Socio-economic, clinical, and behavioral factors associated with study retention among tuberculosis patients in Botswana

Background: Molecular epidemiology has revolutionized the understanding of Mycobacterium tuberculosis (MTB) transmission. Such studies require culture-based genotyping results from the majority of the study population to generate valid inferences. The present investigation aims to describe factors that influence confirmatory culture results within The Kopanyo Study, a large molecular epidemiological study of MTB in Botswana. Methods: We performed liquid culture for MTB confirmation and isolation among patients initially diagnosed with TB in routine clinical practice.Multiple sputumsampleswere collectedper patient to account for variability in sputum production and contaminated samples. Data were gathered via chart review from 29 clinics in Botswana for patients enrolled between September 1st 2012 and August 31st 2013. Generalized estimating equation (GEE) logistic regressionmodelingwas used todetermine factors associated with MTB culture positivity while accounting for multiple samples collected for each patient. This research was approved by the Ethics Committees and Independent Review Boards at the University of Pennsylvania, Centers for Disease Control and Prevention, Botswana Ministry ofHealth,University of Botswana andPrincessMarinaHospital. All study participants provided informed consent. Findings: A total of 1,338 samples collected from 574 TB patients were included in the analysis. Overall, 435 (75.8%) patients had at least one MTB positive culture. Among HIV-infected patients 197/ 278 (70.9%) were culture positive, whereas among HIV-uninfected patients 156/186 (83.9%) were culture positive (p < 0.01). The median time between diagnosis and initiation of culture was four days (interquartile rage 2 6). Among mucopurulent and salivary (clear, mucoid, blood-stained or salivary) samples, 554/738 (75.1%) and 336/548 (61.3%) were culture positive, respectively (p < 0.01). In patients who underwent sputum induction via respiratory methods or gastric aspiration 89/193 (46.1%) were culture positive, while 438/ 596 (73.5%) who voluntarily expectorated sputum were culture positive (p < 0.01). In multivariate analysis, HIV-infection (OR1⁄40.53 95% CI 1⁄4 0.32 e 0.88), age (21-30 years vs. Interpretation: We found that age 21-30 years, HIV-infection, and sputum collection method are factors that must be taken into consideration in studies using MTB isolation. Improved methods of MTB culture detection are necessary for HIV co-infected populations and others with low levels of bacilli in the sputum. Funding: This research has been supported by the David Geffen School of Medicine at UCLA, the UCLA Center for World Health, National Institutes of Health grants R01AI097045, T32MH080634, P30AI45008 (Penn Center for AIDS Research), MH58107 (UCLA Center for HIV Identification, Prevention, and Treatment), 5P30AI028697 (UCLA Center for AIDS Research), and UL1TR000124 (National Center for Advancing Translational Sciences). NIH had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not represent official views of the NIH. Abstract #: 02CD003