas, O J; Rondinone, S N; Frigerio, M J

    1979-01-01

    Experimental Junin virus infection of a New World primate, Callithrix jacchus, was evaluated. The virus produced anorexia, loss of weight, thrombocytopenia, leukopenia, and hemorrhagic and neurological symptoms and terminated in death. Virus was recovered from urine, blood samples and all tissues taken at autopsy. These preliminary observations show that several aspects of the experimental disease in C. jacchus are quite similar to severe natural Argentine hemorrhagic fever of man.

  2. Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever.

    PubMed Central

    McKee, K T; Huggins, J W; Trahan, C J; Mahlandt, B G

    1988-01-01

    Junin virus-infected rhesus macaques received prophylactic and therapeutic ribavirin to assess the potential of this drug for treating humans with Argentine hemorrhagic fever. When ribavirin was administered intramuscularly at the time of experimental infection with the lethal P3790 strain of Junin virus, all animals were protected from clinical disease. A delay in the initiation of therapy until after the onset of illness resulted in improvement and resolution of systemic signs of disease; however, survivors subsequently developed a late-onset central nervous system infection which was fatal in two of three animals. Side effects of ribavirin included thrombocytosis and severe anemia, both of which resolved promptly on withdrawal of drug therapy. Results of this study suggest that ribavirin may prove useful in treating humans with Argentine hemorrhagic fever. PMID:2848441

  3. Viral strain dependent differences in experimental Argentine hemorrhagic fever (Junin virus) infection of guinea pigs.

    PubMed

    Kenyon, R H; Green, D E; Maiztegui, J I; Peters, C J

    1988-01-01

    Guinea pigs infected with low-passage Junin virus of human origin showed viral strain dependent differences in mortality, LD50, time to death, and in viral spread and distribution. Different Junin strains appeared to cause at least two broad patterns of Argentine hemorrhagic fever in guinea pigs. A number of strains of Junin virus caused a viscerotropic type of illness in which virus replicated predominantly in lymph nodes, spleen, and bone marrow. With the most severe visceral forms of Argentine hemorrhagic fever, the guinea pigs became viremic, developed necrosis of spleen, lymph nodes, and bone marrow, showed gastric hemorrhages, and all animals died within 13-15 days. Other Junin strains induced a neurological type of illness with transient viral replication in and lymphocyte depletion of spleen and lymph nodes, with no detectable viremia or viral replication in bone marrow. Subsequently, virus was found in the brain with varying severities of polioencephalitis, and the guinea pigs frequently showed rear leg paralysis before death occurred 28-34 days after inoculation. Not all animals infected with a neurotropic strain developed all these signs. One viral strain induced some signs characteristic of both patterns of illness. Although the disease forms in the guinea pig model did not strictly correlate with those observed in the humans from which these strains were obtained, the different strains of Junin virus consistently caused very different patterns of illness in infected guinea pigs.

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

    PubMed

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

    1995-03-01

    Junin virus, an arenaviridae, is the etiological agent of Argentine hemorrhagic fever. In addition to thrombocytopenia, patients present several alterations in both the blood coagulation and the fibrinolytic system, but diffuse intravascular coagulation could not be demonstrated. To investigate further the activation status of the two systems, levels of thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2, protein C, total and free protein S, C4bBP, antithrombin III, t-PA, PAI-1 and D-dimer were measured. Fourteen patients with a confirmed diagnosis of Argentine hemorrhagic fever were included in the study, 2 were severe, 3 moderate and 9 mild clinical cases, but hemorrhages were slight throughout. Blood samples were collected for 6 consecutive days on admission and on remission. At admission TAT and F1 + 2 levels were increased in 13/14 patients, reaching 0.33 nM (0.06-0.87) and 2.16 nM (0.96-6.5), respectively. PC was low in 4 cases, fPS in 6 and tPS in 2, whereas C4bBP and ATIII values were within normal range. t-PA and D-dimer levels were high in 11/14 patients, reaching 20 ng/ml (2.7-106) and 1660 ng/ml (877-3780) respectively, while PAI-1 was considerably increased in the 2 severe cases and normal in the remainder. These results suggest low level though persistent process of blood coagulation and fibrinolysis activation in this viral hemorrhagic disease. We believe these abnormalities may lead to the well described bleeding manifestations in these patients.

  5. A Host-Oriented Inhibitor of Junin Argentine Hemorrhagic Fever Virus Egress

    PubMed Central

    Lu, Jianhong; Han, Ziying; Liu, Yuliang; Liu, Wenbo; Lee, Michael S.; Olson, Mark A.; Ruthel, Gordon; Freedman, Bruce D.

    2014-01-01

    ABSTRACT There are currently no U.S. Food and Drug Administration (FDA)-approved vaccines or therapeutics to prevent or treat Argentine hemorrhagic fever (AHF). The causative agent of AHF is Junin virus (JUNV); a New World arenavirus classified as a National Institute of Allergy and Infectious Disease/Centers for Disease Control and Prevention category A priority pathogen. The PTAP late (L) domain motif within JUNV Z protein facilitates virion egress and transmission by recruiting host Tsg101 and other ESCRT complex proteins to promote scission of the virus particle from the plasma membrane. Here, we describe a novel compound (compound 0013) that blocks the JUNV Z-Tsg101 interaction and inhibits budding of virus-like particles (VLPs) driven by ectopic expression of the Z protein and live-attenuated JUNV Candid-1 strain in cell culture. Since inhibition of the PTAP-Tsg101 interaction inhibits JUNV egress, compound 0013 serves as a prototype therapeutic that could reduce virus dissemination and disease progression in infected individuals. Moreover, since PTAP l-domain-mediated Tsg101 recruitment is utilized by other RNA virus pathogens (e.g., Ebola virus and HIV-1), PTAP inhibitors such as compound 0013 have the potential to function as potent broad-spectrum, host-oriented antiviral drugs. IMPORTANCE There are currently no FDA-approved vaccines or therapeutics to prevent or treat Argentine hemorrhagic fever (AHF). The causative agent of AHF is Junin virus (JUNV); a New World arenavirus classified as an NIAID/CDC category A priority pathogen. Here, we describe a prototype therapeutic that blocks budding of JUNV and has the potential to function as a broad-spectrum antiviral drug. PMID:24522922

  6. Immune response to vaccination against Argentine hemorrhagic Fever in an area where different arenaviruses coexist.

    PubMed

    Ambrosio, Ana M; Riera, Laura M; Saavedra, María Del Carmen; Sabattini, Marta S

    2006-01-01

    Neutralizing antibody (NT Ab) titers to Candid #1 (C#1) vaccine against Argentine hemorrhagic fever were studied for 2 years post-vaccination in 330 volunteers, to assess whether the kinetics and/or magnitude of this immune response is modified by previous infection with the arena viruses Junin (JUN) and lymphocytic choriomeningitis (LCM). A total of 160 volunteers received C#1, distributed as follows: without detectable pre-infection with arenaviruses (n = 54); with pre-existing antibodies to JUN (n = 55); with pre-existing antibodies to LCM (n = 51). The remaining 170 individuals received placebo. Levels of anti-JUN NT Ab displayed a trend in which titers increased with the virulence of the infecting strain, from C#1 (X = 49), through subclinical JUN infection (X = 229), vaccination following subclinical infection (X = 367) to JUN clinical infection (X =773). It was also found that the mean titer of NT Ab to C#1 did not vary significantly during 2 years of study and was: a) significantly lower than that elicited by wild strains of JUN, both clinical and subclinical infections (p < 0.01); b) significantly increased the titers of pre-existing anti-JUN Ab (p < 0.01); and c) was not modified by pre-existing anti-LCM Ab (p > 0.05). These data indicate that the immune response to C#1 boosts pre-existing immunity to JUN virus and is not changed by previous experience with LCM virus.

  7. Proinflammatory cytokines and elastase-alpha-1-antitrypsin in Argentine hemorrhagic fever.

    PubMed

    Marta, R F; Montero, V S; Hack, C E; Sturk, A; Maiztegui, J I; Molinas, F C

    1999-01-01

    Argentine hemorrhagic fever (AHF) is a disease caused by Junin virus. In the acute phase, patients present hematologic and neurologic involvement with high levels of interferon-alpha and tumor necrosis factor-alpha (TNF-alpha. Nineteen patients with a confirmed diagnosis of AHF were studied: six severe, four moderate and nine mild cases. Serum levels of interleukin-6 (IL-6), IL-6 soluble receptor (IL-6sR), IL-8, IL-10, and elastase-alpha1-antitrypsin complex (E-alpha 1AT) were assayed by ELISAs. Levels of IL-6, IL-8, and IL-10 were high in nine, 12, and 13 patients, respectively, while levels of IL-6sR were high in two patients and low in one patient. Seven patients had increased levels of E-alpha1AT. Significant correlations were found between levels of both IL-8 and IL-10 with those of TNF-alpha as well as between IL-8 and E-alpha 1AT. These data demonstrate activation of pro-inflammatory and anti-inflammatory cytokine pathways, and statistical analysis showed differences among the clinical forms of illness. This study shows that IL-8 plays an essential role in neutrophil activation in AHF patients as demonstrated in other infectious diseases.

  8. Rapid diagnosis of Argentine hemorrhagic fever by reverse transcriptase PCR-based assay.

    PubMed Central

    Lozano, M E; Enría, D; Maiztegui, J I; Grau, O; Romanowski, V

    1995-01-01

    Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by Junín virus. This report demonstrates that a reverse transcriptase (RT) PCR-based assay developed in our laboratory to detect Junín virus in whole blood samples is sensitive and specific. The experiments were conducted in a double-blinded manner using 94 clinical samples collected in the area in which AHF is endemic. The RT-PCR-based assay was compared with traditional methodologies, including enzyme-linked immunosorbent assay, plaque neutralization tests, and occasionally viral isolation. The calculated parameters for RT-PCR diagnosis, with seroconversion as the "gold standard," were 98% sensitivity and 76% specificity. It is noteworthy that 94% of the patients with putative false-positive results (RT-PCR positive and no seroconversion detected) exhibited febrile syndromes of undefined etiology. These results could be interpreted to mean that most of those patients with febrile syndromes were actually infected with Junín virus but did not develop a detectable immune response. Furthermore, 8 laboratory-fabricated samples and 25 blood samples of patients outside the area in which AHF is endemic tested in a similar way were disclosed correctly (100% match). The RT-PCR assay is the only laboratory test available currently for the early and rapid diagnosis of AHF. It is sensitive enough to detect the low viremia found during the period in which immune plasma therapy can be used effectively, reducing mortality rates from 30% to less than 1%. PMID:7542268

  9. Cell-mediated immunity and lymphocyte populations in experimental Argentine hemorrhagic fever (Junín Virus).

    PubMed Central

    Carballal, G; Oubiña, J R; Rondinone, S N; Elsner, B; Frigerio, M J

    1981-01-01

    Guinea pigs infected with the XJ prototype strain of Junín virus reproduce the main features of Argentine hemorrhagic fever, showing hemorrhages, leukothrombocytopenia, and focal lymphoid tissue necrosis. Viral lymphotropism is shown by the presence of viral antigens, severe cytopathic effect, and high virus titers in lymphoid organs. A pronounced depression of humoral immune response to sheep erythrocytes as well as to the virus is described. This study was carried out to determine whether cellular immune response was also modified and which cell populations were affected. Delayed hypersensitivity skin reaction to purified protein derivative was found to be markedly depressed after infection. A noticeable decrease in both percentages and absolute T lymphocyte numbers, detected by E rosettes, in spleen and lymph nodes, together with a low absolute T cell number in peripheral blood, were observed. Total cell counts in spleen, lymph nodes, and peripheral blood were also reduced. On the contrary, no modification in percentages of B lymphocytes, as measured by EAC rosettes, was found. These results indicate that cell-mediated immunity is markedly impaired in guinea pigs infected with the XJ strain of Junín virus. Its relationship with the pathogenesis of the disease is discussed. PMID:6273314

  10. Dengue hemorrhagic fever

    MedlinePlus

    Hemorrhagic dengue; Dengue shock syndrome; Philippine hemorrhagic fever; Thai hemorrhagic fever; Singapore hemorrhagic fever ... and sweaty. These symptoms are followed by a shock -like state. Bleeding appears as tiny spots of ...

  11. 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 ...

  12. [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

  13. 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

  14. Ebola hemorrhagic Fever.

    PubMed

    Burnett, Mark W

    2014-01-01

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

  15. Epidemiology of hemorrhagic fever viruses.

    PubMed

    LeDuc, J W

    1989-01-01

    Twelve distinct viruses associated with hemorrhagic fever in humans are classified among four families: Arenaviridae, which includes Lassa, Junin, and Machupo viruses; Bunyaviridae, which includes Rift Valley fever, Crimean-Congo hemorrhagic fever, and Hantaan viruses; Filoviridae, which includes Marburg and Ebola viruses; and Flaviviridae, which includes yellow fever, dengue, Kyasanur Forest disease, and Omsk viruses. Most hemorrhagic fever viruses are zoonoses, with the possible exception of the four dengue viruses, which may continually circulate among humans. Hemorrhagic fever viruses are found in both temperate and tropical habitats and generally infect both sexes and all ages, although the age and sex of those infected are frequently influenced by the possibility of occupational exposure. Transmission to humans is frequently by bite of an infected tick or mosquito or via aerosol from infected rodent hosts. Aerosol and nosocomial transmission are especially important with Lassa, Junin, Machupo, Crimean-Congo hemorrhagic fever, Marburg, and Ebola viruses. Seasonality of hemorrhagic fever among humans is influenced for the most part by the dynamics of infected arthropod or vertebrate hosts. Mammals, especially rodents, appear to be important natural hosts for many hemorrhagic fever viruses. The transmission cycle for each hemorrhagic fever virus is distinct and is dependent upon the characteristics of the primary vector species and the possibility for its contact with humans.

  16. Dengue hemorrhagic fever.

    PubMed

    Rosen, L

    1996-01-01

    Dengue has been known for more than 200 years. The first dengue viruses were isolated about 50 years ago. Prior to the 1950's, dengue was considered a mild febrile disease, though rare hemorrhagic and fatal cases were known to occur. After that date, the first epidemics of dengue hemorrhagic fever (DHF) appeared in Southeast Asia, and DHF became the most important cause of childhood morbidity and mortality in the region. The emergence of DHF epidemics was first explained by mutations affecting dengue viruses, making them more virulent, but this hypothesis was not retained. Then, the "secondary infection" or "immune enhancement" theory was proposed to explain the increased virulence of dengue viruses when children had a secondary infection. This second hypothesis is still actually favoured. However, observations in Southeast Asia, some Pacific islands, and Americas do not agree with the "secondary infection" hypothesis, which consequently has been modified several times. Recent advances in molecular biology have led to the recognition that some viral strains are more virulent than others. Another hypothesis is the selection of more virulent dengue strains by the new vector Ae. aegypti, replacing the local vector Ae. albopictus, when urbanization and modern transportation increased in Southeast Asia after the last war. Comparisons between epidemics are very difficult, because of the distinction between DHF cases according to WHO criteria and dengue fever (DF) cases with hemorrhages. This distinction has no pathogenic or prognostic grounds, and makes the task of clinicians more difficult. The actual situation in countries facing dengue epidemics makes clear that this disease will continue to be a public health problem for some time to come.

  17. Dengue and dengue hemorrhagic fever.

    PubMed

    Gubler, D J

    1998-07-01

    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 develop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever.

  18. Mosquito-borne hemorrhagic fevers.

    PubMed

    Lupi, Omar

    2011-01-01

    Arboviruses continue to be a significant source of disease, especially in regions where their insect hosts are endemic. This article highlights these diseases, with particular focus on dengue, yellow fever, and viral hemorrhagic fever. A general background is provided, as well information concerning diagnosis and treatment.

  19. [Viral hemorrhagic fever].

    PubMed

    Kager, P A

    1998-02-28

    Viral haemorrhagic fevers, such as Lassa fever and yellow fever, cause tens of thousands of deaths annually outside the Netherlands. The viruses are mostly transmitted by mosquitoes, ticks or via excreta of rodents. Important to travellers are yellow fever, dengue and Lassa and Ebola fever. For yellow fever there is an efficacious vaccine. Dengue is frequently observed in travellers; prevention consists in avoiding mosquito bites, the treatment is symptomatic. Lassa and Ebola fever are extremely rare among travellers; a management protocol can be obtained from the Netherlands Ministry of Health, Welfare and Sports. Diagnostics of a patient from the tropics with fever and haemorrhagic diathesis should be aimed at treatable disorders such as malaria, typhoid fever, rickettsiosis or bacterial sepsis, because the probability of such a disease is much higher than that of Lassa or Ebola fever.

  20. 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 ...

  1. Viral hemorrhagic fevers of South America.

    PubMed

    Tesh, Robert B

    2002-09-01

    This paper reviews the epidemiology and distinguishing features of three viral hemorrhagic fevers (dengue hemorrhagic fever, yellow fever and arenaviral hemorrhagic fever) that have emerged as important public health problems in South America. Although the etiology, natural history and control of the three diseases are different, their clinical manifestations and histopathology findings are similar and can be difficult to differentiate. Consequently, early recognition and correct diagnosis are essential for effective control measures to be initiated.

  2. First outbreak of dengue hemorrhagic fever, Bangladesh.

    PubMed

    Rahman, Mahbubur; Rahman, Khalilur; Siddque, A K; Shoma, Shereen; Kamal, A H M; Ali, K S; Nisaluk, Ananda; Breiman, Robert F

    2002-07-01

    During the first countrywide outbreak of dengue hemorrhagic fever in Bangladesh, we conducted surveillance for dengue at a hospital in Dhaka. Of 176 patients, primarily adults, found positive for dengue, 60.2% had dengue fever, 39.2% dengue hemorrhagic fever, and 0.6% dengue shock syndrome. The Dengue virus 3 serotype was detected in eight patients.

  3. Emerging Infections: Lessons from the Viral Hemorrhagic Fevers

    PubMed Central

    Peters, C. J

    2006-01-01

    Two Institute of Medicine reports since 1992 have emphasized the dangerous and continuing threat to the world from emerging infectious diseases. Working with viral hemorrhagic fevers provides a number of lessons related to the processes that control emergence, the pattern of disease after emergence, and how to cope with these incidents. This short paper uses two arenavirus hemorrhagic fevers to illustrate some of these principles. Argentine and Bolivian hemorrhagic fevers first came to medical attention in the 1950’s. The forces that underlie the emergence of disease in Argentina are not understood, but the Bolivian episode has a reasonably understandable train of events behind it. The Argentine disease had serious impact on the large agricultural economy, and the ecology of the rodent reservoir did not lend itself to control; a vaccine was developed by Argentina and the U.S. with the latter motivated largely by biodefense. The Bolivian disease was controlled in large part by eliminating rodents that invaded towns, and the impact was subsequently below the level needed to trigger drug or vaccine development. These two viruses were important in the recognition of a new family of viruses (Arenaviridae), and this finding of new taxons during the investigation of emerging infectious diseases continues. PMID:18528473

  4. Hemorrhagic fever with renal syndrome.

    PubMed

    Lee, H W; van der Groen, G

    1989-01-01

    Hantaviruses, the causative agents of HFRS, have become more widely recognized. Epidemiologic evidence indicates that these pathogens are distributed worldwide. People who come into close contact with infected rodents in urban, rural and laboratory environments are at particular risk. Transmission to man occurs mainly via the respiratory tract. The epidemiology of the hantaviruses is intimately linked to the ecology of their principal vertebrate hosts. Four distinct viruses are now recognized within the hantavirus genus and that number is likely to increase to six very soon; however, further investigations are necessary. Much more work is still needed before we fully understand the wide spectrum of clinical signs and symptoms of HFRS as well as the pathogenicity of the different viruses in the hantavirus genus of the Bunyaviridae family. HFRS is difficult to diagnose on clinical grounds alone and serological evidence is often needed. A fourfold rise in IgG antibody titer in a 1-week interval, and the presence of the IgM type of antibodies against hantaviruses are good evidence for an acute hantavirus infection. Physicians should be alert for HFRS each time they deal with patients with acute febrile flu-like illness, renal failure of unknown origin and sometimes hepatic dysfunction. Especially the mild form of HFRS is difficult to diagnose. Acute onset, headache, fever, increased serum creatinine, proteinuria and polyuria are signs and symptoms compatible with a mild form of HFRS. Differential diagnosis should be considered for the following diseases in the endemic areas of HFRS: acute renal failure, hemorrhagic scarlet fever, acute abdomen, leptospirosis, scrub typhus, murine typhus, spotted fevers, non-A, non-B hepatitis, Colorado tick fever, septicemia, dengue, heartstroke and DIC. Treatment of HFRS is mainly supportive. Recently, however, treatment of HFRS patients with ribavirin in China and Korea, within 7 days after onset of fever, resulted in a reduced

  5. 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.

  6. Dengue hemorrhagic fever in infants.

    PubMed

    Hongsiriwon, Suchat

    2002-03-01

    A report of 19 cases of serologically-proven dengue hemorrhagic fever (DHF) in infants aged 3-12 months who were admitted to the Department of Pediatrics, Chon Buri Regional Hospital, Thailand, during 1995 to 1998. Subjects were 8 males and 11 females, with the peak age of 8 months. Four cases (21%) had DHF and other common co-infections ie pneumonia (2 cases), Staphylococcus aureus sepsis (1 case) and Haemophilus influenzae meningitis (1 case). The clinical manifestations of the 15 DHF cases were high fever (100%), coryza (93.3%), hepatomegaly (80%), drowsiness (53.3 %), and vomiting (46.7%); rash was observed in only 27%; one-fifth developed febrile convulsions. Sites of bleeding were the skin (petechiae) 58%, gastrointestinal system (melena) 16%, and mucous membrane (epistaxis) 5%; thrombocytopenia and increased hematocrit (> or =20%) were noted in 95% and 84% respectively. The majority of the patients (18 cases, 95%) had primary infection; only one (5%) had secondary infection. The clinical severity of the DHF was Grade I, II, and III (dengue shock syndrome) in 21%, 47% and 32% of cases respectively. After appropriate and effective management, all the infants recovered fully.

  7. [Hemorrhagic fever viruses in Madagascar].

    PubMed

    Fontenille, D; Mathiot, C; Coulanges, P

    1988-01-01

    The authors remind, what are the viral haemorrhagic fevers, and explain the situation in Madagascar. The viruses of Crimée-Congo haemorrhagic fever, Rift valley fever and haemorrhagic fever with renal syndrome are present in Madagascar. There is no real proof about the presence of Dengue viruses. The yellow fever viruses have never been stown off. It seems that there was not diagnosed outbreak of haemorrhagic fever, since the beginning of our century.

  8. [Dengue fever and dengue hemorrhagic fever].

    PubMed

    Fonsmark, L; Poulsen, A; Heegaard, E D

    2000-09-18

    Dengue virus is transmitted by mosquitoes and causes dengue fever/dengue haemorrhagic fever throughout the tropical areas of the world. There is an increasing incidence of dengue infections. Because of increasing travel activity, infection among Danes travelling abroad as well as imported cases are expected to be seen more frequently. In this review we describe the clinical manifestations, diagnosis, pathogenesis, treatment and prevention of the disease.

  9. Animal Models for Viral Hemorrhagic Fever.

    PubMed

    Falzarano, Darryl; Bente, Dennis A

    2014-04-01

    Viral hemorrhagic fever can be caused by one of a diverse group of viruses that come from four different families of RNA viruses. Disease severity can vary from mild self-limiting febrile illness to severe disease characterized by high fever, high-level viremia, increased vascular permeability that can progress to shock, multi-organ failure, and death. Despite the urgent need, effective treatments and preventative vaccines are currently lacking for the majority of these viruses. A number of factors preclude the effective study of these diseases in humans including the high virulence of the agents involved, the sporadic nature of outbreaks of these viruses which are typically in geographically isolated areas with underserviced diagnostic capabilities, and the requirements for high level bio-containment. As a result, animal models that accurately mimic human disease are essential for advancing our understanding of the pathogenesis of viral hemorrhagic fevers. Moreover, animal models for viral hemorrhagic fevers are necessary to test vaccines and therapeutic intervention strategies. Here, we present an overview of the animal models that have been established for each of the hemorrhagic fever viruses and identify which aspects of human disease are modeled. Furthermore, we discuss how experimental design considerations, such as choice of species and virus strain as well as route and dose of inoculation, have an influence on animal model development. We also bring attention to some of the pitfalls that need to be avoided when extrapolating results from animal models. This article is protected by copyright. All rights reserved.

  10. Fatal dengue hemorrhagic fever imported into Germany.

    PubMed

    Schmidt-Chanasit, J; Tenner-Racz, K; Poppert, D; Emmerich, P; Frank, C; Dinges, C; Penning, R; Nerlich, A; Racz, P; Günther, S

    2012-08-01

    Dengue virus (DENV) is an arthropod-borne virus (family Flaviviridae) causing dengue fever or dengue hemorrhagic fever. Here, we report the first fatal DENV infection imported into Germany. A female traveler was hospitalized with fever and abdominal pain after returning from Ecuador. Due to a suspected acute acalculous cholecystitis, cholecystectomy was performed. After cholecystectomy, severe spontaneous bleeding from the abdominal wound occurred and the patient died. Postmortem analysis of transudate and tissue demonstrated a DENV secondary infection of the patient and a gallbladder wall thickening (GBWT) due to an extensive edema.

  11. Dengue hemorrhagic fever: clinical manifestations and management.

    PubMed

    Kabra, S K; Jain, Y; Singhal, T; Ratageri, V H

    1999-01-01

    Dengue virus infection may remain asymptomatic or manifest as nonspecific viral infection to life threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Patients with DHF/DSS have fever, hemorrhagic manifestations along with thrombocytopenia and hemoconcentration. Thrombocytopenia and hemoconcentration are distinguishing features between DHF/DSS and dengue fever (DF). Some patients with dengue fever may have significant bleed and mild thrombocytopenia but no hemoconcentration. These patients are labelled to have dengue fever with unusual bleeds. Laboratory findings in DHF/DSS include rising hematocrit, thrombocytopenia and transformed lymphocytes on peripheral smear. There may be increased transaminases, hyponatremia, transient increase in blood urea nitrogen and creatinine. In severe disease there may be lab evidence of dissemination intravascular coagulation. X-ray film of the chest may show pleural-effusion. Ultrasonogram of abdomen may detect thickened gall bladder wall with hepatomegaly and ascitis. In some patients there may be abnormality in electrocardiogram and echocardiogram. The diagnosis of DHF/DSS is based on typical clinical findings. For confirmation of dengue virus infection viral culture can be done on blood obtained from patients during early phase of illness. In later part of illness antibodies against dengue virus can be demonstrated by various techniques. The treatment of DF is symptomatic. For control of fever nonsteroidal anti-inflammatory drugs should be avoided. DHF/DSS are managed by intravenous fluid infusion with repeated monitoring of vital parameters and packed cell volume (PCV).

  12. Clinical and epidemiological patterns of Argentine haemorrhagic fever

    PubMed Central

    Maiztegui, J. I.

    1975-01-01

    The epidemiology of Argentine haemorrhagic fever (AHF) is closely related to cricetine rodents acting as natural hosts of Junin virus. The endemo-epidemic area, which has increased 5 times since the disease was first recognized 15-20 years ago, is located in a densely populated region of Argentina. It has been shown that the virus of LCM is active in humans and rodents of the AHF endemic area; this demonstrates the simultaneous presence of two arenaviruses pathogenic for man in a given geographic location. The disease is characterized by haematological, renal, neurological and cardiovascular changes. Electron microscopy and immunohistochemical studies have shown cytopathic changes, characteristic intracellular virus-like particles, and antigenic determinants of Junin virus in different organs from 9 cases of AHF. No deposits of immunoglobulins or C3 were found in the kidneys; in addition, an absence of fibrinogen and C3 in the hepatocytes and of immunoglobulins in the spleen was observed. These findings suggest a direct viral pathogenic action in the human disease. Ultrastructural and immunofluorescence studies in tissues of guinea-pigs inoculated with two strains of Junin virus revealed the presence of the same types of virus-like particles and antigenic determinants of Junin virus as were encountered in the human subjects with AHF. ImagesFig. 2Fig. 3 PMID:1085212

  13. 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

  14. Immunological Features Underlying Viral Hemorrhagic Fevers

    PubMed Central

    Messaoudi, Ilhem; Basler, Christopher F.

    2015-01-01

    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

  15. Dengue and dengue hemorrhagic fever.

    PubMed

    Hayes, E B; Gubler, D J

    1992-04-01

    Hundreds of thousands of dengue cases are reported worldwide each year. Given the difficulty in obtaining full reporting, the actual number of human infections is probably much higher than the number reported. Dengue is usually a nonspecific febrile illness that resolves with supportive therapy but the clinical spectrum ranges from asymptomatic infection through severe hemorrhage and sudden fatal shock. The pathophysiology of the severe forms of dengue may be related to sequential infection with different serotypes, variations in virus virulence, interaction of the virus with environmental and host factors or a combination of these factors. Control of dengue at the present time is dependent on control of the principal vector mosquito, A. aegypti. Efforts to achieve such control are now focusing on community education and action towards eliminating this mosquito's breeding sites near human dwellings. Vaccine development continues, but at present the only way to avoid dengue in an area where it is endemic or epidemic is to use repellents and mosquito barriers. The movement of people to and from tropical areas makes dengue an important differential diagnosis in any patient with an acute illness and history of recent travel to tropical areas. Because of continued infestation of the southeastern United States with A. aegypti, indigenous transmission in the continental United States remains a public health concern.

  16. 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

  17. Dengue hemorrhagic fever in Thai society.

    PubMed

    Kantachuvessiri, Aree

    2002-03-01

    Dengue hemorrhagic fever (DHF) is one of the most important infectious diseases in Thailand for many decades. Knowledge of DHF is vital to its control. Like other tropical countries, Thailand is facing this resurgent disease. The Thai National Dengue Prevention and Control Plan has been recently implemented to prevent and reduce the problems resulting from the spread of DHF. In this paper, a three-pronged strategy is offered that will create social mobilization at family, community, and national level and that will, therefore, reduce the socioeconomic and health impacts of DHF.

  18. Surveillance for dengue and dengue hemorrhagic fever.

    PubMed

    Gubler, D J

    1989-01-01

    Dengue and dengue hemorrhagic fever are emerging as major public health problems in most tropical countries. Effective prevention and control programs will depend on improved surveillance designed to provide early warning of dengue epidemics. This article outlines a reasonable approach to dengue surveillance of this kind. Virologic surveillance should be considered the most important element in any such early warning system. Dengue virus transmission should be monitored to determine which serotypes are present, their distribution, and the type of illnesses associated with each. Other key components of an active surveillance system should include monitoring of fever activity and clinical surveillance for cases of severe and fatal disease associated with viral syndromes. Collectively, these three surveillance components can provide an early warning capability permitting emergency mosquito control measures to be implemented and major epidemics to be averted.

  19. [Hemorrhagic fever and the dengue shock syndrome].

    PubMed

    Ramos, C; García, H; Villaseca, J M

    1993-01-01

    Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) are the severe and/or fatal clinical manifestations of dengue fever. Epidemics of DHF/DSS occur mainly in the southeast Asian countries where children are seriously affected and high case-fatality ratio is annually reported. Recently significant epidemics of DHF/DSS have been reported in Cuba, Venezuela and Brazil, which means that reinforcements of the epidemiological surveillance in the countries of the American region that show high virus transmission, are urgently needed. The main purpose of the present article is to review relevant information regarding the clinical manifestations, pathology, diagnostic procedures, treatment of cases, pathophysiologic mechanisms and some data related with specific DHF/DSS epidemics.

  20. Reactive astrogliosis in response to hemorrhagic fever virus: microarray profile of Junin virus-infected human astrocytes

    PubMed Central

    2014-01-01

    Background Arenavirus Junin is the causative agent of Argentine hemorrhagic fever. Limited information is available concerning the pathogenesis of this human disease, especially the pathogenesis of acute and late neurological symptoms. Methods In our study we present for the first time cDNA microarray profile of human astrocytes infected with the virulent strain of Junin virus. Transcriptional profiling was confirmed by quantitative real-time RT-PCR and cytokine/chemokine/growth factor assay. Results We demonstrated the impact of virus infection on immune/inflammatory response/interferon signaling and apoptosis. Pro-apoptotic response and amplification with time of pro-inflammatory cascade of human astrocytes suggested neurodegenerative dysfunctional reactive astrogliosis in response to Junin virus infection. Conclusion Our results suggest potential pathogenic role of astroglial cells in the development of neurological symptoms and late neurological syndrome during Argentine hemorrhagic fever. PMID:25015256

  1. Simian hemorrhagic fever virus: Recent advances

    PubMed Central

    Brinton, Margo A.; Di, Han; Vatter, Heather A.

    2014-01-01

    Simian hemorrhagic fever virus (SHFV) is an understudied arterivirus that typically causes asymptomatic, persistent infections in multiple species of African nonhuman primates (NHPs) which are natural hosts but fatal hemorrhagic fever disease in macaques. SHFV genomes found in different species of African primates have recently been sequenced but no biological data for these viruses has yet been reported. The sequence of one SHFV isolate from a long term persistently infected baboon showed a high degree of identity to the genome of SHFV-LVR, the prototype strain isolated in the 1960s. Similar to what was observed in early studies with the prototype SHFV isolate LVR, infection of Japanese macaques with 100 PFU of the baboon isolate efficiently induced fatal hemorrhagic fever disease in macaques. Consistent with the differential infection outcomes observed in macaques and baboons, SHFV infection of macaque macrophages and dendritic cells is more efficiently than that of baboons and infection induces pro39 inflammatory cytokine production in macaque but not baboon cells. A stable full-length SHFV LVR infectious clone was constructed and basic knowledge about the unique functions of SHFV has been expanded by several recent studies. The SHFV genome encodes extra genes compared to those of other arteriviruses; three instead of two papain-like protease one (PLP1) domains are encoded at the 5’ end and two adjacent sets of four minor structural proteins at the 3’ end. SHFV PLP1α, PLP1β and PLP1γ were each shown to be active proteases in vitro and the three expected nsp1proteins were detected in infected cells. The catalytic Cys of PLP1α is adjacent to an Ala instead of canonical Typ and PLP1γ is unique among arterivirus PLPs in being able to cleave at both downstream and upstream sites. Although the duplicated sets of SHFV minor structural proteins were predicted to be functionally redundant, data obtained with a set of mutant infectious clones, each with the start

  2. Crimean-Congo Hemorrhagic Fever, Mauritania

    PubMed Central

    Nabeth, Pierre; Cheikh, Dah Ould; Lo, Baidy; Faye, Ousmane; Vall, Idoumou Ould Mohamed; Niang, Mbayame; Wague, Bocar; Diop, Djibril; Diallo, Mawlouth; Diallo, Boubacar; Diop, Ousmane Madiagne; Simon, François

    2004-01-01

    From February to August 2003, 38 persons were infected with Crimean-Congo hemorrhagic fever (CCHF) virus in Mauritania; 35 of these persons were residents of Nouakchott. The first patient was a young woman who became ill shortly after butchering a goat. She transmitted the infection to 15 persons in the hospital where she was admitted and four members of her family. In Nouakchott, two disease clusters and 11 isolated cases were identified. The case-fatality ratio was 28.6%. Of the patients not infected by the first case-patient, almost half were butchers, which suggests that the primary mode of animal-to-human transmission was direct contact with blood of infected animals. The hospital outbreak alerted health authorities to sporadic cases that occurred in the following weeks, which would have probably gone otherwise unnoticed. Studies must be conducted to determine the potential risk for continued sporadic outbreaks of CCHF in humans and to propose prevention measures. PMID:15663851

  3. Thermal inactivation of Alkhumra hemorrhagic fever virus.

    PubMed

    Madani, Tariq A; Abuelzein, El-Tayb M E; Azhar, Esam I; Al-Bar, Hussein M S

    2014-10-01

    The physico-chemical and biological characteristics of Alkhumra hemorrhagic fever virus (AHFV) are not yet known. The present study describes the thermal stability of this virus at different temperatures for different periods. The kinetics of thermal inactivation were studied, linear regressions were plotted, the Arrhenius equation was applied, and the activation energy was calculated accordingly. Titers of the residual virus were determined in median tissue culture infective dose (TCID50), and the rate of destruction of infectivity at various temperatures was determined. Infectivity of AHFV was completely lost upon heating for 3 minutes at 60 °C and for 30 min at 56 °C. However, the virus could maintain 33.2 % of its titer after heating for 60 min at 45 °C and 32 % of its titer after heating for 60 min at 50 °C. In conclusion, AHFV is thermo-labile, and its inactivation follows first-order kinetics. PMID:24906524

  4. Epidemiology and pathogenesis of Bolivian hemorrhagic fever.

    PubMed

    Patterson, Michael; Grant, Ashley; Paessler, Slobodan

    2014-04-01

    The etiologic agent of Bolivian hemorrhagic fever (BHF), Machupo virus (MACV) is reported to have a mortality rate of 25-35%. 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 1970s 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.

  5. 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

  6. 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.

  7. Vaccine Platforms to Control Arenaviral Hemorrhagic Fevers.

    PubMed

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

    2012-11-20

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

  8. 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.

  9. [ENT-related diseases in children with hemorrhagic dengue fever].

    PubMed

    Bogomil'skiĭ, M R; Rumiantseva, A G; Sabo, O

    2001-01-01

    ENT affections were studied in 100 children with dengue hemorrhagic fever (DHF) admitted to children's hospital in Pnompen (Cambodia). Leading clinical symptoms, changes in laboratory findings, incidence rate and kind of ENT affections are described.

  10. Dengue hemorrhagic fever in patients with thalassemia.

    PubMed

    Pongtanakul, Bunchoo; Narkbunnam, Nattee; Veerakul, Gavivann; Sanpakit, Kleebsabai; Viprakasit, Vip; Tanphaichitr, Voravarn Tanphaichitr; Suvatte, Vinai

    2005-11-01

    Dengue hemorrhagic fever (DHF) causing by dengue viral infection is endemic in Thailand and Southeast Asian countries where thalassemias are prevalent. Thalassemic patients are also at risk to acquire dengue viral infections and to develop DHF. However, they can have different clinical manifestations and complications as well as more severity than general population requiring special awareness for proper diagnosis and management. We reported 20 thalassemic patients (10 boys and 10 girls) with DHF admitted to Department of Pediatrics, Siriraj Hospital during 1977 to 2001. Their ages ranged from 2-16 years (average 9.5 years). These cases included 5 cases of Hb H disease, 5 cases of Hb H with Hb Constant Spring (CS), 9 cases of beta-thalassemia/Hb E disease and 1 case of beta-thalassemia major. Two cases were in Grade I, 10 cases in grade II, 7 cases in Grade III and one case in grade IV severity of DHF. Though there were evidences of plasma leakage, instead of hemoconcentration, eighteen patients (90 percent) had hematocrit dropped at the range of 11-66% of the initial level. Fifteen patients (75 percent) required at least one packed red cell transfusion. Nine patients (45 percent) had mild bleeding symptoms, one of them had upper gastrointestinal hemorrhage requiring platelet concentrate transfusion. Two patients (10 percent) had serious complications including one with infection-associated hemophagocytic syndrome (IAHS) requiring intravenous immunoglobulin (IVIG) and packed red cell transfusion and the other had generalized seizure due to hyponatremia and hypotension. No mortality was observed among this group of patients. Early recognition of the DHF in thalassemic patients and appropriate packed red cell transfusion in patients with anemic symptoms is warranted to reduce morbidity and mortality in these patients.

  11. 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.

  12. 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

  13. Assessment of dengue hemorrhagic fever in Myanmar.

    PubMed

    Cho-Min-Naing

    2000-12-01

    This study assesses the burden of dengue hemorrhagic fever (DHF) and effectiveness of an intervention package in Myanmar. Disability adjusted life years (DALYs) lost for fatal and non-fatal DHF cases and DALYs averted due to intervention for DHF from 1970-1997 were estimated. The data are based on reported cases and deaths from DHF extracted from annual reports of the Myanmar vector borne disease control program. Sensitivity analyses were performed for robustness of conclusions. DALYs lost from both fatal and non-fatal DHF cases in Myanmar were estimated as 83.83 DALYs per year per million population (range = 83.33-86.32) for the period 1970-1997. DALYs averted from DHF due to intervention were estimated as 134 DALYs per year per million population (range = 47-159). The burden of DHF in Myanmar for the selected year 1990 was 91.3 DALYs per year per million population (range = 90.1-96.5). A comparison was made with China, India and other Asian countries based on information provided by a World Bank study.

  14. [Viral hemorrhagic fevers: what is the risk for travelers?].

    PubMed

    Le Guenno, B

    1997-01-01

    The term hemorrhagic fever covers a number of diseases with different clinical and epidemiologic features. All these diseases are zoonoses but their occurrence is not confined to tropical areas. Some occur in polar zones. Travelers to endemic areas for these diseases are at risk of infection. There are two modes of transmission. Arthropods are vectors for some diseases such as yellow fever, dengue fever, and Rift Valley fever which are carried by mosquitos and Congo-Crimea virus which is carried by ticks. Airborne contamination by rodent excrement is responsible for transmission of hantaviruses and arenaviruses. Nosocomial infection is a risk for health care providers. Some types of hemorrhagic fever such as Bolivian hemorrhagic fever are highly localized, while other types such as dengue are observed worldwide. Judging from the small number of cases observed in European countries, the overall risk for travelers seems low except unless high-risk activities are planned. The main exceptions are yellow fever and dengue which can easily be transmitted to tourists by mosquitos. Yellow fever can be prevented by vaccination. Typical dengue is usually self-limited but hemorrhagic forms require treatment to prevent shock.

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

    PubMed

    Stock, Ingo

    2014-09-01

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

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

    PubMed

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

    2002-08-01

    The mechanisms contributing to bleeding complications in dengue hemorrhagic fever were studied by investigating the pattern of activation of the coagulation and fibrinolytic systems in 50 children with severe dengue hemorrhagic fever. Thirteen patients (26%) died, and activation of coagulation was most pronounced in the deceased group. Fibrinolysis was also activated, but this activation was relatively weak compared with that of coagulation as a result of persistently high plasminogen activator inhibitor levels. Plasminogen activator inhibitor also prevented a switch from the procoagulant to the profibrinolytic state in lethal dengue hemorrhagic fever, which was further enhanced by an acquired protein C deficiency. The present study is the first to demonstrate such a mechanism in a viral infection. This imbalance between coagulation and fibrinolysis may be used as a prognostic marker, but it may also be a target for future therapeutic intervention.

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

    PubMed

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

    2014-11-21

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

  18. A case of dengue hemorrhagic fever in a Japanese child.

    PubMed

    Okuno, Y; Harada, T; Ogawa, M; Okamoto, Y; Maeda, K

    1989-01-01

    A 6-year-old Japanese girl contracted a febrile illness with hemorrhagic manifestations when she traveled in Indonesia. A remarkable decrease in the numbers of platelets and white blood cells was observed in her acute-phase blood specimens. Her father, who accompanied her, showed dengue fever-like symptoms at almost the same time as her illness. It was determined by serological tests that they were infected with dengue virus type 1. Moreover, she showed a secondary antibody response to the flavivirus due to the pre-existing antibody to Japanese encephalitis virus. This is the first confirmed case of dengue hemorrhagic fever (DHF) in Japanese people.

  19. [Clinical observation of 15 Thai children with dengue hemorrhagic fever].

