WHO: H7N9 antiviral resistance likely arose after treatment

Officials from the World Health Organization (WHO) today revealed new information on antiviral resistance and other virus changes related to China's surge in H7N9 avian flu infections, but they said the shifts so far haven't changed the epidemiologic or clinical patterns of the disease in humans.

At a media telebriefing today, a WHO expert said that recently detected signs of resistance to antivirals like oseltamivir (Tamiflu) and zanamivir (Relenza) likely arose after treatment with antivirals in patients with H7N9. Experts added that the WHO is closely monitoring the H7N9 developments, as well as quickly changing events involving other avian flu strains with pandemic potential, such as the spread of highly pathogenic H5N8 to wild birds and poultry to 40 countries.

Two of the scientists who addressed journalists today are directors of WHO collaborating centers on influenza who are in Geneva this week attending meetings to guide the selection of seasonal flu strains for the Northern Hemisphere's 2017-18 flu season. The group will also look at the latest changes in potential pandemic strains, including H7N9, to assess if any new candidate vaccine viruses are needed.

Wenqing Zhang, MD, who leads the WHO's global influenza program, said the main message is that the risk of sustained human-to-human transmission is still low. "However, constant change is the nature of all influenza viruses, and that is why we follow the developments so closely," she said.

Antiviral resistance findings

So far, at least 460 H7N9 infections have been reported in China's fifth wave, its biggest yet, with the total number of cases reported since October accounting for one third of all cases since the novel virus was first detected in humans in 2013, Zhang said.

About 7% of the viruses from human cases in the fifth wave have genetic markers linked to resistance to neuraminidase inhibitors, including oseltamivir, the gold standard for treating the disease. She said the level is similar to earlier waves, with a slight elevation this season that is still lower than what health officials observed in the first wave.

Nearly all of the H7N9 viruses carrying the neuraminidase resistance marker have been from humans, suggesting that most of them developed the marker after treatment and weren't spread by poultry, Zhang said. She said none of the isolates from poultry had signs of neuraminidase inhibitor resistance and only one environmental sample showed the change. "WHO is closely monitoring these developments. So far there is no evidence to recommend changes in clinical management of infection."

Other changes, pandemic vaccine implications

She reiterated an earlier statement that the hemagglutinin mutation seen in three human samples and one environmental specimen involves changes that make the virus highly pathogenic in birds, but there is no evidence that they affect pathogenicity and transmissibility in humans.

Yuelong Shu, PhD, with the Chinese Center for Disease Control and Prevention (China CDC) and director of the WHO's collaborating center there, said one of two Guangdong province patients recently sickened by the virus containing the hemagglutinin mutation has been released from the hospital, and the other is still hospitalized for the treatment of an unrelated chronic condition. Taiwan this week reported that its patient found to be infected with the mutated strain, a 69-year-old man who was exposed to the virus in Guangdong province, has died.

Regarding other changes in the virus, Jackie Katz, PhD, who directs the WHO's collaborating center at the US Centers for Disease Control and Prevention said that, based on findings from multiple labs, H7N9 seems to have diverged two distinct genetic groups. Viruses in one of the groups are similar to candidate vaccine viruses that have been used to produce vaccine for the US Strategic National Stockpile.

At their meeting this week, the influenza experts are discussing the possible need to make additional H7N9 candidate vaccine viruses.

Virus sharing issues

Officials today responded to a report yesterday from Stat that China has not shared any virus isolates since shortly after it was first detected in humans, though they have frequently shared genetic sequences.

Katz said the delay in sharing isolates was linked to new regulations in China that shifted requests for samples from multiple groups to a commerce department outside of China CDC. She said a path forward has now been found to streamline the rapid sharing of viruses. Katz also commended China for rapidly sharing genetic sequences and epidemiologic information, which has been useful for developing timely risk assessments.

See also:

Mar 1 WHO media telebriefing audiofile

Feb 28 Stat story

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