Abstract
Acid Fast Bacilli (AFB) microscopy smear remains the most widely used laboratory diagnostic technique for Pulmonary Tuberculosis (PTB) in low-and-middle income countries. Although it is highly specific, the sensitivity varies between 20–80% in immune-competent people, with only 50% case detection among HIV/TB co-infected patients, hence the need to determine the diagnostic accuracy of Th1 and Th2 cytokine response in AFB microscopy smear negative PTB-HIV co-infected patients. A total of 86 participants were recruited; 70 (81.4%) AFB microscopy smear negative and 16 (18.6%) AFB microscopy smear positive. The AFB microscopy smear negative samples were then cultured using Lowenstein Jensen Medium with 46 being culture-negative and 24 being culture-positive. Blood samples were also collected, cultured using QFT-GIT and the supernatant (plasma) harvested to evaluate cytokine profiles using Enzyme-Linked Immunosorbent Assay. IFN-γ (P < 0.001), TNF-α (P = 0.004), IL-2 (P = 0.004) and IL-4 (P = 0.009) median levels were elevated in PTB culture-positive (AFB microscopy smear negative) as compared to PTB culture-negative (AFB microscopy smear negative) participants. Finally, when Th1 cytokines (IFN-γ, TNF-α and IL-2), Th2 cytokines (IL-6 and IL-10) and T cells were included in the logistic regression fit for PTB outcome, the predictive power of discriminating between those who were AFB smear negative in the diagnosis of PTB was good with cross validated area under the curve (AUC) being 0.87 (95% CI: 0.78, 0.96). This study provides evidence for the ability of Th1 and Th2 cytokines to determine PTB status in AFB microscopy smear negative patients co-infected with HIV.
Highlights
Tuberculosis (TB) is among the main HIV and AIDS defining illnesses[1]
We have identified a combination of multiple cytokines, both Th1 (IFN-γ, TNF-α & IL-2) and Th2 (IL-6, and Il-10) that could discriminate between culture-positive acid-fast bacilli (AFB) smear negative and culture-negative AFB smear negative
It is important to note that culture-negative AFB smear negative individual who have low production of cytokines in response to Mycobacterium tuberculosis-specific antigens might be infected potentially by another disease and not pulmonary tuberculosis (PTB)
Summary
Tuberculosis (TB) is among the main HIV and AIDS defining illnesses[1]. In 2016 there were an estimated 10.4 million new cases of TB worldwide, with 1.2 million people living with HIV developing TB. AFB microscopy smear is the most widely used laboratory technique for pulmonary tuberculosis (PTB) diagnosis in low to middle income countries, such as Kenya. It is highly specific, its sensitivity has been found to vary between 20% and 80%4. This conventional AFB staining method accounts for only 50% case detection among HIV/TB co-infected patients. Sputum samples should be examined even if the chest radiograph appears normal This is because pulmonary cavitations are less common in HIV-positive patients, leading to significantly reduced sensitivity of sputum microscopy for AFB. It is necessary to further examine the sputum samples as culture still remains the mainstay of diagnosis in our setup, with limitation of being very expensive and taking a longer period to get results
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