A Systematic Review and Meta-Analysis of MIP-1α and MIP-1β Chemokines in Malaria in Relation to Disease Severity

Abstract

Background and Objectives: Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β act as signaling molecules that recruit immune cells to sites of infection and inflammation. This study aimed to synthesize evidence on blood levels of MIP-1α and MIP-1β in Plasmodium-infected individuals and to determine whether these levels differ between severe and uncomplicated malaria cases. Materials and Methods: The study protocol was registered in PROSPERO (CRD42024595818). Comprehensive literature searches were conducted in six databases (EMBASE, MEDLINE, Ovid, Scopus, ProQuest, and PubMed) to identify studies reporting blood levels of MIP-1α and MIP-1β in Plasmodium infections and clinical malaria. A narrative synthesis was used to describe variations in MIP-1α and MIP-1β levels between malaria patients and controls and between severe and non-severe malaria cases. Meta-analysis was used to aggregate quantitative data utilizing a random-effects model. Results: A total of 1638 records were identified, with 20 studies meeting the inclusion criteria. Most studies reported significantly higher MIP-1α and MIP-1β levels in malaria patients compared to non-malarial controls. The meta-analysis showed a significant elevation in MIP-1α levels in malaria patients (n = 352) compared to uninfected individuals (n = 274) (p = 0.0112, random effects model, standardized mean difference [SMD]: 1.69, 95% confidence interval [CI]: 0.38 to 3.00, I²: 96.0%, five studies, 626 individuals). The meta-analysis showed no difference in MIP-1α levels between severe malaria cases (n = 203) and uncomplicated cases (n = 106) (p = 0.51, SMD: -0.48, 95% CI: -1.93 to 0.96, I²: 97.3%, three studies, 309 individuals). Conclusions: This study suggests that while MIP-1α and MIP-1β levels are elevated in malaria patients compared to uninfected individuals, these chemokines show a limited ability to differentiate between severe and uncomplicated malaria or predict severe outcomes. Further research is needed to clarify their role in malaria pathogenesis and explore potential clinical applications.

Keywords: MIP-1α; MIP-1β; macrophage inflammatory protein; malaria; meta-analysis; systematic review.

Figure 1

Study flow diagram.

Figure 2

The forest plot shows the standardized mean difference (SMD) in MIP-1α levels between malaria patients and uninfected individuals across five studies [30,32,33,34,44]. Each study is represented by a blue square, with the size reflecting its weight in the meta-analysis. Horizontal lines denote each study’s 95% confidence intervals (CIs). The pooled effect sizes are presented under the common (random) and random effects models, with the overall SMD indicated by a diamond. Black vertical line is no effect line. Black-dashed lines are the overall SMD by common (fixed-) and random-effects models. High heterogeneity was observed among the studies (I² = 96%, p < 0.01).

Figure 3

The forest plot shows the standardized mean difference (SMD) in MIP-1β levels between malaria patients and uninfected individuals across four studies [30,33,34,44]. Each study is represented by a blue square, with the size reflecting its weight in the meta-analysis. Horizontal lines denote each study’s 95% confidence intervals (CIs). The pooled effect sizes are presented under the common (random) and random effects models, with the overall SMD indicated by a diamond. Black vertical line is no effect line. Black-dashed lines are the overall SMD by common (fixed-) and random-effects models. High heterogeneity was observed among the studies (I² = 89%, p < 0.01).

Figure 4

The forest plot shows the standardized mean difference (SMD) in MIP-1α levels between patients with severe and uncomplicated malaria across three studies [33,34,40]. Each study is represented by a blue square, with the size reflecting its weight in the meta-analysis. Horizontal lines denote each study’s 95% confidence intervals (CIs). The pooled effect sizes are presented under the common (random) and random effects models, with the overall SMD indicated by a diamond. Black vertical line is no effect line. Black-dashed lines are the overall SMD by common (fixed-) and random-effects models. High heterogeneity was observed among the studies (I² = 97%, p < 0.01).

Figure 5

The forest plot shows the standardized mean difference (SMD) in MIP-1β levels between patients with severe and uncomplicated malaria across two studies [33,34]. Each study is represented by a gray square, with the size reflecting its weight in the meta-analysis. Horizontal lines denote each study’s 95% confidence intervals (CIs). The pooled effect sizes are presented under the common (random) and random effects models, with the overall SMD indicated by a diamond. Black vertical line is no effect line. Black-dashed lines are the overall SMD by random-effects model. High heterogeneity was observed among the studies (I² = 94%).