Adaptive immunity selects against malaria infection blocking mutations

• Published in: PLoS computational biology Vol. 16; no. 10; p. e1008181
• Main Authors: Penman, Bridget S, Gandon, Sylvain
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.10.2020; PLOS; Public Library of Science (PLoS)
• Subjects: Adaptation; Adaptive immunity; Adaptive Immunity - genetics; Age; Biodiversity and Ecology; Biology and Life Sciences; Blocking; Blood groups; Computational Biology; Costs; Disease transmission; Environmental Sciences; Epidemic models; Epidemiology; Erythrocytes; Evolution, Molecular; Genetic Predisposition to Disease - genetics; Genotype & phenotype; Human populations; Humans; Immunity; Infections; Malaria; Malaria, Falciparum - epidemiology; Malaria, Falciparum - genetics; Malaria, Falciparum - immunology; Malaria, Vivax - epidemiology; Malaria, Vivax - genetics; Malaria, Vivax - immunology; Medicine and Health Sciences; Models, Genetic; Mortality; Mutation; Mutation - genetics; Parasites; Pathogens; Physiological aspects; Plasmodium falciparum - immunology; Plasmodium vivax - immunology; Population; Populations; Success; Vector-borne diseases; Virulence; Indonesia
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1008181

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.