    PubMed

    Chang, C S; Harn, M R; Nimmannitya, S

    1990-03-01

    Fifteen Thai children, diagnosed with dengue hemorrhagic fever and admitted to the Children's Hospital in Bangkok, were studied. All cases were serologically proved to be secondary dengue infections. The clinical signs and symptoms in the first few days of the acute febrile phase were similar to those observed in cases with classical dengue fever, and included continuously high fever, headache, muscle pain, nausea, vomiting and abdominal pain, etc. In the laboratory findings we noted hypoalbuminemia and mild elevation of the GOT and GPT. The hemogram showed an increasing atypical lymphocyte count during the acute febrile period. Prolongations of the partial thromboplastin time and thrombin time were also found, especially in the severe shock cases. All patients had varying degrees of hepatomegaly and pleural effusion from their chest x-rays accompanied by a rapid increase in the hematocrit of more than 20% and a fall in the platelet count to less than 100000/microliters. During the plasma leakage period the patients easily developed shock, even leading to death, unless adequate fluid supplies were given. This is also the major pathophysiological difference between dengue hemorrhagic fever and classical dengue fever. Although some studies concerning the pathogenesis of dengue hemorrhagic fever have been reported, but the exact mechanisms need further investigation.

  20. [Dengue hemorrhagic fever. Experiences from Thailand].

    PubMed

    Sørensen, E

    1992-06-30

    Increased incidence of dengue haemorrhagic fever has been observed in South East Asia. The etiology, clinical features and epidemiology of dengue virus infections are presented, with special emphasis on experience from Thailand. Reduction of sources, in terms of eliminating breeding sites for mosquitos, is the major approach in controlling dengue haemorrhagic fever, an approach which can succeed only through participation by the local community. The involvement of schools has proven to be successful in campaigns to reduce mosquito breeding sites in Thailand.

  1. Seroprevalence of Alkhurma and other hemorrhagic fever viruses, Saudi Arabia.

    PubMed

    Memish, Ziad A; Albarrak, Ali; Almazroa, Mohammad A; Al-Omar, Ibrahim; Alhakeem, Rafat; Assiri, Abdullah; Fagbo, Shamsudeen; MacNeil, Adam; Rollin, Pierre E; Abdullah, Nageeb; Stephens, Gwen

    2011-12-01

    A 2009 deployment of military units from several Saudi Arabian provinces to Jazan Province, Saudi Arabia, enabled us to evaluate exposure to Alkhurma, Crimean-Congo, dengue, and Rift Valley hemorrhagic fever viruses. Seroprevalence to all viruses was low; however, Alkhurma virus seroprevalence was higher (1.3%) and less geographically restricted than previously thought.

  2. [Severe hemorrhagic forms of Rift Valley fever: about 5 cases].

    PubMed

    Salem, Mohamed Lemine Ould; Baba, Sidi El Wafi Ould; Fall-Malick, Fatimetou Zahra; Boushab, Boushab Mohamed; Ghaber, Sidi Mohamed; Mokhtar, Abdelwedoud

    2016-01-01

    Rift Valley fever (RVF) is an arbovirus caused by an RNA virus belonging to family Bunyaviridae (genus phlebovirus). It is a zoonosis that primarily affects animals but it also has the capacity to infect humans, either by handling meat, runts of sick animals or, indirectly, by the bite of infected mosquitoes (Aedes sp, Anopheles sp, Culex sp). In most cases, RVF infection in humans is asymptomatic, but it can also manifest as moderate febrile syndrome with a favorable outcome. However, some patients may develop hemorrhagic syndrome and/or neurological damages with a fatal evolution. We present a case study of the development of 5 patients with RVF associated with hemorrhagic fever syndrome admitted to the internal medicine department at National Hospital Center in Nouakchott (Mauritania), in October 2015. The outcome was favorable for two of the five patients. The other 3 died, two of hemorrhagic shock and one of septic shock. PMID:27642413

  3. Dengue hemorrhagic fever in infancy at Petchabun Hospital, Thailand.

    PubMed

    Witayathawornwong, P

    2001-09-01

    Prospective study of dengue hemorrhagic fever in infancy at the Pediatric Department, Petchabun Hospital during May 1997 to April 1999 is reported. There were 31 patients (2.9%) from total DHF cases of 1,044. Ten patients from 31 (32.2%) were referred from district hospitals. Male to female ratio was 17:14 (1.2:1). Maximal, minimal and median ages were 11.5 months, 22 days and 8 months, respectively. All patients had signs, symptoms and laboratory results compatible with dengue hemorrhagic fever. Serologic response was primary dengue infection. Five patients (16.1%) had gastrointestinal hemorrhage, all of them needed blood transfusion. Crystalline solution was fluid of choice given to all patients. Three patients were complicated with febrile convulsions. All patients had rapid and uneventful recovery.

  4. Prevalence of dengue fever and dengue hemorrhagic fever in Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia.

    PubMed

    Jamaiah, I; Rohela, M; Nissapatorn, V; Maizatulhikma, M M; Norazlinda, R; Syaheerah, H; Tan, H P

    2005-01-01

    Dengue fever and dengue hemorrhagic fever have been known to be endemic and reportable diseases in Malaysia since 1971. Major outbreaks occurred in 1973, 1982 and in 1998. For the past few decades until now. many studies have been performed to investigate the importance of these two diseases in Malaysia. A retrospective study was carried out in Hospital Tengku Ampuan Rahimah Klang to find the prevalence of these diseases. The data was collected from the record department of this hospital starting from the year 1999 until 2003 (5 years). A total of 6,577 cases of dengue fever and 857 cases of dengue hemorrhagic fever were reported. From the year 2000 onwards, cases of dengue fever had increased tremendously. However for the year 2001, there was a slight decrease in the reported cases. Most cases occurred in 2003, increasing from 674 in 1999 to 2,813 in 2003. Highest incidence was seen in Malay males more than 12 years of age. However, the cases of dengue hemorrhagic fever declined tremendously throughout the years. Most cases occurred in 1999 with 674 cases, then declining to only one in the year 2001 before it increased to 60 and 72 in the years 2002 and 2003, respectively. Most cases occurred in patients above 12 years old, the majority of which were Malay males.

  5. 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

  6. Surveillance of dengue hemorrhagic fever cases in Thailand.

    PubMed

    Gunakasem, P; Chantrasri, C; Chaiyanun, S; Simasathien, P; Jatanasen, S; Sangpetchsong, V

    1981-09-01

    A long-term surveillance system is necessary for planning and evaluation of hemorrhagic fever control Dry blood collection and using one dengue 2 antigen have been proved to be an efficient method to detect low and high level of HI antibody, determined to prove dengue infection. The percentage of dengue infection serologically proved from cases reported throughout a 3 year study was 52%. Dengue infected cases were reported outside epidemic period with lowest incidence in January. The majority of dengue proven cases occur at age 6 years. For chikungunya infection, studied in Bangkok metropolis and in this study in 72 provinces shows similar result indicating that chikungunya virus shows no significance in clinical and laboratory study in the surveillance programme. This study provides definite information for the planning and evaluation of hemorrhagic fever control.

  7. 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

  8. 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

  9. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    DOE PAGES

    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.

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

    PubMed

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

    2015-01-01

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

  11. 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

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

    PubMed

    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

    2015-01-01

    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 had a 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 100PFU 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.

  13. Epidemic dengue hemorrhagic fever in rural Indonesia. II. Clinical studies.

    PubMed

    Eram, S; Setyabudi, Y; Sadono, T I; Sutrisno, D S; Gubler, D J; Sulianti Saroso, J

    1979-07-01

    Clinical observations were made on 95 serologically or virologically confirmed dengue fever cases during an epidemic in a rural area of Indonesia in December 1976. The age distribution was similar to that observed in patients with dengue hemorrhagic fever in Jakarta, a highly endemic urban area. The observed disease ranged in severity from undifferentiated fever to shock and death. The majority of patients had acute onset of fever with nausea, vomiting, headache, and abdominal pain. Hepatomegaly was observed in only 19% of the patients. A positive tourniquet test was the most frequently observed hemorrhagic manifestation, but epistaxis was observed in 20% and hematemesis in 6% of the patients. Dengue shock syndrome was observed in 37% of the patients. There were four deaths, three of which were confirmed as due to dengue infection by virus isolation. The data suggest that one, and possibly two, of the fatal cases with virus isolation were primary infections, based on the results of hemagglutination-inhibition test using all four dengue antigens.

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

    PubMed

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

    2011-04-01

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

  15. 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

  16. 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.

  17. Large epidemics of hemorrhagic fevers in Mexico 1545-1815.

    PubMed

    Acuna-Soto, R; Romero, L C; Maguire, J H

    2000-06-01

    In 1545, twenty-four years after the Spanish conquest of the Aztec empire, an epidemic of a malignant form of a hemorrhagic fever appeared in the highlands of Mexico. The illness was characterized by high fever, headache, and bleeding from the nose, ears, and mouth, accompanied by jaundice, severe abdominal and thoracic pain as well as acute neurological manifestations. The disease was highly lethal and lasted three to four days. It attacked primarily the native population, leaving the Spaniards almost unaffected. The hemorrhagic fevers remained in the area for three centuries and the etiologic agent is still unknown. In this report we describe, and now that more information is available, analyze four epidemics that occurred in Mexico during the colonial period with a focus on the epidemic of 1576 which killed 45% of the entire population of Mexico. It is important to retrieve such diseases and the epidemics they caused from their purely historical context and consider the reality that if they were to reemerge, they are potentially dangerous. PMID:11304065

  18. 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

  19. 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.

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

    PubMed

    Bourée, Patrice

    2014-09-01

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

  1. 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

  2. Diagnostic Testing for Hemorrhagic Fevers in Pakistan: 2007–2013

    PubMed Central

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

    2014-01-01

    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

  3. [Active surveillance for dengue and dengue hemorrhagic fever].

    PubMed

    Gubler, D J

    1989-07-01

    Dengue and dengue hemorrhagic fever are emerging as major public health problems in most tropical countries. Effective prevention and control programs will depend on improved surveillance. A new approach to active surveillance is outlined with emphasis on the interepidemic period. The objective is to develop an early warning surveillance system than can predict epidemic dengue. Virologic surveillance is the most important in an early warning system. Dengue virus transmission should be monitored to provide information on which serotypes are present, their distribution, and the type of illness associated with each serotype. Other components of the active surveillance system include fever alert and clinical surveillance for severe and fatal disease associated with viral syndrome. Individually, each component is not very sensitive, but collectively, they provide an early warning capability that allows detection of newly introduced dengue virus serotypes well in advance of epidemic transmission. With such information, emergency mosquito control can be implemented and major epidemics averted.

  4. 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.

  5. 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.

  6. Dengue hemorrhagic fever--U.S.-Mexico border, 2005.

    PubMed

    2007-08-10

    Dengue fever is a mosquito-transmitted disease caused by any of four closely related virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) of the genus Flavivirus. Infection with one of these serotypes provides lifelong immunity to the infecting serotype only. Therefore, persons can acquire a second dengue infection from a different serotype, and second infections place them at greater risk for dengue hemorrhagic fever (DHF), the more severe form of the disease. DHF is characterized by bleeding manifestations, thrombocytopenia, and increased vascular permeability that can lead to life-threatening shock. In south Texas, near the border with Mexico, sporadic, locally acquired outbreaks of dengue fever have been reported previously; however, on the Texas side of the border, these outbreaks have not included recognized cases of locally acquired DHF in persons native to the area. In July 2005, a case of DHF was reported in a resident of Brownsville, Texas. In August 2005, health authorities in the neighboring state of Tamaulipas, Mexico, reported an ongoing dengue outbreak with 1,251 cases of dengue fever, including 223 cases (17.8%) of DHF. To characterize this dengue outbreak, the Texas Department of State Health Services (TDSHS), Mexican health authorities, and CDC conducted a clinical and epidemiologic investigation. This report summarizes the results of that investigation, which determined that the percentage of DHF cases associated with dengue fever outbreaks at the Texas-Tamaulipas border has increased. Health-care providers along the U.S. border with Mexico should be vigilant for DHF and familiar with its diagnosis and management to reduce the number of severe illnesses and deaths associated with outbreaks of dengue fever.

  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. Cytokines as biomarkers of Crimean-Congo hemorrhagic fever.

    PubMed

    Papa, Anna; Tsergouli, Katerina; Çağlayık, Dilek Yağcı; Bino, Silvia; Como, Najada; Uyar, Yavuz; Korukluoglu, Gulay

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a potentially severe disease caused by CCHF virus. As in other viral hemorrhagic fevers, it is considered that the course and outcome of the disease depend on the viral load and the balance among the immune response mediators, and that a fatal outcome is the result of a "cytokine storm." The level of 27 cytokines was measured in serum samples taken from 29 patients during the acute phase of the disease. Two cases were fatal. Among survivors, significant differences between severe and non-severe cases were observed in the levels of IP-10, and MCP-1, while the levels of IL-1b, IL-5, IL-6, IL-8, IL-9, IL-10, IL-15, IP-10, MCP-1, TNF-α, and RANTES differed significantly between fatal and non-fatal cases (P < 0.05). RANTES was negatively correlated with the outcome of the disease. A striking similarity with the cytokine patterns seen in Ebola virus disease was observed. A weak Th1 immune response was seen. The viral load was positively correlated with IL-10, IP-10, and MCP-1 levels, and negatively correlated with the ratio IL-12/IL-10. Especially IP-10 and MCP-1 were significantly associated with the viral load, the severity and outcome of the disease, and they could act as biomarkers and, probably, as potential targets for treatment strategies design. PMID:26118413

  9. The 1996 outbreak of dengue hemorrhagic fever in Delhi, India.

    PubMed

    Anuradha, S; Singh, N P; Rizvi, S N; Agarwal, S K; Gur, R; Mathur, M D

    1998-09-01

    A major outbreak of dengue hemorrhagic fever (DHF) affected more than 10,000 people in Delhi and neighboring areas in 1996. The outbreak started in September, peaked in October to November and lasted till early December. The clinical and laboratory data of 515 adult patients admitted to Lok Nayak Hospital, New Delhi were reviewed. Fever (100%), myalgias and malaise (96%), abdominal pain (10.2%) and vomiting (8.7%) were the prominent presenting features. Hemorrhagic manifestations were seen in all patients- a positive tourniquet test (21.2%), scattered petechial rash (23.07%), confluent rash (2.7%), epistaxis (38.4%), gum bleeds (28.06%) and hematemesis (22.86%) being the major bleeding manifestations. Hepatomegaly was observed in 96% of the patients. Laboratory investigations revealed thrombocytopenia, hemoconcentration and leukopenia. Serological confirmation with a microcapture ELISA technic was done in 143/515 patients. The mortality rate was 6.6% and, multiple bleeding manifestations, severe thrombocytopenia, hypoproteinemia and dengue shock syndrome (DSS) were associated with a higher mortality.

  10. Dengue hemorrhagic fever with special emphasis on immunopathogenesis.

    PubMed

    Kurane, Ichiro

    2007-09-01

    Dengue virus infections are a serious cause of morbidity and mortality in most tropical and subtropical areas of the world; Southeast and South Asia, Central and South America, and the Caribbean. Dengue virus infection can be asymptomatic or causes two forms of illness, dengue fever (DF) and dengue hemorrhagic fever (DHF), which is the severe form of dengue illness and often fatal. Pathogenesis of DHF has been analyzed, and two mechanisms are considered to be responsible. These include dengue serotype cross-reactive immune responses and virulence of the virus. The immunopathological mechanisms include a complex series of immune responses. Rapid increase in the levels of cytokines, especially TNF-alpha, and chemical mediators play a key role in inducing unique clinical manifestations of DHF such as plasma leakage, shock, and hemorrhagic manifestations. It is understood that the process is initiated by infection with a virulent dengue virus, often in the presence of antibodies that enhance dengue virus infection in secondary infection, and then triggered by rapidly elevated cytokines and chemical mediators that were produced by intense immune activation. However, complete understanding of the entire pathological mechanism is far from complete, and further studies are still needed.

  11. 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.

  12. 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

  13. Unique small molecule entry inhibitors of hemorrhagic fever arenaviruses.

    PubMed

    Lee, Andrew M; Rojek, Jillian M; Spiropoulou, Christina F; Gundersen, Anette T; Jin, Wei; Shaginian, Alex; York, Joanne; Nunberg, Jack H; Boger, Dale L; Oldstone, Michael B A; Kunz, Stefan

    2008-07-01

    Viral hemorrhagic fevers caused by the arenaviruses Lassa virus in Africa and Machupo, Guanarito, Junin, and Sabia virus in South America are among the most devastating emerging human diseases with fatality rates of 15-35% and a limited antiviral therapeutic repertoire available. Here we used high throughput screening of synthetic combinatorial small molecule libraries to identify inhibitors of arenavirus infection using pseudotyped virion particles bearing the glycoproteins (GPs) of highly pathogenic arenaviruses. Our screening efforts resulted in the discovery of a series of novel small molecule inhibitors of viral entry that are highly active against both Old World and New World hemorrhagic arenaviruses. We observed potent inhibition of infection of human and primate cells with live hemorrhagic arenaviruses (IC(50)=500-800 nm). Investigations of the mechanism of action revealed that the candidate compounds efficiently block pH-dependent fusion by the arenavirus GPs (IC(50) of 200-350 nm). Although our lead compounds were potent against phylogenetically distant arenaviruses, they did not show activity against other enveloped viruses with class I viral fusion proteins, indicating specificity for arenavirus GP-mediated membrane fusion.

  14. A travel medicine view of dengue and dengue hemorrhagic fever.

    PubMed

    Meltzer, Eyal; Schwartz, Eli

    2009-09-01

    Dengue fever is the most prevalent arboviral infection worldwide, with up to 40% of the world population living in endemic regions. Among travelers to tropical countries, dengue infection is increasingly reported, and it is now a leading cause of post-travel fever. Outbreaks of dengue-like illness were already described since the 18th century, but it is only in the last half century that a severe form of the disease - dengue hemorrhagic fever (DHF) has been described. Although the cause of DHF is not established, the prevailing theory attributes the disease to antibody-dependent enhancement of viral replication, in the presence of a secondary dengue infection. Comparative studies of primary vs. secondary infection are difficult to perform in endemic countries because of the rarity of primary infection except during early infancy. Travelers on the other hand are usually diagnosed with primary infection and are therefore a better study population. Data on dengue and DHF among travelers appears to suggest that severe dengue and DHF occur in similar rates among cases with primary and with secondary infections. Epidemiological and physiological data from travelers suggest that the prevailing theory on the causes of DHF needs to be reconsidered.

  15. 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

  16. Domestically acquired seoul virus causing hemorrhagic fever with renal syndrome-Maryland, 2008.

    PubMed

    Woods, Christian; Palekar, Rakhee; Kim, Peter; Blythe, David; de Senarclens, Olivier; Feldman, Katherine; Farnon, Eileen C; Rollin, Pierre E; Albariño, Cesar G; Nichol, Stuart T; Smith, Margo

    2009-11-15

    Hantaviruses are rodent-borne viruses capable of causing human disease. The Seoul virus is a hantavirus that causes hemorrhagic fever with renal syndrome in East Asia. To our knowledge, we report the first domestically acquired case of hemorrhagic fever with renal syndrome caused by the Seoul virus, confirmed by serology testing, reverse-transcriptase polymerase chain reaction, and nucleotide sequence analysis. The patient presented with myalgias and fever, and developed acute renal failure.

  17. 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

  18. A Syrian golden hamster model recapitulating ebola hemorrhagic fever.

    PubMed

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

    2013-01-15

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

  19. 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.

  20. 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.

  1. 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.

  2. Dengue 1 virus and dengue hemorrhagic fever, French Polynesia, 2001.

    PubMed

    Hubert, Bruno; Halstead, Scott B

    2009-08-01

    An epidemic of dengue 1 virus (DENV-1) occurred in French Polynesia in 2001, 4 years after a DENV-2 epidemic that ended in 1997. Surveillance data from hospitalized case-patients showed that case-patients with dengue hemorrhagic fever (DHF) exhibited a bimodal age distribution with 1 peak among infants 6-10 months of age and a second peak at 4-11 years of age. The relative risk of DHF developing in children born before rather than after the DENV-2 epidemic was 186 (95% confidence interval 26-1,324). Among children born toward the end of the DENV-2 epidemic, a strong temporal association was found between the month of birth and the risk of being hospitalized for DHF. This study documents epidemic pathogenicity associated with the sequence of DENV-2 infection followed by DENV-1 infection.

  3. Dengue hemorrhagic fever in Malaysia: the 1973 epidemic.

    PubMed

    Wallace, H G; Lim, T W; Rudnick, A; Knudsen, A B; Cheong, W H; Chew, V

    1980-03-01

    The first major Malaysian epidemic of dengue hemorrhagic fever with severe manifestations occurred in 1973, with 969 reported cases and 54 deaths. In a detailed study of 138 clinically diagnosed and laboratory confirmed cases at the General Hospital in Kuala Lumpur, hemorrhagic manifestations were observed in 68.7% and shock in 18.1% of the patients. The cases occurred mainly from May to September, largely in urban and suburban areas of the majority of the states in the country. A main focus of infection was Jinjang, a heavily populated outlying district of Kuala Lumpur, where unusually high incidences of morbidity, severe disease and mortality were seen. Severe disease was seen mostly in children under the age of 15 years, although a significant number of adults suffered milder illnesses. The Chinese population was chiefly affected, due to their living in crowded, low-income housing where the vector, Aedes aegypti, occurred in the greatest numbers. All four dengue types were recovered during the epidemic period, although dengue 3 (DEN-3) was incriminated as the major epidemic type. Entomological data revealed high indices of A. aegypti throughout the country and left little doubt that this epidemic was aegypti transmitted. Spraying and fogging operations were carried out in attempts to control vector populations.

  4. Dengue hemorrhagic fever is associated with polymorphisms in JAK1.

    PubMed

    Silva, Luciano K; Blanton, Ronald E; Parrado, Antonio R; Melo, Paulo S; Morato, Vanessa G; Reis, Eliana A G; Dias, Juarez P; Castro, Jesuina M; Vasconcelos, Pedro F C; Goddard, Katrina A B; Barreto, Maurício L; Reis, Mitermayer G; Teixeira, M Glória

    2010-11-01

    To identify genes associated with the clinical presentation of dengue, 50 cases of probable or possible dengue hemorrhagic fever (DHF), 236 dengue fever (DF), and 236 asymptomatic infections were genotyped for 593 single-nucleotide polymorphisms (SNPs) in 56 genes across the type 1 interferon (IFN) response pathway as well as other important candidate genes. By single locus analysis comparing DHF with DF, 11 of the 51 markers with P<0.05 were in the JAK1 gene. Five markers were significantly associated by false discovery rate criteria (q<0.20 when P<6 × 10(-4)). The JAK1 SNPs showed differential distribution by ethnicity and ancestry consistent with epidemiologic observations in the Americas. The association remained significant after controlling for ancestry and income. No association was observed with markers in the gene encoding CD209 (DC-SIGN). An association between DHF and JAK1 polymorphisms is in agreement with expression profiles showing generalized decreased type 1 IFN-stimulated gene expression in these patients.

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

    PubMed

    Mawson, Anthony R

    2013-12-01

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

  6. Dengue hemorrhagic fever outbreak in children in Port Sudan.

    PubMed

    Malik, Amal; Earhart, Kenneth; Mohareb, Emad; Saad, Magdi; Saeed, Mubarak; Ageep, Ali; Soliman, Atef

    2011-03-01

    Dengue fever (DF)/dengue hemorrhagic fever (DHF) has emerged as a global public health problem with countries in Asia and the Pacific sharing more than 70% of the disease burden. In 2004-2005 a total of 312 cases admitted to Pediatric and Sea Port Hospitals in Port Sudan were clinically diagnosed as DHF. The mortality rate recorded was 3.8% (n=12). Of the cases 73.4% were patients 5-15 years of age. A total of 91.2% of cases were admitted during May and June 2005 with 49.4% residing in the eastern region of Port Sudan. Dengue shock syndrome was observed in 37 of 312 (11.9%). All patients had thrombocytopenia with platelets count ranged from <100,000 to <150,000 cell/mm³. Of the 40 sera tested using RAPID-cassette test in the Khartoum Central Public Health Lab, 36 (90%) were dengue IgM positive. A subset of these sera (n=23) were sent to NAMRU-3 and confirmed by IgM-capture ELISA; 9 of 23 were PCR positive for dengue serotype 3.

  7. Crimean-Congo hemorrhagic fever in a dengue-endemic region: lessons for the future.

    PubMed

    Ali, Farheen; Saleem, Taimur; Khalid, Umair; Mehmood, Syed Faisal; Jamil, Bushra

    2010-07-01

    Crimean-Congo hemorrhagic fever and dengue hemorrhagic fever are endemic in Pakistan. However, the overlap of geographic distribution and early clinical features between the two conditions make a reliable diagnosis difficult in the initial stage of illness. A 16-year-old boy presented with a history of hematemesis and high-grade fever. A preliminary diagnosis of dengue hemorrhagic fever was made and supportive treatment was instituted; however, the patient continued to deteriorate clinically. Dengue IgM antibody testing was negative on the third day of admission. Qualitative polymerase chain reaction test for Crimean-Congo hemorrhagic fever viral RNA was sent but the patient expired shortly after the results became available on the sixth day of admission. Considerable resources had to be expended on contact tracing and administration of ribavirin prophylaxis to all the health-care workers who had come in contact with the patient. It is crucial that Crimean-Congo hemorrhagic fever be recognized and treated at an early stage because of longer term financial and health implications for contacts such as health-care workers in the setting of a developing country. Increased surveillance of dengue and Crimean-Congo hemorrhagic fever cases is warranted for the derivation of reasonably reliable, cost-effective and prompt predictors of disease diagnosis. These predictors can help guide future decisions in the management of similar cases. Ultimately, such a strategy may translate into better cost containment in resource-poor settings. Institution of ribavirin prophylaxis in selected patients also merits consideration.

  8. Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused by Distinct Arteriviruses.

    PubMed

    Lauck, Michael; Alkhovsky, Sergey V; Bào, Yīmíng; Bailey, Adam L; Shevtsova, Zinaida V; Shchetinin, Alexey M; Vishnevskaya, Tatyana V; Lackemeyer, Matthew G; Postnikova, Elena; Mazur, Steven; Wada, Jiro; Radoshitzky, Sheli R; Friedrich, Thomas C; Lapin, Boris A; Deriabin, Petr G; Jahrling, Peter B; Goldberg, Tony L; O'Connor, David H; Kuhn, Jens H

    2015-08-01

    Simian hemorrhagic fever (SHF) is lethal for macaques. Based on clinical presentation and serological diagnosis, all reported SHF outbreaks were thought to be caused by different strains of the same virus, simian hemorrhagic fever virus (SHFV; Arteriviridae). Here we show that the SHF outbreaks in Sukhumi in 1964 and in Alamogordo in 1989 were caused not by SHFV but by two novel divergent arteriviruses. Our results indicate that multiple divergent simian arteriviruses can cause SHF. PMID:25972539

  9. Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused by Distinct Arteriviruses

    PubMed Central

    Lauck, Michael; Alkhovsky, Sergey V.; Bào, Yīmíng; Bailey, Adam L.; Shevtsova, Zinaida V.; Shchetinin, Alexey M.; Vishnevskaya, Tatyana V.; Lackemeyer, Matthew G.; Postnikova, Elena; Mazur, Steven; Wada, Jiro; Radoshitzky, Sheli R.; Friedrich, Thomas C.; Lapin, Boris A.; Deriabin, Petr G.; Jahrling, Peter B.; Goldberg, Tony L.; O'Connor, David H.

    2015-01-01

    Simian hemorrhagic fever (SHF) is lethal for macaques. Based on clinical presentation and serological diagnosis, all reported SHF outbreaks were thought to be caused by different strains of the same virus, simian hemorrhagic fever virus (SHFV; Arteriviridae). Here we show that the SHF outbreaks in Sukhumi in 1964 and in Alamogordo in 1989 were caused not by SHFV but by two novel divergent arteriviruses. Our results indicate that multiple divergent simian arteriviruses can cause SHF. PMID:25972539

  10. Viral hemorrhagic fevers: advancing the level of treatment

    PubMed Central

    2012-01-01

    The management of viral hemorrhagic fevers (VHFs) has mainly focused on strict infection control measures, while standard clinical interventions that are provided to patients with other life-threatening conditions are rarely offered to patients with VHFs. Despite its complexity, a proper clinical case management of VHFs is neither futile nor is it lacking in scientific rationale. Given that patient outcomes improve when treatment is started as soon as possible, development and implementation of protocols to promptly identify and treat patients in the earliest phases of diseases are urgently needed. Different pharmacological options have been proposed to manage patients and, as for other life-threatening conditions, advanced life support has been proved effective to address multiorgan failure. In addition, high throughput screening of small molecular libraries has emerged as a novel promising way to find new candidates drugs for VHFs therapy and a relevant number of new molecules are currently under investigation. Here we discuss the current knowledge about VHF clinical management to propose a way to step up the approach to VHFs beyond the mere application of infection control measures. PMID:22458265

  11. 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

  12. 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.

  13. 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.

  14. Dengue hemorrhagic fever in Cuba, 1981: a retrospective seroepidemiologic study.

    PubMed

    Guzmán, M G; Kouri, G P; Bravo, J; Soler, M; Vazquez, S; Morier, L

    1990-02-01

    In Cuba, 2 epidemics of dengue virus occurred: 1 caused by DEN-1 in 1977 and 1 caused by DEN-2 in 1981. The latter was associated with cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). To study viral risk factors for DHF/DSS, a retrospective seroepidemiological survey was conducted in Cerro, a densely populated district in Havana City. The prevalence of plaque reduction neutralizing antibodies to DEN-1 and DEN-2 viruses was measured in 1,295 individuals (children and adults). Of these, 43.7% were immune to DEN-1 virus and 23.6% to DEN-2 virus. Of those individuals who were immune, 26.1% were immune to DEN-1 virus only, 6% to DEN-2 virus only, and 17.6% to both viruses. The DEN-2 virus infection rate in DEN-1 immune individuals was 3.8 times higher than in non-immune individuals. The 5 DHF/DSS cases in the sample had evidence of DEN-1 virus plus DEN-2 virus infections. Three were children and 2 were young adults. No cases were found in individuals infected with DEN-1 virus or DEN-2 virus only. Children infected by DEN-1 virus followed by DEN-2 virus had a high risk of acquiring DHF/DSS. Blacks and whites were equally infected with DEN-1 and DEN-2 viruses.

  15. Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever.

    PubMed

    Bethell, D B; Flobbe, K; Cao, X T; Day, N P; Pham, T P; Buurman, W A; Cardosa, M J; White, N J; Kwiatkowski, D

    1998-03-01

    Dengue shock syndrome is a severe complication of dengue hemorrhagic fever (DHF), characterized by a massive increase in vascular permeability. Plasma cytokine concentrations were prospectively studied in 443 Vietnamese children with DHF, of whom 6 died. Shock was present in 188 children on admission to hospital, and in 71 children it developed later. Contrary to expectations, certain inflammatory markers (interleukin-6 and soluble intercellular adhesion molecule-1) were lower in the group with shock, and this may reflect the general loss of protein from the circulation due to capillary leakage. Only soluble tumor necrosis factor receptor (TNFR) levels showed a consistent positive relationship with disease severity. In patients with suspected DHF without shock, admission levels of sTNFR-75 in excess of 55 pg/mL predicted the subsequent development of shock, with a relative risk of 5.5 (95% confidence interval, 2.3-13.2). Large-scale release of soluble TNFR may be an early and specific marker of the endothelial changes that cause dengue shock syndrome.

  16. Race: a risk factor for dengue hemorrhagic fever.

    PubMed

    de la C Sierra, B; Kourí, G; Guzmán, M G

    2007-01-01

    Cuban DHF/DSS outbreaks have provided evidence of a reduced risk of people of Negroid race for DHF/DSS compared to those of Caucasoid race. These observations from Cuban dengue outbreaks have significant epidemiological interest, as the differences in susceptibility to DHF/DSS among racial groups in Cuba coincide with that reported in African and Black Caribbean populations. In this article, we review the literature on race as a risk factor for DHF/DSS and discuss recent results from ongoing studies. Taking into consideration the origins of contemporary Cuban inhabitants, we propose that the Cuban, Caribbean Black and African populations share a common gene pool that could explain, at least partially, the low incidence of dengue hemorrhagic fever in Cuba and Caribbean and African countries. The central role played by immunological mechanisms in the pathogenesis of DHF/DSS has led us to consider that the polymorphic genes associated with the immune response must be carefully considered among those human genes regulating dengue disease severity that might be distributed unequally in Blacks and Whites.

  17. Dengue and dengue hemorrhagic fever in the Americas.

    PubMed

    Gubler, D J

    1987-08-01

    There has been a constant increase in the incidence of dengue in the Americas over the past 15 years. This has been caused by increased frequency of epidemic activity in most countries, as a result of increased numbers of virus serotypes circulating in the region. The change in disease ecology has resulted in the emergence of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) in the region, first with a major epidemic in Cuba, followed by increased occurrence of sporadic cases of DHF/DSS in many countries. The sequence of events in the Americas in the 1980's has been nearly identical to the pattern observed in Southeast Asia in the 1950's. Prospects for prevention of epidemic DHF/DSS in the American region, therefore, are not good. In the absence of Aedes aegypti eradication, the only hope for effective prevention and control is to develop more effective active surveillance for DHF/DSS and combine that with both emergency and community-based vector control programs.

  18. 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

  19. Pathology of chronic Bolivian hemorrhagic fever in the rhesus monkey.

    PubMed Central

    Mcleod, C. G.; Stookey, J. L.; Eddy, G. A.; Scott, K.

    1976-01-01

    Gross and microscopic lesions of Bolivian hemorrhagic fever (BHF) are described in 10 rhesus monkeys that survived from 30 to 78 days after subcutaneous inoculation with a dose of 10(3) plaque-forming units (PFU) of Machupo virus, a dose which produces a severe and generally fatal disease. Six of the monkeys had been given low doses of homologous immune globulin when initial signs of infection appeared. Monkeys exhibited clinical signs in two phases. The initial signs of acute infection which began to appear about 1 week following inoculation included: diarrhea, depression, anorexia, dehydration, and skin rash. The survivors of this early phase of the illness usually showed improvement before relapsing into the second (or chronic) phase, which was characterized clinically by central nervous system disturbances including incoordination, tremors, convulsions, paresis, and muscle atrophy. Microscopic lesions were similar in both immune globulin-treated and untreated animals. These included widespread lymphoreticular infiltrates in the walls and adventitia of blood vessels of the brain, spinal cord, pancreas, intestine, liver kidney, adrenal, parathyroid, heart, and skeletal muscle. Diffuse lymphocytic infiltrates not confined to the vascular or perivascular tissues were present to a variable degree in many of these and other organs. Several monkeys exhibited lymphocytic inflammation of the choroid, meninges, peripheral nerves, and ganglia. Images Figure 7 Figure 8 Figure 1 Figure 2 Figure 9 Figure 3 Figure 4 Figure 5 Figure 6 PMID:181994

  20. The economic impact of dengue hemorrhagic fever on family level in Southern Vietnam.

    PubMed

    Harving, Mette Lønstrup; Rönsholt, Frederikke Falkencrone

    2007-05-01

    Dengue fever is a viral infection transmitted by mosquitoes (Aedes Aegypti). WHO estimates that 40% of the world's population live in areas endemic for dengue fever, and that there are approximately 50 million cases of dengue infection worldwide every year. This study aims to measure the economic consequences of dengue hemorrhagic fever in Southern Vietnam on family level. Estimating the economic impact of dengue fever/dengue hemorrhagic fever is important in order to prioritize resources for research, prevention, and control. So far no studies from Vietnam concerning this subject have been published. The study is based on standardized interviews. The study includes 175 children at the age 0-15 years, hospitalized in Children's Hospital No 1 in Ho Chi Minh City during a 10-week period in the fall of 2005. The children's parents/caretakers were interviewed on expenses related to the child's disease. The study shows that the average family cost of treating one child is approximately 61 USD including direct and indirect costs. On average, the largest expenses were those related to the initial visit at a local general practitioner, the hospital bill from Children's Hospital No1 and lost income for the parents. Dengue hemorrhagic fever is a large expense for a family and can rightly be considered as a substantial socio-economic burden in Southern Vietnam. Larger studies are needed for a more accurate estimate of the extent of the expenses related to both dengue fever and dengue hemorrhagic fever.

  1. Hanta hemorrhagic fever with renal syndrome: a case report and review.

    PubMed

    Tai, Pei-Wen; Chen, Li-Ching; Huang, Cheng-Hua

    2005-06-01

    Hantavirus infection is seldom reported in Taiwan. The spectrum of clinical severity ranges from mild to severe and may cover Hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome (HFRS). We report a case of HFRS in a 24-year-old soldier presenting with fever, chills, abdominal pain and generalized myalgia. His clinical course progressed through febrile, hypotensive, oliguria and polyuria phases. Hantavirus infection was proven by serology at the second hospital week. The patient was successfully treated with supportive management. Clinicians should be alert to the possibility of HFRS when examining patients with symptoms of fever, renal function impairment, hemorrhagic tendency and with rural exposure in Taiwan.

  2. 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

  3. 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

  4. Relationship between Breteau and House indices and cases of dengue/dengue hemorrhagic fever in Kuala Lumpur, Malaysia.

    PubMed

    Sulaiman, S; Pawanchee, Z A; Arifin, Z; Wahab, A

    1996-09-01

    The relationship between the Breteau index, the House index, and the occurrence of dengue/dengue hemorrhagic fever in the 6 zones of Kuala Lumpur was studied throughout 1994. Cases of dengue/dengue hemorrhagic fever varied between zones and between months, ranging from 0 to 21 cases. In most of the zones in Kuala Lumpur, the occurrence of dengue/dengue hemorrhagic fever has no relationship with the Breteau and House indices. Cases of dengue/dengue hemorrhagic fever occurred in all zones despite the low Breteau and House indices.

  5. Dengue fever with hemorrhagic manifestations: a report of three cases from Puerto Rico.

    PubMed

    López-Correa, R H; Cline, B L; Ramirez-Ronda, C; Bermudez, R; Sather, G E; Kuno, G

    1978-11-01

    During the 1975 dengue epidemic in Puerto Rico, we studied three patients who had serologically confirmed dengue with hemorrhagic manifestations. None of the patients went into shock and none died. Only one of the patients had disease that resembled dengue hemorrhagic fever (DHF) as observed in Southeast Asia. This patient was a 14-year-old boy who had epistaxis, a positive tourniquet test, moderate thrombocytopenia, and significant hemoconcentration. The other two patients had hemorrhagic disease which was of clinical importance, but was not typical of DHF. These cases of dengue with hemorrhagic manifestations are the only ones known to have been documented in Puerto Rico.

  6. Dengue hemorrhagic fever presenting with hemorrhagic pancreatitis and an intramural hematoma of the duodenal wall: a case report and review of the literature.

    PubMed

    Lee, Chun-Yuan; Tsai, Hung-Chin; Lee, Susan Shin-jung; Lin, Chun-Ku; Huang, Jer-Shyung; Chen, Yao-Shen

    2013-05-01

    Dengue fever may present with atypical manifestations. Here we report a 47 year-old male presenting with fever and sore throat for 2 days, followed by epigastric pain and tarry stool for 4 days. The esophagogastroduodenoscopy revealed multiple ulcers with a nodular margin in the duodenal bulb and second portion of the duodenum. A MRI of the abdomen revealed hemorrhagic pancreatitis, with a large intramural hematoma in the second portion of duodenum. The final diagnosis was dengue hemorrhagic fever, grade II, complicated with hemorrhagic pancreatitis and an intramural hematoma of the duodenal wall. Physicians should be aware of the atypical abdominal presentations of dengue fever.

  7. The 1986 dengue and dengue hemorrhagic fever epidemic in Puerto Rico: epidemiologic and clinical observations.

    PubMed

    Dietz, V; Gubler, D J; Ortiz, S; Kuno, G; Casta-Vélez, A; Sather, G E; Gómez, I; Vergne, E

    1996-09-01

    In 1986 Puerto Rico experienced its eleventh dengue outbreak of this century, but the first with simultaneous transmission of three dengue virus serotypes, and the first with significant numbers of severe and fatal hemorrhagic disease. Overall, 10,659 cases were reported; 1,257 cases were laboratory confirmed as having current or recent dengue infection. Dengue 4 (DEN-4) was the predominant serotype (160/363 isolates, 44%) followed by dengue 1 (DEN-1) with 134 isolates (37%) and dengue 2 (DEN-2), 69 isolates (19%). Transmission peaked during September, but large numbers of cases occurred through November. Seventy-one (91%) of Puerto Rico's 78 municipalities had laboratory-confirmed cases. Fifty-one percent of all confirmed cases occurred in metropolitan San Juan. Most cases presented clinically as classical dengue fever, but 37% of all confirmed cases were reported to have developed some type of hemorrhagic manifestation, and 6% reported hematemesis. In addition, 29 laboratory confirmed cases met the WHO case definition for dengue hemorrhagic fever, 3 of which were fatal. Among the 29 laboratory-confirmed cases of dengue hemorrhagic fever/ dengue shook syndrome, virus was isolated from 12; one DEN-1, three DEN-2, and eight DEN-4. Among laboratory confirmed cases, infants less than one year of age were at greater risk of developing dengue hemorrhagic fever/ dengue shook syndrome, hematemesis and any reported hemorrhage than were the other age groups evaluated.

  8. 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

  9. 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

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

    PubMed

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

    2010-07-01

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

  11. Outbreaks of filovirus hemorrhagic fever: time to refocus on the patient.

    PubMed

    Bausch, Daniel G; Feldmann, Heinz; Geisbert, Thomas W; Bray, Mike; Sprecher, A G; Boumandouki, Paul; Rollin, Pierre E; Roth, Cathy

    2007-11-15

    In the 40 years since the recognition of filoviruses as agents of lethal human disease, there have been no specific advances in antiviral therapies or vaccines and few clinical studies on the efficacy of supportive care. On 20 September 2006, experts from 14 countries representing 68 institutions integrally involved in the response to outbreaks of filovirus hemorrhagic fever gathered at the National Microbiology Laboratory of the Public Health Agency of Canada in Winnipeg to discuss possible remedies for this grim situation, in a unique workshop entitled "Marburg and Ebola Hemorrhagic Fever: Feasibility of Prophylaxis and Therapy." A summary of the opportunities for and challenges to improving treatment of filovirus hemorrhagic fevers is presented here. PMID:17940941

  12. [The vaccines based on the replicon of the venezuelan equine encephalomyelitis virus against viral hemorrhagic fevers].

    PubMed

    Petrov, A A; Plekhanova, T M; Sidorova, O N; Borisevich, S V; Makhlay, A A

    2015-01-01

    The status of the various recombinant DNA and RNA-derived candidate vaccines, as well as the Venezuelan equine encephalomyelitis virus (VEEV) replicon vaccine system against extremely hazardous viral hemorrhagic fevers, were reviewed. The VEEV-based replication-incompetent vectors offer attractive features in terms of safety, high expression levels of the heterologous viral antigen, tropism to dendritic cells, robust immune responses, protection efficacy, low potential for pre-existing anti-vector immunity and possibility of engineering multivalent vaccines were tested. These features of the VEEV replicon system hold much promise for the development of new generation vaccine candidates against viral hemorrhagic fevers.

