Molecular Epidemiology of Foot-and-Mouth Disease Virus in the Context of Transboundary Animal Movement in the Far North Region of Cameroon

Transboundary movement of animals is an important mechanism for foot-and-mouth disease virus (FMDV) spread in endemic regions, such as Cameroon. Several transboundary animal trade routes cross the Far North Region of Cameroon, and cattle moved on foot along these routes often come in contact with native (sedentary and transhumant) herds. The purpose of this study was to investigate the role of transboundary trade cattle in the epidemiology of FMDV in the Far North Region of Cameroon. A total of 582 oropharyngeal fluid (OPF) samples were collected from asymptomatic transboundary trade cattle at official border check points and 57 vesicle epithelial tissues were collected from clinically affected native cattle in the Far North Region of Cameroon during 2010–2014. Viral protein 1 (VP1) coding sequences were obtained from 6 OPF samples from transboundary cattle (4 serotype O, 2 serotype SAT2) and 19 epithelial tissue samples from native cattle (7 serotype O, 3 serotype SAT2, 9 serotype A). FMDV serotype O viruses belonged to two topotypes (East Africa-3 and West Africa), and phylogenetic analyses suggested a pattern of continuous transmission in the region. Serotype SAT2 viruses belonged to a single topotype (VII), and phylogenetic analysis suggested a pattern of repeated introductions of different SAT2 lineages in the region. Serotype A viruses belonged to topotype AFRICA/G-IV, and the pattern of transmission was unclear. Spearman rank correlation analysis of VP1 coding sequences obtained in this study from transboundary and native cattle showed a positive correlation between genetic distance and time for serotype O (ρ = 0.71, p = 0.003) and between genetic distance and geographic distance for serotype SAT2 (ρ = 0.54, p = 0.1). These data suggest that transboundary trade cattle participate in the transmission of FMDV in the Far North Region of Cameroon, however the dynamics and direction of transmission could not be determined in this study. Results of this study contribute to the understanding of transboundary FMDV epidemiology in Central Africa and will help to inform control programs in Cameroon and in the region

A scoping review of foot-and-mouth disease risk, based on spatial and spatio-temporal analysis of outbreaks in endemic settings

International audienc

Foot and mouth disease vaccine efficacy in Africa: a systematic review and meta-analysis

BackgroundSeveral factors, such as diverse serotypes, vaccination methods, weak biosecurity, and animal movements, contribute to recurrent Foot-and-Mouth Disease Virus (FMDV) outbreaks in Africa, establishing endemicity. These outbreaks cost over $2 billion annually, prompting a high-priority focus on FMDV vaccination. Despite extensive efforts, vaccine efficacy varies. This study aims to evaluate routine foot and mouth disease (FMD) vaccines in Africa via systematic review and meta-analysis.MethodsA systematic review and meta-analysis were carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was conducted to assess the efficacy of FMDV vaccination using the meta for package of R.ResultsVaccinated animals have roughly a 69.3% lower chance of FMDV infection compared to unvaccinated animals, as indicated by the pooled results from the random-effects model, which showed a risk ratio (RR) of 0.3073. There was a statistically significant heterogeneity (p < 0.05) across all of the included articles.ConclusionOverall findings suggest that if properly planned and implemented, FMDV vaccination programs and strategies in Africa could help control the spread of the disease throughout the continent and beyond

Serological profile of foot-and-mouth disease in wildlife populations of West and Central Africa with special reference to Syncerus caffer subspecies

The role which West and Central African wildlife populations might play in the transmission dynamics of FMD is not known nor have studies been performed in order to assess the distribution and prevalence of FMD in wild animal species inhabiting those specific regions of Africa. This study reports the FMD serological profile extracted from samples (n = 696) collected from wildlife of West and Central Africa between 1999 and 2003. An overall prevalence of FMDV NSP reactive sera of 31.0% (216/696) was estimated, where a significant difference in seropositivity (p = 0.000) was reported for buffalo (64.8%) as opposed to other wild animal species tested (17.8%). Different levels of exposure to the FMDV resulted for each of the buffalo subspecies sampled (p = 0.031): 68.4%, 50.0% and 0% for Nile Buffalo, West African Buffalo and African Forest Buffalo, respectively. The characterisation of the FMDV serotypes tested for buffalo found presence of antibodies against all the six FMDV serotypes tested, although high estimates for type O and SAT 3 were reported for Central Africa. Different patterns of reaction to the six FMDV serotypes tested were recorded, from sera only positive for a single serotype to multiple reactivities. The results confirmed that FMDV circulates in wild ruminants populating both West and Central Africa rangelands and in particular in buffalo, also suggesting that multiple FMDV serotypes might be involved with type O, SAT 2 and SAT 1 being dominant. Differences in serotype and spill-over risk between wildlife and livestock likely reflect regional geography, historical circulation and differing trade and livestock systems

