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Crimean-Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures.

ABSTRACT: Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral zoonosis with a case-fatality rate ranging from 9% to 50% in humans. Although a licensed vaccine to prevent infection by the CCHF virus (CCHFV) exists, its ability to induce neutralizing antibodies is limited and its efficacy against CCHFV remains undetermined. In addition, controlling CCHF infections by eradication of the tick reservoir has been ineffective, both economically and logistically, and the treatment options for CCHF remain limited. In this review, we first critically discuss the existing animal models to evaluate therapeutics for CCHF. We then review the therapeutic options for CCHF that have been investigated in human cases, followed by investigational drugs that have been evaluated in pre-clinical studies. We highlight the importance of understanding human prognostic factors in developing an animal model for CCHF that recapitulates hallmarks of human disease and its implication for selecting therapeutic candidates.

SUBMITTER: Mendoza EJ

PROVIDER: S-EPMC7165601 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Crimean-Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures.

Mendoza E J EJ Warner B B Safronetz D D Ranadheera C C

Zoonoses and public health 20180420 5

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral zoonosis with a case-fatality rate ranging from 9% to 50% in humans. Although a licensed vaccine to prevent infection by the CCHF virus (CCHFV) exists, its ability to induce neutralizing antibodies is limited and its efficacy against CCHFV remains undetermined. In addition, controlling CCHF infections by eradication of the tick reservoir has been ineffective, both economically and logistically, and the treatment options for ...[more]

PMID: 29676526

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Project description:BackgroundCrimean-Congo haemorrhagic fever virus (CCHFV) is a highly pathogenic virus for which a safe and effective vaccine is not yet available, despite being considered a priority emerging pathogen. Understanding transmission patterns and the use of potential effective vaccines are central elements of the future plan against this infection.MethodsWe developed a series of models of transmission amongst livestock, and spillover infection into humans. We use real-world human and animal data from a CCHFV endemic area in Afghanistan (Herat) to calibrate our models. We assess the value of environmental drivers as proxy indicators of vector activity, and select the best model using deviance information criteria. Finally we assess the impact of vaccination by simulating campaigns targeted to humans or livestock, and to high-risk subpopulations (i.e, farmers).FindingsSaturation deficit is the indicator that better explains tick activity trends in Herat. Recent increments in reported CCHFV cases in this area are more likely explained by increased surveillance capacity instead of changes in the background transmission dynamics. Modelling suggests that clinical cases only represent 31% (95% CrI 28%-33%) of total infections in this area. Vaccination campaigns targeting humans would result in a much larger impact than livestock vaccination (266 vs 31 clinical cases averted respectively) and a more efficient option when assessed in courses per case averted (35 vs 431 respectively). Targeted vaccination of farmers is impactful and more efficient, resulting in 19 courses per case averted (95% CrI 7-62) compared to targeting the general population (35 courses 95% CrI 16-107).ConclusionsCCHFV is endemic in Herat, and transmission cycles are well predicted by environmental drivers like saturation deficit. Vaccinating humans is likely to be more efficient and impactful than animals, and importantly targeted interventions to high risk groups like farmers can offer a more efficient approach to vaccine roll-out.

Project description:IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne, zoonotic viral disease that causes haemorrhagic symptoms. Despite having eight confirmed outbreaks between 2013 and 2017, all within Uganda's 'cattle corridor', no targeted tick control programs exist in Uganda to prevent disease. During a seven-month-period from July 2018-January 2019, the Ministry of Health confirmed multiple independent CCHF outbreaks. We investigated to identify risk factors and recommend interventions to prevent future outbreaks.MethodsWe defined a confirmed case as sudden onset of fever (≥37.5°C) with ≥4 of the following signs and symptoms: anorexia, vomiting, diarrhoea, headache, abdominal pain, joint pain, or sudden unexplained bleeding in a resident of the affected districts who tested positive for Crimean-Congo haemorrhagic fever virus (CCHFv) by RT-PCR from 1 July 2018-30 January 2019. We reviewed medical records and performed active case-finding. We conducted a case-control study and compared exposures of case-patients with age-, sex-, and sub-county-matched control-persons (1:4).ResultsWe identified 14 confirmed cases (64% males) with five deaths (case-fatality rate: 36%) from 11 districts in western and central region. Of these, eight (73%) case-patients resided in Uganda's 'cattle corridor'. One outbreak involved two case-patients and the remainder involved one. All case-patients had fever and 93% had unexplained bleeding. Case-patients were aged 6-36 years, with persons aged 20-44 years more affected (AR: 7.2/1,000,000) than persons ≤19 years (2.0/1,000,000), p = 0.015. Most (93%) case-patients had contact with livestock ≤2 weeks before symptom onset. Twelve (86%) lived <1 km from grazing fields compared with 27 (48%) controls (ORM-H = 18, 95% CI = 3.2-∞) and 10 (71%) of 14 case-patients found ticks attached to their bodies ≤2 weeks before symptom onset, compared to 15 (27%) of 56 control-persons (ORM-H = 9.3, 95%CI = 1.9-46).ConclusionsCCHF outbreaks occurred sporadically during 2018-2019, both within and outside 'cattle corridor' districts of Uganda. Most cases were associated with tick exposure. The Ministry of Health should partner with the Ministry of Agriculture, Animal Industry and Fisheries to develop joint nationwide tick control programs and strategies with shared responsibilities through a One Health approach.

Dataset Information

Crimean-Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures.

Publications

Crimean-Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures.

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