Towards the strategic control of endemic foot-and-mouth disease in Africa: new techniques for a neglected problem

Foot-and-mouth disease (FMD) is a very serious viral disease of cloven-hooved animals, which causes immense economic losses through its impacts on animal health, productivity, and consequent trading constraints. While the biology of foot-and-mouth disease virus (FMDV) is quite well-understood as it occurs in outbreak settings in developed countries, this understanding has not been applied to regions of the world where the virus is permanently present. This is particularly unfortunate, since FMD has serious impacts for small-farmers, and previous studies rank FMD as one of the most important livestock diseases associated with poverty. Tanzania has the third largest population of domestic livestock in Africa, and livestock are critical for the nutrition and economic welfare of the millions of people who live in rural Tanzania. Rural communities depend directly on livestock for food, milk, use of animals in crop production, and in raising money through local sales. FMD causes animals to lose weight, reduce milk production, become immobile, and reduce in financial value, and therefore its control is particularly important for communities who depend directly on the well-being of their livestock. FMDV is often found to infect buffalo and other wild ungulates, and wildlife are often suspected to be either the direct of ultimate source of viruses causing disease in domestic livestock. This has led to conflict between the management of wildlife, which is itself a hugely important financial resource in countries like Tanzania, and domestic livestock, with calls for the construction of fences similar to those constructed in southern Africa that serve to reduce contact between domestic livestock and wildlife. There is an urgent need to understand how important wildlife is as a source of FMD for domestic livestock, and to find more environmentally-friendly ways of preventing the virus from moving out from wildlife sanctuaries. FMD can be controlled through the use of vaccination, but the vaccines are not perfect, providing only short-lived protection from the symptoms of the disease rather than infection itself, and protecting against only a limited range of genetic types of the virus. In order to use vaccination effectively, it is critical to know the genetic types of the virus that are likely to cause infection in animals, so that the best vaccines can be chosen. Unfortunately, although quite easily obtained, this knowledge is almost completely lacking from very large areas of Africa in which the virus is thought to be present. This project aims to conduct a large-scale survey of FMD in livestock and wildlife in 10 different areas across Tanzania. Blood samples will be collected from domestic livestock and wildlife and tested for evidence of previous infection by FMD and this will provide a crude picture of the most important types of virus that are present. Where virus is actually isolated we will sequence parts of the genome to obtain much more detailed information on the virus types. We will also focus on one area in northern Tanzania to carry out a more detailed longer-term study, collecting blood samples from herds at regular time intervals and collecting viruses during FMD outbreaks and sequencing them. Using these data, we will be able to determine where virus that causes infections comes from (is it wildlife or other domestic animals in the region, or does it evolve within the herds that its infecting?). We will also study the role of animals that have long-term infections of FMDV, identify other farming practices that are associated with infection by FMDV, and study just how much immune protection caused by infection with one strain can protect animals from infection with other strains.

Despite a sophisticated understanding of the dynamics, control, and evolution of this virus during its periodic incursions into more developed countries, regrettably little of this understanding has been applied to the epidemiology of FMDV in developing countries where the disease is endemic. Tanzania has the third largest livestock population in Africa, and FMD outbreaks occur frequently throughout the country, with particularly severe impacts for pastoral and agro-pastoral families who are most reliant on livestock products for food and economic security. An almost total lack of systematically collected data from epidemiologically integrated studies of FMD in Tanzania is a major obstacle to tackling these problems. Vaccination offers a potential solution, but many different types of FMD virus circulate in Tanzania, and uncertainties about which vaccines to use, their effectiveness, the role of wildlife as sources of infection, and the most appropriate strategies for local and regional control all serve as major impediments to policy development and implementation. This project aims address these knowledge gaps. We will conduct a broad survey of FMD in livestock and wildlife across Tanzania to determine which serotype of viruses have been circulating in each area. Viral capsid (P1) sequencing will be used to determine the precise genetic strains currently found in different species and different areas, and to identify the most suitable vaccines that can be used to control them. We will also focus on one area in northern Tanzania to carry out a longer-term study, collecting regular serological and virus samples from herds. Using these data, we will determine the origins of new virus strains, the role of carrier animals in the maintenance of FMDV, identify risk factors associated with infection, quantify the extent of cross-protective immune responses, and develop and parameterize mathematical models to inform optimal control policies.

This project will identify the strains and serotypes of viruses currently in Tanzania, and improve our understanding of the factors that influence the circulation and maintenance of these viruses. These findings will have important and immediate implications for the design of effective FMD control strategies in sub-Saharan Africa, both at a local scale and at national/regional levels. They will also have broad application to other locations, particularly elsewhere in Africa where similar livestock systems exist. From this project, we will have improved analytical tools which will allow us to develop vaccines that are most likely to be effective in East Africa. We will also have an understanding of the geographic and temporal patterns of genetic diversity, which will help determine the appropriate scales at which selected vaccines should be deployed. Modelling approaches combined with an improved knowledge of risk factors for outbreaks will also allow us to examine the effectiveness of different potential strategies. Beneficiaries. Tanzania has the third largest livestock population in Africa, and livestock are critical for the food-security and livelihoods of the poor. Primary beneficiaries will be these livestock-keepers and the livestock industry in Tanzania, and more widely in sub-Saharan Africa. Outputs of the project will help herd owners optimise herd productivity and offtake (e.g. through targeted vaccination of high-value individuals or draught animals). The results will also have major implications for the development of new regional markets, which will not only create opportunities for commercialisation of the livestock sector but reduce risk and vulnerability of poorer farmers by increasing their access to markets. Additional beneficiaries include wildlife managers and the national and global wildlife heritage; environmentally-sensitive approaches to FMD control around East Africa's protected wildlife areas will support the integrated livestock/wildlife systems that are critical for maintaining the integrity and viability of many of these areas (including UNESCO World Heritage Sites, such as the Serengeti, Ngorongoro and Selous Game Reserve). Increased knowledge of FMD vaccine strains circulating in East Africa will also be of direct benefit to international agencies (e.g. FAO, OIE, AU-IBAR) for policy development and to regional FMD vaccine laboratories and the pharmaceutical industry. The research will generate important information for scientists on the basic biology of cross-protection to heterologous viral challenge. The welfare of livestock will benefit directly from control of a debilitating disease, and also because the development of new mathematical techniques for analysing cross-protection will reduce the need for future animal experiments. Delivery of outputs to beneficiaries. Communication with academic beneficiaries will take place through publications and presentations at conferences, through our interactions with the related FP-7 project on FMDV vaccine improvements, and through our engagement with the EuFMD Commission, particularly the biennial Open Sessions of the Research Group. The multi-sectoral nature of the project partnerships will ensure dissemination of outputs to a wide range of stakeholders, with the Ministry of Livestock Development and Fisheries (MoLD) having primary responsibility for liasing with national policy-makers, international agencies (FAO, OIE, AU-IBAR), and providing materials and media to livestock-keepers through district and village-level livestock extension services, the Tanzania Wildlife Research Institute and Sokoine University of Agriculture thus ensuring integration between livestock and wildlife sectors. The strong connectivity of project partners with communities, veterinary, development and wildlife NGOs will also assist in translation of research findings into appropriate disease control strategies.