Dataset Information

Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali.

ABSTRACT: OBJECTIVE:Ancestral M. tuberculosis complex lineages such as M. africanum are underrepresented among retreatment patients and those with drug resistance. To test the hypothesis that they respond faster to TB treatment, we determined the rate of smear conversion of new pulmonary tuberculosis patients in Bamako, Mali by the main MTBc lineages. METHODS:Between 2015 and 2017, we conducted a prospective cohort study of new smear positive pulmonary tuberculosis patients in Bamako. Confirmed MTBc isolates underwent genotyping by spoligotyping for lineage classification. Patients were followed at 1 month (M), 2M and 5M to measure smear conversion in auramine (AR) and Fluorescein DiAcetate (FDA) vital stain microscopy. RESULT:All the first six human MTBc lineages were represented in the population, plus M. bovis in 0.8% of the patients. The most widely represented lineage was the modern Euro-American lineage (L) 4, 57%, predominantly the T family, followed by L6 (M. africanum type 2) in 22.9%. Ancestral lineages 1, 5, 6 and M. bovis combined amounted to 28.8%. Excluding 25 patients with rifampicin resistance, smear conversion, both by AR and FDA, occurred later in L6 compared to L4 (HR 0.80 (95% CI 0.66-0.97) for AR, and HR 0.81 (95%CI 0.68-0.97) for FDA). In addition we found that HIV negative status, higher BMI at day 0, and patients with smear grade at baseline ? 1+ were associated with earlier smear conversion. CONCLUSION:The six major human lineages of the MTBc all circulate in Bamako. Counter to our hypothesis, we found that patients diseased with modern M. tuberculosis complex L4 respond faster to TB treatment than those with M. africanum L6.

SUBMITTER: Diarra B

PROVIDER: S-EPMC6291124 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali.

Diarra Bassirou B Kone Mahamadou M Togo Antieme Combo Georges ACG Sarro Yeya Dit Sadio YDS Cisse Aissata Boubakar AB Somboro Amadou A Degoga Boureima B Tolofoudie Mohamed M Kone Bourahima B Sanogo Moumine M Baya Bocar B Kodio Ousmane O Maiga Mamoudou M Belson Michael M Orsega Susan S Krit Meryam M Dao Sounkalo S Maiga Ibrahim Izétiegouma II Murphy Robert L RL Rigouts Leen L Doumbia Seydou S Diallo Souleymane S de Jong Bouke Catherine BC

PloS one 20181212 12

<h4>Objective</h4>Ancestral M. tuberculosis complex lineages such as M. africanum are underrepresented among retreatment patients and those with drug resistance. To test the hypothesis that they respond faster to TB treatment, we determined the rate of smear conversion of new pulmonary tuberculosis patients in Bamako, Mali by the main MTBc lineages.<h4>Methods</h4>Between 2015 and 2017, we conducted a prospective cohort study of new smear positive pulmonary tuberculosis patients in Bamako. Confi ...[more]

PMID: 30540823

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Project description:Tuberculosis remains a major global health problem. Laboratory diagnostic methods that allow effective, early detection of cases are central to management of tuberculosis in the individual patient and in the community. Since the 1880s, laboratory diagnosis of tuberculosis has relied primarily on microscopy and culture. However, microscopy fails to provide species- or lineage-level identification and culture-based workflows for diagnosis of tuberculosis remain complex, expensive, slow, technically demanding and poorly able to handle mixed infections. We therefore explored the potential of shotgun metagenomics, sequencing of DNA from samples without culture or target-specific amplification or capture, to detect and characterise strains from the Mycobacterium tuberculosis complex in smear-positive sputum samples obtained from The Gambia in West Africa. Eight smear- and culture-positive sputum samples were investigated using a differential-lysis protocol followed by a kit-based DNA extraction method, with sequencing performed on a benchtop sequencing instrument, the Illumina MiSeq. The number of sequence reads in each sputum-derived metagenome ranged from 989,442 to 2,818,238. The proportion of reads in each metagenome mapping against the human genome ranged from 20% to 99%. We were able to detect sequences from the M. tuberculosis complex in all eight samples, with coverage of the H37Rv reference genome ranging from 0.002X to 0.7X. By analysing the distribution of large sequence polymorphisms (deletions and the locations of the insertion element IS6110) and single nucleotide polymorphisms (SNPs), we were able to assign seven of eight metagenome-derived genomes to a species and lineage within the M. tuberculosis complex. Two metagenome-derived mycobacterial genomes were assigned to M. africanum, a species largely confined to West Africa; the others that could be assigned belonged to lineages T, H or LAM within the clade of "modern" M. tuberculosis strains. We have provided proof of principle that shotgun metagenomics can be used to detect and characterise M. tuberculosis sequences from sputum samples without culture or target-specific amplification or capture, using an accessible benchtop-sequencing platform, the Illumina MiSeq, and relatively simple DNA extraction, sequencing and bioinformatics protocols. In our hands, sputum metagenomics does not yet deliver sufficient depth of coverage to allow sequence-based sensitivity testing; it remains to be determined whether improvements in DNA extraction protocols alone can deliver this or whether culture, capture or amplification steps will be required. Nonetheless, we can foresee a tipping point when a unified automated metagenomics-based workflow might start to compete with the plethora of methods currently in use in the diagnostic microbiology laboratory.

Dataset Information

Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali.

Publications

Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali.

Similar Datasets

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