Assessing improved surveillance of leprosy drug resistance in Madagascar: a pilot study in the Miandrivazo district
Abstract
Background: To curb the emergence of antibiotic-resistant Mycobacterium leprae strains, the WHO recommends monitoring of antimicrobial resistance (AMR). In Madagascar, molecular surveillance of resistance to anti- M. leprae drugs, remains limited geographically and in terms of quantitative data. A clinical trial on leprosy prophylaxis (PEOPLE) conducted in the district of Miandrivazo provided an opportunity to explore the feasibility of an integrated approach for improving leprosy surveillance and resistance monitoring in Madagascar. This study aimed to i) determine the genetic diversity of the identified M. leprae strains, (ii) detect mutations associated with AMR, (iii) evaluate and compare the acceptance rate of low-invasive sampling methods with that of skin biopsies, and (iv) assess seropositivity for anti- M. leprae PGL-I IgM. Methods: Patients were identified through door-to-door screening and skin biopsies (SB), fingerstick blood (FSB) and nasal swabs (NS) were collected. SB were analyzed by RLEP qPCR for detection of M. leprae DNA, resistance testing using LiPA (Line Probe Assay), and resistance analysis and SNP and/or VNTR genotyping using Sanger sequencing and Deeplex Myc-Lep. NS and FSB samples were used to detect bacterial colonization by RLEP qPCR and detect past and/or present infection by measuring anti- M. leprae PGL-I IgM levels. Results: 80 leprosy patients were identified, including 41 multibacillary and 39 paucibacillary. Out of these, 57 accepted NS, 47 FSB, and 33 SB. High levels of anti-PGL-I IgM were detected in 6/47 FSB samples. RLEP qPCR was positive in 4/57 NS samples and 28/33 SB samples. Among SB positive, 12 yielded interpretable results when combining data from LiPA, Deeplex Myc-Lep, and Sanger sequencing. No drug resistance conferring mutations were detected. All strains belonged to the 1D-Malagasy genotype, and VNTR analysis for 7 samples with results available across 9 loci showed 7 unique types, with loci GAA21, GTA9, and AC8a were the most informative for strain differentiation. Conclusion: Despite the small sample size, this study shows that NS and FSB samples are well accepted in patients. No mutations conferring resistance were identified and the M. leprae strains belong to the 1D-Malagasy genotype. These findings support the feasibility of field-based molecular surveillance and provide a foundation for expanding AMR monitoring in Madagascar.
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BibTeX
@article{maharavo2026assessing,
title = {{Assessing improved surveillance of leprosy drug resistance in Madagascar: a pilot study in the Miandrivazo district}},
author = {Luca Maharavo and Stéphanie Ramboarina and Sofie Marijke Braet and Paul Corstjens and Danielle de Jong and Andriamira Randrianantoandro and Lovasoa Mbolamanana Joseph Andrianiriana and Mala Rakoto Andrianarivelo and Jean Luc Berland and Emmanuelle Cambau and Philip Supply and Agathe Jouet and Epco Hasker and Bouke Catherine de Jong and Bertrand Cauchoix and Tahinamandranto Rasamoelina and Luc Hervé Samison and Annemieke Geluk},
journal = {Mycobacteria},
year = {2026},
month = sep,
doi = {10.1186/s44350-026-00022-z},
url = {https://hal.science/hal-05771255v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Assessing improved surveillance of leprosy drug resistance in Madagascar: a pilot study in the Miandrivazo district
AU - Luca Maharavo
AU - Stéphanie Ramboarina
AU - Sofie Marijke Braet
AU - Paul Corstjens
AU - Danielle de Jong
AU - Andriamira Randrianantoandro
AU - Lovasoa Mbolamanana Joseph Andrianiriana
AU - Mala Rakoto Andrianarivelo
AU - Jean Luc Berland
AU - Emmanuelle Cambau
AU - Philip Supply
AU - Agathe Jouet
AU - Epco Hasker
AU - Bouke Catherine de Jong
AU - Bertrand Cauchoix
AU - Tahinamandranto Rasamoelina
AU - Luc Hervé Samison
AU - Annemieke Geluk
PY - 2026
DA - 2026/09/20
JO - Mycobacteria
DO - 10.1186/s44350-026-00022-z
UR - https://hal.science/hal-05771255v1
AB - Background: To curb the emergence of antibiotic-resistant Mycobacterium leprae strains, the WHO recommends monitoring of antimicrobial resistance (AMR). In Madagascar, molecular surveillance of resistance to anti- M. leprae drugs, remains limited geographically and in terms of quantitative data. A clinical trial on leprosy prophylaxis (PEOPLE) conducted in the district of Miandrivazo provided an opportunity to explore the feasibility of an integrated approach for improving leprosy surveillance and resistance monitoring in Madagascar. This study aimed to i) determine the genetic diversity of the identified M. leprae strains, (ii) detect mutations associated with AMR, (iii) evaluate and compare the acceptance rate of low-invasive sampling methods with that of skin biopsies, and (iv) assess seropositivity for anti- M. leprae PGL-I IgM. Methods: Patients were identified through door-to-door screening and skin biopsies (SB), fingerstick blood (FSB) and nasal swabs (NS) were collected. SB were analyzed by RLEP qPCR for detection of M. leprae DNA, resistance testing using LiPA (Line Probe Assay), and resistance analysis and SNP and/or VNTR genotyping using Sanger sequencing and Deeplex Myc-Lep. NS and FSB samples were used to detect bacterial colonization by RLEP qPCR and detect past and/or present infection by measuring anti- M. leprae PGL-I IgM levels. Results: 80 leprosy patients were identified, including 41 multibacillary and 39 paucibacillary. Out of these, 57 accepted NS, 47 FSB, and 33 SB. High levels of anti-PGL-I IgM were detected in 6/47 FSB samples. RLEP qPCR was positive in 4/57 NS samples and 28/33 SB samples. Among SB positive, 12 yielded interpretable results when combining data from LiPA, Deeplex Myc-Lep, and Sanger sequencing. No drug resistance conferring mutations were detected. All strains belonged to the 1D-Malagasy genotype, and VNTR analysis for 7 samples with results available across 9 loci showed 7 unique types, with loci GAA21, GTA9, and AC8a were the most informative for strain differentiation. Conclusion: Despite the small sample size, this study shows that NS and FSB samples are well accepted in patients. No mutations conferring resistance were identified and the M. leprae strains belong to the 1D-Malagasy genotype. These findings support the feasibility of field-based molecular surveillance and provide a foundation for expanding AMR monitoring in Madagascar.
SN - 3004-9555
SN - 3004-9555
ER -