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Study warns drug resistance develops easily with new H7N9 bird flu

05/28/2013 08:54 EDT | Updated 07/28/2013 05:12 EDT
TORONTO - Resistance to the main flu drug Tamiflu seems to develop with some ease in infections with the new H7N9 bird flu, a concerning new study says.

The work, published in the journal The Lancet, suggests that if this virus were to become easily transmitted among people, there might be minimal tools with which to fight it.

H7N9 viruses are already resistant to the only other class of flu medication, the adamantane drugs. And study of other H7 viruses suggests vaccines made to protect against this flu family do not induce high levels of protective antibodies.

In this work, the authors report that in 14 H7N9 patients in Shanghai, two developed resistance to oseltamivir, the generic name for the drug Tamiflu.

"The apparent ease with which antiviral resistance emerges in H7N9 viruses is concerning; it needs to be closely monitored and considered in future pandemic response plans," wrote the authors, from Shanghai Public Health Clinical Centre and the University of Hong Kong.

This is not the only evidence to suggest resistance to Tamiflu and related drugs may arise easily among H7N9 viruses. The genetic sequence of the first spotted H7N9 patient showed a mutation that is known to confer drug resistance in other flu viruses.

And doctors in Taiwan have reported isolating drug-resistant viruses from an H7N9 patient there. That man was infected in China but returned home to Taiwan and was treated there.

The combination of these signs is worrying, said Dr. Malik Peiris, one of the authors and the chair of microbiology at the University of Hong Kong.

"Obviously this is something that arises not very frequently but not infrequently. And that's enough to be quite concerning," Peiris said in an interview.

It is likely the resistance would also be seen to other drugs in the same class as Tamiflu, the neuraminidase inhibitors. Other drugs in this class include zanamivir (sold as Relenza) and peramivir.

In the paper, Peiris and his co-authors cite as yet unpublished data that shows that the mutation lowers the effectiveness of Tamiflu by 100-fold, but only lowers the effectiveness of zanamivir by 30-fold. "Thus, IV (intravenous) zanamivir should be a viable option for therapy of these patients," he said.

The authors said early use of Tamiflu or other drugs in that class is still the best approach for treating these cases when they arise.

And Peiris noted even late treatment in patients who don't develop drug resistance should work. As part of their study the scientists tracked the levels of virus found in the patients over time. They found that even seven or more days into infections, patients had high levels of virus, which is not seen with seasonal flu.

"So ... antiviral treatment really has a wide window for potential benefit," Peiris said, adding that the 12 patients who did not develop resistance responded to the drug.

"It is not as if oseltamivir is useless in these patients."

Dr. Frederick Hayden, an expert in influenza drugs, said something that may have contributed to the development of resistance in these cases was the fact that patients received corticosteroid drugs.

These drugs, which are often used with breathing problems like asthma, have been shown to prolong the period of time in which flu viruses replicate in people. And the longer a replicating virus is exposed to antiviral drugs, the greater the chance that resistance will develop.

As well, studies during other flu outbreaks have shown that there are more secondary bacterial infections in flu patients given corticosteroids and higher rates of death.

"This is an intervention that should be avoided," said Hayden, who teaches at the University of Virginia School of Medicine.

Hayden also noted that drug-resistant H7N9 viruses may not spread as well as the non-resistant viruses. That wouldn't help an individual patient in whom drug resistance develops, but might mean that resistant viruses would not necessarily overtake the susceptible ones and spread broadly.

H7N9 is a new bird flu virus that exploded onto the world's radar at the beginning of April when China began reporting a rapidly rising number of cases. To date, 131 cases have been reported and 37 of these patients have died. All the infections have been contracted in China.

The outbreak appears to have subsided recently, with no new cases reported for the past couple of weeks. But flu experts warn it is not uncommon to see a decline in bird flu activity during the warm months in countries that are afflicted with H5N1 flu, only to see cases pick up again in the fall and winter.

Said Peiris: "I do fear that by winter the problem will resurface."

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