Abstract
BackgroundPlasmodium falciparum merozoite antigens elicit antibody responses in malaria-endemic populations, some of which are clinically protective, which is one of the reasons why merozoite antigens are the focus of malaria vaccine development efforts. Polymorphisms in several merozoite antigen-encoding genes are thought to arise as a result of selection by the human immune system.MethodsThe allele frequency distribution of 15 merozoite antigens over a two-year period, 2007 and 2008, was examined in parasites obtained from children with uncomplicated malaria. In the same population, allele frequency changes pre- and post-anti-malarial treatment were also examined. Any gene which showed a significant shift in allele frequencies was also assessed longitudinally in asymptomatic and complicated malaria infections.ResultsFluctuating allele frequencies were identified in codons 147 and 148 of reticulocyte-binding homologue (Rh) 5, with a shift from HD to YH haplotypes over the two-year period in uncomplicated malaria infections. However, in both the asymptomatic and complicated malaria infections YH was the dominant and stable haplotype over the two-year and ten-year periods, respectively. A logistic regression analysis of all three malaria infection populations between 2007 and 2009 revealed, that the chance of being infected with the HD haplotype decreased with time from 2007 to 2009 and increased in the uncomplicated and asymptomatic infections.ConclusionRh5 codons 147 and 148 showed heterogeneity at both an individual and population level and may be under some degree of immune selection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1304-8) contains supplementary material, which is available to authorized users.
Highlights
Plasmodium falciparum merozoite antigens elicit antibody responses in malaria-endemic populations, some of which are clinically protective, which is one of the reasons why merozoite antigens are the focus of malaria vaccine development efforts
These samples were defined as complicated malaria infections and were representative of the parasite population in Kilifi County since Kilifi District Hospital (KDH) serves a population within an 891 km2 area of 15 administrative locations within the Kilifi Health and Demographic Surveillance System (KHDSS) [34]; and, (3) 11 genotypically distinct laboratory isolates obtained from geographically diverse P. falciparum sources (3D7, cloned from an airport malaria case in The Netherlands; RO33 and Palo Alto, from Africa; K1, Dd2, FCC2 and D10, V1/S from Southeast Asia; Wellcome, nominally from Africa but suspected to have been previously crosscontaminated by parasites of unknown source during culture; HB3 from Honduras and IT from Brazil)
Merozoite gene haplotype frequencies in the uncomplicated malaria infections between 2007 and 2008 Most haplotypes were present as stable frequencies over the two-year period
Summary
Plasmodium falciparum merozoite antigens elicit antibody responses in malaria-endemic populations, some of which are clinically protective, which is one of the reasons why merozoite antigens are the focus of malaria vaccine development efforts. Polymorphisms in several merozoite antigen-encoding genes are thought to arise as a result of selection by the human immune system. Genes involved in immune interactions tend to contain adaptive variation that is maintained by balancing selection [1, 2]. In Plasmodium falciparum balancing selection is evidenced by the presence of multiple polymorphisms in several merozoite antigens, such as merozoite surface protein-1 (MSP-1) [3], apical membrane antigen-1. Since merozoite proteins are targets of host immunity [10,11,12,13] polymorphisms are thought to be maintained by selection from host immune responses. An individual may resist infection to one parasite allele for which they have pre-existing immunity but not to a heterologous allele that they have not yet encountered.
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