Rift Valley Fever Virus Transmission Research Articles

Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal-fetal placental interface.

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal-fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live-attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent on the maternal-facing side. Type I and type III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal-fetal interface.IMPORTANCEA direct comparison of replication of Rift Valley fever virus (RVFV) in sheep and human placental explants reveals comparative efficiencies and permissivity to infection and replication. Vaccine strains of RVFV demonstrated reduced infection and replication capacity in the mammalian placenta. This study represents the first direct cross-host comparison of the vertical transmission capacity of this high-priority emerging mosquito-transmitted virus.

Expanding Understanding of Urban Rift Valley Fever Risk and Associated Vector Ecology at Slaughterhouses in Kisumu, Kenya.

Rift Valley fever virus (RVFV) is an adaptable arbovirus that can be transmitted by a wide variety of arthropods. Widespread urban transmission of RVFV has not yet occurred, but peri-urban outbreaks of RVFV have recently been documented in East Africa. We previously reported low-level exposure in urban communities and highlighted the risk of introduction via live animal influx. We deployed a slaughtered animal testing framework in response to an early warning system at two urban slaughterhouses and tested animals entering the meat value chain for anti-RVFV IgG and IgM antibodies. We simultaneously trapped mosquitoes for RVFV and bloodmeal testing. Out of 923 animals tested, an 8.5% IgG seroprevalence was identified but no evidence of recent livestock exposure was detected. Mosquito species abundance varied greatly by slaughterhouse site, which explained 52% of the variance in blood meals. We captured many Culex spp., a known RVFV amplifying vector, at one of the sites (p < 0.001), and this species had the most diverse blood meals. No mosquito pools tested positive for RVFV antigen using a rapid VecTOR test. These results expand understanding of potential RVF urban disease ecology, and highlight that slaughterhouses are key locations for future surveillance, modelling, and monitoring efforts.

Evidence for circulation of Rift Valley fever virus in wildlife and domestic animals in a forest environment in Gabon, Central Africa.

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by the Rift Valley fever virus (RVFV) that can infect domestic and wild animals. Although the RVFV transmission cycle has been well documented across Africa in savanna ecosystems, little is known about its transmission in tropical rainforest settings, particularly in Central Africa. We therefore conducted a survey in northeastern Gabon to assess RVFV circulation among wild and domestic animals. Among 163 wildlife samples tested using RVFV-specific RT-qPCR, four ruminants belonging to subfamily Cephalophinae were detected positive. The phylogenetic analysis revealed that the four RVFV sequences clustered together with a virus isolated in Namibia within the well-structured Egyptian clade. A cross-sectional survey conducted on sheep, goats and dogs living in villages within the same area determined the IgG RVFV-specific antibody prevalence using cELISA. Out of the 306 small ruminants tested (214 goats, 92 sheep), an overall antibody prevalence of 15.4% (95% CI [11.5-19.9]) was observed with a higher rate in goats than in sheep (20.1% versus 3.3%). RVFV-specific antibodies were detected in a single dog out of the 26 tested. Neither age, sex of domestic animals nor season was found to be significant risk factors of RVFV occurrence. Our findings highlight sylvatic circulation of RVFV for the first time in Gabon. These results stress the need to develop adequate surveillance plan measures to better control the public health threat of RVFV.

Quantifying Rift Valley fever virus transmission efficiency in a lamb-mosquito-lamb model.

Rift Valley fever virus (RVFV) is a (re)emerging mosquito-borne pathogen impacting human and animal health. How RVFV spreads through a population depends on population-level and individual-level interactions between vector, host and pathogen. Here, we estimated the probability for RVFV to transmit to naive animals by experimentally exposing lambs to a bite of an infectious mosquito, and assessed if and how RVFV infection subsequently developed in the exposed animal. Aedes aegypti mosquitoes, previously infected via feeding on a viremic lamb, were used to expose naive lambs to the virus. Aedes aegypti colony mosquitoes were used as they are easy to maintain and readily feed in captivity. Other mosquito spp. could be examined with similar methodology. Lambs were exposed to either 1-3 (low exposure) or 7-9 (high exposure) infectious mosquitoes. All lambs in the high exposure group became viremic and showed characteristic signs of Rift Valley fever within 2-4 days post exposure. In contrast, 3 out of 12 lambs in the low exposure group developed viremia and disease, with similar peak-levels of viremia as the high exposure group but with some heterogeneity in the onset of viremia. These results suggest that the likelihood for successful infection of a ruminant host is affected by the number of infectious mosquitoes biting, but also highlights that a single bite of an infectious mosquito can result in disease. The per bite mosquito-to-host transmission efficiency was estimated at 28% (95% confidence interval: 15 - 47%). We subsequently combined this transmission efficiency with estimates for life traits of Aedes aegypti or related mosquitoes into a Ross-McDonald mathematical model to illustrate scenarios under which major RVFV outbreaks could occur in naïve populations (i.e., R0 >1). The model revealed that relatively high vector-to-host ratios as well as mosquitoes feeding preferably on competent hosts are required for R0 to exceed 1. Altogether, this study highlights the importance of experiments that mimic natural exposure to RVFV. The experiments facilitate a better understanding of the natural progression of disease and a direct way to obtain epidemiological parameters for mathematical models.

