Reconstructing Mayotte 2018-19 Rift Valley Fever outbreak in humans by combining serological and surveillance data.

BACKGROUND: Rift Valley Fever (RVF) is a zoonosis that affects large parts of Africa and the Arabian Peninsula. RVF virus (RVFV) is transmitted to humans through contacts with infected animals, animal products, mosquito bites or aerosols. Its pathogenesis in humans ranges from asymptomatic forms to potentially deadly haemorrhagic fevers, and the true burden of human infections during outbreaks is generally unknown. METHODS: We build a model fitted to both passive surveillance data and serological data collected throughout a RVF epidemic that occurred in Mayotte Island in 2018-2019. RESULTS: We estimate that RVFV infected 10,797 (95% CrI 4,728-16,127) people aged ≥15 years old in Mayotte during the entire outbreak, among which only 1.2% (0.67%-2.2%) were reported to the syndromic surveillance system. RVFV IgG seroprevalence in people ≥15 years old was estimated to increase from 5.5% (3.6%-7.7%) before the outbreak to 12.9% (10.4%-16.3%) thereafter. CONCLUSIONS: Our results suggest that a large part of RVFV infected people present subclinical forms of the disease and/or do not reach medical care that could lead to their detection by the surveillance system. This may threaten the implementation of exhaustive RVF surveillance and adequate control programs in affected countries.

Rift Valley Fever (RVF) is a disease caused by a virus transmitted from livestock animals to humans by mosquito bites, aerosols or direct contact with infected animals or animal products. In some parts of Africa and the Arabian Peninsula, the virus can lead to large outbreaks in both humans and animals. Despite some infected people developing severe forms of the disease, some experience no or mild symptoms. Therefore, infection is often not detected by surveillance systems based on the reporting of symptoms by patients. Here, we use data collected during a RVF outbreak that occurred in 2018­2019 in Mayotte Island, in the Indian Ocean, to model the course of the outbreak in humans. We estimate that, throughout the epidemic, only 1.2% of infected people were detected by the surveillance system. Our results highlight that most human cases may go unreported during RVF outbreaks, making it difficult to monitor the burden of infections.

The role of livestock movements in the spread of Rift Valley fever virus in animals and humans in Mayotte, 2018-19.

Rift Valley fever (RVF) is a vector-borne viral disease of major animal and public health importance. In 2018-19, it caused an epidemic in both livestock and human populations of the island of Mayotte. Using Bayesian modelling approaches, we assessed the spatio-temporal pattern of RVF virus (RVFV) infection in livestock and human populations across the island, and factors shaping it. First, we assessed if (i) livestock movements, (ii) spatial proximity from communes with infected animals, and (iii) livestock density were associated with the temporal sequence of RVFV introduction into Mayotte communes' livestock populations. Second, we assessed whether the rate of human infection was associated with (a) spatial proximity from and (b) livestock density of communes with infected animals. Our analyses showed that the temporal sequence of RVFV introduction into communes' livestock populations was associated with livestock movements and spatial proximity from communes with infected animals, with livestock movements being associated with the best model fit. Moreover, the pattern of human cases was associated with their spatial proximity from communes with infected animals, with the risk of human infection sharply increasing if livestock in the same or close communes were infected. This study highlights the importance of understanding livestock movement networks in informing the design of risk-based RVF surveillance programs.

Estimation of Rift Valley fever virus spillover to humans during the Mayotte 2018-2019 epidemic.

Rift Valley fever (RVF) is an emerging, zoonotic, arboviral hemorrhagic fever threatening livestock and humans mainly in Africa. RVF is of global concern, having expanded its geographical range over the last decades. The impact of control measures on epidemic dynamics using empirical data has not been assessed. Here, we fitted a mathematical model to seroprevalence livestock and human RVF case data from the 2018-2019 epidemic in Mayotte to estimate viral transmission among livestock, and spillover from livestock to humans through both direct contact and vector-mediated routes. Model simulations were used to assess the impact of vaccination on reducing the epidemic size. The rate of spillover by direct contact was about twice as high as vector transmission. Assuming 30% of the population were farmers, each transmission route contributed to 45% and 55% of the number of human infections, respectively. Reactive vaccination immunizing 20% of the livestock population reduced the number of human cases by 30%. Vaccinating 1 mo later required using 50% more vaccine doses for a similar reduction. Vaccinating only farmers required 10 times as more vaccine doses for a similar reduction in human cases. Finally, with 52.0% (95% credible interval [CrI] [42.9-59.4]) of livestock immune at the end of the epidemic wave, viral reemergence in the next rainy season (2019-2020) is unlikely. Coordinated human and animal health surveillance, and timely livestock vaccination appear to be key to controlling RVF in this setting. We furthermore demonstrate the value of a One Health quantitative approach to surveillance and control of zoonotic infectious diseases.

Rift Valley Fever Outbreak, Mayotte, France, 2018-2019.