  13. Comparison of methods for isolation and titration of Crimean-Congo hemorrhagic fever virus.

    PubMed

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

    1986-10-01

    The fluorescence focus assay and the plaque assay in CER cells were compared with mouse inoculation for the isolation and titration of Crimean-Congo hemorrhagic fever virus. The fluorescence focus assay and the plaque assay were of similar sensitivity, but both produced 10- to 100-fold lower titers than did mouse inoculation. For specimens from 26 Crimean-Congo hemorrhagic fever patients in South Africa, virus was isolated from 20 by mouse inoculation and from only 11 by cell culturing. Although cell cultures were less sensitive for the isolation of virus from clinical specimens, they produced diagnostic results much more rapidly.

  14. Dengue virus identification by transmission electron microscopy and molecular methods in fatal dengue hemorrhagic fever.

    PubMed

    Limonta, D; Falcón, V; Torres, G; Capó, V; Menéndez, I; Rosario, D; Castellanos, Y; Alvarez, M; Rodríguez-Roche, R; de la Rosa, M C; Pavón, A; López, L; González, K; Guillén, G; Diaz, J; Guzmán, M G

    2012-12-01

    Dengue virus is the most significant virus transmitted by arthropods worldwide and may cause a potentially fatal systemic disease named dengue hemorrhagic fever. In this work, dengue virus serotype 4 was detected in the tissues of one fatal dengue hemorrhagic fever case using electron immunomicroscopy and molecular methods. This is the first report of dengue virus polypeptides findings by electron immunomicroscopy in human samples. In addition, not-previously-documented virus-like particles visualized in spleen, hepatic, brain, and pulmonary tissues from a dengue case are discussed.

  15. 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.

  16. Emergence of epidemic dengue/dengue hemorrhagic fever as a public health problem in the Americas.

    PubMed

    Gubler, D J; Trent, D W

    1993-12-01

    The incidence of dengue and dengue hemorrhagic fever has increased dramatically in the past 15 years in most urban centers of the tropics. Coincident with this increase has been the emergence of epidemic dengue hemorrhagic fever in the American region. The current changing disease pattern in the Americas is very similar to that which occurred in southeast Asia 30 years ago. The similarities in the evolution of severe disease in the two regions and the possible reasons for the changing disease pattern are discussed.

  17. Application of the pseudo-plaque assay for detection and titration of Crimean-Congo hemorrhagic fever virus.

    PubMed

    Berber, Engin; Canakoglu, Nurettin; Yoruk, Mustafa D; Tonbak, Sukru; Aktas, Munir; Ertek, Mustafa; Bolat, Yusuf; Kalkan, Ahmet; Ozdarendeli, Aykut

    2013-01-01

    A pseudo-plaque assay was developed for detection and quantitation of Crimean-Congo hemorrhagic fever virus Turkey-Kelkit06. Enzyme-catalyzed color development of infected cells probed with anti-Crimean-Congo hemorrhagic fever virus antibodies was used for determining the titer of Crimean-Congo hemorrhagic fever Turkey-Kelkit06 and for its detection in samples from persons infected with the Crimean-Congo hemorrhagic fever virus. The pseudo-plaque assay accuracy was confirmed by comparing pseudo-plaque assay titers with fluorescent immunofocus assay and focus formation assay titers using three stocks of virus. No significant difference in virus titers of Crimean-Congo hemorrhagic fever Turkey-Kelkit06 among the three methods was observed. The pseudo-plaque assay is more sensitive than the fluorescent immunofocus assay for detecting the virus in primary isolates of Crimean-Congo hemorrhagic fever virus collected from humans, but no difference in sensitivity between the two methods was observed in the cell-adapted strain of Crimean-Congo hemorrhagic fever Turkey-Kelkit06. The pseudo-plaque assay is suitable for titration of Crimean-Congo hemorrhagic fever Turkey-Kelkit06, which does not develop plaques, suggesting it may also be suitable for the detection of other viruses.

  18. Geospatial Analysis of Urban Land Use Pattern Analysis for Hemorrhagic Fever Risk - a Review

    NASA Astrophysics Data System (ADS)

    Izzah, L. N.; Majid, Z.; Ariff, M. A. M.; Fook, C. K.

    2016-09-01

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

  19. Crimean-Congo hemorrhagic fever virus in high-risk population, Turkey.

    PubMed

    Gunes, Turabi; Engin, Aynur; Poyraz, Omer; Elaldi, Nazif; Kaya, Safak; Dokmetas, Ilyas; Bakir, Mehmet; Cinar, Ziynet

    2009-03-01

    In the Tokat and Sivas provinces of Turkey, the overall Crimean-Congo hemorrhagic fever virus (CCHFV) seroprevalence was 12.8% among 782 members of a high-risk population. CCHFV seroprevalence was associated with history of tick bite or tick removal from animals, employment in animal husbandry or farming, and being >40 years of age. PMID:19239765

  20. 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

  1. 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

  2. Hemorrhagic Fever with Renal Syndrome in 4 US Soldiers, South Korea, 2005

    PubMed Central

    Moon, Sung-Sil; Gu, Se Hun; Song, Ki-Joon; Baek, Luck Ju; Kim, Heung Chul; Kijek, Todd; O’Guinn, Monica L.; Lee, John S.; Turell, Michael J.; Klein, Terry A.

    2009-01-01

    Four US soldiers acquired hemorrhagic fever with renal syndrome while training near the Demilitarized Zone, South Korea, in 2005. Hantaan virus sequences were amplified by reverse transcription–PCR from patient serum samples and from lung tissues of striped field mice (Apodemus agrarius) captured at training sites. Epidemiologic investigations specified the ecology of possible sites of patient infection. PMID:19891878

  3. Hemorrhagic fever with renal syndrome in 4 US soldiers, South Korea, 2005.

    PubMed

    Song, Jin Won; Moon, Sung Sil; Gu, Se Hun; Song, Ki Joon; Baek, Luck Ju; Kim, Heung Chul; Kijek, Todd; O'Guinn, Monica L; Lee, John S; Turell, Michael J; Klein, Terry A

    2009-11-01

    Four US soldiers acquired hemorrhagic fever with renal syndrome while training near the Demilitarized Zone, South Korea, in 2005. Hantaan virus sequences were amplified by reverse transcription-PCR from patient serum samples and from lung tissues of striped field mice (Apodemus agrarius) captured at training sites. Epidemiologic investigations specified the ecology of possible sites of patient infection.

  4. 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

  5. The first major outbreak of dengue hemorrhagic fever in Delhi, India.

    PubMed

    Dar, L; Broor, S; Sengupta, S; Xess, I; Seth, P

    1999-01-01

    India An outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHS/DSS) occurred in 1996 in India in and near Delhi. The cause was confirmed as dengue virus type 2, by virus cultivation and indirect immunofluorescence with type-specific monoclonal antibodies. This is the largest such outbreak reported from India, indicating a serious resurgence of dengue virus infection.

  6. Crimean-Congo Hemorrhagic Fever in Dubai, United Arab Emirates, 2010: Case Report

    PubMed Central

    Mohamed AL Dabal, Laila; Rahimi Shahmirzadi, Mohmamed Reza; Baderldin, Samar; Abro, Ali; Zaki, Ali; Dessi, Zulfa; Al Eassa, Essa; Khan, Gulfaraz; Shuri, Hassan; Alwan, Abid Mustafa

    2016-01-01

    Introduction Crimean-Congo hemorrhagic fever (CCHF) is a severe infectious disease that is not endemic in the United Arab Emirates (UAE). Case Presentation We report two cases of confirmed CCHF diagnosed in Dubai, UAE, during Hajj season 2010. Both patients presented with an acute history of high-grade fever, skin rash, and hematemesis. Conclusions In spite of maximal supportive measures and intravenous ribavirin therapy, both patients died within a few days from start of illness. More than 250 health care workers came into variable degrees of contact with the index cases, and none of them developed signs or symptoms suggestive of acquiring the illness. Health care workers from nonendemic regions should be aware of zoonotic hemorrhagic fevers imported via infected cattle and ticks and be able to diagnose and properly manage suspected cases in a timely manner. In addition, proper infection-control measures should be undertaken to prevent nosocomial spread of infection. PMID:27795839

  7. [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.

  8. [Dengue fever with hemorrhagic manifestations after a stay in Thailand].

    PubMed

    Krippner, R; Hanisch, G; Kretschmer, H

    1990-06-01

    On returning from a 24-day long stay in Thailand a 30-year-old German woman fell ill with high fever and head and limb aches. Soon after a confluent petechial exanthem was noted, as well as conjunctival and gastrointestinal bleedings. Biochemical findings (fall in haemoglobin concentration and haematocrit, leucopenia and thrombocytopenia, rise in lactate dehydrogenase) and a rise in Dengue antibody titre to 1 : 320 (on the 13th day of illness) confirmed the diagnosis of Dengue fever with haemorrhagic manifestations. This mosquito-transmitted viral disease, while so far only rarely reported in tourists, should be considered in the differential diagnosis of fever of undetermined origin in travellers to the tropics.

  9. [Hemorrhagic fever caused by dengue in 2 tourists].

    PubMed

    Ligtenberg, J J; Hospers, G A; Sprenger, H G; Weits, J

    1991-12-14

    Dengue haemorrhagic fever in two female tourists to Thailand (1990) and Indonesia (1989) respectively, is reported for the first time in the Netherlands. The main symptoms directly after return were high fever, haemorrhagic exanthema, thrombocytopenia and in one patient signs of haemoconcentration. Initially both patients were treated with antibiotics. They recovered after intravenous fluid therapy; one of them received a thrombocyte transfusion. Increasing travel to Asia and South America will result in more tourists returning with this potentially serious arboviral disease (dengue haemorrhagic shock).

  10. Computational genomic analysis of hemorrhagic fever viruses. Viral selenoproteins as a potential factor in pathogenesis.

    PubMed

    Ramanathan, C S; Taylor, E W

    1997-01-01

    A number of distinct viruses are known as hemorrhagic fever viruses based on a shared ability to induce hemorrhage by poorly understood mechanisms, typically involving the formation of blood clots ("disseminated intravascular coagulation"). It is well documented that selenium plays a significant role in the regulation of blood clotting via its effects on the thromboxane/prostacyclin ratio, and effects on the complement system. Selenium has an anticlotting effect, whereas selenium deficiency has a proclotting or thrombotic effect. It is also well documented that extreme dietary selenium deficiency, which is almost never seen in humans, has been associated with hemorrhagic effects in animals. Thus, the possibility that viral selenoprotein synthesis might contribute to hemorrhagic symptoms merits further consideration. Computational genomic analysis of certain hemorrhagic fever viruses reveals the presence of potential protein coding regions (PPCRs) containing large numbers of in-frame UGA codons, particularly in the -1 reading frame. In some cases, these clusterings of UGA codons are very unlikely to have arisen by chance, suggesting that these UGAs may have some function other than being a stop codon, such as encoding selenocysteine. For this to be possible, a downstream selenocysteine insertion element (SECIS) is required. Ebola Zaire, the most notorious hemorrhagic fever virus, has a PCR with 17 UGA codons, and several potential SECIS elements can be identified in the viral genome. One potential viral selenoprotein may contain up to 16 selenium atoms per molecule. Biosynthesis of this protein could impose an unprecedented selenium demand on the host, potentially, leading to severe lipid peroxidation and cell membrane destruction, and contributing to hemorrhagic symptoms. Alternatively, even in the absence of programmed selenoprotein synthesis, it is possible that random slippage errors would lead to increased encounters with UGA codons in overlapping reading

  11. 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...

  12. 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 effects on producers all over the world. The only vector-borne DNA virus is included here (i.e., African swine fever virus), and the herpesviruses discussed have a complex epidemiology characterized by outbreaks ...

  13. Dengue hemorrhagic fever in Trinidad and Tobago: a case for a conservative approach to platelet transfusion.

    PubMed

    Sharma, Anu; Charles, Kenneth; Chadee, Dave; Teelucksingh, Surujpaul

    2012-03-01

    Dengue fever is endemic to Trinidad and Tobago. A retrospective analysis of all adult admissions at a tertiary hospital in Trinidad treated for dengue during January 1-December 31, 2008 was performed. A total of 186 patients were treated during this period: 98.9% (184) of the patients were thrombocytopenic; 45.2% were severely thrombocytopenic; 13 patients showed development of minor hemorrhage and only one case of major hemorrhage; platelet transfusion was given for 7% (13) of the cases; and 6 cases for which platelet transfusion was given did not show evidence of plasma leakage (12 of these cases did not show evidence of hemorrhage). There was a strong association between the lowest platelet value and hemoconcentration (χ(2) = 13.16, P < 0.025). No association was found between giving a platelet transfusion and hemoconcentration or hemorrhage. Thrombocytopenia seen in dengue resolves spontaneously and independent of any transfusion used.

  14. [Study of bone marrow in experimental Argentine Hemorrhagic Fever. Role of the megakaryocyte].

    PubMed

    Oubiña, J R; Carballal, G; La Torre, J; Frigerio, M J; Vásquez, C

    1980-01-01

    In previous morphological studies on bone marrow of guinea pigs infected with Junin virus, the coexistence of viral particles, antigens and cytopathic effects were observed in megakaryocytes. In addition, bone marrow is one of the organs where highest virus titers were obtained. However, although other myeloid cells presented intense cytopathic effect, viral antigens were observed only in reticular cells and virus particles were seen sporadically associated with immature cells. This study was designed to investigate if bone marrow infetivity was due mainly to megakaryocyte infection. Megakaryocyte obtained from infected bone marrow were concentrated in albumin gradients by gravitational sedimentation. Enriched fractions were studied by immunofluorescense /IF) and virus titration. Results showed that fractions containing 8, 6.4 or 15 % of megakaryocytes had titers of 3.81, 4.23 and 2.7 LD50/mñ respectively. On the contrary in depleted fractions (0 % megakaryocytes), titers were 0,5 to 1 log lower (Fig. 1, Table 1). By IF, Junin antigens were located in the cytoplasm of 70 % of megakaryocytes and also in reticular cells, but not in other cell types. These results suggest that megakaryocytes suffer a productive infection that may well account for the thrombocytopenia observed in this experimental infection. However, the detection of infectivity in other cells, in absence of viral antigens and particles remains to be explained.

  15. 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

  16. Hemorrhagic fever virus-induced changes in hemostasis and vascular biology.

    PubMed

    Chen, J P; Cosgriff, T M

    2000-07-01

    Viral hemorrhagic fever (VHF) denotes a virus-induced acute febrile, hemorrhagic disease reported from wide areas of the world. Hemorrhagic fever (HF) viruses are encapsulated, single-stranded RNA viruses that are associated with insect or rodent vectors whose interaction with humans defines the mode of disease transmission. There are 14 HF viruses, which belong to four viral families: Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae. This review presents, in order, the following aspects of VHF: (1) epidemiology, (2) anomalies of platelets and coagulation factors, (3) vasculopathy, (4) animal models of VHFs, (5) pathogenic mechanisms, and (6) treatment and future studies. HF viruses produce the manifestations of VHFs either by direct effects on cellular functions or by activation of immune and inflammatory pathways. In Lassa fever, Rift Valley fever and Crimean-Congo HF, the main feature of fatal illness appears to be impaired/delayed cellular immunity, which leads to unchecked viremia. However, in HF with renal syndrome and dengue HF, the immune response plays an active role in disease pathogenesis. The interplay of hemostasis, immune response, and inflammation is very complex. Molecular biologic techniques and the use of animal models have helped to unravel some of these interactions.

  17. 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.

  18. Association Between Increased Vascular Nitric Oxide Bioavailability and Progression to Dengue Hemorrhagic Fever in Adults.

    PubMed

    Thein, Tun-Linn; Wong, Joshua; Leo, Yee-Sin; Ooi, Eng-Eong; Lye, David; Yeo, Tsin W

    2015-09-01

    In a prospective longitudinal adult study, vascular nitric oxide bioavailability measured as reactive hyperemia index was significantly higher at enrollment in patients who developed dengue hemorrhagic fever (DHF) (n = 11), compared with the non-DHF group (n = 63) and those with other febrile illnesses (n = 25) (P = .01). After adjustment for age, fever day, and body mass index, enrollment reactive hyperemia index was associated with a 4-fold increased risk for DHF, and predicted DHF with an area under the receiver operating curve of 0.86. Increased vascular nitric oxide in dengue is associated with increased vascular permeability and impaired homeostasis and may have utility as a predictor of DHF.

  19. Comparison of clinical features and hematologic abnormalities between dengue fever and dengue hemorrhagic fever among children in the Philippines.

    PubMed

    Carlos, Celia C; Oishi, Kazunori; Cinco, Maria T D D; Mapua, Cynthia A; Inoue, Shingo; Cruz, Deu John M; Pancho, Mary Ann M; Tanig, Carol Z; Matias, Ronald R; Morita, Kouichi; Natividad, Filipinas F; Igarashi, Akira; Nagatake, Tsuyoshi

    2005-08-01

    To demonstrate the differences of clinical features and hematologic abnormalities between dengue fever (DF) and dengue hemorrhagic fever (DHF), 359 pediatric patients admitted St. Luke's Medical Center in Quezon City, between 1999 and 2001 in Metro Manila, and adjoining provinces the Philippines, with a laboratory-confirmed dengue virus infection were evaluated. One third of the patients had DHF, and most of these patients were without shock. Restlessness, epistaxis, and abdominal pain were more associated with DHF. The platelet count was significantly lower in the DHF group than in the DF group before and after defervescence. In the DHF patients, the hematocrit was significantly increased before defervescence, and decreased the day after due to administration of intravenous fluid. Coagulation abnormalities associated with most DHF patients were thrombocytopenia and an increased fibrinolysis, but not disseminated intravascular coagulation. We present recent data on readily obtained clinical and laboratory data that can be used for early diagnosis and consequently earlier appropriate treatment of dengue virus infections.

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

    PubMed Central

    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 8th, 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

  1. Interferon-β therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever.

    PubMed

    Smith, Lauren M; Hensley, Lisa E; Geisbert, Thomas W; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene; Young, Howard A; Rubins, Kathleen H; Karp, Christopher L

    2013-07-15

    There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filovirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filovirus infection.

  2. 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.

  3. First Report of Sylvatic DENV-2-Associated Dengue Hemorrhagic Fever in West Africa

    PubMed Central

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

    2011-01-01

    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

  4. 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.

  5. Hospital-based diagnosis of hemorrhagic fever, encephalitis, and hepatitis in Cambodian children.

    PubMed

    Chhour, Y Meng; Ruble, Gaye; Hong, Rathavuth; Minn, Kyi; Kdan, Yuvatha; Sok, Touch; Nisalak, Ananda; Myint, Khin Saw Aye; Vaughn, David W; Endy, Timothy P

    2002-05-01

    Surveillance was conducted for three clinical syndromes (hemorrhagic fever, encephalitis, and hepatitis) in Cambodian children admitted to the National Pediatric Hospital in Phnom Penh from July 1996 through September 1998. Acute- and convalescent-phase sera, and cerebrospinal fluid, when applicable, underwent diagnostic evaluation for infections with Dengue virus (DENV), Japanese encephalitis virus (JEV), and Hepatitis A, B, C, and E viruses. Of 621 children admitted with hemorrhagic fever, 499 (80%) were confirmed to have either primary or secondary DENV infection. DENV rates were as high as 10.6/100 hospital admissions in September 1998. Of 50 children with clinical encephalitis, 9 (18%) had serologic evidence of JEV infection. Forty-four children had clinical hepatitis, most (55%) due to Hepatitis A virus (HAV). One patient had Hepatitis B virus, and no patients had hepatitis C or E. This study identified a large number of children with vaccine-preventable diseases (JEV and HAV).

  6. Animal models for some important RNA viruses of public health concern in SEARO countries: viral hemorrhagic fever.

    PubMed

    Badole, Sachin L; Yadav, Pragya D; Patil, Dilip R; Mourya, Devendra T

    2015-03-01

    Viral hemorrhagic fevers (VHFs) are major public health problems in the South-East Asia Regional (SEAR) countries. VHFs are a group of illnesses; that are caused by four families of viruses, viz. Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae. All VHFs have common features: they affect several organs and damage the blood vessels. These symptoms are often accompanied by hemorrhage. To understand pathogenesis, genetic and environmental influence that increase the risk of VHFs, efficacy and safety studies on candidate vaccines and testing of various therapeutic agents, appropriate animal models are essential tools in public and animals health. In the current review, the suitable animal models for Flavivirus [Dengue hemorhagic fever (DHF), Kyasanur forest disease (KFD)]; Bunyavirus [Crimean-Congo hemorrhagic fever (CCHF), Hantavirus fever (HF)]; and Paramyxovirus [Nipah virus fever (NiV)] have been reviewed with specific emphasis on emerging and reemerging viruses in SEAR countries.

  7. 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

  8. Exceptional Simian Hemorrhagic Fever Virus Diversity in a Wild African Primate Community

    PubMed Central

    Lauck, Michael; Sibley, Samuel D.; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Chapman, Colin A.; Ting, Nelson; Switzer, William M.; Kuhn, Jens H.; Friedrich, Thomas C.; O'Connor, David H.

    2013-01-01

    Simian hemorrhagic fever virus (SHFV) is an arterivirus that causes severe disease in captive macaques. We describe two new SHFV variants subclinically infecting wild African red-tailed guenons (Cercopithecus ascanius). Both variants are highly divergent from the prototype virus and variants infecting sympatric red colobus (Procolobus rufomitratus). All known SHFV variants are monophyletic and share three open reading frames not present in other arteriviruses. Our data suggest a need to modify the current arterivirus classification. PMID:23077302

  9. [The epidemic of dengue and hemorrhagic dengue fever in the city of Rio de Janeiro, 2001/2002].

    PubMed

    Casali, Clarisse Guimarães; Pereira, Marcelo Ricardo Reis; Santos, Luciana Maria Jabor Garcia; Passos, Maíla Naves Pereira; Fortes, Bruno de Paula Menezes Drumond; Ortiz Valencia, Luis Iván; Alexandre, Aline de Jesus; Medronho, Roberto de Andrade

    2004-01-01

    The following study was intended to evaluate the occurrence of typical signs and symptoms in the cases of classic dengue and hemorrhagic dengue fever, during the 2001-2002 epidemic in the city of Rio de Janeiro. The authors reviewed 155,242 cases notified to the Information System of Notification Diseases, from January/2001 to June/2002: 81,327 cases were classified as classic dengue and 958 as hemorrhagic dengue fever, with a total of 60 deaths. Common symptoms, such as fever, headache, prostration, myalgia, nausea and retro-orbital pain, had a high incidence in both classic and hemorrhagic dengue fever. On the other hand, hemorrhagic signs and other signs of severe disease, such as shock, gastrointestinal bleeding, petechiae, epistaxis, abdominal pain and pleural effusion, were strongly associated to hemorrhagic dengue fever. Besides, the occurrence of death was 34.8 times higher in hemorrhagic dengue fever than in classic dengue (OR = 34.8; CI 19.7-61.3).

  10. Comparative study between Ribavirin and Ribavirin plus Intravenous Immunoglobulin against Crimean Congo hemorrhagic fever

    PubMed Central

    Salehi, Hassan; Salehi, Marzieh; Adibi, Neda; Salehi, Maryam

    2013-01-01

    Background: Crimean Congo hemorrhagic fever (CCHF) has high morbidity and mortality. Therefore the treatment effect of Ribavirin with and without intravenous Immunoglobulin (IVIG) in viral Crimean Congo hemorrhagic fever was evaluated. Materials and Methods: In a clinical trial study, 40 patients with confirmatory positive serology test, 12 (30%) received Ribavirin and IVIG (case group) and 28 (70%) received only ribavirin as standards therapy (control group). The patients were followed and compared by defervescence and other clinical symptoms, and laboratory results such as white blood cell count (WBC), platelets; liver function test (LFT) and duration of hospitalization and mortality rate after eight weeks. Results: The mean (SD) period for defervescence and stopping bleedings was five (0.6) days in case group and five (0.5) days in control group with no significant differences (P = 0.27). The mean period for return of WBC to normal was three (0.6) days in case group and five (0.8) days in control group (P = 0.002). The mean period for return of LFT to normal was three (0.9) days in case group and seven (0.5) days in control group which showed a meaningful difference (P = 0.001) Normalization of platelets was returned within four (0.8) days in case group compared to 6 (0.6) days in control group. Mortality was observed in three cases of each group. Conclusion: Considering our results, using IVIG in viral hemorrhagic fever (VHF) may need further evaluations. PMID:24250699

  11. 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

  12. A novel rhabdovirus associated with acute hemorrhagic fever in central Africa.

    PubMed

    Grard, Gilda; Fair, Joseph N; Lee, Deanna; 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

    2012-09-01

    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 × 10(6) 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.

  13. 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%.

  14. 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

  15. Epidemiology of dengue in Sri Lanka before and after the emergence of epidemic dengue hemorrhagic fever.

    PubMed

    Messer, William B; Vitarana, U Tissa; Sivananthan, Kamalanayani; Elvtigala, Jayanthi; Preethimala, L D; Ramesh, R; Withana, Nalini; Gubler, Duane J; De Silva, Aravinda M

    2002-06-01

    Before 1989, dengue epidemiology in Sri Lanka was characterized by frequent transmission of all four dengue serotypes but a low incidence of dengue hemorrhagic fever (DHF). After 1989, cases of DHF dramatically increased. Here we present the results of epidemiologic studies conducted in Colombo, Sri Lanka before and after epidemic emergence of DHF in 1989. We compared the proportion of dengue cases among people with fever attending clinics from 1980 to 1984 and in 1997 and 1998 to determine if an increase in dengue transmission was associated with more DHF cases being reported. We also compared the relative distribution of dengue virus serotypes circulating in Colombo before and after the emergence of DHF. We detected no significant differences in dengue as a proportion of fever cases or in serotype distribution between the pre and post-DHF periods. We conclude that an increase in virus transmission or a change in circulating serotypes does not explain the epidemic emergence of DHF in Sri Lanka.

  16. Control of massive bleeding in dengue hemorrhagic fever with severe thrombocytopenia by use of intravenous anti-D globulin.

    PubMed

    Yadav, Satya P; Sachdeva, Anupam; Gupta, Dhiren; Sharma, Sunil D; Kharya, Gaurav

    2008-12-01

    Dengue hemorrhagic fever (DHF) is a potentially lethal complication of mosquito borne viral disease, Dengue Fever. Thrombocytopenia is a constant finding in DHF/Dengue Shock Syndrome (DSS). We report two cases that fulfilled the WHO criteria of DSS: high fever, positive tourniquet test, severe thrombocytopenia (<10,000/mm(3)), hemo-concentration (Hematocrit increase >20%), hypotension and bleeding refractory to routine therapeutic measures, who showed dramatic improvement after receiving Intravenous Anti-D globulin (IV anti-D).

  17. Epidemiology of dengue/dengue hemorrhagic fever in Malaysia--a retrospective epidemiological study 1973-1987. Part I: Dengue hemorrhagic fever (DHF).

    PubMed

    Shekhar, K C; Huat, O L

    Dengue hemorrhagic fever (DHF), though endemic in the sixties, emerged as a major public health problem in Malaysia from 1973 onwards. The incidence rate of DHF which was 10.1 per 100,000 in 1973 has fallen down to 1.9 per 100,000 in 1987 with a mean case fatality rate of 6.4 per 100 persons. The Chinese appear to be more prone to DHF with the highest mean morbidity rate of 5.5 per 100,000 and case fatality rate of 6.1%. The incidence of DHF is higher in the males with a higher case fatality rate in females. Male Chinese appear to be mainly affected. The overall age-specific incidence rate is highest in two age groups, viz. 5-9 years and 10-19 years of age with a mean morbidity rate of 4.9 cases per 100,000. The mean age-specific case fatality rate was highest in the 0-4 years age group. Dengue hemorrhagic fever is predominantly an urban disease in Malaysia with a mean incidence rate of 5.3 cases per 100,000 as opposed to 1.2 cases per 100,000 being reported from rural areas. The mean overall incidence of deaths in the urban area is 0.5 compared to 0.1 per 100,000 for rural areas. There is a marked seasonal correlation between DHF cases and rainfall, with a peak in August. While all four serotypes of dengue viruses are found in Malaysia, Den 2 appears to be isolated with greater frequency during all the epidemics.

  18. 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

  19. Hemorrhagic fever in Cambodia is caused by dengue viruses: evidence for transmission of all four serotypes.

    PubMed

    Rathavuth, H; Vaughn, D W; Minn, K; Nimmannitya, S; Nisalak, A; Raengsakulrach, B; Rorabaugh, M L; Yuvatha, K; Sophal, O

    1997-03-01

    Hemorrhagic fever (HF) has been widespread in Cambodia and thought to be due to dengue virus although laboratory confirmation has been lacking. Between 1980 and 1995, 49,420 cases of HF and 3,032 deaths were reported. Cases increased during this period; large epidemics of HF occurred every two to three years. In 1995 there were 10,208 cases of HF with 424 deaths. Over a two day period in August 1995, 40 consecutive cases were investigated at the National Pediatric Hospital in Phnom Penh, Cambodia. All 40 cases were confirmed as dengue by virus identification and/or serology. Mean age was 6.5 years. Of 39 patients with complete medical records, the diagnoses were: dengue fever (n = 3), dengue hemorrhagic fever (DHF) grade 2 (n = 21), DHF grade 3 (n = 10), and DHF grade 4 (n = 5). The serologic response was secondary in 95%. Dengue virus was identified in 13 of 40 cases. All four dengue serotypes were identified. The high frequency of secondary infections, the low mean age of admission, and identification of all four dengue serotypes support the national statistics to show that DHF is highly endemic in Cambodia.

  20. Phenotypic and genotypic characterization of dengue virus isolates differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome.

    PubMed

    Tuiskunen, Anne; Monteil, Vanessa; Plumet, Sébastien; Boubis, Laetitia; Wahlström, Maria; Duong, Veasna; Buchy, Philippe; Lundkvist, Ake; Tolou, Hugues; Leparc-Goffart, Isabelle

    2011-11-01

    Dengue viruses (DENV) cause 50-100 million cases of acute febrile disease every year, including 500,000 reported cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Viral factors have been proposed to influence the severity of the disease, but markers of virulence have never been identified on DENV. Three DENV serotype-1 isolates from the 2007 epidemic in Cambodia that are derived from patients experiencing the various clinical forms of dengue were characterized both phenotypically and genetically. Phenotypic characteristics in vitro, based on replication kinetics in different cell lines and apoptosis response, grouped isolates from DF and DHF patients together, whereas the virus isolate from a DSS patient showed unique features: a lower level of replication in mammalian cells and extensive apoptosis in mosquito cells. Genomic comparison of viruses revealed six unique amino acid residues in the membrane, envelope, and in non-structural genes in the virus isolated from the DSS patient.

  1. 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

  2. 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

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

    PubMed

    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.

  4. 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

  5. Seroprevalence and risk factors of Crimean-Congo hemorrhagic fever in selected seven provinces in Turkey.

    PubMed

    Yagci-Caglayik, Dilek; Korukluoglu, Gülay; Uyar, Yavuz

    2014-02-01

    Turkey has been one of the most endemic regions since 2002, when Crimean-Congo hemorrhagic fever emerged worldwide. The aim of the present study was to estimate the seroprevelance of CCHF virus in humans who reside in rural and urban areas of known endemic and nonendemic selected provinces of Turkey by using commercial ELISA kit. CCHFV IgG antibodies were detected in 2.3% of the population. The most important risk factors for CCHF seropositivity, were older age, male gender, illiterate, farmer, animal husbandry, living in rural residence in adobe houses, and a previous tick bite history.

  6. Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates.

    PubMed

    Geisbert, Thomas W; Daddario-DiCaprio, Kathleen M; Williams, Kinola J N; Geisbert, Joan B; Leung, Anders; Feldmann, Friederike; Hensley, Lisa E; Feldmann, Heinz; Jones, Steven M

    2008-06-01

    Recombinant vesicular stomatitis virus (VSV) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against Marburg virus when administered after exposure and can partially protect macaques after challenge with Zaire ebolavirus. Here, we administered a VSV vector expressing the Sudan ebolavirus (SEBOV) glycoprotein to four rhesus macaques shortly after exposure to SEBOV. All four animals survived SEBOV challenge, while a control animal that received a nonspecific vector developed fulminant SEBOV hemorrhagic fever and succumbed. This is the first demonstration of complete postexposure protection against an Ebola virus in nonhuman primates and provides further evidence that postexposure vaccination may have utility in treating exposures to filoviruses.

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

    PubMed

    Atangana, Abdon; Goufo, Emile Franc Doungmo

    2014-01-01

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

  8. 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

  9. Viruses associated with epidemic hemorrhagic fevers of the Philippines and Thailand.

    PubMed

    HAMMON, W M; RUDNICK, A; SATHER, G E

    1960-04-15

    Epidemiologic, clinical, and etiologic studies were carried out on a newly recognized, frequently fatal, pediatric disease syndrome which occurred in urban areas infested with Aedes aegypti mosquitoes. Four types of dengue virus (two of which are new), chikungunya virus, and another virus yet to be identified were isolated from the blood of patients. Dengue viruses, types 2 and 3, were isolated from the mosquitoes. Ample serologic confirmation was obtained of concurrent hemorrhagic fever and infection with one or more of these viruses. Thus, it was discovered that viruses of previously recognized types and of closely related new types apparently have etiologic roles in a new and highly dangerous epidemic disease syndrome.

  10. A realistic age structured transmission model for dengue hemorrhagic fever in Thailand.

    PubMed

    Pongsumpun, P; Tang, I M

    2001-06-01

    The influence of age structure in the susceptible class of the Susceptible-Infected Recovered (SIR) model used to describe the transmission of dengue hemorrhagic fever (DHF) was studied. This was done by first dividing all of the population classes into cohorts and then writing a set of coupled SIR equations for each cohort. The consequences of assuming different behavior of the transmission rates on the age structure in the DHF incidence rates were determined. In order for the predicted incidence rates to be similar to the DHF incidence patterns observed in several provinces in Thailand during the DHF epidemic in 1998, the transmission rates should be age dependent.

  11. [Adaptation of Crimean-Congo hemorrhagic fever virus to culture in Vero-E6 cells].

    PubMed

    Smirnova, S E; Karganova, G G; Gmyl', L V

    1997-01-01

    Adaptation of the Crimean-Congo hemorrhagic fever (CCHF) virus to continuous culturing in Vero-E6 cells was studied by coculturing of infected and intact cells. Adapted strain Hoja-A exerted a complete cytocidal effect and was characterized by a high level of virus accumulation in the early period of the infection. The resultant strain survived through more than 80 passages and retained the newly acquired properties; lyophilized, it can be stored for a long time. Availability of such a strain opens new vistas in studies of the CCHF agent. PMID:9499243

  12. The Role of Platelets in the Pathogenesis of Viral Hemorrhagic Fevers

    PubMed Central

    Zapata, Juan C.; Cox, Dermot; Salvato, Maria S.

    2014-01-01

    Viral hemorrhagic fevers (VHF) are acute zoonotic diseases that, early on, seem to cause platelet destruction or dysfunction. Here we present the four major ways viruses affect platelet development and function and new evidence of molecular factors that are preferentially induced by the more pathogenic members of the families Flaviviridae, Bunyaviridae, Arenaviridae, and Filoviridae. A systematic search was performed through the main medical electronic databases using as parameters all current findings concerning platelets in VHF. Additionally, the review contains information from conference proceedings. PMID:24921924

  13. Management of severe refractory thrombocytopenia in dengue hemorrhagic fever with intravenous anti-D immune globulin.

    PubMed

    Kharya, Gaurav; Yadav, Satya Prakash; Katewa, Satyendra; Sachdeva, Anupam

    2011-11-01

    Dengue hemorrhagic fever (DHF) is a potentially lethal complication of dengue fever due to shock and/or bleeding. Bleeding in DHF is due to thrombocytopenia and/or coagulopathy. The authors present their experience of usage of intravenous anti-D in 5 children with DHF and severe refractory thrombocytopenia (<10,000/mm(3)). It was administered in a dose of 50 to 75 μg/kg. Mean platelet count was 6800/mm(3) before and 33,600, 44,600, and 79,000/mm(3) after intravenous anti-D administration at 24, 48, and 72 hours, respectively. Average drop in hemoglobin after administration of anti-D was 2.28 g/dL. Intravenous anti-D can possibly be a treatment option for refractory thrombocytopenia in DHF.

  14. Material proximities and hotspots: toward an anthropology of viral hemorrhagic fevers.

    PubMed

    Brown, Hannah; Kelly, Ann H

    2014-06-01

    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.

  15. 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.

  16. 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

  17. Humoral immune response of dengue hemorrhagic fever cases in children from Tegucigalpa, Honduras.

    PubMed

    De Rivera, Ivette Lorenzana; Parham, Leda; Murillo, Wendy; Moncada, Walter; Vazquez, Susana

    2008-08-01

    The humoral immune response in Honduran dengue hemorrhagic fever (DHF) hospitalized pediatric cases from the epidemics of 2004 and 2005 was studied in sera collected from 5 to 7 days of fever onset. A total of 145 cases were included in the study: 40 classified as primary with DHF Grade I or II and 86 classified as secondary; from them, 73 were DHF Grade I or II and 13 were dengue shock syndrome (DSS) Grade III or IV. The highest number of primary cases was found in children < 1 year of age. The highest number of secondary cases was observed in children between 5 and 10 years of age. The IgA values showed a statistically significant difference between primary and secondary groups. The relationship between antibody responses and severity grade is discussed. This is the first study related to the humoral immune response and severity grade in DHF cases in Honduran children.

  18. Clinical intervention and molecular characteristics of a dengue hemorrhagic fever outbreak in Timor Leste, 2005.

    PubMed

    Kalayanarooj, Siripen; Rimal, Hem Sagar; Andjaparidze, Alex; Vatcharasaevee, Varunee; Nisalak, Ananda; Jarman, Richard G; Chinnawirotpisan, Piyawan; Mammen, Mammen P; Holmes, Edward C; Gibbons, Robert V

    2007-09-01

    In response to a January 2005 report of dengue hemorrhagic fever (DHF) in Timor Leste, the World Health Organization sent a team to assist the National Hospital Guido Valadares (NHGV) in Dili with clinical case management and diagnostic support. The hospital reported 67 admissions including 8 deaths (case fatality rate approximately 12%) over the previous weeks with case histories clinically compatible with DHF. During the intervention, an additional 44 suspected dengue patients were admitted to the pediatric ward of NHGV. Among 41 patients with clinical diagnoses of dengue fever or DHF, 38 (93%) were laboratory confirmed. Although cause and effect cannot be definitely attributed, the case fatality rate decreased to 3.6% after the intervention with education about dengue management strategies.

  19. Dengue virus serotype 2 from a sylvatic lineage isolated from a patient with dengue hemorrhagic fever.

    PubMed

    Cardosa, Jane; Ooi, Mong How; Tio, Phaik Hooi; Perera, David; Holmes, Edward C; Bibi, Khatijar; Abdul Manap, Zahara

    2009-01-01

    Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV) infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.

  20. Dengue and dengue hemorrhagic fever in Latin America and the Caribbean.

    PubMed

    Istúriz, R E; Gubler, D J; Brea del Castillo, J

    2000-03-01

    Four serotypes of dengue viruses produce dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. They are the most important arbovirus infections of humans, in terms of both morbidity and mortality, constituting one of the most rapidly expanding and re-emerging infectious disease problems in Latin America. In less than 20 years, the region has transformed itself from hypoendemic to hyperendemic, while serotype circulation in most countries has gone from none or single to multiple. Changes in endemicity have coincided with the emergence and increasing incidence of the severer forms of dengue infection. This article reviews the clinical presentations of these diseases. Health care providers who see patients in or returning from areas of Latin America, the Caribbean, and other tropical areas must consider dengue in the differential diagnosis of patients presenting with compatible symptoms, and must be knowledgeable in the current management of this important disease.

  1. Economic impact of dengue fever/dengue hemorrhagic fever in Thailand at the family and population levels.

    PubMed

    Clark, Danielle V; Mammen, Mammen P; Nisalak, Ananda; Puthimethee, Virat; Endy, Timothy P

    2005-06-01

    Dengue fever and dengue hemorrhagic fever constitute a substantial health burden on the population in Thailand. In this study, the impact of symptomatic dengue virus infection on the families of patients hospitalized at the Kamphaeng Phet Provincial Hospital with laboratory-confirmed dengue in 2001 was assessed, and the disability-adjusted life years (DALYs) lost for fatal and non-fatal cases of dengue were calculated using population level data for Thailand. When we accounted for the direct cost of hospitalization, indirect costs due to loss of productivity, and the average number of persons infected per family, we observed a financial loss of approximately US$61 per family, which is more than the average monthly income in Thailand. The DALYs were calculated using select results from a family level survey, and resulted in an estimated 427 DALYs/million population in 2001. This figure is of the same order of magnitude as the impact of several diseases currently given priority in southeast Asia, such as the tropical cluster (trypanosomiasis, Chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, and onchocerciasis), malaria, meningitis, and hepatitis. These results indicate that dengue prevention, control, and research should be considered equally important as that of diseases currently given priority.

  2. Antibody responses to an immunodominant nonstructural 1 synthetic peptide in patients with dengue fever and dengue hemorrhagic fever.

    PubMed

    Huang, J H; Wey, J J; Sun, Y C; Chin, C; Chien, L J; Wu, Y C

    1999-01-01

    Two flaviviruses, dengue (DEN) virus and Japanese encephalitis (JE) virus, are important because of their global distribution and the frequency of epidemics in tropical and subtropical areas. To study the B-cell epitopes of nonstructural 1 (NS1) glycoprotein and anti-NS1 antibody response in DEN infection, a series of 15-mer synthetic peptides from the predicted B-cell linear epitopes of DEN-2 NS1 protein were prepared. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze antibody responses to these peptides from sera of both DEN and JE patients. One peptide derived from DEN-2 NS1, D2 NS1-P1 (amino acids 1-15), was identified as the immunodominant epitope that reacted with sera from dengue fever (DF) patients but not JE patients. The isotype of D2 NS1-P1-specific antibodies was mainly immunoglobulin M (IgM) in all sera that tested positive. A specificity study demonstrated that sera from all four DEN types reacted with D2 NS1-P1. A dynamics study showed that specific antibodies to this peptide could be detected as early as 2 days after the onset of symptoms. We observed significant anti-D2 NS1-P1 antibody responses in 45% of patients with primary and secondary infections with DF or with dengue hemorrhagic fever. This is the first report demonstrating that significant anti-DEN NS1 antibodies can be induced in the sera of patients with primary DEN infection.

  3. Clinical characteristics and risk factors for concurrent bacteremia in adults with dengue hemorrhagic fever.

    PubMed

    Lee, Ing-Kit; Liu, Jien-Wei; Yang, Kuender D

    2005-02-01

    To better understand the clinical characteristics of concurrent bacteremia (dual infection) in patients with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and identify predictive risk factors for dual infection, 100 patients with DHF/DSS (7 with a dual infection and 93 with DHF/DSS alone [controls]) were enrolled in this study. A patient with DHF/DSS who lacked three or more of the five most frequently observed manifestations other than fever in controls or showed disturbed consciousness was defined as one with unusual dengue manifestations. Patients with a dual infection were older, and tended to have prolonged fever, higher frequencies of acute renal failure, gastrointestinal bleeding, altered consciousness, unusual dengue manifestations, and DSS. Acute renal failure (odds ratio [OR] = 51.45, P = 0.002), and prolonged fever (> 5 days) (OR = 26.07, P = 0.017) were independent risk factors for dual infection. Clinicians should be alert to the potential for concurrent bacteremia when treating patients with DHF/DSS who are at risk for dual infection and manage them accordingly.