Rift Valley Fever Virus Primes Immune Responses in Aedes aegypti Cells.

The ongoing global emergence of arthropod-borne (arbo) viruses has accelerated research into the interactions of these viruses with the immune systems of their vectors. Only limited information exists on how bunyaviruses, such as Rift Valley fever virus (RVFV), are sensed by mosquito immunity or escape detection. RVFV is a zoonotic phlebovirus (Bunyavirales; Phenuiviridae) of veterinary and human public health and economic importance. We have shown that the infection of mosquitoes with RVFV triggers the activation of RNA interference pathways, which moderately restrict viral replication. Here, we aimed to better understand the interactions between RVFV and other vector immune signaling pathways that might influence RVFV replication and transmission. For this, we used the immunocompetent Aedes aegypti Aag2 cell line as a model. We found that bacteria-induced immune responses restricted RVFV replication. However, virus infection alone did not alter the gene expression levels of immune effectors. Instead, it resulted in the marked enhancement of immune responses to subsequent bacterial stimulation. The gene expression levels of several mosquito immune pattern recognition receptors were altered by RVFV infection, which may contribute to this immune priming. Our findings imply that there is a complex interplay between RVFV and mosquito immunity that could be targeted in disease prevention strategies.

Evidence of Eretmapodites subsimplicipes and Aedes albopictus as competent vectors for Rift Valley fever virus transmission in Mayotte

Rift Valley fever (RVF) recently re-emerged in Mayotte. We described, for the first time, that the mosquito species Eretmapodites subsimplicipes, a highly abundant species in Mayotte, is a competent vector for the transmission of RVF virus using three distinct populations native to Mayotte. We also showed that Aedes albopictus specimens are able to transmit RVF virus (RVFV) as previously observed in mosquito populations of other countries emphasizing the need of the increase vigilance for this highly invasive species of global distribution. Altogether, these results underline the epidemiological importance of both species for RVFV transmission in Mayotte and contribute to better understand the RVF epidemiological cycle and help to implement efficient prevention measures.

Phylogenetic Analysis of Wesselsbron Virus Isolated from Field-Captured Mosquitoes during a Rift Valley Fever Outbreak in Kabale District, Uganda-2016.

After confirmation of two human cases of Rift Valley fever (RVF) in March 2016 in the Kabale district of Uganda, an entomological investigation was conducted with a focus on mosquito species composition and abundance of known and potential mosquito vector species, and virus testing to identify species most likely involved in Rift Valley fever virus transmission. This information could be used to forecast risk and facilitate improvement of prevention and response tools for use in preventing or controlling future outbreaks. From these collections, two virus isolates were obtained, one each from a pool of Aedes tricholabis and Ae. gibbinsi. Next-generation sequencing identified both isolates as Wesselsbron virus, family Flaviviridae, a neglected arbovirus of economic importance. These are the first reported Wesselsbron virus isolates from Uganda since 1966.

