Malaria tropica disease arises from molecular hybridization of the pathogen with ABO blood groups and physiological absence of corresponding isoagglutinins
After transmission of infectious sporozoites from the protozoan parasite Plasmodium falciparum by the fly Anopheles gambiae, the parasite's abundant serine synthesis, occurring throughout its life cycle, hypothetically breaks a species barrier and gains access to a metazoan host's evolutionarily first protein glycosylation or (serologically A-like) O-GalNAcα1-Ser/Thr-R, "T nouvelle" (Tn) antigen formation, which the parasite itself cannot perform. In humans, this ancestral, genetically
... enetically undefined first glycosylation of proteins undergoes carbohydrate chain elongation, which is completed after ABO-blood-group allele-specific mucin-type formation. This understanding implies the phenotypic accommodation of the nonimmune IgM molecule, involving downregulation of the corresponding "natural" anti-A and anti-B isoagglutinin activities in non-O blood groups and the generation of additional hybrid bonds in the case of infections, burdening these groups with the risk of developing live-threatening disease. Consequently, the formation of the blood group AB causes the strongest contact with the pathogen, and precluding the activities of both the innate anti-A and anti-B isoagglutinin, makes this group the least protected and finally to the smallest among the ABO-blood groups, whereas blood group O(H) individuals maintaining these critical isoagglutinins, have the least contact with the pathogen, rarely develop severe disease and survive this coevolution in an immunological balance with the pathogen as the largest blood group worldwide.