Pentoxifylline, an inhibitor of
tumor necrosis factor, has been evaluated as an
antimalarial agent in combination with
artesunate in 45 patients with severe
falciparum malaria. Patients were admitted to the intensive care unit at the Hospital for Tropical Diseases in Bangkok, Thailand, and randomly assigned to treatment for 72 hr with a combination of intravenously administered
artesunate and 1) placebo, 2) low-dose
pentoxifylline (0.83 mg/kg/hr), or 3) high-dose
pentoxifylline (1.67 mg/kg/hr). All 45 patients had one or more manifestations of severe
malaria such as
cerebral malaria (n = 18),
renal failure requiring
hemodialysis (n = 9),
azotemia (n = 8),
jaundice (n = 25), or hyperparasitemia (
n = 30). The overall severity was comparable in the three groups. Clinical outcome was assessed with respect to the parasite clearance time and the
fever clearance time in all patients. In addition, a number of subsidiary outcome variables were examined in specific subgroups, including the recovery time from
coma for patients with
cerebral malaria, the duration of intubation in patients with respiratory distress, the number of
hemodialysis treatments needed for patients with
acute renal failure, and the number of units of blood administered to patients requiring transfusion. Concentrations of
tumor necrosis factor were reduced in all three groups at 48 hr
after treatment. No significant differences among the three treatment groups were found for any of the outcome variables examined. We conclude that the addition of
pentoxifylline to
artesunate therapy for severe
malaria produced no evident clinical benefit.