Complement activation in malaria: friend or foe?

• The complement cascade is activated during malaria infection via several pathways.
• There is little evidence that complement activation during malaria infection is beneficial to the host.
• Complement plays a central role in the pathogenesis of severe malaria and placental malaria.

Complement is activated during malaria infection, but there is little evidence that it benefits the host. On the contrary, growing evidence points to the central role of complement activation in the pathogenesis of complicated malaria. Recent evidence suggests a critical role for C5a and the membrane attack complex in the pathogenesis of cerebral malaria, and for C5a in the pathogenesis of placental malaria. In addition, erythrocytes of children with severe malarial anemia have increased deposition of C3b and decreased capacity to regulate complement activation, that probably increase their susceptibility to destruction by liver and splenic macrophages. These observations justify further investigation of the role of complement in malaria and the testing of complement inhibitors as adjunctive treatment for severe malaria.