Dynamic modelling to explore persistence of disease in endemic settings using foot and mouth disease as an exemplar

Foot and mouth disease (FMD) costs over $20bn annually in large part due to control costs and production losses. Endemic regions such as sub-Saharan Africa (SSA) are particularly badly affected. Pastoral livestock keepers experience near yearly outbreaks, but the factors which contribute to persistence remain poorly understood. While epidemiological studies in endemic settings have identified risk factors such as transhumance (the seasonal movement of livestock to find better grazing), and enable understanding of the contemporary state of the system they have yet to explain how infection persists in these regions. Key aspects of a system can be explored relatively quickly and cheaply using modelling. However, modelling of FMD is more common for disease-free settings focusing specifically on disease control – starting with and returning to a system free of disease. While disease control in endemic settings is the ultimate aim, this first requires a better understanding of the mechanisms underlying persistence. For this, models specific to endemic settings are required and must account for key differences compared to disease-free settings. In this project a suite of stochastic models was developed to explore dynamics of a highly infectious, directly transmitted pathogen such as FMD. The models developed explore persistence and infection dynamics across local and regional scales investigating the impact of different factors in pastoralist systems and the perceived persistence of disease from field observations. A within-herd model shows that infection cannot persist for longer than 3 months without reintroduction. Including persistently infectious individuals in the model has little impact on the overall infection of individuals within the herd. This strongly supports the idea reintroduction of the disease is required to give the repeated outbreaks that are characteristic of endemic settings. Although exploring persistence likely requires models that account for transmission between herds, understanding of herd-level infection characteristics can be gained from this within-herd model. In endemic settings natural immunity in animals following infection can result in herd immunity and protection against reinfection. The model indicates the mean duration of herd immunity following a large outbreak in a naïve population is 2 years. The duration of herd immunity depends on the susceptibility of the herd prior to the outbreak, the size of the outbreak and the turnover of the population. Accurately predicting the dynamics of heterogeneous real-world systems requires parameterisations that characterise not only the broad behaviour but also its variation (e.g. between herds and regions). Data from outbreaks can be useful in developing suitable parameterisations. Using R0 as an example, values were estimated using a number of standard methods and compared to values calculated from the underlying epidemiological characteristics of simulated outbreaks. Both epidemiological characteristics and the method used to estimate R0 affect whether R0 is over- or under-estimated. These results do not suggest a universally preferred method for estimating R0 but highlight that an understanding of the underlying epidemiology of a system is required prior to method selection. Inaccurate estimation of R0 can have consequences for vaccine control - where R0 estimates are lower than the true value the population will be under-vaccinated. This is costly and result in ineffective control that allows some infection to remain. The infectious period and post outbreak immune period (POIP) of herds in endemic settings is unknown. These are likely different from disease-free settings where control measures are expected; for example, in FMD-free settings there is no herd-level POIP as infected herds are removed from the population. Mixture distributions were fitted to outputs from simulated outbreaks to give herd-level estimates for the infectious period and POIP. It is shown that, in the absence of intervention, there is a period of herd immunity following 65% of simulated outbreaks. Furthermore, analysis suggests a mean herd-level infectious period of 21.5 days – longer than previously used in the modelling of FMD transmission between herds. This work highlights the importance of obtaining and using herd-level estimates which are appropriate for endemic settings. Poor herd-level estimates of epidemiological characteristics can result in inadequate appreciation of transmission dynamics and key factors in the persistence of infection at regional scales. In turn this will compromise the design and implementation of control measures. As persistence was not observed at the herd level, a metapopulation model framework to explore endemic persistence in pastoral systems was developed. A population of 13000 herds (representative of Cameroon’s Adamawa region) was modelled allowing for local and transhumant contact. Although it was not possible to identify FMD specific parameters characterising between-herd disease spread, persistence and dynamics were explored for a limited range of contact and transmission parameters. The results indicate that seasonal transhumance can contribute to the persistence of infection at a regional level. The observed dynamics of infection and immunity are seasonal with immunity during the period of endemic stability greater than 60%. Timing of peak infection is dependent on seasonal variation in both contact between herds and vaccination. Short-term vaccine-derived immunity was modelled and is characteristic of the protection offered by FMD vaccines. The modelled seasonality of vaccination, and subsequent loss of vaccine-derived immunity, results in an increase in susceptible herds following the transhumant period. It is likely that this seasonal increase in susceptibility helps the persistence of infection as has been observed with other diseases such as measles. There is still much that needs to be understood about the dynamics of FMD transmission in endemic regions. Modelling can work well alongside targeted data collection to understand persistence, infection dynamics and assess control measures (particularly over long time scales) that are difficult to undertake in the field. Exploration of models, like that presented in this work, can highlight areas where data from the field would be beneficial to improve model parameterisation and better reflect the system of interest. Although long-term longitudinal tracking of infection at herd level over a range of scales is likely to be costly to collect and challenging to analyse, data of this nature would help inform both within-herd and between-herd models of transmission

