A variation of the pandemic 2009 A(H1N1) influenza virus that is resistant to oseltamivir (Tamiflu, Roche) appears to be spreading in Australia, at least in the state of New South Wales, according to a letter to the editor published online today in the New England Journal of Medicine.
The report adds extra weight to a recent analysis by the US Centers for Disease Control and Prevention (CDC) that shows an uptick in the same oseltamivir-resistant influenza strain in the United States. If such resistance becomes widespread, it would deprive clinicians of a tried and true antiviral drug to treat serious influenza infections.
The 2 new studies on antiviral resistance comes 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).
In the Australian study, 29 (16%) of 182 patients infected with the pandemic influenza virus between May 2011 and August 2011 harbored a version of the virus that was oseltamivir-resistant, write Aeron Hurt, PhD, a researcher at the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne, Australia, and colleagues. The 182 patients hailed from the New England–Hunter region of New South Wales. Of the 29 patients with the oseltamivir-resistant virus, only 1 had received the antiviral medicine before a virus sample was collected.
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."
Among the patients with the resistant strain, 2 had shared a short car ride, and 8 belonged to 4 households with 2 members each. The remaining 19 patients had no known epidemiological link with each other. Most of the 29 patients lived within 31 miles of the city of Newcastle.
The virus strains of these 29 patients were closely related, "suggesting the spread of a single variant," Dr. Hurt and colleagues write.
Although the virus was resistant to oseltamivir, it was still susceptible to the antiviral medication zanamivir (Relenza, GlaxoSmithKline).
The Australian study was conducted during that country's influenza season, coinciding with winter in the Southern Hemisphere. The authors write that as the Northern Hemisphere heads into winter, public health authorities there should rapidly analyze pandemic virus strains from the outset to determine whether an oseltamivir-resistant version is spreading.
Resistant strains in the United States no longer linked to prior drug exposure
Public health authorities in the United States do not need too much nudging to watch for antiviral resistance. On December 19, Emerging Infectious Diseases, a CDC journal, published an article online reporting that from October 2010 through July 2011, 1.0% of pandemic 2009 A(H1N1) virus strains tested resistant to oseltamivir, up from 0.5% during the 2009 to 2010 influenza season.
Although the increase is small, the epidemiology behind the numbers suggests a low level of community transmission of the rogue virus, according to the authors. During the 2009 to 2010 influenza season, most patients with the resistant virus had been previously exposed to the antiviral drug, and many were severely immunocompromised, which may have increased the risk of developing resistance during oseltamivir treatment. During the 2010 to 2011 period, however, the opposite was true: most patients with the resistant virus had no history of oseltamivir exposure.
The authors call the rise of pandemic 2009 A(H1N1) virus strains with oseltamivir resistance "concerning," in light of how prepandemic versions had mutated to gain this edge. They note that the prevalence of such oseltamivir-resistant strains had risen to 12% in the 2007 to 2008 influenza season, and had topped 99% in the 2008 to 2009 season. This increase was not linked to prior exposure to the antiviral drug.
The loss of oseltamivir from the clinical arsenal would leave physicians and patients with only 1 effective antiviral drug, zanamivir, to treat a severe infection caused by the pandemic virus now in seasonal circulation, write the authors. They note that more than 99% of the strains of this virus are "inherently resistant" to the adamantane family of antivirals.
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Source: http://www.medscape.com/viewarticle/756204?sssdmh=dm1.747366&src=nldne
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