BALTIMORE--Antipyretics, such as aspirin and acetaminophen, may prolong the duration of influenza A infection, data from a recent retrospective study suggest.[1] Although these findings need to be confirmed, they raise a warning flag to physicians and patients alike. “My hope is that our findings will evoke questions and sensitize the medical community to the need for prospective studies in this area,” study coauthor Philip A. Mackowiak, MD, told RESPIRATORY REVIEWS.

Dr. Mackowiak and colleagues examined data from vaccine studies conducted between 1978 and 1987. In these studies, 54 volunteers were infected with influenza A, 45 with Shigella sonnei, and 21 with Rickettsia rickettsii. The subjects were allowed to take aspirin or acetaminophen as needed for symptomatic relief; the drugs were used by 13, 21, and 14 subjects in the respective groups. Because of the retrospective design of the study, “we couldnŐt distinguish between aspirin or acetaminophen in terms of whether one might be more of a problem than another in prolonging illness,” Dr. Mackowiak noted.

THE EFFECTS OF ANTIPYRETICS

In the influenza A group, patients who received antipyretics had a significantly longer duration of illness than did those who did not take antipyretics (8.8 vs 5.3 days). Similarly, the duration of S sonnei infection was significantly longer among subjects who took antipyretics than among those who did not (4.6 vs 1.9 days). In contrast, antipyretics use did not alter the duration of illness in the R rickettsii group. Antipyretic therapy was significantly associated with the duration of influenza A and S sonnei infections even after the researchers controlled the analysis for severity of illness.

Further analysis showed that patients infected with S sonnei were usually given antipyretics late in the course of illness (ie, after the mean duration of illness among subjects not treated with antipyretics). Thus, it appears that the use of antipyretics in this group was the result, rather than the cause, of prolonged illness. In the influenza A group, on the other hand, antipyretics were given early in the course of illness.

IS FEVER BENEFICIAL?

There are two major possible mechanisms underlying these findings, according to Dr. Mackowiak. The first is that antipyretics could eliminate a beneficial effect that fever has on the course of influenza infection. “I think that the preponderance of data in the literature suggests that fever has a beneficial effect on the course of many infections,” explained Dr. Mackowiak, who is Chief of the Medical Care Clinical Center at the Maryland VA Health Care System and Professor and Vice Chairman of Medicine at the University of Maryland School of Medicine in Baltimore.

He acknowledged, however, that the benefits of fever in patients with influenza are still uncertain. “I don’t know for certain about influenza,” he admitted. “I’m not aware of any studies (in animal models, for instance) that have looked specifically at the effect of fever on the course of influenza.”

Alternatively, antipyretics could have some other unknown pharmacologic effect on the duration of influenza infection that is independent of their fever–reducing effect. Support for this hypothesis was found in the present study: “We looked at influenza–infected patients’ temperatures after their maximum temperature was recorded and compared the reduction in temperature among those who received antipyretics at that time with that of those who did not receive antipyretics. We really didnŐt find a difference, suggesting that the antipyretic effect was not mediated by a reduction in temperature.”

--Kristin Della Volpe

Reference
1. Plaisance KI, Kudaravalli S, Wasserman SS, et al. Effect of antipyretic therapy on the duration of illness in experimental influenza A, Shigella sonnei, and Rickettsia rickettsii infections. Pharmacotherapy. 2000;20:1417-1422.