Abstract
Plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) concentrations, a measure of parasite biomass, have been correlated with malaria severity in adults, but not yet in children. We measured plasma PfHRP-2 in Tanzanian children with uncomplicated (n = 61) and cerebral malaria (n = 45; 7 deaths). Median plasma PfHRP-2 concentrations were higher in cerebral malaria (1008 [IQR 342–2572] ng/mL) than in uncomplicated malaria (465 [IQR 36–1426] ng/mL; p = 0.017). In cerebral malaria, natural log plasma PfHRP-2 was associated with coma depth (r = −0.42; p = 0.006) and mortality (OR: 3.0 [95% CI 1.03–8.76]; p = 0.04). In this relatively small cohort study in a mesoendemic transmission area of Africa, plasma PfHRP-2 was associated with pediatric malaria severity and mortality. Further studies among children in areas of Africa with higher malaria transmission and among children with different clinical manifestations of severe malaria will help determine the wider utility of quantitative PfHRP-2 as a measure of parasite biomass and prognosis in sub-Saharan Africa.
Highlights
Sequestration of parasitized red blood cells within the deep organ microvasculature is thought to explain the pathogenicity of Plasmodium falciparum, and results from the ability of parasitized erythrocytes to cytoadhere to endothelial cells in post-capillary venules [1]
Plasma concentration of Plasmodium falciparum histidine-rich protein-2 (PfHRP-2), a measure of total parasite biomass, was associated with malaria severity, depth of coma and mortality in Tanzanian children living in an area with mesoendemic malaria transmission
This supports similar findings in adults from areas of relatively unstable transmission in Asia and Indonesian Papua [4,6]; it is significant because it extends the association between parasite biomass and disease severity to African children, the demographic sub-group with the greatest burden of severe malaria morbidity and mortality
Summary
Sequestration of parasitized red blood cells within the deep organ microvasculature is thought to explain the pathogenicity of Plasmodium falciparum, and results from the ability of parasitized erythrocytes to cytoadhere to endothelial cells in post-capillary venules [1]. Autopsies of cerebral malaria have demonstrated 26– 40 times the burden of Plasmodium falciparum parasites in the deep tissue circulation of the brain compared to peripheral blood [2,3]. This phenomenon is thought to explain the poor association between malaria severity and parasitemia measured by peripheral blood microscopy [4]. Plasma PfHRP-2 levels at presentation correlated with severity of malaria illness in adults from Thailand [4] and Indonesian Papua [6] In both these series, plasma PfHRP-2 was an independent predictor of mortality [4,6]. With high rates of asymptomatic parasitemia in Africa and Papua New Guinea, low plasma PfHRP2 levels in children clinically diagnosed with severe malaria may suggest an alternative non-malarial cause of severe disease with incidental parasitemia
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