Reduced red blood cell deformability in Plasmodium knowlesi malaria

Bridget Barber, Bruce Russell, Matthew Grigg, Rou Zhang, Timothy William, Amirah Amir, Yee Ling Lau, Mark Chatfield, Arjen M. Dondorp, Nicholas Anstey, Tsin Yeo

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The simian parasite Plasmodium knowlesi can cause severe and fatal human malaria. However, little is known about the pathogenesis of this disease. In falciparum malaria, reduced red blood cell deformability (RBC-D) contributes to microvascular obstruction and impaired organ perfusion. In P knowlesi infection, impaired microcirculatory flow has been observed in Macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. However, RBC-D has not been measured in human infection or in the natural host M fascicularis (long-tailed macaques). Using ektacytometry, we measured RBC-D in adults with severe and non-severe knowlesi and falciparum malaria and in healthy controls. In addition, we used micropipette aspiration to determine the relative stiffness of infected RBCs (iRBCs) and uninfected RBCs (uRBCs) in P knowlesi–infected humans and M fascicularis. Ektacytometry demonstrated that RBC-D overall was reduced in human knowlesi malaria in proportion to disease severity, and in severe knowlesi malaria, it was comparable to that of severe falciparum malaria. RBC-D correlated inversely with parasitemia and lactate in knowlesi malaria and HRP2 in falciparum malaria, and it correlated with hemoglobin nadir in knowlesi malaria. Micropipette aspiration confirmed that in humans, P knowlesi infection increased stiffness of both iRBCs and uRBCs, with the latter mostly the result of echinocytosis. In contrast, in the natural host M fascicularis, echinocyte formation was not observed, and the RBC-D of uRBCs was unaffected. In unnatural primate hosts of P knowlesi, including humans, reduced deformability of iRBCs and uRBCs may represent a key pathogenic mechanism leading to microvascular accumulation, impaired organ perfusion, and anemia.
Original languageEnglish
Pages (from-to)433-443
Number of pages11
JournalBlood
Volume2
Issue number4
DOIs
Publication statusPublished - 2018

Fingerprint

Plasmodium knowlesi
Plasmodium malariae
Formability
Blood
Falciparum Malaria
Erythrocytes
Malaria
Cells
Macaca mulatta
Perfusion
Infection
Stiffness
Parasitemia
Macaca
Primates
Anemia
Lactic Acid
Parasites
Hemoglobins

Cite this

Barber, Bridget ; Russell, Bruce ; Grigg, Matthew ; Zhang, Rou ; William, Timothy ; Amir, Amirah ; Lau, Yee Ling ; Chatfield, Mark ; Dondorp, Arjen M. ; Anstey, Nicholas ; Yeo, Tsin. / Reduced red blood cell deformability in Plasmodium knowlesi malaria. In: Blood. 2018 ; Vol. 2, No. 4. pp. 433-443.
@article{b2c2a90cbd7747dd8d5281fd4c73d3ac,
title = "Reduced red blood cell deformability in Plasmodium knowlesi malaria",
abstract = "The simian parasite Plasmodium knowlesi can cause severe and fatal human malaria. However, little is known about the pathogenesis of this disease. In falciparum malaria, reduced red blood cell deformability (RBC-D) contributes to microvascular obstruction and impaired organ perfusion. In P knowlesi infection, impaired microcirculatory flow has been observed in Macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. However, RBC-D has not been measured in human infection or in the natural host M fascicularis (long-tailed macaques). Using ektacytometry, we measured RBC-D in adults with severe and non-severe knowlesi and falciparum malaria and in healthy controls. In addition, we used micropipette aspiration to determine the relative stiffness of infected RBCs (iRBCs) and uninfected RBCs (uRBCs) in P knowlesi–infected humans and M fascicularis. Ektacytometry demonstrated that RBC-D overall was reduced in human knowlesi malaria in proportion to disease severity, and in severe knowlesi malaria, it was comparable to that of severe falciparum malaria. RBC-D correlated inversely with parasitemia and lactate in knowlesi malaria and HRP2 in falciparum malaria, and it correlated with hemoglobin nadir in knowlesi malaria. Micropipette aspiration confirmed that in humans, P knowlesi infection increased stiffness of both iRBCs and uRBCs, with the latter mostly the result of echinocytosis. In contrast, in the natural host M fascicularis, echinocyte formation was not observed, and the RBC-D of uRBCs was unaffected. In unnatural primate hosts of P knowlesi, including humans, reduced deformability of iRBCs and uRBCs may represent a key pathogenic mechanism leading to microvascular accumulation, impaired organ perfusion, and anemia.",
author = "Bridget Barber and Bruce Russell and Matthew Grigg and Rou Zhang and Timothy William and Amirah Amir and Lau, {Yee Ling} and Mark Chatfield and Dondorp, {Arjen M.} and Nicholas Anstey and Tsin Yeo",
year = "2018",
doi = "10.1182/bloodadvances.2017013730",
language = "English",
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pages = "433--443",
journal = "Blood",
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Barber, B, Russell, B, Grigg, M, Zhang, R, William, T, Amir, A, Lau, YL, Chatfield, M, Dondorp, AM, Anstey, N & Yeo, T 2018, 'Reduced red blood cell deformability in Plasmodium knowlesi malaria', Blood, vol. 2, no. 4, pp. 433-443. https://doi.org/10.1182/bloodadvances.2017013730