  4. Crimean–Congo hemorrhagic fever virus nucleoprotein reveals endonuclease activity in bunyaviruses

    PubMed Central

    Guo, Yu; Wang, Wenming; Ji, Wei; Deng, Maping; Sun, Yuna; Zhou, Honggang; Yang, Cheng; Deng, Fei; Wang, Hualin; Hu, Zhihong; Lou, Zhiyong; Rao, Zihe

    2012-01-01

    Crimean–Congo hemorrhagic fever virus (CCHFV), a virus with high mortality in humans, is a member of the genus Nairovirus in the family Bunyaviridae, and is a causative agent of severe hemorrhagic fever (HF). It is classified as a biosafety level 4 pathogen and a potential bioterrorism agent due to its aerosol infectivity and its ability to cause HF outbreaks with high case fatality (∼30%). However, little is known about the structural features and function of nucleoproteins (NPs) in the Bunyaviridae, especially in CCHFV. Here we report a 2.3-Å resolution crystal structure of the CCHFV nucleoprotein. The protein has a racket-shaped overall structure with distinct “head” and “stalk” domains and differs significantly with NPs reported so far from other negative-sense single-stranded RNA viruses. Furthermore, CCHFV NP shows a distinct metal-dependent DNA-specific endonuclease activity. Single residue mutations in the predicted active site resulted in a significant reduction in the observed endonuclease activity. Our results present a new folding mechanism and function for a negative-strand RNA virus nucleoprotein, extend our structural insight into bunyavirus NPs, and provide a potential target for antiviral drug development to treat CCHFV infection. PMID:22421137

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

    PubMed

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

    2014-06-01

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

  6. Retrospective Evaluation of Control Measures for Contacts of Patient with Marburg Hemorrhagic Fever

    PubMed Central

    Isken, Leslie D.; Willemse, Patricia; van den Berkmortel, Franchette; Koopmans, Marion P.G.; van Oudheusden, Danielle E.C.; Bleeker-Rovers, Chantal P.; Brouwer, Annemarie E.; Grol, Richard P.T.M.; Hulscher, Marlies E.J.L.; van Dissel, Jaap T.

    2012-01-01

    After an imported case of Marburg hemorrhagic fever was reported in 2008 in the Netherlands, control measures to prevent transmission were implemented. To evaluate consequences of these measures, we administered a structured questionnaire to 130 contacts classified as either having high-risk or low-risk exposure to body fluids of the case-patient; 77 (59.2%) of 130 contacts responded. A total of 67 (87.0%) of 77 respondents agreed that temperature monitoring and reporting was necessary, significantly more often among high-risk than low-risk contacts (p<0.001). Strict compliance with daily temperature monitoring decreased from 80.5% (62/77) during week 1 to 66.2% (51/77) during week 3. Contacts expressed concern about development of Marburg hemorrhagic fever (58.4%, 45/77) and infecting a family member (40.2%, 31/77). High-risk contacts had significantly higher scores on psychological impact scales (p<0.001) during and after the monitoring period. Public health authorities should specifically address consequences of control measures on the daily life of contacts. PMID:22710186

  7. 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.

  8. Dengue and dengue hemorrhagic fever in the State of Pernambuco, 1995-2006.

    PubMed

    Cordeiro, Marli Tenório; Schatzmayr, Hermann Gonçalves; Nogueira, Rita Maria Ribeiro; Oliveira, Valdete Felix de; Melo, Wellinton Tavares de; Carvalho, Eduardo Freese de

    2007-01-01

    In Pernambuco, the first dengue cases occurred in 1987. After a seven-year interval without autochthonous cases, a new epidemic occurred in 1995. Important aspects of the dengue epidemics during the period 1995-2006 have been analyzed here, using epidemiological, clinical and laboratory data. A total of 378,374 cases were notified, with 612 confirmed cases of dengue hemorrhagic fever and 33 deaths. The mortality rate was 5.4%. The incidence rate increased from 134 to 1,438/100,000 inhabitants, corresponding to the epidemics due to serotypes 2 and 3, in 1995 and 2002, respectively. Dengue mainly affected adults (20-49 years); 40.7% were male and 59.3% were female. From 2003 onwards, the number of cases among individuals younger than 15 years old increased. Out of 225 dengue hemorrhagic fever cases, 42.7% primary and 57.3% secondary infections were identified (p = 0.0279). Neurological manifestations were also observed. From 2002 onwards, serotypes 1, 2 and 3 were circulating; serotype 3 was predominant.

  9. 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

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

    PubMed

    Delgado, Simon; Erickson, Bobbie R; Agudo, Roberto; Blair, Patrick J; Vallejo, Efrain; Albariño, César G; Vargas, Jorge; Comer, James A; Rollin, Pierre E; Ksiazek, Thomas G; Olson, James G; Nichol, Stuart T

    2008-04-18

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

  11. 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

  12. 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

  13. Infectivity titration of hemorrhagic fever with renal syndrome virus: use of immune adherence hemagglutination for detection of virus growth.

    PubMed

    Matsuura, Y; Sugiyama, K; Morita, C; Morikawa, S; Shiga, S; Komatsu, T; Akao, Y; Kitamura, T

    1984-09-01

    Serial dilutions of hemorrhagic fever with renal syndrome viruses were inoculated into Vero-E6 cells in microplates. After 2 weeks of incubation, infected cells were disrupted by freezing and thawing, and virus antigens were detected by immune adherence hemagglutination. The infectivity titers of the virus as determined by this method were in close agreement with those obtained by the immunofluorescent antigen endpoint method. Then, a neutralization method was established. Japanese hemorrhagic fever with renal syndrome isolates, strains SR-11 and TR-352, were found to be distinct from Hantaan virus, strain 76-118, by the neutralization test.

  14. The impact of a program for strengthening dengue hemorrhagic fever case management on the clinical outcome of dengue hemorrhagic fever patients.

    PubMed

    Mayurasakorn, Saengdao; Suttipun, Nipar

    2010-07-01

    This study compared the case fatality ratio (CFR) of dengue shock syndrome (DSS) patients admitted to Buri Ram Hospital, an area with CFR of 0.11, 0.43 and 0.23% in 2002, 2003 and 2004, respectively, to obtain a provincial model for dengue case management using the I. development of a special program for strengthening dengue hemorrhagic fever (DHF) case management (No deaths in DSS patients), II. a retrospective review of the medical records of dengue fever (DF), DHF and DSS patients referred to Buri Ram Hospital. We compared the data during the 3 periods of the implementation of this program. Data was statistically analyzed using chi2 or Fisher's exact test for categorical variables, one-way ANOVA for continuous data with normal distribution and Kruskal-Wallis test for nonparametric variables. The numbers of DF, DHF and DSS cases in Buri Ram were 1332, 1700 and 1630 person, respectively, during 2006-2008. The number of DSS patients increased after implementation of the program: 12.2, 51.2 and 47.22 for 2006, 2007 and 2008, respectively, but the complications of the disease decreased. The CFR during 2006, 2007 and 2008 were 0.15, 0 and 0.06% (p > 0.05). The program for strengthening DHF case management did improve clinical outcomes in dengue patients after the implementation. The CFR in 2008 was only 0.06%, lower than the goal of the Ministry of Public Health (<0.13%). This program is still running, sustaining low CFR in dengue patients. It may be used as a model for other provinces in Thailand that have high dengue deaths.

  15. 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

  16. Characteristics of a dengue hemorrhagic fever outbreak in 2001 in Kaohsiung.

    PubMed

    Lai, Ping-Chang; Lee, Susan Shin-Jung; Kao, Chih-Hsiang; Chen, Yao-Shen; Huang, Chun-Kai; Lin, Wei-Ru; Wann, Shue-Ren; Lin, Hsi-Hsun; Yen, Muh-Yong; Liu, Yung-Ching

    2004-10-01

    A dengue outbreak occurred in Kaohsiung City starting in July in 2001. We studied the clinical profile of all patients admitted to Kaohsiung Veterans General Hospital during this outbreak from July 2001 to January 2002. A total of 25 cases of clinically suspected dengue fever were treated during this period, and 13 of them were confirmed by laboratory results (13/25; 52%). Eleven of the 25 patients (11/25; 44%) were admitted. The mean age of the patients with laboratory confirmation of infection was 53 years (range, 7 to 85 years). Headache (7/13; 53.8%), bone pain (8/13; 61.5%), myalgia (10/13; 76.9%), abdominal pain (7/13; 53.8%), and skin rash (9/13; 69.2%) were the most common presentations. A high proportion of patients were classified as having dengue hemorrhagic fever (DHF) [6/13; 46.2%] and 2 of these patients had dengue shock syndrome (DSS) based on the World Health Organization criteria. Pretibial petechia (6/13; 46.1%), gastrointestinal bleeding (6/13; 46.1%), and hemoptysis (4/13; 30.8%) were the most common hemorrhagic manifestations. The average hospital stay was 7.1 days. Thrombocytopenia was very common and 84.6% patients had a platelet count less than 100,000/mm3. Monocytosis was found in all patients. Few patients required blood or platelet concentrate transfusion. The 2 patients who developed DSS both survived. All patients recovered completely without any obvious sequela. In conclusion, there was a high percentage of DHF among patients in the dengue outbreak in 2001. Increasing rates of DHF compared to previous reports from Taiwan may be a sign of hyperendemicity (multiple serotypes present) of the dengue virus in Kaohsiung City and its greater likelihood elsewhere in Taiwan. Prevention and control of both dengue fever and DHF have thus become increasingly important.

  17. 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

  18. Detection of Crimean-Congo hemorrhagic fever, Hanta, and sandfly fever viruses by real-time RT-PCR.

    PubMed

    Ibrahim, Sofi M; Aitichou, Mohamed; Hardick, Justin; Blow, Jamie; O'Guinn, Monica L; Schmaljohn, Connie

    2011-01-01

    The development of sensitive and specific nucleic acid diagnostic assays for viral pathogens is essential for proper medical intervention. This chapter describes four fluorescence-based PCR assays to detect the Crimean-Congo Hemorrhagic Fever (CCHFV), Andes (ANDV), Hantaan (HANV), and Sandfly Fever Sicilian (SFSV) Viruses. These assays are based on species-specific hydrolysis probes targeting the nucleocapsid protein gene for CCHFV and SFSV and the glycoprotein gene for ANDV and HANV. All four assays were optimized for LightCycler 2.0 (Roche Diagnostics, Indianapolis, IN) or Ruggedized Advanced Pathogen Identification Device (R.A.P.I.D.; Idaho Technology Inc., Salt Lake City, UT). The assays were evaluated using the protocols described in the Subheading 3. The limits of detection were approximately 5, 2, 2, and 5 plaque-forming units (PFUs) for CCHFV, ANDV, HTNV, and SFSV assays, respectively. The sensitivity and specificity of the assays were evaluated with test panels that consisted of 20-60 known positive and 30-135 known negative samples, representing 7-34 genetically diverse bacterial and viral species. The CCHFV assay detected 59 out of the 60 positive samples and no false positives, resulting in 98.3% sensitivity at LOD of 5 PFU and 100% specificity. The ANDV and HTNV assays correctly identified all the positive samples with no false positive reactions; therefore, the sensitivity and specificity of these assays were determined to be 100% at LOD of 2 PFU. The SFSV assay missed three positive samples and cross-reacted with one of 48 negative samples, resulting in 95% sensitivity at LOD of 5 PFU and 98% specificity.

  19. Inhibitors of the Tick-Borne, Hemorrhagic Fever-Associated Flaviviruses

    PubMed Central

    Flint, Mike; McMullan, Laura K.; Dodd, Kimberly A.; Bird, Brian H.; Khristova, Marina L.; Nichol, Stuart T.

    2014-01-01

    No antiviral therapies are available for the tick-borne flaviviruses associated with hemorrhagic fevers: Kyasanur Forest disease virus (KFDV), both classical and the Alkhurma hemorrhagic fever virus (AHFV) subtype, and Omsk hemorrhagic fever virus (OHFV). We tested compounds reported to have antiviral activity against members of the Flaviviridae family for their ability to inhibit AHFV replication. 6-Azauridine (6-azaU), 2′-C-methylcytidine (2′-CMC), and interferon alpha 2a (IFN-α2a) inhibited the replication of AHFV and also KFDV, OHFV, and Powassan virus. The combination of IFN-α2a and 2′-CMC exerted an additive antiviral effect on AHFV, and the combination of IFN-α2a and 6-azaU was moderately synergistic. The combination of 2′-CMC and 6-azaU was complex, being strongly synergistic but with a moderate level of antagonism. The antiviral activity of 6-azaU was reduced by the addition of cytidine but not guanosine, suggesting that it acted by inhibiting pyrimidine biosynthesis. To investigate the mechanism of action of 2′-CMC, AHFV variants with reduced susceptibility to 2′-CMC were selected. We used a replicon system to assess the substitutions present in the selected AHFV population. A double NS5 mutant, S603T/C666S, and a triple mutant, S603T/C666S/M644V, were more resistant to 2′-CMC than the wild-type replicon. The S603T/C666S mutant had a reduced level of replication which was increased when M644V was also present, although the replication of this triple mutant was still below that of the wild type. The S603 and C666 residues were predicted to lie in the active site of the AHFV NS5 polymerase, implicating the catalytic center of the enzyme as the binding site for 2′-CMC. PMID:24663025

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Each of the eight simian hemorrhagic fever virus minor structural proteins is functionally important

    PubMed Central

    Vatter, Heather A.; Di, Han; Donaldson, Eric F.; Baric, Ralph S.; Brinton, Margo A.

    2014-01-01

    The simian hemorrhagic fever virus (SHFV) genome differs from those of other members of the family Arterivirus in encoding two adjacent sets of four minor structural protein open reading frames (ORFs). A stable, full-length, infectious SHFV-LVR cDNA clone was constructed. Virus produced from this clone had replication characteristics similar to those of the parental virus. A subgenomic mRNA was identified for the SHFV ORF previously identified as 2b. As an initial means of analyzing the functional relevance of each of the SHFV minor structural proteins, a set of mutant infectious clones was generated, each with the start codon of one minor structural protein ORF mutated. Different phenotypes were observed for each ortholog of the pairs of minor glycoproteins and all of the eight minor structural proteins were required for the production of infectious extracellular virus indicating that the duplicated sets of SHFV minor structural proteins are not functionally redundant. PMID:25036340

  5. On the Mathematical Analysis of Ebola Hemorrhagic Fever: Deathly Infection Disease in West African Countries

    PubMed Central

    Atangana, Abdon; Goufo, Emile Franc Doungmo

    2014-01-01

    For a given West African country, we constructed a model describing the spread of the deathly disease called Ebola hemorrhagic fever. The model was first constructed using the classical derivative and then converted to the generalized version using the beta-derivative. We studied in detail the endemic equilibrium points and provided the Eigen values associated using the Jacobian method. We furthered our investigation by solving the model numerically using an iteration method. The simulations were done in terms of time and beta. The study showed that, for small portion of infected individuals, the whole country could die out in a very short period of time in case there is not good prevention. PMID:25688348

  6. 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

  7. 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.

  8. Time Series Analysis of Hemorrhagic Fever with Renal Syndrome: A Case Study in Jiaonan County, China

    PubMed Central

    Li, Shujuan; Cao, Wei; Ren, Hongyan; Lu, Liang; Zhuang, Dafang; Liu, Qiyong

    2016-01-01

    Exact prediction of Hemorrhagic fever with renal syndrome (HFRS) epidemics must improve to establish effective preventive measures in China. A Seasonal Autoregressive Integrated Moving Average (SARIMA) model was applied to establish a highly predictive model of HFRS. Meteorological factors were considered external variables through a cross correlation analysis. Then, these factors were included in the SARIMA model to determine if they could improve the predictive ability of HFRS epidemics in the region. The optimal univariate SARIMA model was identified as (0,0,2)(1,1,1)12. The R2 of the prediction of HFRS cases from January 2014 to December 2014 was 0.857, and the Root mean square error (RMSE) was 2.708. However, the inclusion of meteorological variables as external regressors did not significantly improve the SARIMA model. This result is likely because seasonal variations in meteorological variables were included in the seasonal characteristics of the HFRS itself. PMID:27706256

  9. Tick cell lines for study of Crimean-Congo hemorrhagic fever virus and other arboviruses.

    PubMed

    Bell-Sakyi, Lesley; Kohl, Alain; Bente, Dennis A; Fazakerley, John K

    2012-09-01

    Continuous cell lines derived from many of the vectors of tick-borne arboviruses of medical and veterinary importance are now available. Their role as tools in arbovirus research to date is reviewed and their potential application in studies of tick cell responses to virus infection is explored, by comparison with recent progress in understanding mosquito immunity to arbovirus infection. A preliminary study of propagation of the human pathogen Crimean-Congo hemorrhagic fever virus (CCHFV) in tick cell lines is reported; CCHFV replicated in seven cell lines derived from the ticks Hyalomma anatolicum (a known vector), Amblyomma variegatum, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) microplus, and Ixodes ricinus, but not in three cell lines derived from Rhipicephalus appendiculatus and Ornithodoros moubata. This indicates that tick cell lines can be used to study growth of CCHFV in arthropod cells and that there may be species-specific restriction in permissive CCHFV infection at the cellular level.

  10. Genetic Analysis of Crimean-Congo Hemorrhagic Fever Virus in Russia

    PubMed Central

    Yashina, Lyudmila; Vyshemirskii, Oleg; Seregin, Sergei; Petrova, Irina; Samokhvalov, Evgeny; Lvov, Dmitry; Gutorov, Valery; Kuzina, Irina; Tyunnikov, Georgy; Tang, Yi-Wei; Netesov, Sergei; Petrov, Vladimir

    2003-01-01

    Genetic analysis of wild-type Crimean-Congo hemorrhagic fever (CCHF) virus strains recovered in the European part of Russia was performed. Reverse transcriptase PCR followed by direct sequencing was used to recover partial sequences of the CCHF virus medium (M) genome segment (M segment) from four pools of Hyalomma marginatum ticks and six human patients. Phylogenetic analysis of the M-segment sequences from Russian strains revealed a close relatedness of the strains (nucleotide sequence diversity, ≤5.0%). The strains differed significantly from CCHF viruses from other regions of the world (nucleotide sequence diversity, 10.3 to 20.4%), suggesting that CCHF virus strains recovered in the European part of Russia form a distinct group. PMID:12574301

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

    PubMed

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

    2016-02-01

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

  12. Implications of previous subclinical dengue infection but not virus load in dengue hemorrhagic fever.

    PubMed

    Yeh, Wen-Ting; Chen, Rong-Fu; Wang, Lin; Liu, Jien-Wei; Shaio, Men-Fang; Yang, Kuender D

    2006-10-01

    In a study comparing the virus load and immune reaction between patients with primary and secondary dengue-2 (DEN-2) infections in a hospital-based analysis, we found that 40.7% (55/135) of the 135 patients had secondary DEN-2 infection following a DEN-2 outbreak in southern Taiwan. Most of the secondary infections had subclinical primary dengue infections (78.2%; 43/55). Patients with secondary DEN-2 infections had lower platelet counts, and blood interferon-alpha and virus load, but significantly higher interleukin-10 (P=0.030) and anti-DEN-1 neutralization titers (P=0.013) than those with primary infection. Patients with secondary DEN-2 infection also had a higher rate of dengue hemorrhagic fever (DHF) (61.7% vs. 36.3%). A previous subclinical dengue infection is involved in the secondary DEN-2 infection associated with altered immune reaction and higher DHF rate, but lower blood virus load.

  13. Epidemic dengue hemorrhagic fever in rural Indonesia. I. Virological and epidemiological studies.

    PubMed

    Gubler, D J; Suharyono, W; Lubis, I; Eram, S; Sulianti Saroso, J

    1979-07-01

    Virological studies were carried out during an epidemic of dengue hemorrhagic fever in Central Java, Indonesia in 1976. Dengue virus was isolated from the acute sera of 45 of 69 patients (65%). The isolation rate was higher in primary than secondary cases. Dengue 3 was the predominant serotype being transmitted (27 isolates), but both dengue 1 (8 isolates) and dengue 4 (10 isolates) were also being transmitted. A composite picture of magnitude and duration of viremia showed that many patients were circulating over 10(8) MID50 per milliliter dengue 3 virus for the first 3 days of illness and that viremia persisted for 5-6 days in some persons. If all shock cases were considered, there was no relationship between dengue serotype and severity of disease. All three confirmed fatal cases, however, were associated with dengue type 3 infections.

  14. Ecology of the Crimean-Congo hemorrhagic fever endemic area in Albania.

    PubMed

    Papa, Anna; Velo, Enkelejda; Papadimitriou, Evangelia; Cahani, Gjyle; Kota, Majlinda; Bino, Silvia

    2009-12-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Albania. Ticks collected from cattle grazing in the endemic areas of Albania were tested for presence of CCHFV RNA, while serum samples collected from goats, cattle, hares, and birds were tested for the presence of specific IgG antibodies to CCHFV. One of the 31 pools prepared, consisting of four female Hyalomma spp. ticks, was found to carry CCHFV RNA with 99.2-100% homology to sequences detected in patients from the same region. Antibodies were not detected in cattle, hares, and birds, but 2/10 goats presented high titers of IgG antibodies. The shepherd of that flock was a member of a family affected by CCHF 10 days before the collection of goats' sera, and he presented a mild form of the disease.

  15. Alterations in favipiravir (T-705) pharmacokinetics and biodistribution in a hamster model of viral hemorrhagic fever.

    PubMed

    Gowen, Brian B; Sefing, Eric J; Westover, Jonna B; Smee, Donald F; Hagloch, Joseph; Furuta, Yousuke; Hall, Jeffery O

    2015-09-01

    Favipiravir (T-705) is a new anti-influenza drug approved for human use in Japan and progressing through Phase 3 clinical trials in the U.S. In addition to its potent inhibitory effects against influenza virus infection, the compound has been shown to be broadly active against RNA viruses from 9 different families, including the Arenaviridae. Several members of the Arenaviridae family of viruses are significant human pathogens that cause viral hemorrhagic fever, a severe systemic syndrome where vascular leak is a cardinal feature. Because arenaviral infections are unlikely to be diagnosed and treated until the illness has progressed to a more advanced state, it is important to understand the effects of the disease state on favipiravir pharmacokinetics (PK) and biodistribution to help guide therapeutic strategy. During acute arenavirus infection in hamsters, we found reduced plasma favipiravir concentrations and altered kinetics of absorption, elimination and time to maximum drug concentration. In addition, the amounts of the favipiravir M1 primary metabolite were higher in the infected animals, suggesting that favipiravir metabolism may favor the formation of this inactive metabolite during viral infection. We also discovered differences in favipiravir and M1 PK parameters associated with arenavirus infection in a number of hamster tissues. Finally, analysis at the individual animal level demonstrated a correlation between reduced plasma favipiravir concentration with increased disease burden as reflected by weight loss and viral load. Our study is the first to show the impact of active viral infection and disease on favipiravir PK and biodistribution, highlighting the need to consider alterations in these parameters when treating individuals with viral hemorrhagic fever of arenavirus or other etiology.

  16. 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.

  17. Alterations in favipiravir (T-705) pharmacokinetics and biodistribution in a hamster model of viral hemorrhagic fever

    PubMed Central

    Gowen, Brian B.; Sefing, Eric J.; Westover, Jonna B.; Smee, Donald F.; Hagloch, Joseph; Furuta, Yousuke; Hall, Jeffery O.

    2015-01-01

    Favipiravir (T-705) is a new anti-influenza drug approved for human use in Japan and progressing through Phase 3 clinical trials in the U.S. In addition to its potent inhibitory effects against influenza virus infection, the compound has been shown to be broadly active against RNA viruses from 9 different families, including the Arenaviridae. Several members of the Arenaviridae family of viruses are significant human pathogens that cause viral hemorrhagic fever, a severe systemic syndrome where vascular leak is a cardinal feature. Because arenaviral infections are unlikely to be diagnosed and treated until the illness has progressed to a more advanced state, it is important to understand the effects of the disease state on favipiravir pharmacokinetics (PK) and biodistribution to help guide therapeutic strategy. During acute arenavirus infection in hamsters, we found reduced plasma favipiravir concentrations and altered kinetics of absorption, elimination and time to maximum drug concentration. In addition, the amounts of the favipiravir M1 primary metabolite were higher in the infected animals, suggesting that favipiravir metabolism may favor the formation of this inactive metabolite during viral infection. We also discovered differences in favipiravir and M1 PK parameters associated with arenavirus infection in a number of hamster tissues. Finally, analysis at the individual animal level demonstrated a correlation between reduced plasma favipiravir concentration with increased disease burden as reflected by weight loss and viral load. Our study is the first to show the impact of active viral infection and disease on favipiravir PK and biodistribution, highlighting the need to consider alterations in these parameters when treating individuals with viral hemorrhagic fever of arenavirus or other etiology. PMID:26186980

  18. 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

  19. The first epidemic of dengue hemorrhagic fever in the People's Republic of China.

    PubMed

    Qiu, F X; Chen, Q Q; Ho, Q Y; Chen, W Z; Zhao, Z G; Zhao, B W

    1991-04-01

    The first epidemic of dengue in China associated with significant severe and fatal hemorrhagic disease which met the World Health Organization case definition occurred on Hainan Island in 1985-1986. The epidemic began in Zhan County in September 1985, spread throughout the coastal areas, and ultimately involved 13 counties and cities of the island in 1986. The mosquito vector was Aedes aegypti. The morbidity associated with dengue infection on Hainan Island was 1,913 per 100,000 residents, with a case fatality rate of 0.25%. Severe disease was more prevalent in the 10-29-year-old age group. Principal clinical features in laboratory-confirmed cases were fever, osteoarthralgia, hemorrhage and/or shock, and thrombocytopenia. Complications such as acute intravascular hemolysis, diffuse intravascular coagulation, hemoconcentration, pleural effusion, altered mentality, and pneumonia were also observed. One hundred twenty-five isolates of dengue 2 virus were recovered from acute-phase serum samples from 278 patients, and 5 strains of this same virus serotype were isolated from 5 pools of adult Ae. aegypti.

  20. Crimean-Congo hemorrhagic fever: CXCL10 correlates with the viral load.

    PubMed

    Papa, Anna; Yagci Caglayık, Dilek; Christova, Iva; Tsergouli, Katerina; Korukluoglu, Gulay; Uyar, Yavuz

    2015-06-01

    Crimean-Congo hemorrhagic fever (CCHF) is a human disease with high fatality rate. Although its pathogenesis is not elucidated yet, it is considered that cytokines play a significant role in the progression and outcome of the disease. Serum CXCL10 levels were estimated in 35 patients with acute CCHF and were correlated with the viral load, and various demographic and clinical parameters. The mean CXCL10 concentration in the patients' group was higher compared to the respective value in the control group (4421.74 pg/ml vs. 28.47 pg/ml, P < 0.05). A strong positive correlation between CXCL10 and viral load was seen (rs = 0.57, P < 0.001), while the outcome of the disease was related with the viral load (rs = 0.47, P = 0.004) and the presence of hemorrhagic manifestations (P < 0.001). The study provides an insight into the strong correlation between CXCL10 and viral load in acute CCHF cases suggesting that it plays an important role in CCHF pathogenesis.

  1. 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

  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. Clinical and laboratory characteristics and risk factors for fatality in elderly patients with dengue hemorrhagic fever.

    PubMed

    Lee, Ing-Kit; Liu, Jien-Wei; Yang, Kuender D

    2008-08-01

    To better understand the clinical and laboratory characteristics and to identify risk factor(s) for fatality in elderly patients with dengue hemorrhagic fever (DHF), 66 elderly (age > or = 65 years) and 241 non-elderly adults (age, 19-64 years) with DHF were retrospectively analyzed. Compared with non-elderly adults, elderly individuals had significantly lower incidences of fever (P = 0.002), abdominal pain (P = 0.003), bone pain (P < 0.001), and skin rashes (P = 0.002); higher frequencies of concurrent bacteremia (P = 0.049), gastrointestinal bleeding (P = 0.044), acute renal failure (P = 0.001), and pleural effusion (P < 0.010); higher incidence of prolonged prothrombin time (P = 0.025); lower mean hemoglobin level (P < 0.001); longer hospitalization (P = 0.049); and a higher fatality rate (P = 0.006). Five elderly patients with DHF died. When compared with non-fatal elderly patients with DHF, a significant higher frequency in men (P = 0.019), those with chronic obstructive pulmonary disease (P = 0.008), those with dengue shock syndrome (DSS; P < 0.001), and those with acute renal failure (P < 0.001) was found in the elderly counterparts that died. Multivariate analysis showed that only DSS (odd ratio = 77.33, P = 0.001) was an independent risk factor for fatality in elderly patients.

  4. A re-evaluation of the mechanisms leading to dengue hemorrhagic fever.

    PubMed

    Noisakran, Sansanee; Chokephaibulkit, Kulkanya; Songprakhon, Pucharee; Onlamoon, Nattawat; Hsiao, Hui-Mien; Villinger, Francois; Ansari, Aftab; Perng, Guey Chuen

    2009-09-01

    Viremia is one of the features of dengue virus infection among the flaviviruses. Dengue virus infection results in a spectrum of clinical symptoms, ranging from undifferentiated flu-like illness, mild dengue fever, to dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), a life-threatening illness. Several mechanisms have been hypothesized based primarily on data collected from post-acute clinical phase to account for DHF/DSS. Lack of a suitable animal model for DHF/DSS has hindered progress in defining the etiology of DHF/DSS. Levels of circulating dengue virus have been well-correlated to severe dengue disease. However, the cell lineage(s) serving as a primary target for the source of viremia are largely unknown. Results from in vivo and in vitro pilot studies using molecular and more advanced technologies reveal that dengue virus appears to be associated with platelets and the megakaryocytic lineage. The observation may partially explain the dysfunction of platelets observed in dengue affected patients.

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

    PubMed

    Guzman, María G; Kouri, Gustavo

    2003-05-01

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

  6. The first reported outbreak of dengue hemorrhagic fever in Irian Jaya, Indonesia.

    PubMed

    Richards, A L; Bagus, R; Baso, S M; Follows, G A; Tan, R; Graham, R R; Sandjaja, B; Corwin, A L; Punjabi, N

    1997-07-01

    During the months of September 1993 through February 1994, an outbreak of hemorrhagic fever occurred in the city of Jayapura, the provincial capital of Irian Jaya, Indonesia. Seventy-two patients (age range = 1-41 years) with suspected dengue hemorrhagic fever (DHF) were enrolled into the outbreak investigation conducted during October-November 1993. The pediatric patient population consisted of 36 individuals ages 1-12 years of age with a similar male to female ratio. From clinical histories obtained from the children diagnosed with DHF (n = 23), the predominant complaints were fever (100%), headache (96.7%), vomiting (47.8%), abdominal pain (39.1%), back/bone pain (39.1%), cough (39.1%), sore throat (21.7%), convulsions (17.4%), and eye pain (13.0%). Clinical findings of the same pediatric patients included a positive tourniquet test result (100%), thrombocytopenia (100%), hemoconcentration (100%), skin petechiae (43.5%), epistaxis (39.1%), and maculopapular rash (26%). All four of the children diagnosed with DHF grade IV had hepatomegaly, pleural effusion, ascites, cold perspiration, and confusion. Serologic data demonstrated that a majority (46 of 70, 68.7%) of the individuals assessed did not have significant levels of IgM specific for dengue viruses at the time of their admission. However, the nine successful dengue virus isolations were only from these serononreactive cases (19.6%). From the other patients assessed, 11.4% had a primary (or first exposure) serologic response to dengue virus antigen (predominantly IgM); 17.1% had a secondary (or subsequent exposure) serologic response to the same dengue antigens (predominantly IgG response) and 5.7% (four adults) had indeterminate serologic data that could not differentiate between reactivity to dengue or Japanese encephalitis virus antigen preparations. Virus culture of blood samples produced nine dengue virus isolates: DEN- 1 (2), DEN-2 (1), and DEN-3 (6). Japanese encephalitis and influenza viruses were not

  7. The dengue and dengue hemorrhagic fever epidemic in Puerto Rico, 1994-1995.

    PubMed

    Rigau-Pérez, J G; Vorndam, A V; Clark, G G

    2001-01-01

    From June 1, 1994 to May 31, 1995 a total of 24,700 cases of dengue (7.01/1,000 population) were reported to the laboratory-based surveillance system in Puerto Rico (1991-1994, annual average: 2.55/1,000). Dengue virus 2 predominated. The earliest indicator of epidemic activity was the virus isolation rate in May 1994 (14.0% versus 5.7% average). The male-to-female ratio among cases was 1:1.1; 65.4% were younger than 30 years (the 10 to 19 year age group had the highest incidence, 11.8/1,000). At least 5,687 cases (23.0%) showed a hemorrhagic manifestation; 4,662 (18.9%) were hospitalized, and 40 died (0.2%; 10 laboratory-positive). Two cases documented by laboratory were transmitted by unusual routes--intrapartum and through a bone marrow transplant. Among 2,004 hospitalized cases reported by infection control nurses, 139 (6.9%) fulfilled the criteria for dengue hemorrhagic fever (DHF) and another 13 cases (0.6%) had dengue shock syndrome. This epidemic produced the largest number of hospitalizations, DHF cases, and deaths from any dengue epidemic in Puerto Rico. Severity did not change throughout the year. Surveillance capabilities were maintained by temporary, simplified reporting methods, none of which could be recommended as the single method of choice for surveillance; each must be used (on site, or as a service available from a reference laboratory) at the right time in the epidemic cycle. The utility of comparisons of current and previous data underscores the value of long-term surveillance. Our analysis was unable to document whether significantly increased transmission occurred more often in cities where the water supply was rationed or where the local landfill was closed.

  8. 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

  9. 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

  10. 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

  11. Immunopathogenesis of dengue hemorrhagic fever and shock syndrome: role of TAP and HPA gene polymorphism.

    PubMed

    Soundravally, R; Hoti, S L

    2007-12-01

    Clinical outcomes of dengue infection such as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) could be attributed to host genetic factors. The transporters associated with antigen processing (TAP) genes are polymorphic genes located in the human leukocyte antigen (HLA) class II region and are essentially involved in class I antigen presentation. Therefore, these genes might grant susceptibility to severe dengue infection. Hence, the aim of the study was to type the TAP1 gene (using amplification refraction mutation system [ARMS] polymerase chain reaction [PCR]) and HPA1 and HPA2 gene polymorphism (by PCR-sequence specific primers) in different clinical spectrums of dengue infection. The study included 100 controls and 91 DF, 75 DHF, and 32 DSS patients. The results revealed that the frequencies of valine at TAP1 333 and HPA 1b at HPA1 were increased among DHF and DSS, respectively, in comparison to controls (p <0.05). The frequency of genotype TAP1 333 ILE/VAL (61.3%) was significantly higher in DHF compared with control (37%, p = 0.005) or DF (38.9%, p = 0.007) patients. A significantly greater proportion of DHF patients demonstrated HPA1a/1a and HPA 2a/2b genotypes than DF patients. DSS patients were more likely to be heterozygous at HPA1 than DHF (OR = 4.75, p = 0.003). A positive correlation existed between TAP1 333 and HPA1 in DHF (p = 0.017, r = 0.229). This first report on TAP and HPA gene polymorphism in dengue suggested that the heterozygous pattern at the TAP1 333 locus and HPA1a/1a and HPA2a/2b genotypes confer susceptibility to DHF and the HPA1a/1b genotype was determined to be a genetic risk factor for DSS.

  12. Some clinical and epidemiological observations on virologically confirmed dengue hemorrhagic fever.

    PubMed

    Samsi, T K; Wulur, H; Sugianto, D; Bartz, C R; Tan, R; Sie, A

    1990-01-01

    This study is a part of a one year prospective study on dengue hemorrhagic fever (DHF) carried out in the Department of Pediatrics, Sumber Waras Hospital in West Jakarta. Viral isolation and serologic analysis for DHF were done by Namru-2 in Jakarta. The subjects were 151 virologically confirmed DHF Patients admitted to the Department of Pediatrics during the period of September 1987-June 1988, consisting of 82 boys and 69 girls of 6 months-15 years old. The predominant age group was 5 to 9 years, representing 49.7% subjects. Dengue virus was isolated from sera during the first 8 days of illness and in 139 (42.1%) during the first 5 days of illness. Dengue virus type 1, 2, 3 and 4 were isolated from 16.6%, 13.2%, 69.5% and 0.7% subjects, respectively. The clinical manifestations revealed no striking differences between dengue 3 and others except for thrombocytopenia and shock. High fever, hemoconcentration and thrombocytopenia on admission was observed in 30.5%, 8.6% and 8.6% of subjects, respectively. Dengue shock syndrome (DSS) were observed in 23 (15.2%) with 3 (2%) fatal cases. Dengue virus serotype 3 was observed in 20 out of 23 DSS cases (86.9%) and all fatal cases were associated with dengue type 2. This study revealed that dengue 3 is the predominant virus circulating during recent epidemics and is associated with more severe clinical manifestation and with a higher incidence rate of living area.

  13. Dengue hemorrhagic fever: knowledge, attitude and practice in Ang Thong Province, Thailand.

    PubMed

    Kittigul, Leera; Suankeow, Kedsuda; Sujirarat, Dusit; Yoksan, Sutee

    2003-06-01

    A cross-sectional study was carried out between July 1998 and June 1999 to identify dengue virus-infected patients under age 15 admitted to seven government hospitals in Ang Thong Province, a central region of Thailand, and to assess the knowledge, attitude, and practice (KAP) of their care takers. To differentiate dengue cases, clinical evaluation and laboratory diagnosis were used. Serum samples were collected from 90 admitted children and also from 80 healthy students. The dengue cases were classified as dengue fever (9 cases, 12.2%) and dengue hemorrhagic fever (DHF: 65 cases, 87.8%). Nine patients had dengue shock syndrome, but no death occurred. With serological confirmation, primary antibody response was observed in 8 (11.3%) and definite secondary infection in 49 (69%). Out of 41 serum samples, 14 (34.1%) were positive for dengue virus isolation: dengue serotypes 1, 2 or 3. A total of 131 care takers of enrolled children were interviewed in the context of KAP in DHF. The majority of them were mothers with primary school education level. Half of the care takers were workers. DHF knowledge of the care takers of the dengue cases, non-cases, and healthy students was almost the same. However, the care takers of dengue cases recognized petechiae as a danger sign, p-value of 0.006. They had a higher response in prevention, control and treatment of DHF than the other two groups after their children were admitted to hospital, p-value of 0.000. The results indicated that DHF remains a public health problem in this area and the people need more understanding of the disease. Continuous campaigns are required for community participation so as to prevent and control DHF successfully.

  14. Genome Sequences of Simian Hemorrhagic Fever Virus Variant NIH LVR42-0/M6941 Isolates (Arteriviridae: Arterivirus)

    PubMed Central

    Lauck, Michael; Palacios, Gustavo; Wiley, Michael R.; Lǐ, Yànhuá; Fāng, Yīng; Lackemeyer, Matthew G.; Caì, Yíngyún; Bailey, Adam L.; Postnikova, Elena; Radoshitzky, Sheli R.; Johnson, Reed F.; Alkhovsky, Sergey V.; Deriabin, Petr G.; Friedrich, Thomas C.; Goldberg, Tony L.; Jahrling, Peter B.; O’Connor, David H.

    2014-01-01

    Simian hemorrhagic fever virus (SHFV) variant NIH LVR42-0/M6941 is the only remaining SHFV in culture, and only a single genome sequence record exists in GenBank/RefSeq. We compared the genomic sequence of NIH LVR42-0/M6941 acquired from the ATCC in 2011 to NIH LVR42-0/M6941 genomes sequenced directly from nonhuman primates experimentally infected in 1989. PMID:25301647

  15. A comparison of the age distributions in the dengue hemorrhagic fever epidemics in Santiago de Cuba (1997) and Thailand (1998).

    PubMed

    Pongsumpun, P; Yoksan, S; Tan, I M

    2002-06-01

    The age profiles of the infected populations of two dengue hemorrhagic fever (DHF) epidemics, the 1997 epidemic, in Santiago de Cuba and the 1998 epidemic in Thailand, are compared. Using an age-structured model of disease transmission, the dependence of the forces of infection on age was determined for each epidemic. The difference in the behavior of the two epidemics and the role of primary and secondary infection in the development of DHF are discussed.

  16. Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome

    PubMed Central

    2014-01-01

    Background Hemorrhagic fever with renal syndrome (HFRS) has become an important public health concern because of the high incidence and mortality rates, and limited treatment and vaccination. Until now, clinical studies on characteristics and outcomes in critical patients with HFRS have been limited. The aim of this study was to observe the clinical characteristics and cumulative proportions surviving and explore the predictive effects and risk factors for prognosis. Methods A detailed retrospective analysis of clinical records for critical HFRS patients was conducted. The patients enrolled were treated in the centre for infectious diseases, Tangdu Hospital, between January 2008 and August 2012. The clinical characteristics between the survivors and non-survivors were compared by Student’s t-test or Chi-square test. The risk clinical factors for prognosis were explored by logistic regression analysis. The predictive effects of prognosis in clinical and laboratory parameters were analyzed by receiver operating characteristic (ROC) curves. The cumulative proportions surviving at certain intervals in the critical patients were observed by Kaplan-Meier survival analysis. Results Of the 75 patients enrolled, the cumulative proportion surviving was 70.7% at the second week interval, with a 28-day mortality rate of 36.3%. The non-survivors tended to have higher frequencies of agitation, dyspnea, conjunctival hemorrhage, coma, cardiac failure, acute respiratory distress syndrome (ARDS) and encephalopathy (P < .05). ARDS, conjunctival hemorrhage and coma were risk factors for death in the critical patients with HFRS. The non-survivors were found to have lower serum creatinine (Scr) levels (P < .001) and higher incidences of prolonged prothrombin time (PT) (P = .006), activated partial thromboplastin time (APTT) (P = .003) and elevated white blood cells (WBC) levels (P = .005), and the laboratory parameters mentioned above reached statistical

  17. [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

  18. 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

  19. Genome Sequence of Ex-Afghanistan Crimean-Congo Hemorrhagic Fever Virus SCT Strain, from an Imported United Kingdom Case in October 2012.

    PubMed

    Chamberlain, John; Atkinson, Barry; Logue, Christopher H; Latham, Jennie; Newman, Edmund N C; Hewson, Roger

    2013-05-16

    Crimean-Congo hemorrhagic fever (CCHF) virus is a serious human pathogen causing severe hemorrhagic disease with a fatality rate of up to approximately 30%. We have determined the viral genomic sequence from an isolate that caused a fatal case of imported CCHF in the United Kingdom in October 2012.

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

    PubMed Central

    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

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

    PubMed

    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.

  2. Noninvasive measurement of microvascular leakage in patients with dengue hemorrhagic fever.

    PubMed

    Bethell, D B; Gamble, J; Pham, P L; Nguyen, M D; Tran, T H; Ha, T H; Tran, T N; Dong, T H; Gartside, I B; White, N J; Day, N P

    2001-01-15

    Dengue shock syndrome (DSS) is a potentially lethal complication of dengue virus infection associated with hypotension and leakage of plasma water into the extravascular space. To determine whether the underlying pathophysiology of DSS is distinct from that in milder forms of the disease, we assessed microvascular permeability, by use of strain gauge plethysmography, in Vietnamese children with DSS (n=19), or dengue hemorrhagic fever (DHF) without shock (n=16), and in healthy control children (n=15). At admission and after fluid resuscitation, the mean coefficient of microvascular permeability (K(f)) for the patients with dengue was approximately 50% higher than that for the control patients (P=.02). There was no significant difference in K(f) between the 2 groups of patients with dengue; this suggests the same underlying pathophysiology. We hypothesize that in patients with DSS, the fluctuations in K(f) are larger than those in patients with DHF, which leads to short-lived peaks of markedly increased microvascular permeability and consequent hemodynamic shock.

