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Antipyretics reduce the prolonged, high fever characteristic of typhoid fever. The benefits of nonsteroidal drugs in this role have not been quantified. There have been concerns about the safety of antipyretics in typhoid.In a double blind randomized study, 80 Vietnamese children with uncomplicated typhoid fever were randomized to receive identical syrup preparations of ibuprofen (10 mg/kg) or paracetamol (12 mg/kg) every 6 h until 36 h after defervescence. Children with a nalidixic acid-susceptible (NaS) isolate of Salmonella typhi were treated with ofloxacin (15 mg/kg/day) for 3 days and those with a nalidixic acid-resistant (NaR) isolate were treated for 7 days.S. typhi was isolated from 36 of 40 children randomized to ibuprofen (11 isolates NaR) and 37 of 40 randomized to paracetamol (13 isolates NaR). The median (range) fever clearance time (hours) was shorter in the ibuprofen group than the paracetamol group (68, 4 to 260 vs. 104, 12 to 404; P = 0.055) as was the area under the temperature time curve above 37°C (74, 0 to 237 vs. 127, 0 to 573; P = 0.013). The differences occurred predominantly in the children infected with a NaRS. typhi whose infections responded more slowly to antibiotic treatment. There were no major side effects associated with the use of either drug. There were no differences between the two treatment arms in the concentrations of circulating interleukin-6 and tumor necrosis factor α during the course of treatment.The antipyretic effect of ibuprofen is superior to that of paracetamol in children with typhoid fever, particularly those with prolonged fever. Both antipyretics appeared to be safe.