Alteration of Blood Lactate Levels in Severe Falciparum Malaria: A Systematic Review and Meta-Analysis

Abstract

Metabolic acidosis in severe malaria usually occurs in the form of lactic acidosis. The present study aimed to collate articles from the literature that have reported blood lactate levels in patients with severe malaria and tested the hypothesis that blood lactate levels are elevated in patients with malaria compared to those with uncomplicated malaria. Moreover, the difference in lactate levels between patients who died and those who survived was estimated using a meta-analytic approach. Potentially relevant studies were searched for in PubMed, Web of Science, and Scopus. The quality of the included studies was assessed using the Jadad scale and strengthening the reporting of observational studies in epidemiology (STROBE). The pooled mean blood lactate in patients with severe malaria, the pooled weighted mean difference (WMD) of blood lactate between patients with severe malaria and those with uncomplicated malaria, and the pooled WMD and 95% CI of blood lactate between patients who died from and those who survived severe malaria were estimated using the random-effects model. Heterogeneity among the outcomes of the included studies was assessed using Cochran’s Q and I2 statistics. A meta-regression analysis was performed to identify the source(s) of heterogeneity of outcomes among the included studies. A subgroup analysis was further performed to separately analyze the outcomes stratified by the probable source(s) of heterogeneity. Publication bias was assessed by the visual inspection of the funnel plot asymmetry. Of 793 studies retrieved from the searches, 30 studies were included in qualitative and quantitative syntheses. The pooled mean lactate in patients with severe malaria was 5.04 mM (95% CI: 4.44–5.64; I2: 99.9%; n = 30,202 cases from 30 studies). The mean lactate in patients with severe malaria (1568 cases) was higher than in those with uncomplicated malaria (1693 cases) (p = 0.003; MD: 2.46; 95% CI: 0.85–4.07; I2: 100%; nine studies). The mean lactate in patients with severe malaria who died (272 cases) was higher than in those with severe malaria who survived (1370 cases) (p < 0.001; MD: 2.74; 95% CI: 1.74–3.75; I2: 95.8%; six studies). In conclusion, the present study showed a high mean difference in blood lactate level between patients with severe malaria and patients with uncomplicated malaria. In addition, there was a high mean difference in blood lactate level between patients with severe malaria who died compared to those with severe malaria who survived. Further studies are needed to investigate the prognostic value of blood lactate levels to identify patients who are at high risk of developing severe malaria or dying.