Seroepidemiology of Crimean-Congo Hemorrhagic Fever Virus (CCHFV) in Cattle across Three Livestock Pastoral Regions in Kenya

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic disease, endemic in Africa, with a high case fatality rate. There is no efficient treatment or licensed vaccine. This study aimed to determine the prevalence of CCHFV in cattle in extensive grazing systems (both pastoralism and ranching) within the Maasai Mara ecosystem, Nanyuki, and the Ol Pejeta Conservancy in Kenya. We conducted a seroepidemiological study of the sera of 148 cattle from 18 households from the three ecosystems in 2014, 2016, and 2019. Sera from 23 sheep and 17 goats were also obtained from the same households during the same period. Sera were analyzed for the presence of antibodies to CCHFV using the commercially available double-antigen ELISA kit. Overall, 31.5% CCHFV seropositivity was observed. The prevalence of CCHF was analyzed using a multiple logistic mixed model with main predictors. Risk factors associated with exposure to CCHFV were age (p = 0.000) and season (p = 0.007). Our findings suggest exposure to CCHFV and point to cattle as likely reservoirs of CCHFV in Kenya. The findings might play a role in providing better insights into disease risk and dynamics where analysis of tick populations in these regions should be further investigated.

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Worldwide epidemiology of Crimean-Congo Hemorrhagic Fever Virus in humans, ticks and other animal species, a systematic review and meta-analysis

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009299 ◽

2021 ◽

Vol 15 (4) ◽

pp. e0009299

Author(s):

Jean Thierry Ebogo Belobo ◽

Sebastien Kenmoe ◽

Cyprien Kengne-Nde ◽

Cynthia Paola Demeni Emoh ◽

Arnol Bowo-Ngandji ◽

...

Keyword(s):

Systematic Review ◽

Low Income ◽

Animal Species ◽

Meta Analysis ◽

Random Effect ◽

Case Fatality ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus

There are uncertainties about the global epidemiological data of infections due to Crimean-Congo hemorrhagic fever virus (CCHFV). We estimated the global case fatality rate (CFR) of CCHFV infections and the prevalence of CCHFV in humans, ticks and other animal species. We also explored the socio-demographic and clinical factors that influence these parameters. In this systematic review with meta–analyses we searched publications from database inception to 03rd February 2020 in Pubmed, Scopus, and Global Index Medicus. Studies included in this review provided cross-sectional data on the CFR and/or prevalence of one or more targets used for the detection of CCHFV. Two independent investigators selected studies to be included. Data extraction and risk of bias assessment were conducted independently by all authors. Data collected were analysed using a random effect meta-analysis. In all, 2345 records were found and a total of 312 articles (802 prevalence and/or CFR data) that met the inclusion criteria were retained. The overall CFR was 11.7% (95% CI = 9.1–14.5), 8.0% (95% CI = 1.0–18.9), and 4.7% (95% CI = 0.0–37.6) in humans with acute, recent, and past CCHFV infections respectively. The overall CCHFV acute infections prevalence was 22.5% (95% CI = 15.7–30.1) in humans, 2.1% (95% CI = 1.3–2.9) in ticks, and 4.5% (95% CI = 1.9–7.9) in other animal species. The overall CCHFV recent infections seroprevalence was 11.6% (95% CI = 7.9–16.4) in humans and 0.4% (95% CI = 0.0–2.9) in other animal species. The overall CCHFV past infections seroprevalence was 4.3% (95% CI = 3.3–5.4) in humans and 12.0% (95% CI = 9.9–14.3) in other animal species. CFR was higher in low-income countries, countries in the WHO African, South-East Asia and Eastern Mediterranean regions, in adult and ambulatory patients. CCHFV detection rate in humans were higher in CCHFV suspected cases, healthcare workers, adult and hospitalized patients, ticks of the genus Ornithodoros and Amblyomma and in animals of the orders Perissodactyla and Bucerotiformes. This review highlights a significant disease burden due to CCHFV with a strong disparity according to country income levels, geographic regions, various human categories and tick and other animal species. Preventive measures in the light of these findings are expected.

