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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.

IntroductionConsideration of confounding factors about the association between Lower Respiratory Tract Infections (LRTI) in childhood and the development of subsequent wheezing has been incompletely described. We determined the association between viral LRTI at ≤ 5 years of age and the development of wheezing in adolescence or adulthood by a meta-analysis and a sensitivity analysis including comparable studies for major confounding factors.MethodsWe performed searches through Pubmed and Global Index Medicus databases. We selected cohort studies comparing the frequency of subsequent wheezing in children with and without LRTI in childhood regardless of the associated virus. We extracted the publication data, clinical and socio-demographic characteristics of the children, and confounding factors. We analyzed data using random effect model.ResultsThe meta-analysis included 18 publications (22 studies) that met the inclusion criteria. These studies showed that viral LRTI in children ≤ 3 years was associated with an increased risk of subsequent development of wheezing (OR = 3.1, 95% CI = 2.4–3.9). The risk of developing subsequent wheezing was conserved when considering studies with comparable groups for socio-demographic and clinical confounders.ConclusionsWhen considering studies with comparable groups for most confounding factors, our results provided strong evidence for the association between neonatal viral LRTI and the subsequent wheezing development. Further studies, particularly from lower-middle income countries, are needed to investigate the role of non-bronchiolitis and non-HRSV LRTI in the association between viral LRTI in childhood and the wheezing development later. In addition, more studies are needed to investigate the causal effect between childhood viral LRTI and the wheezing development later.Trial registrationReview registration: PROSPERO, CRD42018116955;https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018116955.

Accurate data on the Lassa virus (LASV) human case fatality rate (CFR) and the prevalence of LASV in humans, rodents and other mammals are needed for better planning of actions that will ultimately reduce the burden of LASV infection in sub-Saharan Africa. In this systematic review with meta-analysis, we searched PubMed, Scopus, Africa Journal Online, and African Index Medicus from 1969 to 2020 to obtain studies that reported enough data to calculate LASV infection CFR or prevalence. Study selection, data extraction, and risk of bias assessment were conducted independently. We extracted all measures of current, recent, and past infections with LASV. Prevalence and CFR estimates were pooled using a random-effect meta-analysis. Factors associated with CFR, prevalence, and sources of between-study heterogeneity were determined using subgroup and metaregression analyses. This review was registered with PROSPERO, CRD42020166465. We initially identified 1,399 records and finally retained 109 reports that contributed to 291 prevalence records from 25 countries. The overall CFR was 29.7% (22.3–37.5) in humans. Pooled prevalence of LASV infection was 8.7% (95% confidence interval: 6.8–10.8) in humans, 3.2% (1.9–4.6) in rodents, and 0.7% (0.0–2.3) in other mammals. Subgroup and metaregression analyses revealed a substantial statistical heterogeneity explained by higher prevalence in tissue organs, in case-control, in hospital outbreak, and surveys, in retrospective studies, in urban and hospital setting, in hospitalized patients, and in West African countries. This study suggests that LASV infections is an important cause of death in humans and that LASV are common in humans, rodents and other mammals in sub-Saharan Africa. These estimates highlight disparities between sub-regions, and population risk profiles. Western Africa, and specific key populations were identified as having higher LASV CFR and prevalence, hence, deserving more attention for cost-effective preventive interventions., Author summary Lassa virus (LASV) infection constitutes a major public health threat as it has a direct impact on the mortality of febrile patients, healthcare workers, pregnant women, visitors of endemic countries with a consequential negative impact on national and individual economies. It is necessary to have accurate epidemiological data on LASV infection, in order to prioritize the policies, funding for public health interventions, and health-care planning, especially in sub-Saharan Africa (SSA). Data concerning virus occurrence in rodents and other mammal species can also assist in guiding control of Lassa fever from an ecological perspective. This could include preventive measures such as the protection of food fields by anti-rodent barriers, the protection of rodent predatory fauna, the sanitation of home and particularly the food storage place and the blocking of rodent access to home and food stored. Our systematic review and meta-analysis of LASV infection in SSA has contemporarily and comprehensively summarized the prevalence of current, recent, and past infection both in humans, rodents and other mammals. Broadly, the study showed relatively high CFR estimates in humans. Additionally, Western Africa presented the highest burden of LASV infections compared to other regions. This study emphasized various populations of SSA with relatively high burden of LASV infection. We have identified specific populations at high risk of LASV infection, who may urgently benefit from routine screening, detection and management programmes. Beyond, preventive strategies should be promoted, by educating and raising people’s awareness about LASV infection, and strengthening practitioners’ capacities towards adequate diagnosis and proper management of this infection in SSA.