Plasma Plasmodium falciparum Histidine-Rich Protein-2 concentrations in children with malaria infections of differing severity in Kilifi, Kenya.
Uyoga S., Wanjiku P., Rop JC., Makale J., Macharia AW., Nyutu GM., Shebe M., Awuondo KA., Mturi N., Woodrow CJ., Dondorp AM., Maitland K., Williams TN.
BackgroundMost previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections.MethodsWe estimated P. falciparum parasite loads in three groups of children with malaria infections of differing severity: (1) children with WHO-defined severe malaria (n=1,544); (2) children admitted with malaria but without features of severity (n=200) and; (3) children in the community with asymptomatic parasitemia (n=33).ResultsPeripheral parasitemias were highest in those with uncomplicated malaria (geometric mean 111,064; 95%CI 86,798-141,819 parasites/μl), being almost three times higher than those with severe malaria (39,588; 34,990-44,791 parasites/μl) and >100 times higher than in those with asymptomatic malaria (1,092; 523-2,280 parasites/μl). However, geometric mean PfHRP2 values (95% CI) increased with severity, being 7 (4-12) ng/ml in asymptomatic malaria, 843 (655-1,084) ng/ml in uncomplicated malaria and 1,369 (1,244-1,506) ng/ml in severe malaria. PfHRP2 concentrations were markedly lower in the sub-group of severe malaria patients with concomitant invasive bacterial infections (IBIs) of blood or CSF (GM 312 ng/ml; 95%CI 175-557; p<0.0001) than in those without IBIs (GM 1,439 ng/ml; 1,307-1,584; P<0.001).ConclusionsThe clinical severity of malaria infections related strongly to the total burden of P. falciparum parasites. A quantitative test for plasma concentrations of PfHRP2 could be useful in identifying children at the greatest clinical risk and to identify critically ill children in whom malaria is not the primary cause.