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Plasma Plasmodium falciparum Histidine-rich Protein 2 Concentrations in Children With Malaria Infections of Differing
Sophie Uyoga1, Perpetual Wanjiku1, Jesse C Rop1
1KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
Insights
Plasmodium falciparum parasite loads correlate with malaria severity. Plasma P. falciparum histidine-rich protein 2 (PfHRP2) levels may help identify high-risk patients and those critically ill from non-malarial causes.
Area of Science:
- Infectious Diseases
- Parasitology
- Clinical Medicine
Background:
- Previous studies suggest a link between Plasmodium falciparum parasite load and malaria clinical severity.
- Understanding this relationship is crucial for diagnosing and managing malaria.
Purpose of the Study:
- To investigate the relationship between Plasmodium falciparum parasite loads and clinical severity in children.
- To evaluate the utility of P. falciparum histidine-rich protein 2 (PfHRP2) as a severity marker.
Main Methods:
- Quantified P. falciparum parasite loads in children with severe malaria (n=1544), uncomplicated malaria (n=200), and asymptomatic parasitemia (n=33).
- Measured plasma P. falciparum histidine-rich protein 2 (PfHRP2) concentrations across severity groups.
- Analyzed PfHRP2 levels in severe malaria patients with and without invasive bacterial infections.
Main Results:
- Peripheral parasitemia was highest in uncomplicated malaria, followed by severe and asymptomatic malaria.
- Plasma PfHRP2 concentrations increased with malaria severity.
- PfHRP2 levels were significantly lower in severe malaria patients with invasive bacterial infections compared to those without.
Conclusions:
- Clinical severity of Plasmodium falciparum malaria is strongly associated with parasite burden.
- Plasma PfHRP2 concentration is a potential biomarker for identifying children at high clinical risk.
- PfHRP2 testing may aid in identifying critically ill children where malaria is not the primary cause.
Background:
Most previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections.
Methods:
We estimated P. falciparum parasite loads in 3 groups of children with malaria infections of differing severity: (1) children with World Health Organization-defined severe malaria (n = 1544), (2) children admitted with malaria but without features of severity (n = 200), and (3) children in the community with asymptomatic parasitemia (n = 33).
Results:
Peripheral parasitemias were highest in those with uncomplicated malaria (geometric mean [GM] parasite count, 111 064/μL; 95% confidence interval, CI, 86 798-141 819/μL), almost 3 times higher than in those with severe malaria (39 588/μL; 34 990-44 791/μL) and >100 times higher than in those with asymptomatic malaria (1092/μL; 523-2280/μL). However, the GM P. falciparum histidine-rich protein 2 (PfHRP2) values (95% CI) increased with severity, being 7 (4-12) ng/mL in asymptomatic malaria, 843 (655-1084) ng/mL in uncomplicated malaria, and 1369 (1244-1506) ng/mL in severe malaria. PfHRP2 concentrations were markedly lower in the subgroup of patients with severe malaria and concomitant invasive bacterial infections of blood or cerebrospinal fluid (GM concentration, 312 ng/mL; 95% CI, 175-557 ng/mL; P < .001) than in those without such infections (1439 ng/mL; 1307-1584; P < .001).
Conclusions:
The 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 identifying critically ill children in whom malaria is not the primary cause.
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