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CRIMEAN-CONGO HEMORRHAGIC FEVER (CCHF)

The Professional Medical Journal ◽

10.29309/tpmj/2018.25.02.453 ◽

2018 ◽

Vol 25 (02) ◽

pp. 259-263

Author(s):

Zahidullah Khan ◽

Zahid Fida ◽

Abidullah Khan ◽

Fakhar Zaman ◽

Maimoona Ayub

Keyword(s):

Platelet Count ◽

Teaching Hospital ◽

Case Fatality ◽

Hemorrhagic Fever ◽

Continuous Variables ◽

Cross Sectional ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Total Hospital Stay ◽

Study Setting

Background: Crimean-Congo hemorrhagic fever virus (CCHFV) from theBunyaviridae family causes a highly contagious disease in human called as, Crimean-Congohemorrhagic fever (CCHF). Infection in humans leads to a serious pyrexial illness that oftenresults in death of the patient. Objectives: To evaluate the outcome of patients admitted toKhyber Teaching Hospital (KTH), Peshawar-Pakistan with CCHF. Study Design: Cross-sectional,retrospective, epidemiological study. Setting: Khyber Teaching Hospital (KTH), Peshawar-Pakistan. Period: 2016. Methods: On the basis of final outcome; death or recovery, a total of 11patients diagnosed with CCHF in the year 2016 were divided into two groups. The demographicdetails and symptomatlogy of both the groups were evaluated. Continuous variables wereanalyzed using independent sample t-test on SPSS version 16. Results: Fever was commonin patients who recovered. However, shock and coagulapathy were more commonly seen inpatients expired. The mortality rate was 36.36%. Moreover, age and platelet count on admissionwere indicators of worse outcome, P < 0.05. However, total hospital stay did not predict theoutcome, P > 0.05. Conclusion: The case fatality rate in CCHF is high. Moreover, mortalityrate has an inverse relationship with platelet count on admission and a positive one with thepatient’s age.

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Crimean–Congo Hemorrhagic Fever Virus Past Infections Are Associated with Two Innate Immune Response Candidate Genes in Dromedaries

Cells ◽

10.3390/cells11010008 ◽

2021 ◽

Vol 11 (1) ◽

pp. 8

Author(s):

Sara Lado ◽

Jan Futas ◽

Martin Plasil ◽

Tom Loney ◽

Pia Weidinger ◽

...

Keyword(s):

Candidate Genes ◽

Linear Regression Analysis ◽

Case Fatality ◽

Hemorrhagic Fever ◽

Immune Defense ◽

Innate Immune ◽

Fever Virus ◽

Future Research ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus

Dromedaries are an important livestock, used as beasts of burden and for meat and milk production. However, they can act as an intermediate source or vector for transmitting zoonotic viruses to humans, such as the Middle East respiratory syndrome coronavirus (MERS-CoV) or Crimean–Congo hemorrhagic fever virus (CCHFV). After several outbreaks of CCHFV in the Arabian Peninsula, recent studies have demonstrated that CCHFV is endemic in dromedaries and camel ticks in the United Arab Emirates (UAE). There is no apparent disease in dromedaries after the bite of infected ticks; in contrast, fever, myalgia, lymphadenopathy, and petechial hemorrhaging are common symptoms in humans, with a case fatality ratio of up to 40%. We used the in-solution hybridization capture of 100 annotated immune genes to genotype 121 dromedaries from the UAE tested for seropositivity to CCHFV. Through univariate linear regression analysis, we identified two candidate genes belonging to the innate immune system: FCAR and CLEC2B. These genes have important functions in the host defense against viral infections and in stimulating natural killer cells, respectively. This study opens doors for future research into immune defense mechanisms in an enzootic host against an important zoonotic disease.

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Epidemiological and behavioral factors associated with Crimean–Congo hemorrhagic fever virus infections in humans

Expert Review of Anti-infective Therapy ◽

10.1586/14787210.2013.827890 ◽

2013 ◽

Vol 11 (9) ◽

pp. 897-908 ◽

Cited By ~ 13

Author(s):

Maria Sargianou ◽

Anna Papa

Keyword(s):

Hemorrhagic Fever ◽

Fever Virus ◽

Behavioral Factors ◽

Virus Infections ◽

Crimean Congo Hemorrhagic Fever ◽

Factors Associated ◽

Hemorrhagic Fever Virus

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Crimean-Congo Hemorrhagic Fever Virus Genomics and Global Diversity

Journal of Virology ◽

10.1128/jvi.00752-06 ◽

2006 ◽

Vol 80 (17) ◽

pp. 8834-8842 ◽

Cited By ~ 154

Author(s):

Varough M. Deyde ◽

Marina L. Khristova ◽

Pierre E. Rollin ◽

Thomas G. Ksiazek ◽

Stuart T. Nichol

Keyword(s):

Genetic Recombination ◽

Case Fatality ◽

Hemorrhagic Fever ◽

Severe Illness ◽

Long Distance ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Individual Segment ◽

Cchf Virus ◽

Tree Topologies

ABSTRACT Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high case fatality that occurs in Africa, Europe, the Middle East, and Asia. The complete genomes of 13 geographically and temporally diverse virus strains were determined, and CCHF viruses were found to be highly variable with 20 and 8%, 31 and 27%, and 22 and 10% nucleotide and deduced amino acid differences detected among virus S (nucleocapsid), M (glycoprotein), and L (polymerase) genome segments, respectively. Distinct geographic lineages exist, but with multiple exceptions indicative of long-distance virus movement. Discrepancies among the virus S, M, and L phylogenetic tree topologies document multiple RNA segment reassortment events. An analysis of individual segment datasets suggests genetic recombination also occurs. For an arthropod-borne virus, the genomic plasticity of CCHF virus is surprisingly high.