From November 2018 through July 2019, an outbreak of Rift Valley fever in humans occurred in Mayotte, France; 142 cases were confirmed. Exposure to animals or their biological fluid was reported by 73% of patients. Health authorities have been implementing control measures, including veterinary surveys, vector control interventions, and prevention measures.

Development and validation of a pen side test for Rift Valley fever.

BACKGROUND: Rift Valley fever (RVF) is one of the main vector borne zoonotic diseases that affects a wide range of ruminants and human beings in Africa and the Arabian Peninsula. A rapid and specific test for RVF diagnosis at the site of a suspected outbreak is crucial for the implementation of control measures. METHODOLOGY/PRINCIPAL FINDINGS: A first-line lateral flow immunochromatographic strip test (LFT) was developed for the detection of the nucleoprotein (N) of the RVF virus (RVFV). Its diagnostic performance characteristics were evaluated using reference stocks isolates recovered from different hosts and in geographic regions mimicking clinical specimens and from known RVF negative serum samples. A high level of diagnostic accuracy (DSe (35/35), DSp (167/169)) was observed, including the absence of cross-reactivity with viruses belonging to different genera. CONCLUSION/SIGNIFICANCE: The fact no specialized reagents and laboratory equipment are needed, make this assay a valuable, first-line diagnostic tool in resource-poor diagnostic territories for on-site RVFV detection, however the staff require training.

Co-circulation and characterization of novel African arboviruses (genus Ephemerovirus) in cattle, Mayotte island, Indian Ocean, 2017.

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.

Culicoides Latreille in the sun: faunistic inventory of Culicoides species (Diptera: Ceratopogonidae) in Mayotte (Comoros Archipelago, Indian Ocean).

BACKGROUND: The south-west insular territories of the Indian Ocean have recently received attention concerning the diversity of arthropods of medical or veterinary interest. While a recent study highlighted the circulation of Culicoides-borne viruses, namely bluetongue and epizootic hemorrhagic disease, with clinical cases in Mayotte (comprising two islands, Petite-Terre and Grand-Terre), Comoros Archipelago, no data have been published concerning the species diversity of Culicoides present on the two islands. RESULTS: A total of 194,734 biting midges were collected in 18 sites, covering two collection sessions (April and June) in Mayotte. Our study reports for the first time livestock-associated Culicoides species and recorded at least 17 described Afrotropical species and one undescribed species. The most abundant species during the April collection session were C. trifasciellus (84.1%), C. bolitinos (5.4%), C. enderleini (3.9%), C. leucostictus (3.3%) and C. rhizophorensis (2.1%). All other species including C. imicola represented less than 1% of the total collection. Abundance ranged between 126-78,842 females with a mean and median abundance of 14,338 and 5111 individuals/night/site, respectively. During the June collection, the abundance per night was low, ranging between 6-475 individuals. Despite low abundance, C. trifasciellus and C. bolitinos were still the most abundant species. Culicoides sp. #50 is recorded for the first time outside South Africa. CONCLUSIONS: Our study reports for the first time the Culicoides species list for Mayotte, Comoros Archipelago, Indian Ocean. The low abundance and rare occurrence of C. imicola, which is usually considered the most abundant species in the Afrotropical region, is unexpected. The most abundant and frequent species is C. trifasciellus, which is not considered as a vector species so far, but its role needs further investigation. Further work is needed to describe Culicoides sp. #50 and to carry on faunistic investigations on the other islands of the archipelago as well as in neighboring countries.

Evidence of bluetongue and Epizootic Haemorrhagic disease circulation on the island of Mayotte.

A cross-sectional study was conducted to explore the epidemiological situation in Mayotte regarding two orbiviruses: Bluetongue virus (BTV) and Epizootic Haemorrhagic Disease virus (EHDV). In all, 385 individual asymptomatic cattle were blood-sampled (one EDTA and one serum tube per animal) between February and June 2016. Antibody (ELISA) and genome prevalence (PCR) was assessed. Almost all the selected cattle showed antibodies against both BTV and EHDV, at 99.5% (CI95% [98.00, 100]) and 96.9% (CI95% [94.5, 98.3]), respectively. Most of the cattle acquired antibodies in their first years of age. EHDV and BTV genomes were detected in 25.2% (CI95% [21.1, 29.8]) and 18.2% (CI95% [14.6, 22.4]) of samples, respectively. Coinfection with BTV and EHDV was observed in 9.4% of samples (CI95% [6.8, 12.7]). Cattle under three years old were more frequently reported as positive for genome detection by PCR than older cattle. Five serotypes of BTV and one serotype of EHDV were identified from eight samples: BTV-4, BTV-9, BTV-11, BTV-15, BTV-19 and EHDV-6, of which some were reported in neighbouring areas. BTV and EHDV both circulate in Mayotte and in its surrounding territories.

