¿Es la resistencia de Mycobacterium leprae a los medicamentos un verdadero motivo de preocupación? Primera aproximación a la vigilancia molecular de pacientes colombianos multibacilares con tratamiento previo para lepra y sin él

Abstract

Introduction:There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods. Objective: To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period. Materials and methods: We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses. Results: From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined. Conclusions:The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.

Antimicrobial Resistance among Leprosy Patients in Brazil: Real-World Data Based on the National Surveillance Plan

“…The multivariate analysis model used showed that none of the demographic or clinical variables influenced the occurrence of drug resistance. The same results were found in studies in Colombia (24), China (25), and India (26). This may indicate that AMR is more related to the inherent characteristics of the bacillus and that it is probably influenced by factors such as irregular use of antimicrobials (27).…”

Mycobacterium leprae’s Infective Capacity Is Associated with Activation of Genes Involved in PGL-I Biosynthesis in a Schwann Cells Infection Model

“…The recurrent case's sample came from a patient who, 40 months before, had completed MDT. The appearance of new clinical signs and the recurrence diagnosis included positive bacillary viability and negative test to drug resistance determined by mutations in the drug resistance-determining region (DRDR) for the folP1, rpo β, and gyrA genes from M. leprae [24].…”

“…Factors influencing recurrence include delayed initial diagnosis, high initial bacillary loads, and leprosy in multibacillary patients [18]. This clinical manifestation differs from processes such as drug resistance and reinfection, the latter in patients who have been cured and years later start the disease again with a new strain of M. leprae [23,24].…”

A systematic review of Mycobacterium leprae DNA gyrase mutations and their impact on fluoroquinolone resistance

“…[13,25,26] The prior use of FQ was reported in 18 studies (Table 4). [13,[24][25][26]29,[32][33][34][35][36][37][38][39][40][41][42][43][44] Mutations in gyrA (Tables 1, 4) Among the 18 substitutions described in GyrA, nine were inside and seven outside the QRDR, and two were inside the intein (Table 1). The A91 substitution was the most prevalent.…”

“…Multiple substitutions in GyrA were found in three strains (Table 4). [29,35,41] Double mutations in gyrA have been described and associated with highlevel resistance. [45] They may result from a two-step selection of FQ-resistant mutants, which unlikely occurs in the extremely slow growing M. leprae.…”