Plasmodium falciparum Histidine-Rich Protein-2 Plasma Concentrations Are Higher in Retinopathy-Negative Cerebral Malaria Than in Severe Malarial Anemia

BACKGROUND Malaria retinopathy has been proposed as marker of "true" cerebral malaria (CM), ie, coma due to Plasmodium falciparum vs coma due to other causes, with incidental P falciparum parasitemia. Plasma P falciparum histidine-rich protein-2 (PfHRP2) concentrations distinguish retinopathy-positive (RP) from retinopathy-negative (RN) CM but have not been compared between RN CM and other forms of severe malaria or asymptomatic parasitemia (AP). METHODS We compared plasma PfHRP2 concentrations in 260 children with CM (247 examined for retinopathy), 228 children with severe malarial anemia (SMA), and 30 community children with AP. RESULTS Plasmodium falciparum HRP2 concentrations were higher in children with RP CM than RN CM (P = .006), with an area under the receiver operating characteristic curve of 0.61 (95% confidence interval, 0.53-0.68). Plasmodium falciparum HRP2 concentrations and sequestered parasite biomass were higher in RN CM than SMA (both P < .03) or AP (both P < .001). CONCLUSIONS Plasmodium falciparum HRP2 concentrations are higher in children with RN CM than in children with SMA or AP, suggesting that P falciparum is involved in disease pathogenesis in children with CM. Plasmodium falciparum HRP2 concentrations may provide a more feasible and consistent assessment of the contribution of P falciparum to severe disease than malaria retinopathy.