Abstract:
Introduction: The interaction between Mycobacterium tuberculosis and HIV leads to rapid progression of tuberculosis (TB) and human
immunodeficiency virus (HIV)-induced immunosuppression. Diagnosis of TB in these patients is more difficult due to its atypical presentations
giving contradicting results. The overall aim of this study was to evaluate the ability of pro-inflammatory cytokine (Th1) and anti-inflammatory
cytokine (Th2) to discriminate between culture-positive and -negative smear status in HIV-TB co-infected patients. Methods: In a prospective
cohort, a total of 86 study participants were recruited: 46 culture-negative and 40 culture-positive. Blood and sputum samples were collected from
all participants. The blood was then analyzed using FACSCalibur flow cytometer to immunophenotype the cells and ELISA performed for cytokine
profiles. Sputum samples were analyzed to determine smear status using direct microscopy and Lowenstein Jensen medium. Statistical analyses
were performed using R software. Independent samples t-test was used to compare means between the two groups, while the medians were
compared using two-sample Wilcoxon rank sum test. Pearson's Chi-square test was used to compare the proportion of male and female
participants across the culture and AFB smear status. In order to determine the predictive power of Th1 and Th2 in discriminating Pulmonary
Tuberculosis status (PTB) (culture status was used as a confirmatory test), binary logistic regression models were fitted for Th1 covariates [IFN-γ,
TNF-α, IL-2 and IL-12(p70)] and Receiver Operating Characteristic (ROC) curves plotted. Results: The overall mean age of the participants was
39 years (SD=12), 42% being male. Although, lymphocytes counts were higher in culture-positive relative to culture-negative, the CD8, CD19, and
CD16/CD56 were comparable in the two groups. The CD4 counts differed between the two groups (P=0.012). The Th1 showed a better
discrimination between culture-positive and -negative PTB individuals; IFN-γ (P=0.001), TNF-α (P=0.001), IL-2 (P=0.001) and IL-12(p70)
(P=0.016). The Th2 cytokines (IL-4, IL-6 and IL-10) were comparable between the culture-positive and -negative groups. However, when the
combination of Th1 cytokines [IFN-γ, TNF-α, IL-2 and IL-12(p70)] was fitted in binary logistic regression models, the predictive power was high
with area under curve (AUC) being 89.7% in discriminating PTB. Conclusion: This study provides evidence for the ability of a combination of Th1
cytokines in discriminating against culture-positive and culture-negative PTB.