Reduced red blood cell deformability in Plasmodium knowlesi malaria. / Barber, Bridget; Russell, Bruce; Grigg, Matthew; Zhang, Rou ; William, Timothy; Amir, Amirah; Lau, Yee Ling ; Chatfield, Mark; Dondorp, Arjen M.; Anstey, Nicholas; Yeo, Tsin.

In: Blood, Vol. 2, No. 4, 2018, p. 433-443.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Reduced red blood cell deformability in Plasmodium knowlesi malaria

AU - Barber, Bridget

AU - Russell, Bruce

AU - Grigg, Matthew

AU - Zhang, Rou

AU - William, Timothy

AU - Amir, Amirah

AU - Lau, Yee Ling

AU - Chatfield, Mark

AU - Dondorp, Arjen M.

AU - Anstey, Nicholas

AU - Yeo, Tsin

PY - 2018

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N2 - The simian parasite Plasmodium knowlesi can cause severe and fatal human malaria. However, little is known about the pathogenesis of this disease. In falciparum malaria, reduced red blood cell deformability (RBC-D) contributes to microvascular obstruction and impaired organ perfusion. In P knowlesi infection, impaired microcirculatory flow has been observed in Macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. However, RBC-D has not been measured in human infection or in the natural host M fascicularis (long-tailed macaques). Using ektacytometry, we measured RBC-D in adults with severe and non-severe knowlesi and falciparum malaria and in healthy controls. In addition, we used micropipette aspiration to determine the relative stiffness of infected RBCs (iRBCs) and uninfected RBCs (uRBCs) in P knowlesi–infected humans and M fascicularis. Ektacytometry demonstrated that RBC-D overall was reduced in human knowlesi malaria in proportion to disease severity, and in severe knowlesi malaria, it was comparable to that of severe falciparum malaria. RBC-D correlated inversely with parasitemia and lactate in knowlesi malaria and HRP2 in falciparum malaria, and it correlated with hemoglobin nadir in knowlesi malaria. Micropipette aspiration confirmed that in humans, P knowlesi infection increased stiffness of both iRBCs and uRBCs, with the latter mostly the result of echinocytosis. In contrast, in the natural host M fascicularis, echinocyte formation was not observed, and the RBC-D of uRBCs was unaffected. In unnatural primate hosts of P knowlesi, including humans, reduced deformability of iRBCs and uRBCs may represent a key pathogenic mechanism leading to microvascular accumulation, impaired organ perfusion, and anemia.

AB - The simian parasite Plasmodium knowlesi can cause severe and fatal human malaria. However, little is known about the pathogenesis of this disease. In falciparum malaria, reduced red blood cell deformability (RBC-D) contributes to microvascular obstruction and impaired organ perfusion. In P knowlesi infection, impaired microcirculatory flow has been observed in Macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. However, RBC-D has not been measured in human infection or in the natural host M fascicularis (long-tailed macaques). Using ektacytometry, we measured RBC-D in adults with severe and non-severe knowlesi and falciparum malaria and in healthy controls. In addition, we used micropipette aspiration to determine the relative stiffness of infected RBCs (iRBCs) and uninfected RBCs (uRBCs) in P knowlesi–infected humans and M fascicularis. Ektacytometry demonstrated that RBC-D overall was reduced in human knowlesi malaria in proportion to disease severity, and in severe knowlesi malaria, it was comparable to that of severe falciparum malaria. RBC-D correlated inversely with parasitemia and lactate in knowlesi malaria and HRP2 in falciparum malaria, and it correlated with hemoglobin nadir in knowlesi malaria. Micropipette aspiration confirmed that in humans, P knowlesi infection increased stiffness of both iRBCs and uRBCs, with the latter mostly the result of echinocytosis. In contrast, in the natural host M fascicularis, echinocyte formation was not observed, and the RBC-D of uRBCs was unaffected. In unnatural primate hosts of P knowlesi, including humans, reduced deformability of iRBCs and uRBCs may represent a key pathogenic mechanism leading to microvascular accumulation, impaired organ perfusion, and anemia.

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