Abstract
BackgroundAs Plasmodium falciparum and Plasmodium vivax co-exist in most malaria-endemic regions outside sub-Saharan Africa, malaria control strategies in these areas must target both species in order to succeed. Population genetic analyses can predict the effectiveness of interventions including vaccines, by providing insight into patterns of diversity and evolution. The aim of this study was to investigate the population genetics of leading malaria vaccine candidate AMA1 in sympatric P. falciparum and P. vivax populations of Papua New Guinea (PNG), an area of similarly high prevalence (Pf = 22.3 to 38.8%, Pv = 15.3 to 31.8%).MethodsA total of 72 Pfama1 and 102 Pvama1 sequences were collected from two distinct areas, Madang and Wosera, on the highly endemic PNG north coast.ResultsDespite a greater number of polymorphic sites in the AMA1 genes of P. falciparum (Madang = 52; Wosera = 56) compared to P. vivax (Madang = 36, Wosera = 34), the number of AMA1 haplotypes, haplotype diversity (Hd) and recombination (R) was far lower for P. falciparum (Madang = 12, Wosera = 20; Hd ≤0.92, R ≤45.8) than for P. vivax (Madang = 50, Wosera = 38; Hd = 0.99, R = ≤70.9). Balancing selection was detected only within domain I of AMA1 for P. vivax, and in both domains I and III for P. falciparum.ConclusionsHigher diversity in the genes encoding P. vivax AMA1 than in P. falciparum AMA1 in this highly endemic area has important implications for development of AMA1-based vaccines in PNG and beyond. These results also suggest a smaller effective population size of P. falciparum compared to P. vivax, a finding that warrants further investigation. Differing patterns of selection on the AMA1 genes indicate that critical antigenic sites may differ between the species, highlighting the need for independent investigations of these two leading vaccine candidates.
Highlights
As Plasmodium falciparum and Plasmodium vivax co-exist in most malaria-endemic regions outside sub-Saharan Africa, malaria control strategies in these areas must target both species in order to succeed
Diversity is an indicator of the evolutionary fitness of a parasite population as high genetic diversity provides greater potential for adaptation to changing environmental conditions and for immune escape, which is facilitated by antigenic polymorphism [11]
Six P. falciparum AMA1 (PfAMA1) DII residues (Asp348, Lys351, Gln352, Phe385, Asp388 and Arg389) reported to be critical for binding of the 4G2 inhibitory antibody [81] were conserved amongst the PfAMA1 Papua New Guinea (PNG) sequences analysed. This is the first study of comparative P. falciparum and P. vivax genetic diversity to be conducted in a setting of high or similar co-endemicity, and the first study to directly compare the diversity of sympatric parasite populations in PNG
Summary
As Plasmodium falciparum and Plasmodium vivax co-exist in most malaria-endemic regions outside sub-Saharan Africa, malaria control strategies in these areas must target both species in order to succeed. Greater morbidity and mortality from malaria is attributed to infection with Plasmodium falciparum, Plasmodium vivax is responsible for much of the global malaria burden. This species can cause severe disease [1,2,3,4], has a broader geographic distribution than P. falciparum and is increasingly being recognized as less responsive to malaria control measures [5]. The greater diversity of P. vivax has been demonstrated using a panel of global isolates [8] and in an endemic area of Cambodia with low transmission of both species [9,10]. Defining the genetic diversity of P. falciparum and P. vivax parasite populations can provide important insight into malaria epidemiology and parasite evolution, in addition to how well the local parasite population might respond to interventions such as malaria vaccines [19]
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