Elevated neopterin in tuberculosis and co-infection with HIV and the effect of treatment: A systematic review, meta-analysis, and meta-regression

Abstract

BackgroundNeopterin (NEO) is a marker of immune stimulation. Increased NEO levels have been associated with autoimmune diseases, infections, and malignancies. Studies of NEO alterations in tuberculosis (TB) with or without HIV co-infection show inconsistent results. Moreover, challenges exist regarding TB diagnosis in people with HIV. MethodsWe did a systematic review and meta-analysis of studies comparing urinary, pleural, and blood NEO levels between patients with TB or HIV-TB co-infection as the case group and subjects without TB and HIV or subjects with HIV without TB as the control group, respectively. ResultsBlood NEO levels in patients with active TB were higher than healthy controls, with a large effect size of 1.99. Patients with TB had higher blood NEO levels before anti-tuberculosis therapy (ATT) than after ATT for months or when treatment ended with moderate effect sizes (1.13–1.46). meta-analysis of studies of patients with HIV-TB co-infection yielded similar results, with higher blood NEO levels in patients than controls that remained significant in subgroups of studies on pulmonary TB (PTB) patients and serum NEO and higher blood NEO levels in patients before than after ATT. ConclusionMeta-analyses reveal alteration in NEO levels in different specimens, e.g., blood, urine, and pleural fluid, in patients with TB with or HIV-TB co-infection compared to the control groups. Future studies need to investigate the utility of NEO as a diagnostic/prognostic biomarker for TB. Also, cellular and molecular mechanisms linking NEO and TB remain to be addressed.