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SAN DIEGO -- Flu experts are watching China uneasily these days after some unsettling changes in the H7N9 avian influenza A strain during the 2016-17 epidemic in that country.
The fifth wave of the virus, which was first seen in humans in 2013, saw a "huge surge in cases," the CDC's Tim Uyeki, MD, told a symposium here at the annual IDWeek meeting, sponsored jointly by the (IDSA), the (PIDS), the (SHEA), and the (HIVMA).
After the first year, Uyeki said, the case totals in following seasons were roughly stable or declining, but the fifth saw some 764 cases, almost half the cumulative total of 1,562 over all 5 years, according to the World Health Organization.
But what worries the experts is not just the numbers. After 4 years of relative stability, the virus began to show changes during the most recent wave, including a newfound ability to escape vaccines and to resist antiviral drugs, Uyeki said.
As well, the virus was seen in a greatly expanded territory and began -- for the first time -- to cause illness in the birds it infects.
For those reasons, a new CDC model -- the -- puts H7N9 at the head of a list of animal flu strains that might cause a pandemic among humans.
In the first four waves, the virus was mainly borne by poultry (who were unharmed by it) and the way people caught it was by exposure to infected birds, often in large poultry markets. There was some human-to-human transmission but it was not easy. When clusters of cases emerged, it was usually because of exposure to a common avian source, rather than transmission among people.
Still, most reported cases resulted in hospital admission and some 40% of admitted patients died, Uyeki said. "That's been consistent since 2013," he told ľֱ, "and 40% is extremely serious illness."
But in 2016-17, Uyeki said, the virus showed "significant antigenic drift" to the point where the experts said it no longer belonged to the older Pearl River Delta lineage, but now merited a new name -- the Yangtze River Delta lineage.
The new lineage was "no longer well controlled" by the vaccines that had been developed to protect against the earlier lineage, he said, and roughly 10% of isolates now showed markers of resistance to the main class of anti-influenza drugs -- the neuraminidase inhibitors. In earlier years such markers had been seen in about 4% of isolates.
As well, late in the season, the virus suddenly started to kill infected birds. From a "low pathogenic" avian flu, it had become "highly pathogenic" and 10 Chinese provinces saw outbreaks among their poultry stocks.
There is little data yet on how that change will affect people -- Uyeki said there have only been 28 recorded human cases so far -- but experts are looking to the sixth wave with some trepidation.
On the positive side, if the virus affects birds, it will be easier for health officials to follow outbreaks and perhaps to take preventive measures, commented Andy Pavia, MD, of the University of Utah, who moderated the session at which Uyeki spoke.
"It would be a lot easier to track and control the high-path species because at least you know where to look," Pavia told ľֱ.
How humans will be affected is the open question, he said, noting that "the changes that make it high path for birds are not the same as those that make it more transmissible among humans."
One thing that's important for a flu virus to spread efficiently among people is the ability to bind to receptors in the upper airway. Seasonal influenza strains have that ability but usually have a low case fatality rate. The highly pathogenic H5N1 avian flu binds only to receptors in the lower respiratory tract and so only rarely infects people but kills 60% of the people it does infect.
The H7N9 flu lies somewhere in the middle, Uyeki said -- it prefers receptors in the lower respiratory tract but can bind to those in the upper regions.
"In general," Pavia said, "everybody in the flu field is worried about the fifth epidemic."
"There's spread to a much larger area in China, it's still causing a lot of cases in areas where they've done a pretty god job of trying to clean up the poultry markets, and the sheer numbers makes you wonder what's coming next."