Adaptive immunity selects against malaria infection blocking mutations

Abstract

The mutation responsible for Duffy negativity, which impedes Plasmodium vivax infection, has reached high frequencies in certain human populations. Conversely, mutations capable of blocking the more lethal P. falciparum have 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 infection per se are unlikely to succeed. Our results (i) explain the rarity of strain-transcending P. falciparum infection blocking adaptations in humans; (ii) make the surprising prediction that mutations which block P. falciparum infection 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 of P. vivax malaria may be built up over the course of many infections.

The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion

“…A recent theoretical evolutionary study may shed some light on these patterns 43 . If it is possible to gain adaptive immunity against the worst impacts of P. falciparum malaria after experiencing relatively few blood stage infections, this limits the advantage of a mutation which partially blocks P. falciparum invasion.…”

The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion

“…A recent theoretical evolutionary study may shed some light on these pattern 41 . If it is possible to gain adaptive immunity against the worst impacts of P. falciparum malaria after experiencing relatively few blood stage infections, this limits the advantage of a mutation which partially blocks P. falciparum invasion.…”

Malaria among the elderly in five communities of Osun East district, Southwest Nigeria: Prevalence and association with non-communicable diseases

“… 14 – 16 However, there is also a possibility that old age and the presence of non-communicable diseases (NCDs) lead to the attenuation of this immunity. 17 , 18 These may put elderly persons at a significantly higher risk of malaria and its unacceptable sequelae. 15 , 19 , 20 …”