Increased interferon-γ levels and risk of severe malaria: a meta-analysis

Interferon (IFN)-gamma contributes to the pathogenesis of severe malaria; however, its mechanism remains unclear. Herein, differences in IFN-gamma levels between patients with severe and uncomplicated malaria were evaluated using qualitative and quantitative (meta-analysis) approaches. The systematic review protocol was registered at PROSPERO (ID: CRD42022315213). The searches for relevant studies were performed in five databases, including PubMed, Scopus, Embase, MEDLINE and Web of Science, between 1 January and 10 July 2022. A meta-analysis was conducted to pool the mean difference (MD) of IFN-gamma levels between patients with severe malaria and those with uncomplicated malaria using a random-effects model (DerSimonian and Laird method). Overall, qualitative synthesis indicated that most studies (14, 58.3%) reported no statistically significant difference in IFN-gamma levels between patients with severe malaria and those with uncomplicated malaria. Meanwhile, remaining studies (9, 37.5%) reported that IFN-gamma levels were significantly higher in patients with severe malaria than those in patients with uncomplicated malaria. Only one study (4.17%) reported that IFN-gamma levels were significantly lower in patients with severe malaria than those in patients with uncomplicated malaria. The meta-analysis results indicated that patients with severe malaria had higher mean IFN-gamma levels than those with uncomplicated malaria (p < 0.001, MD: 13.63 pg/mL, 95% confidence interval: 6.98-20.29 pg/mL, I-2: 99.02%, 14 studies/15 study sites, 652 severe cases/1096 uncomplicated cases). In summary, patients with severe malaria exhibited higher IFN-gamma levels than those with uncomplicated malaria, although the heterogeneity of the outcomes is yet to be elucidated. To confirm whether alteration in IFN-gamma levels of patients with malaria may indicate disease severity and/or poor prognosis, further studies are warranted.

Automated summary

This study evaluated the differences in IFN-gamma levels between patients with severe and uncomplicated malaria using qualitative and quantitative approaches. The qualitative synthesis showed that most studies found no statistically significant difference in IFN-gamma levels, while some studies reported higher levels in severe malaria patients. The meta-analysis confirmed that patients with severe malaria had higher mean IFN-gamma levels than those with uncomplicated malaria.