Deep inside a high-security laboratory an hour from Melbourne, scientists working behind air-locked doors inject six-week-old chickens with a virus that has killed one in five people it’s known to have infected.
The pathogen is H7N9 bird flu, and it came to Australia’s second-biggest city 12 days ago in a 0.5 milliliter sample -- 10 would fit on a teaspoon -- from a patient in China’s Anhui province. Antibodies from the chickens will help create tests for the virus, part of a race to head off a global outbreak.
While disease trackers have yet to pinpoint how the 127 human infections in China and Taiwan occurred, they say contact with poultry is the most likely cause. Birds carry the disease without showing symptoms, making tests to monitor farms and markets vital to halting its spread, said Peter Daniels, assistant director of the Australian Animal Health Laboratory.
“If one in five people getting infected die, that’s a pretty frightening infection,” said Daniels, 64, whose lab is the world’s largest high-security bio-containment research facility. “It may be that it won’t start spreading person to person. But if it does, the world is facing a severe disease situation.”
An earlier bird flu strain known as H5N1, first isolated from a farmed goose in China’s Guangdong province in 1996, has infected wild birds and domestic poultry in more than 60 countries over the past decade. That virus, which killed 60 percent of the 628 people known to have been infected, doesn’t spread efficiently from human to human. That’s unlike a novel swine flu virus known as H1N1 that emerged in Mexico in 2009 and spread worldwide in months.
Wild birds are the primary natural reservoir for influenza viruses capable of causing pandemics, according to the Centers for Disease Control and Prevention in Atlanta. The 1918 Spanish Flu pandemic, which killed as many as 50 million people, began when an avian flu virus jumped to people who had no immunity to the new strain, doctors say.
H7N9 isn’t known to have infected humans before, so no one has immunity to it. Drugmakers including Melbourne-based CSL Ltd. (CSL) and Beijing-based Sinovac Biotech Ltd. (SVA) have started to prepare for the possible need to make immunizations, which would be triggered by widespread human-to-human infections in multiple regions.
H7N9 has already moved outside mainland China. Last week, officials in Taiwan reported a case in a 53-year-old man who had just returned to Taiwan via Shanghai after a business trip to the eastern city of Suzhou. The man is in critical condition, doctors said. Government officials in Yokohama, on the outskirts of Tokyo, are testing wild birds for avian flu after 17 crows and a pigeon were found dead, Yomiuri Shimbun said yesterday.
The virus might have evolved from at least four different sources, according to research by Chinese scientists published today in The Lancet medical journal. One of H7N9’s genes may have come from ducks, while another might have been transferred from birds migrating in east Asia, the scientists found. The avian flu bug’s six internal genes probably came from two different groups of H9N2 viruses isolated from chickens, they said.
“Extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched,” they wrote in the study.
The research was funded by the China Ministry of Science and Technology, the National Natural Sciences Foundation of China, China Health and Family Planning Commission, and the Chinese Academy of Sciences.
In the past week, the Australian Animal Health Laboratory, or AAHL as its known locally, dispatched samples of the virus’s genetic material to Indonesia and Vietnam as reagents for tests that can detect the H7N9 virus in tissue specimens, which would indicate acute infection, Daniels said. Three more countries will receive specimens this week, with further shipments planned.
Those tests use so-called polymerase chain reaction, or PCR, methods to detect H7N9 and subsequently diagnose cases. AAHL has been playing a key role in validating and evaluating materials for PCR testing, said Juan Lubroth, chief veterinary officer for the Food and Agriculture Organization of the United Nations in Rome.
“They’re helping us send out around 8,000 PCR tests to each country in the region,” Lubroth said in a telephone interview yesterday. “That is a big help to the region to ensure that we have the detection capability.”
Opened in 1985 by the Australian government, AAHL looks like an enormous, grey concrete bunker. Its six floors have 65,000 square meters (700,000 square feet) of space, a labyrinth of laboratories and animal enclosures. The only windows to the outside are in the cafeteria. The building was designed to operate for 100 years, withstanding 1-in-10,000-year natural disasters such as 300 kilometer-per-hour winds and magnitude 5.8 earthquakes.
The H7N9 antibodies are being raised in the center’s Diagnostic Emergency Response Laboratory, opened five years ago in a part of the building once used for bottle-washing. It can process 10,000 antibody tests and 1,000 genetic tests a day, Daniels said. Inside the secure building lab, capable of safely handling the most lethal and virulent biological agents known to mankind, the H7N9 virus is replicated in sterile, fertilized hen’s eggs inside an air-locked chamber.
The lab is also producing antisera -- blood serum containing antibodies -- against H7N9 in ferrets for the World Health Organization. The material will be used to assist in identifying infections in people, said Ian Barr, deputy director of the WHO’s Collaborating Center for Reference and Research on Influenza in Melbourne.
That center, on the fringe of Melbourne’s downtown, was the original destination for the specimen from China. After being transported on a commercial flight from Beijing in a tightly packed vial inside a sealed foam carton, the virus was replicated in 15 eggs before samples were sent to Daniels’ lab three days later, Barr said.
“It grows very well, this virus,” Barr said.
The ferret research will help public health officials understand the new virus’s ability to cause disease in mammals, and to determine whether it spreads via direct contact alone or can be transmitted by coughing and sneezing.
Early indications from experiments with ferrets in the U.S. suggest that infections caused by the virus aren’t as severe as those from the H5N1 bird flu strain, typically not extending beyond the respiratory tract, Barr said, adding that more research is needed to validate the findings. Antisera collected from the ferrets will help scientists determine whether H7N9 is undergoing important genetic changes, he said.
Antibodies generated by the virus in ferrets will also help test candidate vaccines currently being developed, said John McCauley, director of the WHO collaborating center at the MRC National Institute for Medical Research in London. The experiments, which began about two weeks ago, will conclude in about a week, he said.
“We need to remain very vigilant,” Barr said. “It’s still on the precipice of potentially tipping over from isolated animal-human infections to something more serious.”
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