Comparison of allele frequencies of Plasmodium falciparum merozoite antigens in malaria infections sampled in different years in a Kenyan population

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.

Proteome-wide mapping of immune features onto Plasmodium protein three-dimensional structures

“…Immunologically relevant polymorphisms are expected to be maintained at a high frequency within a population. A minor allele frequency (MAF) threshold of 5% is commonly used to distinguish between high- and low-frequency polymorphisms 55 – 58 . Correspondingly, polymorphic residues with a MAF ≥ 5% had significantly higher RSA than all polymorphic residues (p = 0.04, Mann-Whitney test), with a median RSA of 0.52.…”

Parasite-Related Genetic and Epigenetic Aspects and Host Factors Influencing Plasmodium falciparum Invasion of Erythrocytes

“…The former (invasion ligands) enable parasite adhesion and, during the first steps of invasion, ligand selection associated with the parasite's invasion phenotype (Nery et al, 2006; Iyer et al, 2007). Several invasion phenotypes associated with invasion ligand expression have been described for P. falciparum , thereby enabling isolates obtained from infected patients and laboratory strains to be classified into groups (Nery et al, 2006; Ochola-Oyier et al, 2016). Parasite ligand selection has notably been seen in studies involving African populations where differences in invasion ligand expression have been found.…”

“…For example, slightly higher eba175 gene expression and lower eba181 gene expression have been observed when comparing a Ghanaian population to a Senegalese one and possible correlation of this invasion pattern to patients' immunological responses and endemicity levels (Bowyer et al, 2015). Population studies enable analyzing invasion phenotype occurrence and the detection of the most important invasion proteins which could be exploited for developing therapeutic strategies and preventative measures (Bowyer et al, 2015; Ochola-Oyier et al, 2016).…”

“…Some highly expressed P. falciparum proteins, like EMP1, are recognized by the host's immune system, thereby inducing antibody production (Turner et al, 2015; Abdi et al, 2016). Certain host populations' immune-response traits (e.g., the prevalence of some human leukocyte antigen alleles) have led different parasite strains to preferentially express some invasion proteins rather than others (Nery et al, 2006; Bowyer et al, 2015; Ochola-Oyier et al, 2016). This phenomenon has also been linked to the appearance of chronic infection in some patients (Abdi et al, 2016).…”

“…Sialic acid-dependent parasites are essentially associated with greater expression of ligands needing sialic acid moieties in erythrocyte membrane receptors, such as members of the Pf EBA protein family (i.e., Pf EBA175, Pf EBA140, Pf EBA181, Pf EBL1) and some members of the Pf Rh family (i.e., Pf Rh1) (Cowman et al, 2017). Parasite ligands which do not need these moieties for binding to erythrocyte surface receptors prevail in sialic-acid-independent parasites (i.e., some members of the Pf Rh protein family, like Pf Rh2b and Pf Rh4) (Dolan et al, 1990; Nery et al, 2006; Ochola-Oyier et al, 2016; Cowman et al, 2017). It is also known that the parasite can switch from one invasion phenotype to another (depending on a particular host's environment or culture conditions) by varying the expression of its key invasion ligands (Stubbs et al, 2005; Awandare et al, 2018).…”