Within-Host Heterogeneity of Mycobacterium Tuberculosis Infection is Associated with Poor Early Treatment Response: a Prospective Cohort Study

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coinfection, HIV/TB, mixed infection, tuberculosis, within-host heterogeneity

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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).

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Journal of Infectious Diseases, v. 213, issue 11, p. 1796-1799