Tumour necrosis factor-α as a prognostic biomarker of severe malaria: a systematic review and meta-analysis

Background: Tumour necrosis factor-alpha (TNF-alpha) levels are reportedly altered during malaria. In this systematic review and meta-analysis, we aimed to collect and compare data on TNF-alpha 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-alpha 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-alpha 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-alpha levels than those with uncomplicated malaria (P < 0.001, pooled MD = 79.02 pg/ml, 95% CI: 63.68-94.35 pg/ml, I-2: 99.5%, n = 26 studies). Furthermore, fatal cases had no difference in the mean TNF-alpha levels in comparison with survived cases (P = 0.055, pooled MD = 82.38 pg/ml, 95% CI: -1.93 to 166.69 pg/ml, I-2 : 99.54%, n = 5 studies). Finally, patients with uncomplicated malaria showed higher mean TNF-alpha levels than those with asymptomatic malaria (P < 0.001, pooled MD = 45.10 pg/ml, 95% CI: 18.45-71.76 pg/ml, I-2 : 97.09%, n = 5 studies). Conclusion: This systematic review and meta-analysis confirmed the increase of TNF-alpha levels in patients with severe malaria. Therefore, TNF-alpha may be alternatively used as a prognostic biomarker of severe malaria.