{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:16:39Z","timestamp":1781907399751,"version":"3.54.5"},"reference-count":36,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Multidrug therapy for leprosy is highly effective and the recommended standard of care for leprosy worldwide. However, reports of antimicrobial resistance (AMR) have emerged globally. This study aimed to estimate the frequency of primary and secondary AMR associated with leprosy in patients treated at the Alfredo da Matta Foundation, Manaus, Amazonas, Brazil, as well as to determine the circulating subtypes of\n              <jats:italic toggle=\"yes\">Mycobacterium leprae<\/jats:italic>\n              in this population. A total of 315 biopsy samples were investigated for variants in leprosy AMR-associated genes (\n              <jats:italic toggle=\"yes\">rpoB, folP1, gyrA<\/jats:italic>\n              ); a subset of 163 samples was also investigated for 5 additional candidate genes:\n              <jats:italic toggle=\"yes\">gyrB, ctpC, ctpI, ribD<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">fadD9<\/jats:italic>\n              . Patients were categorized into new cases, relapses, and suspected treatment failures. For statistical analysis, Pearson\u2019s chi-square or Fisher\u2019s exact test was employed for categorical variables, while mean and SD were calculated for continuous variables, with a significance level of 5%. Variant analysis detected 10 resistant\n              <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n              isolates displaying mutations in the\n              <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n              (2, 0.6%) and\n              <jats:italic toggle=\"yes\">folP1<\/jats:italic>\n              (8, 2.5%) genes. In addition, variants in\n              <jats:italic toggle=\"yes\">gyrB<\/jats:italic>\n              (1, 0.6%),\n              <jats:italic toggle=\"yes\">ctpC<\/jats:italic>\n              (6, 3.7%),\n              <jats:italic toggle=\"yes\">ribD<\/jats:italic>\n              (4, 2.4%), and\n              <jats:italic toggle=\"yes\">fadD9<\/jats:italic>\n              (15, 9.2%) were detected. Nine out of 10 resistant isolates were observed in the relapse group (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = 0,0014). Despite the low variant frequencies observed, variant detection highlights the need for expanded antimicrobial monitoring and surveillance. The impact of mutations in\n              <jats:italic toggle=\"yes\">ribD<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">fadD9<\/jats:italic>\n              on therapeutic response remains unclear, underscoring the need for further research. Genotyping revealed subtype-4 predominance (79.6%). Our findings highlight the importance of comprehensive AMR monitoring, particularly in relapse cases.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01550-24","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T13:04:06Z","timestamp":1747746246000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Classic and new candidate markers for drug resistance in a large cohort of leprosy patients from the Amazon state, Brazil"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3069-2434","authenticated-orcid":true,"given":"Cynthia de Oliveira","family":"Ferrreira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]},{"name":"Genomic Health Surveillance Network: Optimization of Assistance and Research in the State of Amazon (REGESAM)","place":["Manaus, Brazil"]},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Medicina Tropical, Universidade do Estado do Amazonas\u2013UEA","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Luiz","family":"Leturiondo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]},{"name":"Genomic Health Surveillance Network: Optimization of Assistance and Research in the State of Amazon (REGESAM)","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Gurgel","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaqueline Bentes","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Fernanda de Andrade","family":"Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Bianca Oliveira","family":"Rego","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Caldas","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamires Bastos","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-6005","authenticated-orcid":true,"given":"Gisely Cardoso","family":"Melo","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Medicina Tropical, Universidade do Estado do Amazonas\u2013UEA","place":["Manaus, Brazil"]},{"name":"Instituto de Pesquisa