Increased transmission of Mycobacterium tuberculosis Beijing genotype strains associated with resistance to streptomycin: a population-based study

PLoS One. 2012;7(8):e42323. doi: 10.1371/journal.pone.0042323. Epub 2012 Aug 13.

Abstract

Background: Studies have shown that the Mycobacterium tuberculosis Beijing genotype is an emerging pathogen that is frequently associated with drug resistance. This suggests that drug resistant Beijing strains have a relatively high transmission fitness compared to other drug-resistant strains.

Methods and findings: We studied the relative transmission fitness of the Beijing genotype in relation to anti-tuberculosis drug resistance in a population-based study of smear-positive tuberculosis patients prospectively recruited and studied over a 4-year period in rural Vietnam. Transmission fitness was analyzed by clustering of cases on basis of three DNA typing methods. Of 2531 included patients, 2207 (87%) were eligible for analysis of whom 936 (42%) were in a DNA fingerprint cluster. The clustering rate varied by genotype with 292/786 (37%) for the Beijing genotype, 527/802 (67%) for the East-African Indian (EAI) genotype, and 117/619 (19%) for other genotypes. Clustering was associated with the EAI compared to the Beijing genotype (adjusted odds ratio (OR(adj)) 3.4: 95% CI 2.8-4.4). Patients infected with streptomycin-resistant strains were less frequently clustered than patients infected with streptomycin-susceptible strains when these were of the EAI genotype (OR(adj) 0.6, 95% CI 0.4-0.9), while this pattern was reversed for strains of the Beijing genotype (OR(adj) 1.3, 95% CI 1.0-1.8, p for difference 0.002). The strong association between Beijing and MDR-TB (OR(adj) 7.2; 95% CI 4.2-12.3) existed only if streptomycin resistance was present.

Conclusions: Beijing genotype strains showed less overall transmissibility than EAI strains, but when comparisons were made within genotypes, Beijing strains showed increased transmission fitness when streptomycin-resistant, while the reverse was observed for EAI strains. The association between MDR-TB and Beijing genotype in this population was strongly dependent on resistance to streptomycin. Streptomycin resistance may provide Beijing strains with a fitness advantage over other genotypes and predispose to multidrug resistance in patients infected with Beijing strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cluster Analysis
  • DNA Fingerprinting
  • DNA, Bacterial / analysis
  • DNA, Bacterial / genetics
  • Drug Resistance, Bacterial / drug effects
  • Drug Resistance, Bacterial / genetics*
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Multiple / genetics
  • Female
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / physiology
  • Risk Factors
  • Rural Population / statistics & numerical data
  • Streptomycin / pharmacology*
  • Tuberculosis, Pulmonary / transmission*
  • Young Adult

Substances

  • DNA, Bacterial
  • Streptomycin

Grants and funding

Financial support for this study was provided by KNCV Tuberculosis Foundation, the Medical Committee Netherlands-Vietnam, the World Health Organization and the TBadapt project (037919). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.