  3. 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

  4. 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.

  5. Propagation and titration of Alkhumra hemorrhagic fever virus in the brains of newborn Wistar rats.

    PubMed

    Madani, Tariq A; Kao, Moujahed; Abuelzein, El-Tayeb M E; Azhar, Esam I; Al-Bar, Hussein M S; Abu-Araki, Huda; Bokhary, Rana Y; Ksiazek, Thomas G

    2014-04-01

    Alkhumra hemorrhagic fever virus (AHFV) is a novel flavivirus identified first in Saudi Arabia. In this study, successful propagation of AHFV in the brains of newborn Wistar rats is described and the median rat lethal dose (RLD50) is determined. AHFV-RNA-positive human sera diluted 1:10 were injected intracerebrally into 16, ≤24h old rats. Post-inoculation, the rats were observed daily for 30 days. Brains of moribund rats were tested for AHFV-RNA using RT-PCR and cultured in LLC-MK2 cells. The titer of the isolated virus was determined and expressed in median tissue culture infectious dose (TCID50). To determine the RLD50, AHFV brain suspension was 10-fold diluted serially and each dilution was inoculated in the cerebral hemispheres of 10 rats for a total of 90 rats. Three days post-inoculation, the rats developed tremor, irritability, convulsion, opisthotonus, and spastic paresis starting in the hind limbs and ascending to involve the whole body. All infected rats died within 3-7 days with histopathologically confirmed meningoencephalitis. AHFV-RNA was detected in the brains of all infected rats and the virus titer was 10(9.4) RLD50/ml. The virus titer in LLC-MK2 was 10(8.2) TCID50/ml. In conclusion, AHFV was propagated successfully to high titers in the brains of newborn Wistar rats.

  6. Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever

    PubMed Central

    McLay, Lisa; Ansari, Aftab; Liang, Yuying; Ly, Hinh

    2012-01-01

    A number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. Lassa virus, found in West Afri ca, causes severe hemorrhagic fever (HF), while the other principal Old World arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. The New World agents, including Junin, Machupo and Sabia virus, are highly pathogenic for humans. Arenaviral HF is characterized by high viremia and general immune suppression, the mechanism of which is unknown. Studies using viral reverse genetics, cell-based assays, animal models and human genome-wide association analysis have revealed potential mechanisms by which arenaviruses cause severe disease in humans. Each of the four viral gene products (GPC, L polymerase, NP, and Z matrix protein) and several host-cell factors (e.g., α-dystroglycan) are responsible for mediating viral entry, genome replication, and the inhibition of apoptosis, translation and interferon-beta (IFNβ) production. This review summarizes current knowledge of the role of each viral protein and host factor in the pathogenesis of arenaviral HF. Insights from recent studies are being exploited for the development of novel therapies. PMID:23261843

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

    PubMed Central

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

    2008-01-01

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

  8. 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

  9. Laboratory diagnosis of Ebola hemorrhagic fever during an outbreak in Yambio, Sudan, 2004.

    PubMed

    Onyango, Clayton O; Opoka, Martin L; Ksiazek, Thomas G; Formenty, Pierre; Ahmed, Abdullahi; Tukei, Peter M; Sang, Rosemary C; Ofula, Victor O; Konongoi, Samson L; Coldren, Rodney L; Grein, Thomas; Legros, Dominique; Bell, Mike; De Cock, Kevin M; Bellini, William J; Towner, Jonathan S; Nichol, Stuart T; Rollin, Pierre E

    2007-11-15

    Between the months of April and June 2004, an Ebola hemorrhagic fever (EHF) outbreak was reported in Yambio county, southern Sudan. Blood samples were collected from a total of 36 patients with suspected EHF and were tested by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G and M antibodies, antigen ELISA, and reverse-transcription polymerase chain reaction (PCR) of a segment of the Ebolavirus (EBOV) polymerase gene. A total of 13 patients were confirmed to be infected with EBOV. In addition, 4 fatal cases were classified as probable cases, because no samples were collected. Another 12 patients were confirmed to have acute measles infection during the same period that EBOV was circulating. Genetic analysis of PCR-positive samples indicated that the virus was similar to but distinct from Sudan EBOV Maleo 1979. In response, case management, social mobilization, and follow-up of contacts were set up as means of surveillance. The outbreak was declared to be over on 7 August 2004.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. [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.

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

    PubMed

    Mostafavi, Ehsan; Chinikar, Sadegh; Moradi, Maryam; Bayat, Neda; Meshkat, Mohsen; Fard, Mohammad Khalili; Ghiasi, Seyyed Mojtaba

    2013-01-01

    Crimean Congo hemorrhagic fever (CCHF) is a viral zoonosis, which is usually transmitted via tick bites or close contact with infected blood or tissue. This disease can cause a case fatality rate of up to 25%-30% in humans. CCHF Infection in birds is less documented. An ostrich can reproduce viruses and can also play the role of a mechanical vector, by transporting infected ticks without becoming ill. In March 2007, three butchers and one worker in an ostrich farm were infected with CCHF in central part of Iran. Considering the role ostriches play in transmitting the disease, serum samples from five ostriches of that farm were taken and sent to the laboratory for CCHF ELISA tests. The result of the IgG test was positive for one (20%) of the ostriches. At the same time, serum samples of eight sheep from the same farm were sent for IgG testing, two (25%) of which were positive. This was the first report of CCHF infection of an ostrich in Iran and tracing CCHF IgG against this ostrich and the afore-mentioned sheep may have revealed that the disease in the worker was the cause of transmission of this disease from these animals or their ticks.

  17. 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.

  18. Prevalence of hemorrhagic fever with renal syndrome in Qingdao City, China, 2010–2014

    PubMed Central

    Jiang, Fachun; Zhang, Zhentang; Dong, Liyan; Hao, Bi; Xue, Zaifeng; Ma, Dongqiang; Su, Hang; Wen, Hong-ling; Yu, Hao; Yu, Xue-jie

    2016-01-01

    Hemorrhagic fever with renal syndrome (HFRS) was considered to be transmitted by Apodemus agrarius and Rattus norvegicus, the principal animal hosts of Hantaan virus and Seoul virus, respectively. The aim of this study is to determine the correlation of HFRS incidence with capture rate and hantavirus infection rate of rodent species in Qingdao City, China. We collected HFRS patients’ information and captured field and residential rodents in Qingdao City, China from 2010 to 2014. The correlations of HFRS incidence to rodent capture rate and hantavirus infection rate of rodents were analyzed statistically. The main findings of this study are that the high HFRS incidence (19.3/100,000) is correlated to the capture rate of field Mus musculus (p = 0.011, r = 0.037); but surprisingly it did not correlated to the capture rate of the principal rodent hosts Apodemus agrarius and Rattus norvegicus and the hantavirus infection rate of these rodent species in the field or residential area. These novel findings suggest that Mus musculus, a nontraditional animal host of hantavirus may play an important role in hantavirus transmission in Qingdao City. PMID:27786303

  19. 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).

  20. Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever.

    PubMed

    Cam, B V; Fonsmark, L; Hue, N B; Phuong, N T; Poulsen, A; Heegaard, E D

    2001-12-01

    We present a prospective case-control study of 27 serologically confirmed dengue hemorrhagic fever (DHF) patients with severe central nervous system symptoms. Dengue associated encephalopathy accounted for 0.5% of 5,400 patients admitted with DHF. The mortality rate among children with encephalopathy was 22%, with the survivors experiencing a complete recovery. Liver enzymes and bilirubin were significantly elevated in the study group. In analysis of the cerebrospinal fluid (CSF), reverse transcriptase-polymerase chain reaction revealed dengue-3-specific RNA in one evaluated case. Dengue-specific immunoglobulin M was detected in CSF in 14 of 22 assessable patients, indicating a localized infection. Magnetic resonance imaging scans showed cerebral edema in the majority of patients, although encephalitis-like changes were less common. There was an equal distribution of primary and secondary infections. On the basis of previous reports and of the findings of our study, DHF probably encompasses an expanding clinical spectrum that infrequently involves encephalitis due to a direct neurotropic effect of dengue virus.

  1. 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.

  2. Differences in clinical features between children and adults with dengue hemorrhagic fever/dengue shock syndrome.

    PubMed

    Namvongsa, Vannyda; Sirivichayakul, Chukiat; Songsithichok, Sirilak; Chanthavanich, Pornthep; Chokejindachai, Watcharee; Sitcharungsi, Raweerat

    2013-09-01

    This retrospective study was conducted to assess the differences in clinical features between children and adults with dengue hemorrhagic fever/ dengue shock syndrome (DHF/DSS) admitted to Ratchaburi Hospital, Ratchaburi Province, Thailand. A total of 273 patients with DHF/DSS admitted to Ratchaburi Hospital during January 2007 to May 2008 were included in the study. The median age (range) of studied subjects was 16 years (6 months to 62 years) and the ratio of adults to children was 1.6:1. Forty-eight percent of subjects were 16-30 years old. The common signs, symptoms and clinical features were: nausea/vomiting (74.0%), a positive tourniquet test (73.0%), anorexia (67.0%), hemoconcentration (58.0%), headache (54.0%), abdominal tenderness (43.0%), myalgia (39.0%) and pleural effusion (20.0%). Children had anorexia, a positive tourniquet test, abdominal tenderness and a convalescent rash more frequently than adults. Children also had significantly more prominent plasma leakage as shown by lower serum albumin and sodium and a higher prevalence of pleural effusion, ascites and shock. Although not statistically significant, the prevalence of bleeding in children was higher than in adults but more adults needed blood transfusion. This study provides additional insight into the clinical picture of DHF/DSS in adults and children and may be beneficial for clinicians caring for these adults and children.

  3. Potential association of dengue hemorrhagic fever incidence and remote senses land surface temperature, Thailand, 1998.

    PubMed

    Nitatpattana, Narong; Singhasivanon, Pratap; Kiyoshi, Honda; Andrianasolo, Haja; Yoksan, Sutee; Gonzalez, Jean-Paul; Barbazan, Philippe

    2007-05-01

    A pilot study was designed to analyze a potential association between dengue hemorrhagic fever (DHF) incidence and, temperature computed by satellite. DHF is a mosquito transmitted disease, and water vapor and humidity are known to have a positive effect on mosquito life by increasing survival time and shortening the development cycle. Among other available satellite data, Land Surface Temperature (LST) was chosen as an indicator that combined radiated earth temperature and atmospheric water vapor concentration. Monthly DHF incidence was recorded by province during the 1998 epidemic and obtained as a weekly combined report available from the National Ministry of Public Health. Conversely, LST was calculated using remotely sensed data obtained from thermal infrared sensors of NOAA satellites and computed on a provincial scale. Out of nine selected study provinces, five (58.3%) exhibited an LST with a significant positive correlation with rainfall (p < 0.05). In four out of nineteen surveyed provinces (21.3%), LST showed a significant positive correlation with DHF incidence (p < 0.05). Positive association between LST and DHF incidence was significantly correlated in 75% of the cases during non-epidemic months, while no correlation was found during epidemic months. Non-climatic factors are supposed to be at the origin of this discrepancy between seasonality in climate (LST) and DHF incidence during epidemics.

  4. Haiti: absence of dengue hemorrhagic fever despite hyperendemic dengue virus transmission.

    PubMed

    Halstead, S B; Streit, T G; Lafontant, J G; Putvatana, R; Russell, K; Sun, W; Kanesa-Thasan, N; Hayes, C G; Watts, D M

    2001-09-01

    In 1994-1996, 185 strains of dengue (DEN) virus types 1, 2, and 4 were recovered from febrile United States and other United Nations military personnel in Haiti. We wondered whether risk factors for dengue hemorrhagic fever (DHF) existed and, if so, were DHF cases occurring among Haitian children. Dengue transmission rates were studied in 210 school children (6-13 years old) resident in Carrefour Borough, Port-au-Prince, Haiti. When sera were tested for plaque-reduction neutralizing antibodies to DEN 1-4 viruses, nearly 85% had antibodies to two or more DEN serotypes. The annual transmission rate was estimated at 30%, a rate observed in countries endemic for DHE Haitian DEN 2 isolates were genotype I, which are repeatedly associated with DHF cases in Southeast Asia and American regions. Despite positive virologic pre-conditions, DHF cases were not recorded by experienced Port-au-Prince pediatricians. These observations, which are reminiscent of those in Africa, provide further evidence of a dengue resistance gene in black populations.

  5. 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.

  6. Dengue hemorrhagic fever patients with acute abdomen: clinical experience of 14 cases.

    PubMed

    Khor, Boon-Siang; Liu, Jien-Wei; Lee, Ing-Kit; Yang, Kuender D

    2006-05-01

    Among 328 patients with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 14 (4 men and 10 women, median age 44 years) had acute abdomen. DHF/DSS was initially suspected in only 2 of these 14 patients. Presumptive diagnoses of acute cholecystitis (6 acalculus and 4 calculus cholecystitis) were made in 10 patients, non-specific peritonitis in three patients, and acute appendicitis in one patients. Cholecystectomy, percutaneous transhepatic gallbladder drainage, and appendectomy were performed in three patients. Transfused blood in the three patients who underwent invasive procedures and the 11 patients who received supportive treatment included packed red blood cells (24 versus 0 units; P = 0.048), fresh frozen plasma (84 versus 0 units; P = 0.048), and platelets (192 versus 180 units; P = 0.003). Patients who underwent invasive procedures also had prolonged time in the hospital (median = 11 versus 7 days; P = 0.015). To avoid unnecessary invasive procedure-related morbidity and mortality, this report underscores the importance of a careful differential diagnosis in patients with acute abdomen in a dengue-endemic setting.

  7. 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

  8. Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses.

    PubMed

    Radoshitzky, Sheli R; Kuhn, Jens H; Spiropoulou, Christina F; Albariño, César G; Nguyen, Dan P; Salazar-Bravo, Jorge; Dorfman, Tatyana; Lee, Amy S; Wang, Enxiu; Ross, Susan R; Choe, Hyeryun; Farzan, Michael

    2008-02-19

    Transferrin receptor 1 (TfR1) is a cellular receptor for the New World hemorrhagic fever arenaviruses Machupo (MACV), Junín (JUNV), and Guanarito (GTOV). Each of these viruses is specifically adapted to a distinct rodent host species, but all cause human disease. Here we compare the ability of these viruses to use various mammalian transferrin receptor 1 (TfR1) orthologs, including those of the South American rodents that serve as reservoirs for MACV, JUNV, and GTOV (Calomys callosus, Calomys musculinus, and Zygodontomys brevicauda, respectively). Retroviruses pseudotyped with MACV and JUNV but not GTOV glycoproteins (GPs) efficiently used C. callosus TfR1, whereas only JUNV GP could use C. musculinus TfR1. All three viruses efficiently used Z. brevicauda TfR1. TfR1 orthologs from related rodents, including house mouse (Mus musculus) and rat (Rattus norvegicus), did not support entry of these viruses. In contrast, these viruses efficiently used human and domestic cat TfR1 orthologs. We further show that a local region of the human TfR1 apical domain, including tyrosine 211, determined the efficiency with which MACV, JUNV, and GTOV used various TfR1 orthologs. Our data show that these New World arenaviruses are specifically adapted to the TfR1 orthologs of their respective rodent hosts and identify key commonalities between these orthologs and human TfR1 necessary for efficient transmission of these viruses to humans.

  9. Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever.

    PubMed

    McLay, Lisa; Ansari, Aftab; Liang, Yuying; Ly, Hinh

    2013-02-01

    A number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. Lassa virus, found in West Africa, causes severe hemorrhagic fever (HF), while the other principal Old World arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. The New World agents, including Junin, Machupo and Sabia virus, are highly pathogenic for humans. Arenaviral HF is characterized by high viremia and general immune suppression, the mechanism of which is unknown. Studies using viral reverse genetics, cell-based assays, animal models and human genome-wide association analysis have revealed potential mechanisms by which arenaviruses cause severe disease in humans. Each of the four viral gene products (GPC, L polymerase, NP, and Z matrix protein) and several host-cell factors (e.g., α-dystroglycan) are responsible for mediating viral entry, genome replication, and the inhibition of apoptosis, translation and interferon-beta (IFNβ) production. This review summarizes current knowledge of the role of each viral protein and host factor in the pathogenesis of arenaviral HF. Insights from recent studies are being exploited for the development of novel therapies.

  10. Characterization of the cellular receptors for the South American hemorrhagic fever viruses Junin, Guanarito, and Machupo.

    PubMed

    Rojek, Jillian M; Spiropoulou, Christina F; Kunz, Stefan

    2006-06-01

    The New World arenaviruses Junin, Machupo, and Guanarito are the causative agents of hemorrhagic fevers (HF) with high mortality in humans. The cellular receptor for Old World arenaviruses and one subgroup of the New World arenaviruses (Clade C) have been identified as alpha-dystroglycan (alpha-DG). In contrast, the receptor(s) of the South American HF viruses, which belong to the Clade B New World arenaviruses, are currently unknown. To begin to characterize the cellular receptors used by these pathogens, we generated recombinant retroviral pseudotypes with the glycoproteins of Guanarito, Junin, and Machupo. Infection with the South American HF viruses is independent of alpha-DG and functional receptors for Guanarito, Junin, and Machupo were found on most human cell types and cells derived from non-human primate and rodents. Guanarito, Junin, and Machupo share a common receptor, which is distinct from the receptor(s) used by the closely related non-pathogenic Clade B virus Amapari, and the genetically more distant Clade A and C New World arenaviruses. We show that the cellular receptor(s) for the South American HF viruses are proteins or protein-linked entities and that infection is not dependent on protein-linked N-glycans, O-glycans, or glycosaminoglycans.

  11. Human hemorrhagic Fever causing arenaviruses: molecular mechanisms contributing to virus virulence and disease pathogenesis.

    PubMed

    Shao, Junjie; Liang, Yuying; Ly, Hinh

    2015-05-21

    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.

  12. 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

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

    PubMed

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

    2010-04-01

    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. 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.

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

    PubMed

    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.

  16. 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

  17. 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

  18. [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

  19. 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

  20. 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.

  1. The Epidemic Characteristics and Changing Trend of Hemorrhagic Fever with Renal Syndrome in Hubei Province, China

    PubMed Central

    Zhang, Yi-Hui; Ge, Liang; Liu, Li; Huo, Xi-Xiang; Xiong, Hai-Rong; Liu, Yuan-Yuan; Liu, Dong-Ying; Luo, Fan; Li, Jin-Lin; Ling, Jia-Xin; Chen, Wen; Liu, Jing; Hou, Wei; Zhang, Yun; Fan, Hong; Yang, Zhan-Qiu

    2014-01-01

    Background Hemorrhagic fever with renal syndrome (HFRS) is caused by different hantaviruses within the Bunyaviridae family. HFRS is a fulminant, infectious disease that occurs worldwide and is endemic in all 31 provinces of China. Since the first HFRS case in Hubei Province was reported in 1957, the disease has spread across the province and Hubei has become one of the seriously affected areas in China with the greatest number of reported HFRS cases in the 1980's. However, the epidemic characteristics of HFRS in Hubei are still not entirely clear and long-term, systematic investigations of this epidemic area have been very limited. Methods The spatiotemporal distribution of HFRS was investigated using data spanning the years 1980 to 2009. The annual HFRS incidence, fatality rate and seasonal incidence between 1980 and 2009 were calculated and plotted. GIS-based spatial analyses were conducted to detect the spatial distribution and seasonal pattern of HFRS. A spatial statistical analysis, using Kulldorff's spatial scan statistic, was performed to identify clustering of HFRS. Results A total of 104,467 HFRS cases were reported in Hubei Province between 1980 and 2009. Incidence of and mortality due to HFRS declined after the outbreak in 1980s and HFRS cases have been sporadic in recent years. The locations and scale of disease clusters have changed during the three decades. The seasonal epidemic pattern of HFRS was characterized by the shift from the unimodal type (autumn/winter peak) to the bimodal type. Conclusions Socioeconomic development has great influence on the transmission of hantaviruses to humans and new epidemic characteristics have emerged in Hubei Province. It is necessary to reinforce preventative measures against HFRS according to the newly-presented seasonal variation and to intensify these efforts especially in the urban areas of Hubei Province. PMID:24658382

  2. 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.

  3. 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

  4. RIG-I Mediates an Antiviral Response to Crimean-Congo Hemorrhagic Fever Virus

    PubMed Central

    Spengler, Jessica R.; Patel, Jenish R.; Chakrabarti, Ayan K.; Zivcec, Marko; García-Sastre, Adolfo; Spiropoulou, Christina F.

    2015-01-01

    ABSTRACT In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA genomes of several RNA viruses. RIG-I binds to viral RNA, eliciting an antiviral response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever virus (CCHFV), a negative-sense RNA virus with a 5′-monophosphorylated genome, is a highly pathogenic zoonotic agent with significant public health implications. We found that, during CCHFV infection, RIG-I mediated a type I interferon (IFN) response via MAVS. Interfering with RIG-I signaling reduced IFN production and IFN-stimulated gene expression and increased viral replication. Immunostimulatory RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG-I coimmunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV RNA. This report serves as the first description of a pattern recognition receptor for CCHFV and highlights a critical signaling pathway in the antiviral response to CCHFV. IMPORTANCE CCHFV is a tick-borne virus with a significant public health impact. In order for cells to respond to virus infection, they must recognize the virus as foreign and initiate antiviral signaling. To date, the receptors involved in immune recognition of CCHFV are not known. Here, we investigate and identify RIG-I as a receptor involved in initiating an antiviral response to CCHFV. This receptor initially was not expected to play a role in CCHFV recognition because of characteristics of the viral genome. These findings are important in understanding the antiviral response to CCHFV and support continued investigation into the spectrum of potential viruses recognized by RIG-I. PMID:26223644

  5. Development and characterization of a mouse model for Marburg hemorrhagic fever.

    PubMed

    Warfield, Kelly L; Bradfute, Steven B; Wells, Jay; Lofts, Loreen; Cooper, Meagan T; Alves, D Anthony; Reed, Daniel K; VanTongeren, Sean A; Mech, Christine A; Bavari, Sina

    2009-07-01

    The lack of a mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV), and has created a bottleneck in the development of antiviral therapeutics. Primary isolates of the filoviruses, i.e., ebolavirus (EBOV) and MARV, are not lethal to immunocompetent adult mice. Previously, pathological, virologic, and immunologic evaluation of a mouse-adapted EBOV, developed by sequential passages in suckling mice, identified many similarities between this model and EBOV infections in nonhuman primates. We recently demonstrated that serially passaging virus recovered from the liver homogenates of MARV-infected immunodeficient (SCID) mice was highly successful in reducing the time to death in these mice from 50 to 70 days to 7 to 10 days after challenge with the isolate MARV-Ci67, -Musoke, or -Ravn. In this study, we extended our findings to show that further sequential passages of MARV-Ravn in immunocompetent mice caused the MARV to kill BALB/c mice. Serial sampling studies to characterize the pathology of mouse-adapted MARV-Ravn revealed that this model is similar to the guinea pig and nonhuman primate MHF models. Infection of BALB/c mice with mouse-adapted MARV-Ravn caused uncontrolled viremia and high viral titers in the liver, spleen, lymph node, and other organs; profound lymphopenia; destruction of lymphocytes within the spleen and lymph nodes; and marked liver damage and thrombocytopenia. Sequencing the mouse-adapted MARV-Ravn strain revealed differences in 16 predicted amino acids from the progenitor virus, although the exact changes required for adaptation are unclear at this time. This mouse-adapted MARV strain can now be used to develop and evaluate novel vaccines and therapeutics and may also help to provide a better understanding of the virulence factors associated with MARV.

  6. Decreases in dengue transmission may act to increase the incidence of dengue hemorrhagic fever.

    PubMed

    Nagao, Yoshiro; Koelle, Katia

    2008-02-12

    Dengue hemorrhagic fever (DHF) is a potentially fatal manifestation of an infection with the mosquito-borne dengue virus. Because of the social and economic costs of DHF, many countries in Asia and South America have initiated public health measures aimed at vector control. Despite these measures, DHF incidence rates do not appear to be declining. The effectiveness of vector control in reducing dengue transmissibility has thereby been questioned. Here, we revisit this conclusion using epidemiological data from Thailand. We first show, with age incidence data, that dengue transmission rates have fallen since 1981; surprisingly, however, these declines are not associated with decreases in DHF incidence. Instead, district-level analyses indicate a nonmonotonic relationship between the basic reproductive number R0 and DHF incidence. To understand this relationship, we formulated three mathematical models, which differ in their assumptions of transient between-serotype cross-protection. Unlike the first two models, the previously unconsidered third model with clinical cross-protection can reproduce this nonmonotonic relationship. Simulation of this model with nonstationary R0 reproduces several previously unexplained patterns of dengue dynamics, including a transition from a approximately 2-year cycle to a approximately 4-year cycle and a transient trough in DHF incidence in provinces with rapid R0 declines. These results imply that DHF incidence can be effectively controlled with a sufficiently large reduction in R0 but that moderate reductions may be counterproductive. More broadly, these results show that assuming parameter stationarity in systems with approximate stationarity in disease incidence is unjustified and may result in missed opportunities to understand the drivers of disease variability.

  7. 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.

  8. 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

    2012-10-12

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

  9. Development and evaluation of loop-mediated isothermal amplification assay for detection of Crimean Congo hemorrhagic fever virus in Sudan.

    PubMed

    Osman, Hana A M; Eltom, Kamal H; Musa, Nasreen O; Bilal, Nasreldin M; Elbashir, Mustafa I; Aradaib, Imadeldin E

    2013-06-01

    Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) activity has been detected in Kordufan region of the Sudan in 2008 with high case-fatality rates in villages and rural hospitals in the region. Therefore, in the present study, a reverse transcription (RT) loop-mediated isothermal amplification (RT-LAMP) assay was developed and compared to nested RT-PCR for rapid detection of CCHFV targeting the small (S) RNA segment. A set of RT-LAMP primers, designed from a highly conserved region of the S segment of the viral genome, was employed to identify all the Sudanese CCHFV strains. The sensitivity studies indicated that the RT-LAMP detected 10fg of CCHFV RNA as determined by naked eye turbidity read out, which is more likely the way it would be read in a resource-poor setting. This level of sensitivity is good enough to detect most acute cases. Using agarose gel electrophoresis, the RT-LAMP assay detected as little as 0.1fg of viral RNA (equivalent to 50 viral particle). There was 100% agreement between results of the RT-LAMP and the nested PCR when testing 10-fold serial dilution of CCHFV RNA. The specificity studies indicated that there was no cross-reactivity with other related hemorrhagic fever viruses circulating in Sudan including, Rift Valley fever virus (RVFV), Dengue fever virus, and yellow fever virus. The RT-LAMP was performed under isothermal conditions at 63°C and no special apparatus was needed, which rendered the assay more economical and practical than real-time PCR in such developing countries, like Sudan. In addition, the RT-LAMP provides a valuable tool for rapid detection and differentiation of CCHFV during an outbreak of the disease in remote areas and in rural hospitals with resource-poor settings.

  10. 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

  11. Dengue in Greece in 1927 and 1928 and the pathogenesis of dengue hemorrhagic fever: new data and a different conclusion.

    PubMed

    Rosen, L

    1986-05-01

    A massive outbreak of dengue, with a high incidence of hemorrhagic manifestations and a high death rate, occurred in Athens and neighboring areas of Greece in 1927 and 1928. For many years it was believed that the episode had been caused by dengue type 1 virus. Recently, it was claimed that dengue type 2 virus also was present in Athens in 1928, and this report is cited in support of the hypotheses that dengue hemorrhagic fever is almost always the result of sequential infection with different dengue serotypes and that infection with dengue type 2 following dengue type 1 is particularly pathogenic. In the present study of 258 Greek residents born from 1914 to 1938, it was also found that dengue type 2 had occurred in Greece--but after 1928. No evidence was found that that virus had occurred in the country during, or within 13 years before, the 1927-1928 epidemic.

  12. Probable Crimean-Congo hemorrhagic fever virus transmission occurred after aerosol-generating medical procedures in Russia: nosocomial cluster.

    PubMed

    Pshenichnaya, Natalia Yurievna; Nenadskaya, Svetlana Alexeevna

    2015-04-01

    We report here a fatal case of laboratory confirmed Crimean-Congo hemorrhagic fever (CCHF), which caused nosocomial infection in eight health care workers (HCWs), who had provided medical care for the patient. All the HCWs survived. The report demonstrates that airborne transmission of CCHF is a real risk, at least when the CCHF patient is in a ventilator. During performance of any aerosol-generating medical procedures for any CCHF patient airborne precautions should always be added to standard precautions, in particular, airway protective N95 mask or equivalent standard, eye protection, single airborne precaution room, or a well-ventilated setting. PMID:25576827

  13. 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.

  14. Can Serum Ferritin Level Predict Disease Severity in Patients with Crimean-Congo Hemorrhagic Fever?

    PubMed Central

    Metanat, Maliheh; Sharifi-Mood, Batool; Tabatabaei, Mehdi; Sarraf-Shirazi, Mohammad

    2013-01-01

    Objective: Crimean-Congo hemorrhagic fever (CCHF) is an acute viral disease. Several factors have already been suggested to explain the pathogenesis as well as predict the disease severity. In our study we aim to investigate the role of serum ferritin level as a possible predicting factor of disease severity in these patients. Materials and Methods: We evaluated all patients with laboratory confirmed diagnosis of CCHF who were admitted to Boo-Ali Hospital of Zahedan from May 2011 to June 2012. Confirmation of the disease determined using the presence of anti- CCHFV IgM in the serum by enzyme-linked immunosorbent assay (ELISA) or by polymerase chain reaction(PCR). After ethical approval, patients were categorized into two groups of mild and severe disease according to disseminated intravascular coagulation (DIC) severity using the scoring system of International Society on Thrombosis and Hemostasis (ISTH). Serum ferritin levels were evaluated and compared between these two groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the optimal cutoff value of serum ferritin for predicting the disease severity. Results: A total of 42 patients (36 men, 6 women, age range: 17–78 years) were included in this study, of whom 38% had Persian and 62% had Baloch ethnicity. According to DIC severity score, 54.7% of the patients had severe disease and 45.3% had mild disease. The area under the ROC curve was 0.896 and 95% CI was 0.801–0.991 (p<0.0001). A cut-off point of 1060 ng/dL, had a sensitivity of 78.9%, a specificity of 87%, a positive predictive value of 6% and a negative predictive value of 100%. Positive and negative likelihood ratios for this serum ferritin level were 6.05 and 0.24, respectively. Conclusion: Increased serum ferritin level has a significant positive correlation with disease severity in patients with CCHF and can evaluate the prognosis of these patients with a high sensitivity and specificity. PMID:25610262

  15. 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.

  16. 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

  17. [First case of dengue hemorrhagic fever with shock syndrome in Martinique].

    PubMed

    Mansuy, J M; Delor, R; Mehdaoui, H; Elizabeth, L

    1996-01-01

    Since mid 95, many Caribbean islands and America's countries suffer from a new outbreak of an epidemic of dengue fever and dengue haemorrhagic fever. Until today, no case of dengue haemorrhagic fever was reported in Martinique (FWI) in spite of the high prevalence of dengue fever in the island. The first identified case asserts the severity of illness. In Martinique, these arbovirosis is often underestimated. Nowadays, the disease prevention must become one of the principal targets of the medical corporation and the Public Health Authorities. Consequently, epidemiologic survey and principally vector's control must be reinforced.

  18. High Genetic Diversity and Adaptive Potential of Two Simian Hemorrhagic Fever Viruses in a Wild Primate Population

    PubMed Central

    Weiler, Andrea; Sibley, Samuel D.; Dinis, Jorge M.; Bergman, Zachary; Nelson, Chase W.; Correll, Michael; Gleicher, Michael; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Chapman, Colin; Kuhn, Jens H.; Hughes, Austin L.; Friedrich, Thomas C.; Goldberg, Tony L.; O'Connor, David H.

    2014-01-01

    Key biological properties such as high genetic diversity and high evolutionary rate enhance the potential of certain RNA viruses to adapt and emerge. Identifying viruses with these properties in their natural hosts could dramatically improve disease forecasting and surveillance. Recently, we discovered two novel members of the viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 and SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. Nearly nothing is known about the biological properties of SHFVs in nature, although the SHFV type strain, SHFV-LVR, has caused devastating outbreaks of viral hemorrhagic fever in captive macaques. Here we detected SHFV-krc1 and SHFV-krc2 in 40% and 47% of 60 wild red colobus tested, respectively. We found viral loads in excess of 106–107 RNA copies per milliliter of blood plasma for each of these viruses. SHFV-krc1 and SHFV-krc2 also showed high genetic diversity at both the inter- and intra-host levels. Analyses of synonymous and non-synonymous nucleotide diversity across viral genomes revealed patterns suggestive of positive selection in SHFV open reading frames (ORF) 5 (SHFV-krc2 only) and 7 (SHFV-krc1 and SHFV-krc2). Thus, these viruses share several important properties with some of the most rapidly evolving, emergent RNA viruses. PMID:24651479

  19. 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.

  20. Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model▿ †

    PubMed Central

    Bente, Dennis A.; Alimonti, Judie B.; Shieh, Wun-Ju; Camus, Gaëlle; Ströher, Ute; Zaki, Sherif; Jones, Steven M.

    2010-01-01

    Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic syndrome in humans but not in its vertebrate animal hosts. The pathogenesis of the disease is largely not understood due to the lack of an animal model. Laboratory animals typically show no overt signs of disease. Here, we describe a new small-animal model to study CCHFV pathogenesis that manifests clinical disease, similar to that seen in humans, without adaptation of the virus to the host. Our studies revealed that mice deficient in the STAT-1 signaling molecule were highly susceptible to infection, succumbing within 3 to 5 days. After CCHFV challenge, mice exhibited fever, leukopenia, thrombocytopenia, and highly elevated liver enzymes. Rapid viremic dissemination and extensive replication in visceral organs, mainly in liver and spleen, were associated with prominent histopathologic changes in these organs. Dramatically elevated proinflammatory cytokine levels were detected in the blood of the animals, suggestive of a cytokine storm. Immunologic analysis revealed delayed immune cell activation and intensive lymphocyte depletion. Furthermore, this study also demonstrated that ribavirin, a suggested treatment in human cases, protects mice from lethal CCHFV challenge. In conclusion, our data demonstrate that the interferon response is crucial in controlling CCHFV replication in this model, and this is the first study that offers an in-depth in vivo analysis of CCHFV pathophysiology. This new mouse model exhibits key features of fatal human CCHF, proves useful for the testing of therapeutic strategies, and can be used to study virus attenuation. PMID:20739514

  1. High genetic diversity and adaptive potential of two simian hemorrhagic fever viruses in a wild primate population.

    PubMed

    Bailey, Adam L; Lauck, Michael; Weiler, Andrea; Sibley, Samuel D; Dinis, Jorge M; Bergman, Zachary; Nelson, Chase W; Correll, Michael; Gleicher, Michael; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Chapman, Colin; Kuhn, Jens H; Hughes, Austin L; Friedrich, Thomas C; Goldberg, Tony L; O'Connor, David H

    2014-01-01

    Key biological properties such as high genetic diversity and high evolutionary rate enhance the potential of certain RNA viruses to adapt and emerge. Identifying viruses with these properties in their natural hosts could dramatically improve disease forecasting and surveillance. Recently, we discovered two novel members of the viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 and SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. Nearly nothing is known about the biological properties of SHFVs in nature, although the SHFV type strain, SHFV-LVR, has caused devastating outbreaks of viral hemorrhagic fever in captive macaques. Here we detected SHFV-krc1 and SHFV-krc2 in 40% and 47% of 60 wild red colobus tested, respectively. We found viral loads in excess of 10(6)-10(7) RNA copies per milliliter of blood plasma for each of these viruses. SHFV-krc1 and SHFV-krc2 also showed high genetic diversity at both the inter- and intra-host levels. Analyses of synonymous and non-synonymous nucleotide diversity across viral genomes revealed patterns suggestive of positive selection in SHFV open reading frames (ORF) 5 (SHFV-krc2 only) and 7 (SHFV-krc1 and SHFV-krc2). Thus, these viruses share several important properties with some of the most rapidly evolving, emergent RNA viruses.

  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.

  3. A clinical study of the patients with dengue hemorrhagic fever during the epidemic of 1996 at Lucknow, India.

    PubMed

    Agarwal, R; Kapoor, S; Nagar, R; Misra, A; Tandon, R; Mathur, A; Misra, A K; Srivastava, K L; Chaturvedi, U C

    1999-12-01

    This paper describes the clinical findings in 206 patients with dengue fever (DF) or with dengue hemorrhagic fever (DHF) during the epidemic of 1996 at Lucknow. The age group affected most was 11 to 30 years and 21% of the patients were less than 10 years old. The male:female ratio was 1.9:1. The onset was abrupt in all the patients, severe frontal headache was observed in 97%, myalgia in 90%, skin rash in 40%, vomiting in 29% and arthralgia in knee and hip joints in 9%. Anuria was seen in two patients. Lymphadenopathy was noted in 14%, hepatomegaly in 4%, being associated with mild jaundice in one patient, and splenomegaly in 2% of the patients. Involvement of the heart and lungs was seen in one patient each and no case with encephalitis was recorded. Hemorrhages from various sites were observed in 54% patients and 17 patients had profound shock. The commonest bleeding site was gums. Profound shock was preceded by various warning signs, the commonest being sudden hypotension. Among the patients with profound shock the mortality was 47% while the overall fatality rate was 3.8%. A number of the risk factors existed for a long time in this part of the world, but what precipitated the present epidemic at this time, is not known.

  4. Novel molecular beacon probe-based real-time RT-PCR assay for diagnosis of Crimean-Congo hemorrhagic fever encountered in India.

    PubMed

    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.

  5. Clinical manifestations of dengue hemorrhagic fever in Puerto Rico, 1990-1991. Puerto Rico Association of Epidemiologists.

    PubMed

    Rigau-Pérez, J G

    1997-05-01

    The aim of the study reported here was to demonstrate that dengue hemorrhagic fever occurs in Puerto Rico, that it is underreported, and that this underreporting is due partly to underdiagnosis in hospitals. Surveillance for severe dengue identified 986 hospitalizations for suspected dengue in 1990-1991. At the time, on the basis of available clinical and laboratory data, the surveillance system routinely identified 20 DHF cases, including three with dengue shock syndrome (DSS). Our subsequent review of these 986 patients' hospital records identified 102 whose records supported a clinical diagnosis of DHF (88) or DSS (14). Of the 102, there were 57 with positive virologic or serologic results for dengue and that met the World Health Organization criteria for DHF (fever, hemorrhagic manifestations, thrombocytopenia, and excessive capillary permeability). This group of 57 patients had a mean age of 38 years, contained a preponderance of males (34, 59.3%), included eight cases of DSS, and involved two (3.5%) fatalities (in females 16 and 55 years old). Hemorrhagic manifestations were mild; hemoconcentration, hypoalbuminemia, and elevated aspartate and alanine aminotransferase (AST and ALT) levels were frequently encountered. The median duration of hospitalization was five days. The clinical description of these laboratory-positive DHF cases in Puerto Rico is consistent with previous descriptions of DHF in the medical literature; but the patients' age distribution is similar to the pattern typically found in the Americas (where all age groups tend to be affected), as opposed to Southeast Asia (where mostly younger children are affected). The number of DHF cases identified by our study was nearly three times that reported through the established surveillance system. Our findings indicate that recognition and reporting of DHF by local clinicians needs to be improved.

  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. A program for prevention and control of epidemic dengue and dengue hemorrhagic fever in Puerto Rico and the U.S. Virgin Islands.

    PubMed

    Gubler, D J; Casta-Valez, A

    1991-01-01

    The ongoing resurgence of Aedes aegypti in the Americas--abetted by poor mosquito control, urbanization, and increased air travel--has led to dengue hyperendemicity, more frequent dengue epidemics, and the emergence of dengue hemorrhagic fever (DHF). This article describes a program developed to cope with this situation that emphasizes disease prevention rather than general mosquito control measures.

  8. 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

  9. Prothrombin time and partial thromboplastin time as a predictor of bleeding in patients with dengue hemorrhagic fever.

    PubMed

    Chua, M N; Molanida, R; de Guzman, M; Laberiza, F

    1993-01-01

    Eighty-nine pediatric patients admitted at the University of Santo Tomas Hospital from June to December 1992, with the clinical diagnosis of dengue hemorrhagic fever (DHF) were studied with the following objectives: To determine the possible use of hematocrit, platelet count, prothrombin time (PT) and partial thromboplastin time (PTT) as predictors of bleeding and outcome in patient with DHF. The following were established: PTT can be an index in predicting bleeding in DHF. The tendency to bleed is greater with prolongation of > 30 seconds; platelet count can be a predictor of mortality, with death six times greater among those platelet count < 50,000/microliters than those whose platelet count was > 50,000/microliters. PT can also predict bleeding in patients with DHF.

  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. Field investigations of an outbreak of Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: arthropod studies.

    PubMed

    Reiter, P; Turell, M; Coleman, R; Miller, B; Maupin, G; Liz, J; Kuehne, A; Barth, J; Geisbert, J; Dohm, D; Glick, J; Pecor, J; Robbins, R; Jahrling, P; Peters, C; Ksiazek, T

    1999-02-01

    During the final weeks of a 6-month epidemic of Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo, an extensive collection of arthropods was made in an attempt to learn more of the natural history of the disease. A reconstruction of the activities of the likely primary case, a 42-year-old man who lived in the city, indicated that he probably acquired his infection in a partly forested area 15 km from his home. Collections were made throughout this area, along the route he followed from the city, and at various sites in the city itself. No Ebola virus was isolated, but a description of the collections and the ecotopes involved is given for comparison with future studies of other outbreaks.

  12. Dengue hemorrhagic fever in Jakarta, Indonesia in 1988: isolation of dengue virus from patient whole blood using cell cultures.

    PubMed

    Fujita, N; Hotta, S; Konishi, E; Esaki, H; Sumarmo; Sujudi

    1997-03-01

    During an outbreak of dengue hemorrhagic fever (DHF) in Jakarta, Indonesia in 1988, we attempted to isolate dengue virus using mosquito cells and a medium containing heparin. Whole blood, immediately after being drawn from patients, was inoculated into Aedes albopictus cell cultures temporarily maintained in the heparin-containing medium. The overall virus isolation rate was 25% (17 of 69) samples collected within three days after admission of the patients to hospital. No virus was obtained thereafter. The successful virus isolation was apparently not related to titers of anti-dengue virus hemagglutination-inhibiting antibodies present in patients' sera. The viruses were recovered from cases of each of the four World Health Organization grades of DHF without significant differences. The technique is simple and easily performed at bedside.

  13. Acute myocarditis in dengue hemorrhagic fever: a case report and review of cardiac complications in dengue-affected patients.

    PubMed

    Lee, Ing-Kit; Lee, Wen-Huei; Liu, Jien-Wei; Yang, Kuender D

    2010-10-01

    We report a case of dengue hemorrhagic fever (DHF) complicated by acute myocarditis and review the literature. A 65-year-old woman experienced DHF due to dengue virus serotype 3, complicated with acute myocarditis and acute pulmonary edema. Clinically this masqueraded as acute myocardial infarction, with an electrocardiographically depressed ST segment in precordial leads and elevated serum cardiac-specific troponin I level. Under supportive management, the patient recovered 3 days later. A total of 18 pertinent articles involving 339 dengue-affected patients with cardiac complications were found by PubMed search. Clinical manifestations of cardiac complications varied considerably, from self-limiting tachy-brady arrhythmia to severe myocardial damage, leading to hypotension and pulmonary edema. Although rare, a fatal outcome was reported in some cases of dengue with cardiac complications. To avoid otherwise preventable morbidity and mortality, physicians should have a high index of suspicion for cardiac complications in patients with dengue illness and should manage this accordingly.

