Imbalanced Distribution of Plasmodium falciparum EBA-175 Genotypes Related to Clinical Status in Children from Bakoumba, Gabon

Abstract

Objective: The erythrocyte binding antigen 175 kDa (EBA-175) of Plasmodium falciparum is one of the major ligands for red blood cell invasion by merozoites. EBA-175 is a dimorphic antigen but the role that dimorphism plays in host parasite interaction is not fully understood. In this study, we sought to determine the distribution of EBA-175 genotypes and its pathogenetic influence. Methods:The nested polymerase chain reaction was used to determine the genotypes of P. falciparum isolates from asymptomatic and symptomatic Gabonese children.Results: CAMP strains (C-segment) and FCR-3 strains (F-segment) were found in 13/50 (26%) and 19/50 (38%) symptomatic children, respectively and in 16/66 (24%) and 46/66 (70%) asymptomatic children, respectively. The prevalence of mixed C-/F-infection was 18/50 (36%) and 4/66 (6%) in symptomatic and asymptomatic children, respectively. Conclusions:These results show that mixed C-/F-infection is associated with clinical malaria (χ 2 , P <0.01) and may have important therapeutic implications. The antigenic diversity of Plasmodium falciparum is the main obstacle to antimalarial vaccine development. Erythrocyte-binding antigen 175 kDa (EBA-175), expressed on the merozoite surface, is involved in P. falciparum binding to erythrocytes. [1][2][3][4][5] In animal models, immunization with synthetic EBA-175 peptides encompassing amino acids 1062 to 1103 elicits antibodies that inhibit merozoite invasion by 80% in vitro. These antibodies appear to act by preventing EBA-175 binding to erythrocytes. 6 In addition, a significant reduction in parasitemia was recently reported in monkeys immunized with EBA-175 is composed of 7 regions (region I-VII) and possesses 2 cysteine-rich segments (F1 and F2) located at the N-terminus in region II (figure 1). These cysteine-rich segments, F1 and F2, are responsible for glycophorin A binding to the erythrocyte membrane 4 and contain a very small number of polymorphic regions. EBA-175 region III is located in the central part of the gene, and genomic studies of two P. falciparum strains revealed two highly dimorphic segments in region III,8,9 Dimorphism is referred to as the F-fragment in the FCR-3 strain and the C-fragment in the CAMP strain. The two segments are inserted at different positions of region III and differ in length by 27 amino acids. These two alleles are both conserved, and Plasmodium merozoites, which are haploid, can possess one or the other, but not both.The role of EBA-175 antigen dimorphism in host-parasite interactions is not fully understood. Preliminary evidence suggests that the initial molecular interaction involves binding of the conserved domain (region II of EBA-175) to glycophorin A sialic acid residues, followed by proteolytic cleavage of EBA-175 and binding of the dimorphic C-and F-segments to the glycophorin A backbone. 8,9 Likewise, the role of this dimorphism in acquired protective immunity to field strains is not known. It was recently shown that EBA-175 is able to use

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

“…This result is therefore consistent with our previously reported data. 30 Overall, our study demonstrated the predominance of the allelic family K1 of MSP-1 locus clearly, confirming data reported elsewhere. 31,32 However, no significant association was found between the occurrence of the K1 genotype and severe malaria; K1 was observed in 82% and 90% PRBC from individuals with severe and uncomplicated malaria, respectively.…”

Distribution of erythrocyte binding antigen 175 (EBA-175) alleles and ABO blood groups in a hypoendemic area in Senegal

“…Similarly, in Bakoumba, Gabon, the F-fragment was more prevalent in children [19]. Similar frequencies were also described in Nigeria, The Gambia, Gabon, and South Africa [20].…”

Submicroscopic Plasmodium falciparum Infections Before and After Sulfadoxine-Pyrimethamine and Artesunate Association Treatment in Dienga, Southeastern Gabon

“…Block 2 of merozoite surface protein (MSP)-1, block 3 of MSP-2, and erythrocyte binding antigen (EBA)-175 were amplified by nested PCR as previously reported. [14][15][16] Briefly, after amplification, 10 µl of each nested PCR product were analyzed by electrophoresis on a 1.5% agarose gel. PCR-positive samples at day 0 and day 14 were processed concomitantly and the bands compared.…”