According to World Health Organization researchers there is a rise in Australia in the number of seasonal influenza cases resistant to Tamiflu, the most commonly used antiviral drug. The rise in such cases involving the pandemic 2009 A (H1N1) flu strain, also known as swine flu, took place during Australia's most recent winter: May through August of 2011.
“In 2007/2008, a different A (H1N1) influenza virus developed Tamiflu-resistance,” explained WHO research scientist Aeron C. Hurt, who reported the spike. “On that occasion, it was first detected in large numbers in Europe. However, within 12 months the virus had spread globally, such that virtually every A (H1N1) virus around the world was resistant to this drug,” he explained. Hurt added, “This previous situation demonstrated the speed and potential for a Tamiflu-resistant virus to spread worldwide. Our concern is that this current pandemic 2009 A(H1N1) Tamiflu-resistant virus may also spread globally.” Hurt, who is based in the Collaborating Centre for Reference and Research on Influenza in North Melbourne, outlined his observations in the Dec. 29 issue of the New England Journal of Medicine.
For the study Hurt and his team obtained viral samples from 182 H1N1 flu patients (aged from one month to 74 years) who were being cared for either in an emergency department or an intensive care unit, or by their general practitioner, during the recent winter in Australia. In all, 29 of the patients (or 16 percent) were found to have a form of H1N1 that was resistant to both Tamiflu (oseltamivir) and an older class of adamantine treatments (rimantadine and amantadine).
Five of the resistant patients were under the age of 5 years. Only one of the patients had been treated with Tamiflu prior to viral sampling, while three had previously been vaccinated with the 2011 influenza vaccine.
Further lab tests revealed that it would take more than 500 times the concentration of Tamiflu usually prescribed for nonresistant flu strains just to cut key aspects of resistant viral activity in half. However, these resistant strains remained “fully sensitive” to treatment with another drug - Relenza (zanamivir).
The team noted that July marked the high point of resistant cases, most of which were found within a 30-mile or so radius of Australia's seventh-largest urban center, Newcastle. Some were located in Sydney, the country's largest city.
The researchers add that some of the resistant cases involved related patients: in four households, two family members had been diagnosed with resistant H1N1. In two other cases, the patients were linked simply by having shared a short car ride.
Hurt pointed out that the resistant strain does not appear to cause more serious illness than “normal” strains, and that no one has died as a result. But he did suggest that the very real prospect that such resistant strains could spread far beyond the shores of Australia is alarming. “Tamiflu is widely used in the U.S.A. and other parts of the world such as Japan,” he noted. “If the virus spreads widely, then there is potential that patients will be treated with a drug that will have little or no benefit. The biggest impact may be in individuals, such as the elderly or immune-compromised, who have a higher risk of complications from influenza infection and most commonly benefit from early and effective antiviral treatment.”
According to earlier studies, the oseltamivir-resistant virus is detected in less than 1% of patients with the pandemic 2009 A (H1N1) virus who have not been treated previously with the antiviral. In addition, “transmission has been documented only in closed settings or settings involving close contact with infected persons.”
Dr. Len Horovitz, a pulmonary specialist with North Shore-LIJ/Lenox Hill Hospital in New York City, explained that, although other non-Tamiflu treatments remain effective, the advent of resistant flu strains can waste valuable time. “Flu medications have to be given within 24 to 48 hours of the onset of symptoms or they do no good,” he said. “So this is a real problem, because we live in a global village. People will get on a plane in Australia and come to my office. This will not be isolated to one part of the world,” he added. “So what I tell people is that immunization is paramount,” Horovitz said. “It's important that anybody over the age of 6 months get vaccinated, and that includes pregnant women for whom there is a mercury-free vaccine. If we all did this, we would have very low levels of flu. People wouldn't get it to begin with. And then we wouldn't have to worry whether the drugs we have work or not.”
The new studies on antiviral resistance come on the heels of a CDC report released December 23 that describes yet another way in which influenza viruses are mutating. The CDC has disclosed that since July 2011, 12 patients have been infected with a swine-origin A (H3N2) virus that borrows a gene from the pandemic 2009 A(H1N1) virus (the latter virus is now considered seasonal, and seasonal influenza vaccines are designed to guard against it).