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

Haruhiko Ishioka, Aniruddha Ghose, Prakaykaew Charunwatthana, Richard Maude, Katherine Plewes, Hugh William Fluellen Kingston, Benjamas Intharabut, Charles Woodrow, Kesinee Chotivanich, Abdullah Sayeed, Mahatab Hasan, Nicholas Day, Abul Faiz, Nicholas J White, Amir Hossain, Arjen Dondorp

Research output: Contribution to journalArticleResearchpeer-review

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; R2 = 0.35).

Conclusions: Sequestration of parasitized red blood cells and reduced RCD both contribute to decreased microcirculatory flow in severe disease.
Original languageEnglish
Pages (from-to)788-793
Number of pages6
JournalJournal of Infectious Diseases
Volume213
Issue number5
DOIs
Publication statusPublished - 2016

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Falciparum Malaria
Erythrocytes
Linear Models
Lactic Acid
Plasmodium falciparum
Malaria
Bangladesh
Parasitemia
Glycolysis
Hyperlactatemia
Bilirubin
Biomass
Survivors
Parasites
Lasers
Regression Analysis
Mortality

Cite this

Ishioka, H., Ghose, A., Charunwatthana, P., Maude, R., Plewes, K., Kingston, H. W. F., ... Dondorp, A. (2016). Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria. Journal of Infectious Diseases, 213(5), 788-793. https://doi.org/10.1093/infdis/jiv502
Ishioka, Haruhiko ; Ghose, Aniruddha ; Charunwatthana, Prakaykaew ; Maude, Richard ; Plewes, Katherine ; Kingston, Hugh William Fluellen ; Intharabut, Benjamas ; Woodrow, Charles ; Chotivanich, Kesinee ; Sayeed, Abdullah ; Hasan, Mahatab ; Day, Nicholas ; Faiz, Abul ; White, Nicholas J ; Hossain, Amir ; Dondorp, Arjen. / Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria. In: Journal of Infectious Diseases. 2016 ; Vol. 213, No. 5. pp. 788-793.
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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; R2 = 0.35).Conclusions: Sequestration of parasitized red blood cells and reduced RCD both contribute to decreased microcirculatory flow in severe disease.",
author = "Haruhiko Ishioka and Aniruddha Ghose and Prakaykaew Charunwatthana and Richard Maude and Katherine Plewes and Kingston, {Hugh William Fluellen} and Benjamas Intharabut and Charles Woodrow and Kesinee Chotivanich and Abdullah Sayeed and Mahatab Hasan and Nicholas Day and Abul Faiz and White, {Nicholas J} and Amir Hossain and Arjen Dondorp",
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Ishioka, H, Ghose, A, Charunwatthana, P, Maude, R, Plewes, K, Kingston, HWF, Intharabut, B, Woodrow, C, Chotivanich, K, Sayeed, A, Hasan, M, Day, N, Faiz, A, White, NJ, Hossain, A & Dondorp, A 2016, 'Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria', Journal of Infectious Diseases, vol. 213, no. 5, pp. 788-793. https://doi.org/10.1093/infdis/jiv502

Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria. / Ishioka, Haruhiko; Ghose, Aniruddha; Charunwatthana, Prakaykaew; Maude, Richard; Plewes, Katherine; Kingston, Hugh William Fluellen; Intharabut, Benjamas; Woodrow, Charles; Chotivanich, Kesinee; Sayeed, Abdullah; Hasan, Mahatab; Day, Nicholas; Faiz, Abul; White, Nicholas J; Hossain, Amir; Dondorp, Arjen.

In: Journal of Infectious Diseases, Vol. 213, No. 5, 2016, p. 788-793.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria

AU - Ishioka, Haruhiko

AU - Ghose, Aniruddha

AU - Charunwatthana, Prakaykaew

AU - Maude, Richard

AU - Plewes, Katherine

AU - Kingston, Hugh William Fluellen

AU - Intharabut, Benjamas

AU - Woodrow, Charles

AU - Chotivanich, Kesinee

AU - Sayeed, Abdullah

AU - Hasan, Mahatab

AU - Day, Nicholas

AU - Faiz, Abul

AU - White, Nicholas J

AU - Hossain, Amir

AU - Dondorp, Arjen

PY - 2016

Y1 - 2016

N2 - 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; R2 = 0.35).Conclusions: Sequestration of parasitized red blood cells and reduced RCD both contribute to decreased microcirculatory flow in severe disease.

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U2 - 10.1093/infdis/jiv502

DO - 10.1093/infdis/jiv502

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SP - 788

EP - 793

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

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