Paving the way for human vaccination against Rift Valley fever virus: A systematic literature review of RVFV epidemiology from 1999 to 2021

Background: Rift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, Arabia, and the Indian Ocean. This systematic review’s objective was to consolidate understanding of RVFV epidemiology during 1999-2021 and highlight knowledge gaps relevant to plans for human vaccine trials. Methodology/Principal Findings: The review is registered with PROSPERO (CRD42020221622). Reports of RVFV infection or exposure among humans, animals, and/or vectors in Africa, the Arabian Peninsula, and the Indian Ocean during the period January 1999 to June 2021 were eligible for inclusion. Online databases were searched for publications, and supplemental materials were recovered from official reports and research colleagues. Exposures were classified into five groups: 1) acute human RVF cases, 2) acute animal cases, 3) human RVFV sero-surveys, 4) animal sero-surveys, and 5) insect infections. Human risk factors, circulating RVFV lineages, and surveillance methods were also tabulated. In meta-analysis of risks, summary odds ratios were computed using random-effects modeling. 1104 unique human or animal RVFV transmission events were reported in 39 countries during 1999-2021. Outbreaks among humans or animals occurred at rates of 5.8/year and 12.4/year, respectively, with Mauritania, Madagascar, Kenya, South Africa, and Sudan having the most human outbreak years. Men had greater odds of RVFV infection than women, and animal contact, butchering, milking, and handling aborted material were significantly associated with greater odds of exposure. Animal risk was linked to location, proximity to water, and exposure to other herds or wildlife. RVFV was detected in a variety of mosquito vectors during interepidemic periods, confirming ongoing transmission. Conclusions/Significance: With broad variability in surveillance, case finding, survey design, and RVFV case confirmation, combined with uncertainty about populations-at-risk, there were inconsistent results from location to location. However, it was evident that RVFV transmission is expanding its range and frequency. Gaps assessment indicated the need to harmonize human and animal surveillance and improve diagnostics and genotyping. Given the frequency of RVFV outbreaks, human vaccination has strong potential to mitigate the impact of this now widely endemic disease.