The Human Spleen in Malaria: Filter or Shelter?

The human spleen is an immune sentinel and controls red blood cell (RBC) quality. By mechanically retaining subsets of infected RBCs, the spleen may reduce the pace at which the parasite biomass increases before the adaptive immune response operates. Conversely, the spleen may contribute to malaria pathogenesis, particularly anemia that is associated with splenomegaly. Large spleens may also shelter parasites in chronic carriers. Upon treatment with artemisinins, the spleen clears circulating parasites by pitting and releases 'once-infected' RBCs in circulation. This triggers postartesunate delayed hemolysis and explains the long post-treatment positivity of histidine-rich protein 2 (HRP2)-based dipsticks. Importantly, splenic retention of RBCs also applies to gametocytes, the clearance of which may be enhanced by stiffening them with drugs, a potential way to block malaria transmission.