{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:35:28Z","timestamp":1793208928353,"version":"4.5.0"},"reference-count":68,"publisher":"American Chemical Society (ACS)","license":[{"start":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:00:00Z","timestamp":1793145600000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chagas disease, caused by Trypanosoma cruzi, remains a neglected tropical disease with limited therapeutic options. Although benznidazole and nifurtimox are the available antiparasitic treatments, assessing treatment efficacy in adults with chronic Chagas disease remains challenging due to the absence of validated biomarkers or surrogate end points. Conventional serology assays often require years to decades to detect treatment-associated changes, limiting their utility in clinical trials and drug development. Biomarker development is further complicated by intermittent parasitemia, persistent antibody responses, the lack of direct measures of tissue parasite clearance, and limited longitudinal biorepositories for validation. This position paper critically evaluates biomarkers, including nonconventional serological markers such as T. cruzi 29 kDa flagellar calcium-binding protein (F29), glycosylphosphatidylinositol-anchored trypomastigote (tGPI)-mucins, and alpha-galactosyl (\u03b1-Gal) epitope; molecular approaches; and multiplex serological platforms such as MultiCruzi. Their potential utility, supporting evidence, methodological limitations, reproducibility, and validation status are assessed within a fit-for-purpose scientific and regulatory framework. Although several biomarkers have shown promise in detecting early treatment-associated biological signals, none currently has sufficient evidence to qualify as a validated surrogate end point in adult chronic Chagas disease. Early biomarker changes should therefore be interpreted as indicators of treatment-associated biological activity rather than direct evidence of parasitological cure or a durable clinical benefit. Beyond summarizing the biomarker landscape, this paper addresses the evidentiary and regulatory challenges associated with biomarker qualification and proposes a roadmap for future qualification efforts. Progress will require standardized methodologies, independent prospective validation, longer term follow-up, and robust evidence, demonstrating that biomarker changes reliably predict clinically meaningful outcomes.<\/jats:p>","DOI":"10.1021\/acsinfecdis.5c01096","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:02:08Z","timestamp":1791554528000},"source":"Crossref","is-referenced-by-count":0,"title":["A Perspective\non Biomarkers, Candidates for Surrogate\nEnd Points to Accelerate Successful Development of New Antiparasitic\nAgents for the Treatment of Chronic Chagas Disease"],"prefix":"10.1021","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7198-3214","authenticated-orcid":true,"given":"Tiffany","family":"Loy","sequence":"first","affiliation":[{"name":"Novartis Pharma AG , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u0301a-Jesus","family":"Pinazo","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative (DNDi) , ,","place":["Rio de Janeiro, Brazil, 20010-20"]},{"name":"Instituto de Salud Carlos III (CIBERINFEC, ISCIII) , , ,","place":["Madrid, Spain, 28029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Alonso-Padilla","sequence":"additional","affiliation":[{"name":"Instituto de Salud Carlos III (CIBERINFEC, ISCIII) , , ,","place":["Madrid, Spain, 28029"]},{"name":"Barcelona Institute for Global Health (ISGlobal) , ,","place":["Barcelona, Spain, 08036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Altcheh","sequence":"additional","affiliation":[{"name":"Parasitology Service, Hospital de Nin\u0303os \u2033Ricardo Gutierrez\u2033 and Instituto Multidisciplinario de Investigacion en Patologias Pediatricas (IMIPP)-CONICET-GCBA , ,","place":["Buenos Aires, Argentina, 1330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Braud-Pe\u0301rez","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Scandale","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative (DNDi) , ,","place":["Geneva, Switzerland, 1202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Go\u0301mez-Burgaz","sequence":"additional","affiliation":[{"name":"Chemo Research S.L. , ,","place":["Madrid, Spain, 28050"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Saade","sequence":"additional","affiliation":[{"name":"INFYNITY Biomarkers , ,","place":["Lyon, France, 69009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Barreira","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative (DNDi) , ,","place":["Geneva, Switzerland, 1202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha S.","family":"Hochberg","sequence":"additional","affiliation":[{"name":"Novartis Biomedical Research , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhild","family":"Angyalosi","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maan","family":"Zrein","sequence":"additional","affiliation":[{"name":"INFYNITY Biomarkers , ,","place":["Lyon, France, 69009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Chatelain","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative (DNDi) , ,","place":["Geneva, Switzerland, 1202"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"issue":"2","key":"2026102813073766400_cit1","doi-asserted-by":"publisher","first-page":"ITC17","DOI":"10.7326\/AITC202302210","article-title":"Chagas disease","volume":"176","author":"Hochberg","year":"2023","journal-title":"Ann. 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