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Serologic and molecular evidence for circulation of Crimean-Congo hemorrhagic fever virus in ticks and cattle in Zambia

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009452 ◽

2021 ◽

Vol 15 (6) ◽

pp. e0009452

Author(s):

Masahiro Kajihara ◽

Martin Simuunza ◽

Ngonda Saasa ◽

George Dautu ◽

Akina Mori-Kajihara ◽

...

Keyword(s):

Phylogenetic Analyses ◽

Case Fatality ◽

Hemorrhagic Fever ◽

Epidemiologic Studies ◽

Immunofluorescence Assay ◽

Molecular Evidence ◽

African Countries ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Cchf Virus

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonosis with a high case fatality rate in humans. Although the disease is widely found in Africa, Europe, and Asia, the distribution and genetic diversity of CCHF virus (CCHFV) are poorly understood in African countries. To assess the risks of CCHF in Zambia, where CCHF has never been reported, epidemiologic studies in cattle and ticks were conducted. Through an indirect immunofluorescence assay, CCHFV nucleoprotein-specific serum IgG was detected in 8.4% (88/1,047) of cattle. Among 290 Hyalomma ticks, the principal vector of CCHFV, the viral genome was detected in 11 ticks. Phylogenetic analyses of the CCHFV S and M genome segments revealed that one of the detected viruses was a genetic reassortant between African and Asian strains. This study provides compelling evidence for the presence of CCHFV in Zambia and its transmission to vertebrate hosts.

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Immunocompetent mouse model for Crimean-Congo hemorrhagic fever virus

eLife ◽

10.7554/elife.63906 ◽

2021 ◽

Vol 10 ◽

Author(s):

David W Hawman ◽

Kimberly Meade-White ◽

Shanna Leventhal ◽

Friederike Feldmann ◽

Atsushi Okumura ◽

...

Keyword(s):

Mouse Model ◽

Severe Disease ◽

Case Fatality ◽

Febrile Illness ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Type I ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Viral Determinants

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.

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Immunocompetent Mouse Model for Crimean-Congo Hemorrhagic Fever Virus

10.1101/2020.11.05.369520 ◽

2020 ◽

Author(s):

David W. Hawman ◽

Kimberly Meade-White ◽

Shanna Leventhal ◽

Friederike Feldmann ◽

Atsushi Okumura ◽

...

Keyword(s):

Mouse Model ◽

Severe Disease ◽

Case Fatality ◽

Febrile Illness ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Type I ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Viral Determinants

AbstractCrimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.

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Immunogenicity of a DNA-Based Sindbis Replicon Expressing Crimean–Congo Hemorrhagic Fever Virus Nucleoprotein

Vaccines ◽

10.3390/vaccines9121491 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1491

Author(s):

Thomas Tipih ◽

Mark Heise ◽

Felicity Jane Burt

Keyword(s):

Immune Response ◽

Sindbis Virus ◽

Cytokine Production ◽

Antiviral Drug ◽

Case Fatality ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Virus Vector ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus

Crimean–Congo hemorrhagic fever virus (CCHFV) infrequently causes hemorrhagic fever in humans with a case fatality rate of 30%. Currently, there is neither an internationally approved antiviral drug nor a vaccine against the virus. A replicon based on the Sindbis virus vector encoding the complete open reading frame of a CCHFV nucleoprotein from a South African isolate was prepared and investigated as a possible candidate vaccine. The transcription of CCHFV RNA and recombinant protein production by the replicon were characterized in transfected baby hamster kidney cells. A replicon encoding CCHFV nucleoprotein inserted in plasmid DNA, pSinCCHF-52S, directed transcription of CCHFV RNA in the transfected cells. NIH-III heterozygous mice immunized with pSinCCHF-52S generated CCHFV IgG specific antibodies with notably higher levels of IgG2a compared to IgG1. Splenocytes from mice immunized with pSinCCHF-52S secreted IFN-γ and IL-2, low levels of IL-6 or IL-10, and no IL-4. No specific cytokine production was registered in splenocytes of mock-immunized mice (p < 0.05). Thus, our study demonstrated the expression of CCHFV nucleoprotein by a Sindbis virus vector and its immunogenicity in mice. The spectrum of cytokine production and antibody profile indicated predominantly Th1-type of an anti-CCHFV immune response. Further studies in CCHFV-susceptible animals are necessary to determine whether the induced immune response is protective.

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