{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:47:42Z","timestamp":1793724462492,"version":"4.6.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["MCT\/CNPq\/MS-SCTIE-DECIT 35\/2005"],"award-info":[{"award-number":["MCT\/CNPq\/MS-SCTIE-DECIT 35\/2005"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["MCT\/CNPq\/CT-Sa\u00fade\/MS\/SCTIE\/DECIT N\u00ba 034\/2008"],"award-info":[{"award-number":["MCT\/CNPq\/CT-Sa\u00fade\/MS\/SCTIE\/DECIT N\u00ba 034\/2008"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["MCTI\/CNPq\/MS-SCTIE \u2013 Decit N\u00b0 40\/2012"],"award-info":[{"award-number":["MCTI\/CNPq\/MS-SCTIE \u2013 Decit N\u00b0 40\/2012"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004612","name":"Funda\u00e7\u00e3o Arauc\u00e1ria","doi-asserted-by":"publisher","award":["FA 247\/2015"],"award-info":[{"award-number":["FA 247\/2015"]}],"id":[{"id":"10.13039\/501100004612","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Damien Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Leprosy has been treated with multidrug therapy, which has been distributed for free across the globe and regarded as highly efficient. However, the impossibility of growing Mycobacterium leprae in axenic media has historically impaired assessments of M. leprae resistance, a parameter only recently detectable through molecular methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic, population-based search for M. leprae resistance in suspected leprosy relapse cases and contacts was performed in Prata Village, an isolated, hyperendemic, former leprosy colony located in the Brazilian Amazon. Results led to an extended active search involving the entire Prata population. Confirmed leprosy cases were investigated for bacterial resistance using a combination of in vivo testing and direct sequencing of resistance genes folP1, rpoB, and gyrA. A molecular epidemiology analysis was performed using data from 17 variable number tandem repeats (VNTR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mycobacterium leprae was obtained from biopsies of 37 leprosy cases (18 relapses and 19 new cases): 16 (43.24%) displayed drug-resistance variants. Multidrug resistance to rifampicin and dapsone was observed in 8 relapses and 4 new cases. Single resistance to rifampicin was detected in 1 new case. Resistance to dapsone was present in 2 relapses and 1 new case. Combined molecular resistance and VNTR data revealed evidence of intra-familial primary transmission of resistant M. leprae.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A comprehensive, population-based systematic approach to investigate M. leprae resistance in a unique population revealed an alarming scenario of the emergence and transmission of resistant strains. These findings may be used for the development of new strategies for surveillance of drug resistance in other populations.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz570","type":"journal-article","created":{"date-parts":[[2019,6,29]],"date-time":"2019-06-29T03:10:37Z","timestamp":1561777837000},"page":"2054-2061","source":"Crossref","is-referenced-by-count":43,"title":["Emergence and Transmission of Drug-\/Multidrug-resistant Mycobacterium leprae in a Former Leprosy Colony in the Brazilian Amazon"],"prefix":"10.1093","volume":"70","author":[{"given":"Patr\u00edcia S","family":"Rosa","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena R S","family":"D\u2019Espindula","sequence":"first","affiliation":[{"name":"Graduate Program in Health Sciences, School of Medicine, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1, Curitiba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C L","family":"Melo","sequence":"first","affiliation":[{"name":"Centro de Refer\u00eancia Nacional em Dermatologia Sanit\u00e1ria Dona Lib\u00e2nia, Fortaleza, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda N B","family":"Fontes","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology Applied in Mycobacteria, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J","family":"Finardi","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a F F","family":"Belone","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz G C","family":"Sartori","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla A A","family":"Pires","sequence":"first","affiliation":[{"name":"Core of Tropical Diseases, Universidade Federal do Par\u00e1, Bel\u00e9m, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleverson T","family":"Soares","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio B","family":"Marques","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J D","family":"Branco","sequence":"first","affiliation":[{"name":"Centro de Refer\u00eancia Nacional em Dermatologia Sanit\u00e1ria Dona Lib\u00e2nia, Fortaleza, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida M F