Anemia is a major complication of
malaria, driven largely by loss of uninfected RBCs during
infection. RBC clearance through loss of
complement regulatory
proteins (CRPs) is a significant contributor to
anemia in Plasmodium falciparum
infection, but its role in Plasmodium vivax
infection is unknown. CRP loss increases RBC susceptibility to macrophage clearance, a process that is also regulated by CD47. We compared CRPs and CD47 expression on infected and uninfected RBCs in adult patients with vivax and
falciparum malaria and different
anemia severities from Papua, Indonesia. Complement activation and parasite-specific
complement-fixing
antibodies were measured by ELISA. Levels of CR1 and CD55 were reduced in severe
anemia in both falciparum and
vivax malaria. Loss of CRPs and CD47 was restricted to uninfected RBCs, with infected RBCs having higher expression. There was no association among
complement-fixing
antibodies, complement activation, and CRP loss. Our findings demonstrate that CRP loss is a pan-species, age-independent mechanism of malarial
anemia. Higher levels of CRP and CD47 expression on infected RBCs suggest that parasites are protected from
complement-mediated destruction and macrophage clearance. Lack of associations between protective
antibodies and CRP loss highlight that
complement pathogenic and protective pathways are distinct mechanisms during
infection.