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

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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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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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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Detection of the RNA for new multicomponent virus in patients with Crimean-Congo hemorrhagic fever in southern Russia

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1192 ◽

2020 ◽

Author(s):

Vladimir Ternovoi ◽

Anastasia Gladysheva ◽

Alexandra Sementsova ◽

Anna Zaykovskaya ◽

Anna Volynkina ◽

...

Keyword(s):

Phylogenetic Analyses ◽

Hemorrhagic Fever ◽

European Part ◽

Viral Rna ◽

Crimean Congo Hemorrhagic Fever ◽

Viral Genomes ◽

Cchf Virus ◽

European Part Of Russia ◽

Human Sera ◽

Southern Russia

Background: Recently, a new multicomponent RNA-containing virus was described and called as Jingmen tick virus (JMTV) supposedly belonging to flaviviruses. A virus consists of four viral particles and JMTV was firstly isolated from ticks in China and South America. Aims: Detection viral RNA specific for JMTV complex, sequencing genome fragments and taxonomy identification novel virus from JMTV complex in patients with Crimean-Congo hemorrhagic fever (CCHF) from southern European part of Russia. Materials and methods: Panel of 20 randomly selected sera from patients with confirmed Crimean-Congo hemorrhagic fever was collected in 2016 and was used for detection JMTV and CCHF viral RNA by PCR with experimental primers. Subsequent sequencing of isolated fragments of viral genomes was used for identification JMTV and CCHF virus genetic materials and phylogenetic analyses. Results: The viral RNAs of the CCHF virus and JMTV were detected in blood of four patients. Sequencing of the isolated PCR fragment of S segment CCHF virus allowed identifying these RNA isolates as Europe 1 lineage, subgroups Va and Vb of the CCHF virus that is a typical for the southern European part of the Russia. The nucleotide sequences of segment 2 (GP glycoprotein) of the JMTV were also detected by RP PCR and sequencing in these human sera. The new JMTV isolates were clustered together by phylogenetic analysis. The level of nucleotide identity for newly discovered JMTV isolates was only about 81-82% with comparison to the previously described European variants (Kosovo) of the JMTV. Conclusions: The results suggest that viral genomic RNA for new multicomponent flavivirus named as Manych virus and related to the JMTV complex was discovered in sera of CCHF patients in Russia.

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Crimean-Congo hemorrhagic fever virus antibody prevalence in Mauritanian livestock (cattle, goats, sheep and camels) is stratified by the animal’s age

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009228 ◽

2021 ◽

Vol 15 (4) ◽

pp. e0009228

Author(s):

Ansgar Schulz ◽

Yahya Barry ◽

Franziska Stoek ◽

Aliou Ba ◽

Jana Schulz ◽

...

Keyword(s):

Clinical Symptoms ◽

Small Ruminants ◽

Hemorrhagic Fever ◽

Immunofluorescence Assay ◽

Fever Virus ◽

Crimean Congo Hemorrhagic Fever ◽

Prevalence Studies ◽

Hemorrhagic Fever Virus ◽

Generalized Linear Mixed Effects ◽

The Impact

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most widespread zoonotic arthropod-borne viruses in many parts of Africa, Europe and Asia. It belongs to the family of Nairoviridae in the genus of Orthonairovirus. The main reservoir and vector are ticks of the genus Hyalomma. Livestock animals (such as cattle, small ruminants and camels) develop a viremias lasting up to two weeks with absence of clinical symptoms, followed by seroconversion. This study was carried out to assess risk factors that affect seroprevalence rates in different species. In total, 928 livestock animal samples (cattle = 201; sheep = 247; goats = 233; camels = 247) from 11 out of 13 regions in Mauritania were assayed for CCHFV-specific immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assays (ELISA) (including a novel indirect camel-IgG-specific CCHFV ELISA). Inconclusive results were resolved by an immunofluorescence assay (IFA). A generalized linear mixed-effects model (GLMM) was used to draw conclusions about the impact of certain factors (age, species, sex and region) which might have influenced the CCHFV antibody status of surveyed animals. In goats and sheep, about 15% of the animals were seropositive, whereas in cattle (69%) and camels (81%), the prevalence rate was significantly higher. On average, cattle and camels were up to twice to four times older than small ruminants. Interestingly, the seroprevalence in all species was directly linked to the age of the animals, i.e. older animals had significantly higher seroprevalence rates than younger animals. The highest CCHFV seroprevalence in Mauritania was found in camels and cattle, followed by small ruminants. The large proportion of positive animals in cattle and camels might be explained by the high ages of the animals. Future CCHFV prevalence studies should at least consider the age of surveyed animals in order to avoid misinterpretations.

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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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Differential Cell Line Susceptibility to Crimean-Congo Hemorrhagic Fever Virus

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.648077 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shiyu Dai ◽

Qiaoli Wu ◽

Xiaoli Wu ◽

Cheng Peng ◽

Jia Liu ◽

...

Keyword(s):

Cell Lines ◽

Ex Vivo ◽

Animal Cell ◽

Hemorrhagic Fever ◽

Viral Disease ◽

Permissive Cell ◽

Hek 293 ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Cchf Virus

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease of global concerns due to the increasing incidence and lack of effective treatments. The causative agent, CCHF virus (CCHFV), has been characterized for years; however, its tropism in cell lines of different host and tissue origins remains unclear. This study characterized the susceptibility of 16 human and 6 animal cell lines to CCHFV. Increased viral load and viral nucleoprotein expression, and productive CCHFV replication were detected in human vascular (HUVEC), renal (SW-13 and HEK-293), hepatic (Huh7), and cerebral (U-87 MG) cell lines, which were considered CCHFV-highly permissive cell lines. Renal cell lines derived from monkey and dog could also support CCHFV replication. This study evaluated the susceptibility of different cell lines to CCHFV and identified CCHFV-permissive cell lines. Our findings raise concerns regarding the use of cell lines in ex vivo studies of CCHFV and may have important implications for further fundamental research, which would promote understanding of CCHFV pathogenesis and transmission, as well as benefit designing strategies for disease prevention and control.

