Tumor Necrosis Factor and Disease Severity in Children with Falciparum Malaria

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ケ312 pg per milliliter) than in the 55 who survived (184ケ32 pg per milliliter; P<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<0.02), hyperparasitemia (P<0.002), age under three years (P<0.03), and severity of illness as measured by a prognostic index (P<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ケ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. (N Engl J Med 1989; 320:1586–91.) THE most severe complication of Plasmodium falciparum infection is cerebral malaria, from which more than 1 million children die annually in sub-Saharan Africa.1,2 Little is known about the pathogenesis of this condition.3,4 Recent reports suggest that the cytokine tumor necrosis factor, produced primarily by activated macrophages and T lymphocytes,5,6 may be an important component of the host response to malaria. Elevated concentrations of tumor necrosis factor have been noted in the serum of patients with malaria,7,10 and treatment with anti–tumor necrosis factor antibodies protected mice from the cerebral complications of Plasmodium berghei infection.11 Effects similar to those of endotoxins have. © 1989, Massachusetts Medical Society. All rights reserved.