Rift Valley fever (RVF) in ungulates and humans is caused by a mosquito-borne RVF phlebovirus (RVFV). Live attenuated vaccines are used in livestock (sheep and cattle) to control RVF in endemic regions during outbreaks. The ability of two or more different RVFV strains to reassort when co-infecting a host cell is a significant veterinary and public health concern due to the potential emergence of newly reassorted viruses, since reassortment of RVFVs has been documented in nature and in experimental infection studies. Due to the very limited information regarding the frequency and dynamics of RVFV reassortment, we evaluated the efficiency of RVFV reassortment in sheep, a natural host for this zoonotic pathogen. Co-infection experiments were performed, first in vitro in sheep-derived cells, and subsequently in vivo in sheep. Two RVFV co-infection groups were evaluated: group I consisted of co-infection with two wild-type (WT) RVFV strains, Kenya 128B-15 (Ken06) and Saudi Arabia SA01-1322 (SA01), while group II consisted of co-infection with the live attenuated virus (LAV) vaccine strain MP-12 and a WT strain, Ken06. In the in vitro experiments, the virus supernatants were collected 24 h post-infection. In the in vivo experiments, clinical signs were monitored, and blood and tissues were collected at various time points up to nine days post-challenge for analyses. Cell culture supernatants and samples from sheep were processed, and plaque-isolated viruses were genotyped to determine reassortment frequency. Our results show that RVFV reassortment is more efficient in co-infected sheep-derived cells compared to co-infected sheep. In vitro, the reassortment frequencies reached 37.9% for the group I co-infected cells and 25.4% for the group II co-infected cells. In contrast, we detected just 1.7% reassortant viruses from group I sheep co-infected with the two WT strains, while no reassortants were detected from group II sheep co-infected with the WT and LAV strains. The results indicate that RVFV reassortment occurs at a lower frequency in vivo in sheep when compared to in vitro conditions in sheep-derived cells. Further studies are needed to better understand the implications of RVFV reassortment in relation to virulence and transmission dynamics in the host and the vector. The knowledge learned from these studies on reassortment is important for understanding the dynamics of RVFV evolution.

Rift Valley fever is a viral epidemic illness prevalent in Africa that can be fatal or result in debilitating sequelae in humans. No vaccines are available for human use. We aimed to evaluate the safety and immunogenicity of a non-replicating simian adenovirus-vectored Rift Valley fever (ChAdOx1 RVF) vaccine in humans.
We conducted a phase 1, first-in-human, open-label, dose-escalation trial in healthy adults aged 18-50 years at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Participants were required to have no serious comorbidities or previous history of receiving an adenovirus-based vaccine before enrolment. Participants were non-randomly allocated to receive a single ChAdOx1 RVF dose of either 5 × 109 virus particles (vp), 2·5 × 1010 vp, or 5 × 1010 vp administered intramuscularly into the deltoid of their non-dominant arm; enrolment was sequential and administration was staggered to allow for safety to be assessed before progression to the next dose. Primary outcome measures were assessment of adverse events and secondary outcome measures were Rift Valley fever neutralising antibody titres, Rift Valley fever GnGc-binding antibody titres (ELISA), and cellular response (ELISpot), analysed in all participants who received a vaccine. This trial is registered with ClinicalTrials.gov (NCT04754776).
Between June 11, 2021, and Jan 13, 2022, 15 volunteers received a single dose of either 5 × 109 vp (n=3), 2·5 × 1010 vp (n=6), or 5 × 1010 vp (n=6) ChAdOx1 RVF. Nine participants were female and six were male. 14 (93%) of 15 participants reported solicited local adverse reactions; injection-site pain was the most frequent (13 [87%] of 15). Ten (67%) of 15 participants (from the 2·5 × 1010 vp and 5 × 1010 vp groups only) reported systemic symptoms, which were mostly mild in intensity, the most common being headache (nine [60%] of 15) and fatigue (seven [47%]). All unsolicited adverse events reported within 28 days were either mild or moderate in severity; gastrointestinal symptoms were the most common reaction (at least possibly related to vaccination), occurring in four (27%) of 15 participants. Transient decreases in total white cell, lymphocyte, or neutrophil counts occurred at day 2 in some participants in the intermediate-dose and high-dose groups. Lymphopenia graded as severe occurred in two participants in the 5 × 1010 vp group at a single timepoint, but resolved at the subsequent follow-up visit. No serious adverse events occurred. Rift Valley fever neutralising antibodies were detectable across all dose groups, with all participants in the 5 × 1010 vp dose group having high neutralising antibody titres that peaked at day 28 after vaccination and persisted through the 3-month follow-up. High titres of binding IgG targeting Gc glycoprotein were detected whereas those targeting Gn were comparatively low. IFNγ cellular responses against Rift Valley fever Gn and Gc glycoproteins were observed in all participants except one in the 5 × 1010 vp dose group. These IFNγ responses peaked at 2 weeks after vaccination, were highest in the 5 × 1010 vp dose group, and tended to be more frequent against the Gn glycoprotein.