Inter-epidemic Rift Valley fever virus infection incidence and risks for zoonotic spillover in northern Tanzania.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that has caused epidemics involving people and animals across Africa and the Arabian Peninsula. A number of studies have found evidence for the circulation of RVFV among livestock between these epidemics but the population-level incidence of infection during this inter-epidemic period (IEP) is rarely reported. General force of infection (FOI) models were applied to age-adjusted cross-sectional serological data to reconstruct the annual FOI and population-level incidence of RVFV infection among cattle, goats, and sheep in northern Tanzania from 2009 through 2015, a period without reported Rift Valley fever (RVF) cases in people or animals. To evaluate the potential for zoonotic RVFV spillover during this period, the relationship between village-level livestock RVFV FOI and human RVFV seropositivity was quantified using multi-level logistic regression. The predicted average annual incidence was 72 (95% Credible Interval [CrI] 63, 81) RVFV infections per 10,000 animals and 96 (95% CrI 81, 113), 79 (95% CrI 62, 98), and 39 (95% CrI 28, 52) per 10,000 cattle, sheep, and goats, respectively. There was variation in transmission intensity between study villages, with the highest estimated village-level FOI 2.49% (95% CrI 1.89, 3.23) and the lowest 0.12% (95% CrI 0.02, 0.43). The human RVFV seroprevalence was 8.2% (95% Confidence Interval 6.2, 10.9). Human seropositivity was strongly associated with the village-level FOI in livestock, with the odds of seropositivity in an individual person increasing by around 1.2 times (95% CrI 1.1, 1.3) for each additional annual RVFV seroconversion per 1,000 animals. A history of raw milk consumption was also positively associated with human seropositivity. RVFV has circulated at apparently low levels among livestock in northern Tanzania in the period since the last reported epidemic. Although our data do not allow us to confirm human RVFV infections during the IEP, a strong association between human seropositivity and the FOI in cattle, goats, and sheep supports the hypothesis that RVFV circulation among livestock during the IEP poses a risk for undetected zoonotic spillover in northern Tanzania. We provide further evidence for the likely role of raw milk consumption in RVFV transmission from animals to people.

Heterogeneity of Rift Valley fever virus transmission potential across livestock hosts, quantified through a model-based analysis of host viral load and vector infection.

Quantifying the variation of pathogens' life history traits in multiple host systems is crucial to understand their transmission dynamics. It is particularly important for arthropod-borne viruses (arboviruses), which are prone to infecting several species of vertebrate hosts. Here, we focus on how host-pathogen interactions determine the ability of host species to transmit a virus to susceptible vectors upon a potentially infectious contact. Rift Valley fever (RVF) is a viral, vector-borne, zoonotic disease, chosen as a case study. The relative contributions of livestock species to RVFV transmission has not been previously quantified. To estimate their potential to transmit the virus over the course of their infection, we 1) fitted a within-host model to viral RNA and infectious virus measures, obtained daily from infected lambs, calves, and young goats, 2) estimated the relationship between vertebrate host infectious titers and probability to infect mosquitoes, and 3) estimated the net infectiousness of each host species over the duration of their infectious periods, taking into account different survival outcomes for lambs. Our results indicate that the efficiency of viral replication, along with the lifespan of infectious particles, could be sources of heterogeneity between hosts. Given available data on RVFV competent vectors, we found that, for similar infectious titers, infection rates in the Aedes genus were on average higher than in the Culex genus. Consequently, for Aedes-mediated infections, we estimated the net infectiousness of lambs to be 2.93 (median) and 3.65 times higher than that of calves and goats, respectively. In lambs, we estimated the overall infectiousness to be 1.93 times higher in individuals which eventually died from the infection than in those recovering. Beyond infectiousness, the relative contributions of host species to transmission depend on local ecological factors, including relative abundances and vector host-feeding preferences. Quantifying these contributions will ultimately help design efficient, targeted, surveillance and vaccination strategies.

Rift Valley fever, Mauritania, 2020: Lessons from a one health approach

A new outbreak of Rift Valley fever (RVF) occurred in Mauritania from September to November 2020, involving 78 reported human cases and 186 reported animal cases. Eleven out of the 13 regions of the country were affected by the epidemic, with the highest number of both human and animal cases in Tagant, Assaba and Brakna regions. The most affected animal species in this outbreak was camels, followed by small ruminants. Among the 10 mosquito species caught, 7 species, Culex poicilipes, Cx. quinquefasciatus, Cx. antennatus, Cx. univitattus, Aedes vexans, Mansonia africana and Ma. uniformis, are known to be involved in the transmission of RVF virus. Phylogenetic analyses based on the partial NSs gene revealed close proximity between the human/animal Mauritania 2020 viral strains and the Mauritania 2015/Niger 2016 strains, suggesting re-emergence of the RVF virus in the country since the last reported outbreak in 2015.

Climate Conditions During a Rift Valley Fever Post-epizootic Period in Free State, South Africa, 2014-2019.

