A systematic review and meta-analysis of inflammatory biomarkers associated with malaria infection and disease severity.

Inflammatory biomarkers; C-reactive protein (CRP), Interleukin 6 (IL-6), and tumor necrosis factor- alpha (TNF-α) play a very crucial role in disease pathogenesis. Studies conducted earlier showed the associativity of these biomarkers with malaria severity. Meta-analysis of individual biomarkers was done in many studies, while in a few others, all these candidates were estimated, but the findings were inconclusive. Therefore, a systematic review and meta-analyses were performed to evaluate differences in biomarkers mentioned above in complicated and uncomplicated malaria patients. Studies focussed on CRP, IL-6, and TNF-α with quantitative data on complicated and uncomplicated malaria patients were searched on PubMed, Scopus, and Google Scholar. The quality of the studies selected for this review was checked following Newcastle-Ottawa Scale guidelines. The standard mean difference and confidence interval of biomarkers in the targeted groups were calculated using the random effects model. Egger's test and funnel plot asymmetry were performed to assess the publication bias. Thirteen studies that qualified the inclusion criteria were considered for this meta-analysis. CRP levels were higher in complicated malaria patients than uncomplicated ones (P < 0.00001, pooled SMD: 0.90 mg/L, 95 % CI: 0.51 to 1.30 mg/L, I: 80 %, six studies). IL-6 levels were elevated in complicated cases (P < 0.00001, pooled SMD: 0.89 pg/ml, 95 % CI: 0.66 to 1.12, I: 99 %, four studies) and TNF-α also showed an increase in severe complicated patients (P < 0.00001, pooled SMD: 1.18 pg/ml, 95 % CI: 1 to 1.36, I: 99 %, six studies). In most of the included studies, CRP, IL-6, and TNF-α were higher in complicated malaria patients. Nevertheless, the results of a few studies were not convincing. Due to the lack of specificity in all individual biomarkers, none had adequate diagnostic accuracy. Considering the role of pro-inflammatory cytokines in the CRP activation pathway in malaria progression, the combination of these biomarkers should be used in monitoring the disease severity.