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Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by a phlebovirus and transmitted by Aedes mosquitoes. Humans can also be infected through direct contact with blood (aerosols) or tissues (placenta, stillborn) of infected animals. Although severe clinical cases can be observed, infection with RVF virus (RVFV) in humans is, in most cases, asymptomatic or causes a febrile illness without serious symptoms. In small ruminants RVFV mainly causes abortion and neonatal death. The distribution of RVFV has been well documented in many African countries, particularly in the north (Egypt, Sudan), east (Kenya, Tanzania, Somalia), west (Senegal, Mauritania) and south (South Africa), but also in the Indian Ocean (Madagascar, Mayotte) and the Arabian Peninsula. In contrast, the prevalence of RVFV has rarely been investigated in central African countries. We therefore conducted a large serological survey of rural populations in Gabon, involving 4,323 individuals from 212 randomly selected villages (10.3% of all Gabonese villages). RVFV-specific IgG was found in a total of 145 individuals (3.3%) suggesting the wide circulation of Rift Valley fever virus in Gabon. The seroprevalence was significantly higher in the lakes region than in forest and savannas zones, with respective rates of 8.3%, 2.9% and 2.2%. In the lakes region, RVFV-specific IgG was significantly more prevalent in males than in females (respectively 12.8% and 3.8%) and the seroprevalence increased gradually with age in males but not in females. Although RVFV was suggested to circulate at a relatively high level in Gabon, no outbreaks or even isolated cases have been documented in the country. The higher prevalence in the lakes region is likely to be driven by specific ecologic conditions favorable to certain mosquito vector species. Males may be more at risk of infection than females because they spend more time farming and hunting outside the villages, where they may be more exposed to mosquito bites and infected animals. Further investigations are needed to determine the putative sylvan cycle of RVFV, including the mosquito species and the reservoir role of wild animals in the viral maintenance cycle.

We screened 650 febrile patients from Benin for Rift Valley fever and Crimean-Congo hemorrhagic fever viruses during 2022-2023. None were positive by reverse transcription PCR; 1.1% and 0.3%, respectively, had virus-specific IgG. False-positive results from malaria-associated antibodies likely reacting with histidine-tagged viral antigens mandate careful validation of serologic tests in malaria-endemic regions.

Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in livestock and humans. The virus has caused recurrent outbreaks in Africa and the Arabian Peninsula since its discovery in 1931. This review sought to evaluate RVFV seroprevalence across the African continent in livestock, wildlife and humans in order to understand the spatio-temporal distribution of RVFV seroprevalence and to identify knowledge gaps and areas requiring further research. Risk factors associated with seropositivity were identified and study designs evaluated to understand the validity of their results. The Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to produce a protocol to systematically search for RVFV seroprevalence studies in PubMed and Web of Science databases. The Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement guided the evaluation of study design and analyses. A total of 174 RVFV seroprevalence studies in 126 articles fulfilled the inclusion criteria. RVFV seroprevalence was recorded in 31 African countries from 1968 to 2016 and varied by time, species and country. RVFV seroprevalence articles including either livestock and humans or livestock and wildlife seroprevalence records were limited in number (8/126). No articles considered wildlife, livestock and human seroprevalence concurrently, nor wildlife and humans alone. Many studies did not account for study design bias or the sensitivity and specificity of diagnostic tests. Future research should focus on conducting seroprevalence studies at the wildlife, livestock and human interface to better understand the nature of cross-species transmission of RVFV. Reporting should be more transparent and biases accounted for in future seroprevalence research to understand the true burden of disease on the African continent.

Rift Valley fever virus (RVFV) is a negative-sense arbovirus that causes several severe diseases, including hemorrhagic fever in ruminants and humans. There are currently no FDA-approved vaccines or therapeutics for RVFV. The viral nonstructural protein NSs acts like a molecular Harry Houdini, the world-famous escape artist, to help the virus evade the host’s innate immune response and serves as the main virulence factor of RVFV. In this review, we discuss the molecular mechanisms by which NSs interacts with multiple factors to modulate host processes, evade the host immune response, and facilitate viral replication. The impact of NSs mutations that cause viral attenuation is also discussed. Understanding the molecular mechanisms by which NSs evades the host innate immune response is crucial for developing novel therapeutics and vaccines targeting RVFV.

