Emergence of dual-resistant influenza viruses poses public health concern

Issue: January 2011

Increasing antiviral resistance among certain influenza viruses and a lack of alternative antiviral treatment options have raised public health concerns, according to data from two new studies published in the Journal of Infectious Diseases.

Although the spread of influenza strains with resistance to adamantanes has been well documented, a new CDC report confirms that resistance to oseltamivir (Tamiflu, Roche) and adamantanes has been on the rise during the past 3 years.

Larisa V. Gubareva, MD, PhD, and colleagues analyzed 28 seasonal H1N1 viruses from 2008 to 2010 with dual resistance from the United States, Canada, China, Kenya and Vietnam.

Viruses retained susceptibility to only inhaled zanamivir (Relenza, GlaxoSmithKline). One dual-resistant virus of the 1,753 tested was collected during the 2007-2008 influenza season, 21 dual-resistant viruses of the 1,426 tested were from 2008-2009 and 7 of 25 were from 2009-2010 — reflecting an increase from 0.06% to 1.5% to 28%, respectively.

This analysis demonstrates that additional antiviral resistance can rapidly develop in a previously single-resistant strain as a result of mutation, drug response or gene exchange with another virus, the researchers wrote.

“Because only two classes of antiviral agents are approved, the detection of viruses with resistance to drugs in both classes is concerning. If circulation of viruses with dual resistance becomes more widespread among any of the predominant circulating influenza A viruses, treatment options will be extremely limited. New antiviral agents and strategies for antiviral therapy are likely to be necessary in the future,” Gubareva said in a press release.

In another study, Catherine Moore, of the Public Health Wales National Health Service Trust, and colleagues examined data from an outbreak of oseltamivir-resistant pandemic H1N1 infection, which was the first confirmed person-to-person transmission of this dually resistant strain that occurred in a hematology unit in the United Kingdom.

From Oct. 29 to Nov. 25, 2009, researchers identified 11 cases of the H1N1 2009 virus in the hematology unit; eight were resistant to oseltamivir; half of which resulted from direct transmission of the resistant virus. According to the researchers, immunocompromised patients were more susceptible to the emergence of oseltamivir-resistant H1N1 virus on treatment and also transmitted the virus to others, despite often having no influenza symptoms or having completed antiviral therapy.

Based on the results of the study, researchers suggest active screening of patients for oseltamivir-resistant H1N1 viruses and altering treatment guidelines to include zanamivir, to which the viruses remained susceptible, rather than oseltamivir in hematology patients diagnosed with H1N1, as well as patients who are immunocompromised.

Frederick G. Hayden, MD, of the University of Virginia School of Medicine, and Menno D. de Jong, MD, of the University of Amsterdam, in an accompanying editorial, said there was a need for timely monitoring at community and global levels for variants emerging in nonhuman hosts and for rapid changes in local antiviral-susceptibility patterns, as well as creative preventive and therapeutic choices for antiviral-resistant influenza viruses.

“Intravenous zanamivir, presently, would be the most reasonable antiviral choice when oseltamivir-resistance is proven or suspected in seriously ill H1N1 patients,” Hayden and de Jong wrote, adding that future research should focus on the effectiveness of zanamivir and combination antiviral therapy in addition to the development of new antivirals.

For more information:

Hayden FG. J Infect Dis. 2011;203:6-10.
Moore C. J Infect Dis. 2011;203:18-24.
Sheu TG. J Infect Dis. 2011;203:13-17.

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