Virus phylogeography at the wild/domestic animal interface

With the recent advances in sequencing technology it is increasingly common to find freely available large genomic datasets composed of thousands of genetic samples of viral or bacterial origin. Because Bayesian approaches possess multiple advantages against more traditional phylogenetic methods, such methods are considered as a standard tool to study the evolution and circulation of fast-evolving pathogens such as viruses. With those Bayesian phylogenetic approaches, the evolutionary and transmission parameters of fast evolving infectious diseases can be estimated to inform their control of in both epidemic and endemic contexts. Zoonoses are diseases that have passed from a non-human animal to a human population. The emergence of such diseases in human populations can be caused by environmental changes bringing wild and domestic animals closer to each other facilitating the transmission to humans. Phylogenetic approaches can help us to understand how disease can be transmitted between wild and domestic animal populations. Using recently developed Bayesian phylogenetic methods the first aim of this thesis was to understand and study the transmission of infectious disease amongst wild and domestic animal populations. Therefore, I performed those epidemiological analysis in an endemic context, using both Eurasian avian influenza sequences and African foot-and-mouth disease virus (FMDV). The second aim was to develop a software capable of reducing potential sampling bias between multiple populations while analysing large genetic datasets in a short running time compared to currently available phylogenetic methods. I first studied the transmission and reassortment pattern of avian influenza within Europe and Asia using internal segments sequences (PB2) originated from wild and domestic birds. Using both a non-structured and structured coalescent approach I determined that the two continents constitute distinct demes that are sporadically connected. Most of the reassortment pattern observed occurred within western Europe and Eastern China. I also determined that while wild Anseriformes are responsible for most of the of the virus circulation in Europe, domestic Anseriformes birds are responsible for the virus movements in Asia. The circulation of the virus between Asia and Europe being mostly done by both domestic and wild Anseriformes birds. Secondly, to understand the patterns of FMDV, I compared the transmission patterns of four FMDV (FMDO, FMDA, FMD SAT1, FMD SAT2) serotypes and estimated the factors influencing the circulation of these viruses in Africa using a discrete and a continuous phylogeographic approach. One conclusion of this chapter is that FMDV strains currently circulating in African livestock were probably introduced in the early 18th century trough livestock movements for the serotype A/O and reintroduced from wild Buffalo population after the African rinderpest epidemic for the SAT serotypes. I also show that movements of domestic cattle were responsible of the FMDV propagation and circulation in Africa with a small role played by wild animal populations. Thirdly, using advanced Bayesian structured coalescent model approximations, I studied the role played by antelope in the transmission of FMDV SAT1 and SAT2 in Africa. I found that for both serotypes antelopes seem to act as an intermediate host between buffalo and cattle. In the last part of the thesis I present a new software “Epitree-sim” that allows the fast estimation of phylogenetic trees and transmission patterns between demes using a fast dating algorithm and repeated subsampling of the sequence analysed

Neglected zoonotic diseases and cross-border livestock movements in northern Côte d'Ivoire : towards local and regional integrated control

