A new genetic analysis shows the H7N9 bird flu in China may have been spreading quietly for weeks or months in domestic animals. But it mutates once it infects a person, giving birth to new viruses that feel more at home inside the human body.
Doctors have diagnosed 102 people in China with H7N9 and 20 people have died of it, according to the Chinese news agency Xinhua. So far they are all in eastern China, with one case in Beijing, but China has welcomed World Health Organization experts to help figure out where the virus has come from, how far it has spread, and how big a threat it really is.
The new Dutch study suggests the virus has been spreading unnoticed among domestic animals in China, and that a certain mutation may make it deadlier in people. In 2003, a strain of flu called H7N7 spread to 255 poultry farms in the Netherlands, forcing the slaughter of 30 million chickens. About 450 people got mild illness and one veterinarian died from an H7N7 infection.
Researchers compared the genetic sequences of viruses from that outbreak to the new H7N9 virus. It has enough mutations to suggest it's been changing over time --although it's impossible to put a precise time frame on it. Influenza viruses are prone to making mistakes as they replicate, giving rise to all sorts of different mutations, often within the same person or animal.
Virus taken from the vet who died in 2003 had a genetic mutation that made the virus particularly virulent. It probably evolved inside the patient’s body, Marcel Jonges of the National Institute for Public Health and the Environment and colleagues say. “Remarkably,” they wrote in the journal Eurosurveillance, four samples taken from Chinese patients who died have the same mutation.
The gene sequences also suggest the virus has been quietly infecting animals, they added. “The data are suggestive of (silent) spread and adaptation in domestic animals before the novel A(H7N9) virus was identified in humans,” they wrote. And, they noted, in the Dutch H7N7 outbreak, many of the human patients had eye infections known as conjunctivitis.
Chinese health experts are testing healthy people who have been in contact with H7N9 patients. They haven’t found much evidence that people have been infected and spread the infection without becoming sick themselves, but it may be important to check their eyes, the researchers suggest. Flu viruses can infect the eyes and the H7 strains may be easier to find there, they said.
The quiet spread has been making H7N9 hard to track. Avian influenza viruses can be highly pathogenic, or low pathogenic. The other bird flu virus out there that worries health experts, H5N1, is a highly pathogenic virus. It’s easy to track in chickens, because it kills off flocks en masse, although it doesn’t make most ducks sick. Officials can cull flocks as soon as it shows up.
But H7N9 doesn’t seem to make birds ill, so it’s hard to tell what species are infected and how widespread it is. There’s also not a good, easy-to-use test for it yet.
“It is a sneaky virus,” says Hon Ip, who’s been tracking bird flu viruses for the U.S. Geological Survey’s National Wildlife Health Center in Madison, Wis. He’s seen flu viruses mix more than once to infect new species, such as when a bird flu virus called H3N8 infected and killed seals off the New England coast in 2011.
“This is exactly similar to the situation currently with the H7N9 virus, which is also an avian influenza virus that causes disease in a mammalian species, namely people,” Ip said in a telephone interview.
China’s State Forestry Administration said its checks have so far found no H7N9 virus in more than 800 wild birds sampled in five cities and provinces where human infections have been reported.
Last week, a study published in the New England Journal of Medicine suggested several different bird flu viruses mixed genes to give rise to the new H7N9 strain. Flu viruses often swap their genetic material in this way -- the H1N1 virus that caused the 2009 swine flu pandemic was a mixture of bird, pig and human viruses.
Rongbao Gao of the the Chinese Center for Disease Control and Prevention in Beijing and colleagues said their team’s genetic analysis traced the virus to a colorful and common species of finch called a brambling. It mixed with viruses from two other bird types, including, evidently a duck from the Yangtze River Delta and a wild bird from Korea, to make the new H7N9 strain.
So how are people getting infected? In the case of H5N1, almost all the 600-odd people infected since 2003 have had direct contact with poultry. But many of the Chinese H7N9 patients say they haven’t.
“One possible explanation for this could simply be recall bias -- people often forget what they have done,” says Dr. Eric Toner of the Center for Biosecurity at the University of Pittsburgh Medical Center.
“Another explanation could be that human-to-human spread of the disease is occurring but has not yet been detected, even though close observation of more than 1,000 known contacts of confirmed cases has yet to show evidence of transmission,” Toner adds in his blog.
It could be that restaurants are spreading the virus if they slaughter birds on site, Toner says, or other animals could be carrying it, Toner says. Pigs often give new flu viruses to people but Chinese authorities say they haven’t found H7N9 in pigs so far.
There’s no evidence anyone outside China has been infected. But U.S. officials warned doctors this week to keep an eye out for it.
“This is a 'novel' (non-human) virus and therefore has the potential to cause a pandemic if it were to change to become easily and sustainably spread from person-to-person,” the Centers for Disease Control and Prevention said in a statement.
“So far, this virus has not been determined to have that capability. However, influenza viruses constantly change and it’s possible that this virus could gain that ability,” it added.
The CDC briefed infectious disease experts on what to do. Anyone who has severe symptoms and has recently traveled to China should be treated immediately with antiviral drugs – either Tamiflu or Relenza, the CDC says.
“Given the anticipated lack of preexisting immunity to H7N9 viruses, the potential for rapid progression, severe disease, and fatal outcomes with H7N9 infection, and low adverse event profile of neuraminidase inhibitors, treatment with oseltamivir or inhaled zanamivir should be initiated when confirmed cases, probable cases, or H7N9 cases under investigation are recognized, even if more than 48 hours from illness onset and even for apparently uncomplicated illness,” the CDC advises.