Fitness components and natural selection: why are there different patterns on the emergence of drug resistance in Plasmodium falciparum and Plasmodium vivax?

Abstract

BackgroundConsidering the distinct biological characteristics of Plasmodium species is crucial for control and elimination efforts, in particular when facing the spread of drug resistance. Whereas the evolutionary fitness of all malarial species could be approximated by the probability of being taken by a mosquito and then infecting a new host, the actual steps in the malaria life cycle leading to a successful transmission event show differences among Plasmodium species. These “steps” are called fitness components. Differences in terms of fitness components may affect how selection imposed by interventions, e.g. drug treatments, differentially acts on each Plasmodium species. Thus, a successful malaria control or elimination programme should understand how differences in fitness components among different malaria species could affect adaptive evolution (e.g. the emergence of drug resistance). In this investigation, the interactions between some fitness components and natural selection are explored.MethodsA population-genetic model is formulated that qualitatively explains how different fitness components (in particular gametocytogenesis and longevity of gametocytes) affect selection acting on merozoites during the erythrocytic cycle. By comparing Plasmodium falciparum and Plasmodium vivax, the interplay of parasitaemia and gametocytaemia dynamics in determining fitness is modelled under circumstances that allow contrasting solely the differences between these two parasites in terms of their fitness components.ResultsBy simulating fitness components, it is shown that selection acting on merozoites (e.g., on drug resistant mutations or malaria antigens) is more efficient in P. falciparum than in P. vivax. These results could explain, at least in part, why resistance against drugs, such as chloroquine (CQ) is highly prevalent in P. falciparum worldwide, while CQ is still a successful treatment for P. vivax despite its massive use. Furthermore, these analyses are used to explore the importance of understanding the dynamic of gametocytaemia to ascertain the spreading of drug resistance.ConclusionsThe strength of natural selection on mutations that express their advantage at the merozoite stage is different in P. vivax and P. falciparum. Species-specific differences in gametocytogenesis and longevity of gametocytes need to be accounted for when designing effective malaria control and elimination programmes. There is a need for reliable data on gametocytogenesis from field studies.

Genome-Wide Patterns of Genetic Polymorphism and Signatures of Selection in Plasmodium vivax

“…P. vivax has marked differences in the timing for the development of different stages and the target cells, when compared with other Plasmodium species that infect humans. Such differences could have an effect on the efficacy of selection acting on different stages ( Schneider and Escalante 2013 ). For instance, the helicases found under selection (specifically, the DEAD-BOX domain) are proteins putatively involved in the development of gametocytes ( Mair et al 2006 ) or that could be involved in other stage-specific processes.…”

The evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (MSP-9), in Plasmodium vivax and closely related species

“…Thus, the genetic polymorphism found in the MSP9 orthologs of the two major human parasites may be the result of different mechanisms of interaction with the host. It is worth noting that it has been hypothesized that natural selection is less efficient when acting at the blood stage of P. vivax than P. falciparum (Schneider and Escalante 2013). Such predictions, together with the contrasting patterns observed in orthologous merozoite proteins such as MSP-1, MSP-10 (Pacheco et al 2007; 2012) and the one studied here; further reinforce the notion that the differences between P. falciparum and P. vivax need to be considered so findings in one species are not simply translated to the other.…”

Genetic diversity of Plasmodium falciparum and genetic profile after artemisinin-based combination therapy (ACTs) deployment in Cameroon for the management of uncomplicated malaria in Children

“…The aim of this study was to perform a molecular characterisation of highly polymorphic markers in P. [42,63]. Moreover, more amplified product was found for the msp2 gene than msp1 amplified products, this could be explained by non-synonymous substitutions introduced in template DNA that could jeopardize the proper annealing of the primer at its binding site in msp1 gene or could be explained by the fact that natural selection is more efficient when acting on msp-1 than msp-2 [59,64]suggesting that msp-1 as compared with msp2 proteins are under strong functional constraints in a complex interaction with the host leading to an increased in host's immunological response [65]. The two markers including msp-1 (16 genotypes) and msp-2 (27 genotypes) revealed considerably greater parasite diversity than glurp (5 genotypes).…”