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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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Reverse Genetics for Crimean-Congo Hemorrhagic Fever Virus

Journal of Virology ◽

10.1128/jvi.77.10.5997-6006.2003 ◽

2003 ◽

Vol 77 (10) ◽

pp. 5997-6006 ◽

Cited By ~ 73

Author(s):

Ramon Flick ◽

Kirsten Flick ◽

Heinz Feldmann ◽

Fredrik Elgh

Keyword(s):

Reporter Gene ◽

Reverse Genetics ◽

Hemorrhagic Fever ◽

Eukaryotic Cell ◽

Health Concern ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Pol I ◽

Prophylactic Measures ◽

Cchf Virus

ABSTRACT The widespread geographical distribution of Crimean-Congo hemorrhagic fever (CCHF) virus (more than 30 countries) and its ability to produce severe human disease with high mortality rates (up to 60%) make CCHF a major public health concern worldwide. We describe here the successful establishment of a reverse genetics technology for CCHF virus, a member of the genus Nairovirus, family Bunyaviridae. The RNA polymerase I (pol I) system was used to generate artificial viral RNA genome segments (minigenomes), which contained different reporter genes in antisense (virus RNA) or sense (virus-complementary RNA) orientation flanked by the noncoding regions of the CCHF virus S segment. Reporter gene expression was observed in different eukaryotic cell lines following transfection and subsequent superinfection with CCHF virus, confirming encapsidation, transcription, and replication of the pol I-derived minigenomes. The successful transfer of reporter gene activity to fresh cells demonstrated the generation of recombinant CCHF viruses, thereby confirming the packaging of the pol I-derived minigenomes into progeny viruses. The system offers a unique opportunity to study the biology of nairoviruses and to develop therapeutic and prophylactic measures against CCHF infections. In addition, we demonstrated for the first time that the human pol I system can be used to develop reverse genetics approaches for viruses in the family Bunyaviridae. This is important since it might facilitate the manipulation of bunyaviruses with cell and host tropisms restricted to primates.

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Evidence for recombination in Crimean-Congo hemorrhagic fever virus

Journal of General Virology ◽

10.1099/vir.0.80974-0 ◽

2005 ◽

Vol 86 (8) ◽

pp. 2333-2338 ◽

Cited By ~ 42

Author(s):

Alexander N. Lukashev

Keyword(s):

Phylogenetic Trees ◽

Hemorrhagic Fever ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Bootscan Analysis ◽

Phylogenetic Studies ◽

Cchf Virus ◽

L Segment ◽

Virus Strains ◽

Multiple Recombination

Crimean-Congo hemorrhagic fever (CCHF) virus has attracted considerable attention recently and a number of phylogenetic studies have been published, based mostly on partial sequences of S and M RNA segments. In this study, available full-length S, M and L segment sequences of CCHF virus were checked for recombination. Similarity plots and bootscan analysis of the S segment suggested multiple recombination events between southern European, Asian and African CCHF virus strains, with additional evidence provided by phylogenetic trees, the hidden Markov model and probabilistic divergence measures methods. No unambiguous signs of recombination were observed for M and L segments; however, the results did not exclude the possibility of this. These findings, coupled with a recent report on reassortment in CCHF virus, suggest caution when assessing CCHF virus phylogeny based on short sequence fragments.

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Cross-Reaction or Co-Infection? Serological Discrimination of Antibodies Directed against Dugbe and Crimean-Congo Hemorrhagic Fever Orthonairovirus in Nigerian Cattle

Viruses ◽

10.3390/v13071398 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1398

Author(s):

Julia Hartlaub ◽

Oluwafemi B. Daodu ◽

Balal Sadeghi ◽

Markus Keller ◽

James Olopade ◽

...

Keyword(s):

Indirect Immunofluorescence ◽

Hemorrhagic Fever ◽

Immunofluorescence Assay ◽

Cross Reaction ◽

African Countries ◽

Crimean Congo Hemorrhagic Fever ◽

Transmission Cycle ◽

N Protein ◽

Seroprevalence Data ◽

Human Infections

Dugbe orthonairovirus (DUGV) and Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) are tick-borne arboviruses within the order Bunyavirales. Both viruses are endemic in several African countries and can induce mild (DUGV, BSL 3) or fatal (CCHFV, BSL 4) disease in humans. Ruminants play a major role in their natural transmission cycle. Therefore, they are considered as suitable indicator animals for serological monitoring studies to assess the risk for human infections. Although both viruses do not actually belong to the same serogroup, cross-reactivities have already been reported earlier—hence, the correct serological discrimination of DUGV and CCHFV antibodies is crucial. In this study, 300 Nigerian cattle sera (150 CCHFV seropositive and seronegative samples, respectively) were screened for DUGV antibodies via N protein-based ELISA, indirect immunofluorescence (iIFA) and neutralization assays. Whereas no correlation between the CCHFV antibody status and DUGV seroprevalence data could be demonstrated with a newly established DUGV ELISA, significant cross-reactivities were observed in an immunofluorescence assay. Moreover, DUGV seropositive samples did also cross-react in a species-adapted commercial CCHFV iIFA. Therefore, ELISAs seem to be able to reliably differentiate between DUGV and CCHFV antibodies and should preferentially be used for monitoring studies. Positive iIFA results should always be confirmed by ELISAs.

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