A hypothesis about the chronicity of malaria infection.
It is generally accepted that malaria evolves as a chronic blood infection by escaping the immune responses directed against a series of antigens that express variable epitopes and/or by selecting parasite populations with distinct polymorphic antigens. However, exacting in vitro studies, performed with clinically well-defined biological material, have correlated the state of protection of African adults (in whom low-grade infection persists) with an indirect defence mechanism where the antibodies are effective owing to their ability to cooperate with blood monocytes. Further studies showed that the antibody bridges the parasite (at the merozoite stage) with a monocyte and triggers the release of mediators which have a parasitistatic, reversible and non-antigen-specific effect. The fact that the parasite directly triggers the antiparasite effect leads Pierre Druilhe and Jean-Louis Pérignon to formulate here an alternative hypothesis for the chronicity of malaria infection, which would rely on conserved antigenic targets and, in contrast with direct mechanisms, would not select emerging mutated parasites. The above two mechanisms are discussed in the context of their fitness with clinical and parasitological observations. It is proposed that they are not mutually exclusive but, rather, may come into play successively as patients gradually evolve from high-grade symptomatic to low-grade asymptomatic parasitic infection.