Management of Influenza
In most years epidemics of influenza cause a significant increase in morbidity and mortality worldwide. With the availability of a new class of antivirals targeting the viral protein neuraminidase, there are new options for the control of influenza. The use of the older antiviral agents (M2 inhibitors: amantadine and rimantadine) is limited because of lack of activity against influenza B viruses, unfavourable tolerability in the case of amantadine and rapid emergence of resistance in a substantial proportion of treated persons. Neuraminidase inhibitors (NAIs) are potent and selective drugs that inhibit influenza neuraminidase, an enzyme that promotes the release of influenza virus from infected cells and facilitates virus spread within the respiratory tract. In contrast to the M2 inhibitors, NAIs have broader anti-influenza activity, better tolerance than amantadine and the frequency of resistance emergence is expected to be lower based on the lower incidence of resistant isolates emerging during the clinical trials.
AIs provide an important new option for the treatment of influenza and will play an important role in its management. Although the current data on viral resistance are very reassuring, it will be important to continue to monitor the broad use of NAIs in general practice. Therefore, collaborative virological surveillance systems have been set up to monitor the use of NAIs in clinical practice.
KeywordsInfluenza Influenza Virus Oseltamivir Amantadine Zanamivir
The authors would like to acknowledge the assistance of P. Ward, Roche Global Development, Welwyn, UK, E. Covington, Roche Discovery, Welwyn, UK and Dr B. Graves, Roche Discovery, Welwyn, UK (fig. 1) in the preparation of this manuscript, and D. Mendel, formerly of Gilead Sciences, California, USA, for virus sensitivity testing.
- 1.Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2000; 49(RR-03): 1–38Google Scholar
- 4.Management of Influenza in the Southern Hemisphere Trialists (MIST) Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infection. Lancet 1998; 352: 1977–81Google Scholar
- 12.Leneva IA, Roberts N, Webster RG, et al. The neuraminidase inhibitor oseltamivir is efficacious against A/Hong Kong/ 156/97 (H5N1) and H9N2 influenza virus. Antiviral Res 2000; 46: A53Google Scholar
- 14.Aoki F, Macleod M, Paggiaro P, et al. Maximising benefits of influenza treatment with oral oseltamivir — results of the IMPACT study [abstract # 978]. In: Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, 17–20 Sept 2000: 481Google Scholar
- 15.Whitley RJ, Hayden FG, Reisinger KS, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001. In pressGoogle Scholar
- 19.Aoki FY. Amantadine and rimantadine. In: Nicholson KG, Webster RG, Hay AJ, editors. Textbook of influenza. Oxford: Blackwell Science, 1998: 457–76Google Scholar
- 29.Bantia S, Ananth S, Horn L, et al. Generation and characterization of a mutant of influenza A virus selected with the neuraminidase inhibitor RWJ-270201. Antiviral Res 2000; 46: A60Google Scholar
- 32.Covington E, Mendel DB, Escarpe P, et al. Phenotypic and genotypic assay of influenza virus neuraminidase indicates a low incidence of viral drug resistance during treatment with oseltamivir [#P-326]. J Clin Virol 2000; 18(1–3): 253Google Scholar
- 34.Gubareva LV, Tai CY, Mendel DB, et al. Oseltamivir treatment of experimental influenza A/Texas/36/91 (H1N1) virus infection in humans: selection of a novel neuraminidase variant. Antiviral Res 2000; 46: A59Google Scholar
- 36.Ives J, Carr J, Roberts N, et al. An oseltamivir treatment-selected influenza A/N2 virus with a R292K mutation in the neuraminidase gene has reduced infectivity in vivo [abstract #P-321]. J Clin Virol 2000; 18(1–3): 251Google Scholar
- 37.Ives J, Carr J, Roberts N, et al. An oseltamivir treatment-selected influenza A/Wuhan/359/95 virus with an E119V mutation in the neuraminidase gene has reduced infectivity in vivo [#P-330]. J Clin Virol 2000; 18(1–3): 255Google Scholar
- 38.Carr J, Ives J, Roberts N, et al. Virological assessment in vitro and in vivo of an influenza H1N1 virus with a H274Y mutation in the neuraminidase gene. Antiviral Res 2000; 46: A59Google Scholar