Influenza A viruses (H1N1 subtype) that are resistant to the drug oseltamivir circulated widely in the U.S. during the 2007-2008 influenza season, with an even higher prevalence of drug resistance during the current 2008-2009 influenza season, according to a new study.
During the 2007-2008 influenza season, increased levels of resistance to the influenza drug oseltamivir (marketed as Tamiflu) were detected for the first time in the United States and worldwide. In addition, early 2008-2009 influenza season surveillance data suggest that oseltamivir resistance among influenza A(H1N1) viruses will most likely be higher, according to background information in the article. It was unknown whether some resistant viruses would cause clinical illness similar to other influenza viruses.
Nila J. Dharan, M.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues examined the trends and characteristics of patients infected with oseltamivir-resistant and -susceptible influenza A(H1N1) virus. These viruses, identified and submitted to the CDC by U.S. public health laboratories between September 2007 and May 2008 and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance.
During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19 percent of circulating influenza viruses in the United States. Resistance to oseltamivir was identified among 142 of 1,155 U.S. influenza A(H1N1) viruses (12 percent) tested during the 2007-2008 influenza season. Data were available for 99 persons infected with oseltamivir-resistant influenza and 182 persons infected with oseltamivir-susceptible influenza from this period.
Among resistant cases, median (midpoint) age was 19 years, 5 patients (5 percent) were hospitalized, and 4 patients (4 percent) died. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. The researchers did not find an association between use of oseltamivir and cases of illness due to infection with oseltamivir-resistant A(H1N1) viruses in the United States.
Preliminary data from the early 2008-2009 influenza season indicates that oseltamivir resistance among A(H1N1) viruses continues at high levels. As of February 19, 2009, resistance to oseltamivir had been identified among 264 of 268 (98.5 percent) U.S. influenza A(H1N1) viruses tested.
"The emergence of oseltamivir resistance has highlighted the need for the development of new antiviral drugs and rapid diagnostic tests that determine viral subtype or resistance, as well as improved representativeness and timeliness of national influenza surveillance for antiviral resistance," the authors write.
They add that on December 19th, 2008, the CDC released interim recommendations for the use of influenza antiviral medications based on the early surveillance data from the 2008-2009 influenza season. "The guidelines recommend that clinicians consider the results of patient testing and local influenza surveillance data on circulating types and subtypes of influenza viruses in deciding whether oseltamivir alone could be used. These guidelines provide options, including preferential use of [the anti-viral drug] zanamivir or a combination of oseltamivir and [the anti-viral drug] rimantadine, which might be more appropriate in treating patients who might have influenza caused by an oseltamivir-resistant virus."
"Additional options for the treatment and prophylaxis of influenza virus infection are critically needed," according to the authors.
Editorial: The Evolution of Influenza Resistance and Treatment
In an accompanying editorial, David M. Weinstock, M.D., of the Dana-Farber Cancer Institute, Boston, and Gianna Zuccotti, M.D., of Brigham and Women's Hospital, Boston, and Contributing Editor, JAMA, Chicago, comment on the findings regarding influenza.
"The understanding of influenza biology and epidemiology has advanced markedly; however, the global dissemination of oseltamivir-resistant influenza came as a great surprise. Undoubtedly, new surprises await in the perpetual struggle with influenza as one thing is certain—the organism will continue to evolve. Anticipating the rapid and endless changes in influenza biology and dynamics will require faster diagnostics to molecularly characterize specimens, extensive surveillance among humans and animals, and more rapid and [flexible] systems for translating basic and epidemiological discoveries into clinically applicable interventions. For now, the best tools to mitigate influenza infection are tried-and-true—vaccination, social distancing, hand washing, and common sense."
- Nila J. Dharan; Larisa V. Gubareva; John J. Meyer; Margaret Okomo-Adhiambo; Reginald C. McClinton; Steven A. Marshall; Kirsten St. George; Scott Epperson; Lynnette Brammer; Alexander I. Klimov; Joseph S. Bresee; Alicia M. Fry; for the Oseltamivir-Resistance Working Group. Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States. JAMA, 2009;0(2009):2009.294
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