Spatial and Molecular Epidemiological Approaches for Evaluating Dynamics of Foot-and-Mouth Disease Virus in India and Vietnam

Abstract

Foot and mouth disease virus (FMDV) is still endemic in many regions worldwide. Many widespread FMDV lineages have emerged from South Asia, and subsequently spread to other regions, including Southeast Asia, making these two regions important epicenters for FMDV evolution and transboundary transmission. The progressive control pathway (PCP) proposed by the World Animal Health Organization and the Food and Agriculture Organization (OIE/FAO) provides a framework for countries to reduce the incidence of the disease, with the ultimate goal of achieving zonal or country-wide freedom from disease. The PCP pathway is outcome-oriented and relies on a self-evaluation process before being accredited by the OIE and obtaining the official status for a given stage. Different epidemiological methods are acceptable for evaluation of the progress at each stage, yet OIE/FAO does not provide specific guidelines in regard to methods for epidemiological evaluation. In this dissertation, the objective was to demonstrate how recent and newly developed epidemiological approaches can be applied to support progression through PCP stages in South and Southeast Asia. Two countries in those two regions, India and Vietnam, both countries in stage 3, were used as case studies to examine how commonly available types of epidemiological data, such as reported outbreaks and sequence data, can be analyzed to understand the spatial dynamics of FMDV circulation, assess the effectiveness of vaccination programs, and delineate high-and low-risk areas. Ultimately, this work will serve as a proof-of-concept for novel methods for genomic surveillance, which could be used as a cost-effective means to generate sequence data needed for surveillance and epidemiological analysis and help the countries to move towards stage 4 of the PCP. The first chapter provides an overview of the PCP with a focus on stages 1-3, epidemiological approaches typically used to support PCP activities, and the FMD situation in India and Vietnam. The second chapter specifically explores FMD situation in India and applies Bayesian space-time regressions to investigate factors underlying the spatial heterogeneity in risk of reported outbreaks, including an assessment of how mass vaccination impacted the spatial and temporal distribution of disease. However, such spatial models account for population connectivity by incorporating spatial autocorrelation amongst contiguous spatial units, which is likely a poor representation of population connectivity for highly mobile hosts such as livestock. The third chapter explores the ways to improve Bayesian space-time regression models using the phylogeography to account for patterns of population connectivity. Finally, monitoring circulating virus strains and rapid detection of novel strains is a necessary component of FMD control as part of the PCP, and sequence data also enables a number of other epidemiological approaches to understand virus circulation in a country. Conventional methods to acquire sequence data in the field are not efficient as a means for routing genomic surveillance, and it may be more effective to identify sentinel surveillance points to detect emerging outbreaks, such as slaughterhouses. Genomic surveillance at slaughterhouses was explored in the fourth chapter using FMDV sequence data from Vietnam. The final chapter is an overview of demonstrated methods to improve FMD control measures and support progression in PCP stages in FMD endemic countries in endemic regions of South and Southeast Asia.