Influence of M. tuberculosis lineage variability within a clinical trial for pulmonary tuberculosis.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Nahid, P; Bliven, EE; Kim, EY; Mac Kenzie, WR; Stout, JE; Diem, L; Johnson, JL; Gagneux, S; Hopewell, PC; Kato-Maeda, M; Tuberculosis Trials Consortium,

Published Date

  • May 20, 2010

Published In

Volume / Issue

  • 5 / 5

Start / End Page

  • e10753 -

PubMed ID

  • 20505778

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0010753

Language

  • eng

Conference Location

  • United States