title: Within-Host Heterogeneity of Mycobacterium tuberculosis Infection Is Associated With Poor Early Treatment Response: A Prospective Cohort Study.
abstract: 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).
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Ted
authors.initials: T
authors.lastname: Cohen
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Leonid
authors.initials: L
authors.lastname: Chindelevitch
authors.affiliation: Infection Prevention and Control, University of KwaZulu-Natal, Durban.
authors.forename: Reshma
authors.initials: R
authors.lastname: Misra
authors.affiliation: Brigham and Women's Hospital.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Kempner
authors.affiliation: Partners in Health, Boston, Massachusetts.
authors.forename: Jerome
authors.initials: J
authors.lastname: Galea
authors.affiliation: Infection Prevention and Control, University of KwaZulu-Natal, Durban.
authors.forename: Prashini
authors.initials: P
authors.lastname: Moodley
authors.affiliation: Department of Internal Medicine, Edendale Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa.
authors.forename: Douglas
authors.initials: D
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D018740:Genetic Heterogeneity; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D011446:Prospective Studies; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D061665:Time-to-Treatment; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents
keywords: HIV/TB; coinfection; mixed infection; tuberculosis; within-host heterogeneity