Physiological Correlates of Bat Rabies Pathogenesis and Epizootiology
Type of Degreedissertation
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Rabies virus (RABV) is one model pathogen to consider for studying the dynamics of emerging infectious diseases under both laboratory and field conditions. The evolutionary history of RABV is characterized by regularly documented spillover infections and a series of notable host shifts. RABV is not a single, genetically homogeneous and unvarying virus, but a virus that has undergone genetic changes in adapting to local hosts and local habitats, such that each variant occupies a unique ecologic niche. The opportunity for re-emergence of rabies in mesocarnivores and the likelihood of sustained transmission of RABV in different species is influenced in part by host and variant-specific factors. Understanding pathogen maintenance and transmission within the natural reservoir may facilitate early detection strategies and targeted interventions prior to human spillover. As such, the general focus of this dissertation is to integrate a contemporary molecular, comparative, and ecological approach to complement our existing knowledge on bat rabies epizootiology and pathogenesis. The multidisciplinary approach of Chapter 2 consists of examining the physiologic response and phylogenetic relationships among bat RABV variants circulating the United States, including those implicated in recent and historical spillover infections in humans and mesocarnivores. To gain insight into viral pathogenesis and identify clinical features among individuals associated with experimental RABV infection, I along with the help of many collaborators evaluated the use of infrared thermography to detect thermographic changes associated with experimental RABV infection in captive big brown bats. These data suggest that infrared thermography has utility for discriminating rabid bats in natural field settings. In addition, focusing upon RABV circulating in the United States between 2008 - 2013 confirmed spillover events of bat RABV among carnivores and identified cross-species transmission events caused by four lineages of RABV associated with insectivorous bats. Rabies in bats is considered enzootic throughout the New World, but few comparative data are available for most countries in the region. The remedy for this lack of knowledge, Chapter 3 extends information on the geographic distribution of RABV circulation among bats to assess the broader public and veterinary health risks associated with bats in Guatemala. The detection of RABV neutralizing antibodies demonstrated viral circulation among multiple bat species in Guatemala. These data indicate that the proportion of seropositive bats varies significantly across trophic guilds, suggestive of complex intraspecific compartmentalization of RABV perpetuation. Chapter 4 seeks to address potential host shifts by examining differences in susceptibility, pathogenesis, and neurovirulence of major US RABV variants associated with bats and carnivores. The results of this study determined that the incubation period is influenced significantly by variant. These data also support the concept that spillover infections of biologically relevant North American RABV can be transient or dead ends, but dependent upon the isolate, dose, and route, could result in a sustained transmission when epizootiological conditions are ideal. Taken together, this dissertation suggests that the balance between pathogenesis and epizootiology is unique to the RABV variant and particular host.