Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria.
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.
Mahidol Oxford Tropical Medicine Research Unit Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Haruhiko
H
Ishioka
Chittagong Medical College Hospital.
Aniruddha
A
Ghose
Mahidol Oxford Tropical Medicine Research Unit Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Prakaykaew
P
Charunwatthana
Mahidol Oxford Tropical Medicine Research Unit Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, United Kingdom.
Richard
R
Maude
Mahidol Oxford Tropical Medicine Research Unit.
Katherine
K
Plewes
Mahidol Oxford Tropical Medicine Research Unit.
Hugh
H
Kingston
Mahidol Oxford Tropical Medicine Research Unit.
Benjamas
B
Intharabut
Mahidol Oxford Tropical Medicine Research Unit Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, United Kingdom.
Charlie
C
Woodrow
Mahidol Oxford Tropical Medicine Research Unit Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Kesinee
K
Chotivanich
Chittagong Medical College Hospital.
Abdullah Abu
AA
Sayeed
Chittagong Medical College Hospital.
Mahtab Uddin
MU
Hasan
Mahidol Oxford Tropical Medicine Research Unit Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, United Kingdom.
Nicholas P
NP
Day
Mahidol Oxford Tropical Medicine Research Unit Malaria Research Group and Dev Care Foundation, Dhaka, Bangladesh.
Abul
A
Faiz
Mahidol Oxford Tropical Medicine Research Unit Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, United Kingdom.
Nicholas J
NJ
White
Chittagong Medical College Hospital.
Amir
A
Hossain
Mahidol Oxford Tropical Medicine Research Unit Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, United Kingdom.
Arjen M
AM
Dondorp
D000328:Adult; D001459:Bangladesh / Q000453:epidemiology; D004907:Erythrocyte Deformability / Q000502:physiology*; D005260:Female; D006801:Humans; D007773:Lactates / Q000097:blood*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D007773:Lactates
Plasmodium falciparum; hyperlactatemia; malaria; parasite biomass; red blood cell deformability