Transmission and evolution of a persistent pathogen: anthrax infection dynamics comparing two natural systems

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Anthrax is a globally distributed disease of wildlife, livestock, and humans. Successful prediction of and response to outbreaks of anthrax is limited by a lack of understanding of the geographic differences in the ecology of the pathogen as well as the pattern of disease outbreaks. This project will investigate the roles of host, pathogen, and environment to understand how the pathogen - host interaction evolves and contributes to the differences in anthrax occurrence between two study areas. The two areas, both in southern Africa, have very different anthrax outbreak dynamics, which are representative of variation in anthrax systems world-wide. In Etosha National Park, Namibia, there are smaller outbreaks, affecting grazing zebra, annually in wet seasons. In contrast, in Kruger National Park, South Africa, larger outbreaks affecting browsing kudu occur in dry seasons on roughly a decadal scale. The project builds on detailed records of disease and population dynamics in each park as well as archived pathogen samples and will involve new data collection and analyses and mathematical modeling to understand these different dynamics. Education, training, and scientific and public outreach are essential components of this research. Postdoctoral researchers and undergraduate and graduate students from diverse backgrounds will be trained in field, laboratory, and quantitative techniques emphasizing cutting-edge genomics, and statistical and dynamic modeling approaches. The causative agent of anthrax (the bacterium Bacillus anthracis), is often invoked as a textbook example for the evolution of high virulence and prolonged environmental survival. This project will link within-host, between-host, and in-environment processes, to understand how conflicting selective pressures impact pathogen diversity, host resistance, disease incidence, and ultimately, how these processes may drive host-pathogen co-evolution. This collaborative research team will compare anthrax dynamics in two wildlife systems, integrating long-term field studies, host and pathogen genomics, microbiology, and statistical and dynamic modeling. The project addresses three related questions: (1) how does pathogen diversity affect trade-offs between pathogen transmission and virulence? (2) how does host diversity affect trade-offs between pathogen transmission and virulence? and (3) how do landscape-scale patterns of transmission and host movement affect virulence-transmission trade-offs and host-pathogen population dynamics? Researchers will link variability in B. anthracis genomes to phenotype (i.e., pathogen survival in the environment, virulence to hosts, and transmission across host and geographic range). Researchers will identify host genes under pathogen-mediated selection in two primary host species, plains zebra (Equus quagga) and greater kudu (Tragelaphus strepsiceros). Researchers will build landscape-level models of epidemiology and population dynamics incorporating host movement, transmission routes, pathogen virulence, and host resistance. Finally, researchers will build models predicting anthrax transmission dynamics across ecosystems. In a broader sense, this research will facilitate the development of predictive tools to better manage public health and related policies for complex, multi-host zoonotic diseases such as anthrax.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.