ABSTRACT: Project 1, The Epidemiology of Post-Treatment Lyme Disease Syndrome A proportion of early Lyme disease patients who have been treated with standard antibiotic regimens experience persistent ill health for weeks to months, a condition known as Post Treatment Lyme Disease Syndrome or “PTLDS”. The biologic basis for persistent Lyme disease remains to be described. The overarching goal of our Program Project proposal is to generate fundamental knowledge about recovery from Lyme disease, a growing human health problem worldwide, and better understand the mechanisms of progression to PTLDS. In this epidemiological Project 1, we shall determine PTLDS incidence through a prospective standardized assessment of a large patient cohort at the start of treatment for early Lyme disease. We are particularly interested in the role of coinfections as potential factors in the development of PTLDS: there are 4 other zoonotic agents transmitted by deer ticks, as well as flea or mosquito-borne infections in northeastern U.S. sites, and thus Lyme disease cases may be concurrently or sequentially exposed to these other infections. We shall re-examine pre-morbidity or concurrent clinical risk factors as a predictor for PTLDS. Finally, we shall estimate the burden of PTLDS, seeking to place its public health importance into context of other chronic disease in the study sites. This Project leverages the acute (early) Lyme disease enrollments across a large study network of our Program Project, and complements this major effort with a serological survey based in long-term tick borne disease study sites in coastal New England communities. Results from our questionnaires and coinfection studies, framed by the analyses of all samples by the Diagnostic Core, will help inform the findings of Project 2 (host immune dysregulation and autoantibodies), which in turn will place premorbid or other risk associations of PTLDS into context. Ultimately, the findings from the proposed epidemiological project may contribute to modalities for preventing, treating, and reducing the public health burden of PTLDS.