Abstract
Background Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear.MethodologyThe adherence properties of P. vivax infected red blood cells (PvIRBC) were evaluated under static and flow conditions.Principal Findings P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA) and hyaluronic acid (HA), the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5). Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD) shear stress reducing maximum attachment by 50% was 0.06 (0.02) Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37°C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39°C adherence began earlier and peaked at 24 hours.SignificanceAdherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.
Highlights
Vital organ dysfunction and death from P falciparum malaria results from microvascular obstruction caused by the sequestration of red cells containing mature forms of the parasite
We have investigated the adherence of P. vivax (N = 33) to the placental glycosaminoglycans chondroitin sulphate A (CSA) and hyaluronic acid (HA), the putative receptors for P. falciparum placental adherence [10,11]
Malnutrition, developmental retardation, severe anaemia, acute pulmonary oedema and encephalopathy are all well documented with vivax malaria [6,24,25,26]
Summary
Vital organ dysfunction and death from P falciparum malaria results from microvascular obstruction caused by the sequestration of red cells containing mature forms of the parasite. P.falciparum infections in pregnancy are associated with a consistent reduction in birth weight, in primigravidae This is a major risk factor for neonatal death. Intrauterine growth retardation is associated with the accumulation of P.falciparum infected red cells in the placenta This accumulation results from the adherence of a specific and relatively conserved red cell surface expressed domain of the antigenically variant membrane protein (PfEMP1) to the placental glycosaminoglycan chondroitin sulphate A, and to secondary receptors such as hyaluronic acid and immunoglobulins [1,2,3,4,5]. P. vivax infections in pregnancy cause abortions [10] and reduce birthweight which increases the risk of neonatal death, the mechanism underlying early fetal loss or the intrauterine growth retardation is unclear [11].
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