ChAdOx1 RVF was safe, well tolerated, and immunogenic when administered as a single dose in this study population. The data support further clinical development of ChAdOx1 RVF for human use.
UK Department of Health and Social Care through the UK Vaccines Network, Oak Foundation, and the Wellcome Trust.
For the Swahili translation of the abstract see Supplementary Materials section.

The vulnerable populations in the protracted humanitarian crisis in South Sudan are faced with constrained access to health services and frequent disease outbreaks. Here, we describe the experiences of emergency mobile medical teams (eMMT) assembled by the World Health Organization (WHO) South Sudan to respond to public health emergencies. Interventions: the eMMTs, multidisciplinary teams based at national, state and county levels, are rapidly deployed to conduct rapid assessments, outbreak investigations, and initiate public health response during acute emergencies. The eMMTs were deployed to locations affected by flooding, conflicts, famine, and disease outbreaks. We reviewed records of deployment reports, outreach and campaign registers, and analyzed the key achievements of the eMMTs for 2017 through 2020. Achievements: the eMMTs investigated disease outbreaks including cholera, measles, Rift Valley fever and coronavirus disease (COVID-19) in 13 counties, conducted mobile outreaches in emergency locations in 38 counties (320,988 consultations conducted), trained 550 healthcare workers including rapid response teams, and supported reactive measles vaccination campaigns in seven counties [148,726, (72-125%) under-5-year-old children vaccinated] and reactive oral cholera vaccination campaigns in four counties (355,790 vaccinated). The eMMT is relevant in humanitarian settings and can reduce excess morbidity and mortality and fill gaps that routine health facilities and health partners could not bridge. However, the scope of the services offered needs to be broadened to include mental and psychosocial care and a strategy for ensuring continuity of vaccination services and management of chronic conditions after the mobile outreach is instituted.

Livestock abortion is an important cause of productivity losses worldwide and many infectious causes of abortion are zoonotic pathogens that impact on human health. Little is known about the relative importance of infectious causes of livestock abortion in Africa, including in subsistence farming communities that are critically dependent on livestock for food, income, and wellbeing. We conducted a prospective cohort study of livestock abortion, supported by cross-sectional serosurveillance, to determine aetiologies of livestock abortions in livestock in Tanzania. This approach generated several important findings including detection of a Rift Valley fever virus outbreak in cattle; high prevalence of C. burnetii infection in livestock; and the first report of Neospora caninum, Toxoplasma gondii, and pestiviruses associated with livestock abortion in Tanzania. Our approach provides a model for abortion surveillance in resource-limited settings. Our findings add substantially to current knowledge in sub-Saharan Africa, providing important evidence from which to prioritise disease interventions.

