A systematic review and meta-analysis of Plasmodium infections and erythrocyte sedimentation rate in relation to disease severity

Abstract

BACKGROUND: Given the global burden of malaria and its impact on public health, there is a pressing need to understand the role of routine hematological parameters, particularly erythrocyte sedimentation rate (ESR), in malaria diagnosis and prognosis. This systematic review and meta-analysis aimed to comprehensively examine the differences in ESR between malaria patients and non-malarial controls, as well as between severe and non-severe malaria cases. METHODS: This systematic review and meta-analysis followed the PRISMA guidelines and was registered with PROSPERO (CRD42023482332). Comprehensive searches were conducted in ProQuest, Embase, Ovid, MEDLINE, PubMed, Scopus, and Google Scholar from inception to July 1, 2025, using terms related to "erythrocyte sedimentation rate" and "malaria." Studies were included if they reported ESR levels in malaria patients compared to non-malarial controls, or in severe versus non-severe malaria cases. Non-original studies, those without extractable ESR data, or those lacking appropriate comparison groups were excluded. Data extraction and quality assessment were independently performed by two reviewers using the Joanna Briggs Institute critical appraisal checklists. A meta-analysis using a random-effects model was conducted to estimate standardized mean differences (SMD) in ESR levels between groups. Heterogeneity was assessed with the I² statistic, and further explored through meta-regression, subgroup analyses, and sensitivity analyses. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: The review identified 19 studies that met the inclusion criteria. The qualitative synthesis revealed that a majority of these studies, which employed various research designs, consistently observed elevated ESR in symptomatic malaria cases across different populations and age groups. The meta-analysis confirmed significantly higher ESR levels in malaria patients than non-malarial controls (P = 0.0171, SMD: 3.0037, 95% confidence interval [CI]: 0.5347-5.4726, random effects model, I2 = 97.3%, 11 studies). However, a significant publication bias was detected (Egger's test, P = 0.005), suggesting that the pooled estimates may be influenced by selective reporting. The meta-analysis also demonstrated that severe malaria cases have higher ESR levels compared to non-severe cases (P = 0.0014, SMD: 2.2556, 95% CI: 0.8759-3.6354, random effects model, I²: 96.1%, 4 studies). CONCLUSION: The findings of this study indicate that elevated ESR is frequently reported in malaria patients and may be more pronounced in severe cases. However, the very high between-study heterogeneity and the presence of publication bias limit confidence in the robustness of these associations. While ESR may hold potential as a supportive diagnostic or prognostic marker when combined with other clinical and laboratory parameters, its independent utility in malaria remains uncertain and requires further investigation.