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

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.Author summary: Crimean-Congo hemorrhagic fever is one of the most severe zoonotic viral disease that occurs in humans. It is therefore necessary to provide public health stakeholders, research funding agencies and healthcare workers with accurate data on the burden of this disease in order to guide decision-making priorities. Our study is the first systematic review with meta-analysis to provide global data on CCHFV CFR in humans, CCHFV prevalence and seroprevalence in humans, ticks and other animal species. This review is also the first to maps CCHFV CRF, prevalence, and seroprevalence in humans, ticks and other animal species according to the country income level, geographic region, various human categories, and extensive tick and animal species. Broadly, the study showed elevated CFR in low-income countries, WHO regions of Africa, South-East Asia and Eastern Mediterranean, and adult and outpatient patients. In addition, the prevalence and seroprevalence of CCHFV were higher in CCHFV suspected cases, healthcare workers, adults and hospitalized patients, ticks of the genus Ornithodoros and Amblyomma, and animals of the orders Perissodactyla and Bucerotiformes. Finally, our findings show that more attention needs to be paid to low-income countries particularly in WHO regions of Africa, South-East Asia, and Eastern Mediterranean in order to prevent human deaths due to CCHFV. In particular low-income countries and adults should benefit from emergency measures aimed at improving the management of patients with CCHF and reducing exposure of humans and animals to ticks. This meta-analysis further shows that apart from the monitoring and control of CCHFV in humans, a special attention should also be given to role played by non-Hyalomma tick species and other animal species, both domestic and wild.