Patricia F. Fitzpatrick Dimond Ph.D. Technical Editor of Clinical OMICs President of BioInsight Communications

H7N9 has killed six people so far. Find out what’s being done about it.

As the New York Times reported on Saturday that a sixth person has died from a mysterious avian-borne virus, Chinese officials advised its citizens to avoid live poultry, and slaughtered more than 20,000 birds at a wholesale market in Shanghai.

The Chinese government was responding to the detection of H7N9 in a pigeon, the first time the flu has been detected in domesticated birds including pigeons, chickens, and quail.

And scientists have warily watched, as they recall the model for bird flu, the H5N1 virus, which became lethal when it moved from birds to people. Since the lethality of H7N9 is established, great concern exists regarding its transmissibility among humans.

Worrisome Numbers

In a CDC briefing to CIDRAP News, CDC director Tom Frieden, M.D., said there has been no person-to-person transmission and no epidemiologic link between any of the cases so far. But, he added, “There are two families where there was illness in the family around the time of a confirmed case, and those situations are being investigated by Chinese authorities to see if there was person-to-person transmission.”

He further noted that, “with a contagious flu virus, you would expect to find 20 or 30 cases among 100 close contacts of an infected person, but none have been found in the Chinese contact investigations so far. In addition, many or most of the cases have direct contact with live poultry,” he added.

As of April 7, China reported a total of 21 cases of human infection with H7N9 flu, all in the eastern part of the country. Most of the 21 have become severely ill, and six of them have died; however, milder infections may be going undetected.

There could be additional infections both among animals and humans in other regions, and authorities have stepped up measures to monitor cases of pneumonia with unexplained causes, said Liang Wannian, director of the Chinese health agency’s H7N9 flu prevention and control office.

These numbers, health officials say, are particularly worrisome because although the virus has infected a very small number of people, it has killed or critically sickened a high proportion of them. And while its virulence is worrisome enough, WHO officials said that genetic evaluation of the H7N9 virus shows it has the ability to mutate readily, saying “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.”

What’s Being Done So Far

To deal with the outbreak and head off a worse scenario, the Chinese government has launched a full-court press to detect infection sources and taken public health measures. Although some, according to the times, asked why it took so long to publicly announce the outbreak of the H7N9 virus, public health experts have commended the government for responsiveness and transparency in the five days since officials identified the first victims.

Experts say the virus appears to respond to existing influenza medications like Tamiflu and Relenza, and in the U.S., the CDC said it had begun working on a vaccine for the new flu.

Since the H1N1 swine flu pandemic of 2009, in which drug makers took six months to develop and distribute effective vaccines, manufacturers have been stepping up efforts to produce shots faster to deal with the rapid spread of disease. According to Michael Shaw, Ph.D., associate laboratory director in the CDC’s Influenza Division, it will take at least a month to create the seed vaccine, even though the agency is building a synthetic version rather than waiting for a virus sample to arrive from China. Because China has posted the genetic sequences of the virus on public databanks, synthetic genes encoding the virus’s outer spikes in a laboratory can be built, and they can be attached to a viral “backbone,” one that has already been proven to grow well in laboratory and in the sterile chicken eggs in which flu vaccines are made.

Once produced, the CDC says, the vaccine will be tested in ferrets; then the animals will be challenged with flu to see whether they become ill. Ferrets have been used extensively in influenza research because the pathogenesis of the influenza virus in ferrets is very similar to that observed in humans. Contact ferret models have also been used to evaluate transmissibility of the influenza virus in humans in order to determine the pandemic potential. Making flu vaccine seed strains using reverse genetics is nothing new, as 29 approved vaccine candidates have been made in this way, Dr. Shaw said. Those include 22 H5 vaccines, three H9, and four H7, he added.

Will We Get a Vaccine?

Experts from around the world are in daily talks about the threat posed by a deadly new strain of bird flu in China, including discussions on if and when to start making a vaccine. But any decision to initiate mass production of H7N9 vaccines will be a tough decision to make. Jeremy Farrar, D.Phil., infectious disease expert and director of Oxford University’s research unit in Vietnam, said, “It is an incredibly difficult decision because once you make it you have to change from making seasonal flu vaccines and go to making a vaccine for this virus.” And dedicated manufacturing of a vaccine against H7N9 vaccine could cause shortages of vaccine against normal season flu.

Vaccine manufacturers include Sanofi Pasteur, the world’s largest flu vaccine manufacturer, said it was in continuous contact with the WHO through the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), but it was too soon to know the significance of the Chinese cases.

CDC says it continues to monitor the situation closely, coordinating with domestic and international partners in a number of areas, including gathering more information to make a knowledgeable public health risk assessment and developing a candidate vaccine virus. CDC also is reviewing posted genetic sequencing of the new H7N9 viruses and assessing possible implications in terms of the viruses’ transmissibility and severity.

Dr. Shaw told GEN that, “The biggest public health concern at the moment is that the virus has already adapted to infecting humans, and that it has mutations that suggest it has infected mammals sometime in its evolution. But, it’s reassuring that it’s not moving from human to human thus far. Also, the human and avian sequences we have from China show us that the virus is still mutating; it hasn’t stabilized and could still change.”

Right now he said, the Chinese have checked more than 600 contacts of patients and all those individuals have been negative for the virus. “But,” he added, “we are in a situation where we think it is in our interest that we have a vaccine candidate ready for production if needed. Sustained human spread would be the trigger to widespread production, and having a candidate vaccine virus ready to go that has been tested is important.”

And right now, he said, the policy is “watchful waiting while putting the pieces in place for a vaccine rollout should it be needed.”

Patricia Fitzpatrick Dimond, Ph.D. ([email protected]), is technical editor at Genetic Engineering & Biotechnology News.

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