  14. Application of an autoregressive integrated moving average model for predicting the incidence of hemorrhagic fever with renal syndrome.

    PubMed

    Li, Qi; Guo, Na-Na; Han, Zhan-Ying; Zhang, Yan-Bo; Qi, Shun-Xiang; Xu, Yong-Gang; Wei, Ya-Mei; Han, Xu; Liu, Ying-Ying

    2012-08-01

    The Box-Jenkins approach was used to fit an autoregressive integrated moving average (ARIMA) model to the incidence of hemorrhagic fever with renal Syndrome (HFRS) in China during 1986-2009. The ARIMA (0, 1, 1) × (2, 1, 0)(12) models fitted exactly with the number of cases during January 1986-December 2009. The fitted model was then used to predict HFRS incidence during 2010, and the number of cases during January-December 2010 fell within the model's confidence interval for the predicted number of cases in 2010. This finding suggests that the ARIMA model fits the fluctuations in HFRS frequency and it can be used for future forecasting when applied to HFRS prevention and control. PMID:22855772

  15. Validation of probability equation and decision tree in predicting subsequent dengue hemorrhagic fever in adult dengue inpatients in Singapore.

    PubMed

    Thein, Tun L; Leo, Yee-Sin; Lee, Vernon J; Sun, Yan; Lye, David C

    2011-11-01

    We developed a probability equation and a decision tree from 1,973 predominantly dengue serotype 1 hospitalized adult dengue patients in 2004 to predict progression to dengue hemorrhagic fever (DHF), applied in our clinic since March 2007. The parameters predicting DHF were clinical bleeding, high serum urea, low serum protein, and low lymphocyte proportion. This study validated these in a predominantly dengue serotype 2 cohort in 2007. The 1,017 adult dengue patients admitted to Tan Tock Seng Hospital, Singapore had a median age of 35 years. Of 933 patients without DHF on admission, 131 progressed to DHF. The probability equation predicted DHF with a sensitivity (Sn) of 94%, specificity (Sp) 17%, positive predictive value (PPV) 16%, and negative predictive value (NPV) 94%. The decision tree predicted DHF with a Sn of 99%, Sp 12%, PPV 16%, and NPV 99%. Both tools performed well despite a switch in predominant dengue serotypes.

  16. A Virus-Like Particle System Identifies the Endonuclease Domain of Crimean-Congo Hemorrhagic Fever Virus

    PubMed Central

    Devignot, Stephanie; Bergeron, Eric; Nichol, Stuart; Mirazimi, Ali

    2015-01-01

    ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV; genus Nairovirus) is an extremely pathogenic member of the Bunyaviridae family. Since handling of the virus requires a biosafety level 4 (BSL-4) facility, little is known about pathomechanisms and host interactions. Here, we describe the establishment of a transcriptionally competent virus-like particle (tc-VLP) system for CCHFV. Recombinant polymerase (L), nucleocapsid protein (N) and a reporter minigenome expressed in human HuH-7 cells resulted in formation of transcriptionally active nucleocapsids that could be packaged by coexpressed CCHFV glycoproteins into tc-VLPs. The tc-VLPs resembled authentic virus particles in their protein composition and neutralization sensitivity to anti-CCHFV antibodies and could recapitulate all steps of the viral replication cycle. Particle attachment, entry, and primary transcription were modeled by infection of naive cells. The subsequent steps of genome replication, secondary transcription, and particle assembly and release can be obtained upon passaging the tc-VLPs on cells expressing CCHFV structural proteins. The utility of the VLP system was demonstrated by showing that the endonuclease domain of L is located around amino acid D693, as was predicted in silico by B. Morin et al. (PLoS Pathog 6:e1001038, 2010, http://dx.doi.org/10.1371/journal.ppat.1001038). The tc-VLP system will greatly facilitate studies and diagnostics of CCHFV under non-BSL-4 conditions. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is an extremely virulent pathogen of humans. Since the virus can be handled only at the highest biosafety level, research is restricted to a few specialized laboratories. We developed a plasmid-based system to produce virus-like particles with the ability to infect cells and transcribe a reporter genome. Due to the absence of viral genes, the virus-like particles are unable to spread or cause disease, thus allowing study of aspects of CCHFV biology under relaxed

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

    PubMed

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

    2015-05-01

    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

  18. 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 ...

  19. Crimean-Congo hemorrhagic fever nosocomial infection in a immunosuppressed patient, Pakistan: case report and virological investigation.

    PubMed

    Hasan, Zahra; Mahmood, Faisal; Jamil, Bushra; Atkinson, Barry; Mohammed, Murtaza; Samreen, Azra; Altaf, Lamia; Moatter, Tariq; Hewson, Roger

    2013-03-01

    Crimean-Congo hemorrhagic fever (CCHF) is endemic in the Baluchistan province, Pakistan. Sporadic outbreaks of CCHF occur throughout the year especially in individuals in contact with infected livestock. Nosocomial transmission remains a risk due to difficulties in the diagnosis of CCHF and limited availability of facilities for the isolation of suspected patients. Rapid diagnosis of CCHF virus infection is required for early management of the disease and to prevent transmission. This study describes the case of a 43-year-old surgeon who contracted CCHF during a surgical procedure in Quetta, Baluchistan and who was transferred to a tertiary care facility at the Aga Khan University Hospital, Karachi within 1 week of contracting the infection. Diagnosis of CCHF was made using a rapid real-time reverse transcription polymerase chain reaction (RT-PCR) assay for CCHF viral RNA. The patient had chronic hepatitis B and hepatitis D infection for which he had previously received a liver transplant. He proceeded to develop classic hemorrhagic manifestations and succumbed to the infection 14 days post-onset of disease. There was no further nosocomial transmission of the CCHF during the hospital treatment of the surgeon. Early diagnosis of CCHF enables rapid engagement of appropriate isolation, barrier nursing and infection control measures thus preventing nosocomial transmission of the virus.

  20. Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia.

    PubMed

    Porter, Kevin R; Beckett, Charmagne G; Kosasih, Herman; Tan, Ratna Irsiana; Alisjahbana, Bachti; Rudiman, Pandji Irani Fianza; Widjaja, Susana; Listiyaningsih, Erlin; Ma'Roef, Chairin Nisa; McArdle, James L; Parwati, Ida; Sudjana, Primal; Jusuf, Hadi; Yuwono, Djoko; Wuryadi, Suharyono

    2005-01-01

    A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.

  1. Can hematocrit and platelet determination on admission predict shock in hospitalized children with dengue hemorrhagic fever? A clinical observation from a small outbreak.

    PubMed

    Wiwanitkit, Viroj; Manusvanich, Pornake

    2004-01-01

    Dengue infection is a major public health problem, affecting children in the Southeast Asia region. In Thailand, the dengue hemorrhagic fever is still a major infectious disease among the children with up to two to three epidemics per year. Hemoconcentration accompanied by platelet depletion are the predominant laboratory signs of dengue hemorrhagic fever. Findings from 23 hospitalized patients with dengue hemorrhafic fever in a small outbreak in a provincial hospital in Thailand are reported. The question if hematocrit and platelet determination on admission can predict shock in hospitalized children with dengue hemorrhagic fever was studied. The data from the discharge summary of these patients were studied, focusing on the admission hematology laboratory data. Regression analysis was used to test the correlation between the admission hematology laboratory data (hematocrit, white blood cell count, and platelet) and the focused outcome (shock or no shock). Of these 23 patients, shock did not develop in 19, and shock developed in four. There was no significant difference in admission hematology laboratory data between both groups (p < 0.05). The regression analysis revealed no significant correlation between the studied hematology laboratory data and the focused outcome (p > 0.05). It means that the three studied investigations on admission cannot predict shock in our hospitalized dengue hemorrhagic cases. From this study, it can imply that closed monitoring of dengue hemorrhagic patients is necessary. The general practitioner cannot rely on the admission hematology laboratory data to predict shock in these patients. Additionally, it might confirm that, although dengue infection can be fatal, with proper supportive treatment, especially hospitalization and hydration for severe cases, the outcome is very good.

  2. 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 ...

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

    PubMed Central

    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

  4. 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).

  5. The defined antigen substrate sphere system with direct immunohistoperoxidase for detection of soluble dengue antigen in sera of patients with dengue hemorrhagic fever.

    PubMed

    Boonpucknavig, S; Bunnag, C; Vuttiviroj, O; Nimmannitya, S

    1978-09-01

    The defined antigen substrate sphere system is a simple method for detecting antigen or antibody in the circulation. The technic is based on the coupling of antigen or antibody with Sepharose 4B beads that have been activated by cyanogen bromide. In this study the activated beads were exposed to dengue antigen in the serum from a patient with dengue hemorrhagic fever and then stained with antidengue antibody conjugated with horseradish peroxidase. The positive reaction showed brown beads by light microscopy, whereas the negative reaction gave colorless beads. The authors examined 134 specimens from 91 cases. The results were positive in 53.85%. The dengue antigen appeared in the sera on the day before shock or subsidence of fever. The percentages of sera containing soluble dengue antigen were greatest on the day of shock or subsidence of fever (33.33%) and on the fifth day of fever (28.07%). The highest titers of soluble dengue antigen (1:40 to 1:80) appeared in the sera of patients who had Grade III disease on the day of shock. The dengue antigen appeared most often in sera that had high titers of dengue antibody. It is postulated that this detected dengue antigen may be a part of soluble immune complexes formed during the hyperimmune stage of the immune response, and plays a significant role in the pathogenesis of dengue hemorrhagic fever and shock syndrome.

  6. 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

  7. Relationship between body size and severity of dengue hemorrhagic fever among children aged 0-14 years.

    PubMed

    Pichainarong, Natchaporn; Mongkalangoon, Noparat; Kalayanarooj, Siripen; Chaveepojnkamjorn, Wisit

    2006-03-01

    A hospital based case-control study was conducted from October 2002 to November 2003 among children aged 0-14 years at Queen Sirikit National Institute of Child Health (Children's Hospital), Bangkok, Thailand. This study focused on body size and severity of dengue hemorrhagic fever (DHF) in children. One hundred five patients diagnosed as having DHF grade III or IV were the cases and 105 diagnosed as having DHF grade I or II were controls. They were matched at a ratio of 1:1 by their gender and age (within 5 years). Normal growth charts were used to differentiate child body size into normal, thin and obese. Data were collected using face to face interviews with caregivers, questionnaires, laboratory and physical examination reports as research tools. Multiple logistic regression analysis revealed that only two variables were related to severity of DHF: obesity (OR = 3.00, 95 % CI = 1.20-7.48) and dengue virus type II (OR = 4.94, 95 % CI = 2.57-9.47), respectively. Other variables were childhood factors: duration of breast-feeding, education, and parity; caregivers factors: age, gender, marital status, education, occupation, family income, knowledge of DHF, antipyretic type, treatment before hospitalization, and duration of fever; environmental factors: history of DHF patients in house, house pattern, time from house to hospital, and residence; and etiological factors: type of infection and history of DHF among children. These factors showed no significant association (p > 0.05). This result can be utilized in a preventive and control program, particularly in more aggressive management of overweight children. Health personnel should continue to provide health education, particularly, signs and symptoms of shock, to the community and private sectors. Government and Non-Government Protective Projects in primary schools (5-9 years children) should be continued in the high risk groups.

  8. Alternate hypothesis on the pathogenesis of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in dengue virus infection.

    PubMed

    Noisakran, Sansanee; Perng, Guey Chuen

    2008-04-01

    Dengue fever, caused by infection with dengue virus, is not a new disease, but recently because of its serious emerging health threats, coupled with possible dire consequences including death, it has aroused considerable medical and public health concerns worldwide. Today, dengue is considered one of the most important arthropod-borne viral diseases in humans in terms of morbidity and mortality. Globally, it is estimated that approximate 50 to 100 million new dengue virus infections occur annually. Among these, there are 200,000 to 500,000 cases of potential life-threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), characterized by thrombocytopenia and increased vascular permeability. The death rate associated with the more severe form DHF/DSS is approximately 5%, predominantly in children under the age of 15. Although intensive efforts have been made to study the early clinical pathophysiology of dengue infection with the objective to identify the potential cause of DHF, results or data that have accumulated from different regions of the world involving studies of different ethnicity groups are inconsistent at present in terms of identifying a unified hypothesis for the pathogenesis of DHF/DSS. Thus, the potential mechanisms involved in the pathogenesis of DHF and DSS remain elusive. The purpose of this review is to identify alternate factors, such as innate immune parameters, hyper-thermal factors, conditioning of neutralizing antibody, concept of vector transmission, and physical status of virus in viremic patients that may play a role in the induction of DHF and DSS, which might have directly or indirectly contributed to the discrepancies that are noted in the literature reported to date. It is the hope that identification of an alternative explanation for the pathogenesis of DHF/DSS will pave the way for the institution of new strategies for the prevention of this complicated disease.

  9. Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome.

    PubMed

    Wills, Bridget A; Oragui, Emmanuelle E; Stephens, Alick C; Daramola, Olufunmilayo A; Dung, Nguyen Minh; Loan, Ha Thi; Chau, Nguyen Vinh; Chambers, Mary; Stepniewska, Kasia; Farrar, Jeremy J; Levin, Michael

    2002-08-01

    The pathophysiological basis of hemorrhage in dengue infections remains poorly understood, despite the increasing global importance of these infections. A large prospective study of 167 Vietnamese children with dengue shock syndrome documented only minor prolongations of prothrombin and partial thromboplastin times but moderate to severe depression of plasma fibrinogen concentrations. A detailed study of 48 children revealed low plasma concentrations of the anticoagulant proteins C, S, and antithrombin III, which decreased with increasing severity of shock, probably because of capillary leakage. Concurrent increases in the levels of thrombomodulin, tissue factor, and plasminogen activator inhibitor type 1 (PAI-1) indicated increased production of these proteins. Thrombomodulin levels suggestive of endothelial activation correlated with increasing shock severity, whereas PAI-1 levels correlated with bleeding severity. Dengue virus can directly activate plasminogen in vitro. Rather than causing true disseminated intravascular coagulation, dengue infection may activate fibrinolysis primarily, degrading fibrinogen directly and prompting secondary activation of procoagulant homeostatic mechanisms.

  10. Long-term disease surveillance in Bandundu region, Democratic Republic of the Congo: a model for early detection and prevention of Ebola hemorrhagic fever.

    PubMed

    Lloyd, E S; Zaki, S R; Rollin, P E; Tshioko, K; Bwaka, M A; Ksiazek, T G; Calain, P; Shieh, W J; Kondé, M K; Verchueren, E; Perry, H N; Manguindula, L; Kabwau, J; Ndambi, R; Peters, C J

    1999-02-01

    After the large-scale outbreak of Ebola hemorrhagic fever (EHF) in Bandundu region, Democratic Republic of the Congo, a program was developed to help detect and prevent future outbreaks of EHF in the region. The long-term surveillance and prevention strategy is based on early recognition by physicians, immediate initiation of enhanced barrier-nursing practices, and the use of an immunohistochemical diagnostic test performed on formalin-fixed skin specimens of patients who die of suspected viral hemorrhagic fever. The program was implemented in September 1995 during a 4-day workshop with 28 local physicians representing 17 of 22 health zones in the region. Specimen collection kits were distributed to clinics in participating health zones, and a follow-up evaluation was conducted after 6 months. The use of a formalin-fixed skin specimen for laboratory confirmation of EHF can provide an appropriate method for EHF surveillance when linked with physician training, use of viral hemorrhagic fever isolation precautions, and follow-up investigation. PMID:9988195

  11. MINIGENOMES, TRANSCRIPTION AND REPLICATION COMPETENT VIRUS-LIKE PARTICLES AND BEYOND: REVERSE GENETICS SYSTEMS FOR FILOVIRUSES AND OTHER NEGATIVE STRANDED HEMORRHAGIC FEVER VIRUSES

    PubMed Central

    Hoenen, Thomas; Groseth, Allison; de Kok-Mercado, Fabian; Kuhn, Jens H.; Wahl-Jensen, Victoria

    2012-01-01

    Reverse-genetics systems are powerful tools enabling researchers to study the replication cycle of RNA viruses, including filoviruses and other hemorrhagic fever viruses, as well as to discover new antivirals. They include full-length clone systems as well as a number of life cycle modeling systems. Full-length clone systems allow for the generation of infectious, recombinant viruses, and thus are an important tool for studying the virus replication cycle in its entirety. In contrast, life cycle modeling systems such as minigenome and transcription and replication competent virus-like particle systems can be used to simulate and dissect parts of the virus life cycle outside of containment facilities. Minigenome systems are used to model viral genome replication and transcription, whereas transcription and replication competent virus-like particle systems also model morphogenesis and budding as well as infection of target cells. As such, these modeling systems have tremendous potential to further the discovery and screening of new antivirals targeting hemorrhagic fever viruses. This review provides an overview of currently established reverse genetics systems for hemorrhagic fever-causing negative-sense RNA viruses, with a particular emphasis on filoviruses, and the potential application of these systems for antiviral research. PMID:21699921

  12. 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

  13. 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

  14. Transstadial Transmission and Long-term Association of Crimean-Congo Hemorrhagic Fever Virus in Ticks Shapes Genome Plasticity

    PubMed Central

    Xia, Han; Beck, Andrew S.; Gargili, Aysen; Forrester, Naomi; Barrett, Alan D. T.; Bente, Dennis A.

    2016-01-01

    The trade-off hypothesis, the current paradigm of arbovirus evolution, proposes that cycling between vertebrate and invertebrate hosts presents significant constraints on genetic change of arboviruses. Studying these constraints in mosquito-borne viruses has led to a new understanding of epizootics. The trade-off hypothesis is assumed to be applicable to tick-borne viruses too, although studies are lacking. Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the family Bunyaviridae, is a major cause of severe human disease worldwide and shows an extraordinary amount of genetic diversity compared to other arboviruses, which has been linked to increased virulence and emergence in new environments. Using a transmission model for CCHFV, utilizing the main vector tick species and mice plus next generation sequencing, we detected a substantial number of consensus-level mutations in CCHFV recovered from ticks after only a single transstadial transmission, whereas none were detected in CCHFV obtained from the mammalian host. Furthermore, greater viral intra-host diversity was detected in the tick compared to the vertebrate host. Long-term association of CCHFV with its tick host for 1 year demonstrated mutations in the viral genome become fixed over time. These findings suggest that the trade-off hypothesis may not be accurate for all arboviruses. PMID:27775001

  15. Mechanism of preferential packaging of negative sense genomic RNA by viral nucleoproteins in Crimean-Congo hemorrhagic Fever virus.

    PubMed

    Dayer, Mohammad Reza; Dayer, Mohammad Saaid; Rezatofighi, Seyedeh Elham

    2015-04-01

    The Crimean-Congo Hemorrhagic Fever (CCHF) is an infectious disease of high virulence and mortality caused by a negative sense RNA nairovirus. The genomic RNA of CCHFV is enwrapped by its nucleoprotein. Positively charged residues on CCHFV nucleoprotein provide multiple binding sites to facilitate genomic RNA encapsidation. In the present work, we investigated the mechanism underlying preferential packaging of the negative sense genomic RNA by CCHFV nucleoprotein in the presence of host cell RNAs during viral assembly. The work included genome sequence analyses for different families of negative and positive sense RNA viruses, using serial docking experiments and molecular dynamic simulations. Our results indicated that the main determinant parameter of the nucleoprotein binding affinity for negative sense RNA is the ratio of purine/pyrimidine in the RNA molecule. A negative sense RNA with a purine/pyrimidine ratio (>1) higher than that of a positive sense RNA (<1) exhibits higher affinity for the nucleoprotein. Our calculations revealed that a negative sense RNA expresses about 0.5 kJ/mol higher binding energy per nucleotide compared to a positive sense RNA. This energy difference produces a binding energy high enough to make the negative sense RNA, the preferred substrate for packaging by CCHFV nucleoprotein in the presence of cellular or complementary positive sense RNAs. The outcome of this study may contribute to ongoing researches on other viral diseases caused by negative sense RNA viruses such as Ebola virus which poses a security threat to all humanity.

  16. Evaluation of Prognostic Values of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Crimean-Congo Hemorrhagic Fever Patients

    PubMed Central

    Gurbuz, Yunus; Ozturk, Baris; Tutuncu, Emin Ediz; Sencan, Irfan; Cicek Senturk, Gonul; Altay, Fatma Aybala

    2015-01-01

    Background: Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease in Turkey, and was responsible for many deaths in endemic regions during the last decade. The pathogenesis of the disease is not fully understood yet. Objectives: In this study we aimed to determine the levels of tissue plasminogen activator (tPA) and Plasminogen activator inhibitor-1 (PAI-1) as predictors of prognosis in CCHF. Patients and Methods: Patients who were diagnosed by the polymerase chain reaction (PCR) and IgM positivity in the reference laboratory were included in this study. Tissue Plasminogen activator and PAI-1 levels were measured by the enzyme linked immunosorbent assay (ELISA) using a commercial kit (human t-PA ELISA and human PAL-1 ELISA; BioVendor research and diagnostic products, BioVendor-Laboratorni medicina a.s., Brno, Czech Republic). Results: A total of 46 patients participated in this study. The significant differences between recovering patients and the patients who died, regarding Aspartate aminotransferase (AST), Creatine Phosphokinase (CPK), Lactate Dehydrogenase (LDH), Prothrombin Time (PT), activated Partial Thromboplastin time (aPTT), and thrombocyte and fibrinogen levels, were consistent with many clinical studies in the literature. The fatal cases were found to have higher tPA and PAI-1 levels in contrast to the patients who completely recovered. Conclusions: We think that these findings may help the progress of understanding of CCHF pathogenesis. PMID:26587219

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

    PubMed Central

    Wu, Wei; Guo, Junqiao; An, Shuyi; Guan, Peng; Ren, Yangwu; Xia, Linzi; Zhou, Baosen

    2015-01-01

    Background Cases of hemorrhagic fever with renal syndrome (HFRS) are widely distributed in eastern Asia, especially in China, Russia, and Korea. It is proved to be a difficult task to eliminate HFRS completely because of the diverse animal reservoirs and effects of global warming. Reliable forecasting is useful for the prevention and control of HFRS. Methods Two hybrid models, one composed of nonlinear autoregressive neural network (NARNN) and autoregressive integrated moving average (ARIMA) the other composed of generalized regression neural network (GRNN) and ARIMA were constructed to predict the incidence of HFRS in the future one year. Performances of the two hybrid models were compared with ARIMA model. Results The ARIMA, ARIMA-NARNN ARIMA-GRNN model fitted and predicted the seasonal fluctuation well. Among the three models, the mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of ARIMA-NARNN hybrid model was the lowest both in modeling stage and forecasting stage. As for the ARIMA-GRNN hybrid model, the MSE, MAE and MAPE of modeling performance and the MSE and MAE of forecasting performance were less than the ARIMA model, but the MAPE of forecasting performance did not improve. Conclusion Developing and applying the ARIMA-NARNN hybrid model is an effective method to make us better understand the epidemic characteristics of HFRS and could be helpful to the prevention and control of HFRS. PMID:26270814

  18. Modeling and Predicting Hemorrhagic Fever with Renal Syndrome Trends Based on Meteorological Factors in Hu County, China

    PubMed Central

    Le, Jing; Li, Haitao; Yan, Yongping; Xu, Zhikai

    2015-01-01

    Background Hu County is a serious hemorrhagic fever with renal syndrome (HFRS) epidemic area, with notable fluctuation of the HFRS epidemic in recent years. This study aimed to explore the optimal model for HFRS epidemic prediction in Hu. Methods Three models were constructed and compared, including a generalized linear model (GLM), a generalized additive model (GAM), and a principal components regression model (PCRM). The fitting and predictive adjusted R2 of each model were calculated. Ljung-Box Q tests for fitted and predicted residuals of each model were conducted. The study period was stratified into before (1971–1993) and after (1994–2012) vaccine implementation epochs to avoid the confounding factor of vaccination. Results The autocorrelation of fitted and predicted residuals of the GAM in the two epochs were not significant (Ljung-Box Q test, P>.05). The adjusted R2 for the predictive abilities of the GLM, GAM, and PCRM were 0.752, 0.799, and 0.665 in the early epoch, and 0.669, 0.756, and 0.574 in the recent epoch. The adjusted R2 values of the three models were lower in the early epoch than in the recent epoch. Conclusions GAM is superior to GLM and PCRM for monthly HFRS case number prediction in Hu County. A shift in model reliability coincident with vaccination implementation demonstrates the importance of vaccination in HFRS control and prevention. PMID:25875211

  19. Discovery Proteomics And Nonparametric Modeling Pipeline In The Development Of A Candidate Biomarker Panel For Dengue Hemorrhagic Fever

    PubMed Central

    Brasier, Allan R; Garcia, Josefina; Wiktorowicz, John E.; Spratt, Heidi M.; Comach, Guillermo; Ju, Hyunsu; Recinos, Adrian; Soman, Kizhake; Forshey, Brett M.; Halsey, Eric S.; Blair, Patrick J.; Rocha, Claudio; Bazan, Isabel; Victor, Sundar S; Wu, Zheng; Stafford, Susan; Watts, Douglas; Morrison, Amy C.; Scott, Thomas W.; Kochel, Tadeusz J.

    2013-01-01

    Secondary Dengue viral infection can produce capillary leakage associated with increased mortality known as Dengue Hemorrhagic Fever (DHF). Because the mortality of DHF can be reduced by early detection and intensive support, improved methods for its detection are needed. We applied multidimensional protein profiling to predict outcomes in a prospective Dengue surveillance study in South America. Plasma samples taken from initial clinical presentation of acute Dengue infection were subjected to proteomics analyses using ELISA and a recently developed biofluid analysis platform. Demographics, clinical laboratory measurements, 9 cytokines and 419 plasma proteins collected at the time of initial presentation were compared between the DF and DHF outcomes. Here, the subject’s gender, clinical parameters, 2 cytokines and 42 proteins discriminated between the outcomes. These factors were reduced by multivariate adaptive regression splines (MARS) that a highly accurate classification model based on 8 discriminant features with an AUC of 0.999. Model analysis indicated that the feature-outcome relationship were non-linear. Although this DHF risk model will need validation in a larger cohort, we conclude that approaches to develop predictive biomarker models for disease outcome will need to incorporate nonparametric modeling approaches. PMID:22376251

  20. Development of a real-time RT-PCR assay for the detection of Crimean-Congo hemorrhagic fever virus.

    PubMed

    Atkinson, Barry; Chamberlain, John; Logue, Christopher H; Cook, Nicola; Bruce, Christine; Dowall, Stuart D; Hewson, Roger

    2012-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is a virulent tick-borne disease with a case fatality rate ranging from 10-50% for tick-borne transmission, and up to 80% for nosocomial transmission. Human cases have been reported in over 30 countries across Europe, Asia, and Africa. It appears to be spreading to new areas with several countries reporting their first human cases of CCHF disease within the past 10 years. We report a novel real-time RT-PCR assay designed to amplify a conserved region of the CCHF virus S segment. It is capable of detecting strains from all 7 groups of CCHF, including the AP92 strain that until recently represented a lineage of strains that were not associated with human disease. The limit of detection of the assay is 5 copies of target RNA, and the assay shows no cross-reactivity with other viruses from within the same genus, or with viruses causing similar human disease.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

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

    PubMed

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

    2014-01-01

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

  7. Discovery proteomics and nonparametric modeling pipeline in the development of a candidate biomarker panel for dengue hemorrhagic fever.

    PubMed

    Brasier, Allan R; Garcia, Josefina; Wiktorowicz, John E; Spratt, Heidi M; Comach, Guillermo; Ju, Hyunsu; Recinos, Adrian; Soman, Kizhake; Forshey, Brett M; Halsey, Eric S; Blair, Patrick J; Rocha, Claudio; Bazan, Isabel; Victor, Sundar S; Wu, Zheng; Stafford, Susan; Watts, Douglas; Morrison, Amy C; Scott, Thomas W; Kochel, Tadeusz J

    2012-02-01

    Secondary dengue viral infection can produce capillary leakage associated with increased mortality known as dengue hemorrhagic fever (DHF). Because the mortality of DHF can be reduced by early detection and intensive support, improved methods for its detection are needed. We applied multidimensional protein profiling to predict outcomes in a prospective dengue surveillance study in South America. Plasma samples taken from initial clinical presentation of acute dengue infection were subjected to proteomics analyses using ELISA and a recently developed biofluid analysis platform. Demographics, clinical laboratory measurements, nine cytokines, and 419 plasma proteins collected at the time of initial presentation were compared between the DF and DHF outcomes. Here, the subject's gender, clinical parameters, two cytokines, and 42 proteins discriminated between the outcomes. These factors were reduced by multivariate adaptive regression splines (MARS) that a highly accurate classification model based on eight discriminant features with an area under the receiver operator curve (AUC) of 0.999. Model analysis indicated that the feature-outcome relationship were nonlinear. Although this DHF risk model will need validation in a larger cohort, we conclude that approaches to develop predictive biomarker models for disease outcome will need to incorporate nonparametric modeling approaches.

  8. A survey of knowledge, attitude and practice of the prevention of dengue hemorrhagic fever in an urban community of Thailand.

    PubMed

    Swaddiwudhipong, W; Lerdlukanavonge, P; Khumklam, P; Koonchote, S; Nguntra, P; Chaovakiratipong, C

    1992-06-01

    To evaluate the effect of a health education program on the prevention and control of dengue hemorrhagic fever (DHF) in the municipality of Mae Sot, Tak Province, a survey of adult residents, mainly housewives, was conducted in late April 1990 to assess their knowledge of DHF and practice of preventive methods. A total of 417 respondents from 417 households selected by a systematic-cluster sampling method were interviewed. More than 90% of them knew that the disease is transmitted by Aedes mosquitos and indicated water jars and water retention in the houses as the common breeding places. However, the other two common breeding places, ant-traps and cement baths, were less frequently mentioned. This finding was consistent with the greater proportion of respondents who reported no larval control methods for these two kinds of containers than for the others. Covering water containers was the most common practice to prevent mosquito breeding in drinking-water containers whereas addition of abate (temephos sand granules) or changing stored water frequently was commonly used for non-drinking water storage. Larval control for ant-traps was mainly accomplished by the addition of chemicals, including abate, salt, oil or detergent. Health education efforts in this area could induce the majority of respondents to accept themselves as responsible for the Aedes control program. Health education by health personnel played an important role in disseminating DHF information and prevention methods. Radio and television were the main effective mass media for public health education on DHF in this area.

  9. 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.

  10. Clinical characteristics, risk factors, and outcomes in adults experiencing dengue hemorrhagic fever complicated with acute renal failure.

    PubMed

    Lee, Ing-Kit; Liu, Jien-Wei; Yang, Kuender D

    2009-04-01

    In a retrospective study, acute renal failure (ARF) was found in 10 (3.3%) among 304 hospitalized adults with dengue hemorrhagic fever (DHF), and 6 (60%) of the 10 patients with ARF died, whereas all 294 patients without ARF (controls) survived (P < 0.001). Compared with the controls, DHF patients with ARF were found to be significantly older (P = 0.002) and male predominant (P < 0.001) and to have higher frequency of previous stroke (P = 0.005), chronic renal insufficiency (P = 0.046), dengue shock syndrome (DSS; P < 0.001), gastrointestinal bleeding (P < 0.001), and concurrent bacteremia (P = 0.009), lower hemoglobin (P = 0.003) and serum albumin levels (P = 0.003), and higher incidences of prolonged prothrombin time (P < 0.001), elevated aspartate aminotransferase (P < 0.001), and alanine aminotransferase levels (P < 0.001). Multivariate analysis showed DSS (odd ratio = 220.0; P < 0.001) was an independent risk factor for development of ARF in DHF patients. The high fatality rate in DHF patients complicated with ARF in our series underscore the importance of clinicians' alertness to this potentially fatal complication so that initiation of timely appropriate treatment is possible.

  11. Antibody-capture ELISA for detection of immunoglobulin M antibodies in sera from Japanese encephalitis and dengue hemorrhagic fever patients.

    PubMed

    Bundo, K; Igarashi, A

    1985-05-01

    Immunoglobulin M (IgM) antibody titers in paired sera from 19 encephalitis and 44 dengue hemorrhagic fever (DHF) patients in Thailand and 42 Japanese encephalitis (JE) patients in Japan were measured by the antibody capture ELISA and applied to distinguish JE virus infection from dengue virus infection. Titer distribution and the ratio of the titers against JE and dengue antigens led to the following diagnostic criteria. The specimens can be considered as positive with JE when IgM-ELISA titer showed over 200 against JE and 4-fold or more higher than titers against any types of dengue antigens. The specimens can be considered as positive with dengue infection when IgM ELISA titer showed over 200 against one of the 4 types of dengue antigens and 4-fold or more higher than against JE antigen. Based on these criteria, 41 of 42 patients in Japan and 11 of 19 encephalitis patients in Thailand could be diagnosed as having JE virus infection while 2 of 19 encephalitis patients in Thailand and 26 of 44 DHF patients in Thailand could be diagnosed as having dengue virus infections.

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

    PubMed

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

    2014-05-01

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

  13. Low Adiposity during Early Infancy Is Associated with a Low Risk for Developing Dengue Hemorrhagic Fever: A Preliminary Model

    PubMed Central

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

    2014-01-01

    Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection. PMID:24533162

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

    PubMed

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

    2014-01-01

    Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection. PMID:24533162

  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. Effect of red blood cell glucose-6-phosphate dehydrogenase deficiency on patients with dengue hemorrhagic fever.

    PubMed

    Tanphaichitr, Voravarn S; Chonlasin, Rachaneekorn; Suwantol, Lerlugsn; Pung-Amritt, Parichat; Tachavanich, Kalaya; Yogsan, Suthee; Viprakasit, Vip

    2002-08-01

    Eighty nine males aged 1-13 years diagnosed with dengue haemorrhagic fever (DHF) and admitted to the Department of Pediatrics Siriraj Hospital from March 1998 to April 2000 were included in this study. 17 cases (19.1%) had red blood cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and 72 cases (80.9%) had normal G-6-PD enzyme activities. Most of the patients were classified as DHF grade II in severity. 3 of 17 G-6-PD deficient cases had serious complications and all of them had acute intravascular hemolysis requiring blood transfusions. One of these also had hematemesis, one had azothemia and the other one had renal failure and severe liver failure with hepatic encephalopathy. In the cases without obvious hemolytic or hepatic complications, G-6-PD deficient cases had mildly but significantly higher total birirubin and indirect bilirubin, as well as a lower hematocrit than those who had normal G-6-PD. Reticulocyte count was low during the acute phase, however, during recovery, the levels were significantly increased in both groups. In the non G-6-PD deficient group, G-6-PD enzyme levels were significantly decreased during the acute phase compared to the normal controls but rose significantly to normal levels during the recovery phase. There were no statistically significant differences in other laboratory data. All patients recovered fully from DHF. The prevalence of G-6-PD deficiency in male patients who had DHF in this study was 19.1 per cent which was higher than the prevalence in a previous study of 12 per cent in Bangkok. This may imply that G-6-PD deficient males suffer more from DHF compared to normal G-6-PD subjects.

  17. 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

  18. 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

  19. 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

  20. 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

  1. Effect of health education on community participation in control of dengue hemorrhagic fever in an urban area of Thailand.

    PubMed

    Swaddiwudhipong, W; Chaovakiratipong, C; Nguntra, P; Koonchote, S; Khumklam, P; Lerdlukanavonge, P

    1992-06-01

    Dengue hemorrhagic fever (DHF), a disease transmitted by Aedes mosquitos, remains a serious public health problem in Thailand. This paper describes the effect of health education efforts on a community-based DHF vector control program in the municipality of Mae Sot District, Tak Province, northern Thailand, from 1988 through 1990. In 1988, public health education on DHF and larval control through mass media, lectures and discussions reduced the Aedes Breteau index from 241 in March to 126 in June 1988. In 1989 and 1990, twice a year house-to-house visits by trained health workers were added to the health education campaigns. Aedes larval indices were decreased far more in the epidemic year of 1990 than in 1989. During this 3-year period, water-storage containers for drinking, washing, bathing and ant-traps were the primary sources of larval habitats, accounting for about 90% of the total breeding places. Reduction of Aedes larvae in these sources was due to various larval control measures. By August 1990 water containers for non-drinking purposes were the remaining important breeding places. The introduction of larvivorous fish may be an effective method of larval control for these containers. Most houses were supplied by public piped water system; however, a shortage of piped water for a period of time resulted in a significant increase in the number of water containers. An adequate water supply to the community should be provided continuously to prevent creation of new breeding places. Modifying behavioral practices to reduce domestic man-made water containers should be encouraged.

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

    PubMed Central

    McCluskey, Adam; Robinson, Phillip J.; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L.; Lauck, Michael; Friedrich, Thomas C.; Goldberg, Tony L.

    2014-01-01

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

  3. A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease

    PubMed Central

    Dowall, SD; Buttigieg, KR; Findlay-Wilson, SJD; Rayner, E; Pearson, G; Miloszewska, A; Graham, VA; Carroll, MW; Hewson, R

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal with no approved vaccine available. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus nucleoprotein. Cellular and humoral immunogenicity was confirmed in 2 mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. Despite the immune responses generated post-immunisation, the vaccine failed to protect animals from lethal disease in a challenge model. PMID:26309231

  4. Analysis of repeat hospital admissions for dengue to estimate the frequency of third or fourth dengue infections resulting in admissions and dengue hemorrhagic fever, and serotype sequences.

    PubMed

    Gibbons, Robert V; Kalanarooj, Siripen; Jarman, Richard G; Nisalak, Ananda; Vaughn, David W; Endy, Timothy P; Mammen, Mammen P; Srikiatkhachorn, Anon

    2007-11-01

    Immunity to a single dengue virus (DENV) infection does not provide heterologous immunity to subsequent infection. In fact, the greatest risk for dengue hemorrhagic fever (DHF) is with a second DENV serotype exposure. The risk for DHF with a third or fourth dengue infection relative to a first or second exposure is not known. An analysis of our database of children admitted to the Queen Sirikit National Institute of Child Health and Kamphaeng Phet Provincial Hospital with suspected dengue illness revealed that the number of dengue admissions caused by a third or fourth DENV infection was extremely low (0.08-0.8%). Once admitted, the risk for DHF relative to dengue fever was not different for those experiencing third or fourth DENV infections over those experiencing a second DENV infection. We document new dengue serotype infection sequences leading to DHF of 1-4, 2-3, 3-1, and 3-4.

  5. The effect of a unique propolis compound (Propoelix™) on clinical outcomes in patients with dengue hemorrhagic fever

    PubMed Central

    Soroy, Lardo; Bagus, Sulistyo; Yongkie, Iswandi Purnama; Djoko, Wibisono

    2014-01-01

    Background Dengue fever is a mosquito-borne virus belonging to the family Flaviviridae. It is an old virus that has re-emerged globally over the past 20 years and now causes a global burden of 50 million infections per year across approximately 100 countries. Despite this, there is no safe vaccine available, and therapy is largely supportive. Its pathogenesis is multifaceted and currently still poorly understood, leading to a lack of disease-specific therapy. Propolis is a natural antiviral and anti-inflammatory product derived from the saps of plants and mixed with the saliva of honeybees. Propoelix™ is a uniquely potent and water-soluble extract of propolis containing high concentrations of anti-inflammatory compounds like caffeic acid phenethyl ester. Objective The primary objective is to determine the effectiveness of a unique propolis extract (Propoelix™) on the clinical course of patients with dengue hemorrhagic fever (DHF). The secondary objective is to examine the effect of Propoelix™ on tumor necrosis factor-α (TNF-α) levels in patients with DHF. Methods A double-blind, randomized, placebo-controlled trial was conducted at the Department of Internal Medicine, Gatot Soebroto Central Army Hospital in Jakarta, Indonesia, from May 2012 to July 2013. Sixty-three patients who met the inclusion criteria were enrolled in the trial. Patients were randomized to receive either two capsules of Propoelix™ 200 mg three times a day or placebo daily for 7 days. Clinical and laboratory variables of both groups, including the anti-inflammatory marker TNF-α, were investigated. Patients were deemed technically fit for discharge if their platelet counts had recovered and exceeded 100,000/μL but were all observed as inpatients for 7 days. Results There were 31 patients in the Propoelix™ treatment group and 32 patients in the placebo group. Platelet counts in the Propoelix™-treated group showed a trend toward a faster recovery by day 3 of admission and became

  6. 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 ...

  7. 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.

  8. 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

  9. Characterization of monoclonal antibodies to Junin virus nucleocapsid protein and application to the diagnosis of hemorrhagic fever caused by South American arenaviruses.

    PubMed

    Nakauchi, Mina; Fukushi, Shuetsu; Saijo, Masayuki; Mizutani, Tetsuya; Ure, Agustín E; Romanowski, Victor; Kurane, Ichiro; Morikawa, Shigeru

    2009-08-01

    Junin virus (JUNV), Machupo virus, Guanarito virus, Sabia virus, and Chapare virus are members of New World arenavirus clade B and are the etiological agents of viral hemorrhagic fevers that occur in South America. In this study, we produced three monoclonal antibodies (MAbs) to the recombinant nucleocapsid protein of JUNV, designated C6-9, C11-12, and E4-2. The specificity of these MAbs was examined by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay, and an epitope-mapping method. Using these MAbs, we developed antigen (Ag) capture ELISA systems. We showed that by using MAb C6-9, JUNV Ag was specifically detected. On the other hand, by using MAb C11-12 or E-4-2, the Ags of all human pathogenic South American arenaviruses were detected. The combined use of these Ag capture ELISA systems in the present study may be useful for the diagnosis of acute-phase viral hemorrhagic fever due to infection by a South American arenavirus.

  10. [Genetic relatedness of the dengue 3 virus isolated in the outbreak of dengue hemorrhagic fever in Nicaragua, 1994].

    PubMed

    Guzmán, M G; Rosario, D; Muné, M; Alvarez, M; Rodríguez, R; Kourí, G

    1996-01-01

    It is reported the isolation of 2 dengue strains, 3 in samples from Nicaraguan patients suffering from dengue with hemorrhagic manifestations, which showed the reintroduction of this serotype in the region after being 17 years out of circulation. It is also reported the genetic characterization of the isolated strain, which, according to its classification, belongs to the group of dengue 2 strains isolated in Southeast Asi and which have been associated to hemorrhagic dengue. These results suggest the origin of this strain.

  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. Epidemiology of dengue/dengue hemorrhagic fever in Malaysia--a retrospective epidemiological study. 1973-1987. Part II: Dengue fever (DF).

    PubMed

    Shekhar, K C; Huat, O L

    Dengue fever (DF) has been endemic in Malaysia since 1902 and reached epidemic proportions in 1973. The incidence rate of the disease in 1973 was 5.4 cases per 100,000 and reached 10.4 cases per 100,000 in 1987. The Chinese are the main ethnic community affected showing an overall morbidity rate of 9.0 cases per 100,000 followed by Malays 2.9 cases per 100,000 and Indians 2.4 cases per 100,000. The ethnic race ratio between Chinese, Malays and Indians which was 3.7:1:1.3 in 1975 reached 3.7:1:0.9 in 1987. The attack rates were observed to be higher in the males. The mean male:female ratio among Chinese was 1.1:1, while for Malays and Indians it was 1.5:1. The age-specific morbidity rate was highest in the 10- to 19-year age group followed by the 20- to 29-year age group. Epidemics of dengue fever were found to occur seasonally with the appearance of two peaks, viz. one in June and the other in August. Dengue fever, a rural disease before, has established itself as an urban disease.

