A Prospective Study of Persistent Symptoms of Lyme Disease

ABSTRACT: OVERALL Despite years of research, there is no diagnostic test for post-treatment Lyme disease syndrome (PTLDS); there is no consensus treatment for PTLDS; there is no agreement on the mechanisms causing disease or even how frequently it happens. And while there have been intriguing findings by many outstanding

researchers, they have not been independently confirmed and have mostly been done in small populations that have identified PTLDS patients retrospectively without serial follow up after the diagnosis of acute Lyme disease. It is highly unlikely that there will be a breakthrough in understanding the disease without a major

change in the way we approach studying the disease. We hypothesize that one of the reasons why PTLDS has been so intractable to understand is that the causes are multifactorial and involve a confluence of events including prior/concurrent exposures, immunological responses and specific bacterial characteristics. In this case, researchers examining only one potential aspect

of the disease are unlikely to uncover the full complexity of the origins of disease. We are proposing a prospective study of PTLDS, enrolling and following subjects from the time they are diagnosed with acute Lyme disease until they recover or develop PTLDS. We have assembled a unique team of clinicians,

epidemiologists, immunologists, microbiologists and statisticians with a deep understanding of Lyme disease and a history of collaboration to tackle the understanding of PTLDS together. Subjects will undergo a battery of tests, taking advantage of new technologies allowing unbiased analysis of both human immune and

bacterial factors. These high-throughput tests will be supplemented with focused testing of hypotheses that have arisen through prior research, by our group as well as others. Though these studies we will understand the differences in co-infections with other tick-borne diseases, specific inflammatory patterns, distribution of cell

types and their reactions, autoantibody formation, auto-reacting T cells, antibiotic resistance and persistence of B. burgdorferi, binding and dissemination of B. burgdorferi strains and shedding of peptidoglycan between patients with PTLDS and RLD. In addition, as part of this process, we will also be developing one of the

largest, well characterized specimen banks that will be shared with the research community for additional testing in a way that results can be aggregated to continually broaden our understanding of PTLDS. Our highly experienced group is operating under no illusions about how difficult and complex this study will be

to complete. However, we believe that this type of effort is needed to move the field-- which is essentially no closer to a consensus understanding of PTLDS today that it was 30-years ago-- and to make progress for the health of the afflicted patients.