Jason K. Blackburn - US grants

Understanding the ecology of outbreaks of diseases like anthrax as well as associations between landscape ecology and specific bacterial genotypes is essential for improving prevention and control of the disease in wildlife, livestock, and humans. The mechanisms through which the anthrax pathogen is transmitted at fine spatial and temporal scales are poorly characterized. This doctoral dissertation research project will combine molecular analysis of Bacillus anthracis, the causative bacterium of anthrax, with spatio-temporal epizootic data to explore anthrax dynamics in North America across different spatial and temporal scales, multiple genetic sub-lineages, and multiple mammalian host systems. The doctoral student will seek answers to the following questions: Do potential evolutionary changes in B. anthracis from infected animal hosts and necrophagous flies suggest mechanisms of pathogen transmission at a local scale? Are there associations among ecological conditions, epidemiology, and genetic diversity within outbreaks in different ecological settings and host systems? What are the broad scale spatio-temporal patterns of genetic diversity of B. anthracis across two important anthrax foci in North America? The student will use an existing collection of B. anthracis isolates and anthrax epizootic data from ecologically distinct geographic areas. New isolates and epizootic data will be collected from outbreaks occurring during the study period. High-resolution single-nucleotide repeat (SNR) analysis will characterize genetic diversity among and within multiple locus variable number of tandem repeat- (MLVA) defined genotypes across study sites. Trend surface analysis with vector velocity mapping will be used to analyze disease movement through host populations across the landscape and will be overlain with maps of genotypes to evaluate associations between genetic diversity and disease transmission.

This project will help fill important gaps in knowledge about anthrax transmission and will specifically evaluate whether genetic analysis can inform spatio-temporal models of anthrax transmission. Anthrax transmission is likely influenced by fine scale environmental characteristics, genetic lineage, host species and behaviors, and arthropods as well as other as-yet-unknown variables. This project will encompass multiple genetic lineages of the pathogen and multiple host systems, including a study area in Texas with annual, enzootic anthrax with wildlife and mixed wildlife/livestock host populations and a study area in Montana experiencing a reemergence of anthrax in wildlife. Project results will provide insight into the genetic diversity and evolution of an important spillover pathogen. The results also will inform public health strategies for prevention of wildlife, livestock, and human disease and will provide insight as to whether strategies should be tailored to the local ecology. As a Doctoral Dissertation Research Improvement award, this award also will provide support to enable a promising student to establish a strong independent research career.

? DESCRIPTION (provided by applicant): Indirect pathogen transmission can be vectored or environmentally-mediated. The latter is the primary mode of infection for a number of important multi-host diseases in wildlife and livestock, including several zoonoses (diseases that spillover into humans) and is explicitly linked to host movements and foraging in areas where the pathogen is maintained in environmental reservoirs. Calculating R0 in such systems requires that we estimate the contribution of each reservoir to new cases. To do this we must unpack the transmission process into its pathogen shedding, environmental persistence, and host contact (pathogen ingestion or inhalation) components. Such contact rates can be characterized from a combination of local host movement and foraging patterns driven by larger-scale seasonal resource selection. Persistent environmental pathogen reservoirs can be modeled as individual, local infectious zones with their own demography and spatial distribution; life history of these zones influence host foraging locally. In this 4-year EEID project, we provide a novel combined geospatial and mathematical approach for estimating R0 for environmentally-mediated transmission. We will then assess efficacies of control strategies impacting different components of the transmission process. Toward this, we propose the following specific aims: Specific Aim 1: Derive functions to describe host-specific contact rates with local infectious zones by quantifying host movement and foraging behavior, characterizing the spatial distribution and demography of local infectious zones, characterizing the environmental factors controlling host foraging and pathogen persistence; Specific Aim 2: Apply these functions to estimating R0 for anthrax (indirect transmission of Bacillus anthracis) using empirical datasets from two regions with active anthrax in free ranging herbivores-contrasting systems with and without disease control; Specific Aim 3: Evaluate the conceptual and practical impact of our novel R0 estimates as related to disease control strategies for wildlife and livestock systems, including those where human disease remains a major threat.