Genotyping comparison of<i>Mycobacterium leprae</i>isolates by VNTR analysis from nasal samples in a Brazilian endemic region

Lima, Luana Nepomueceno Costa; Frota, Cristiane Cunha; Suffys, Phillip Noel; Fontes, Amanda Nogueira Brum; Mota, Rosa Maria Salani; Almeida, Rosa Lívia Freitas de; Pontes, Maria Araci de Andrade; Gonçalves, Heitor de Sá; Kendall, Carl; Kerr, Lígia Regina Franco Sansigolo

doi:10.1080/20477724.2018.1427308

Cited by 4 publications

(8 citation statements)

References 28 publications

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“…However, the importance of genotyping NS as well as skin biopsies or SSS to better understand transmission has been previously discussed (69), as the nasal respiratory route remains one of the most plausible modes of infection (12,13). In a recent study, skin biopsies and NS of patients were compared by VNTR typing and the authors found that out of 38 patients, differences between SSS and NS in seven loci were observed in 33 patients (70). Although the M. leprae genomes from SSS and NS analysed in our study were almost identical, we observed that genomes obtained from NS harboured more mutations, especially in previously reported (29) hypermutated genes.…”

Section: Discussioncontrasting

confidence: 46%

Detection of new Mycobacterium leprae subtype in Bangladesh by genomic characterization to explore transmission patterns

Tió-Coma

Avanzi

Verhard

et al. 2020

Preprint

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Mycobacterium leprae, the causative agent of leprosy, is an unculturable bacterium with a considerably reduced genome (3.27 Mb) compared to homologues mycobacteria from the same ancestry. M. leprae transmission is suggested to occur through aerosols but the exact mechanisms of infection remains unclear. In 2001, the genome of M. leprae was first described and subsequently four genotypes (1-4) and 16 subtypes (A-P) were identified providing means to study global transmission patterns for leprosy. We investigated M. leprae carriage as well as infection in leprosy patients (n=60) and healthy household contacts (HHC; n=250) from Bangladesh using molecular detection of the bacterial element RLEP in nasal swabs (NS) and slit skin smears (SSS). In parallel, we explored bacterial strain diversity by whole-genome sequencing (WGS) and Sanger sequencing. In the studied cohort in Bangladesh, M. leprae DNA was detected in 33.3% of NS and 22.2% of SSS of patients with bacillary index of 0 whilst in HHC 18.0% of NS and 12.3% of SSS were positive. The majority of the M. leprae strains detected in this study belonged to genotype 1D (55%), followed by 1A (31%). Importantly, WGS allowed the identification of a new M. leprae genotype, designated 1B-Bangladesh (14%), which clustered separately between the 1A and 1B strains. Moreover, we established that the genotype previously designated 1C, is not an independent subtype but clusters within the 1D genotype. Intraindividual differences were present between the M. leprae strains obtained including mutations in hypermutated genes, suggesting mixed colonization/infection or in-host evolution. In summary, we observed that M. leprae is present in asymptomatic contacts of leprosy patients fueling the concept that these individuals contribute to the current intensity of transmission. Our data therefore emphasize the importance of sensitive and specific tools allowing post-exposure prophylaxis targeted at M. leprae-infected or -colonized individuals.

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Section: Discussioncontrasting

confidence: 46%

Detection of new Mycobacterium leprae subtype in Bangladesh by genomic characterization to explore transmission patterns

Tió-Coma

Avanzi

Verhard

et al. 2020

Preprint

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“…Among 38 patients, MLVA patterns were also available from nasal swabs, with the exclusion of alleles 6–3 and 18–8, not performed in this sample type and as described recently, difference in copy number of the alleles with highest DI was observed in the M . leprae genotypes when comparing both samples in a considerable number of patients [ 43 ]. Upon inclusion of the genotypes of M .…”

Section: Resultsmentioning

confidence: 99%

“…leprae genotypes present in skin biopsy and nasal secretion is described and discussed in detail elsewhere [ 43 ]. While all isolates presently presented four copies of (GGT)5, one nasal swab sample presented six copies of this allele [ 43 ] and although other alleles than that of four copies are described with very low frequency in Brazil [ 16 ], they are more frequent in countries like Thailand [ 27 ] and the Philippines [ 25 ]. Contrary to the single allele with two copies of 23–3 described by Lima et al [ 43 ], in 8% of our patients, a single copy of this marker was observed.…”

