Influenza virus strains show increasing drug resistance and ability to spread

Two new studies raise public health concerns about increasing antiviral resistance among certain influenza viruses, their ability to spread, and a lack of alternative antiviral treatment options. The findings are published in the January 1 issue of The Journal of Infectious Diseases. (Please see below for links to these articles online.)

Influenza viruses are treated with two classes of drugs: M2 blockers (adamantanes) and neuraminidase inhibitors (NAIs), including oseltamivir and zanamivir. While the spread of influenza strains with resistance to one class of drugs has been well documented in recent years, a new report from Larisa Gubareva, MD, PhD and colleagues at the Centers for Disease Control and Prevention (CDC) and at health agencies in West Virginia, Texas, and Canada, confirms that dual resistance can emerge in several ways and has been on the rise during the past three years.

The study analyzed 28 seasonal H1N1 viruses with dual resistance from 2008 to 2010 from five countries, revealing that additional antiviral resistance could rapidly develop in a previously single-resistant strain as a result of mutation, drug response, or gene exchange with another virus.

Although dual resistant viruses are still rare, the investigators noted an increase in the number of tested viruses with this resistance, from 0.06 percent (2007-2008) to 1.5 percent (2008-2009) to 28 percent (2009-2010); however, during the 2009-2010 season the number of circulating seasonal H1N1 viruses was low, and only 25 viruses were tested. "Because only two classes of antiviral agents are approved, the detection of viruses with resistance to drugs in both classes is concerning," said Dr. Gubareva. "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."

A second study, conducted by Catherine Moore and colleagues in the United Kingdom, examined an outbreak of oseltamivir resistant (OR) pandemic H1N1 infection in a hematology unit in the UK. The study is the first to confirm person-to-person transmission of this dually resistant strain through molecular epidemiologic methods. The 2009 pandemic H1N1 virus was inherently resistant to adamantine, but was susceptible to and treated with oseltamivir. However, by October 2009, emergence of OR H1N1 had been documented in rare patients on oseltamivir therapy.

In the hematology unit that Moore and colleagues studied, eight of the 11 pandemic H1N1 virus infections were resistant to oseltamivir, with half of those cases resulting from direct transmission of the resistant virus. Immunocompromised patients were more susceptible to the emergence of OR H1N1 virus on treatment and also transmitted the virus to others, despite often having no influenza symptoms or having completed antiviral therapy. As a result, the screening of patients for OR H1N1 viruses became particularly important, and treatment guidelines were altered to include treatment with zanamivir, to which the viruses remained susceptible.