Rift Valley fever (RVF) is a serious life-threatening disease with severe clinical manifestations and health consequences for humans and a wide range of domestic animals. In September 2000, an RVF outbreak was reported in the Jazan region in the south-west part of Saudi Arabia with 886 human cases including 124 deaths. This review provides: a) an overview of the RVF control programme in Saudi Arabia, and b) an assessment of some of the control measures that have been launched since the early recognition of RVF. Currently, with the exception of Saudi Arabia, devastating outbreaks of RVF continue to occur and the number of countries reporting cases has increased rapidly. At least 19 large outbreaks including substantial numbers of human and animal deaths have been reported for the period between 2000 and 2018. In contrast to the aforementioned situation in endemic areas, the RVF control programme that was set up in Saudi Arabia has completely reversed the risk of re-occurrence of RVF over the past 18 years and provided long-term protection against Rift Valley fever virus (RVFV) exposure. The control programme involved: a) vector control campaigns (using conventional and microbial insecticides, drainage and filling of water swamps with soil, and mosquito surveillance) and b) host-driven controls such as sustained vaccination campaigns, regular examination of sentinel herds, including seasonal surveillance reinforcement (targeted sero-surveillance during rainy seasons), and serological examination of clandestine animal imports kept at Al-Twal quarantine station, at the border with Yemen. The effectiveness of the current control programme can be demonstrated not only by the decrease in antibody prevalence of RVF virus-specific immunoglobulin M, from 12.3% (95% confidence interval [CI]: 6.8-17.8) in 2000 to 0.10% (95% CI: 0.01-0.2) in 2017, but also by the absence of human and animal cases since the 2000 outbreak. The mosquito infection rates with RVFV have also declined, from 0.045 per 1,000 for the genus Culex in 2014 to zero from 2015 to 2018. Additionally, the integrated vector management methods targeting outdoor habitats in the Jazan region substantially contributed to vector control and should be considered one of the most important factors contributing to the significant reduction of malaria case incidence from 2000 to 2014. The Saudi current control initiative could be used as a guideline for control of RVF or as a suitable model for other endemic countries.
La fièvre de la vallée du Rift (FVR) est une maladie grave, parfois mortelle, qui provoque d\'importantes manifestations cliniques et affecte la santé humaine ainsi que celle de nombreuses espèces d\'animaux domestiques. En septembre 2000, un foyer de FVR a été signalé dans la région de Jazan, dans le sud-ouest de l\'Arabie saoudite, avec 886 cas humains déclarés, dont 124 décès. Les auteurs présentent les résultats d\'une étude de synthèse portant sur : a) le programme de contrôle de la FVR mis en place par l\'Arabie saoudite ; et b) l\'évaluation de certaines mesures de contrôle parmi celles qui ont été appliquées depuis la détection précoce de la FVR dans le pays. Actuellement, en dehors de l\'Arabie saoudite qui constitue une exception, des foyers dévastateurs de FVR continuent de se déclarer et le nombre de pays signalant des cas augmente rapidement. Au moins 19 foyers majeurs ayant entraîné un nombre important de décès chez l\'homme comme chez les animaux ont été signalés durant la période de 2000 à 2018. Contrairement à la situation observée dans ces zones d\'endémie, en Arabie saoudite le programme de lutte contre la FVR s\'est traduit par une inversion complète du risque de nouveaux foyers au cours des 18 années écoulées et a apporté une protection durable contre l\'exposition au virus de la FVR. Le programme de lutte comprenait les éléments suivants : a) des campagnes de lutte contre les vecteurs (utilisation d\'insecticides traditionnels et microbiens, drainage et remblaiement des marécages, surveillance des populations de moustiques) ; et b) des mesures de contrôle axées sur les populations hôtes, en particulier des campagnes de vaccination soutenues, un examen régulier des troupeaux sentinelles, un renforcement de la surveillance saisonnière (surveillance sérologique ciblée pendant la saison des pluies) et un dépistage sérologique des animaux importés clandestinement et maintenus dans la station de quarantaine d\'Al-Twal, à la frontière avec le Yémen. L\'efficacité du programme de contrôle actuel peut être démontrée non seulement par la diminution de la prévalence des anticorps sériques d\'immunoglobuline M spécifiques du virus de la FVR, qui est passée de 12,3 % (intervalle de confiance [IC] à 95 % : 6,8-17,8) en 2000 à 0,10 % (IC à 95 % : 0,01-0,2) en 2017, mais aussi par l\'absence de cas humains et animaux depuis le foyer de 2000. Les taux d\'infection des moustiques par le virus de la FVR ont également diminué, passant de 0,045 pour 1 000 chez le moustique du genre Culex en 2014, à zéro infection de 2015 à 2018. De plus, les méthodes de gestion intégrée des vecteurs appliquées dans les habitats extérieurs ont largement contribué à la lutte antivectorielle dans la région de Jazan et peuvent être considérées comme l\'un des principaux facteurs de la baisse significative de l\'incidence des cas de paludisme de 2000 à 2014. L\'initiative saoudienne de lutte contre la FVR pourrait servir de fil conducteur des stratégies de contrôle de cette maladie, voire de modèle applicable par d\'autres pays où elle sévit à l\'état endémique.
