Cases reported in new regions of China.
The H7N9 avian flu virus greatly expanded its geographical range over the weekend, with two human cases reported in Beijing in the north of China, and another two in the central Henan province. Previously, the virus had been restricted to Shanghai and neighbouring regions on the eastern seaboard. Experts worry that H7N9 could start to fan out across large areas of China, and beyond.
There is still no evidence of any sustained human-to-human spread of the H7N9 virus. But the World Health Organization confirmed on Saturday that Chinese authorities are investigating two clusters of human cases. Although these can arise as a result of infection from a common source, they can also be a sign of limited human-to-human transmission.
"I think we need to be very, very concerned" about the latest developments, says Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam.
Threat of mild cases
The Beijing Municipal Health Bureau also announced on Sunday that a 4-year-old contact of a hospitalized 7-year-old had tested positive for the virus, despite showing no symptoms. This is the first known asymptomatic case. Along with several mild cases already reported, it suggests that the virus might be more widespread among humans than reports imply.
Perhaps counter-intuitively, such mild cases are "very worrying", says Farrar. Reduced virulence can often suggest that the virus has gained genetic adaptions that help it to infect human beings — and thus to spread.
Experts say that the surge in human cases is troubling, with 63 infections and 14 deaths reported as of Monday, up from 24 cases barely a week before. China reported its first cases of H7N9 on 31 March; in just over two weeks since then, the number of H7N9 cases has grown to exceed the 45 cases of H5N1 avian flu that China has reported over the decade since that virus began causing human outbreaks.
If that pace keeps up or accelerates, H7N9 "could be a significant public-health problem” even if it can be caught only from animals, says Marc Lipsitch, an epidemiologist at the Harvard School of Public Health in Boston, Massachusetts.
Tough to combat
Genetic analyses of H7N9 show that it has several mutations that make it better adapted to humans than H5N1. "This looks very different from H5N1," says Farrar. "We never saw this number of presumed avian/animal to human transmissions in such a short space of time."
H7N9 is also proving a more difficult foe in other ways. Concern that the virus would be next to impossible to track or control because it does not cause serious illness in birds has been reinforced by the cases in Beijing and Henan, which appeared with no warning.
In the case of H5N1, outbreaks in poultry precede human outbreaks and tell public-health workers where the threat lies. But with H7N9, only the appearance of human cases shows where the silent spread in birds or other animal reservoirs is heading, says Vincent Martin, interim head of the Emergency Prevention System for Transboundary Animal and Plant Pests and Diseases in Rome, part of the Food and Agriculture Organization (FAO) of the United Nations.
Chinese authorities have already identified H7N9 in birds at markets in Shanghai and other cities. But despite intensive surveillance of poultry, wild birds, pigs and other animals, the animal reservoirs remain largely unknown. "With so little knowledge of the possible reservoir host, we're a bit walking in the mist here," says Marius Gilbert, who studies epidemiology and ecology of avian flu viruses at the Free University of Brussels.
The virus may have reached Beijing and Henan through the poultry trade, which is extensive in China, with trade routes criss-crossing the length and breadth of the country. That could mean that the main reservoir of virus in animals is still restricted to the Shanghai region.
But it is also possible, says Gilbert, that H7N9 has been spreading silently in poultry or other animals over a far greater area. If so, "new cases will keep popping up left, right and centre".
Either mechanism could transport the virus far beyond China's borders. "Neighbouring countries need to be on high alert," says Martin, adding that the FAO is in daily contact with countries as far away as Africa, to discuss the surveillance and other measures needed to try to prevent the introduction of the virus.
Nailing down transmission routes in China alone is a huge challenge; the vast country is home to some 6 billion poultry birds as well as many migratory and other wild species that may have a role in spreading the virus. On Wednesday, Martin will convene a meeting of international experts at the FAO in Rome to help to draw up surveillance guidelines for China and the wider region.
Despite the difficulties of detecting H7N9 in birds, Martin remains optimistic that as long as the virus does not start to spread among humans, the number of human cases can be contained by taking urgent measures — such as keeping poultry flocks away from wild birds and people, and restructuring live-bird markets.
"It's too soon to say how big a threat H7N9 poses because we don't know how many animals of which species have it, how genetically diverse it is or what the geographic extent is," says Lipsitch. "It looks as though it will be at least as challenging as H5N1."
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Related external links
World Health Organization H7N9 site
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Butler, D. H7N9 bird flu poised to spread. Nature (2013). https://doi.org/10.1038/nature.2013.12801