LAUSR

BACKGROUND Tumour necrosis factor-alpha (TNF-α) levels are reportedly altered during malaria. In this systematic review and meta-analysis, we aimed to collect and compare data on TNF-α levels between patients with malaria of varying severity and healthy asymptomatic positive controls. METHODS We searched PubMed, Scopus, and Web of Science for studies that reported TNF-α levels in malaria cases of different severity and healthy asymptomatic positive controls using a combination of search terms. The quality of the included studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. To compare the TNF-α levels among fatal cases, severe cases, uncomplicated cases, and healthy asymptomatic positive controls, we applied the random-effects model that assumed the existence of variations between studies. The effect estimate was pooled mean difference (MD) with a 95% confidence interval (CI). RESULTS From 1694 studies, we included 31 studies that met our eligibility criteria for systematic review and meta-analysis. Patients with severe malaria showed higher mean TNF-α levels than those with uncomplicated malaria (p < 0.001, pooled MD = 79.02 pg/mL, 95% CI: 63.68-94.35 pg/mL, I2: 99.5%, n = 26 studies). Furthermore, fatal cases had no difference in the mean TNF-α levels in comparison with survived cases (p = 0.055, pooled MD = 82.38 pg/mL, 95% CI: -1.93-166.69 pg/mL, I2: 99.54%, n = 5 studies). Finally, patients with uncomplicated malaria showed higher mean TNF-α levels than those with asymptomatic malaria (p < 0.001, pooled MD = 45.10 pg/mL, 95% CI: 18.45-71.76 pg/mL, I2: 97.09%, n = 5 studies). CONCLUSION This systematic review and meta-analysis confirmed the increase of TNF-α levels in patients with severe malaria. Therefore, TNF-α may be alternatively used as a prognostic biomarker of severe malaria. TRIAL REGISTRATION Not applicable.