Association of Severe Malaria with a SpecificPlasmodium falciparumGenotype in French Guiana

Abstract

Why severe Plasmodium falciparum malaria occurs in only a small percentage of patients is unclear. The possibility that specific parasite characteristics contribute to severity has been investigated in French Guiana, a hypoendemic area, where parasite diversity is low and all patients with severe cases are referred to a single intensive care unit. Parasite genotyping in geographically and temporally matched patients with mild and severe disease showed that the association of a specific msp-1 allele (B-K1) with a specific var gene (var-D) was overrepresented among patients with severe versus mild disease (47% vs. 3%, respectively; P<.001). Moreover, this genotype combination was consistently observed in the most severe clinical cases. Reverse-transcription polymerase chain reaction demonstrated programmed expression of var-D in vivo, which is consistent with its potential implication in severe disease. These results provide field evidence of an association of severe malaria with specific genetic characteristics of parasites and open the way for intervention strategies targeting key virulence factors of parasites.

Cytoadherence and Genotype of Plasmodium falciparum Strains from Symptomatic Children in Franceville, Southeastern Gabon

“…For example, in French Guiana, it has been demonstrated that a specific MSP-1 allele (B-K1) bearing a specific variant gene (var-D) has been linked to severe malaria. 33 In Dienga, a village situated in southeastern Gabon approximately 200 km from Franceville where the present study was carried out, the K1 and Mad20 families of MSP-1 were predominantly found in symptomatic individuals compared to asymptomatics. 23 By contrast, in Nigeria it has been shown that the presence of the K1 and MAD20 alleles was significantly associated with asymptomatic malaria, and consequently, a reduced risk of developing the symptomatic disease.…”

“…This result confirmed previous data reported elsewhere 2 and reinforces the conclusion that coma is the only manifestation caused by cytoadhesion of PRBC to the brain vascular endothelium via variant surface antigen. 43 Indeed, it has been documented that severe malaria is associated with expression of the variant surface antigen group A, [44][45][46] group B, 47 groups A or B/A, 48 groups A and B, 49 and group D. 33 Moreover, the postmortem analysis of the brain revealed that all coma cases did not have sequestered parasites in cerebral capillaries. 50 There is also evidence suggesting that severe malaria is associated with expression of PfEMP1 variants that do not bind to CD36.…”

Cytoadherence characteristics to endothelial receptors ICAM-1 and CD36 ofPlasmodium falciparumpopulations from severe and uncomplicated malaria cases

“…Interestingly, another recent study by the Rogerson's group suggested that the dominant clones sequestered in deep organ during severe malaria are usually the same as those in peripheral circulation (Dembo et al, 2006), which supports continued experimental work using circulating parasites. Several studies have used merozoites surface proteins (msp-1 and/or msp-2) polymorphism to describe circulating parasite populations and some authors reported the association of particular genotypes with severity of malaria attack (Ariey et al, 2001;Mockenhaupt et al, 2003;Ranjit et al, 2005;Farooq et al, 2006). However, these associations were described as possibly restricted to geographical areas.…”

Microsatellite Characterization of Plasmodium falciparum from Cerebral and Uncomplicated Malaria Patients in Southern Vietnam

“…We used a set of nine putatively neutral microsatellite markers, instead of surface antigen genes under strong selection pressure (1,4,16,21), to compare the genetic backgrounds of sympatric isolates from patients with cerebral and uncomplicated malaria. We tested the hypothesis that parasites causing cerebral malaria were more genetically related than expected by chance, instead of looking for associations between particular genotypes or antigenic variants and morbidity.…”