Abstract
BackgroundThe erythrocyte binding antigen-175 (EBA-175) on Plasmodium falciparum merozoites mediates sialic acid dependent binding to glycophorin A on host erythrocytes and, therefore, plays a crucial role in cell invasion. Dimorphic allele segments have been found in its encoding gene with a 342 bp segment present in FCR-3 strains (F-segment) and a 423 bp segment in CAMP strains (C-segment). Possible associations of the dimorphism with severe malaria have been analysed in a case-control study in northern Ghana.MethodsBlood samples of 289 children with severe malaria and 289 matched parasitaemic but asymptomatic controls were screened for eba-175 F- and C-segments by nested polymerase chain reaction.ResultsIn children with severe malaria, prevalences of F-, C- and mixed F-/C-segments were 70%, 19%, and 11%, respectively. The C-segment was found more frequently in severe malaria cases whereas mixed infections were more common in controls. Infection with strains harbouring the C-segment significantly increased the risk of fatal outcome.ConclusionThe results show that the C-segment is associated with fatal outcome in children with severe malaria in northern Ghana, suggesting that it may contribute to the virulence of the parasite.
Highlights
Malaria parasites invade host erythrocytes via interaction between merozoite surface ligands and erythrocyte receptors [1,2]
Geometric mean parasite density (GMPD) was 30,200/μL and hyperparasitaemia (>250,000/μL) was present in 64 children (22%)
The GMPD of parasitaemic controls was 1,738/μL
Summary
Malaria parasites invade host erythrocytes via interaction between merozoite surface ligands and erythrocyte receptors [1,2]. A large exon 1 is divided into regions I-VI and codes for a tandem array of two DBL domains in region II (Fl and F2) forming the putative ligand site as well as the c-cys domain, region VI Both domains have numerous conserved cystein and hydrophobic amino acid residues supporting their functional relevance. This dimorphism is characterized by an insertion of either a 342 bp segment in FCR-3 strains (F-segment) or a 423 bp segment in CAMP strains (C-segment) [7,10] Both segments share little homology and are located at slightly different positions with the F-segment being 273 bp upstream of the C-segment. The erythrocyte binding antigen-175 (EBA-175) on Plasmodium falciparum merozoites mediates sialic acid dependent binding to glycophorin A on host erythrocytes and, plays a crucial role in cell invasion.
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