Oseltamivir and the influenza alphabet.

Received 24 April 2006; accepted 25 April 2006; electronically published 26 June 2006. Reprints or correspondence: Dr. Stephen G. Baum, Dept. of Medicine, Beth Israel Medical Center, Baird Hall 20, Rm. 20, First Ave. at 16th St., New York, NY 10003 (sbaum@ chpnet.org). Clinical Infectious Diseases 2006; 43:445–6 2006 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2006/4304-0009$15.00 The recent emergence of avian influenza, with its attendant high mortality rate, has refocused attention on influenza as a potentially devastating infectious disease. Human-to-human spread of avian influenza is a strong possibility for the future, but currently, outbreaks of human influenza lead to tens of thousands of excess deaths annually in the United States alone. The mainstay of coping with yearly outbreaks of influenza has been (and remains) vaccination, although the vaccine sometimes does not contain the circulating offending strain, as happened in 2004. In that situation, and when high-risk populations in settings such as long-term care facilities have not been vaccinated, there has been increasing reliance on anti-influenza drugs. For several decades, the adamantine drugs amantidine and rimantidine were the only drugs available as prophylactic and therapeutic agents. These drugs are effective only against influenza type A because they inhibit a mu channel involved in uncoating and specific to type A. Even that type-specific efficacy has come into question, because the current influenza A strain is resistant to amantidine and rimantidine, resulting in the Centers for Disease Control and Prevention’s recommendation that these drugs not be used during this flu season. In the past decade, 2 drugs, oseltamivir and zanamivir, were designed and developed to be effective against both influenza A and influenza B. These drugs work as inhibitors of neuraminidase, an enzyme (and the N antigen) on the surface of influenza viruses that cleaves the bond between budding daughter virus particles and the outer membrane of the infected and dying cell. This cleavage process, common to both influenza A and B viruses, allows the nascent virions to leave that cell and move on to new, uninfected cells. In vitro, addition of anti-neuraminidase antibodies to influenza-infected cell cultures does not limit the number of plaques but does limit their size through inhibition of cell-to-cell spread. Oseltamivir, an oral agent, and zanamivir, an inhaled powder, have been used for both prophylaxis and treatment of influenza, but zanamivir is not currently recommended in the United States for prophylaxis. In this issue of Clinical Infectious Diseases, Kawai et al. [1] report the results of a large, prospective, multicenter study from Japan that spanned the influenza seasons of 2004 and 2005 and that demonstrated a significant difference in the effectiveness of oseltamivir for the treatment of influenza A versus influenza B. Febrile patients, who were seen at 36 clinics, were screened for influenza A or B using several commercially available rapid test kits, each of which had an acceptably high sensitivity and specificity. Influenza A was documented in 1818 patients, and influenza B was documented in 1485 patients. The time between onset of fever and initiation of oseltamivir therapy was stratified in 12h periods up to 48 h, and the time after starting treatment at which the temperature returned to normal was recorded. Twenty-one patients with influenza A and 27 patients with influenza B received no anti-influenza drugs. The ages of patients were also stratified into 4 groups (0–6 years, 7–15 years, 16–64 years, and 164 years). Duration of fever in treated patients was significantly shorter than that in untreated patients in both the influenza A and influenza B arms, but the number of untreated patients was small, and there is no information about administration of nonspecific antipyretics, such as salicylates or acetaminophen. In all age strata, the duration from treatment inception to afebrility was longer for patients with influenza B than it was for those with influenza A. Patients of different ages had varying responses to oseltamivir treatment, with patients aged 7–15 years showing the most salutary effect in terms of fever duration in both the influenza A and B arms. However the difference between the shortest and longest mean duration was only ∼4–5 h. For both infections, the group that started therapy 25–36 h after onset had a statistically significant shorter duration of fever, but