Will the H7N9 Avian Flu Spread to People Outside Mainland China?

High-risk areas might include Shandong province (where the first case of 104 among humans was reported April 23) and a belt extending around the Bohai sea to Liaoning province in the north. But cases beyond China might be just a matter of time

By Declan Butler and Nature magazine

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CLICK MAP FOR DATA: Flight routes from the outbreak regions would quickly carry any human-transmissible virus to huge population centers in Europe, North America and Asia. Estimated numbers of people residing within two hours' travel time of destination airport calculated using gridded population-density maps and a data set of global travel times. Image: A. J. Tatem, Z. Huang and S. I. Hay (2013). Unpublished data. (A.J.T., University of Southampton, UK; Z.H., University of Florida, Gainesville; S.I.H., University of Oxford, UK.)

Scientists do not yet fully understand how the H7N9 avian influenza virus is spreading in China, or why the pattern of sporadic human cases looks like it does. But mapping the risks of known factors in the past geographical spread of avian flu viruses and human infections might provide some clues.

The first known cases of human infection with H7N9 were reported in China on 31 March, with two cases in Shanghai on the eastern seaboard and one in the neighboring province of Anhui. As of 22 April, the World Health Organization (WHO) has tallied 104 confirmed cases, including 21 deaths, and the virus has expanded its geographical range to neighboring Jiangsu and Zhejiang provinces, as well as Beijing in the north and Henan in the center of the country.

On 23 April, China's state news agency, Xinhua, reported a 36-year-old man in serious condition in the city of Zaozhuang, midway between Shanghai and Beijing — the first case from Shandong province (not shown on map). The biggest number of cases has been reported in Shanghai, with 32, and Hangzhou in Zhejiang province, with 27; Huzhou in Zhejiang province has reported 10 cases, as has Nanjing in Jiangsu province.

To stem the current surge of human cases, scientists must identify the sources of the virus, and the route by which it infects humans. Birds at live markets have been suspected as one source, but tens of thousands of tests in poultry and other animals elsewhere have so far failed to turn up significant levels of the virus.

It is far from easy to devise effective ways to sample birds and animals for testing in a country with some 6 billion domestic birds and 0.5 billion pigs — not to mention a vast population of wild birds, including many migratory species. Although the risk factors for the spread of H7N9 are not known, voluminous research on its cousin, the H5N1 virus that has caused 622 confirmed cases and 371 deaths since 2003, may help inform analyses. This, in turn, would help scientists and health officials to target their surveillance and control efforts.

For H5N1, researchers integrate large data sets that combine information on many potentially important factors, such as poultry trade routes, the numbers of birds being transported, the distribution of live-bird markets and their supply routes, waterfowl numbers, land use and human population densities. To these, they add the distribution of H5N1 cases in poultry, and as well as positive H5N1 results from active surveillance in markets.

Marius Gilbert, a co-author of one such study published in PLoS Pathogens in 2011 paper, and an expert in the epidemiology and ecology of avian flu viruses at the Free University of Brussels, says that although the risk factors for H7N9 may be different, given the current dearth of information, H5N1 risk maps are probably a good starting point for identifying areas most at risk.

Indeed, when human cases of H7N9 are overlaid on a risk map that Marius and his co-authors supplied to Nature, they seem to fall within the highest risk areas for H5N1. The map suggests that high-risk areas for H7N9 might include Shandong province (which reported its first case on 23 April) and a belt extending around the Bohai Sea to Liaoning province in the north.

Gilbert was one of more than 30 international experts who gathered at the Food and Agriculture Organization of the United Nations in Rome for a two-day meeting last week to discuss the current H7N9 outbreaks. At that meeting, he says, risk modeling and mapping were discussed as one means to devise targeted surveillance. Such information could also be used to help to modify farming and trade practices to reduce the risk of human exposure to the virus. As more is learned about H7N9, such models can be further refined.

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