Abstract
BackgroundCerebral malaria is one of the most severe manifestations of Plasmodium falciparum malaria. The sequestration of parasitized red blood cells (PRBCs) to brain microvascular endothelium has been shown to contribute to the pathophysiology of cerebral malaria. Recent studies reported increased levels of von Willebrand factor (VWF) and reduced activity of VWF-cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), in patients with cerebral malaria.MethodsAssociation of six single nucleotide polymorphisms (SNPs) of the ADAMTS13 gene with cerebral malaria was examined in 708 Thai patients with P. falciparum malaria.ResultsAmong six SNPs, the derived allele of a SNP located in intron 28, rs4962153-A, was significantly associated with protection against cerebral malaria when 115 cerebral malaria patients were compared with 367 mild malaria patients (Fisher's exact P-value = 0.0057; OR = 0.27; 95% CI = 0.096-0.76). Significant association was also detected between 115 cerebral malaria and 593 non-cerebral malaria (226 non-cerebral severe malaria and 367 mild malaria) patients (Fisher's exact P-value = 0.012; OR = 0.30; 95% CI = 0.11-0.83).ConclusionsExcessive adhesion of PRBCs to the platelet-decorated ultra-large VWF (ULVWF) appears to enhance the sequestration of PRBCs to cerebral microvascular endothelium. The genetic association observed in the present study implies that the regulation of platelet-decorated ULVWF strings by ADAMTS13 may play a role in the development of cerebral malaria.
Highlights
Cerebral malaria is one of the most severe manifestations of Plasmodium falciparum malaria
This study reports a significant association of common ADAMTS13 polymorphism with protection against cerebral malaria in Thai patients with falciparum malaria
There was no significant difference in allele frequency of rs4962153-A between noncerebral severe and cerebral malaria groups (P-value = 0.082), a slight tendency towards protection against cerebral malaria was observed in this comparison as well
Summary
Cerebral malaria is one of the most severe manifestations of Plasmodium falciparum malaria. The excessive sequestration of parasitized red blood cells (PRBCs) to brain microvascular endothelium has been suggested to contribute to the pathophysiology of cerebral malaria [1], yet the pathogenesis of cerebral malaria remains poorly understood. A number of ADAMTS13 mutations causing congenital thrombotic thrombocytopaenic purpura (TTP), a rare life-threatening disease characterized by thrombocytopenia, microangiopathic haemolytic anaemia, renal failure, and neurological deficits including coma, have been identified [6,8]. These symptoms are key features of severe falciparum malaria. This study reports a significant association of common ADAMTS13 polymorphism with protection against cerebral malaria in Thai patients with falciparum malaria
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have