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. 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. 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.

Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV) found in Africa and the Middle East. Outbreaks can cause extensive morbidity and mortality in humans and livestock. Following the diagnosis of two acute human RVF cases in Kabale district, Uganda, we conducted a serosurvey to estimate RVFV seroprevalence in humans and livestock and to identify associated risk factors. Humans and animals at abattoirs and villages in Kabale district were sampled. Persons were interviewed about RVFV exposure risk factors. Human blood was tested for anti-RVFV IgM and IgG, and animal blood for anti-RVFV IgG. 655 human and 1051 animal blood samples were collected. Anti-RVFV IgG was detected in 78 (12%) human samples; 3 human samples (0.5%) had detectable IgM only, and 7 (1%) had both IgM and IgG. Of the 10 IgM-positive persons, 2 samples were positive for RVFV by PCR, confirming recent infection. Odds of RVFV seropositivity were greater in participants who were butchers (odds ratio [OR] 5.1; 95% confidence interval [95% CI]: 1.7-15.1) and those who reported handling raw meat (OR 3.4; 95% CI 1.2-9.8). No persons under age 20 were RVFV seropositive. The overall animal seropositivity was 13%, with 27% of cattle, 7% of goats, and 4% of sheep seropositive. In a multivariate logistic regression, cattle species (OR 9.1; 95% CI 4.1-20.5), adult age (OR 3.0; 95% CI 1.6-5.6), and female sex (OR 2.1; 95%CI 1.0-4.3) were significantly associated with animal seropositivity. Individual human seropositivity was significantly associated with animal seropositivity by subcounty after adjusting for sex, age, and occupation (p < 0.05). Although no RVF cases had been detected in Uganda from 1968 to March 2016, our study suggests that RVFV has been circulating undetected in both humans and animals living in and around Kabale district. RVFV seropositivity in humans was associated with occupation, suggesting that the primary mode of RVFV transmission to humans in Kabale district could be through contact with animal blood or body fluids.

Rift Valley fever (RVF) is a zoonotic viral disease that causes epidemics and epizootics among humans and livestock, resulting in substantial health and socioeconomic consequences. Currently, there are no RVF vaccines licensed for humans, but several candidates show promise in early-stage development. Existing gaps in RVF epidemiological data and challenges associated with predicting RVF outbreak risk complicate the planning of efficacy studies, making the pathway to licensure for promising candidates unclear. In June 2024, the Coalition for Epidemic Preparedness Innovations (CEPI) convened a two-day workshop in Nairobi, Kenya, to discuss RVF epidemiology, modeling priorities, and specific gaps relevant to human RVF vaccine development. The workshop included representatives from multiple RVF-endemic countries, key global collaborators, and international health organizations. Workshop participants identified five key priorities: (1) Looking beyond outbreaks: There is a need to better characterize the complex One Health epidemiology of RVF and understand interepidemic persistence of the virus; (2) Better data for better models: Epidemiological modeling is crucial for research, prediction, and planning, but it requires accurate and representative data; (3) New, improved and accessible diagnostics and serological assays: These are needed to inform epidemiology and case definitions, without which RVF research will continue to suffer due to paucity of data and challenges in determining infection and exposure; (4) Defining use cases, regulatory pathways, and implementation strategies for human vaccines: Clarity on these topics will facilitate licensure and effective use of RVF vaccines; and (5) People-centered approaches: Community engagement and involvement of social and behavioral scientists are key to the success of human vaccine research and development and implementation, particularly as the virus impacts livestock and livelihoods. Workshop participants welcomed a renewed focus for RVF epidemiology and modeling, and expressed enthusiasm for continued multidisciplinary collaborations to support enabling sciences for human RVF vaccine research and development.

Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A ‘One Health’ vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.

