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Abstract
<title>Abstract</title> <p> Despite the proven efficacy multidrug therapy (MDT), drug resistance continues to be reported globally. In Niger, the historical period of long-term dapsone monotherapy may explain the emergence and persistence of these resistant strains, challenging the success of leprosy control programs. To address this challenge, this study focuses a long-term bacteriological monitoring. Specially, we report a case of a primary molecular dapsone-resistant strain identified at the Centre National Dermato-Lèpre (CNDL) in Niamey, the national center for leprosy. A two-year surveillance study screened 24 patients with multibacillary (MB) leprosy presenting a bacteriological index (BI) ≥ 2+. Genetic resistance mutations in <italic>rpoB</italic> , <italic>folP1</italic> , and <italic>gyrA</italic> genes (conferring resistance to rifampicin, dapsone, and fluoroquinolones, respectively) were investigated using multiplex PCR followed by the GenoType LepraeDR test. One patient with primary molecular resistance to dapsone representing a prevalence of 4.16% within the cohort was identified and monitored during a 12-month MDT regimen. Bacteriological follow-up evaluated both the BI and the morphological index (MI) at baseline and at the end of treatment. Following 12 months of MDT, the patient showed a decrease of 1.33 points in the BI. The MI dropped drastically from 69% to 1%, indicating near-complete clearing of viable bacilli. These results confirm the therapeutic efficacy of standard MDT against dapsone-resistance <italic>Mycobacterium leprae</italic> strains. However, the residual 1% MI suggests the persistence of viable mutated bacilli. Strict, long-term monitoring of this patient remains crucial to prevent clinical relapse and contain the transmission of drug-resistant leprosy in Niger. </p>