Role of complement in severe malarial anemia

Plasmodium falciparum is responsible for the deaths of hundreds of thousands of children every year. Most of these deaths are the result of complications such as severe malarial anemia (SMA). There are now considerable data that suggest that complement plays a role in the development of anemia during malaria infection by opsonization of uninfected erythrocytes with C3 fragments which can lead to phagocytosis of erythrocytes. The increased susceptibility to complement deposition of erythrocytes seems to be related to the loss of complement regulatory proteins, in particular CR1, and to age-related decreases in their expression in young children. Further, there is evidence that malaria treatment exacerbates complement activation and may lead to increased opsonization of uninfected erythrocytes. The evidence suggests that complement is an attractive target for adjunctive therapy during the treatment of SMA. Genetic studies have not revealed any strong associations between CR1 polymorphisms and severe malarial anemia. Further genetic association studies between polymorphisms of the complement genes and susceptibility to SMA are needed to identify additional potential therapeutic targets.