title: Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country.
abstract: 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.
authors.affiliation: Instituto Colombiano de Medicina Tropical-Universidad CES Sabaneta, Antioquia, Colombia.
authors.forename: Camilo
authors.initials: C
authors.lastname: Beltrán-Alzate
authors.affiliation: Sanatorio de Agua de Dios, Agua de Dios Cundinamarca, Colombia.
authors.forename: Fernando
authors.initials: F
authors.lastname: López Díaz
authors.affiliation: Instituto Colombiano de Medicina Tropical-Universidad CES Sabaneta, Antioquia, Colombia.
authors.forename: Marcela
authors.initials: M
authors.lastname: Romero-Montoya
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Rama
authors.initials: R
authors.lastname: Sakamuri
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Miyako
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Instituto Colombiano de Medicina Tropical-Universidad CES Sabaneta, Antioquia, Colombia.|Facultad de Medicina. Universidad CES, Medellín, Colombia.
authors.forename: Nora
authors.identifier: http://orcid.org/0000-0002-4716-6636
authors.initials: N
authors.lastname: Cardona-Castro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000235:genetics*; D002648:Child; D003105:Colombia / Q000453:epidemiology; D004269:DNA, Bacterial / Q000235:genetics; D003622:Dapsone / Q000494:pharmacology / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D007917:Leprostatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007918:Leprosy / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015242:Ofloxacin / Q000494:pharmacology / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012008:Recurrence; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D018571:Sentinel Surveillance; D012867:Skin / Q000382:microbiology; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007917:Leprostatic Agents; D003622:Dapsone; D015242:Ofloxacin; D012293:Rifampin