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

**Authors:** Saruda Kuraeiad, Kwuntida Uthaisar Kotepui, Aongart Mahittikorn, Nsoh Godwin Anabire, Frederick Ramirez Masangkay, Polrat Wilairatana, Kinley Wangdi, Manas Kotepui

PMC · DOI: 10.3390/medicina61040676 · 2025-04-06

## TL;DR

This study reviews and analyzes blood levels of MIP-1α and MIP-1β in malaria patients to see if they can distinguish between severe and mild cases.

## Contribution

The study provides a systematic review and meta-analysis of MIP-1α and MIP-1β levels in malaria, assessing their potential as biomarkers for disease severity.

## Key findings

- MIP-1α and MIP-1β levels are significantly higher in malaria patients compared to uninfected individuals.
- MIP-1α levels do not differ between severe and uncomplicated malaria cases.
- The chemokines show limited ability to predict severe malaria outcomes.

## 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.

## Linked entities

- **Proteins:** CCL3 (C-C motif chemokine ligand 3), CCL4 (C-C motif chemokine ligand 4)
- **Diseases:** malaria (MONDO:0005136)

## Full-text entities

- **Genes:** CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}
- **Diseases:** inflammation (MESH:D007249), infection (MESH:D007239), Malaria (MESH:D008288)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12028554/full.md

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Source: https://tomesphere.com/paper/PMC12028554