Phylogenomic assessment of drug-resistant Mycobacterium tuberculosis strains from Beira, Mozambique

Tuberculosis (Edinb). 2020 Mar:121:101905. doi: 10.1016/j.tube.2020.101905. Epub 2020 Jan 29.

Abstract

Background: Mozambique is a high-burden tuberculosis (TB) country where TB/HIV co-infection and drug resistant TB (DR-TB) incidence is increasing. Whole genome sequencing (WGS) comprehensively describes the molecular epidemiology of TB, allows prediction of DR-TB phenotypes, lineages strains identification and better understanding of transmission chains.

Objective: To describe genetic diversity of DR-TB Mycobacterium tuberculosis isolated in Beira, Mozambique.

Methods: Descriptive cross-sectional study with 35 M. tuberculosis isolates, resistant to at least one first-line drug on molecular drug-susceptibility tests (DST). Variant identification, DR prediction and phylogenetic analysis provided by WGS, drug-susceptibility pattern compared to line-probe assay (LPA): Genotype MTBDRTMplus and MTBDRTMsl.

Findings: Lineage 4 (L4) was the most prevalent: 25 (71.4%) isolates; 5 (14.3%) L1 and 5 (14.3%) L2. WGS showed 33/35 (94.3%) isolates resistant to at least one drug, two pan-susceptible isolates that were previously diagnosed as DR-TB with genotype MTBDRplus. Concordance between WGS and LPA: 88.6% for isoniazid (INH), 85.7% to rifampicin (RPM), 91.4% for quinolones and 100% to second line injectable drugs. There were three possible TB transmission chains, 10 strains showing recent transmission.

Conclusion: WGS provided reliable information about the most frequent lineages related to DR-TB in Beira, Mozambique: L4.3 (LAM), L2 (Beijing) and L1 (EAI) and possible recent transmission chain.

Keywords: Drug-resistant; Mozambique; Mycobacterium tuberculosis; Phylogeny; Whole genome sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / therapeutic use
  • Cross-Sectional Studies
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Genotype
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Epidemiology
  • Mozambique / epidemiology
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Phenotype
  • Phylogeny
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / microbiology*
  • Tuberculosis, Multidrug-Resistant / transmission
  • Whole Genome Sequencing

Substances

  • Antitubercular Agents