US-UK EEID Collab: Persistence of a highly contagious pathogen: ecological and evolutionary mechanisms in foot-and-mouth disease virus

Foot-and-mouth disease (FMD) affects livestock and wild animals, African buffalo especially. The disease is widely distributed in the developing world and the lack of effective control in these territories is a constant threat to developed countries like the USA and UK where the disease does not normally occur due to rigid control policies. This highly contagious viral disease causes a fever and painful blisters on the feet, teats and in the mouth, leading to lameness, a drop in milk production, loss of appetite and condition and significant social and economic impact.

Countries that want to export to high value markets like the UK and USA need to demonstrate total control of FMD, as a consequence FMD distorts the global trade of livestock and their products. Clearly, countries who have invested in eradicating the disease do not want it back, for example; introduction of FMD into the UK in 2001 cost over US$ 9 million to control and resulted in the slaughter of over 6 million animals. FMD undermines trade, impedes investment in the livestock sector, stops poor people having access to markets and limits options for their future and the future of their families. As a consequence, FMD is considered to be the most economically important disease of livestock and the World Health Organisation for Animal Health and the Food and Agricultural Organization of the United Nations have recently joined forces to establish a strategy for global FMD control.

In Africa, African buffalo are the natural reservoir host for FMD, the virus is maintained in herds for long periods of time and buffalo act as a source of infection for livestock, wildlife and other buffalo. We do not understand how the virus is maintained in buffalo populations or how the virus is transmitted from buffalo, to other animals. In addition, vaccines used to protect cattle are not very effective for the types of viruses present in buffalo, which are diverse and constantly mutating and changing. This situation creates friction in developing countries between the livestock producers, with a need for efficient livestock production systems to alleviate poverty, and conservationists trying to preserve wildlife populations and ecosystems.

The aim of this project is to determine the primary mechanism of FMD virus persistence in buffalo populations and understand how the virus constantly undergoes mutation and change in buffalo populations. Global FMD eradication, or control, will never be achieved unless we understand these mechanisms. Understanding inter-annual persistence will be invaluable for identifying troughs of low risk that can be exploited as a time for effective intervention and control strategies for livestock populations. Our findings will be scalable to buffalo populations throughout Africa. Understanding how virus is maintained in buffalo and transmitted to susceptible animals will allow us to develop better livestock vaccines and control policies to support economic development and preserve wildlife in Africa.

Understanding how extremely contagious, acute, strongly immunizing pathogens persist, especially in moderately sized populations, represents a puzzle in disease ecology. We will investigate how foot-and-mouth disease virus (FMDV) persists in its reservoir host. Foot-and-mouth disease (FMD) inflicts severe economic losses and is arguably the most important trade-restricting livestock disease. Extreme contagiousness is a key feature of FMD, however acute infection is characterised by a short viraemic phase, a rapid, effective and long lived immune response and a short infectious period. Following acute infection, most buffalo become carriers, and virus can be detected in oesophageal-pharyngeal scrapings for years. Although transmission by carrier buffalo has been demonstrated, most attempts at affecting transmission have failed. Given the apparent inefficiency of transmission, it would seem unlikely that carriers are the usual source of infection in herds. FMDV maintains a high force of infection in buffalo herds, consistent with a common mechanism for inter-annual persistence. We will combine small-scale transmission experiments and longitudinal data from a confined collared buffalo herd, allowing us to compile a dataset of unprecedented detail on FMDV transmission, host immunity, host contact networks and viral evolution. We will investigate the conditions under which carriers resume shedding of virus and transmission and explore the role of viral genetic and antigenic evolution during both acute and carrier phase in FMDV persistence. We will use a series of mathematical models to test which conditions are compatible with FMDV persistence in populations, and validate models using samples from 200 free-ranging buffalo collected previously. We will determine how the virus evolves and how new antigenic variants are generated in buffalo populations. Ultimately, an understanding of FMDV persistence in the wildlife reservoir is required to achieve global FMD control.

Africa has been endowed with abundance of wildlife, and in many regions, wildlife and their ecosystems have been well protected within national parks and game reserves. The near-symbiotic association between FMDV and African buffalo is unique, contributing to an epidemiological situation that presents an impasse to rural development. The global socio-economic impact of FMD is colossal. This impact can be separated into two components: the direct losses due to a reduction in production and changes in herd structure creating a food security issue and contributing to malnutrition; and indirect losses that relate to the significant costs of FMD control and management and poor access to markets, impeding investment in the livestock sector and limiting options for poor farmers and their families. Inevitably, in communities neighbouring ecosystems that contain African buffalo, the domestic animal / wildlife interface presents unique challenges to livestock disease control. In addition, the on-going creation of transfrontier conservation areas in southern and eastern Africa presents a particular challenge to the management of FMD because they render the domestic animal / wildlife interface increasingly intense and complex. This unique situation has necessitated that African countries invest in regular vaccination programmes if they are to effectively manage FMD and consequently participate in international and regional trade in livestock and livestock products. Since 2000, numerous outbreaks of FMD were recorded in vaccinated cattle populations in southern Africa. In all these outbreaks the source of virus was traced to buffalo, with subsequent spread from buffalo to cattle. The FAO and the World Organisation for Animal Health (OIE) are joining forces to combat FMD on a global scale, laying out a detailed strategy for global control. Unless we understand how FMDV is maintained in the wildlife reservoir host, global control will not be a reality.

This project will directly contribute to understanding the mechanisms for inter-annual persistence of FMDV and the high rate of infection in naïve buffalo, and ultimately transmission from buffalo herds to livestock. We will determine the role of persistently infected carrier animals, virus evolution and antigenic drift for FMDV persistence at the population level. Understanding the mechanisms for inter-annual persistence in herds will be invaluable for identifying inter-epidemic troughs that can be exploited as a time for effective intervention and control strategies for at-risk livestock populations. Our findings will be scalable to buffalo populations throughout Africa and will be invaluable for answering broader policy questions on vaccinate-to-live FMDV control strategies and FMDV persistence for global control. In the long term, there are 6 major impacts that will arise from the proposed work:
1. Provide new knowledge and disease models for FMD control and policy options in endemic countries
2. Provide strong foundation knowledge and identify feasible options for wildlife conservation projects and decision makers to preserve wildlife populations and ecosystems
3. Influence global FMD control policies
4. Support and directly address a significant problem facing poor livestock producers
5. Mitigate for risk of incursions into FMD free regions
6. Strengthen research, infrastructure and FMDV control capacity in Africa.