Abstract
Despite a 30% decline in mortality since 2000, malaria still affected 219 million subjects and caused 435,000 deaths in 2017. Red blood cells (RBC) host Plasmodium parasites that cause malaria, of which Plasmodium falciparum is the most pathogenic. The deformability of RBC is markedly modified by invasion and development of P. falciparum. Surface membrane area is potentially impacted by parasite entry and development, the cytoskeleton is modified by parasite proteins and cytosol viscosity is altered by parasite metabolism. RBC hosting mature parasites (second half of the asexual erythrocytic cycle) are abnormally stiff but the main reason for their absence from the circulation is their adherence to endothelial cells, mediated by parasite proteins exposed at the infected-RBC surface. By contrast, the circulation of non-adherent rings and gametocytes, depends predominantly on deformability. Altered deformability of rings and of uninfected-RBC altered by malaria infection is an important determinant of malaria pathogenesis. It also impacts the response to antimalarial therapy. Unlike conventional antimalarials that target mature stages, currently recommended first-line artemisinin derivatives and the emerging spiroindolones act on circulating rings. Methods to investigate the deformability of RBC are therefore critical to understand the clearance of infected- and uninfected-RBC in malaria. Herein, we review the main methods to assess the deformability of P. falciparum infected-RBC, and their contribution to the understanding of how P. falciparum infection causes disease, how the parasite is transmitted and how antimalarial drugs induce parasite clearance.
Highlights
Red blood cells (RBC) are essential for oxygen delivery to organs and must circulate in narrow blood vessels without being destroyed
Works demonstrated that infected RBC (iRBC) deformability is an important determinant of malaria pathogenesis (Miller et al, 1971; Cranston et al, 1984)
This indirectly highlighted the major role of the spleen in malaria, partly through its ability to control the deformability of RBC
Summary
Red blood cells (RBC) are essential for oxygen delivery to organs and must circulate in narrow blood vessels without being destroyed. Drug-induced alterations of the deformability of iRBC may impact the efficacy of antimalarial regimens and the pace of treatment-induced parasite clearance These observations on malaria pathogenesis and the deformability of RBC were generated through different methods. The deformability of P. falciparum-infected RBC was first monitored by a rheoscope (counterrotating transparent cone-and-plate chamber to measure elongation of RBC under shear stress) which assesses the shape of individual RBC (Cranston et al, 1984) This method provided the first demonstration of a reduced deformability of iRBC which may induce their retention in the spleen. Ektacytometry uses a Laserassisted Optical Rotational Red Cell Analyzer (LORRCA, RR Mechatronics, Netherlands) to measure the diffraction pattern of sheared RBC resuspended in a viscous medium at 37◦C to determine their elongation index (EI). RBC infected with rings and mature stages require 1.5 and 4–6 times more pressure than normal RBC to enter into 3 μm-wide pipettes, respectively
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