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Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the Indian Ocean. RVF occurs mainly in livestock but also affects humans with severe clinical manifestations, including neurological disorders. However, human neuropathogenesis of Rift Valley fever virus (RVFV) is still poorly characterized. To study the interactions between RVFV and the central nervous system (CNS), we focused on RVFV infection of astrocytes, the major glial cells of the CNS that have several supporting roles including immune response regulation. We confirmed the permissiveness of astrocytes to RVFV infection and highlighted a strain-dependent infectivity. We showed that RVFV infection of astrocytes induced cell apoptosis and observed that the RVFV Non-Structural protein NSs, a known virulence factor, potentially delayed apoptosis by sequestrating activated-caspase 3 in the nucleus. Our study also showed that RVFV-infected astrocytes upregulated expression of genes associated with inflammatory and type I interferon responses at the mRNA level, but not at the protein level. This inhibition of immune response is potentially due to a NSs-dependent mechanism of mRNA nuclear export inhibition. Together, these results highlighted the direct impact of RVFV infection on the human CNS through the induction of apoptosis and a possible inhibition of early-onset immune responses that are crucial for the host survival.

Rabies is a lethal zoonotic encephalomyelitis that causes an estimated 59,000 human deaths yearly worldwide. Although developing countries of Asia and Africa bear the heaviest burden, surveillance and disease detection in these countries is often hampered by the absence of local laboratories able to diagnose rabies and/or the difficulties of sample shipment from low-access areas to national reference laboratories. Filter papers offer a convenient cost-effective alternative for the sampling, shipment, and storage of biological materials for the diagnosis of many pathogens including rabies virus, yet the properties of diagnostic tests using this support have not been evaluated thoroughly. Sensitivity and specificity of molecular diagnosis of rabies infection using a reverse transcription followed by a hemi-nested polymerase chain reaction (RT-hn-PCR) either directly on brain tissue or using brain tissue dried on filter paper were assessed on 113 suspected field animal samples in comparison to the direct fluorescent antibody test (FAT) recommended by the World Health Organization as one of the reference tests for rabies diagnosis. Impact of the duration of the storage was also evaluated. The sensitivity and the specificity of RT-hn-PCR i) on brain tissue were 96.6% (95% CI: [88.1–99.6]) and 92.7% (95% CI: [82.4–98.0]) respectively and ii) on brain tissue dried on filter paper 100% (95% CI: [93.8–100.0]) and 90.9% (95% CI: [80.0–97.0]) respectively. No loss of sensitivity of RT-hn-PCR on samples of brain tissue dried on filter paper left 7 days at ambient temperature was detected indicating that this method would enable analyzing impregnated filter papers sent to the national reference laboratory at ambient temperature within a 1-week shipment time. It could therefore be an effective alternative to facilitate storage and shipment of samples from low-access areas to enhance and expand rabies surveillance., Author summary Dogs are responsible for 99% of human rabies deaths. Facilitating diagnostic of rabid dogs can help further identify i) people who were exposed to rabies in order to encourage them to seek post exposure prophylaxis and ii) other exposed animals to break the transmission chain (i.e. prevent them from further transmitting the virus to other people and animals). Yet, the reference diagnostic method for animal rabies requires brain samples to be collected post-mortem and shipped under temperature-controlled conditions. The shipping of such samples is complex in low-access areas, especially in low income countries, which are often those that bear the heaviest rabies burden. Filter papers offer a convenient alternative for biological sample shipment and storage. Here the efficiency of a molecular diagnostic method applied to brain tissue dried on filter paper is compared to one of the reference methods, the direct fluorescent antibody test. Our results show it has an excellent sensitivity (it does not miss any positive samples), even when filter papers are left 7 days at ambient temperature. These results let us foresee a cost-effective alternative facilitating shipment, storage and testing of samples from rabies suspected animals from low-access areas. This could considerably enhance and expand rabies surveillance in low-income countries, allowing a more comprehensive evaluation of rabies burden, and thus reinforcing arguments for allocating funds to rabies control policies.

Additional file 1: Table S1. List of specimens included in this study, along with their identification numbers (voucher code), countries and GenBank accession numbers for each DNA region.

Additional file 2: Table S1. Characteristics of trapping sites. Table S2. Temporal variables considered on mixed-effect negative binomial hurdle models. Table S3. Non-dynamic variables considered on mixed-effect negative binomial hurdle models.

International audience; Mayotte is an island located in the Mozambique Channel, between Mozambique and Madagascar, in the South Western Indian Ocean region. A severe syndrome of unknown aetiology has been observed seasonally since 2009 in cattle (locally named "cattle flu"), associated with anorexia, nasal discharge, hyperthermia and lameness. We sampled blood from a panel of those severely affected animals at the onset of disease signs and analysed these samples by next-generation sequencing. We first identified the presence of ephemeral bovine fever viruses (BEFV), an arbovirus belonging to the genus Ephemerovirus within the family Rhabdoviridae, thus representing the first published sequences of BEFV viruses of African origin. In addition, we also discovered and genetically characterized a potential new species within the genus Ephemerovirus, called Mavingoni virus (MVGV) from one diseased animal. Finally, both MVGV and BEFV have been identified in cattle from the same herd, evidencing a co-circulation of different ephemeroviruses on the island. The clinical, epidemiological and virological information strongly suggests that these viruses represent the etiological agents of the observed "cattle flu" within this region. This study highlights the importance of the strengthening and harmonizing arboviral surveillance in Mayotte and its neighbouring areas, including Africa mainland, given the importance of the diffusion of infectious diseases (such as BEFV) mediated by animal and human movements in the South Western Indian Ocean area.

Rift Valley fever (RVF) is a major zoonotic and arboviral hemorrhagic fever. The conditions leading to RVF epidemics are still unclear, and the relative role of climatic and anthropogenic factors may vary between ecosystems. Here, we estimate the most likely scenario that led to RVF emergence on the island of Mayotte, following the 2006–2007 African epidemic. We developed the first mathematical model for RVF that accounts for climate, animal imports and livestock susceptibility, which is fitted to a 12-years dataset. RVF emergence was found to be triggered by the import of infectious animals, whilst transmissibility was approximated as a linear or exponential function of vegetation density. Model forecasts indicated a very low probability of virus endemicity in 2017, and therefore of re-emergence in a closed system (i.e. without import of infected animals). However, the very high proportion of naive animals reached in 2016 implies that the island remains vulnerable to the import of infectious animals. We recommend reinforcing surveillance in livestock, should RVF be reported is neighbouring territories. Our model should be tested elsewhere, with ecosystem-specific data., Author summary Rift Valley fever (RVF) is an arboviral hemorrhagic fever affecting primarily livestock in Africa and in the Arabian Peninsula. The conditions leading to RVF emergence are not fully understood, mainly because of data scarcity. Applied to the island of Mayotte (our ecosystem under study), for which 12 years RVF serological dataset are available, and by using a mechanistic model, we demonstrate that RVF epidemics related mainly to the introduction of infectious animals. Our work confirms that anthropogenic factors, such as livestock movements, need to be accounted for in order to understand the epidemiology of this disease. Our model should be tested elsewhere, with ecosystem-specific data.

Susceptibility values (LC50 and LC90 expressed in mg of active ingredient/m²) of different European populations of Culicoides imicola to different active ingredients. Mortality was recorded 24 h after 1 h exposure to different concentrations. Table S5b. Susceptibility values (LC50 and LC90 expressed in mg of active ingredient/m²) of different African populations of Culicoides imicola to different active ingredients. Mortality was recorded 24 h after 1 h exposure to different concentrations. (DOC 54 kb)