Rift Valley fever (RVF) virus and Coxiella burnetii infections are significant public health concerns in East Africa, causing recurring outbreaks. However, the prevalence of these pathogens among febrile patients in Ethiopia remains unknown. This study aimed to determine the prevalence and associated factors of these infections among febrile patients. A multisite cross-sectional study was conducted among 415 randomly selected adult febrile patients from health facilities in Shinile and Dire Dawa, Ethiopia, between March 01, 2023, and February 28, 2024. Serum samples were tested for the presence of antibodies against RVF virus and C. burnetii infections using various Enzyme Linked Immunosorbent Assays. Polymerase Chain Reaction (PCR) was used to detect RVF virus RNA and C. burnetii DNA in blood samples. A multivariable logistic regression model was used to identify predictive factors. A p value <0.05 was considered statistically significant. Of the 402 serum samples analyzed, 21 (5.2%) tested positive for immunoglobulin G (IgG) antibodies against RVF virus, and 86 (21.4%) tested positive for C. burnetii Phase I and Phase II antibodies. No RVF virus IgM was detected. Among the C. burnetii antibodies positive sera, 6 (7.0%) were positive for Phase II IgG antibodies. No blood samples tested positive for RVF virus RNA or C. burnetii DNA. Febrile patients aged ≥35 years had significantly higher odds of RVF virus exposure (AOR: 3.1, 95% CI: 1.3-7.8). Females (AOR: 1.7, 95% CI: 1.1-2.9), rural residents (AOR: 2.4, 95% CI: 1.3-4.5), and febrile patients who disposed of dead animals (AOR: 2.6, 95% CI: 1.2-5.6) exhibited significantly higher odds of C. burnetii infection. This study reveals significant but underrecognized exposure to RVF virus (5.2%) and C. burnetii (21.4%) infections among febrile patients. Risk factors for RVF included older age, whereas C. burnetii infection was associated with females, rural residents, and exposure to dead animals. Health authorities are advised to consider these infections in the differential diagnosis of fever, implement active surveillance, and target public health interventions.

Multiple outbreaks of Rift Valley Fever (RVF) with devastating effects have occurred in East Africa. These outbreaks cause disease in both livestock and humans and affect poor households most severely. Communities living in areas practicing nomadic livestock movement may be at higher risk of infection. This study sought to i) determine the human exposure to Rift Valley fever virus (RVFV) in populations living within nomadic animal movement routes in Kenya; and ii) identify risk factors for RVFV infection in these communities. A cross-sectional descriptive study design was used. Samples were collected from the year 2014 to 2015 in a community-based sampling exercise involving healthy individuals aged ≥18 years from Isiolo, Tana River, and Garissa counties. In total, 1210 samples were screened by ELISA for the presence of immunoglobulin IgM and IgG antibodies against RVFV. Positive results were confirmed by plaque reduction neutralization test. Overall, IgM and IgG prevalence for all sites combined was 1.4% (95% CI 0.8-2.3%) and 36.4% (95% CI 33.8-39.2%), respectively. Isiolo County recorded a non-significant higher IgG prevalence of 38.8% than Garissa 35.9% and Tana River 32.2% (Chi square = 2.5, df = 2, p = 0.287). Males were significantly at higher risk of infection by RVFV than females (OR = 1.67, 95% CI 1.17-2.39, p<0.005). Age was significantly associated with RVFV infection (Wald Chi = 94.2, df = 5, p<0.0001). Individuals who had regular contact with cattle (OR = 1.38, 95%CI 1.01-1.89) and donkeys (OR = 1.38, 95%CI 1.14-1.67), or contact with animals through birthing (OR = 1.69, 95%CI 1.14-2.51) were significantly at a greater risk of RVFV infection than those who did not. This study demonstrated that although the Isiolo County has been classified as being at medium risk for RVF, virus infection appeared to be as prevalent in humans as in Tana River and Garissa, which have been classified as being at high risk. Populations in these counties live within nomadic livestock movement routes and therefore at risk of being exposed to the RVFV. Interventions to control RVFV infections therefore, should target communities living along livestock movement pathways.