The H7N9 flu emerged in humans in eastern China in February 2013, sickening 133 people and killing about a third of them before winding down in May. It seemed that the outbreak was over, but it reemerged in October 2013 and has been spreading steadily since.
“H7N9 viruses should be considered as a major candidate to emerge as a pandemic strain in humans,” they wrote in a study published Wednesday by the journal Nature.
According to the World Health Organization, 571 people have had laboratory-confirmed H7N9 infections and 212 people have died. All but three cases were in China, Hong Kong and Taiwan. The others involved a Chinese traveler to Malaysia and two Canadians who had visited China.
The virus developed in birds before spreading to humans. Like the H5N1 bird flu and the H1N1 swine flu, it contains a combination of genes that are new to people.
All flu viruses are made of just eight genes. Two of those genes make the proteins that stud the surface of the virus. Hemagglutinin (H), helps invading flu particles latch on to cells. Once inside, the virus hijacks the host cell’s machinery to make hundreds of copies of itself. When those copies are ready to spread to other cells, the neurominidase (N) protein allows them to get out.
Scientists have identified 18 types of hemagglutinin proteins and 11 types of neurominidase proteins. All of them have infected birds, but only some of them have been documented in people.
So far, H7N9 is spreading primarily among chickens in live-poultry markets, according to the authors of the Nature study. Researchers tested market chickens in 15 cities in the Chinese provinces of Zhejiang, Guangdong, Jiangxi, Jiangsu and Shandong. Infected chickens were found in seven of those cities.
What’s more, each of those seven cities also had at least one case of human infection with H7N9, the study authors wrote.
To figure out how this virus managed to make a comeback, the research team sequenced the complete genomes of 438 samples of H7N9 found in poultry, as well as 19 samples taken from human hospital patients in Shenzhen. They also sequenced 263 related bird flu viruses.
The RNA sequences of the hemagglutinin genes confirmed that the H7N9 viruses now circulating are descendants of the viruses that appeared in the spring of 2013. The viruses probably hitched a ride around China inside chickens that were transported along trade routes. The current viruses can be grouped into three categories, or “clades.” All of them are descendants of the viruses that appeared in the spring of 2013.
One of the clades likely originated in the Yangtze River delta region and then spread to other provinces as chickens were transported to distant markets. Another clade was mainly limited to Jiangxi, though it somehow spread to two people in Taiwan.
A third clade has been found in only Guangdong, but it is responsible for more human infections than either of the other two. The proliferation of these viruses suggests it is prevalent in chickens there, according to the study.
When the researchers looked at the neuraminidase genes, they found evidence that multiple strains of H7N9 have been circulating in Guangdong. When two or more flu viruses infect the same body, they can mix and match their genetic material.
Overall, this second wave of H7N9 influenza viruses represents “a major increase in genetic diversity” compared with the viruses in the first wave, the study authors wrote. Unless live poultry markets are permanently closed, merchants stop transporting chickens from region to region, and other control measures are put in place, the virus will “persist and cause a substantial number of severe human infections.”
So far, most people were sickened by handling infected chickens; cases of the virus spreading directly from person to person have been limited. That might change if the virus mutates, as happened with the H1N1 swine flu pandemic that began 2009. Or it might not, like the H5N1 bird flu that emerged in 2003.
But as long as chickens are on the move, it’s a safe bet that H7N9 will spread too, the researchers warned.
“It is probable that the H7N9 virus is now present across most of China,” they wrote. “Given the current pattern of dissemination, it will only be a matter of time before poultry movement spreads this virus beyond China by cross-border trade.”