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The goal of this project is to develop a general methodology for incorporating bacterial phylogenetics based on WGS into predictive models for infectious diseases using transformative and interdisciplinary research incorporating ecology, economics, molecular biology, and epidemiology. These methods and models will be applied towards better understanding the principles and dynamics governing transmission of mycobacterial infection.This work was supported by the USDA-NIFA AFRI [grant number # 2014-67015-2240] as part of the joint USDA-NSF-NIH-BBSRC-BSF Ecology and Evolution of Infectious Diseases program.

Recent evidence of circulation of multiple strains within herds and mixed infections of cows marks the beginning of a rethink of our knowledge on Mycobacterium avium ssp. paratuberculosis (MAP) epidemiology. Strain typing opens new ways to investigate MAP transmission. This work presents a method for reconstructing infection chains in a setting of endemic Johne's disease on a well-managed dairy farm. By linking genomic data with demographic field data, strain-specific differences in spreading patterns could be quantified for a densely sampled dairy herd. Mixed infections of dairy cows with MAP are common, and some strains spread more successfully. Infected cows remain susceptible for co-infections with other MAP genotypes. The model suggested that cows acquired infection from 1-4 other cows and spread infection to 0-17 individuals. Reconstructed infection chains supported the hypothesis that high shedding animals that started to shed at an early age and showed a progressive infection pattern represented a greater risk for spreading MAP. Transmission of more than one genotype between animals was recorded. In this farm with a good MAP control management program, adult-to-adult contact was proposed as the most important transmission route to explain the reconstructed networks. For each isolate, at least one more likely ancestor could be inferred. Our study results help to capture underlying transmission processes and to understand the challenges of tracing MAP spread within a herd. Only the combination of precise longitudinal field data and bacterial strain type information made it possible to trace infection in such detail.

Austria is officially bovine tuberculosis (TB) free, but during the last decade the west of the country experienced sporadic TB cases in cattle. Free-ranging red deer are known to be the maintenance host of Mycobacterium (M.) caprae in certain areas in Austria, where cattle can become infected on alpine pastures shared with deer. The epidemiology of TB in deer in alpine regions is still poorly understood. To inform decisions on efficient interventions against TB in deer, a method is needed to better capture the infection dynamics on population level. A total of 4,521 free-ranging red deer from Austria's most western Federal state Vorarlberg were TB-tested between 2009 and 2018. M. caprae was confirmed in samples from 257 animals. Based on descriptions of TB-like lesions, TB positive animals were categorized with a newly developed lesion score called "Patho Score." Analyses using this Patho Score allowed us to distinguish between endemic, epidemic and sporadic TB situations and revealed different roles of subgroups of infected deer in infection dynamics. Overall, deer in poor condition, deer of older age and stags were the subgroups that were significantly more often TB positive (p = 0.02 or smaller for all subgroups). Deer in poor condition (p < 0.001) and stags (p = 0.04) also showed more often advanced lesions, indicating their role in mycobacterial spread. TB was never detected in fawns, while hinds were the subgroup that showed the fewest advanced lesions. Analysis of outbreaks of TB and lesion development in yearlings provided some evidence for the role of winter feeding as a source for increased infection transmission. Sporadic cases in TB-free areas appear to precede outbreaks in these areas. These currently TB-free areas should receive particular attention in sampling schemes to be able to detect early spreading of the infection. The Patho Score is a quick, easy-to-apply and reproducible tool that provides new insights on the epidemiology of TB in deer at po