Livestock trade network: potential for disease transmission and implications for risk-based surveillance on the island of Mayotte.

The island of Mayotte is a department of France, an outermost region of the European Union located in the Indian Ocean between Madagascar and the coast of Eastern Africa. Due to its close connection to the African mainland and neighbouring islands, the island is under constant threat of introduction of infectious diseases of both human and animal origin. Here, using social network analysis and mathematical modelling, we assessed potential implications of livestock movements between communes in Mayotte for risk-based surveillance. Our analyses showed that communes in the central region of Mayotte acted as a hub in the livestock movement network. The majority of livestock movements occurred between communes in the central region and from communes in the central region to those in the outer region. Also, communes in the central region were more likely to be infected earlier than those in the outer region when the spread of an exotic infectious disease was simulated on the livestock movement network. The findings of this study, therefore, suggest that communes in the central region would play a major role in the spread of infectious diseases via livestock movements, which needs to be considered in the design of risk-based surveillance systems in Mayotte.

Drivers for Rift Valley fever emergence in Mayotte: A Bayesian modelling approach.

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.

Absence of Evidence of Rift Valley Fever Infection in Eulemur fulvus (Brown Lemur) in Mayotte During an Interepidemic Period.

The potential role of Eulemur fulvus (brown lemur) in the epidemiology of Rift Valley fever (RVF) in Mayotte, during an interepidemic period, was explored. In February and March 2016, 72 animals were blood sampled and tested for RVF. No evidence of RVF genome or antibodies was found in the samples. The role of other wild mammals on the island should, however, be further investigated.

The Epidemiology of Rift Valley Fever in Mayotte: Insights and Perspectives from 11 Years of Data.

Rift Valley fever (RVF) is a zoonotic arboviral disease that is a threat to human health, animal health and production, mainly in Sub-Saharan Africa. RVF virus dynamics have been poorly studied due to data scarcity. On the island of Mayotte in the Indian Ocean, off the Southeastern African coast, RVF has been present since at least 2004. Several retrospective and prospective serological surveys in livestock have been conducted over eleven years (2004-15). These data are collated and presented here. Temporal patterns of seroprevalence were plotted against time, as well as age-stratified seroprevalence. Results suggest that RVF was already present in 2004-07. An epidemic occurred between 2008 and 2010, with IgG and IgM peak annual prevalences of 36% in 2008-09 (N = 142, n = 51, 95% CI [17-55]) and 41% (N = 96, n = 39, 95% CI [25-56]), respectively. The virus seems to be circulating at a low level since 2011, causing few new infections. In 2015, about 95% of the livestock population was susceptible (IgG annual prevalence was 6% (N = 584, n = 29, 95% CI [3-10])). Monthly rainfall varied a lot (2-540mm), whilst average temperature remained high with little variation (about 25-30°C). This large dataset collected on an insular territory for more than 10 years, suggesting a past epidemic and a current inter-epidemic period, represents a unique opportunity to study RVF dynamics. Further data collection and modelling work may be used to test different scenarios of animal imports and rainfall pattern that could explain the observed epidemiological pattern and estimate the likelihood of a potential re-emergence.

A Stochastic Model to Study Rift Valley Fever Persistence with Different Seasonal Patterns of Vector Abundance: New Insights on the Endemicity in the Tropical Island of Mayotte.

Rift Valley fever (RVF) is a zoonotic vector-borne disease causing abortion storms in cattle and human epidemics in Africa. Our aim was to evaluate RVF persistence in a seasonal and isolated population and to apply it to Mayotte Island (Indian Ocean), where the virus was still silently circulating four years after its last known introduction in 2007. We proposed a stochastic model to estimate RVF persistence over several years and under four seasonal patterns of vector abundance. Firstly, the model predicted a wide range of virus spread patterns, from obligate persistence in a constant or tropical environment (without needing vertical transmission or reintroduction) to frequent extinctions in a drier climate. We then identified for each scenario of seasonality the parameters that most influenced prediction variations. Persistence was sensitive to vector lifespan and biting rate in a tropical climate, and to host viraemia duration and vector lifespan in a drier climate. The first epizootic peak was primarily sensitive to viraemia duration and thus likely to be controlled by vaccination, whereas subsequent peaks were sensitive to vector lifespan and biting rate in a tropical climate, and to host birth rate and viraemia duration in arid climates. Finally, we parameterized the model according to Mayotte known environment. Mosquito captures estimated the abundance of eight potential RVF vectors. Review of RVF competence studies on these species allowed adjusting transmission probabilities per bite. Ruminant serological data since 2004 and three new cross-sectional seroprevalence studies are presented. Transmission rates had to be divided by more than five to best fit observed data. Five years after introduction, RVF persisted in more than 10% of the simulations, even under this scenario of low transmission. Hence, active surveillance must be maintained to better understand the risk related to RVF persistence and to prevent new introductions.