Cl\u00ednica Carlos Borborema, Funda\u00e7\u00e3o de Medicina Tropical Dr Heitor Vieira","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Sammarco","family":"Rosa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Instituto Lauro de Souza Lima","place":["Bauru, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo T\u00e1vora","family":"Mira","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, School of Medicine and Life Sciences, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1","place":["Curitiba, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Avanzi","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Talhari","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Funda\u00e7\u00e3o Hospitalar Alfredo da Matta-FUHAM","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"217","volume-title":"Hansen\u00edase","author":"Talhari S","year":"2015","unstructured":"Talhari S, Penna GO, Gon\u00e7alves HS, OliveiraO. 2015. Hansen\u00edase. 5th ed, p 217. Rio de Janeiro: DiLivros.","edition":"5"},{"key":"e_1_3_4_3_2","first-page":"409","article-title":"Global leprosy (Hansen disease) update, 2022: new paradigm \u2013 control to elimination","author":"World Health Organization","year":"2023","unstructured":"World Health Organization. 2023. Global leprosy (Hansen disease) update, 2022: new paradigm \u2013 control to elimination. Wkly Epidemiol Rec Available from:409\u2013430. https:\/\/www.who.int\/publications\/i\/item\/who-wer9837-409-430.","journal-title":"Wkly Epidemiol Rec"},{"key":"e_1_3_4_4_2","first-page":"9352","volume-title":"Boletim epidemiol\u00f3gico: Hansen\u00edase","author":"Minist\u00e9rio da Sa\u00fade (Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente)","year":"2024","unstructured":"Minist\u00e9rio da Sa\u00fade (Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente). 2024. Boletim epidemiol\u00f3gico: Hansen\u00edase, p 9352\u20137864. https:\/\/www.gov.br\/saude\/pt-br\/centrais-de-conteudo\/publicacoes\/boletins\/epidemiologicos\/especiais\/2024\/be_hansen-2024_19jan_final.pdf\/view."},{"key":"e_1_3_4_5_2","unstructured":"Secretaria de Vigil\u00e2ncia Em Sa\u00fade. 2022. Protocolo Cl\u00ednico e Diretrizes Terap\u00eauticas Da Hansen\u00edase. http:\/\/bvsms.saude.gov.br\/bvs\/publicacoes\/ protocolo_clinico_diretrizes_terapeuticas_hanseniase.pdf."},{"key":"e_1_3_4_6_2","unstructured":"WHO. 2021. Towards zero leprosy. Global leprosy (Hansen\u2019s Disease) strategy 2021\u20132030. WHO. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789290228509"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.029389-0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01688-14"},{"key":"e_1_3_4_9_2","volume-title":"Asia RO for S-E. A guide for surveillance of antimicrobial resistance in leprosy: 2017 update","author":"World Health Organization (WHO) Asia RO for S-E","year":"2017","unstructured":"World Health Organization (WHO) Asia RO for S-E. 2017. Asia RO for S-E. A guide for surveillance of antimicrobial resistance in leprosy: 2017 update. Vol. Available from. https:\/\/apps.who.int\/iris\/handle\/10665\/259357."},{"key":"e_1_3_4_10_2","unstructured":"Minist\u00e9rio Da Sa\u00fade (Secretaria de Vigil\u00e2ncia Em Sa\u00fade e Ambiente). 2023. Boletim epidemiol\u00f3gico: detec\u00e7\u00e3o de muta\u00e7\u00f5es gen\u00e9ticas de M. leprae associadas \u00e0 resist\u00eancia aos antimicrobianos no Brasil. 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Drugs susceptibility testing in leprosy patients from C\u00f4te d\u2019Ivoire reveals multidrugs resistance combination cases to dapsone, rifampicin and ofloxacin. Am J Microbiol Res 8:160\u2013163.","journal-title":"Am J Microbiol Res"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idnow.2022.04.001"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.07.007"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S368682"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(22)00117-3"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104649"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01550-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01550-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T13:04:12Z","timestamp":1747746252000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01550-24"}},"subtitle":[],"editor":[{"given":"Sarah","family":"Doernberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":36,"alternative-id":["10.1128\/aac.01550-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01550-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,20]]},"assertion":[{"value":"2024-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01550-24"}}