The H7N9 bird flu that first emerged in 2013 has spread quickly across China and mutated into different strains that are now mixing with other flu viruses — all troubling signals that H7N9 is "a major candidate to emerge as a pandemic strain in humans," according to a new paper.
In a Nature paper published Wednesday, an international team of scientists called for stronger control measures and better surveillance to dampen China's growing bird flu threat. The paper comes on the heels of a recent uptick in H7N9 cases and a February report from the World Health Organization, warning that the "world needs to be concerned" about the increasingly worrisome mix of influenza viruses now circulating.
"Because there are so many different viruses (now mixing), I think the pandemic potential of H7N9 virus has increased," said Dr. Yi Guan with the Centre of Influenza Research at the University of Hong Kong, a leading bird flu expert and one of the study's authors.
"We want to sound an alarm to the world."
According to the WHO's latest figures, H7N9 has caused 602 infections and 227 deaths since the virus first emerged in February 2013, with the vast majority in mainland China. In January, Canada also reported North America's first known H7N9 cases after a British Columbia couple became mildly sick after travelling to China.
The WHO says there is no evidence the virus is spreading easily between people, however, and patients are likely being infected through direct contact with birds or contaminated environments.
In this latest study, the researchers — based in China, Australia and the United States — collected samples from more than 20,000 live chickens and ducks at poultry markets to investigate China's second wave of H7N9 infections.
The virus first emerged in February 2013 but caused a second, larger wave eight months later, which infected more than twice as many people and spread the disease farther south — most notably to Guangdong province, which detected its first human patient in August 2013 and now has the highest number of reported cases.
Of the 16,299 chicken samples, 3 per cent were positive for H7N9; none of the duck samples tested positive.
After sequencing more than 430 H7N9 genomes — which were compared to viral samples from 19 patients — the researchers determined that H7N9's second wave was caused by strains that evolved from the first outbreak, with the virus likely spreading along trade routes. Second-wave strains have also mutated further to form at least three distinct genetic groups, the study reported.
The researchers believe H7N9 has established itself in chicken populations and probably already present across the country. "It is only a matter of time before poultry movement spreads this virus beyond China," they conclude.
"H7N9 is fully entrenched in China and will continue to remain a zoonotic and potential pandemic threat for many years to come," said Dr. Malik Peiris, another study co-author and Guan's colleague at the University of Hong Kong, in an email.
In addition to the H7N9 viruses, the researchers sequenced more than 260 other influenza strains found in their bird samples. One was entirely new — H7N6, which appears to have emerged from the mixing of H7N9 with H5N6, another novel bird flu that has killed two people since it was first detected last year.
As the WHO explained in a recent report, flu viruses that mix together in the bodies of their infected hosts can swap genes to "constantly reinvent themselves in a dazzling array of possible combinations" — something that appears to be happening now at "an accelerated pace."
"H7N6 is just one of the new reassortants," Guan said. "In total, we actually identified 48 different reassortants. That many. So this is bad news."
Guan believes much stronger control measures are needed to stop this dangerous mixing of viruses in China's bird populations. His paper proposes permanently closing live poultry markets, moving towards a centralized slaughtering system, and preventing inter-regional poultry trade in times of outbreak.
But Guan would also like to see boosted surveillance of poultry and wild birds, which are "silent spreaders" of H7N9 since they do not show symptoms when infected.
This unique feature sets H7N9 apart from other bird flus, like H5N1, where mass bird die-offs often signal the arrival of a new outbreak. Currently, H7N9 is mostly announcing itself through human infections. "We shouldn’t be using humans as the sentinels," Guan said.
This new Nature study is just the latest warning signal from what the WHO recently described as an increasingly "volatile world of influenza viruses."
Since the beginning of 2014, 20 countries have notified the Organization for Animal Health of 41 outbreaks involving H5 and H7 viruses, the two most worrisome influenza subtypes, according to WHO.
This is in addition to China's ongoing H7N9 threat, an alarming spurt of H5N1 cases in Egypt — which reported more cases in the last four months than any country has in a year — and multiple bird flu viruses that have recently popped up.
"The emergence of so many novel viruses has created a diverse virus gene pool," the WHO said. "The consequences for animal and human health are unpredictable yet potentially ominous."
For Dr. Michael Osterholm, an infectious disease expert with the University of Minnesota, the new Nature paper demonstrates that H7N9 is well on its path towards becoming an effective human-to-human pathogen — the "critical link in the creation of a pandemic flu."
But trying to stop these viruses from spreading and evolving in birds is as futile as "stopping the wind in Chicago," he said.
"The one thing we can do to truly take all of this off the table is the development of a truly game-changing flu vaccine," said Osterholm, who published a report calling for this in 2012. "We have no machinery set up globally to do that, none."