Background: Neglected zoonotic diseases (NZDs) are less prioritized in Africa, which is in contrast to their impacts on human and animal health and livestock production. Brucellosis, Q fever and Rift Valley fever (RVF) are among the most common NZDs that occur in Western Africa. Cross-border livestock movements are frequent in Africa given the centuries-old practice of mobile pastoralism. They are described to be associated with the spread of “highly contagious epidemic animal diseases with significant economic and food security concerns, known as Transboundary Animal Diseases -TADs”, which include NZDs of interest in this PhD thesis. Although movements are central to livestock production in the Economic Community of West African States (ECOWAS), they are mostly uncontrolled. Additionally, veterinary services of the neighboring countries have hardly collaborated with respect to cross-border control of diseases. Currently the epidemiology as well as the public health and economic importance of TADs in general and NZDs in particular remain unknown in the region. The aim of this research was to generate epidemiological data on NZDs and TADs in order to assess their economic impact as well as to design appropriate regional control strategies. Methods: Multi-stage cross-sectional cluster surveys in livestock and humans between 2012 and 2014 in a random selection of 63 villages and a sample of 633 cattle, 622 small ruminants and about 100 people were conducted. Sera were tested with the Rose Bengal Plate Test (RBPT); indirect ELISAs for Brucella spp., B. ovis and C. burnetii; and a competitive ELISA for B. melitensis and RVF. Then questionnaires were administered regarding NZD risk factors. The economic impact of brucellosis on milk, meat and hide productions were calculated for Côte d’Ivoire using a stochastic projection matrix model which simulated the demographic growth and compared cattle productions with and without brucellosis. Regarding cross-border control of livestock movements and diseases, thirteen focus group discussions with mobile pastoralists, agropastoralists and farmers as well as eleven key-informant interviews with animal health professionals and livestock movement supporting agencies were conducted. Additionally, cross-sectional serological surveys on brucellosis and Q fever in humans (n = 76), cattle, sheep and goats (n = 537) in slaughterhouses along pastoral corridors in northern Côte d’Ivoire and Abidjan were also performed. Main results: The seroprevalence of Brucella spp. adjusted for clustering was 4.6% in cattle, 0% in sheep and goats and 5.3% in humans. In cattle, age, mixed-herding with other livestock species and having joint hygromas were significant predictors. The seroprevalence of Q fever was 13.9%, 9.4% and 12.4% in cattle, sheep and goats, respectively. The seroprevalence of RVF was 3.9% in cattle, 2.4% in sheep and 0% in goats. Abortion was a significant predictor of seropositivity in ewes. About 4% of the cattle had antibodies against both Q fever and RVF. The Ivorian cattle population was simulated and estimated to be about 1,885,123 and 1,906,961 with and without the disease in 2015, respectively. An overall intrinsic growth rate of 1.8% and 17.4% meat offtake rate were derived. The cumulated net present cost attributable to brucellosis infection was estimated at FCFA 14,455 x 106 (95% CI: 6,278–22,906). The incremental live cattle asset value was projected to FCFA 3,826 x 106 (95% CI: 1–7,6) in 2015. Regarding cross-border livestock mobility, key-informant interviews and group discussions identified almost 30,000 cattle from 200 mobile pastoralists involved each year in uncontrolled cross-border movements between Mali, Côte d’Ivoire and Burkina Faso. TADs such as Contagious Bovine Pleuropneumonia (CBPP), Foot-and-Mouth Disease (FMD), tuberculosis, lumpy skin disease, pasteurellosis, brucellosis and Blackleg were ranked to be the most important diseases in cattle whereas “peste des petits ruminants” (PPR) was the only disease reported in sheep and goats. Lack of veterinary staff and transportation means in veterinary services, poor cross-border veterinary collaboration and harmonization of disease control activities were the main constraints to controlling their spread. The study identified over-arching themes regarding the challenges and needs for cross-border control of TADs and movements and established a program for the harmonization of disease control activities in the three countries. Conclusions: Our results provide updated epidemiological and economic descriptions of NZDs in Côte d’Ivoire. The research identified key diseases, areas of increased livestock movements, corridors/routes, and needs for cross-border control of movements and diseases in the Sudano-Guinean savanna. Cross-border collaboration should be promoted for the implementation of an effective and durable control. There is an urgent need for cost-effectiveness studies to complement our economic impact estimations as well as studies to better explore and understand the added value of cross-border cross-sectoral collaboration and coordination regarding feasible movement and disease control