College of Veterinary Medicine
Non Technical Summary
US-UK Collaborative: Persistence of a highly contagious pathogen:Ecological and evolutionary mechanisms in FMD.The persistence of rapidly transmitting, acute pathogens in their natural host populations represents one of the fundamental puzzles in disease ecology: highly contagious pathogens tend to reduce the pool of susceptible hosts to very low numbers, increasing their own risk of extinction during epidemic troughs. This vulnerability constrains the range of pathogen life histories that result in viable population dynamics; nonetheless, highly transmissible pathogens do occur - despite causing rapid host immunity or death.The proposed study will investigate how one of the most contagious animal pathogens known to man, foot-and-mouth disease virus (FMDV), overcomes these challenges and persists in isolated populations of its reservoir host, the African buffalo. This study will be one of the first to address this problem head-on, dissecting the contributions of ecological and evolutionary mechanisms to pathogen persistence. Specifically, the study will evaluate (i) whether co-infection by common respiratory pathogens and / or malnutrition during the dry season can trigger FMDV transmission from carrier buffalo; and (ii) the role of viral antigenic shift in limiting host immunity to FMDV at epidemiologically relevant time scales.The centerpiece of the project is a cohort study, in which a captive buffalo herd will be monitored intensively over three years, measuring host-to-host contacts, and tracing FMDV transmission events using viral phylogenetic methods. The investigators will map host contacts onto pathogen transmission, and tease apart the role of behavioral, physiological and immunological drivers in generating heterogeneity in disease transmission among hosts. They will discover whether FMDV transmission from carrier buffalo tends to coincide with secondary pathogenic exposures and / or malnutrition during the dry season - and test whether these associations are causal using a controlled challenge experiment. They will measure rates of viral antigenic evolution directly, and establish the contribution of super-infection by new antigenic variants to FMDV transmission dynamics. Complementary to these empirical approaches the project team will develop mathematical models to extrapolate to other host populations and to provide logical validation for the hypothesized mechanisms underlying FMDV persistence. Samples from 200 free-ranging buffalo, collected previously by the PI, will ensure that the models capture realistic levels of temporal variability in buffalo immunity and co-infection patterns. The study thus combines a strong theoretical framework with controlled experiments and longitudinal observational data from captive and free-living buffalo, to provide both rigor and biological realism.Intellectual Merit. This will be one of the first studies to track transmission events in a near-natural host population comprehensively, overlay the resulting transmission network with animal contact patterns, and identify immunologic and physiologic drivers of heterogeneity in disease transmission. Building on the investigators' previous work on FMDV and buffalo, the study moves away from the paradigm of transmission from carrier hosts during stress-induced immunosuppression, and presents innovative new ideas for ecological and evolutionary drivers of pathogen persistence: for some highly contagious pathogens, robust long-term persistence may depend on co-infection by common pathogens and seasonal variation in host immunity, driven ultimately by resource fluctuations. If true, implications of this finding would be far-reaching, in that it suggests fundamentally different dynamics of contagious, acute pathogens along gradients of environmental variability.Broader impacts. This project will build scientific capacity by supporting integrated training for postdoctoral scientists and students recruited from South Africa, the US and the UK. The project will build strong links between US, UK, and South African institutions, as a basis for future effective collaborations on understanding and controlling animal infectious diseases. A summer research program will provide students with inter-cultural and inter-disciplinary research training opportunities. Results from the study will be communicated directly to relevant veterinary and conservation agencies by policy experts on the project team. Extremely contagious pathogens that cause acute disease are among the most important global public and animal health concerns, because of their high burden of morbidity and mortality, their violent outbreaks, and as potential threats to biosecurity. Understanding the biology of extremely contagious pathogens in their reservoir hosts is an urgent priority because it ultimately underpins control and prevention of the devastating diseases they cause.
Animal Health Component
Research Effort Categories
Goals / Objectives
The major goal of this study is to understand how an extremely contagious pathogen, foot-and-mouth disease virus (FMDV), persists in populations of its reservoir host, the African buffalo. Two non-exclusive hypotheses will be investigated: 1. (Ecological) - Carrier hosts may be triggered to transmit infection when they are co-infected by other respiratory pathogens during nutritional restriction in the dry season. 2. (Evolutionary) - Antigenic shifts may limit the duration of effective immunity to FMDV in buffalo.
We will work at Kruger National Park (KNP), South Africa, building on long-standing collaborations with colleagues at South African National Parks and the South African State Veterinary Service. We will (Aim 1) develop a series of mathematical models, representing our hypotheses, as a theoretical framework for our study. We will then take advantage of a unique experimental set-up at KNP, allowing us to conduct (Aim 2) a cohort study in which we intensively monitor immunity, infection, contacts and viral evolution in a buffalo herd confined under near-natural conditions, and (Aim 3) controlled FMDV challenge experiments, to test the effects of our hypothesized environmental triggers for FMDV transmission from carrier buffalo directly. In addition, (Aim 4) we will use a set of 1200 samples collected over three years from 200 buffalo at KNP (during Jolles' previous study), to investigate timing and severity of protein restriction, and the frequency of respiratory co-infections in free-ranging buffalo. We will thus integrate experimental and empirical studies using captive and free-ranging buffalo, with theoretical approaches, to test how ecological and evolutionary mechanisms may contribute to robust FMDV persistence in populations of its reservoir host, the African buffalo.