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Increased eosinophil activity in acute Plasmodium falciparum infection--association with cerebral malaria
J A Kurtzhals1, C M Reimert, E Tette
1Immunology Unit, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.
Insights
Eosinophil counts change during Plasmodium falciparum malaria, decreasing in symptomatic cases but increasing in asymptomatic infections. Eosinophil activation markers are high in severe malaria, suggesting tissue involvement rather than reduced production.
Area of Science:
- Immunology
- Infectious Diseases
- Hematology
Background:
- Eosinophils play a role in immune responses.
- Plasmodium falciparum causes malaria, a significant global health issue.
Purpose of the Study:
- To investigate the eosinophil response during Plasmodium falciparum infection in Ghanaian children.
- To understand the role of eosinophils in malaria pathogenesis, particularly severe forms.
Main Methods:
- Longitudinal cohort study of initially parasite-free children.
- Hospital-based study of pediatric malaria patients (cerebral malaria, severe anemia, uncomplicated malaria).
- Measurement of peripheral eosinophil counts, plasma eosinophil cationic protein (ECP), and eosinophil protein X (EPX).
Main Results:
- Asymptomatic P. falciparum infection increased eosinophil counts; symptomatic malaria decreased them.
- Pediatric malaria patients had low eosinophil counts during acute illness, with subsequent eosinophilia post-cure.
- Elevated plasma ECP and EPX levels were observed in acute malaria, especially cerebral malaria, despite low eosinophil counts, indicating activation and potential tissue sequestration/destruction.
- Granule protein levels correlated with inflammatory markers (TNF) and T cell activation (sIL-2R).
Conclusions:
- Low eosinophil counts in acute malaria are likely due to tissue sequestration and destruction, not reduced production.
- Eosinophil activation, indicated by granule protein release, is linked to inflammatory responses and T cell activation in malaria.
- Eosinophil granule proteins may contribute to both malaria control and severe malaria pathogenesis, independent of a Th2-like response.
Abstract:
To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.