Assessment of Antimicrobial Resistance in M. leprae Strains From Kiribati

Kiribati has one of the highest rates of leprosy worldwide. A nationwide screening and chemoprophylaxis program for household leprosy contacts was introduced in 2018. In 2022, population-wide screening and rifamycin-based treatment or chemoprophylaxis for leprosy and tuberculosis was introduced as part of the PEARL and COMBINE studies. Largescale rifamycin use theoretically risks selection of resistant Mycobacterium leprae strains. This study aimed to elucidate the baseline antimicrobial resistance (AMR) profile of M. leprae isolates in Kiribati using a novel molecular method.

Mycobacterium leprae genomes from skin biopsies of patients clinically diagnosed with leprosy in Kiribati between 2017 and 2024 were analysed. We used an M. leprae specific repetitive element (RLEP) PCR to confirm the presence of M. leprae DNA. Samples with sufficient DNA (cycle threshold (CT) value < 30) proceeded for resistance testing. A combination of nested and heminested PCR assays was used to amplify the drug resistance determining regions (DRDR's) for dapsone (folP1), rifampicin (rpoB) and fluoroquinolones (gyrA) followed by DNA Sanger sequencing.

216 skin biopsies (multibacillary [MB], n = 155, paucibacillary [PB], n = 61) underwent confirmatory testing. 192/216 (89%) samples were PCR positive (median Ct value 24.5 [range 12.0-44.4]), including 145 MB cases (median CT 21.1 [range 12.0-42.0]) and 47 PB cases (median CT 34.0 [range 14.8-37.0]). Twenty-four (11%) samples were PCR negative and 21 of these underwent histopathological testing, with 12 (57%) showing changes consistent with leprosy. 116 (60%) positive samples proceeded to AMR testing (MB, n = 106; PB, n = 10). In 10 cases (9%), dapsone resistance-conferring mutations were identified in the folP1 region. No mutations were identified in the rpoB or gyrA genes.

Molecular analysis of skin biopsies revealed moderate-level dapsone resistance but no rifampicin resistance in Kiribati. Establishing this baseline AMR profile will enable a before-versus-after intervention analysis of antimicrobial resistance in M. leprae isolates in Kiribati.