Influence of M. tuberculosis lineage variability within a clinical trial for pulmonary tuberculosis.
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.
Nahid
Payam
P
Division of Pulmonary and Critical Care Medicine, Francis J. Curry National Tuberculosis Center, San Francisco General Hospital, University of California San Francisco, San Francisco, California, USA. pnahid@ucsf.edu
Bliven
Erin E
EE
Kim
Elizabeth Y
EY
Mac Kenzie
William R
WR
Stout
Jason E
JE
Diem
Lois
L
Johnson
John L
JL
Gagneux
Sebastien
S
Hopewell
Philip C
PC
Kato-Maeda
Midori
M
D000465:Algorithms; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000382:microbiology*