Abstract
Monocyte chemoattractant protein-1 (MCP-1) or C-C Motif Chemokine Ligand 2 (CCL-2) is a key chemokine implicated in the inflammatory response to malaria. The objective of the study was to synthesize the evidence on variations in MCP-1/CCL-2 levels in relation to Plasmodium spp. infections and the severity of malaria. The protocol for this systematic review and meta-analysis was registered at PROSPERO (CRD42024565867). To identify relevant studies, a comprehensive search strategy was conducted using major databases, including PubMed, Scopus, Embase, Medline, Journals@Ovid, and Nursing & Allied Health Premium. The Joanna Briggs Institute (JBI) critical appraisal checklists were used to determine the risk of bias in selected studies. The pooled standardized mean difference (SMD, Hedge's g) and their 95% confidence interval (CI) were estimated using the random-effects model. Thirty-three studies, with a total of 6,804 participants enrolled, were included in the systematic review. Most studies (60.6%) were published between 2010 and 2019; the majority (57.6%) were conducted in Africa. The predominant Plasmodium species studied was P. falciparum (66.7%). The meta-analysis revealed no significant difference in MCP-1/CCL-2 levels between Plasmodium-infected and uninfected individuals (P: 0.16, SMD: 0.99, 95% CI: -0.39-2.37, I(2): 97.2%, number of participants: 2140). Subgroup analysis found an increase in MCP-1/CCL-2 levels in children with Plasmodium infections, with no heterogeneity observed (I(2): 0%). Subgroup analysis found no difference in MCP-1/CCL-2 levels between P. falciparum-infected participants and uninfected participants, as well as between P. falciparum or non-P. falciparum-infected participants and uninfected participants. The meta-analysis revealed significantly higher MCP-1/CCL-2 levels in participants with severe Plasmodium infections compared to those with non-severe malaria (P: 0.04, SMD: 1.51, 95% CI: 0.06-2.95, I(2): 98.5%, number of participants: 1371). The systematic review and meta-analysis suggest no statistically significant difference in MCP-1/CCL-2 levels in participants with Plasmodium infections overall. However, there was a significant increase in MCP-1/CCL-2 levels in patients with severe malaria. These findings suggest that MCP-1/CCL-2 may have potential as a prognostic biomarker for severe malaria. Future research should focus on large-scale, well-designed studies to validate the role of MCP-1/CCL-2 in malaria and further explore its prognostic potential.