Rift Valley fever virus (RVFV) activity in Southern Africa tends to occur during periods of sustained elevated rainfall, cooler than normal conditions, and abundant vegetation cover creating ideal conditions for the increase and propagation of populations of RVFV mosquito vectors. These climatic and ecological conditions are modulated by large-scale tropical-wide El Niño–Southern Oscillation (ENSO) phenomena. The aim of this 5-year study was to investigate climatic conditions during Rift Valley fever “post-epizootic” period in Free State province of the Republic of South Africa, which historically experienced the largest RVF outbreaks in this country. We collected satellite-derived rainfall, land surface temperature (LST), and normalized difference vegetation index (NDVI) data since 2014 to understand broad environmental conditions in the years following a period of sustained and widespread large RVF outbreaks (2008–2011) in the region. We found this post-epizootic/interepizootic period to be characterized by below-normal rainfall (~-500 mm), above LSTs (~+12°C), depressed NDVI (60% below normal), and severe drought as manifested particularly during the 2015–2016 growing season. Such conditions reduce the patchwork of appropriate habitats available for emergence of RVFV vectors and diminish chances of RVFV activity. However, the 2016–2017 growing season saw a marked return to somewhat wetter conditions without any reported RVFV transmission. In general, the aggregate vector collections during this 5-year period follow patterns observed in climate measurements. During the 2017–2018 growing season, late and seasonally above average rainfall resulted in a focal RVF outbreak in one location in the study region. This unanticipated event is an indicator of cryptic RVF activity during post-epizootic period and may be a harbinger of RVFV activity in the coming years.

Susceptibility and barriers to infection of Colorado mosquitoes with Rift Valley fever virus.

Rift Valley fever virus (RVFV) causes morbidity and mortality in humans and domestic ungulates in sub-Saharan Africa, Egypt, and the Arabian Peninsula. Mosquito vectors transmit RVFV between vertebrates by bite, and also vertically to produce infectious progeny. Arrival of RVFV into the United States by infected mosquitoes or humans could result in significant impacts on food security, human health, and wildlife health. Elucidation of the vectors involved in the post-introduction RVFV ecology is paramount to rapid implementation of vector control. We performed vector competence experiments in which field-collected mosquitoes were orally exposed to an epidemic strain of RVFV via infectious blood meals. We targeted floodwater Aedes species known to feed on cattle, and/or deer species (Aedes melanimon Dyar, Aedes increpitus Dyar, Aedes vexans [Meigen]). Two permanent-water-breeding species were targeted as well: Culiseta inornata (Williston) of unknown competence considering United States populations, and Culex tarsalis Coquillett as a control species for which transmission efficiency is known. We tested the potential for midgut infection, midgut escape (dissemination), ovarian infection (vertical transmission), and transmission by bite (infectious saliva). Tissues were assayed by plaque assay and RT-qPCR, to quantify infectious virus and confirm virus identity. Tissue infection data were analyzed using a within-host model under a Bayesian framework to determine the probabilities of infection outcomes (midgut-limited infection, disseminated infection, etc.) while estimating barriers to infection between tissues. Permanent-water-breeding mosquitoes (Cx. tarsalis and Cs. inornata) exhibited more efficient horizontal transmission, as well as potential for vertical transmission, which is contrary to the current assumptions of RVFV ecology. Barrier estimates trended higher for Aedes spp., suggesting systemic factors in the differences between these species and Cx. tarsalis and Cs. inornata. These data indicate higher potential for vertical transmission than previously appreciated, and support the consensus of RVFV transmission including a broad range of potential vectors.

Modelling the persistence and control of Rift Valley fever virus in a spatially heterogeneous landscape

The persistence mechanisms of Rift Valley fever (RVF), a zoonotic arboviral haemorrhagic fever, at both local and broader geographical scales have yet to be fully understood and rigorously quantified. We developed a mathematical metapopulation model describing RVF virus transmission in livestock across the four islands of the Comoros archipelago, accounting for island-specific environments and inter-island animal movements. By fitting our model in a Bayesian framework to 2004–2015 surveillance data, we estimated the importance of environmental drivers and animal movements on disease persistence, and tested the impact of different control scenarios on reducing disease burden throughout the archipelago. Here we report that (i) the archipelago network was able to sustain viral transmission in the absence of explicit disease introduction events after early 2007, (ii) repeated outbreaks during 2004–2020 may have gone under-detected by local surveillance, and (iii) co-ordinated within-island control measures are more effective than between-island animal movement restrictions.