Section: Discussionmentioning

confidence: 99%

“…While all isolates presently presented four copies of (GGT)5, one nasal swab sample presented six copies of this allele [ 43 ] and although other alleles than that of four copies are described with very low frequency in Brazil [ 16 ], they are more frequent in countries like Thailand [ 27 ] and the Philippines [ 25 ]. Contrary to the single allele with two copies of 23–3 described by Lima et al [ 43 ], in 8% of our patients, a single copy of this marker was observed. A further finding by Lima et al was the observation that some individuals presented differences in copy number in five to seven loci, including less variable ones, being highly suggestive for multiple infection or more extensive intra-patient strain evolution.…”

Section: Discussionmentioning

confidence: 99%

“…leprae genotyping, including China [ 17 ], Thailand [ 27 ], Colombia [ 31 ] and India [ 24 ]. Although investigation of HHC is part of the leprosy program in Brazil, this is not always being performed and in Fortaleza in particular, this seems to be the case in about 50% of the patients [ 43 ]. The lack of association between clustering and house hold in the present study is probably due to the inclusion of new patients only and without contact investigation and inclusion of patients from the same house hold.…”

Section: Discussionmentioning

confidence: 99%

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Genotyping of Mycobacterium leprae for better understanding of leprosy transmission in Fortaleza, Northeastern Brazil

Fontes¹,

Lima²,

Mota

et al. 2017

PLoS Negl Trop Dis

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Leprosy is endemic in large part of Brazil with 28,761 new patients in 2015, the second largest number worldwide and reaches 9/10.000 in highly endemic regions and 2.7/10.000 in the city of Fortaleza, Ceará, Northeast Brazil. For better understanding of risk factors for leprosy transmission, we conducted an epidemiologic study supplemented by 17 locus VNTR and SNP 1–4 typing of Mycobacterium leprae in skin biopsy samples from new multibacillary (MB) patients diagnosed at a reference center in 2009 and 2010. Among the 1,519 new patients detected during the study period, 998 (65.7%) were MB and we performed DNA extraction and genotyping on 160 skin biopsy samples, resulting in 159 (16%) good multilocus VNTR types. Thirty-eight of these patients also provided VNTR types from M. leprae in nasal swabs. The SNP-Type was obtained for 157 patients and 87% were of type 4. Upon consideration all VNTR markers, 156 different genotypes and three pairs with identical genotypes were observed; no epidemiologic relation could be observed between individuals in these pairs. Considerable variability in differentiating index (DI) was observed between the different markers and the four with highest DI [(AT)15, (TA)18, (AT)17 and (GAA)21] frequently demonstrated differences in copy number when comparing genotypes from both type of samples. Excluding these markers from analysis resulted in 83 genotypes, 20 of which included 96 of the patients (60.3%). These clusters were composed of two (n = 8), three (n = 6), four (n = 1), five (n = 2), six (n = 1), 19 (n = 1) and 23 (n = 23) individuals and suggests that recent transmission is contributing to the maintenance of leprosy in Fortaleza. When comparing epidemiological and clinical variables among patients within clustered or with unique M. leprae genotypes, a positive bacterial index in skin biopsies and knowledge of working with someone with the disease were significantly associated with clustering. A tendency to belong to a cluster was observed with later notification of disease (mean value of 3.4 months) and having disability grade 2. A tendency for lack of clustering was observed for patients who reported to have lived with another leprosy case but this might be due to lack of inclusion of household contacts in the study. Although clusters were spread over the city, kernel analysis revealed that some of the patients belonging to the two major clusters were spatially related to some neighborhoods that report poverty and high disease incidence in children. Finally, inclusion of genotypes from nasal swabs might be warranted. A major limitation of the study is that sample size of 160 patients from a two year period represents only 15% of the new patients and this could have weakened statistical outcomes. This is the first molecular epidemiology study of leprosy in Brazil and although the high clustering level suggests that recent transmission is the major cause of disease in Fortaleza; the existence of two large clusters needs further investigation.

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Hi-plex deep amplicon sequencing for identification, high-resolution genotyping and multidrug resistance prediction of Mycobacterium leprae directly from patient biopsies by using Deeplex Myc-Lep

Jouet,

Braet,

Gaudin

et al. 2023

eBioMedicine

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Genotyping comparison ofMycobacterium lepraeisolates by VNTR analysis from nasal samples in a Brazilian endemic region

Cited by 4 publications

References 28 publications

Detection of new Mycobacterium leprae subtype in Bangladesh by genomic characterization to explore transmission patterns

Detection of new Mycobacterium leprae subtype in Bangladesh by genomic characterization to explore transmission patterns

Genotyping of Mycobacterium leprae for better understanding of leprosy transmission in Fortaleza, Northeastern Brazil

Hi-plex deep amplicon sequencing for identification, high-resolution genotyping and multidrug resistance prediction of Mycobacterium leprae directly from patient biopsies by using Deeplex Myc-Lep

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