D","family":"Baptista","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1zara M","family":"Trino","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana R V","family":"Fachin","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00edlia B","family":"Xavier","sequence":"first","affiliation":[{"name":"Core of Tropical Diseases, Universidade Federal do Par\u00e1, Bel\u00e9m, Brazil"},{"name":"Center for Biological and Health Sciences, Universidade do Estado do Par\u00e1, Bel\u00e9m, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos C","family":"Floriano","sequence":"first","affiliation":[{"name":"Department of Dermatology, Universidade Federal de S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somei","family":"Ura","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana M","family":"Di\u00f3rio","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wladimir F B","family":"Delanina","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton O","family":"Moraes","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology Applied in Mycobacteria, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos C L","family":"Virmond","sequence":"first","affiliation":[{"name":"Division of Research and Education, Instituto Lauro de Souza Lima, Bauru, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N","family":"Suffys","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology Applied in Mycobacteria, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo T","family":"Mira","sequence":"first","affiliation":[{"name":"Graduate Program in Health Sciences, School of Medicine, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1, Curitiba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2020050606275846500_CIT0001","doi-asserted-by":"crossref","first-page":"e293","DOI":"10.1016\/S1473-3099(17)30418-8","article-title":"Multidrug therapy for leprosy: a game changer on the path to elimination","volume":"17","author":"Smith","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2020050606275846500_CIT0002","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0140-6736(64)92482-1","article-title":"Sulphone resistance in leprosy. an experimental and clinical study","volume":"2","author":"Pettit","year":"1964","journal-title":"Lancet"},{"key":"2020050606275846500_CIT0003","first-page":"129","article-title":"Primary dapsone-resistant leprosy","volume":"48","author":"Pearson","year":"1977","journal-title":"Lepr Rev"},{"key":"2020050606275846500_CIT0004","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/S0140-6736(76)92071-7","article-title":"Rifampin-resistant leprosy","volume":"2","author":"Jacobson","year":"1976","journal-title":"Lancet"},{"key":"2020050606275846500_CIT0005","first-page":"1","article-title":"Chemotherapy of leprosy for control programmes","volume":"675","author":"World Health Organization","year":"1982","journal-title":"World Health Organ Tech Rep Ser"},{"key":"2020050606275846500_CIT0006","first-page":"280","article-title":"Primary resistance to single and multiple drugs in leprosy\u2013a mouse footpad study","volume":"67","author":"Shetty","year":"1996","journal-title":"Lepr Rev"},{"key":"2020050606275846500_CIT0007","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0140-6736(05)60888-4","article-title":"Multidrug-resistance to dapsone, rifampicin, and ofloxacin in Mycobacterium leprae","volume":"349","author":"Cambau","year":"1997","journal-title":"Lancet"},{"key":"2020050606275846500_CIT0008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2018.03072","article-title":"Insights on Mycobacterium leprae efflux pumps and their implications in drug resistance and virulence","volume":"9","author":"Machado","year":"2018","journal-title":"Front Microbiol"},{"key":"2020050606275846500_CIT0009","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1093\/jac\/dkx227","article-title":"Molecular mechanisms of clofazimine resistance in Mycobacterium tuberculosis","volume":"72","author":"Yew","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2020050606275846500_CIT0010","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1084\/jem.112.3.445","article-title":"The experimental disease that follows the injection of human leprosy bacilli into foot-pads of mice","volume":"112","author":"Shepard","year":"1960","journal-title":"J Exp Med"},{"key":"2020050606275846500_CIT0011","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1128\/JCM.01688-14","article-title":"Identification of primary drug resistance to rifampin in Mycobacterium leprae strains from leprosy patients in Amazonas State, Brazil","volume":"52","author":"Contreras Mej\u00eda","year":"2014","journal-title":"J Clin Microbiol"},{"key":"2020050606275846500_CIT0012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7883\/yoken.63.1","article-title":"Drug resistance in leprosy","volume":"63","author":"Matsuoka","year":"2010","journal-title":"Jpn