La fiebre del valle del Rift (FVR) es una grave enfermedad, a veces mortal, que tiene graves manifestaciones clínicas y consecuencias sanitarias para el ser humano y diversos animales domésticos. En septiembre de 2000 se notificó un brote de FVR en la región de Jizán (en el sudoeste de Arabia Saudí) que afectó a 886 personas, de las cuales fallecieron 124. En este artículo los autores: a) presentan una síntesis del programa de lucha contra la FVR en Arabia Saudí; y b) valoran algunas de las medidas de control implantadas desde que se empezó a detectar la enfermedad. Actualmente, con la excepción de Arabia Saudí, siguen produciéndose devastadores brotes de FVR y va en rápido aumento el número de países que notifican casos. En los años que van de 2000 a 2018 se han comunicado al menos 19 brotes de grandes proporciones, que han causado la muerte de un número considerable de personas y animales. En contraste con esta situación reinante en zonas de endemicidad, en los últimos 18 años el programa de lucha que se instauró en Arabia Saudí ha invertido completamente el riesgo de resurgencia de la enfermedad y ofrecido protección duradera contra la exposición al virus de la FVR. Este programa se declina en: a) campañas de lucha contra el vector (con empleo de insecticidas convencionales y microbianos, drenaje y relleno de zonas pantanosas y vigilancia de las poblaciones de mosquitos); y b) controles de las poblaciones de hospedadores, por ejemplo mediante campañas sostenidas de vacunación, inspecciones periódicas de rebaños centinela, con vigilancia reforzada en ciertas épocas (serovigilancia específica en las temporadas de lluvias), y análisis serológicos de los animales importados clandestinamente y mantenidos en el centro de cuarentena de Al-Twal, situado en la frontera con el Yemen. De la eficacia del vigente programa de lucha, dan fe no solo la caída de la prevalencia de inmunoglobulinas M dirigidas específicamente contra el virus de la FVR, que pasó de un 12,3% (intervalo de confianza [IC] al 95%: 6,8-17,8) en 2000 a un 0,10% (IC 95%: 0,01-0,2) en 2017, sino también la ausencia de casos en humanos y animales desde el brote del año 2000. También ha disminuido la tasa de infección de mosquitos por el virus de la FVR, que pasó de 0,045 por 1 000 ejemplares del género Culex en 2014 a cero entre 2015 y 2018. Además, los métodos de lucha antivectorial integrada aplicados en hábitats al aire libre de la región de Jizán contribuyeron sustancialmente al control del vector. En este sentido, conviene ver estas medidas como uno de los principales factores que han influido en la sustancial reducción de la incidencia de casos de paludismo entre 2000 y 2014. La iniciativa saudí actualmente en curso podría servir de guía para combatir la FVR o como modelo adecuado para otros países donde la enfermedad es endémica.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen with significant human and veterinary health consequences that periodically emerges in epizootics. RVFV causes fetal loss and death in ruminants and in humans can lead to liver and renal disease, delayed-onset encephalitis, retinitis, and in some cases severe haemorrhagic fever. A live attenuated vaccine candidate (DDVax), was developed by the deletion of the virulence factors NSs and NSm from a clinical isolate, ZH501, and has proven safe and immunogenic in rodents, pregnant sheep and non-human primates. Deletion of NSm also severely restricted mosquito midgut infection and inhibited vector-borne transmission. To demonstrate environmental safety, this study investigated the replication, dissemination and transmission efficiency of DDVax in mosquitoes following oral exposure compared to RVFV strains MP-12 and ZH501. Infection and dissemination profiles were also measured in mosquitoes 7 days after they fed on goats inoculated with DDvax or MP-12. We hypothesized that DDVax would infect mosquitoes at significantly lower rates than other RVFV strains and, due to lack of NSm, be transmission incompetent. Exposure of Ae. aegypti and Cx. tarsalis to 8 log10 plaque forming units (PFU)/ml DDVax by artificial bloodmeal resulted in significantly reduced DDVax infection rates in mosquito bodies compared to controls. Plaque assays indicated negligible transmission of infectious DDVax in Cx. tarsalis saliva (1/140 sampled) and none in Ae. aegypti saliva (0/120). Serum from goats inoculated with DDVax or MP-12 did not harbour detectable infectious virus by plaque assay at 1, 2 or 3 days post-inoculation. Infectious virus was, however, recovered from Aedes and Culex bodies that fed on goats vaccinated with MP-12 (13.8% and 4.6%, respectively), but strikingly, DDvax-positive mosquito bodies were greatly reduced (4%, and 0%, respectively). Furthermore, DDVax did not disseminate to legs/wings in any of the goat-fed mosquitoes. Collectively, these results are consistent with a beneficial environmental safety profile.

