ABSTRACT
Recent studies suggest that M. tuberculosis lineage and host genetics interact to impact how active tuberculosis presents clinically. We determined the phylogenetic lineages of M. tuberculosis isolates from participants enrolled in the Tuberculosis Trials Consortium Study 28, conducted in Brazil, Canada, South Africa, Spain, Uganda and the United States, and secondarily explored the relationship between lineage, clinical presentation and response to treatment. Large sequence polymorphisms and single nucleotide polymorphisms were analyzed to determine lineage and sublineage of isolates. Of 306 isolates genotyped, 246 (80.4%) belonged to the Euro-American lineage, with sublineage 724 predominating at African sites (99/192, 51.5%), and the Euro-American strains other than 724 predominating at non-African sites (89/114, 78.1%). Uneven distribution of lineages across regions limited our ability to discern significant associations, nonetheless, in univariate analyses, Euro-American sublineage 724 was associated with more severe disease at baseline, and along with the East Asian lineage was associated with lower bacteriologic conversion after 8 weeks of treatment. Disease presentation and response to drug treatment varied by lineage, but these associations were no longer statistically significant after adjustment for other variables associated with week-8 culture status.
Subject(s)
Mycobacterium tuberculosis/genetics , Phylogeny , Randomized Controlled Trials as Topic , Tuberculosis, Pulmonary/microbiology , Algorithms , Humans , Mycobacterium tuberculosis/isolation & purification , Risk FactorsABSTRACT
The role of microbial factors in outcomes of tuberculosis treatment has not been well studied. We performed a case-control study to evaluate the association between a Beijing strain and tuberculosis treatment outcomes. Isolates from patients with culture-positive treatment failure (n = 8) or relapse (n = 54) were compared with isolates from randomly selected controls (n = 296) by using spoligotyping. Patients with Beijing strains had a higher risk for relapse (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.0-4.0, p = 0.04) but not for treatment failure. Adjustment for factors previously associated with relapse had little effect on the association between Beijing strains and relapse. Beijing strains were strongly associated with relapse among Asian-Pacific Islanders (OR 11, 95% CI 1.1-108, p = 0.04). Active disease caused by a Beijing strain was associated with increased risk for relapse, particularly among Asian-Pacific Islanders.
Subject(s)
Antibiotics, Antitubercular/therapeutic use , Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/genetics , Rifampin/analogs & derivatives , Tuberculosis, Pulmonary/genetics , Tuberculosis/genetics , Asian People/statistics & numerical data , Case-Control Studies , China , HIV Infections/complications , Humans , Mycobacterium tuberculosis/isolation & purification , Recurrence , Rifampin/therapeutic use , Risk Factors , Treatment Failure , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis/microbiology , Tuberculosis, Pulmonary/drug therapyABSTRACT
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