Within-Host Heterogeneity of Mycobacterium tuberculosis Infection Is Associated With Poor Early Treatment Response: A Prospective Cohort Study

J Infect Dis. 2016 Jun 1;213(11):1796-9. doi: 10.1093/infdis/jiw014. Epub 2016 Jan 14.


The clinical management of tuberculosis is a major challenge in southern Africa. The prevalence of within-host genetically heterogeneous Mycobacterium tuberculosis infection and its effect on treatment response are not well understood. We enrolled 500 patients with tuberculosis in KwaZulu-Natal and followed them through 2 months of treatment. Using mycobacterial interspersed repetitive units-variable number of tandem repeats genotyping to identify mycobacterial heterogeneity, we report the prevalence and evaluate the association of heterogeneity with treatment response. Upon initiation of treatment, 21.1% of participants harbored a heterogeneous M. tuberculosis infection; such heterogeneity was independently associated with a nearly 2-fold higher odds of persistent culture positivity after 2 months of treatment (adjusted odds ratio, 1.90; 95% confidence interval, 1.03-3.50).

Keywords: HIV/TB; coinfection; mixed infection; tuberculosis; within-host heterogeneity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antitubercular Agents / therapeutic use*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Genetic Heterogeneity*
  • HIV Infections / complications
  • Humans
  • Male
  • Mycobacterium tuberculosis / genetics*
  • Prospective Studies
  • South Africa
  • Sputum / microbiology
  • Time-to-Treatment
  • Tuberculosis, Pulmonary / complications
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / microbiology*


  • Antitubercular Agents