Adaptive immunity selects against malaria infection blocking mutations.

The mutation responsible for Duffy negativity, which impedesPlasmodium vivaxinfection, has reached high frequencies in certain human populations. Conversely, mutations capable of blocking the more lethalP.falciparumhave not succeeded in malarious zones. Here we present an evolutionary-epidemiological model of malaria which demonstrates that if adaptive immunity against the most virulent effects of malaria is gained rapidly by the host, mutations which prevent infectionper seare unlikely to succeed. Our results (i) explain the rarity of strain-transcendingP.falciparuminfection blocking adaptations in humans; (ii) make the surprising prediction that mutations which blockP.falciparuminfection are most likely to be found in populations experiencing low or infrequent malaria transmission, and (iii) predict that immunity against some of the virulent effects ofP.vivaxmalaria may be built up over the course of many infections. Author summary Malaria has profoundly influenced human evolution. However, humans have adapted to two major malaria parasites,Plasmodium falciparumandPlasmodium vivax, by strikingly different strategies. The Duffy negative blood group impairsP.vivaxentry to red blood cells and reduces the chance of becoming infected. No equivalent blocking adaption againstP.falciparumhas evolved to become widespread, despite the existence of candidate mutations. We show that rapidly gained adaptive immunity to malaria virulence limits the success of infection blocking mutations. This could account for humans' contrasting adaptations toP.falciparumandP.vivax. Our results highlight the critical role of adaptive immunity in determining how vertebrate hosts evolve in response to pathogen selection, and provide a new framework within which to understand this process.