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.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis

“…Finally, none of these studies reported antibiotic resistance pattern of M. leprae. There are reports on drug resistance in leprosy patients [45][46][47][48][49] and can be one of the reasons of the relapse rate increase in the last years [50]. Considering some of the areas with leprosy had also high incidence of resistant tuberculosis (such us India) and MDT share rifampin as an important drug with sensitive tuberculosis, closer follow-up and drug resistance studies should be done in these areas.…”

Molecular surveillance of antimicrobial resistance and transmission pattern of Mycobacterium leprae in Chinese leprosy patients

“…Nevertheless, no effective BI change was observed in some leprosy cases, even if MDT was prescribed for more than 1-year (Supplementary Table 1) [10–19]. The factors influencing the lack of BI decline remain unknown, but high initial BI and no decline in BI at RFT are possible signs of AMR [12].…”

Transmissão da hanseníase na Bahia, 2001-2015: modelagem a partir de regressão por pontos de inflexão e estatística de varredura espacial*

“…Non-cured individuals, apart from contributing to continuing transmission, can develop permanent physical disabilities, reactional states and drug resistance. 26,27 The second piece of evidence relates to the percentage of contacts examined. This is an indicator of the capacity of health services to undertake surveillance of case contacts and thus increase timely detection of new cases.…”

“…3 Currently, in addition to being in first place in terms of prevalence (1.10/10,000 inhab. in 2016), Brazil is in second place after India with regard to the absolute number of new cases. In 2016 alone, 25,218 new leprosy cases were diagnosed in Brazil, 1,696 of which occurred in people under 15 years old.…”