Over 100 Years of Rift Valley Fever: A Patchwork of Data on Pathogen Spread and Spillover.

During the past 100 years, Rift Valley fever virus (RVFV), a mosquito-borne virus, has caused potentially lethal disease in livestock, and has been associated with significant economic losses and trade bans. Spillover to humans occurs and can be fatal. Here, we combined data on RVF disease in humans (22 countries) and animals (37 countries) from 1931 to 2020 with seroprevalence studies from 1950 to 2020 (n = 228) from publicly available databases and publications to draw a more complete picture of the past and current RVFV epidemiology. RVFV has spread from its original locus in Kenya throughout Africa and into the Arabian Peninsula. Throughout the study period seroprevalence increased in both humans and animals, suggesting potentially increased RVFV exposure. In 24 countries, animals or humans tested positive for RVFV antibodies even though outbreaks had never been reported there, suggesting RVFV transmission may well go unnoticed. Among ruminants, sheep were the most likely to be exposed during RVF outbreaks, but not during periods of cryptic spread. We discuss critical data gaps and highlight the need for detailed study descriptions, and long-term studies using a one health approach to further convert the patchwork of data to the tale of RFV epidemiology.

Laboratory demonstration of the vertical transmission of Rift Valley fever virus by Culex tarsalis mosquitoes.

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus with proven ability to emerge into naïve geographic areas. Limited field evidence suggests that RVFV is transmitted vertically from parent mosquito to offspring, but until now this mechanism has not been confirmed in the laboratory. Furthermore, this transmission mechanism has allowed for the prediction of RVFV epizootics based on rainfall patterns collected from satellite information. However, in spite of the relevance to the initiation of epizootic events, laboratory confirmation of vertical transmission has remained an elusive research aim for thirty-five years. Herein we present preliminary evidence of the vertical transmission of RVFV by Culex tarsalis mosquitoes after oral exposure to RVFV. Progeny from three successive gonotrophic cycles were reared to adults, with infectious RVFV confirmed in each developmental stage. Virus was detected in ovarian tissues of parental mosquitoes 7 days after imbibing an infectious bloodmeal. Infection was confirmed in progeny as early as the first gonotrophic cycle, with infection rates ranging from 2.0–10.0%. Virus titers among progeny were low, which may indicate a host mechanism suppressing replication.

Reproducing the Rift Valley fever virus mosquito-lamb-mosquito transmission cycle

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that is pathogenic to ruminants and humans. The virus is endemic to Africa and the Arabian Peninsula where outbreaks are characterized by abortion storms and mortality of newborns, particularly in sheep herds. Vector competence experiments in laboratory settings have suggested that over 50 mosquito species are capable of transmitting RVFV. Transmission of mosquito-borne viruses in the field is however influenced by numerous factors, including population densities, blood feeding behavior, extrinsic incubation period, longevity of vectors, and viremia levels in vertebrate hosts. Animal models to study these important aspects of RVFV transmission are currently lacking. In the present work, RVFV was transmitted to European (Texel-swifter cross-breed) lambs by laboratory-reared Aedes aegypti mosquitoes that were infected either by membrane feeding on a virus-spiked blood meal or by feeding on lambs that developed viremia after intravenous inoculation of RVFV. Feeding of mosquitoes on viremic lambs resulted in strikingly higher infection rates as compared to membrane feeding. Subsequent transmission of RVFV from lamb to lamb by infected mosquitoes was highly efficient in both models. The animal models described here can be used to study mosquito-mediated transmission of RVFV among the major natural target species and to evaluate the efficacy of vaccines against mosquito-mediated RVFV infection.

Identification and characterisation of mosquitoes from different locations in Qatar in 2017-2019.

Mosquito-borne infections have considerable consequences for public health. The mere presence of a single case of vector-borne disease (VBD) introduces a risk to the local community particularly when associated with the compatible vector, host, and suitable environmental factors. Presently, there is no well-established vector control and surveillance programme in Qatar; therefore, the likelihood of VBDs spreading is undetermined. As a result, there is a pressing need to address this gap and enable successful management of VBDs. This study presents the results of three consecutive field surveys conducted between 2017 and 2019 with the aim of defining the types and distribution of mosquitoes that are of public health importance in Qatar. The results of the adult mosquito trappings show that the southern house mosquito Culex quinquefasciatus is the most widespread and abundant mosquito species, followed by Cx. perexiguus, both species representing a risk of West Nile virus transmission. All sampling methods show that the malaria vector Anopheles stephensi is widespread including in urbanised areas, suggesting a risk of local malaria transmission. The wetland mosquito Aedes caspius is also widespread, representing a risk of Rift Valley fever virus transmission. The dengue vector Ae. aegypti was not detected and can be considered neither widespread nor abundant, suggesting a minimal risk for local transmission of dengue, chikungunya and Zika viruses. Interestingly, the study detected Culiseta longiareolata for the first time in Qatar. Regular field studies are needed to further address the knowledge gaps in terms of distribution, ecology, and biting habits of different mosquito species currently present in Qatar to accurately assess the risk of mosquito-borne diseases.

