Insights into the genetic diversity of Mycobacterium tuberculosis in Tanzania

PLoS One. 2019 Apr 12;14(4):e0206334. doi: 10.1371/journal.pone.0206334. eCollection 2019.

Abstract

Background: Human tuberculosis (TB) is caused by seven phylogenetic lineages of the Mycobacterium tuberculosis complex (MTBC), Lineage 1-7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, strain variation in the MTBC influences the outcome of TB infection and disease. In Tanzania, such molecular epidemiological studies of TB however are scarce in spite of a high TB burden.

Methods and findings: Here we used SNP-typing to characterize a nationwide collection of 2,039 MTBC clinical isolates representative of 1.6% of all new and retreatment TB cases notified in Tanzania during 2012 and 2013. Four lineages, namely Lineage 1-4 were identified within the study population. The distribution and frequency of these lineages varied across regions but overall, Lineage 4 was the most frequent (n = 866, 42.5%), followed by Lineage 3 (n = 681, 33.4%) and 1 (n = 336, 16.5%), with Lineage 2 being the least frequent (n = 92, 4.5%). We found Lineage 2 to be independently associated with female sex (adjusted odds ratio [aOR] 2.14; 95% confidence interval [95% CI] 1.31 - 3.50, p = 0.002) and retreatment cases (aOR 1.67; 95% CI 0.95 - 2.84, p = 0. 065) in the study population. We found no associations between MTBC lineage and patient age or HIV status. Our sublineage typing based on spacer oligotyping on a subset of Lineage 1, 3 and 4 strains revealed the presence of mainly EAI, CAS and LAM families. Finally, we detected low levels of multidrug resistant isolates among a subset of 144 retreatment cases.

Conclusions: This study provides novel insights into the MTBC lineages and the possible influence of pathogen-related factors on the TB epidemic in Tanzania.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / genetics*
  • Phylogeny*
  • Polymorphism, Single Nucleotide*
  • Tanzania / epidemiology
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / genetics*
  • Tuberculosis, Pulmonary / microbiology

Grants and funding

This work was supported by the Swiss National Science Foundation (grants 310030_166687, IZRJZ3_164171, IZLSZ3_170834 and CRSII5_177163 to SG; http://www.snf.ch), the European Research Council (309540-EVODRTB to SG; https://erc.europa.eu) and SystemsX.ch (http://www.systemsx.ch to SG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.