J Infect Dis"},{"key":"2020050606275846500_CIT0013","doi-asserted-by":"crossref","first-page":"269","DOI":"10.47276\/lr.83.3.269","article-title":"Drug-resistant leprosy: monitoring and current status","volume":"83","author":"Williams","year":"2012","journal-title":"Lepr Rev"},{"key":"2020050606275846500_CIT0014","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1128\/JCM.06561-11","article-title":"Drug and multidrug resistance among Mycobacterium leprae isolates from Brazilian relapsed leprosy patients","volume":"50","author":"da Silva Rocha","year":"2012","journal-title":"J Clin Microbiol"},{"key":"2020050606275846500_CIT0015","volume-title":"Guidelines for global surveillance of drug resistance in Leprosy","author":"World Health Organization","year":"2009"},{"key":"2020050606275846500_CIT0016","doi-asserted-by":"crossref","first-page":"e0005041","DOI":"10.1371\/journal.pntd.0005041","article-title":"Leprosy drug resistance surveillance in Colombia: the experience of a sentinel country","volume":"10","author":"Beltr\u00e1n-Alzate","year":"2016","journal-title":"PLOS Negl Trop Dis"},{"key":"2020050606275846500_CIT0017","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1093\/cid\/ciw572","article-title":"Transmission of drug-resistant leprosy in Guinea-Conakry detected using molecular epidemiological approaches","volume":"63","author":"Avanzi","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2020050606275846500_CIT0018","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jgar.2017.10.010","article-title":"Molecular detection of multidrug-resistant Mycobacterium leprae from Indian leprosy patients","volume":"12","author":"Lavania","year":"2018","journal-title":"J Glob Antimicrob Resist"},{"key":"2020050606275846500_CIT0019","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.cmi.2018.02.022","article-title":"Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009\u20132015","volume":"24","author":"Cambau","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2020050606275846500_CIT0020","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.cmi.2018.02.022","article-title":"Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15","volume":"24","author":"Cambau","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2020050606275846500_CIT0021","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1086\/652007","article-title":"A major gene controls leprosy susceptibility in a hyperendemic isolated population from north of Brazil","volume":"201","author":"L\u00e1zaro","year":"2010","journal-title":"J Infect Dis"},{"key":"2020050606275846500_CIT0022","doi-asserted-by":"crossref","first-page":"e0006117","DOI":"10.1371\/journal.pntd.0006117","article-title":"Genotyping of Mycobacterium leprae for better understanding of leprosy transmission in Fortaleza, Northeastern Brazil","volume":"11","author":"Fontes","year":"2017","journal-title":"PLOS Negl Trop Dis"},{"key":"2020050606275846500_CIT0023","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1126\/science.aah3783","article-title":"Red squirrels in the British Isles are infected with leprosy bacilli","volume":"354","author":"Avanzi","year":"2016","journal-title":"Science"},{"key":"2020050606275846500_CIT0024","volume-title":"A guide for surveillance of antimicrobial resistance in leprosy: 2017 update","author":"World Health Organization","year":"2017"},{"key":"2020050606275846500_CIT0025","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S1473-3099(18)30012-4","article-title":"Are leprosy case numbers reliable?","volume":"18","author":"Salgado","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"2020050606275846500_CIT0026","doi-asserted-by":"crossref","first-page":"O619","DOI":"10.1111\/1469-0691.12609","article-title":"Genome-wide re-sequencing of multidrug-resistant Mycobacterium leprae Airaku-3","volume":"20","author":"Singh","year":"2014","journal-title":"Clin Microbiol Infect"},{"key":"2020050606275846500_CIT0027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-02576-z","article-title":"Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae","volume":"9","author":"Benjak","year":"2018","journal-title":"Nat Commun"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciz570\/30042343\/ciz570.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/70\/10\/2054\/33174547\/ciz570.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/70\/10\/2054\/33174547\/ciz570.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T11:06:21Z","timestamp":1663844781000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/70\/10\/2054\/5526733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,7,1]]},"published-print":{"date-parts":[[2020,5,6]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciz570","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,5,15]]},"published":{"date-parts":[[2019,7,1]]}}}