Large herbivore loss has complex effects on mosquito ecology and vector-borne disease risk.

Loss of biodiversity can affect transmission of infectious diseases in at least two ways: by altering host and vector abundance or by influencing host and vector behaviour. We used a large herbivore exclusion experiment to investigate the effects of wildlife loss on the abundance and feeding behaviour of mosquito vectors and to explore consequences for vector-borne disease transmission. Large herbivore loss affected both mosquito abundance and blood-feeding behaviour. For Aedes mcintoshi, the dominant mosquito species in our study and a primary vector of Rift Valley fever virus (RVFV), abundance decreased with large herbivore loss, while blood feeding on humans increased. Despite an elevated human biting rate in the absence of large herbivores, we estimated that the potential for RVFV transmission to humans doubles in the presence of large herbivores. These results demonstrate that multiple effects of biodiversity loss on vectors can lead to counterintuitive outcomes for human disease risk.

The influence of raw milk exposures on Rift Valley fever virus transmission.

Rift Valley fever virus (RVFV) is a zoonotic phlebovirus that can be transmitted to humans or livestock by mosquitoes or through direct contact with contaminated bodily fluids and tissues. Exposure to bodily fluids and tissues varies by types of behaviors engaged for occupational tasks, homestead responsibilities, or use in dietary or therapeutic capacities. While previous studies have included milk exposures in their analyses, their primary focus on livestock exposures has been on animal handling, breeding, and slaughter. We analyzed data from multiple field surveys in Kenya with the aim of associating RVFV infection to raw milk exposures from common animal species. Of those with evidence of prior RVFV infection by serology (n = 267), 77.2% engaged in milking livestock compared to 32.0% for 3,956 co-local seronegative individuals (p < 0.001), and 86.5% of seropositive individuals consumed raw milk compared to 33.4% seronegative individuals (p < 0.001). Individuals who milked and also consumed raw milk had greater odds of RVFV exposure than individuals whose only contact to raw milk was through milking. Increased risks were associated with exposure to milk sourced from cows (p < 0.001), sheep (p < 0.001), and goats (p < 0.001), but not camels (p = 0.98 for consuming, p = 0.21 for milking). Our data suggest that exposure to raw milk may contribute to a significant number of cases of RVFV, especially during outbreaks and in endemic areas, and that some animal species may be associated with a higher risk for RVFV exposure. Livestock trade is regulated to limit RVFV spread from endemic areas, yet further interventions designed to fully understand the risk of RVFV exposure from raw milk are imperative.

Individual-based network model for Rift Valley fever in Kabale District, Uganda.

Rift Valley fever (RVF) is a zoonotic disease, that causes significant morbidity and mortality among ungulate livestock and humans in endemic regions. In East Africa, the causative agent of the disease is Rift Valley fever virus (RVFV) which is primarily transmitted by multiple mosquito species in Aedes and Mansonia genera during both epizootic and enzootic periods in a complex transmission cycle largely driven by environmental and climatic factors. However, recent RVFV activity in Uganda demonstrated the capability of the virus to spread into new regions through livestock movements, and underscored the need to develop effective mitigation strategies to reduce transmission and prevent spread among cattle populations. We simulated RVFV transmission among cows in 22 different locations of the Kabale District in Uganda using real world livestock data in a network-based model. This model considered livestock as a spatially explicit factor in different locations subjected to specific vector and environmental factors, and was configured to investigate and quantitatively evaluate the relative impacts of mosquito control, livestock movement, and diversity in cattle populations on the spread of the RVF epizootic. We concluded that cattle movement should be restricted for periods of high mosquito abundance to control epizootic spreading among locations during an RVF outbreak. Importantly, simulation results also showed that cattle populations with heterogeneous genetic diversity as crossbreeds were less susceptible to infection compared to homogenous cattle populations.