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Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country

An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, wher...

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Autores principales: Beltrán-Alzate, Camilo, López Díaz, Fernando, Romero-Montoya, Marcela, Sakamuri, Rama, Li, Wei, Kimura, Miyako, Brennan, Patrick, Cardona-Castro, Nora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051701/
https://www.ncbi.nlm.nih.gov/pubmed/27706165
http://dx.doi.org/10.1371/journal.pntd.0005041
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author Beltrán-Alzate, Camilo
López Díaz, Fernando
Romero-Montoya, Marcela
Sakamuri, Rama
Li, Wei
Kimura, Miyako
Brennan, Patrick
Cardona-Castro, Nora
author_facet Beltrán-Alzate, Camilo
López Díaz, Fernando
Romero-Montoya, Marcela
Sakamuri, Rama
Li, Wei
Kimura, Miyako
Brennan, Patrick
Cardona-Castro, Nora
author_sort Beltrán-Alzate, Camilo
collection PubMed
description An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu), suggesting multidrug resistance. One isolate had a double mutation in folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that required in vivo evaluation of their association or not with drug resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to drug resistance and were isolated from relapsed patients; the likelihood of relapse was significantly associated with the presence of confirmed resistance mutations (OR range 20.1–88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. In summary, the current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapse in leprosy patients. A high frequency of DRDR mutations for rifampicin was seen in a region where dapsone monotherapy was used extensively.
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spelling pubmed-50517012016-10-27 Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country Beltrán-Alzate, Camilo López Díaz, Fernando Romero-Montoya, Marcela Sakamuri, Rama Li, Wei Kimura, Miyako Brennan, Patrick Cardona-Castro, Nora PLoS Negl Trop Dis Research Article An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu), suggesting multidrug resistance. One isolate had a double mutation in folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that required in vivo evaluation of their association or not with drug resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to drug resistance and were isolated from relapsed patients; the likelihood of relapse was significantly associated with the presence of confirmed resistance mutations (OR range 20.1–88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. In summary, the current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapse in leprosy patients. A high frequency of DRDR mutations for rifampicin was seen in a region where dapsone monotherapy was used extensively. Public Library of Science 2016-10-05 /pmc/articles/PMC5051701/ /pubmed/27706165 http://dx.doi.org/10.1371/journal.pntd.0005041 Text en © 2016 Beltrán-Alzate et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Beltrán-Alzate, Camilo
López Díaz, Fernando
Romero-Montoya, Marcela
Sakamuri, Rama
Li, Wei
Kimura, Miyako
Brennan, Patrick
Cardona-Castro, Nora
Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country
title Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country
title_full Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country
title_fullStr Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country
title_full_unstemmed Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country
title_short Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country
title_sort leprosy drug resistance surveillance in colombia: the experience of a sentinel country
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051701/
https://www.ncbi.nlm.nih.gov/pubmed/27706165
http://dx.doi.org/10.1371/journal.pntd.0005041
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