Once again an animal influenza A virus has crossed the species barrier to cause an appreciable number of human cases. Now, two months after the first known human infections with the H7N9 virus, the question is: which of the paths set by previous emerging influenza viruses will it follow?
One predecessor, H5N1, generated alarm owing to its high pathogenicity in humans. It has proved to be a tenacious adversary, remaining endemic in poultry across large parts of Asia, but thankfully it has not adapted to humans and person-to-person transmission remains rare.
A second, H7N7, caused a number of mostly mild human infections in the Netherlands in 2003, with some evidence of limited person-to-person spread, but extensive poultry culling controlled it. A third, the H1N1 swine influenza virus that emerged in 2009, successfully adapted to humans and caused a pandemic.
So will H7N9 prove to be controllable? Will it remain entrenched in animals? Or will it, like the H1N1 virus, stably adapt to humans and cause a pandemic? The fine line between foresight and alarmism can only be drawn in retrospect. Nevertheless, my colleagues and I consider that H7N9 has many of the traits that make a new flu virus worrisome.
The H7N9 haemagglutinin protein — which binds to target cells — resembles those of other avian flu viruses that cause only mild disease in birds. This means that the virus is likely to spread silently in domestic and probably wild birds.
Human infections are therefore the sentinel events, and the numbers and geographic extent of human cases — all of them so far in China — suggest that a hidden epidemic in other animals is well under way.
The small number of poultry in which H7N9 has so far been detected is rather puzzling, as are the 20% of people infected with the virus who have not reported exposure to poultry. Nevertheless, domestic birds are likely to be the main source of human infections. And the animal epidemic is likely to spread farther, with large suppliers distributing poultry across China. Flying wild birds are another possible mode of spread.
Given that the virus probably does not cause severe disease in birds, and the uncertainty surrounding the animal source, containing the animal epidemic poses an enormous challenge.