Investigating drug resistance of Mycobacterium leprae in the Comoros: an observational deep-sequencing study

Despite strong leprosy control measures, including effective treatment, leprosy persists in the Comoros. As of May, 2022, no resistance to anti-leprosy drugs had been reported, but there are no nationally representative data. Post-exposure prophylaxis (PEP) with rifampicin is offered to contacts of...

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Published in:The Lancet. Microbe 2022-09, Vol.3 (9), p.e693-e700
Main Authors: Marijke Braet, Sofie, Jouet, Agathe, Aubry, Alexandra, Van Dyck-Lippens, Magalie, Lenoir, Esteban, Assoumani, Younoussa, Baco, Abdallah, Mzembaba, Aboubacar, Cambau, Emmanuelle, Vasconcellos, Sidra Ezidio Gonçalves, Rigouts, Leen, Suffys, Philip Noel, Hasker, Epco, Supply, Philip, de Jong, Bouke Catherine
Format: Article
Language:English
Subjects:
Bacteriology
Comoros
Dapsone - pharmacology
Drug Resistance, Bacterial - genetics
Drug Therapy, Combination
Genetics
Human health and pathology
Humans
Infectious diseases
Leprostatic Agents - pharmacology
Leprosy - drug therapy
Life Sciences
Microbiology and Parasitology
Mycobacterium leprae - genetics
Rifampin - pharmacology
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Summary:Despite strong leprosy control measures, including effective treatment, leprosy persists in the Comoros. As of May, 2022, no resistance to anti-leprosy drugs had been reported, but there are no nationally representative data. Post-exposure prophylaxis (PEP) with rifampicin is offered to contacts of patients with leprosy. We aimed to conduct a countrywide drug resistance survey and investigate whether PEP led to the emergence of drug resistance in patients with leprosy. In this observational, deep-sequencing analysis we assessed Mycobacterium leprae genomes from skin biopsies of patients in Anjouan and Mohéli, Comoros, collected as part of the ComLep (NCT03526718) and PEOPLE (NCT03662022) studies. Skin biopsies that had sufficient M leprae DNA (>2000 bacilli in 2 μl of DNA extract) were assessed for the presence of seven drug resistance-associated genes (ie, rpoB, ctpC, ctpI, folP1, gyrA, gyrB, and nth) using Deeplex Myc-Lep (targeted next generation deep sequencing), with a limit of detection of 10% for minority M leprae bacterial populations bearing a polymorphism in these genes. All newly registered patients with leprosy for whom written informed consent was obtained were eligible for inclusion in the survey. Patients younger than 2 years or with a single lesion on the face did not have biopsies taken. The primary outcome of our study was the proportion of patients with leprosy (ie, new cases, patients with relapses or reinfections, patients who received single (double) dose rifampicin-PEP, or patients who lived in villages where PEP was distributed) who were infected with M leprae with a drug-resistant mutation for rifampicin, fluoroquinolone, or dapsone in the Comoros. Between July 1, 2017, and Dec 31, 2020, 1199 patients with leprosy were identified on the basis of clinical criteria, of whom 1030 provided a skin biopsy. Of these 1030 patients, 755 (73·3%) tested positive for the M leprae-specific repetitive element-quantitative PCR (qPCR) assay. Of these 755 patients, 260 (34·4%) were eligible to be analysed using Deeplex Myc-Lep. 251 (96·5%) were newly diagnosed with leprosy, whereas nine (3·4%) patients had previously received multidrug therapy. 45 (17·3%) patients resided in villages where PEP had been administered in 2015 or 2019, two (4·4%) of whom received PEP. All seven drug resistance-associated targets were successfully sequenced in 216 samples, 39 samples had incomplete results, and five had no results. No mutations were detected in any of t
ISSN:2666-5247
2666-5247
DOI:10.1016/S2666-5247(22)00117-3