Ecological, epidemiological, and molecular drivers of cross-species pathogen transmission among humans and non-human primates: from malaria to rhinovirus

Abstract

Malaria constitutes a major source of human mortality and morbidity worldwide. Although the bulk of this public health burden is caused by four human-adapted parasite species, these represent less than 1% of the malaria parasite diversity found in the natural world. The expansion of human populations into biodiversity hotspots has elevated exposure to novel malaria parasites, and evidence of primate-to-human transmission has begun to accumulate. There now exists a tangible public health imperative to critically evaluate the ecological and molecular mechanisms governing the host-specificity of malaria parasites in order to identify which species pose a material threat to human populations. The purpose of this dissertation is to elucidate the ecological, epidemiological, and molecular variables that govern the transmission of infectious diseases among humans and non-human primates. In Chapter 1, I provide a conceptual framework for zoonotic disease emergence and discuss the ecological and molecular barriers to cross-species transmission of malaria parasites. In Chapter 2, we quantify the ecological drivers of malaria transmission among wild chimpanzee hosts in equatorial Africa and map spatiotemporal variation in the risk that these parasites pose to local human populations. In Chapters 3 and 4, we review the molecular mechanisms governing the host-specificity of non-human primate malaria parasites and develop a method for the generation of immortalized erythroid progenitor cell lines from small volumes of peripheral blood, offering a genetically tractable model system for studies of malaria host-specificity. In Chapter 5, we identify human rhinovirus C as the cause of a lethal respiratory outbreak in a community of wild chimpanzees in western Uganda and demonstrate a species-wide genetic susceptibility to this virus, underscoring the profound conservation implications of human-to-ape virus transmission. In Chapter 6, I conclude the dissertation by discussing non-human primate malaria parasite diversity in the context of global health and review historical and contemporary evidence of malaria cross-species transmission. It is my hope that the studies presented in this dissertation will catalyze cooperation among stakeholders in the public health and scientific research communities by highlighting malaria zoonosis as a topic that warrants further consideration in discussions of malaria eradication.