Influence of M. tuberculosis lineage variability within a clinical trial for pulmonary tuberculosis
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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.
Published Version (Please cite this version)10.1371/journal.pone.0010753
Publication InfoBliven, EE; Diem, L; Gagneux, S; Hopewell, PC; Johnson, JL; Kato-Maeda, M; ... Stout, Jason Eric (2010). Influence of M. tuberculosis lineage variability within a clinical trial for pulmonary tuberculosis. PLoS ONE, 5(5). pp. e10753. 10.1371/journal.pone.0010753. Retrieved from https://hdl.handle.net/10161/4542.
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Professor of Medicine
My research focuses on the epidemiology, natural history, and treatment of tuberculosis and nontuberculous mycobacterial infections. I am also interested in the impact of HIV infection on mycobacterial infection and disease, and in examining health disparities as they relate to infectious diseases, particularly in immigrant populations.