Increased Blood Concentrations of Malondialdehyde in Plasmodium Infection: A Systematic Review and Meta-Analysis

Abstract

Several studies have evaluated the relationship between malondialdehyde (MDA) concentrations and Plasmodium infections; however, the findings remain inconclusive. This study synthesized differences in MDA concentrations among patients with different levels of clinical severity, uninfected controls, and different Plasmodium species. The research protocol was registered in PROSPERO (CRD42023393540). Systematic literature searches for relevant studies were performed using the Embase, MEDLINE, Ovid, ProQuest, PubMed, Scopus, and Google Scholar databases. Qualitative and quantitative syntheses (meta-analyses) of distinct MDA concentrations between the disease groups were performed. Twenty-three studies met the eligibility criteria and were included in the systematic review. Overall, MDA concentrations were significantly elevated in participants with malaria relative to uninfected controls (p < 0.01, Cohen d: 2.51, 95% confidence interval (CI): 1.88-3.14, I²: 96.22%, 14 studies). Increased MDA concentrations in participants with malaria compared with uninfected controls were found in studies that enrolled patients with P. falciparum malaria (p < 0.01, Cohen d: 2.50, 95% CI: 1.90-3.10, I²: 89.7%, 7 studies) and P. vivax malaria (p < 0.01, Cohen d: 3.70, 95% CI: 2.48-4.92, I²: 90.11%, 3 studies). Our findings confirm that MDA concentrations increase during Plasmodium infection, indicating a rise in oxidative stress and lipid peroxidation. Thus, MDA levels can be a valuable biomarker for evaluating these processes in individuals with malaria. However, further research is necessary to fully elucidate the intricate relationship between malaria, antioxidants, oxidative stress, and the specific role of MDA in the progression of malaria.

Keywords: MDA; antioxidant; lipid peroxidation; malaria; malondialdehyde; oxidant.

Figure 1

Study selection diagram.

Figure 2

Forest plot showing differences in MDA concentration between participants with malaria and uninfected controls. Blue square, MDA concentration; green diamond, pooled Cohen d; gray line, no difference in MDA concentration between the two groups; red line, pooled Cohen d. Test of overall effect (p = 0.00) indicates increased MDA concentration in malaria patients compared with uninfected controls [34,36,37,38,40,42,43,44,47,48,49,50,53,54]. Abbreviations: N, number of participants; mean, mean MDA concentrations (using Cohen d as an effect estimate, any unit of mean MDA concentration can be used in the meta-analysis); SD, standard deviation; CI, confidence interval.

Figure 3

Forest plot of differences in MDA concentration between participants with malaria and uninfected controls (stratified by Plasmodium species) [36,38,40,42,43,47,48,49,53,54]. Blue square, MDA concentration; green diamond, pooled Cohen d; crimson diamond, pooled Cohen d in each subgroup; gray line, no difference in MDA concentration between the two groups; red line, pooled Cohen d. Abbreviations: N, number of participants; mean, mean MDA concentrations (using the Cohen d as an effect estimate, any unit of mean MDA concentrations can be used in the meta-analysis); SD, standard deviation.

Figure 4

Forest plot of differences in MDA concentration between participants with malaria and uninfected controls (stratified by the study’s quality) [34,36,37,38,40,42,43,44,47,48,49,50,53,54]. Blue square, MDA concentration; green diamond, pooled Cohen d; crimson diamond, pooled Cohen d of subgroups; gray line, no difference in MDA concentration between the two groups; red line, pooled Cohen d. Abbreviations: N, number of participants; mean, mean MDA concentrations (using the Cohen d as an effect estimate, any unit of mean MDA concentrations can be used in the meta-analysis); SD, standard deviation; CI, confidence interval.

Figure 5

Leave-one-out meta-analysis demonstrating the meta-analysis results (malaria vs. uninfected controls) [34,36,37,38,40,42,43,44,47,48,49,50,53,54] after one study was removed at a time and the meta-analysis was rerun. Green dot, pooled Cohen d; gray horizontal line, 95% CI of Cohen d, red line, pooled Cohen d. Abbreviations: CI, confidence interval.

Figure 6

Funnel plot presenting the Cohen d of individual studies (blue dot) on the left and right sides of the pooled Cohen d (red line).