Background Rift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, the Arabian Peninsula, 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) arthropod 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 infection 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.

The Rift Valley fever virus (RVFV) is a zoonotic arbovirus that can also transmit directly to humans from livestock. Previous studies have shown consumption of sick animal products are risk factors for RVFV infection, but it is difficult to disentangle those risk factors from other livestock rearing activities. Urban areas have an increased demand for animal source foods, different vector distributions, and various arboviruses are understood to establish localized urban transmission cycles. Thus far, RVFV is an unevaluated public health risk in urban areas within endemic regions. We tested participants in our ongoing urban cohort study on dengue (DENV) and chikungunya (CHIKV) virus for RVFV exposure and found 1.6% (57/3,560) of individuals in two urban areas of Kenya had anti-RVFV IgG antibodies. 88% (50/57) of RVFV exposed participants also had antibodies to DENV, CHIKV, or both. Although livestock ownership was very low in urban study sites, RVFV exposure was overall significantly associated with seeing goats around the homestead (OR = 2.34 (CI 95%: 1.18–4.69, p = 0.02) and in Kisumu, RVFV exposure was associated with consumption of raw milk (OR = 6.28 (CI 95%: 0.94–25.21, p = 0.02). In addition, lack of piped water and use of small jugs (15–20 liters) for water was associated with a higher risk of RVFV exposure (OR = 5.36 (CI 95%: 1.23–16.44, p = 0.01) and this may contribute to interepidemic vector-borne maintenance of RVFV. We also investigated perception towards human vaccination for RVFV and identified high acceptance (91% (97/105) at our study sites. This study provides baseline evidence to guide future studies investigating the urban potential of RVFV and highlights the unexplored role of animal products in continued spread of RVFV.

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Rift Valley fever virus (RVFV) is a zoonotic arbovirus that has profound impact on domestic ruminants and can also be transmitted to humans via infected animal secretions. Urban areas in endemic regions across Africa have susceptible animal and human hosts, dense vector distributions, and source livestock (often from high risk locations to meet the demand for animal protein). Yet, there has never been a documented urban outbreak of RVF. To understand the likely risk of RVFV introduction to urban communities from their perspective and guide future initiatives, we conducted focus group discussions with slaughterhouse workers, slaughterhouse animal product traders, and livestock owners in Kisumu City and Ukunda Town in Kenya. For added perspective and data triangulation, in-depth interviews were conducted one-on-one with meat inspector veterinarians from selected slaughterhouses. A theoretical framework relevant to introduction, transmission, and potential persistence of RVF in urban areas is presented here. Urban livestock were primarily mentioned as business opportunities, but also had personal sentiment. In addition to slaughtering risks, perceived risk factors including consumption of fresh milk. High risk groups’ knowledge and experience with RVFV and other zoonotic diseases impacted their consideration personal risk, with consensus towards lower risk in the urban setting compared to rural areas as determination of health risk was said to primarily rely on hygiene practices rather than the slaughtering process. Groups relied heavily on veterinarians to confirm animal health and meat safety, yet veterinarians reported difficulty in accessing RVFV diagnostics. We also identified vulnerable public health regulations including corruption in meat certification outside of the slaughterhouse system, and blood collected during slaughter being used for food and medicine, which could provide a means for direct RVFV community transmission. These factors, when compounded by diverse urban vector breeding habitats and dense human and animal populations, could create suitable conditions for RVFV to arrive an urban center via a viremic imported animal, transmit to locally owned animals and humans, and potentially adapt to secondary vectors and persist in the urban setting. This explorative qualitative study proposes risk pathways and provides initial insight towards determining how urban areas could adapt control measures and plan future initiatives to better understand urban RVF potential.

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.