  13. [Titration of the antibodies to the Crimean hemorrhagic fever virus in a drop of the cell suspension from infected tissue cultures by means of indirect immunofluorescence].

    PubMed

    Zgurskaia, G N; Chumakov, M P

    1977-01-01

    A comparatively simple method has been developed and tested for the detection and titration of antibody to Crimean hemorrhagic fever virus (CHF) by indirect immunofluorescence on slides with previously prepared acetone-inactivated virus in drops of cell suspension from infected BHK-21 and 6619 cell cultures. The antibody titers determined by the indirect immunofluorescence procedures were 4- and 8-fold higher than those determined by the complement-fixation test. This opens the possibility of using non-infectious antigens of cell suspensions for detection or titration by the FA procedure of antibody to CHF virus which may be of importance to diagnostic laboratories which have no conditions for work with live virus.

  14. 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.

  15. Dengue hemorrhagic Fever caused by sequential dengue 1-3 virus infections over a long time interval: Havana epidemic, 2001-2002.

    PubMed

    Alvarez, Mayling; Rodriguez-Roche, Rosmari; Bernardo, Lídice; Vázquez, Susana; Morier, Luis; Gonzalez, Daniel; Castro, Osvaldo; Kouri, Gustavo; Halstead, Scott B; Guzman, Maria G

    2006-12-01

    A dengue epidemic caused by dengue virus 3 (DENV-3) occurred in Cuba in 2001-2002. It included cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). We report neutralizing antibody studies on sera from 54 of 78 DHF/DSS patients that provide evidence of infections occurring in the sequence DENV-1 followed by DENV-3. No sera showed infection in the sequence DENV-2 followed by DENV-3. Some sera showed a pattern of infection in the sequence DENV-1 followed by DENV-2 and then DENV-3. However definitive categorization of a tertiary infection was not possible because of broadly reactive antibodies, which could have been raised by infections in the sequence DENV-1 then DENV-3.

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

    PubMed

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

    2008-03-01

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

  17. Using an Autoregressive Integrated Moving Average Model to Predict the Incidence of Hemorrhagic Fever with Renal Syndrome in Zibo, China, 2004-2014.

    PubMed

    Wang, Tao; Zhou, Yunping; Wang, Ling; Huang, Zhenshui; Cui, Feng; Zhai, Shenyong

    2016-07-22

    Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, where human cases account for 90% of the total global cases. Zibo City is one of the most seriously affected areas in Shandong Province, China. Therefore, there is an urgent need for monitoring and predicting HFRS incidence in Zibo to make the control of HFRS more effective. In this study, we constructed an autoregressive integrated moving average (ARIMA) model for monthly HFRS incidence in Zibo from 2004 to 2013. The ARIMA (3,1,1) × (2,1,1)12 model is reliable with a high validity, which can be used to predict the next year's HFRS incidence in Zibo. The forecast results suggest that the HFRS incidence in Zibo will experience a slight growth in the next year. PMID:26370428

  18. Site 1 protease is required for proteolytic processing of the glycoproteins of the South American hemorrhagic fever viruses Junin, Machupo, and Guanarito.

    PubMed

    Rojek, Jillian M; Lee, Andrew M; Nguyen, NgocThao; Spiropoulou, Christina F; Kunz, Stefan

    2008-06-01

    The cellular proprotein convertase site 1 protease (S1P) has been implicated in the proteolytic processing of the glycoproteins (GPs) of Old World arenaviruses. Here we report that S1P is also involved in the processing of the GPs of the genetically more-distant South American hemorrhagic fever viruses Guanarito, Machupo, and Junin. Efficient cleavage of Guanarito virus GP, whose protease recognition sites deviate from the reported S1P consensus sequence, indicates a broader specificity of S1P than anticipated. Lack of GP processing of Junin virus dramatically reduced production of infectious virus and prevented cell-to-cell propagation. Infection of S1P-deficient cells resulted in viral persistence over several weeks without the emergence of escape variants able to use other cellular proteases for GP processing.

  19. 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

  20. A two-tube multiplex real-time RT-PCR assay for the detection of four hemorrhagic fever viruses: severe fever with thrombocytopenia syndrome virus, Hantaan virus, Seoul virus, and dengue virus.

    PubMed

    Li, Zhifeng; Qi, Xian; Zhou, Minghao; Bao, Changjun; Hu, Jianli; Wu, Bin; Wang, Shenjiao; Tan, Zhongmin; Fu, Jianguang; Shan, Jun; Zhu, Yefei; Tang, Fenyang

    2013-09-01

    The aim of this study was to develop and evaluate a two-tube multiplex real-time RT-PCR assay for the detection and identification of four viral hemorrhagic fever (VHF) pathogens, severe fever with thrombocytopenia syndrome virus (SFTSV), Hantaan virus (HTNV), Seoul virus (SEOV), and dengue virus (DENV), from human clinical samples. The two-tube multiplex real-time RT-PCR assay we developed has a sensitivity of 10 copies/μL for each of the targets, and the performance was linear within the range of at least 10(7) transcript copies. Moreover, we evaluated the specificity of the assay using other virus RNA as template, and found no cross-reactivity. This new assay is able to detect SFTSV, HTNV, SEOV and DENV in two reactions and brings a cost of 40 % compared to separate reactions. Evaluation of this assay with clinical serum samples from laboratory-confirmed patients and healthy donors showed 100 % clinical diagnostic sensitivity and over 99 % specificity. The assay was applied for scanning 346 clinical samples collected from patients admitted to the hospital with suspected VHF and compared with virus isolation and immunofluorescence assay (IFA). The assay indentified 59 SFTSV-, 12 HTNV-, 11 SEOV- and 9 DENV-positive samples and showed higher sensitivity. This assay thus provides a reliable and cost-effective screening tool for early clinical diagnosis of SFTSV, HTNV, SEOV and DENV in the acute phase.

  1. Molecular analysis of Crimean-Congo hemorrhagic fever virus and Rickettsia in Hyalomma marginatum ticks removed from patients (Spain) and birds (Spain and Morocco), 2009-2015.

    PubMed

    Palomar, Ana M; Portillo, Aránzazu; Mazuelas, David; Roncero, Lidia; Arizaga, Juan; Crespo, Ariñe; Gutiérrez, Óscar; Márquez, Francisco J; Cuadrado, Juan F; Eiros, José M; Oteo, José A

    2016-07-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) was detected in Spain in 2010. The presence of CCHFV in Hyalomma marginatum ticks from migratory birds passing through Morocco during the spring migration strengthened the hypothesis of the arrival of infected ticks transported by birds to the Iberian Peninsula. Furthermore, Hyalomma species are vectors of bacterial infections such as spotted fever rickettsioses. CCHFV and Rickettsia were screened in Hyalomma ticks from Spain attached to patients (n=12) and birds (n=149). In addition, Rickettsia was investigated in 52 Hyalomma ticks from Morocco (previously reported as CCHFV-infected). No sample collected in Spain showed an infection with CCHFV. Two ticks removed from patients (16.7%), as well as 47 (31.5%) and 4 (7.7%) from birds, collected in Spain and Morocco respectively, were infected with Rickettsia aeschlimannii. Rickettsia sibirica subsp. mongolitimonae was also found in 2 ticks from birds collected in Spain (1.3%). The risk of CCHFV-infected ticks attached to migratory birds to reach the North of Spain is low. This study corroborates the presence of R. aeschlimannii in Spain and Morocco, and supports that H. marginatum can be a potential vector of R. sibirica subsp. mongolitimonae in the Iberian Peninsula.

  2. Primary sequence of the envelope glycoprotein of a dengue type 2 virus isolated from patient with dengue hemorrhagic fever and encephalopathy.

    PubMed

    Sistayanarain, A; Maneekarn, N; Polprasert, B; Sirisanthana, V; Makino, Y; Fukunaga, T; Sittisombut, N

    1996-06-01

    Dengue viruses exist in nature as a collection of highly similar but not identical members (quasispecies). In order to correlate the presence of viral quasispecies with rare occurrence of unusual clinical manifestations in dengue-infected individuals, a dengue type 2 virus was isolated from the peripheral blood of a 12-year-old boy who presented with fever, headache, drowsiness and tonic seizure of the left arm, and subsequently manifested symptoms and signs of dengue hemorrhagic fever. Analysis of the envelope glycoprotein sequence of the encephalopathy-associated virus and two other dengue type 2 viruses from the same epidemic season in Chiang Mai, Thailand revealed that all three viruses belonged to the subtype IIIa of the five-subtype phylogenetic nomenclature system for dengue type 2 virus. The encephalopathy-associated dengue virus was more divergent from the others and was characterized by an Ala-->Val substitution at the position 173 of the envelope glycoprotein. This substitution mapped to the central domain 1 which was not known to be involved directly in envelope-receptor interaction.

  3. 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

  4. 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...

  5. Comprehensive Multiplex One-Step Real-Time TaqMan qRT-PCR Assays for Detection and Quantification of Hemorrhagic Fever Viruses

    PubMed Central

    Li, Jiandong; Qu, Jing; He, Chengcheng; Zhang, Shuo; Li, Chuan; Zhang, Quanfu; Liang, Mifang; Li, Dexin

    2014-01-01

    Background Viral hemorrhagic fevers (VHFs) are a group of animal and human illnesses that are mostly caused by several distinct families of viruses including bunyaviruses, flaviviruses, filoviruses and arenaviruses. Although specific signs and symptoms vary by the type of VHF, initial signs and symptoms are very similar. Therefore rapid immunologic and molecular tools for differential diagnosis of hemorrhagic fever viruses (HFVs) are important for effective case management and control of the spread of VHFs. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay is one of the reliable and desirable methods for specific detection and quantification of virus load. Multiplex PCR assay has the potential to produce considerable savings in time and resources in the laboratory detection. Results Primers/probe sets were designed based on appropriate specific genes for each of 28 HFVs which nearly covered all the HFVs, and identified with good specificity and sensitivity using monoplex assays. Seven groups of multiplex one-step real-time qRT-PCR assays in a universal experimental system were then developed by combining all primers/probe sets into 4-plex reactions and evaluated with serial dilutions of synthesized viral RNAs. For all the multiplex assays, no cross-reactivity with other HFVs was observed, and the limits of detection were mainly between 45 and 150 copies/PCR. The reproducibility was satisfactory, since the coefficient of variation of Ct values were all less than 5% in each dilution of synthesized viral RNAs for both intra-assays and inter-assays. Evaluation of the method with available clinical serum samples collected from HFRS patients, SFTS patients and Dengue fever patients showed high sensitivity and specificity of the related multiplex assays on the clinical specimens. Conclusions Overall, the comprehensive multiplex one-step real-time qRT-PCR assays were established in this study, and proved to be specific, sensitive

  6. 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

  7. [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

  8. 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

  9. 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

  10. Treatment of late stage disease in a model of arenaviral hemorrhagic fever: T-705 efficacy and reduced toxicity suggests an alternative to ribavirin.

    PubMed

    Gowen, Brian B; Smee, Donald F; Wong, Min-Hui; Hall, Jeffery O; Jung, Kie-Hoon; Bailey, Kevin W; Stevens, John R; Furuta, Yousuke; Morrey, John D

    2008-01-01

    A growing number of arenaviruses are known to cause viral hemorrhagic fever (HF), a severe and life-threatening syndrome characterized by fever, malaise, and increased vascular permeability. Ribavirin, the only licensed antiviral indicated for the treatment of certain arenaviral HFs, has had mixed success and significant toxicity. Since severe arenaviral infections initially do not present with distinguishing symptoms and are difficult to clinically diagnose at early stages, it is of utmost importance to identify antiviral therapies effective at later stages of infection. We have previously reported that T-705, a substituted pyrazine derivative currently under development as an anti-influenza drug, is highly active in hamsters infected with Pichinde virus when the drug is administered orally early during the course of infection. Here we demonstrate that T-705 offers significant protection against this lethal arenaviral infection in hamsters when treatment is begun after the animals are ill and the day before the animals begin to succumb to disease. Importantly, this coincides with the time when peak viral loads are present in most organs and considerable tissue damage is evident. We also show that T-705 is as effective as, and less toxic than, ribavirin, as infected T-705-treated hamsters on average maintain their weight better and recover more rapidly than animals treated with ribavirin. Further, there was no added benefit to combination therapy with T-705 and ribavirin. Finally, pharmacokinetic data indicate that plasma T-705 levels following oral administration are markedly reduced during the latter stages of disease, and may contribute to the reduced efficacy seen when treatment is withheld until day 7 of infection. Our findings support further pre-clinical development of T-705 for the treatment of severe arenaviral infections.

  11. 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

  12. 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.

  13. 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

  14. Favorable outcomes for both mother and baby are possible in pregnant women with Crimean-Congo hemorrhagic fever disease: a case series and literature review.

    PubMed

    Gozel, Mustafa Gokhan; Elaldi, Nazif; Engin, Aynur; Akkar, Ozlem Bozoklu; Bolat, Fatih; Celik, Cem

    2014-01-01

    To assess the impact of Crimean-Congo hemorrhagic fever (CCHF) infection during pregnancy on maternal and fetal outcomes, we present the clinical and laboratory findings and outcomes of 5 pregnant women with CCHF infection as well as fetal outcomes. We also reviewed previously reported cases with CCHF infection in pregnant women. All pregnant women with CCHF infection who had been hospitalized between August 2007 and September 2011 were included. The gestational ages at the time of CCHF infection were 8, 18, 20, 21 and 32 weeks. CCHF infection was acquired during the 1st trimester in only 1 case and resulted in spontaneous abortion. The other 4 pregnant women completely recovered, all reached a healthy full-term gestation and 4 term babies were born. All infants had normal birth weight and were found to be healthy on their first examination and follow-up. In the literature concerning CCHF infection in pregnancy, 8 published articles including case reports or case series and 1 poster presentation including 1 case could be accessed. In conclusion, there is a risk of vertical transmission of CCHF infection, and infections acquired early in gestation had a poor prognosis for the fetus. PMID:24732981

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

    PubMed

    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

  16. Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines.

    PubMed

    Velasquez, Clara Vasquez; Roman, Arthur Dessi; Lan, Nguyen Thi Phuong; Huy, Nguyen Tien; Mercado, Edelwisa Segubre; Espino, Fe Esperanza; Perez, Ma Lucila M; Huong, Vu Thi Que; Thuy, Tran Thi; Tham, Vo Dinh; Nga, Cao Thi Phi; Ha, Tran Thi Ngoc; Bilar, Josie M; Bajaro, Jemimah Dawn P; Baello, Benilda Q; Kikuchi, Mihoko; Yasunami, Michio; Morita, Kouichi; Watanabe, Naohiro; Karbwang, Juntra; Hirayama, Kenji

    2015-05-01

    We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of shock suggesting a possible role of mast cells in dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles, which encode the Human Chymase and α- and β- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR=3.52, p<0.0001; OR=3.37, p<0.0001, respectively) and with DHF in Ho Chi Minh City (OR=2.54, p=0.0084). Also, a statistically significant association was observed when DHF and DSS were combined in Vinh Long (OR=1.5, p=0.034) and the Philippines (OR=2.36, p=0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR=1.5, p=0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection.

  17. Comparison of the effects of oral hydration and intravenous fluid replacement in adult patients with non-shock dengue hemorrhagic fever in Taiwan.

    PubMed

    Lee, Ing-Kit; Lee, Wen-Huei; Yang, Kuender D; Liu, Jien-Wei

    2010-08-01

    The level of plasma leakage is mild to moderate in patients with non-shock dengue hemorrhagic fever (DHF grade I and grade II), and the necessity of intravenous fluid replacement for these patients remains controversial. We conducted an observational study in adult patients (>18 years) with non-shock DHF admitted to a medical centre in southern Taiwan comparing the effects of oral hydration [group 1 (n=19); age (mean+/-SD) 54.6+/-15.5 years] and intravenous fluid replacement, with a volume of >40ml/kg/day in the first 72h of hospitalization [group 2 (n=30); age 55.9+/-11.6 years]. No significant difference was found in demographics, clinical manifestations, and mean peak level of hematocrit between the two groups. Patients in group 2 had a significantly longer hospital stay compared to those in group 1 (P=0.007), and there was a trend suggesting patients in group 2 were prone to develop pleural effusion and/or pulmonary edema. No difference was found in daily mean pulse pressure, mean hematocrit level, and mean platelet count between the groups for the duration of the 7 days in hospital. All 49 patients survived. Our data suggest that oral hydration may be as effective as intravenous fluid replacement for adults with non-shock DHF and this warrants investigation in a larger series of patients.

  18. Susceptibility to dengue hemorrhagic fever in vietnam: evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes.

    PubMed

    Loke, Hsin; Bethell, Delia; Phuong, Cao Xuan Thanh; Day, Nick; White, Nicholas; Farrar, Jeremy; Hill, Adrian

    2002-07-01

    Dengue is an increasingly important cause of morbidity and mortality in the tropics, with more than a billion people at risk each year. Immunologic enhancement is thought to contribute to disease pathogenesis. Only a very small proportion of infected individuals develop life-threatening dengue hemorrhagic fever (DHF). In a large case-control study with 400 DHF patients and 300 matched controls, we have assessed five polymorphic non-HLA host genetic factors that might influence susceptibility to DHF. The less frequent t allele of a variant at position 352 of the vitamin D receptor (VDR) gene was associated with resistance to severe dengue (P = 0.03). Homozygotes for the arginine variant at position 131 of the Fc gammaRIIA gene, who have less capacity to opsonize IgG2 antibodies, may also be protected from DHF (one-tailed P = 0.03). No associations were found with polymorphisms in the mannose binding lectin, interleukin-1 (IL-4), and IL-1 receptor antagonist genes. Further studies to confirm these associations are warranted.

  19. 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

  20. The effect of inflammatory cytokines and the level of vitamin D on prognosis in Crimean-Congo hemorrhagic fever

    PubMed Central

    Parlak, Emine; Ertürk, Ayşe; Çağ, Yasemin; Sebin, Engin; Gümüşdere, Musa

    2015-01-01

    Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne viral disease. Its pathogenesis basically involves endothelial damage. The aim of this study was to determine serum IL2, IL6, IL 10 and 25 OH Vitamin D levels in patients with CCHF and also to reveal their role in the clinical course and prognosis of the disease. Diagnosis of CCHF was confirmed using the positive polymerase chain reaction (PCR) test and/or positive IgM antibody by enzyme-linked immunosorbent assay (ELISA). Serum IL-2, IL-6, IL-10 and total 25 OH Vitamin D levels were also measured using ELISA. Eighty CCHF patients and 110 healthy controls were enrolled. IL2, IL6 and IL10 levels were significantly higher in the patient group. IL 6 and IL 10 levels were significantly higher in the fatal group. There was a positive correlation between Vitamin D and AST (r=0.402; P<0.001), and another positive correlation between IL-6 and CK (r=0.714; P<0.001). High IL6 and L10 levels are a significant indicator of fatality. Cytokines are only one of the factors responsible for mortality. We conclude that the pathogenesis of the disease can be better understood by elucidating the complicated cytokine network. PMID:26770432

  1. Computer-based comparison of structural features of envelope protein of Alkhurma hemorrhagic fever virus with the homologous proteins of two closest viruses.

    PubMed

    Mohabatkar, Hassan

    2011-06-01

    The aim of this study was prediction of epitopes and medically important structural properties of protein E of Alkhurma hemorrhagic fever virus (AHFV) and comparing these features with two closely relates viruses, i.e. Kyasanur Forest disease virus (KFDV) and Tick-borne encephalitis virus (TBEV) by bioinformatics tools. Prediction of evolutionary distance, localization, sequence of signal peptides, C, N O glycosylation sites, transmembrane helices (TMHs), cysteine bond positions and B cell and T cell epitopes of E proteins were performed. 2D-MH, Virus-PLoc, Signal-CF, EnsembleGly, MemBrain, DiANNA, BCPREDS and MHCPred servers were applied for the prediction. According to the results, the evolutionary distance of E protein of AHFV and two other viruses was almost equal. In all three proteins of study, residues 1-35 were predicted as signal sequences and one asparagine was predicted to be glycosylated. Results of prediction of transmembrane helices showed one TMH at position 444-467 and the other one at position 476-490. Twelve cysteines were potentially involved to form six disulfide bridges in the proteins. Four parts were predicted as B cell epitopes in E protein of AHFV. One epitope was conserved between three proteins of study. The only conserved major histocompatibility complex (MHC) binding epitope between three viruses was for DRB0401 allele. As there are not much experimental data available about AHFV, computer-aided study and comparison of E protein of this virus with two closely related flaviviruses can help in better understanding of medical properties of the virus.

  2. [Dengue fever in the Primorye Territory].

    PubMed

    Popov, A F; Simakova, A I; Kiriakov, V Iu; Petukhova, S A; Dadalova, O B; Sokotun, S A; Shapovalenko, A M

    2014-01-01

    Eighteen cases of dengue fever were imported to the Primorye Territory in 2012-2013. The cases were related to visits to Thailand, Indonesia, and Vietnam. Of the 18 patients, 17 and 1 had classic and hemorrhagic dengue fever, respectively.

  3. Hazara virus infection is lethal for adult type I interferon receptor-knockout mice and may act as a surrogate for infection with the human-pathogenic Crimean-Congo hemorrhagic fever virus.

    PubMed

    Dowall, Stuart D; Findlay-Wilson, Stephen; Rayner, Emma; Pearson, Geoff; Pickersgill, Janice; Rule, Antony; Merredew, Natasha; Smith, Hazel; Chamberlain, John; Hewson, Roger

    2012-03-01

    Hazara virus (HAZV) is closely related to the Crimean-Congo hemorrhagic fever virus (CCHFV). HAZV has not been reported to cause human disease; work with infectious material can be carried out at containment level (CL)-2. By contrast, CCHFV causes a haemorrhagic fever in humans and requires CL-4 facilities. A disease model of HAZV infection in mice deficient in the type I interferon receptor is reported in this study. Dose-response effects were seen with higher doses, resulting in a shorter time to death and earlier detection of viral loads in organs. The lowest dose of 10 p.f.u. was still lethal in over 50 % of the mice. Histopathological findings were identified in the liver, spleen and lymph nodes, with changes similar to a recent mouse model of CCHFV infection. The findings demonstrate that inoculation of mice with HAZV may act as a useful surrogate model for the testing of antiviral agents against CCHFV.

  4. Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever

    PubMed Central

    Neumann, Melanie; Bernreuther, Christian; Lehmann, Maria; Krasemann, Susanne; Wurr, Stephanie; Emmerich, Petra; de Lamballerie, Xavier; Ölschläger, Stephan; Günther, Stephan

    2014-01-01

    Background Mice lacking the type I interferon receptor (IFNAR−/− mice) reproduce relevant aspects of Crimean-Congo hemorrhagic fever (CCHF) in humans, including liver damage. We aimed at characterizing the liver pathology in CCHF virus-infected IFNAR−/− mice by immunohistochemistry and employed the model to evaluate the antiviral efficacy of ribavirin, arbidol, and T-705 against CCHF virus. Methodology/Principal Findings CCHF virus-infected IFNAR−/− mice died 2–6 days post infection with elevated aminotransferase levels and high virus titers in blood and organs. Main pathological alteration was acute hepatitis with extensive bridging necrosis, reactive hepatocyte proliferation, and mild to moderate inflammatory response with monocyte/macrophage activation. Virus-infected and apoptotic hepatocytes clustered in the necrotic areas. Ribavirin, arbidol, and T-705 suppressed virus replication in vitro by ≥3 log units (IC50 0.6–2.8 µg/ml; IC90 1.2–4.7 µg/ml). Ribavirin [100 mg/(kg×d)] did not increase the survival rate of IFNAR−/− mice, but prolonged the time to death (p<0.001) and reduced the aminotransferase levels and the virus titers. Arbidol [150 mg/(kg×d)] had no efficacy in vivo. Animals treated with T-705 at 1 h [15, 30, and 300 mg/(kg×d)] or up to 2 days [300 mg/(kg×d)] post infection survived, showed no signs of disease, and had no virus in blood and organs. Co-administration of ribavirin and T-705 yielded beneficial rather than adverse effects. Conclusions/Significance Activated hepatic macrophages and monocyte-derived cells may play a role in the proinflammatory cytokine response in CCHF. Clustering of infected hepatocytes in necrotic areas without marked inflammation suggests viral cytopathic effects. T-705 is highly potent against CCHF virus in vitro and in vivo. Its in vivo efficacy exceeds that of the current standard drug for treatment of CCHF, ribavirin. PMID:24786461

  5. Genetic characterization and molecular clock analyses of the Crimean-Congo hemorrhagic fever virus from human and ticks in India, 2010-2011.

    PubMed

    Yadav, Pragya D; Cherian, Sarah S; Zawar, Divya; Kokate, Prasad; Gunjikar, Rashmi; Jadhav, Santosh; Mishra, Akhilesh C; Mourya, Devendra T

    2013-03-01

    A nosocomial outbreak of Crimean Congo hemorrhagic fever (CCHF) was reported among humans in Ahmadabad district, Gujarat, India during January, 2011. In the present study we provide the complete genomic sequences of four CCHFV isolates derived from two human patients and two pools of Hyalomma anatolicum ticks during the period of this outbreak and the complete S segment sequence of two retrospective human serum samples, positive for CCHFV in 2010. Sequence-based molecular characterization of the Indian CCHFV showed that they possessed the functional motifs known to occur in the S, M and L gene segment products as in other CCHF viruses. The S segment of the six Indian CCHF viruses showed 99.8% nucleotide identity. Notably both tick isolates shared 100% nucleotide identity with one of the Indian human isolates of 2011. Phylogenetic analysis based on the S segment demonstrated that the Indian CCHFV isolates formed a distinct cluster in the Asian-Middle East group IV of CCHF viruses. The S segment was closest to a Tajikistan strain TADJ/HU8966 of 1990 (98.5% nucleotide identity) and was of South-Asia 2 type while the M segment was of type M2. Both M and L segments were closest to an Afghanistan strain Afg09-2990 of 2009 (93% and 98% nucleotide identity, respectively). The Indian isolates were thus identified as a South-Asia 2/M2 far-east virus combination and the differing parental origin in the S and L/M segments is suggestive that it may be an intra-genotypic reassortant. Molecular clock studies further revealed that the ancestry of the viruses was not very recent and dated back to about 33years on the basis of the S segment while it was about 15years based on the M segment. Thus though the 2011 outbreak may not have resulted from a very recent introduction, considering that so far there is no evidence of multiple circulating strains in the country, the possibility of a recent re-introduction of the virus from any of the neighboring countries cannot be ruled out. The

  6. Travelers' Health: Viral Hemorrhagic Fevers

    MedlinePlus

    ... Global TravEpiNet Mobile Apps RSS Feeds Chapter 3 Infectious Diseases Related to Travel Recommend on Facebook Tweet Share ... Guerrant RL, Walker DH, Weller PF, editors. Tropical Infectious Diseases: Principles, Pathogens and Practice. 3rd ed. Philadelphia: Elsevier; ...

  7. A Prospective Nested Case-Control Study of Dengue in Infants: Rethinking and Refining the Antibody-Dependent Enhancement Dengue Hemorrhagic Fever Model

    PubMed Central

    Libraty, Daniel H.; Acosta, Luz P.; Tallo, Veronica; Segubre-Mercado, Edelwisa; Bautista, Analisa; Potts, James A.; Jarman, Richard G.; Yoon, In-Kyu; Gibbons, Robert V.; Brion, Job D.; Capeding, Rosario Z.

    2009-01-01

    Background Dengue hemorrhagic fever (DHF) is the severe and life-threatening syndrome that can develop after infection with any one of the four dengue virus (DENV) serotypes. DHF occurs almost exclusively in individuals with secondary heterologous DENV infections and infants with primary DENV infections born to dengue immune mothers. The widely accepted explanation for the pathogenesis of DHF in these settings, particularly during infancy, is antibody-dependent enhancement (ADE) of DENV infection. Methods and Findings We conducted a prospective nested case-control study of DENV infections during infancy. Clinical data and blood samples were collected from 4,441 mothers and infants in up to two pre-illness study visits, and surveillance was performed for symptomatic and inapparent DENV infections. Pre-illness plasma samples were used to measure the associations between maternally derived anti-DENV3 antibody-neutralizing and -enhancing capacities at the time of DENV3 infection and development of infant DHF. The study captured 60 infants with DENV infections across a wide spectrum of disease severity. DENV3 was the predominant serotype among the infants with symptomatic (35/40) and inapparent (15/20) DENV infections, and 59/60 infants had a primary DENV infection. The estimated in vitro anti-DENV3 neutralizing capacity at birth positively correlated with the age of symptomatic primary DENV3 illness in infants. At the time of symptomatic DENV3 infection, essentially all infants had low anti-DENV3 neutralizing activity (50% plaque reduction neutralizing titers [PRNT50] ≤50) and measurable DENV3 ADE activity. The infants who developed DHF did not have significantly higher frequencies or levels of DENV3 ADE activity compared to symptomatic infants without DHF. A higher weight-for-age in the first 3 mo of life and at illness presentation was associated with a greater risk for DHF from a primary DENV infection during infancy. Conclusions This prospective nested case

  8. Heat Shock Protein 70 Family Members Interact with Crimean-Congo Hemorrhagic Fever Virus and Hazara Virus Nucleocapsid Proteins and Perform a Functional Role in the Nairovirus Replication Cycle

    PubMed Central

    Surtees, Rebecca; Dowall, Stuart D.; Shaw, Amelia; Armstrong, Stuart; Hewson, Roger; Carroll, Miles W.; Mankouri, Jamel; Edwards, Thomas A.

    2016-01-01

    ABSTRACT The Nairovirus genus of the Bunyaviridae family contains serious human and animal pathogens classified within multiple serogroups and species. Of these serogroups, the Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole members CCHFV and Hazara virus (HAZV). CCHFV is an emerging zoonotic virus that causes often-fatal hemorrhagic fever in infected humans for which preventative or therapeutic strategies are not available. In contrast, HAZV is nonpathogenic to humans and thus represents an excellent model to study aspects of CCHFV biology under conditions of more-accessible biological containment. The three RNA segments that form the nairovirus genome are encapsidated by the viral nucleocapsid protein (N) to form ribonucleoprotein (RNP) complexes that are substrates for RNA synthesis and packaging into virus particles. We used quantitative proteomics to identify cellular interaction partners of CCHFV N and identified robust interactions with cellular chaperones. These interactions were validated using immunological methods, and the specific interaction between native CCHFV N and cellular chaperones of the HSP70 family was confirmed during live CCHFV infection. Using infectious HAZV, we showed for the first time that the nairovirus N-HSP70 association was maintained within both infected cells and virus particles, where N is assembled as RNPs. Reduction of active HSP70 levels in cells by the use of small-molecule inhibitors significantly reduced HAZV titers, and a model for chaperone function in the context of high genetic variability is proposed. These results suggest that chaperones of the HSP70 family are required for nairovirus replication and thus represent a genetically stable cellular therapeutic target for preventing nairovirus-mediated disease. IMPORTANCE Nairoviruses compose a group of human and animal viruses that are transmitted by ticks and associated with serious or fatal disease. One member is Crimean-Congo hemorrhagic fever

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

    PubMed Central

    Carvalho, Denise Maciel; Garcia, Fernanda Gonçalves; Terra, Ana Paula Sarreta; Lopes Tosta, Ana Cristina; Silva, Luciana de Almeida; Castellano, Lúcio Roberto; Silva Teixeira, David Nascimento

    2014-01-01

    Background. During dengue virus (DV) infection, monocytes produce tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1) on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1) serum levels and innate immune response (TLR4 expression and TNF-α/NO production) of DV infected patients presenting different clinical outcomes. Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA), TNF-α production by peripheral blood mononuclear cells (PBMCs), and TLR4 expression on CD14+ cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF) was detected compared to patients with dengue hemorrhagic fever (DHF). Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-α production) when compared to DF patients. Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes. PMID:25580138

  10. Contemporary Argentine Cinema during Neoliberalism

    ERIC Educational Resources Information Center

    Rocha, Carolina

    2009-01-01

    In this article I analyze contemporary Argentine cinematic production assessing the impact of Law 24,377 that was implemented in 1995 and that provided much-needed funds for national productions. By looking at film production and consumption, the emergence of young filmmakers and the performance of both commercial films and those belonging to the…

  11. Chikungunya fever.

    PubMed

    Kucharz, Eugene J; Cebula-Byrska, Ilona

    2012-06-01

    Chikungunya fever (CF) is an acute illness caused by Chikungunya virus (CHIKV) belonging to the alphavirus genus of the Alphaviruses (Togaviridae) family. The virus is transmitted by Aedes mosquitoes. CF is primarily tropical disease occurring in Africa, Asia and Indian Ocean islands but in the last decade an outbreak of CHIKV autochthonous infections were reported in Italy and France. It is associated with viral genome mutations facilitating transmission of the disease by Aedes albopictus, a mosquito occurring in several European countries. The CF is highly symptomatic, characterized by fever, cutaneuos rash and severe athralgia and arthritis. In some patients severe neurological or hemorrhagic manifestations occur. The disease is self-limiting but a part of the patients suffers from a long-lasting arthritis akin to rheumatoid arthritis. Treatment is only symptomatic. Prevention includes reduction of mosquito bite (mosquito net, repellent) or application of measures against mosquito larvae. Vaccination is not currently available but investigations are in progress. CF presents a significant worldwide health problem affecting in the last decade millions of person, and currently dangerous also for European countries.

  12. Hemorrhagic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Hemorrhagic stroke is the less common type. It happens when ... an artery wall that breaks open. Symptoms of stroke are Sudden numbness or weakness of the face, ...

  13. Selection of the Argentine indicator region

    NASA Technical Reports Server (NTRS)

    Ramirez, C. J.; Reed, C. R. (Principal Investigator)

    1982-01-01

    Determined from available Argentine crop statistics, selection of the Indicator Region was based on the highest wheat, corn, and soybean producing provinces, which were: Buenos Aires, Cordoba, Entre Rios, and Santa Fe. Each province in Argentina was examined for the availability of LANDSAT data; area, yield and production statistics; crop calendars; and other ancillary data. The Argentine Indicator Region is described.

  14. Serological Evaluation of Crimean-Congo Hemorrhagic Fever in Humans with High-Risk Professions Living in Enzootic Regions of Isfahan Province of Iran and Genetic Analysis of Circulating Strains

    PubMed Central

    Ghiasi, Seyed M.; Naddaf, Saeed; Piazak, Norair; Moradi, Maryam; Razavi, Mohammad R.; Afzali, Neda; Haeri, Ali; Mostafavizadeh, Kamyar; Ataei, Behrouz; Khalilifard-Brojeni, Mohammad; Husseini, Sayed M.

    2012-01-01

    Abstract Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease that is asymptomatic in infected livestock, but causes a serious threat to humans with a mortality rate up to 50%. Although the CCHF virus (CCHFV) is often transmitted by ticks, livestock-to-human and human-to-human transmission also occurs. In the current study, we focused on CCHF in the province of Isfahan, located in the center of Iran and deemed to be the second most infected province. Human and livestock sera and resident ticks in the livestock are collected from different regions of the province and analyzed with specific IgG ELISA and RT-PCR tests. Overall, 12% and 12.7% of studied human and livestock populations were IgG positive, respectively. The genome of CCHFV was detected in 9% of ticks resident in livestock involved in this survey. The CCHFV isolates from infected ticks were genetically examined. Nucleotide sequence of the S-segment revealed that the different isolates were closely related to each other, with nucleotide sequence identities higher than 98%. Phylogenetic analysis demonstrated that a variant isolate clustered with the Iraq strain. This high proportion of IgG-positive sera and nearly high proportion of infected ticks increases the risk of CCHF outbreaks in the province and probably posits a great danger to other provinces. PMID:22217167

  15. Tropical fevers: Management guidelines

    PubMed Central

    Singhi, Sunit; Chaudhary, Dhruva; Varghese, George M.; Bhalla, Ashish; Karthi, N.; Kalantri, S.; Peter, J. V.; Mishra, Rajesh; Bhagchandani, Rajesh; Munjal, M.; Chugh, T. D.; Rungta, Narendra

    2014-01-01

    Tropical fevers were defined as infections that are prevalent in, or are unique to tropical and subtropical regions. Some of these occur throughout the year and some especially in rainy and post-rainy season. Concerned about high prevalence and morbidity and mortality caused by these infections, and overlapping clinical presentations, difficulties in arriving at specific diagnoses and need for early empiric treatment, Indian Society of Critical Care Medicine (ISCCM) constituted an expert committee to develop a consensus statement and guidelines for management of these diseases in the emergency and critical care. The committee decided to focus on most common infections on the basis of available epidemiologic data from India and overall experience of the group. These included dengue hemorrhagic fever, rickettsial infections/scrub typhus, malaria (usually falciparum), typhoid, and leptospira bacterial sepsis and common viral infections like influenza. The committee recommends a ‘syndromic approach’ to diagnosis and treatment of critical tropical infections and has identified five major clinical syndromes: undifferentiated fever, fever with rash / thrombocytopenia, fever with acute respiratory distress syndrome (ARDS), fever with encephalopathy and fever with multi organ dysfunction syndrome. Evidence based algorithms are presented to guide critical care specialists to choose reliable rapid diagnostic modalities and early empiric therapy based on clinical syndromes. PMID:24678147

  16. Infections with two dengue viruses in Greece in the 20th century. Did dengue hemorrhagic fever occur in the 1928 epidemic?

    PubMed

    Papaevangelou, G; Halstead, S B

    1977-03-01

    From contemporary clinical accounts we hypothesized that the 1928 dengue epidemic in Greece may have been an earlier occurrence of dengue hemorrhagic fiver/dengue shock syndrome (DHF/DSS). To study the possibility that two different dengue viruses may have been involved, serums from 62 Athenians alive during the epidemic were examined for dengue antibodies; 73 per cent showed evidence of prior dengue infection. Monotypic neutralizing antibodies were found to two different dengue viruses, types 1 and 2. A large proportion of the sampled population had evidence of two or more past dengue infections. Since there is no evidence that dengue viruses have been transmitted in Greece since 1928, during the epidemic a very large number of persons immune to one dengue type must have acquired infections with a secon type. The virological criteria for secondary infection DHF/DSS are thus satisfied. Although DHF/DSS is currently restricted to Asia and the Pacific, the Greek oubreak suggests a biological potential for fatal consequences of dengue infections in Caucasians, particularly the elderly.

  17. [THE DYNAMICS OF THE MORBIDITY RATE OF HEMORRHAGIC FEVER WITH RENAL SYNDROME IN THE POPULATION OF THE CITY OF NABEREZHNYE CHELNY].

    PubMed

    Leont'ev, V V

    2015-01-01

    In the article there are considered the environmental and biological prerequisites for the dynamics of hemorrnagic fever with renal syndrome (HFRS) morbidity rate in the population of the city of Naberezhnye Chelny and the municipal districts located in the north-eastern part of the Republic of Tatarstan, a subdivision of Russian Federation. The territory of the Republic of Tatarstan is included into the body of Volga Federal District of the Russian Federation and is located within the boundaries in coniferous taiga and temperate forests, forest-steppe and steppe geographical areas. The endowment of large forests as well as weather and climatic conditions play an important role in the activity and rhythmicity of this natural focal viral infection, the virus carriers of which are mouse-like rodents. The virus belongs to the family Bunyaviridae and is a representative of the genus Hantavirus. On the base of the epidemiological and clinical data of State Autonomous Healthcare Institution "Naberezhno-Chelninskaya Infectious Diseases Hospital" there was performed the analysis of seasonal and the long-term HFRS morbidity rate from 2008 to 2012 with consideration of age and gender cohorts during the period from 2008 to 2012. There were shown both the seasonal character of the development of infectious disease and its unstable rhythmicity in the long-term dynamics. The most number of cases was observed in the summer-autumn period. 84,32% out of all disease cases were occurred in the male population, adults' morbidity rate was averagely 28 times more than the children's morbidity rate, which was due to the more frequent stay in the foci of the virus circulation. In the long-term dynamics the fever development is indirectly related with the weather and climate conditions of the whole region that influence on biology and the dynamics of rodents' population. So 2010 was differed by anomalously hot summer that led to a significant reduction in the number of the disease cases

  18. A case of familial Mediterranean fever and polyarteritis nodosa complicated by spontaneous perirenal and subcapsular hepatic hemorrhage requiring multiple arterial embolizations.

    PubMed

    Akar, Servet; Goktay, Yigit; Akinci, Baris; Tekis, Dilek; Biberoglu, Kadir; Birlik, Merih; Onen, Fatos; Tunca, Mehmet; Akkoc, Nurullah

    2005-01-01

    The association of familial Mediterranean fever (FMF) and polyarteritis nodosa (PAN) has been well established. These patients have been reported to have an overall better prognosis than other PAN patients. Herein we report a patient with FMF and PAN who died of sepsis following a severe course of recurrent bleeding episodes which required multiple embolization attempts. The 39-year-old Turkish male presented with abdominal pain of 1-month duration. He had been diagnosed with FMF at the age of 24. On admission, he had pallor with general ill appearance. Rebound tenderness was obtained in the right upper abdominal quadrant. He had mild anemia, leukocytosis, thrombocytosis, and hypoalbuminemia. On the 2nd day of his admission, he developed hypotension with a rapid decline in hemoglobin level. Abdominal angiography showed multiple aneurysms in the branches of renal arteries, superior mesenteric artery, and hepatic arterial system including left renal infarct, suggesting PAN. He was put on high-dose steroids and oral cyclophosphamide. Despite medical treatment, he developed intense abdominal pain, hypotension, tachycardia, and a rapid fall in hemoglobin on four occasions. Active bleeding sites were embolized in two different angiography sessions. Although the patient experienced no more recurrent bleeding, he died of multiorgan dysfunction syndrome resulting from sepsis 6 weeks after admission. Polyarteritis nodosa associated with FMF may follow a grave course despite immunosuppressive therapy. Arterial embolization should be considered in the presence of bleeding aneurysms in addition to immunosuppressive therapy.

  19. Yellow Fever

    MedlinePlus

    ... tropical and subtropical areas in South America and Africa. The virus is transmitted to people by the ... fever Maps of Yellow fever endemic areas in Africa and South America Yellow fever vaccination Prevention Vaccine ...

  20. Trap-mulching Argentine ants.

    PubMed

    Silverman, Jules; Sorenson, Clyde E; Waldvogel, Michael G

    2006-10-01

    Argentine ant, Linepithema humile (Mayr), management is constrained, in large part, by polydomy where nestmates are distributed extensively across urban landscapes, particularly within mulch. Management with trap-mulching is a novel approach derived from trap-cropping where ants are repelled from a broad domain of nest sites to smaller defined areas, which are subsequently treated with insecticide. This concept was field-tested with mulch surrounding ornamental trees replaced with a narrow band of pine (Pinus spp.) needle mulch (trap) within a much larger patch of repellent aromatic cedar (Juniperus spp.) mulch. After ants reestablished around the trees, the pine needle mulch band was treated with 0.06% fipronil (Termidor). Poor results were obtained when the trap extended from the tree trunk to the edge of the mulched area. When the trap was applied as a circular band around the tree trunk reductions in the number of foraging ants were recorded through 14 d compared with an untreated mulch control, but not for longer periods. Reductions in the number of ant nests within mulch were no different between the trap mulch and any of the other treatments. We conclude that trap-mulching offers limited benefits, and that successful management of Argentine ants will require implementation of complementary or perhaps alternative strategies.

  1. [Dengue fever: clinical features].

