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.