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Abstract Some anti‐mycobacterial drugs are known to cause QT interval prolongation, potentially leading to life‐threatening ventricular arrhythmia. However, the highest leprosy and tuberculosis burden occurs in settings where electrocardiographic monitoring is challenging. The feasibility and accuracy of alternative strategies, such as the use of automated measurements or a mobile electrocardiogram (mECG) device, have not been evaluated in this context. As part of the phase II randomized controlled BE‐PEOPLE trial evaluating the safety of bedaquiline‐enhanced post‐exposure prophylaxis (bedaquiline and rifampicin, BE‐PEP, versus rifampicin, SDR‐PEP) for leprosy, all participants had corrected QT intervals (QTc) measured at baseline and on the day after receiving post‐exposure prophylaxis. The accuracy of mECG measurements as well as automated 12L‐ECG measurements was evaluated. In total, 635 mECGs from 323 participants were recorded, of which 616 (97%) were of sufficient quality for QTc measurement. Mean manually read QTc on 12L‐ECG and mECG were 394 ± 19 and 385 ± 18 ms, respectively (p

IntroductionLeprosy, one of the oldest known human diseases, continues to pose a global challenge for disease control due to an incomplete understanding of its transmission pathways. Ticks have been proposed as a potential contributor in leprosy transmission due to their importance as vectors for other infectious diseases.MethodsIn 2010, a sampling of ticks residing on cattle was conducted on the islands Grande Comore, Anjouan, and Mohéli which constitute the Union of the Comoros where leprosy remains endemic. To investigate the potential role of ticks as a vector in transmission of leprosy disease, molecular analyses were conducted.ResultsOut of the 526 ticks analysed, none were found to harbour Mycobacterium leprae DNA, as determined by a quantitative polymerase chain reaction (qPCR) assay targeting a family of dispersed repeats (RLEP) specific to M. leprae.DiscussionTherefore, our results suggest that in the Union of the Comoros, ticks are an unlikely vector for M. leprae.

Summary: Background: Expansion of antimicrobial resistance monitoring and epidemiological surveillance are key components of the WHO strategy towards zero leprosy. The inability to grow Mycobacterium leprae in vitro precludes routine phenotypic drug susceptibility testing, and only limited molecular tests are available. We evaluated a culture-free targeted deep sequencing assay, for mycobacterial identification, genotyping based on 18 canonical SNPs and 11 core variable-number tandem-repeat (VNTR) markers, and detection of rifampicin, dapsone and fluoroquinolone resistance-associated mutations in rpoB/ctpC/ctpI, folP1, gyrA/gyrB, respectively, and hypermutation-associated mutations in nth. Methods: The limit of detection (LOD) was determined using DNA of M. leprae reference strains and from 246 skin biopsies and 74 slit skin smears of leprosy patients, with genome copies quantified by RLEP qPCR. Sequencing results were evaluated versus whole genome sequencing (WGS) data of 14 strains, and versus VNTR-fragment length analysis (FLA) results of 89 clinical specimens. Findings: The LOD for sequencing success ranged between 80 and 3000 genome copies, depending on the sample type. The LOD for minority variants was 10%. All SNPs detected in targets by WGS were identified except in a clinical sample where WGS revealed two dapsone resistance-conferring mutations instead of one by Deeplex Myc-Lep, due to partial duplication of the sulfamide-binding domain in folP1. SNPs detected uniquely by Deeplex Myc-Lep were missed by WGS due to insufficient coverage. Concordance with VNTR-FLA results was 99.4% (926/932 alleles). Interpretation: Deeplex Myc-Lep may help improve the diagnosis and surveillance of leprosy. Gene domain duplication is an original putative drug resistance-related genetic adaptation in M. leprae. Funding: EDCTP2 programme supported by the European Union (grant number RIA2017NIM-1847 -PEOPLE). EDCTP, R2Stop: Effect:Hope, The Mission To End Leprosy, the Flemish Fonds Wetenschappelijk Onderzoek.

The World Health Organization (WHO) endorsed diagnosis of leprosy (also known as Hansen’s disease) entirely based on clinical cardinal signs, without microbiological confirmation, which may lead to late or misdiagnosis. The use of slit skin smears is variable, but lacks sensitivity. In 2017–2018 during the ComLep study, on the island of Anjouan (Union of the Comoros; High priority country according to WHO, 310 patients were diagnosed with leprosy (paucibacillary = 159; multibacillary = 151), of whom 263 were sampled for a skin biopsy and fingerstick blood, and 260 for a minimally-invasive nasal swab. In 74.5% of all skin biopsies and in 15.4% of all nasal swabs, M. leprae DNA was detected. In 63.1% of fingerstick blood samples, M. leprae specific antibodies were detected with the quantitative αPGL-I test. Results show a strong correlation of αPGL-I IgM levels in fingerstick blood and RLEP-qPCR positivity of nasal swabs, with the M. leprae bacterial load measured by RLEP-qPCR of skin biopsies. Patients with a high bacterial load (≥50,000 bacilli in a skin biopsy) can be identified with combination of counting lesions and the αPGL-I test. To our knowledge, this is the first study that compared αPGL-I IgM levels in fingerstick blood with the bacterial load determined by RLEP-qPCR in skin biopsies of leprosy patients. The demonstrated potential of minimally invasive sampling such as fingerstick blood samples to identify high bacterial load persons likely to be accountable for the ongoing transmission, merits further evaluation in follow-up studies. Author summary Leprosy is the oldest infectious disease known to humankind. We still do not succeed in curbing its transmission, with more than 200,000 new patients detected worldwide each year. Identifying persons with a high burden of bacteria is key to curb transmission. To identify these persons, bacteria are counted in invasive and painful samples like slit skin smears and skin biopsies. We evaluated whether we can use less invasive samples, like fingerstick blood or nasal swabs, to determine the bacterial load. We found that the level of antibodies against M. leprae (αPGL-I IgM) in fingerstick blood correlates well with the bacterial load determined in skin biopsies from the same leprosy patient. Therefore, a high level of antibodies against M. leprae in fingerstick blood might identify persons who pose a potential risk for transmission of leprosy and could be prioritized for contact screening, which is essential for control of the disease.