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

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 MTBDR^TMplus and MTBDR^TMsl.

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.

Fig. 1.

Maximum likelihood phylogenetic tree based on single nucleotide polymorphisms obtained from whole genome sequencing of M. tuberculosis complex (MTBC) strains from Beira, Mozambique. Representatives of each MTBC lineage (L1 to L7) were included in the phylogenetic analyses.