H7N9 Influenza Strain Resistant To Antivirals, But Tests Fail To Identify Resistance

Thursday, July 18, 2013
By Paul Martin

Redorbit.com
July 16, 2013

Some strains of the avian H7N9 influenza that emerged in China this year have developed resistance to the only antiviral drugs available to treat the infection, but testing for antiviral resistance can give misleading results, helping hasten the spread of resistant strains.

The authors of a study published in mBio®, the online open-access journal of the American Society for Microbiology, characterized viruses taken from the first person known to be stricken with H7N9 influenza and found that 35% of those viruses are resistant to oseltamivir (commercially known as Tamiflu) and zanamivir (Relenza), front line drugs used for treating H7N9 infections. However, lab testing of the viruses, which detects the activity of a viral enzyme, fails to detect that these strains are resistant, so monitoring for the development of resistance using this technique would prove futile.

“If H7N9 does acquire human-to-human transmissibility, what do we have to treat it with until we have a vaccine? Oseltamivir. We would be in big trouble,” says corresponding author Robert Webster of St. Jude Children’s Research Hospital in Memphis, Tennessee. Resistant strains of H7N9 can flourish in patients treated with oseltamivir or zanamivir, he says, inadvertently leading to the spread of resistant infections.

In the mBio study, the authors tested antiviral susceptibility of an H7N9 strain isolated from the first confirmed human case of avian H7N9 influenza using a method that tests the activity of the neuraminidase enzyme. The reassuring results were, unfortunately, misleading: the enzyme-based test indicated that the flu strain was susceptible to NA inhibiting antiviral drugs, but it is not.

A closer look at the viral isolate revealed it is actually made up of two distinct types of H7N9 viruses. Roughly 35% of the viruses carry the R292K mutation, making them resistant to NA inhibitors, and 65% are sensitive to these same drugs. The enzyme-based testing gave misleading results, says Webster, because the functioning wild-type enzymes masked the presence of the non-functioning mutant enzymes.

Using NA inhibitors to treat a patient infected with a resistant strain of H7N9 only encourages the virus to proliferate and can lead to enhanced spread of the resistant strain. The authors write that these results prove that it is crucial to use a gene-based surveillance technique that can detect these resistant influenza strains in a mixed infection.

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