{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:27:39Z","timestamp":1780500459933,"version":"3.54.1"},"reference-count":187,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Banbury Center of Cold Spring Harbor Laboratory"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infection-associated chronic illnesses (IACIs) encompass a spectrum of poorly understood syndromes often marked by significant neurologic and multisystem symptoms following an infectious event.<\/jats:p>\n                  <jats:p>This review focuses on several diseases representative of the IACI spectrum. These are post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) and multiple sclerosis (MS). Their clinical and biological complexity, combined with a lack of clear diagnostic criteria and objective available laboratory biomarkers, makes them difficult to distinguish from conditions with overlapping features. This presents challenges for research studies, as well as diagnosis and clinical management. This diagnostic ambiguity, coupled with heterogeneous patient presentations, has led to challenges in research, including misclassification of study participants and inconsistent or irreproducible findings. Some PTLDS research exemplifies these issues, which also extend to other IACIs.<\/jats:p>\n                  <jats:p>To advance the field, we highlight key methodological refinements and approaches for studying IACIs, including rigorous participant selection, standardized sample collection protocols, and the use of appropriate control groups, including those with microbiologic proof of the initial infection when known and technologically feasible. We also address broader influences on research quality, such as stigma, historical neglect, and the urgency to find treatments, which have contributed to the proliferation of poorly controlled studies and questionable practices. Drawing lessons from past challenges, we propose a path forward grounded in fit-for-purpose methodological rigour to improve scientific understanding and support evidence-based therapeutic development for IACIs.<\/jats:p>","DOI":"10.1093\/brain\/awag016","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:52:29Z","timestamp":1771505549000},"page":"1842-1859","source":"Crossref","is-referenced-by-count":0,"title":["Designing studies for post-treatment Lyme disease and other infection-associated chronic illnesses"],"prefix":"10.1093","volume":"149","author":[{"given":"Paul M","family":"Arnaboldi","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, New York Medical College , Valhalla, NY 10595 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2708-6046","authenticated-orcid":false,"given":"Jacqueline","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ichan School of Medicine , New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0927-5855","authenticated-orcid":false,"given":"Avindra","family":"Nath","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia K","family":"Coyle","sequence":"additional","affiliation":[{"name":"Department of Neurology, Stony Brook University Health Sciences Center School of Medicine , Stony Brook, NY 11794 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Richard","family":"McCombie","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Marie","family":"Wellins","sequence":"additional","affiliation":[{"name":"Stony Brook School of Nursing, Stony Brook University , Stony Brook, NY 11794 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Allegretta","sequence":"additional","affiliation":[{"name":"National Multiple Sclerosis Society , New York, NY 10017 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-041X","authenticated-orcid":false,"given":"Jonas","family":"Bergquist","sequence":"additional","affiliation":[{"name":"Department of Chemistry\u2014BMC, Analytical Chemistry and Neurochemistry, Uppsala 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