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Influenza: Problems with Prevention and Treatment

Oseltamivir-resistant influenza virus strains are both communicable and pathogenic, and the intranasal live attenuated influenza vaccine has limitations.

As the world awaits the next influenza pandemic, questions remain regarding the best way to manage seasonal influenza illness. New studies highlight the emergence of oseltamivir resistance in influenza A H1N1 viruses and examine the effectiveness of influenza vaccines.

Oseltamivir blocks the release of influenza virus from infected cells by inhibiting neuraminidase. Because this antiviral closely resembles sialic acid, the natural substrate of neuraminidase, experts believed that oseltamivir-resistant influenza viruses would be unlikely to arise, and, if they did emerge, their virulence would be reduced. However, oseltamivir-resistant strains were noted worldwide during the 2007–2008 influenza season. Gooskens and colleagues describe a nosocomial outbreak of oseltamivir-resistant influenza A H1N1 infection that involved in-hospital transmission of the strain to three patients (2 of whom died) and probably also to five healthcare workers who developed influenza-like illness but were not tested for H1N1.

Dharan and colleagues analyzed 99 cases of infection with oseltamivir-resistant influenza A H1N1 virus (from among 142 cases known to have occurred in the U.S. in 2007–2008). None of the patients had taken oseltamivir — or had household contacts who had done so — before they developed influenza; four of the patients died. Clinical symptoms and outcomes were similar between oseltamivir-resistant cases and oseltamivir-susceptible cases with which they were compared.

During the shortage of trivalent inactivated vaccine (TIV) in 2004, the U.S. Department of Defense agreed to preferentially use the live attenuated influenza vaccine (LAIV; administered intranasally) for routine immunization of service members. Wang and colleagues used Defense Medical Surveillance System data to assess the effectiveness of TIV and LAIV in active-duty military personnel aged 17 to 49 who were stationed in the U.S. during the 2004–2005, 2005–2006, or 2006–2007 influenza season. Data were available for >1 million service members each year, with immunization rates ranging from 51.9% in 2004–2005 to 78.4% in 2006–2007. The proportion of immunized personnel receiving LAIV increased from 33.5% in 2004–2005 to 47.9% in 2006–2007. During each influenza season, the overall incidence of healthcare encounters for pneumonia or influenza was highest among unimmunized personnel and lowest among TIV recipients. Only in 2006–2007, when levels of TIV and LAIV administration were similar, were the two vaccines associated with similar reductions in incidence of healthcare encounters. Among vaccine-naive individuals, however, LAIV and TIV showed comparable effectiveness in 2005–2006 and 2006–2007 (the only years for which this comparison was done).

Comment: These reports highlight ongoing challenges to influenza-control efforts. The findings, in conjunction with surveillance data from the 2008–2009 influenza season, indicate that oseltamivir-resistant influenza A H1N1 strains are readily communicable and are as pathogenic as oseltamivir-susceptible ones. Editorialists note that the regional incidence of oseltamivir-resistant strains does not correlate with local use of the agent, suggesting that resistant viruses are as "fit" as susceptible viruses and could persist indefinitely. The fact that TIV is more effective than LAIV in a highly immunized adult population highlights a relative weakness of LAIV. The attenuated virus strains in LAIV probably require a brief period of replication within the recipient to induce influenza-specific immunity, and such replication may be impaired by neutralizing antibodies in previously immunized individuals.

— Richard T. Ellison III, MD

Published in Journal Watch Infectious Diseases March 11, 2009

Citation(s):

Gooskens J et al. Morbidity and mortality associated with nosocomial transmission of oseltamivir-resistant influenza A(H1N1) virus. JAMA 2009 Mar 11; 301:1042.

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Dharan NJ et al. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA 2009 Mar 11; 301:1034.

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Wang Z et al. Live attenuated or inactivated influenza vaccines and medical encounters for respiratory illnesses among US military personnel. JAMA 2009 Mar 4; 301:945.

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Weinstock DM and Zuccotti G. The evolution of influenza resistance and treatment. JAMA 2009 Mar 11; 301:1066.

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