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Tumor necrosis factor and severe malaria
Insights
High tumor necrosis factor-alpha (TNF alpha) levels are linked to severe malaria manifestations in children, including hyperparasitemia and anemia. These elevated TNF alpha levels are not specific to cerebral malaria.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Plasmodium falciparum malaria is a major cause of childhood illness and mortality.
- Tumor necrosis factor-alpha (TNF alpha) is a pro-inflammatory cytokine implicated in malaria pathogenesis.
- The specific role of TNF alpha in different malaria clinical presentations requires further elucidation.
Purpose of the Study:
- To investigate the association between plasma TNF alpha concentrations and Plasmodium falciparum infection in Zairian children.
- To determine if TNF alpha levels correlate with specific clinical manifestations of severe malaria.
Main Methods:
- Plasma TNF alpha concentrations were measured in children with severe malaria, mild malaria, and other illnesses.
- Parasite density, clinical signs (anemia, hypoglycemia, cerebral malaria), and outcomes were recorded.
- Statistical analyses, including multiple linear regression, were used to assess associations.
Main Results:
- Children with P. falciparum infection had significantly higher plasma TNF alpha levels than aparasitemic children.
- TNF alpha levels decreased significantly in parasitemic children from day 0 to day 7.
- Elevated TNF alpha was independently associated with hyperparasitemia and severe anemia, and increased with parasite density.
- TNF alpha levels were similarly elevated in children with cerebral malaria and other severe malaria signs, but not specifically linked to fatal outcomes.
Conclusions:
- High plasma TNF alpha levels are associated with several severe malaria manifestations in children, including hyperparasitemia and severe anemia.
- TNF alpha elevation is not specific to cerebral malaria and is not directly correlated with fatal outcomes in this cohort.
- These findings highlight the complex role of TNF alpha in P. falciparum infection severity.
Abstract:
To investigate the relation of tumor necrosis factor-alpha (TNF alpha) to Plasmodium falciparum infection, plasma TNF alpha concentrations were measured in Zairian children with severe malaria, mild malaria, or other illnesses. The initial geometric mean plasma concentration of TNF alpha among 61 children with P. falciparum infection, (71 pg/ml) was higher than the level in 26 severely ill, aparasitemic children (10 pg/ml; P less than .001). Among 29 parasitemic children, initial geometric mean TNF alpha levels decreased from 77 to 5 pg/ml (P less than .001) at day 7. TNF alpha levels increased with parasite density and were associated with hyperparasitemia, severe anemia, hypoglycemia, and young age but not with cerebral malaria or fatal outcome. However, TNF alpha levels were elevated equally in children with cerebral malaria and with other signs of severe malaria. With multiple linear regression, TNF alpha levels were elevated independently in children with hyperparasitemia (P = .001) and severe anemia (P = .04). In this study, high TNF alpha levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria.