Two more H7N9 cases cited; virus may be adapting to mammals

Apr 3, 2013 (CIDRAP News) – Chinese authorities reported two more human illnesses caused by the H7N9 avian influenza strain today, one of them fatal, as experts said genetic evidence suggests that the virus may be starting to adapt to mammals.

The two new cases bring the total to nine, all in eastern China, including three deaths. Meanwhile, the mystery of what animal species the virus came from remained unsolved, and officials said they still don't believe it is spreading from person to person.

The two latest cases were in Zhejiang province, according to media and government reports. A 38-year-old male chef fell ill on Mar 7 and died 20 days later, the European Centre for Disease Prevention and Control (ECDC) said in a press release. The other case was in a 67-year-old retired man from Hangzhou who has been hospitalized since Mar 25, the agency said, quoting the Zhejiang health department.

A Reuters report, citing Xinhua, said the 38-year-old was working in Jiangsu province, where five of the other cases were found, and died in a hospital in Hangzhou on Mar 27.

There are no epidemiologic links among the six latest cases, including today's pair and the four reported yesterday, the ECDC reported. It said monitoring of 350 contacts of these cases has revealed no illnesses so far.

"There is currently no evidence of human-to-human transmission of the influenza A(H7N9) virus," the agency said.

The H7N9 virus is an avian subtype that has never been found in humans before. Signs that it may be evolving into a strain that can spread in mammals come from studies of genetic sequences that Chinese officials deposited into the GISAID database.

Nancy Cox, PhD, director of the Influenza Division at the US Centers for Disease Control and Prevention (CDC), told CIDRAP News, "We had undertaken a very thorough analysis of the gene sequences that the China CDC had deposited in the GISAID database, and we did note that there were some molecular signs of possible adaptation in mammals. We also saw a particular genetic sequence that would indicate that these viruses have replicated in domestic poultry, as opposed to wild birds."

Cox said investigators found changes in the virus's receptor binding site that would indicate that it might attach more easily to mammalian cell receptors than avian viruses do. The same changes were noted by Chinese scientists, she noted.

A question-and-answer statement from the World Health Organization (WHO) today offered similar observations.

"Analysis of the genes of these viruses suggests that although they have evolved from avian (bird) viruses, they show signs of adaptation to growth in mammalian species," the WHO said. "These adaptations include an ability to bind to mammalian cells, and to grow at temperatures close to the normal body temperature of mammals (which is lower than that of birds)."

Richard Webby, PhD, director of the WHO collaborating center for influenza studies at St. Jude Children's Research Hospital in Memphis, was more emphatic about signs that the virus is evolving in a mammalian direction, according to a Canadian Press (CP) report published last night.

"This thing doesn't any longer look like a poultry virus," Webby told the CP. "It really looks to me like it's adapted in a mammalian host somewhere."

He said it's not clear what the mammalian host is, but the likeliest bets are pigs and humans. Identifying the mammalian host is critical for reducing human exposure and preventing more cases, he added.

Webby suggested that the virus may take off in humans or vanish back into nature, much as the H5N1 avian flu virus did after its 1997 emergence in Hong Kong, according to the story. The latter virus resurfaced in 2003 and proceeded to spread over much of the world.

As reported previously, other experts who were quoted in a Nature news story yesterday also said they saw genetic features suggesting that the virus is adapting to mammals.

Chinese officials and other experts have said the virus probably came from poultry, but Cox said today that its animal source remains unknown. "The obvious things would be concerns about viruses in birds or pigs or both, but influenza is always throwing us a curveball, so we don't want to rule out other animal sources," she commented.

The WHO Q&A statement today said, "Some of the confirmed cases had contact with animals or with an animal environment, but the virus has not thus far been found in animals. It is not yet known how these persons became infected. The possibility of animal-to-human transmission is being investigated, as is the possibility of person-to-person transmission."

In a brief statement late yesterday, the US CDC said it is following the situation closely and collaborating with domestic and international partners to assess the risk and develop a candidate vaccine virus, among other things. The agency said it was too early to speculate about the significance of the human cases.

Meanwhile, the ECDC today issued a risk assessment that offered some new details about the virus.

The assessment confirmed earlier reports that H7N9 is a reassortant that contains hemagglutinin (H) and neuraminidase (N) from another H7N9 strain and has six other gene segments from an H9N2 virus. Some human H9N2 infections have occurred and have usually involved uncomplicated illness, but a more severe case was seen in one immunocompromised patient.

The H7N9 virus has a specific mutation, called E627K, in its PB2 gene that was also found in an H7N7 virus that caused the death of a Dutch veterinarian in 2003, the ECDC reported. The same mutation has been linked to high virulence, host range adaptation, and airborne transmission in H5 viruses, but its significance in this setting is not yet clear.

In other comments, the ECDC said that H7 vaccine candidate strains have been developed in response to previous human H7 flu cases. "These candidate strains may not efficiently cross protect against the novel A(H7N9) strain, but the fact that they are moving towards development does indicate a degree of preparedness globally," the agency said.

The ECDC also said that one H7N9 isolate contained a neuraminidase substation that confers resistance to oseltamivir (Tamiflu) in H3N2 viruses. Despite this, the agency expects that tests will confirm that the virus is sensitive to the antiviral drug, and a WHO statement today said preliminary testing in China suggests that that's the case.

The WHO said it saw no evidence of ongoing H7N9 transmission and added that no trade or travel restrictions are currently warranted.

See also:

Apr 3 ECDC risk assessment

Apr 3 ECDC press release

Apr 3 WHO question-and-answer bulletin

Apr 2 CDC statement

Apr 2 CP story

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