{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:57:07Z","timestamp":1787021827762,"version":"build-2736575974"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordination for the Improvement of Higher Education Personnel \u00e2\u20ac\u201c Brazil","award":["Finance Code 001"],"award-info":[{"award-number":["Finance Code 001"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Leprosy remains endemic in many regions despite the global rollout of multidrug therapy (MDT). Clinical cure\u2014defined by completion of a time-based MDT regimen\u2014may not reflect proper bacteriological clearance, particularly in patients with persistent reactions or neurological symptoms. We aimed to assess subclinical disease activity in multibacillary patients who completed an extended 24-dose MDT course.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this retrospective case series, between January 2016 and November 2023, 131 multibacillary patients treated at the Petrolina Infectious Diseases Service (SEINPE) underwent skin biopsy upon completing 24 monthly MDT doses. Disease activity was evaluated by histopathology (H&amp;E and Fite\u2013Faraco staining; n\u2009=\u2009123), slit-skin smear with bacilloscopic and morphological indices (BI, n\u2009=\u2009126; MI, n\u2009=\u200974), qPCR for\n                      <jats:italic>M. leprae<\/jats:italic>\n                      (n\u2009=\u2009101), and nude mice footpad inoculation (n\u2009=\u200945) at Instituto Lauro de Souza Lima, Bauru, Brazil. Drug-resistance mutations were detected by sequencing (\n                      <jats:italic>folP1, rpoB, gyrA<\/jats:italic>\n                      ; n\u2009=\u200988). Neurological function was assessed using a Simplified Neurological Assessment (n\u2009=\u2009117).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Histopathology revealed active disease or bacillary persistence in 62\/123 specimens (50.41%), while 29\/45 inoculations (64.44%) yielded viable bacilli. qPCR detected\n                      <jats:italic>M. leprae<\/jats:italic>\n                      DNA in 96\/101 patients (95.05%). Known resistance mutations were identified in 2\/88 patients (2.27%). Clinically, 89\/131 patients (67.94%) no longer exhibited skin lesions post-MDT; however, neurological impairment increased from 70\/131 (53.44%) at diagnosis to 114\/131 (87.02%) at discharge. The proportion with grade 2 disability increased from 5\/100 (5.00%) to 27\/117 (23.08%). Exact 95% CIs are reported in the manuscript.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      More than half of patients treated with an extended 24-dose MDT regimen harbored persistent\n                      <jats:italic>M. leprae<\/jats:italic>\n                      activity despite apparent dermatological cure, and most experienced worsening neural function. Time-based discharge criteria alone are inadequate to confirm cure. We recommend integrating post-treatment histopathological, molecular, and inoculation assessments\u2014particularly in patients with persistent reactions or neurological complaints\u2014to identify therapeutic failure, guide retreatment, and prevent long-term disability.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0013616","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T18:35:41Z","timestamp":1764095741000},"page":"e0013616","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic failure of multidrug therapy for leprosy: A retrospective case series in a hyperendemic Brazilian City"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-5799","authenticated-orcid":true,"given":"Andrea Maia Fernandes de Ara\u00fajo","family":"Fonseca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Sammarco","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea de Faria Fernandes","family":"Belone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleverson Teixeira","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele de Faria Ferreira","family":"Bertoluci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana Madeira","family":"Di\u00f3rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Raquel Vincenzi","family":"Fachin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Feliciano","family":"do Carmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Bezerra","family":"de Almeida Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"issue":"12","key":"pntd.0013616.ref001","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1093\/brain\/awac008","article-title":"Association between ultrasonography foetal anomalies and autism spectrum disorder","volume":"145","author":"O Regev","year":"2022","journal-title":"Brain"},{"issue":"5396","key":"pntd.0013616.ref002","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1126\/science.282.5396.2076","article-title":"Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae","volume":"282","author":"A Rambukkana","year":"1998","journal-title":"Science"},{"issue":"4","key":"pntd.0013616.ref003","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1046\/j.1365-4362.2000.00910.x","article-title":"Onychomycosis and Trichosporon beigelii in Korea","volume":"39","author":"MH Han","year":"2000","journal-title":"Int J Dermatol"},{"key":"pntd.0013616.ref004","unstructured":"Brasil. 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