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.

Highlights

  • Considering the distinct biological characteristics of Plasmodium species is crucial for control and elimination efforts, in particular when facing the spread of drug resistance

  • The results presented here are further discussed in terms of the importance of understanding gametocytaemia, in terms of its pivotal role in malaria transmission, and in ascertaining the effect that natural selection has on the parasite population in terms of spreading mutations that may compromise the lifespan of tools used for control and elimination

  • By contrasting P. vivax and P. falciparum, this investigation illustrates how differences in fitness components, time of gametocyte production and their lifespan, have a critical effect on the efficacy of selection acting on mutations that express their phenotypic effect at the merozoite stage in these two parasite species

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Summary

Introduction

Considering 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 infecting a new host, the actual steps in the malaria life cycle leading to a successful transmission event show differences among Plasmodium species They differ in key aspects of their basic biology, geographic range, and evolutionary origins [1,2,3,4] Such distinctive characteristics affect control and elimination managements of these two malarias; in terms of (i) treatment of their associated clinical diseases and (ii) the design of new control tools, such as choosing candidates for anti-malarial vaccines

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