Two cases with rapid development of drug-resistant 2009 H1N1 influenza reported

Scientists have reported two cases in which people with compromised immune systems who became ill with 2009 H1N1 influenza developed drug-resistant strains of virus after less than two weeks on therapy.

Doctors from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have said that medics, who treat prolonged influenza infection should be aware that even a short course of antiviral treatment may lead to drug-resistant virus.

They also said that the authors, and clinicians should take into mind this possibility while developing initial treatment strategies for their patients who have impaired immune function.

Both patients in the new report developed resistance to the key influenza drug oseltamivir (Tamiflu), and one also demonstrated clinical resistance to another antiviral agent, now in experimental testing, intravenous peramivir, said senior authors Dr. Matthew J. Memoli and Dr. Jeffery K. Taubenberger.

This is the first reported case of clinically significant peramivir-resistant 2009 H1N1 illness, say the scientists.

The people in the current case report had immune limitations due to blood stem cell transplants that occurred several years previously. Both recovered from their influenza infections.

“While the emergence of drug-resistant influenza virus is not in itself surprising, these cases demonstrate that resistant strains can emerge after only a brief period of drug therapy. We have a limited number of drugs available for treating influenza and these findings provide additional urgency to efforts to develop antivirals that attack influenza virus in novel ways,” said NIAID Director Anthony S. Fauci.

The 2009 H1N1 influenza virus is susceptible to just one of the two available classes of anti-influenza drugs, the neuraminidase inhibitors. Besides oseltamivir, other neuraminidase inhibitors are zanamivir (Relenza), which is inhaled, and the intravenously administered investigational drug peramivir.

It was shown that some strains contained a genetic mutation (the H275Y mutation) that makes the virus less susceptible to some neuraminidase inhibitors.

The two people in the current case study had pre-existing medical conditions that impaired their immune system function before contracting 2009 H1N1 flu.

In the newly described cases, the mutation appeared after 14 days in one individual and after nine days in the second.

Protection from influenza virus

A University of Alberta-led research team has discovered the genetic detector that allows ducks to live, unharmed, as the host of influenza.

The duck’s virus detector gene, called retinoic acid inducible gene-I, or RIG-I, enables a duck’s immune system to contain the virus, which typically spreads from ducks to chickens, where it mutates and can evolve to be a human threat like the H5N1 influenza virus.

The first human H5N1 cases were in Hong Kong in 1997. Eighteen people with close contact to chickens became infected and six died.

The research by Katharine Magor, a U of A associate professor of biology, shows that chickens do not have a RIG-I gene.

A healthy chicken can die within 18 hours after infection, but researchers have successfully transferred the RIG-I gene from ducks to chicken cells.

The chicken’s defenses against influenza were augmented and RIG-I reduced viral replication by half.

One potential application of this research could affect the worldwide poultry industry by production of an influenza-resistant chicken created by transgenesis.

The study appears in the online, early edition of Proceedings from the National Academy of Sciences .