Competition and the Evolution of Reproductive Restraint in Malaria Parasites

Abstract

All organisms must trade off resource allocation between different life processes that determine their survival and reproduction. Malaria parasites replicate asexually in the host but must produce sexual stages to transmit between hosts. Because different specialized stages are required for these functions, the division of resources between these life-history components is a key problem for natural selection to solve. Despite the medical and economic importance of these parasites, their reproductive strategies remain poorly understood and often seem counterintuitive. Here, we tested recent theory predicting that in-host competition shapes how parasites trade off investment in in-host replication relative to between-host transmission. We demonstrate, across several genotypes, that Plasmodium chabaudi parasites detect the presence of competing genotypes and facultatively respond by reducing their investment in sexual stages in the manner predicted to maximize their competitive ability. Furthermore, we show that genotypes adjust their allocation to sexual stages in line with the availability of exploitable red blood cell resources. Our findings are predicted by evolutionary theory developed to explain life-history trade-offs in more traditionally studied multicellular taxa and suggest that the answer to the long-standing question of why so few transmission stages are produced is that in most natural infections heavy investment in reproduction may compromise in-host survival.

The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy

“…However, in a rodent malaria model, P. chabaudi in laboratory mice, we and others have experimentally demonstrated that densities of individual clones within an infection are severely suppressed when coinfecting clones are present (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). This competitive suppression substantially reduces the density of transmission stages (42,43), and hence transmission of individual clones to mosquitoes (33,35,36).…”

“…Instead, the competition between coinfecting malaria parasites probably arises from competition for resources. Most likely, this competition is for access to red blood cells (44,(46)(47)(48)(49)(50)(51)(52)(53), although other resources, such as glucose, may also be involved (40). Immune-mediated apparent competition, wherein the immune response provoked by one strain suppresses the population densities of a coinfecting strain (11), likely also plays a major role (41,54).…”

Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies

“…Greater multiplicity of infection in higher transmission settings could result in higher parasite densities if host immune systems cannot respond to the diversity of parasites or if parasites increase growth rates in the presence of competing clones 14,63 . In addition to transmission intensity, we also observed age-associated variations in RDT detection.…”

The molecular epidemiology of parasite infections: Tools and applications

“…The potential clinical impact of this had been demonstrated previously in rodent models of P. chabaudi [158]. The far reaching implications of such mixed infections on vaccination and drug treatment strategies in malaria, with respect to interfering with competitive interactions and promoting increased virulence, are now well known and continue to be the subject of much debate [159].…”