Plasma Plasmodium falciparum Histidine-Rich Protein-2 Concentrations Do Not Reflect Severity of Malaria in Papua New Guinean Children

Abstract

Background. In areas of unstable malaria transmission, plasma Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) concentrations parallel total parasite biomass and thus infection severity. However, where transmission is more intense, plasma PfHRP-2 might not reliably predict complications and mortality. Methods. As part of a prospective case-control study of severe pediatric illness in Madang, Papua New Guinea, we recruited 220 children aged 6 months to 10 years with severe falciparum malaria, 48 with uncomplicated malaria, and 139 healthy controls. Groups were matched by age, sex, and province of parental birth. Plasma PfHRP-2 levels were quantified by validated immunoassay. Results. Detectable plasma PfHRP-2 concentrations were present in 21 healthy controls (15.1%). Although plasma PfHRP-2 levels were higher in the children with clinical malaria (P < .001), there was no difference between those with uncomplicated and severe infections (median, 584 and 456 ng/mL, respectively [interquartile range, 77-1114 and 113-1113 ng/mL, respectively]; P = .43). Log parasitemia, hemoglobin, log plasma bilirubin, and plasma creatinine levels were independently associated with plasma PfHRP-2 levels in multiple regression analysis (P = .014), but coma, blood lactate level, and plasma bicarbonate level were not. The 1 severely ill child who died had a plasma PfHRP-2 concentration of 483 ng/mL, close to the group median. Conclusions. The clinical and prognostic utility of plasma PfHRP-2 concentrations depends on the epidemiologic circumstances. In areas of intense malaria transmission, plasma PfHRP-2 reflects recent as well as present infections.