Resistance to anti-leprosy drugs in multi-bacillary leprosy patients: The need for transformative action

Background Leprosy, caused by Mycobacterium leprae, remains a significant public health challenge, particularly in endemic regions. While multidrug therapy (MDT) has been effective, the emergence of antimicrobial resistance (AMR) to key drugs such as rifampicin, dapsone, and ofloxacin threatens leprosy control programs. Resistance mechanisms include mutations in genes such as rpoB (rifampicin), folP1 (dapsone), and gyrA (ofloxacin). Drug resistance contributes to treatment failures, prolonged transmission, and the emergence of severe complications, necessitating enhanced surveillance and diagnostic capabilities. Aims This study aimed to determine the rates of primary and secondary AMR in M. leprae among multi-bacillary leprosy patients attending a tertiary care institute in Uttarakhand. It also sought to identify patterns of genetic mutations associated with resistance. Methods This prospective, cross-sectional study was conducted from July 2022 to June 2024. Patients with a bacteriological index (BI) ≥2, fulfilling specific clinical criteria [treatment-naive, chronic or recurrent erythema nodosum leprosum (ENL), relapse or persistent positive morphological index (MI)] were recruited. Slit skin smears (SSS) were processed using polymerase chain reaction (PCR) -based gene amplification to detect mutations in rpoB, folP1 and gyrA. Amplified DNA samples were sequenced and analysed for resistance-associated mutations. Demographic and clinical data, including type of leprosy, BI, MI, and treatment history, were also collected. Results Out of 47 samples tested, 43 were successfully amplified. Resistance was detected in eight cases (17%). Primary resistance was noted in 4/20 treatment-naive patients (20%). Rifampicin resistance, attributed to the F439L mutation, was the most common (n = 4). Dapsone resistance due to P55L and P55S mutations was identified in two cases, while ofloxacin resistance associated with A91V and G89C mutations was seen in two cases. Limitations The study's findings are limited by its sample size and the focus on a single tertiary care centre, potentially restricting the generalisability of results. Additionally, not all samples were successfully amplified for analysis. Conclusion This study underscores the critical need for routine AMR testing in high-risk leprosy cases. Regional variations in resistance patterns necessitate localised surveillance to guide effective treatment strategies. Enhanced diagnostic capabilities, patient education, and policy-level interventions are essential to combat the rising threat of AMR in leprosy.