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Study Objectives. To determine whether antipyretic therapy prolongs the course of experimental influenza A, Shigella sonnei, and Rickettsia rickettsii infections.

Design. Retrospective observational study.

Setting. University Center for Vaccine Development.

Subjects. Fifty-four volunteers with experimentally induced influenza A, 45 with S. sonnei, and 21 with R. rickettsii infections participated.

Interventions. Subjects from the six influenza A studies were challenged intranasally. If they met certain criteria, they were offered aspirin or acetaminophen for symptomatic relief. Subjects from the three Shigella studies were challenged with the bacteria and then given trimethoprim-sulfamethoxazole. Acetaminophen also could be administered. In the one R. rickettsii trial, subjects were inoculated intradermally and treated with tetracycline. Again, acetaminophen was administered for symptomatic relief.

Measurements and Main Results. Data, excerpted from subjects' study records, were evaluated using Wilcoxon tests, Spearman's correlation coefficients, and multiple regression analysis. Two-tailed hypotheses with a value of 0.05 were used for all of the analyses. There was a striking correlation between antipyretic therapy and duration of illness in subjects infected with influenza A and S. sonnei, but not R. rickettsii.

Conclusions. Multivariate analysis suggested that antipyretic therapy prolonged illness in subjects infected with influenza A, but its use was the result of prolonged illness in those infected with S. sonnei. The precise nature of these relationships requires a prospective, randomized, placebo-controlled trial.