This study reports the monitoring of several emerging viral pathogens in Mauritania, which was carried out by the analysis of bovine and camel samples taken at the slaughterhouse of Nouakchott. Blood and serum were collected by random sampling from 159 camels and 118 cattle in March 2013 at the large animals abattoir in Nouakchott. Serological tests for Rift Valley Fever (RVF), Peste des Petits Ruminants (PPR), West Nile disease (WND), epizootic haemorrhagic disease (EHD) and African horse sickness (AHS) were carried out using commercial ELISA kits. The samples, which resulted positives for PPR, WND and AHS, were tested with the confirmatory virus neutralization test (VNT). According to ELISA results, serological prevalence of RVF was 45% (95% CI 52.3-37.7) in camels and 16% (95% CI 22.6-9.4) in cattle. The difference between the observed prevalences in camels and in cattle was significant (p value ≤ 0.01). PPR was absent in camels and had 12% prevalence (95% CI, 17.86-6.14) in cattle. Furthermore, camels showed 92% (95% CI, 96.1-87.9) prevalence of WNV, 73% (95% CI, 82.3-63.64) of EHD and 3% (95% CI, 5.6-0.4) of AHS. This data are of relevance since provided useful feedbacks on the circulation of the pathogens in field. Moreover, this survey provided new information on the susceptibility of camels to several emerging pathogens and on the possible use of this species as sentinel animal.

Rift Valley fever (RVF) is a disease caused by RVF virus (RVFV) which can cause infections in a range of wild and domestic ruminants as well as in humans and characterized by an increased incidence of abortion in ruminants. This study aims to survey the seroprevalence and risk factors of this zoonose among aborted sheep in Kurdistan province, the west of Iran. 182 blood samples were collected from aborted sheep during the past one month under age groups <1, ≥1-3, >3-5 year in four seasons in two groups of border and non-border cities of Kurdistan province. The presence of RVFV-specific Antibodies was investigated by using competitive ELISA. Indirect immunofluorescence assay (IIFA) was used to confirm positive samples, after separation of serum, as well as blood samples were analyzed for description of hematological parameters. Of a total sheep sampled 1.65 % (n = 3) were positive for RVFV antibodies in both test. The results of IIFA were correlated with the ELISA results. All of the positive samples showed leucopenia and had significant relation with seroprevalence of RVF (P < 0.05). The seroprevalence of RVF in the border cities were significantly higher than other group (P < 0.05) Age of sheep and season had no significant effect on prevalence of RVF (P > 0.05). Results obtained in this study indicated the presence of low-level RVFV circulation among the sheep of Kurdistan Province in Iran, so it is necessary to carry out further studies in other areas of Iran. Doing an epidemiologically study aimed at isolating RVFV in the ruminants of Kurdistan province is recommended. The risk factor of bordering with Iran\'s western neighbor (Iraq) requires seriously control of the exchange of animals and the relevant products between the two countries.

暂无摘要。

Rift Valley fever (RVF) is a zoonotic disease of great public health and economic importance transmitted by mosquitoes. The main method of preventing the disease is vaccination of susceptible livestock before outbreaks occur. Studies on RVF vaccines have focused on the production processes, safety, and efficacy standards but those on uptake and adoption levels are rare. This study sought to understand the barriers faced by men and women farmers in the uptake of livestock vaccines to inform strategies for optimizing the use of vaccines against RVF in East Africa. The cross-sectional qualitative study utilized the pairwise ranking technique in sex disaggregated focus group discussions to identify and rank these barriers. Results indicate that men and women farmers experience barriers to vaccine uptake differentially. The barriers include the direct and indirect cost of vaccines, distances to vaccination points, availability of vaccination crushes, intra-household decision making processes and availability of information on vaccination campaigns. The study concludes that vaccine provision does not guarantee uptake at the community level. Hence, these barriers should be considered while designing vaccination strategies to enhance community uptake because vaccine uptake is a complex process which requires buy-in from men and women farmers, veterinary departments, county/district and national governments, and vaccine producers.