    PubMed

    Dellamonica, P

    2009-10-01

    The vector for dengue fever and chikungunya, Aedes albopictus, was recently identified in Southeastern France, although the usual vector for dengue fever is Aedes aegypti, raising the possibility of cases occurring among the local population via viraemic individuals returning from endemic areas. Dengue fever is usually transmitted by Aedes aegypti. It is due to an arbovirus-flavivirus of which four different serotypes are known: Den 1 to 4. Each serotype is responsible for specific prolonged immunity but no cross-reactivity exists between serotypes. Clinically, the onset is abrupt with frontal headache, retro-orbital pain, myalgia, joint pain, prostration and, in many cases, a macular rash usually sparing the face and extremities. Haemorrhagic signs may occur, such as petechiae, purpura, epistaxis or bleeding gingivae. Two severe forms of dengue fever, particularly among children below 3 years of age, include dengue haemorrhagic fever (DHF) and DHF with shock (dengue shock syndrome). If a case is suspected in metropolitan France, the diagnosis should be systematically confirmed by positive specific IgM, RT-PCR or viral isolation. Treatment of dengue fever, whether in its uncomplicated form or with hemorrhagic manifestations or shock, remains symptomatic. There is no specific anti-viral treatment. A case should be notified to allow French health authorities to take the appropriate measures for vector control.

  2. Epizootic hemorrhagic disease in yaks (Bos grunniens).

    PubMed

    Van Campen, Hana; Davis, Charlie; Flinchum, John D; Bishop, Jeanette V; Schiebel, Anita; Duncan, Colleen; Spraker, Terry

    2013-05-01

    An epizootic of hemorrhagic disease associated with Epizootic hemorrhagic disease virus serotype 2 (EHDV-2) infections in yaks from 5 herds occurred in Colorado between August 21 and October 3, 2012. Affected yaks presented with fever, lethargy, anorexia, dyspnea, and swollen conjunctivae. Ulcerated dental pads, mucoid sanguineous nasal discharge, petechial hemorrhages in multiple organs, pulmonary edema, and serosanguinous fluid in the thorax, abdomen, and pericardial sac were observed at necropsy. Blood and tissue samples from 8 yaks with similar clinical signs and necropsy findings were positive for EHDV-2 by reverse transcription polymerase chain reaction and 5 yaks were seropositive for EHDV. Tests for malignant catarrhal fever (Ovine herpesvirus 2), Bovine viral diarrhea virus, Bovine herpesvirus 1, Foot-and-mouth disease virus, and Vesicular stomatitis virus were negative. The findings indicate that yaks are susceptible to infection with EHDV-2 and exhibit the clinical signs, and gross and histologic lesions of hemorrhagic disease observed in other ruminant species. PMID:23572453

  3. Obstetric hemorrhage.

    PubMed

    Clark, Steven L

    2016-03-01

    Despite the availability of potent drugs, effective surgical techniques, and extensive blood banking facilities, post-partum hemorrhage remains a major cause of death in the United States. A hemorrhage bundle developed by the New York Safe Motherhood Initiative provides clear guidelines for reducing such deaths. This bundle focuses on risk assessment, preparation, diagnosis, and the provision of several management algorithms. Implementation of the protocols and approaches contained in this document, or their equivalent, on a systems basis and a consideration of several additional recommendations for individual care will reduce the likelihood of death from hemorrhage.

  4. Subarachnoid Hemorrhage

    MedlinePlus

    ... can result from the rupture of an intracranial aneurysm — a weakened, dilated area of a blood vessel ... blood vessels in the brain even after the aneurysm that caused the hemorrhage is treated. Most of ...

  5. Rheumatic fever

    MedlinePlus

    ... an ASO test) Complete blood count (CBC) Electrocardiogram (EKG) Sedimentation rate (ESR -- a test that measures inflammation ... criteria include: Fever High ESR Joint pain Abnormal EKG You'll likely be diagnosed with rheumatic fever ...

  6. Dengue Fever

    MedlinePlus

    ... away from areas that have a dengue fever epidemic, the risk of contracting dengue fever is small for international travelers./p> Reviewed by: Elana Pearl Ben-Joseph, ... Nile Virus First Aid: Vomiting Are Insect Repellents With DEET ...

  7. Dengue Fever

    MedlinePlus

    ... Search Button Leading research to understand, treat, and prevent infectious, immunologic, and allergic diseases NIAID Home Health & ... NIAID News & Events Volunteer NIAID > Health & Research Topics > Dengue Fever > Understanding Dengue Fever Understanding Cause Transmission Symptoms ...

  8. Yellow fever

    MedlinePlus

    ... against yellow fever. Some countries require proof of vaccination to gain entry. If you will be traveling to an area where yellow fever is common: Sleep in screened housing Use mosquito repellents Wear ...

  9. [Clinical observations of dengue fever among children].

    PubMed

    Hwang, K P; Su, S C; Chiang, C H

    1989-01-01

    From November 1987 to October 1988, seventy-seven cases diagnosed as dengue fever and confirmed by viral culture or serological examination in the Pediatric Department of Kaohsiung Medical College Hospital were studied. In nearly two thirds (64.9%) of the total cases, the ages were between 10 and 14 years old. No significant sexual difference could be found in this study. Two peaks of cases distribution occurred at November 1987 and October 1988. The major clinical manifestations of Dengue Fever were fever, headache, skin rash and cough. Nearly half of the total cases had nausea, vomiting, myalgia and skin itching. 29 cases (37.7%) had hemorrhagic complications during the course of disease. The most common features of hemorrhage was petechiae followed by epistaxis. Two cases were confirmed as hemorrhagic dengue fever and one was also dengue shock syndrome. Most (92.5%) of the cases had body temperatures over 38.5 degrees C at the onset of the disease. The mean duration of fever was 5.9 days. No fatality was found. It is concluded that eradication of vectors in the school environment might be one of the major points of disease control according to the age distribution of this study. The appearance of hemorrhagic dengue fever is a major problem and should be closely followed by clinicians and workers of public health in Taiwan.

  10. Hemorrhagic Fever with Renal Syndrome (HFRS)

    MedlinePlus

    ... acute kidney failure, which can cause severe fluid overload. The severity of the disease varies depending upon ... Dialysis may be required to correct severe fluid overload. Intravenous ribavirin, an antiviral drug, has been shown ...

  11. [Dengue and dengue hemorrhagic fever: research priorities].

    PubMed

    Guzmán, María G; García, Gissel; Kourí, Gustavo

    2006-03-01

    Dengue is one of the most important infectious diseases in tropical and subtropical countries. At present, the only strategy available to reduce the incidence of dengue is vector control. The World Health Organization and the Pan American Health Organization have called on all nations to take the needed steps to help diminish the burden of this disease and its medical and socioeconomic impact. It is hoped that it will be possible to reverse the increase in dengue and help control its spread through a coordinated, effective international response, along with epidemiological, clinical, and virological research that brings together the most advanced methods and techniques. This piece summarizes the most up-to-date information on dengue, analyzes current epidemiologic trends in the Region of the Americas, discusses the main global and Western Hemisphere initiatives to control the disease, and presents the main areas of research that should be developed in the immediate future.

  12. Terpenoids and bibenzyls from three Argentine liverworts.

    PubMed

    Nagashima, Fumihiro; Asakawa, Yoshinori

    2011-12-16

    A new rosane diterpenoid, 3a-hydroxy-5,15-rosadien-11-one (3), was isolated, together with a known rosane diterpenoid, 5,15-rosadiene-3,11-dione (4), and an aromadendrane sesquiterpenoid, ent-cyclocolorenone (5), from the Et(2)O extract of an unidentified Argentine liverwort Anastrophyllum species. Moreover, four known sesquiterpene lactones 6-9 and two known bibenzyls 10, 11 were isolated from the Et(2)O extracts of Argentine Frullania brasiliensis and Radula voluta, respectively. The structures of compounds 3-11 were determined by the use of NMR techniques.

  13. Transfusion support in patients with dengue fever.

    PubMed

    Kaur, Paramjit; Kaur, Gagandeep

    2014-09-01

    Dengue fever has emerged as a global public health problem in the recent decades. The clinical spectrum of the disease ranges from dengue fever to dengue hemorrhagic fever and dengue shock syndrome. The disease is characterized by increased capillary permeability, thrombocytopenia and coagulopathy. Thrombocytopenia with hemorrhagic manifestations warrants platelet transfusions. There is lack of evidence-based guidelines for transfusion support in patients with dengue fever. This contributes to inappropriate use of blood components and blood centers constantly face the challenge of inventory management during dengue outbreaks. The current review is aimed to highlight the role of platelets and other blood components in the management of dengue. The review was performed after searching relevant published literature in PubMed, Science Direct, Google scholar and various text books and journal articles.

  14. [Dengue fever].

    PubMed

    Pick, N; Potasman, I

    1995-07-01

    Dengue fever is a viral disease, transmitted to man via mosquito bites. It is endemic in tropical regions (10 million infected annually) and is characterized by high fever, headache, myalgia, lethargy, vomiting, rash and neutropenia. The upward trend in the number of young Israelis visiting tropical countries increases the number of those potentially exposed to this disease. We present 4 Israelis who returned with dengue fever from Thailand.

  15. Yellow fever.

    PubMed

    Monath, Thomas P; Vasconcelos, Pedro F C

    2015-03-01

    Yellow fever, a mosquito-borne flavivirus disease occurs in tropical areas of South America and Africa. It is a disease of major historical importance, but remains a threat to travelers to and residents of endemic areas despite the availability of an effective vaccine for nearly 70 years. An important aspect is the receptivity of many non-endemic areas to introduction and spread of yellow fever. This paper reviews the clinical aspects, pathogenesis, and epidemiology of yellow fever, with an emphasis on recent changes in the distribution and incidence of the disease. Recent knowledge about yellow fever 17D vaccine mechanism of action and safety are discussed.

  16. [Alveolar hemorrhage].

    PubMed

    Traclet, J; Lazor, R; Cordier, J-F; Cottin, V

    2013-04-01

    Diffuse alveolar hemorrhage (DAH) is defined by the presence of red blood cells originating from the lung capillaries or venules within the alveoli. The diagnosis is established on clinical features, radiological pattern, and especially bronchoalveolar lavage. Diffuse alveolar hemorrhage may have many immune or non-immune causes. Immune causes of DAH include vasculitides, connective tissue diseases, especially systemic lupus erythematosus, and antiglomerular basement membrane antibody disease (Goodpasture's syndrome). Treatment is both supportive and causal, often based on high dose corticosteroids and immunosuppressive therapy (especially intravenous cyclophosphamide). Plasma exchanges are performed in antiglomerular basement membrane antibody disease and systemic lupus erythematosus, and are considered in systemic vasculitis. Non-immune causes of DAH mainly include heart diseases, coagulation disorders, infections, drug toxicities and idiopathic DAH. Treatment of non-immune DAH is that of its cause. Whatever the cause, DAH is an emergency requiring prompt assessment and early treatment.

  17. [Hemorrhagic enteropathy].

    PubMed

    Brobmann, G F; van Lessen, H; Springorum, H W; Thomas, C

    1976-10-21

    Intestinal infarction in the absence of organic vascular occlusion received increasing attention in recent years. The clinical picture is discussed based on results in 9 cases, an attempt to suggest a possible pathophysiological mechanism is made. Prophylactic digitalisation especially in the elderly patient in the absence of severe heart failure and in cases with already low mesenteric perfusion may lead to a further vasoconstriction and to hemorrhagic enteropathy. Therapeutic possibilities are discussed. PMID:1086816

  18. [Dengue fever. Another infectious disease out of control?].

    PubMed

    Jensenius, M; Gundersen, S G

    1997-11-30

    In the 1950s dengue fever left its home in South-East Asia. The result, as we see it 40 years later, is terrifying. From being an almost unknown infection, dengue fever is today's most common arboviral disease with up to 100 million cases annually. In addition, the clinical picture has changed from a benign influenza-like disorder (classic dengue fever) to a serious disease with bleeding and hypovolemic shock (dengue hemorrhagic fever). In this article the authors give an overview of the present epidemiology, prognosis and possible preventive measures against dengue fever.

  19. Dengue fever: a resurgent risk for the international traveler.

    PubMed

    Lange, W R; Beall, B; Denny, S C

    1992-03-01

    The incidence of dengue fever, an acute febrile illness transmitted by the Aedes aegypti mosquito, is on the rise. High fever, severe headache, skin rash and a variety of constitutional symptoms are hallmarks of classic dengue fever. Dengue hemorrhagic fever, a severe manifestation associated with secondary infection, most often occurs in children. Treatment of classic dengue fever is supportive, whereas urgent rehydration therapy is often required in more severe forms. Community-based and personal strategies for avoiding the mosquito vector represent the best methods of prevention, although vaccine development programs are under way.

  20. [Rift Valley fever].

    PubMed

    Pépin, M

    2011-06-01

    Rift Valley Fever (RVF) is a zoonotic arbovirosis. Among animals, it mainly affects ruminants, causing abortions in gravid females and mortality among young animals. In humans, RVF virus infection is usually asymptomatic or characterized by a moderate fever. However, in 1 to 3% of cases, more severe forms of the disease (hepatitis, encephalitis, retinitis, hemorrhagic fever) can lead to the death of infected individuals or to major sequels. The RVF virus (Bunyaviridae, genus Phlebovirus) was identified for the first time in the 1930s in Kenya. It then spread over almost all African countries, sometimes causing major epizootics/epidemics. In 2000, the virus was carried out of Africa, in the Middle East Arabian Peninsula. In 2007-2008, Eastern-African countries, including Madagascar, reported significant episodes of RVF virus, this was also the case for the Comoros archipelago and the French island of Mayotte. This ability to spread associated with many vectors, including in Europe, and high viral loads in infected animals led the health authorities worldwide to warn about the potential emergence of RVF virus in areas with a temperate climate. The awareness has increased in recent years with climate changes, which may possibly modify the vector distribution and competence, and prompted many RVF virus-free countries to better prepare for a potential implantation of RVF.

  1. SAC-B, Argentine scientific satellite

    NASA Technical Reports Server (NTRS)

    Gulich, J. M.; White, C.

    1994-01-01

    The project and the missions of the Argentine scientific satellite, SAC-B, are summarized. SAC-B is an international cooperative project between NASA and the Secretariat of State of Science and Technology of the Argentine Republic. The objective of SAC-B is to advance the study of solar physics and astrophysics through the examination of solar flares, gamma ray burst sources and the diffuse soft X-ray cosmic background. The scientific payload comprises an instrument to measure the temporal evolution of X-ray emissions from solar flares as well as nonsolar gamma ray bursts, a combined soft X-ray and gamma ray burst detector, a diffuse X-ray background detector, and an energetic neutral atoms detector.

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

    PubMed

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

    2016-05-01

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

  3. [Yellow fever].

    PubMed

    Sabbatani, Sergio; Fiorino, Sirio

    2007-06-01

    After the discovery of the New World, yellow fever proved to be an important risk factor of morbidity and mortality for Caribbean populations. In the following centuries epidemic risk, expanded by sea trade and travel, progressively reached the settlements in North America and Brazil as well as the Atlantic seaboard of tropical and equatorial Africa. In the eighteenth century and the first half of the nineteenth century epidemics of yellow fever were reported in some coastal towns in the Iberian peninsula, French coast, Great Britain and Italy, where, in 1804 at Leghorn, only one epidemic was documented. Prevention and control programs against yellow fever, developed at the beginning of the twentieth century in Cuba and in Panama, were a major breakthrough in understanding definitively its aetiology and pathogenesis. Subsequently, further advances in knowledge of yellow fever epidemiology were obtained when French scientists, working in West and Central Africa, showed that monkeys were major hosts of the yellow fever virus (the wild yellow fever virus), besides man. In addition, advances in research, contributing to the development of vaccines against the yellow fever virus in the first half of the nineteenth century, are reported in this paper. PMID:17599002

  4. Acute Hemorrhagic Edema of Infancy.

    PubMed

    Serra E Moura Garcia, C; Sokolova, A; Torre, M L; Amaro, C

    2016-01-01

    Acute Hemorrhagic Edema of Infancy is a small vessel leucocytoclastic vasculitis affecting young infants. It is characterized by large, target-like, macular to purpuric plaques predominantly affecting the face, ear lobes and extremities. Non-pitting edema of the distal extremities and low-grade fever may also be present. Extra-cutaneous involvement is very rare. Although the lesions have a dramatic onset in a twenty-four to forty-eight hour period, usually the child has a non-toxic appearance. In most cases there are no changes in laboratory parameters. The cutaneous biopsy reveals an inflammatory perivascular infiltrate. It is a benign and auto-limited disease, with complete resolution within two to three weeks leaving no sequelae in the majority of cases. No recurrences are described. We report a case of a 42-day old girl admitted at our hospital with Acute Hemorrhagic Edema of Infancy.

  5. [Cerebral hemorrhage].

    PubMed

    Nakase, Hiroyuki; Motoyama, Yasushi; Yamada, Shuichi

    2016-04-01

    Intracerebral hemorrhage (ICH) remains a serious condition for which early aggressive care is warranted. Japanese evidence-based stroke guidelines were published in 2015 to present the current and comprehensive recommendations for the diagnosis and treatment of stroke. In the spontaneous ICH, topics focused on prevention, management in the acute and chronic stage, complications, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, and other pathologies of ICH. The management of ICH in pregnancy and the puerperium was newly added. These guidelines provide a framework for goal-directed treatment of the patient with ICH. PMID:27333758

  6. Postpartum hemorrhage.

    PubMed

    Su, Cindy W

    2012-03-01

    Postpartum hemorrhage (PPH) is a very common obstetric emergency with high morbidity and mortality rates worldwide. Understanding its etiology is fundamental to effectively managing PPH in an acute setting. Active management of the third stage of labor is also a key component in its prevention. Management strategies include conservative measures (medications, uterine tamponade, and arterial embolization) as well as surgical interventions (arterial ligations, compression sutures, and hysterectomy). Creating a standardized PPH protocol and running simulation-based drills with a multidisciplinary team may also help decrease maternal morbidity and improve perinatal outcomes, although further studies are needed. PMID:22309588

  7. Q Fever.

    PubMed

    Shishido, Akira A; Letiaia, Andrew G; Hartzell, Joshua D

    2016-01-01

    Q fever is a significant infectious disease threat to US military personnel deployed in the Middle East. Its environmental stability, aerosol transmission, and animal reservoir make it a considerable risk for deployed troops due to its potential for weaponization and risk of natural infection. It presents as a flu-like illness that responds promptly to antimicrobial therapy. Q fever should be suspected in patients presenting with a compatible febrile illness in an endemic area and especially if the individual has been exposed to livestock. Diagnosis is confirmed with serologic blood tests, but empiric therapy should be initiated when Q fever is considered. If left untreated, patients with acute Q fever can develop severe complications as well as chronic disease manifesting several months after the initial infection.

  8. Rheumatic Fever

    MedlinePlus

    ... always tell your doctor or dentist about your history of rheumatic fever before you have a surgical or dental procedure. Such procedures may cause bacteria to enter the bloodstream and infect your heart ...

  9. Q Fever.

    PubMed

    Shishido, Akira A; Letiaia, Andrew G; Hartzell, Joshua D

    2016-01-01

    Q fever is a significant infectious disease threat to US military personnel deployed in the Middle East. Its environmental stability, aerosol transmission, and animal reservoir make it a considerable risk for deployed troops due to its potential for weaponization and risk of natural infection. It presents as a flu-like illness that responds promptly to antimicrobial therapy. Q fever should be suspected in patients presenting with a compatible febrile illness in an endemic area and especially if the individual has been exposed to livestock. Diagnosis is confirmed with serologic blood tests, but empiric therapy should be initiated when Q fever is considered. If left untreated, patients with acute Q fever can develop severe complications as well as chronic disease manifesting several months after the initial infection. PMID:26874100

  10. Lassa Fever

    MedlinePlus

    ... an acute viral illness that occurs in west Africa. The illness was discovered in 1969 when two ... Lassa fever is endemic in parts of west Africa including Sierra Leone, Liberia, Guinea and Nigeria; however, ...

  11. Dengue fever.

    PubMed

    Payling, K J

    1997-04-01

    Dengue fever, and its more serious haemorrhagic form, is increasingly being found among UK travellers to tropical and sub-tropical countries. This Update examines transmission, the main symptoms and nursing care of affected people.

  12. Dengue fever

    MedlinePlus

    ... and netting can help reduce the risk of mosquito bites that can spread dengue fever and other infections. Limit outdoor activity during mosquito season, especially when they are most active, at ...

  13. Q Fever

    PubMed Central

    Maurin, M.; Raoult, D.

    1999-01-01

    Q fever is a zoonosis with a worldwide distribution with the exception of New Zealand. The disease is caused by Coxiella burnetii, a strictly intracellular, gram-negative bacterium. Many species of mammals, birds, and ticks are reservoirs of C. burnetii in nature. C. burnetii infection is most often latent in animals, with persistent shedding of bacteria into the environment. However, in females intermittent high-level shedding occurs at the time of parturition, with millions of bacteria being released per gram of placenta. Humans are usually infected by contaminated aerosols from domestic animals, particularly after contact with parturient females and their birth products. Although often asymptomatic, Q fever may manifest in humans as an acute disease (mainly as a self-limited febrile illness, pneumonia, or hepatitis) or as a chronic disease (mainly endocarditis), especially in patients with previous valvulopathy and to a lesser extent in immunocompromised hosts and in pregnant women. Specific diagnosis of Q fever remains based upon serology. Immunoglobulin M (IgM) and IgG antiphase II antibodies are detected 2 to 3 weeks after infection with C. burnetii, whereas the presence of IgG antiphase I C. burnetii antibodies at titers of ≥1:800 by microimmunofluorescence is indicative of chronic Q fever. The tetracyclines are still considered the mainstay of antibiotic therapy of acute Q fever, whereas antibiotic combinations administered over prolonged periods are necessary to prevent relapses in Q fever endocarditis patients. Although the protective role of Q fever vaccination with whole-cell extracts has been established, the population which should be primarily vaccinated remains to be clearly identified. Vaccination should probably be considered in the population at high risk for Q fever endocarditis. PMID:10515901

  14. Orchid Fever

    ERIC Educational Resources Information Center

    Oliver, Phillip

    2004-01-01

    Exotic, captivating, and seductive, orchids have long fascinated plant lovers. They first attracted the attention of Westerners in the 17th century, when explorers brought back samples from South America and Asia. By the mid-1800s, orchid collecting had reached a fever pitch, not unlike that of the Dutch tulip craze of the 1630s, with rich (and…

  15. Scarlet fever.

    PubMed

    2016-04-27

    Essential facts Scarlet fever is characterised by a rash that usually accompanies a sore throat and flushed cheeks. It is mainly a childhood illness. While this contagious disease rarely poses a danger to life today, outbreaks in the past led to many deaths.

  16. Dengue fever complicated by hemophagocytosis

    PubMed Central

    Koshy, Maria; Mishra, Ajay Kumar; Agrawal, Bhumi; Kurup, Akhil Rajendra; Hansdak, Samuel George

    2016-01-01

    Dengue is a common acute viral febrile illness in the tropics. Although the usual presentation is that of a self-limiting illness, its complications are protean. We report a 29-year-old man who presented with an acute febrile illness and was diagnosed with dengue hemorrhagic fever. Despite appropriate supportive therapy, the patient initially improved, but subsequently had clinical deterioration. Evaluation revealed features of hemophagocytic lymphohistiocytosis. He was successfully treated with glucocorticoids and had an uneventful recovery. This case adds to the limited adult cases of virus-associated hemophagocytic syndrome in the literature and the need for prompt recognition and treatment of this rare complication. PMID:27274854

  17. Dengue fever complicated by hemophagocytosis.

    PubMed

    Koshy, Maria; Mishra, Ajay Kumar; Agrawal, Bhumi; Kurup, Akhil Rajendra; Hansdak, Samuel George

    2016-01-01

    Dengue is a common acute viral febrile illness in the tropics. Although the usual presentation is that of a self-limiting illness, its complications are protean. We report a 29-year-old man who presented with an acute febrile illness and was diagnosed with dengue hemorrhagic fever. Despite appropriate supportive therapy, the patient initially improved, but subsequently had clinical deterioration. Evaluation revealed features of hemophagocytic lymphohistiocytosis. He was successfully treated with glucocorticoids and had an uneventful recovery. This case adds to the limited adult cases of virus-associated hemophagocytic syndrome in the literature and the need for prompt recognition and treatment of this rare complication. PMID:27274854

  18. Vaccines for prevention of bluetongue and epizootic hemorrhagic disease in livestock: A North American perspective

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bluetongue (BT) and epizootic hemorrhagic disease (EHD) are non-contagious, insect transmitted diseases of domestic and wild ruminants caused by related but distinct viruses. Both BT (BTV) and EHD (EHDV) viruses cause hemorrhagic fevers in susceptible ruminants; however BT is principally a disease o...

  19. Boutonneuse fever.

    PubMed Central

    Moraga, F A; Martinez-Roig, A; Alonso, J L; Boronat, M; Domingo, F

    1982-01-01

    Sixty children, aged between 2 and 10 years, had boutonneuse fever during the summer months of 1979 and 1980. They presented with fever and a generalised maculopapular rash. The tàche noire could be seen at the site of the tick bite in 38 (63%) of them. The antibody response, assayed nonspecifically, by the Weil-Felix reaction was positive in 52. A singe titre of more than 1:80 or a 4-fold increase between two paired specimens separated by a 7-day interval was considered diagnostic. Maximum titres were reached at the end of the second week of convalescence in 81% of patients. Treatment with oral oxytetracycline was effective in all cases. Images Fig. 1 Fig. 2 Fig. 3 PMID:7065712

  20. Exploration of Possible Astroblemes in the Argentine Puna

    NASA Astrophysics Data System (ADS)

    Acevedo, R. D.; Alonso, R.; Rocca, M.; Klajnik, K.; Tálamo, E.

    2014-09-01

    Potential three new astrobleme sites have been detected by remote sensors and checked in situ in Argentine Puna: an elevated plateau that it has remained stable and invariable across long geological periods.

  1. A Descriptive Study of the Argentine Music Teacher.

    ERIC Educational Resources Information Center

    Gratzer, Dina; Sima, Marta

    1987-01-01

    Reports on a research study which examined the professional status of music teachers in Argentina. Describes various areas of concern for Argentine music teachers including general training, the workplace, teacher training and musical activities. (RKM)

  2. Zika fever.

    PubMed

    Martínez de Salazar, Pablo; Suy, Anna; Sánchez-Montalvá, Adrián; Rodó, Carlota; Salvador, Fernando; Molina, Israel

    2016-04-01

    Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between Zika infection and complications, such as microencephaly or Guillem-Barré syndrome. PMID:26993436

  3. Zika fever.

    PubMed

    Martínez de Salazar, Pablo; Suy, Anna; Sánchez-Montalvá, Adrián; Rodó, Carlota; Salvador, Fernando; Molina, Israel

    2016-04-01

    Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between Zika infection and complications, such as microencephaly or Guillem-Barré syndrome.

  4. Typhoid fever.

    PubMed

    Wain, John; Hendriksen, Rene S; Mikoleit, Matthew L; Keddy, Karen H; Ochiai, R Leon

    2015-03-21

    Control of typhoid fever relies on clinical information, diagnosis, and an understanding for the epidemiology of the disease. Despite the breadth of work done so far, much is not known about the biology of this human-adapted bacterial pathogen and the complexity of the disease in endemic areas, especially those in Africa. The main barriers to control are vaccines that are not immunogenic in very young children and the development of multidrug resistance, which threatens efficacy of antimicrobial chemotherapy. Clinicians, microbiologists, and epidemiologists worldwide need to be familiar with shifting trends in enteric fever. This knowledge is crucial, both to control the disease and to manage cases. Additionally, salmonella serovars that cause human infection can change over time and location. In areas of Asia, multidrug-resistant Salmonella enterica serovar Typhi (S Typhi) has been the main cause of enteric fever, but now S Typhi is being displaced by infections with drug-resistant S enterica serovar Paratyphi A. New conjugate vaccines are imminent and new treatments have been promised, but the engagement of local medical and public health institutions in endemic areas is needed to allow surveillance and to implement control measures.

  5. Pheromone disruption of Argentine ant trail integrity

    USGS Publications Warehouse

    Suckling, D.M.; Peck, R.W.; Manning, L.M.; Stringer, L.D.; Cappadonna, J.; El-Sayed, A. M.

    2008-01-01

    Disruption of Argentine ant trail following and reduced ability to forage (measured by bait location success) was achieved after presentation of an oversupply of trail pheromone, (Z)-9-hexadecenal. Experiments tested single pheromone point sources and dispersion of a formulation in small field plots. Ant walking behavior was recorded and digitized by using video tracking, before and after presentation of trail pheromone. Ants showed changes in three parameters within seconds of treatment: (1) Ants on trails normally showed a unimodal frequency distribution of walking track angles, but this pattern disappeared after presentation of the trail pheromone; (2) ants showed initial high trail integrity on a range of untreated substrates from painted walls to wooden or concrete floors, but this was significantly reduced following presentation of a point source of pheromone; (3) the number of ants in the pheromone-treated area increased over time, as recruitment apparently exceeded departures. To test trail disruption in small outdoor plots, the trail pheromone was formulated with carnuba wax-coated quartz laboratory sand (1 g quartz sand/0.2 g wax/1 mg pheromone). The pheromone formulation, with a half-life of 30 h, was applied by rotary spreader at four rates (0, 2.5, 7.5, and 25 mg pheromone/m2) to 1- and 4-m2 plots in Volcanoes National Park, Hawaii. Ant counts at bait cards in treated plots were significantly reduced compared to controls on the day of treatment, and there was a significant reduction in ant foraging for 2 days. These results show that trail pheromone disruption of Argentine ants is possible, but a much more durable formulation is needed before nest-level impacts can be expected. ?? 2008 Springer Science+Business Media, LLC.

  6. Pheromone disruption of Argentine ant trail integrity.

    PubMed

    Suckling, D M; Peck, R W; Manning, L M; Stringer, L D; Cappadonna, J; El-Sayed, A M

    2008-12-01

    Disruption of Argentine ant trail following and reduced ability to forage (measured by bait location success) was achieved after presentation of an oversupply of trail pheromone, (Z)-9-hexadecenal. Experiments tested single pheromone point sources and dispersion of a formulation in small field plots. Ant walking behavior was recorded and digitized by using video tracking, before and after presentation of trail pheromone. Ants showed changes in three parameters within seconds of treatment: (1) Ants on trails normally showed a unimodal frequency distribution of walking track angles, but this pattern disappeared after presentation of the trail pheromone; (2) ants showed initial high trail integrity on a range of untreated substrates from painted walls to wooden or concrete floors, but this was significantly reduced following presentation of a point source of pheromone; (3) the number of ants in the pheromone-treated area increased over time, as recruitment apparently exceeded departures. To test trail disruption in small outdoor plots, the trail pheromone was formulated with carnuba wax-coated quartz laboratory sand (1 g quartz sand/0.2 g wax/1 mg pheromone). The pheromone formulation, with a half-life of 30 h, was applied by rotary spreader at four rates (0, 2.5, 7.5, and 25 mg pheromone/m(2)) to 1- and 4-m(2) plots in Volcanoes National Park, Hawaii. Ant counts at bait cards in treated plots were significantly reduced compared to controls on the day of treatment, and there was a significant reduction in ant foraging for 2 days. These results show that trail pheromone disruption of Argentine ants is possible, but a much more durable formulation is needed before nest-level impacts can be expected. PMID:19034574

  7. Methicillin Hemorrhagic Cystitis

    PubMed Central

    Bracis, R.; Sanders, C. V.; Gilbert, D. N.

    1977-01-01

    Interstitial nephritis is a recognized complication of methicillin therapy. Hemorrhagic cystitis due to methicillin has not been emphasized. Evidence of hemorrhagic cystitis developed in six patients receiving methicillin therapy and was confirmed by cystoscopy in three of them. PMID:907335

  8. [The dengue fever in Mexico. Knowledge for improving the quality in health].

    PubMed

    Fajardo-Dolci, Germán; Meljem-Moctezuma, José; Vicente-González, Esther; Venegas-Páez, Francisco Vicente; Mazón-González, Betania; Aguirre-Gas, Héctor Gerardo

    2012-01-01

    Dengue is a systemic infectious disease of viral etiology, transmitted by Aedes mosquitoes. It causes between 50 and 100 million cases annually over 100 countries. In most of the cases it presents as influenza-like illness or undifferentiated fever and more than 500,000 patients develop dengue hemorrhagic fever. In America, dengue fever is considered the most important resurgent disease and its hemorrhagic form is becoming more relevant, especially given the steady increase in the number of deaths. The first outbreaks of dengue in America were described in 1635. Since the apparition of dengue hemorrhagic fever, in 1962, it has been considered a public health problem because half of the population lives in endemic areas. The purpose of this paper is to carry a briefly review of the epidemiology, clinical features, pathophysiology, prevention and treatment of dengue fever, as well as create recommendations in order to improve the quality of care and decrease mortality in these patients.

  9. Unusual neurologic manifestations occurring during dengue fever infection.

    PubMed

    Patey, O; Ollivaud, L; Breuil, J; Lafaix, C

    1993-06-01

    This is a report on dengue fever in two young patients in France that were infected in New Caledonia and Thailand. Both presented with unusual neurologic manifestations. The first patient developed a focal subarachnoid hemorrhage that was associated with transient thrombocytopenia. No neurologic vascular malformation was detected; a mild dengue hemorrhagic fever after a previous dengue infection was suspected. The second patient showed peripheral facial palsy one week after apyrexia without any other etiology except the dengue infection. This case was probably a postinfectious syndrome associated with dengue virus. Both patients recovered spontaneously. The circumstances of the neurologic manifestations in these patients may be attributed to the dengue fever virus. However, although neurologic complications reported for dengue fever are unusual, it is reasonable to consider these manifestations as being due to immunopathologic consequences.

  10. A case of hemorrhagic dengue without hypovolemia in an adult.

    PubMed

    Pan, H Y; Chow, J S

    1984-09-01

    Dengue hemorrhagic fever, though prevalent in South East Asia was diagnosed for the first time in Hong Kong. The subject in this report made frequent visits to endemic areas including the Philippines. Hypovolemia was not evident at the time of presentation. The nature and the status of the disease in this area are discussed.

  11. [Typhoid fever].

    PubMed

    Marchou, B

    1996-01-15

    Endemic in regions with poor hygienic conditions, Enteric fevers are imported in France by returning travellers. They are caused by Salmonella strains, mainly S. Typhi, transmitted via fecal-oral route. Salmonella reach the blood stream after proliferating in mesenteric lymph nodes. At an initial stage blood and bone marrow cultures, later on Widal-Felix serology permit diagnosis. Antibiotics have rendered death exceptional. Quinolones and ceftriaxone allow treatments shorter than 10 days. Immunization (Typhim Vi) and improvement of hygienic standards are the cornerstone of prevention.

  12. Maternal mortality from hemorrhage.

    PubMed

    Haeri, Sina; Dildy, Gary A

    2012-02-01

    Hemorrhage remains as one of the top 3 obstetrics related causes of maternal mortality, with most deaths occurring within 24-48 hours of delivery. Although hemorrhage related maternal mortality has declined globally, it continues to be a vexing problem. More specifically, the developing world continue to shoulder a disproportionate share of hemorrhage related deaths (99%) compared with industrialized nations (1%). Given the often preventable nature of death from hemorrhage, the cornerstone of effective mortality reduction involves risk factor identification, quick diagnosis, and timely management. In this monograph we will review the epidemiology, etiology, and preventative measures related to maternal mortality from hemorrhage.

  13. Carbohydrate supply limits invasion of natural communities by Argentine ants.

    PubMed

    Rowles, Alexei D; Silverman, Jules

    2009-08-01

    The ability of species to invade new habitats is often limited by various biotic and physical factors or interactions between the two. Invasive ants, frequently associated with human activities, flourish in disturbed urban and agricultural environments. However, their ability to invade and establish in natural habitats is more variable. This is particularly so for the invasive Argentine ant (Linepithema humile). While biotic resistance and low soil moisture limits their invasion of natural habitats in some instances, the effect of food availability has been poorly explored. We conducted field experiments to determine if resource availability limits the spread and persistence of Argentine ants in remnant natural forest in North Carolina. Replicated transects paired with and without sucrose solution feeding stations were run from invaded urban edges into forest remnants and compared over time using baits and direct counts at feeding stations. Repeated under different timing regimes in 2006 and 2007, access to sucrose increased local Argentine ant abundances (1.6-2.5 fold) and facilitated their progression into the forest up to 73 +/- 21% of 50-m transects. Resource removal caused an expected decrease in Argentine ant densities in 2006, in conjunction with their retreat to the urban/forest boundary. However, in 2007, Argentine ant numbers unexpectedly continued to increase in the absence of sugar stations, possibly through access to alternative resources or conditions not available the previous year such as honeydew-excreting Hemiptera. Our results showed that supplementing carbohydrate supply facilitates invasion of natural habitat by Argentine ants. This is particularly evident where Argentine ants continued to thrive following sugar station removal.

  14. Prevention of Dengue Fever: An Exploratory School-Community Intervention Involving Students Empowered as Change Agents

    ERIC Educational Resources Information Center

    Jayawardene, Wasantha P.; Lohrmann, David K.; YoussefAgha, Ahmed H.; Nilwala, Dayani C.

    2011-01-01

    Background: Dengue fever and dengue hemorrhagic fever (DF/DHF) are epidemic and endemic in tropical and subtropical countries including Sri Lanka. Numerous structural and community interventions have been shown to be effective in interrupting the life cycle of mosquitoes that transmit DF/DHF; however, these interventions are not always implemented…

  15. Rift valley fever in the US: Commerce networks, climate, and susceptible vector and host populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rift Valley fever (RVF) is a mosquito-borne hemorrhagic viral disease with substantial negative impacts on public and animal health in its endemic range of sub-Saharan Africa. Rift Valley fever virus (RVFV) could enter the United States and lead to widespread morbidity and mortality in humans, domes...

  16. [Epidemiology of dengue and hemorrhagic dengue in Santiago, Cuba 1997].

    PubMed

    Valdés, L; Guzmán, M G; Kourí, G; Delgado, J; Carbonell, I; Cabrera, M V; Rosario, D; Vázquez, S

    1999-07-01

    A dengue epidemic that Cuba reported in 1997 registered more than 500,000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by serotype 2 of the virus. This time 344,203 clinical cases were reported, 10,312 of which were severe cases of hemorrhagic fever that led to 158 fatalities (101 of them among children). The reintroduction of dengue, and specifically of dengue viral serotype 2 (Jamaica genotype), was quickly detected in January 1997 through an active surveillance system with laboratory confirmation of cases in the municipality of Santiago de Cuba, in the province of the same name. The main epidemiological features of this outbreak are reported in this paper. A total of 3,012 cases were reported and serologically confirmed. These included 205 cases classified as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 12 of which were case fatalities (all among adults). Secondary infection with dengue virus was one of the most important risk factors for DHF/DSS. Ninety-eight percent of the DHF/DSS cases and 92% of the fatal cases had contracted a secondary infection. It was the first time dengue hemorrhagic fever was documented as a secondary infection 16 to 20 years after initial infection. Belonging to the white racial group was another important risk factor for DHF/DSS, as had been observed during the 1981 epidemic. During the most recent epidemic it was demonstrated that the so called "fever alert" is not useful for early detection of an epidemic. Measures taken by the country's public health officials prevented spread of the epidemic to other municipalities plagued by Aedes aegypti.

  17. Drug fever caused by propofol in the intensive care unit.

    PubMed

    Yatabe, Tomoaki; Yamashita, Koichi; Yokoyama, Masataka

    2015-10-01

    Few studies have reported that fever is caused by intravenous sedative drugs even though these agents are widely used. We present a case of propofol-induced drug fever. A 57-year-old woman underwent hepatic segmentectomy. Although she was diagnosed with type I glycogen storage disease when in her twenties, her liver function was normal. As the operative hemorrhage was high, the patient was transferred to the intensive care unit (ICU). Her temperature at ICU admission was 35.8 °C, and sedation with propofol and dexmedetomidine was initiated. Two hours after admission to the ICU, the patient had a fever of 38-39.5 °C. Remittent fever persisted until day 5 after surgery. Because of her persistent fever, pneumonia was suspected and antibiotics were initiated on day 4 after surgery. As the fever persisted after the initiation of antibiotics, drug fever was suspected. On day 5 after surgery, propofol infusion was discontinued and the patient was extubated. Her temperature of 37.7 °C at the discontinuation of propofol infusion, and rapidly decreased to 36.1 °C in the following 3 h. Propofol-induced drug fever must be considered in cases of fever of unknown origin when patients receive propofol and appear inappropriately well for the degree of fever that they have.

  18. [Dengue fever during pregnancy. Cases report].

    PubMed

    Rosado León, Rocio; Muñoz Rodríguez, Mario R; Soler Huerta, Elizabeth; Parissi Crivelli, Aurora; Méndez Machado, Gustavo F

    2007-11-01

    Dengue is known as an endemic disease of tropical and subtropical regions. It was considered a disease very frequent on kids, but recently an increase was reported on adult people. Some of these cases were related to pregnant women, for that reason, we decided to check eight cases, including just the mothers who presented dengue virus infection through ELISA IgM. IgG and ELISA IgM studies. Five products were determined between 3 and 9-born-babies. Eight cases of dengue were analyzed during pregnancy, three cases of fever dengue and five cases of hemorrhagic dengue; main complications detected were threat of abortion, and premature labour, postsurgical bleeding with desiccant haematoma of uterine artery, oligohydramnios, as well as pleural effusion, two of the neonates were classified as septic for presenting fever. In no case, IgG or IgM for fever dengue was detected in neonates.

  19. Fundus Findings in Dengue Fever: A Case Report

    PubMed Central

    Şahan, Berna; Tatlıpınar, Sinan; Marangoz, Deniz; Çiftçi, Ferda

    2015-01-01

    Dengue fever is a flavivirus infection transmitted through infected mosquitoes, and is endemic in Southeast Asia, Central and South America, the Pacific, Africa and the Eastern Mediterranean region. A 41-year-old male patient had visual impairment after travelling to Thailand, which is one of the endemic areas. Cotton wool spots were observed on fundus examination. Fundus fluorescein angiography showed minimal vascular leakage from areas near the cotton wool spots and dot hemorrhages in the macula. Dengue fever should be considered in patients with visual complaints who traveled to endemic areas of dengue fever. PMID:27800237

  20. Acute cerebral paragonimiasis presenting as hemorrhagic stroke in a child.

    PubMed

    Chen, Zhi; Zhu, Gang; Lin, Jiangkai; Wu, Nan; Feng, Hua

    2008-08-01

    A hemorrhagic stroke in children is rarely secondary to cerebral paragonimiasis. We describe a 9-year-old boy in whom an intracerebral hemorrhage was the leading clinical indication of acute cerebral paragonimiasis. He was hospitalized because of a sudden onset of headache, right hemiparesis, and dysarthria. A computed tomography scan revealed an intracerebral hemorrhage in the left parietal lobe. Magnetic resonance angiography did not confirm any vascular abnormalities at the location of the hematoma. Four weeks later, he presented with right hemiparesis again, and fever. A diagnosis of cerebral paragonimiasis was based on repeated magnetic resonance imaging of the brain and an enzyme-linked immunosorbent assay for paragonimiasis. The patient gradually recovered with praziquantel treatment. Cerebral paragonimiasis should be considered in the differential diagnosis of hemorrhagic strokes in children in areas where paragonimiasis is epidemic.