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Tumor necrosis factor and disease severity in children with falciparum malaria
G E Grau1, T E Taylor, M E Molyneux
1Department of Pathology, Centre Médical Universitaire, Geneva, Switzerland.
Insights
Elevated tumor necrosis factor (TNF) levels in children with severe Plasmodium falciparum malaria correlate with increased mortality and disease severity, particularly in cases of cerebral malaria and hypoglycemia. Further research is needed to confirm TNF's role in disease pathogenesis.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Severe Plasmodium falciparum malaria is a significant cause of mortality in children.
- Tumor necrosis factor (TNF) is a pro-inflammatory cytokine implicated in various disease states.
Purpose of the Study:
- To investigate the association between serum concentrations of tumor necrosis factor (TNF) and the clinical outcomes of severe Plasmodium falciparum malaria in children.
- To explore the relationship between TNF levels and specific clinical manifestations such as cerebral malaria and hypoglycemia.
Main Methods:
- Serum concentrations of TNF were measured in 65 Malawian children diagnosed with severe Plasmodium falciparum malaria.
- Clinical data, including consciousness, hypoglycemia, parasitemia, age, and disease severity, were recorded at presentation.
- TNF levels were compared between survivors and non-survivors, and correlations with clinical parameters were analyzed.
Main Results:
- Mean serum TNF concentrations were significantly higher in children who died compared to survivors.
- Increased TNF levels were strongly associated with higher mortality rates, hypoglycemia, hyperparasitemia, younger age, and greater disease severity.
- TNF levels decreased significantly in convalescent patients, indicating a transient elevation during acute illness.
Conclusions:
- Elevated serum TNF levels are frequently observed in children with severe Plasmodium falciparum malaria, especially those with cerebral malaria or hypoglycemia.
- High TNF concentrations are a significant indicator of poor prognosis and increased mortality risk in severe malaria.
- The precise role of TNF in the pathogenesis of severe malaria symptoms warrants further investigation.
Abstract:
To investigate the role of tumor necrosis factor in Plasmodium falciparum infections, we measured serum concentrations of this cytokine in 65 Malawian children with severe falciparum malaria. Of these children (mean age, 5.3 years), 55 were unconscious and 10 had hypoglycemia at presentation. Although there was considerable overlap, the mean (+/- SEM) initial serum concentration of tumor necrosis factor was significantly higher in the 10 patients who died (709 +/- 312 pg per milliliter) than in the 55 who survived (184 +/- 32 pg per milliliter; P less than 0.02). The mortality rate increased with the concentration of tumor necrosis factor: at a level of less than 100 pg per milliliter, 1 of 24 patients died; at 100 to 500 pg per milliliter, 6 of 34 patients; and at more than 500 pg per milliliter, 3 of 7 patients. High concentrations of tumor necrosis factor were also associated with hypoglycemia (P less than 0.02), hyperparasitemia (P less than 0.002), age under three years (P less than 0.03), and severity of illness as measured by a prognostic index (P less than 0.0005). The highest serum concentrations of tumor necrosis factor were found in patients who died shortly after admission. The concentrations in cerebrospinal fluid were within the normal range in all patients. In serum samples obtained from 38 convalescent patients, the concentration of tumor necrosis factor declined to a mean of 16 +/- 3 pg per milliliter. We conclude that the level of tumor necrosis factor is frequently increased in patients with severe falciparum malaria, particularly in those with cerebral malaria or hypoglycemia. To determine whether it is important in the pathogenesis of the signs and symptoms of the disease requires further study.