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J Infect Dis. 2016 Mar 1;213(5):788-93. doi: 10.1093/infdis/jiv502. Epub 2015 Oct 22.

Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria.

Author information

1
Mahidol Oxford Tropical Medicine Research Unit Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
2
Chittagong Medical College Hospital.
3
Mahidol Oxford Tropical Medicine Research Unit Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, United Kingdom.
4
Mahidol Oxford Tropical Medicine Research Unit.
5
Mahidol Oxford Tropical Medicine Research Unit Malaria Research Group and Dev Care Foundation, Dhaka, Bangladesh.

Abstract

BACKGROUND:

Hyperlactatemia is a strong predictor of mortality in severe falciparum malaria. Sequestered parasitized erythrocytes and reduced uninfected red blood cell deformability (RCD) compromise microcirculatory flow, leading to anaerobic glycolysis.

METHODS:

In a cohort of patients with falciparum malaria hospitalized in Chittagong, Bangladesh, bulk RCD was measured using a laser diffraction technique, and parasite biomass was estimated from plasma concentrations of Plasmodium falciparum histidine-rich protein 2 (PfHRP2). A multiple linear regression model was constructed to examine their associations with plasma lactate concentrations.

RESULTS:

A total of 286 patients with falciparum malaria were studied, of whom 224 had severe malaria, and 70 died. Hyperlactatemia (lactate level, ≥ 4 mmol/L) was present in 111 cases. RCD at shear stresses of 1.7 Pa and 30 Pa was reduced significantly in patients who died, compared with survivors, individuals with uncomplicated malaria, or healthy individuals (P < .05, for all comparisons). Multiple linear regression analysis showed that the plasma PfHRP2 level, parasitemia level, total bilirubin level, and RCD at a shear stress of 1.7 Pa were each independently correlated with plasma lactate concentrations (n = 278; R(2) = 0.35).

CONCLUSIONS:

Sequestration of parasitized red blood cells and reduced RCD both contribute to decreased microcirculatory flow in severe disease.

KEYWORDS:

Plasmodium falciparum; hyperlactatemia; malaria; parasite biomass; red blood cell deformability

PMID:
26494775
PMCID:
PMC4747623
DOI:
10.1093/infdis/jiv502
[Indexed for MEDLINE]
Free PMC Article

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