Analysis of H7N9 in China finds age, geographic shifts

A detailed epidemiologic analysis of illnesses in China's fifth and biggest wave of H7N9 avian influenza activity, still under way, found a few shifts in the epidemiologic pattern, with middle-age adults more likely to be infected and the reach of the disease extending from urban to more rural areas.

So far, reassuringly, the disease in humans doesn't seem more severe than the earlier four waves. A research team based in China published its findings in the Jun 2 early online edition of The Lancet Infectious Diseases.

More middle-aged, rural adults affected

The group's review includes 1,220 lab-confirmed cases reported since February 2013 when the first H7N9 infections were detected in humans. For the fifth wave, they include 447 cases reported in mainland China as of Feb 23. Since then, the country has reported many more cases, with a number of northern provinces affected, some of which have reported their first human illnesses.

Notably, the fifth wave began earlier than usual and has seen not only an unprecedented number of illnesses—at least 722 cases so far, compared with 319 in the next-largest wave. But the current wave has also witnessed the emergence of a highly pathogenic version of H7N9 in poultry and in humans that contains genetic mutations, including one for resistance to neuraminidase inhibitors, the most commonly used flu antivirals.

When the virus first emerged in humans in 2013, older people were the hardest-hit group. According to the new analysis, however, the proportion of cases in middle-aged adults has increased steadily, from 41% during the first wave to 57% in the fifth wave.

During the first three waves of H7N9 illnesses, large percentage of the human cases were among those living urban areas. But over the past two waves, the proportions of cases from semi-urban and rural residents has grown, making up about 60% of the cases, reflecting a steady rise from 39% reported during the first wave.

When the researchers looked at cases by geographic location, they found that in affected provinces, the virus had spread to more districts and counties, a sign of broader spread.

Possible explanations for changes

The early start to the latest H7N9 wave might be linked to environmental changes, such as weather conditions, but more research is needed to tease out seasonality factors, the team reported.

Wider geographic expansion suggests that H7N9 viruses have extended their reach in poultry since the first human infections were detected, perhaps a consequence of its circulating in poultry as a low-pathogenic strain that causes few if any symptoms in birds. Researchers said that closure of live-poultry markets in areas where human cases were detected could have moved infected ready-for-market poultry into areas with no or less strict market closure rules.

The increase in human cases likely means that H7N9 prevalence in poultry is probably higher than before, the group wrote, adding that exposure patterns might change with the emergence of the highly pathogenic strain.

The risk of death from H7N9 has increased across the five waves, but the researchers didn't see a significant difference between fatality rates in the fourth and fifth waves. Antiviral therapy started slightly earlier for patients hospitalized with H7N9 over the past two waves, but that improvement wasn't paired with a reduced fatality risk.

Experts alarmed by rural shift

In an accompanying editorial, two virologists said the size of the fifth wave and the transition to a highly pathogenic form in poultry raise several questions, especially regarding what has changed and if the changes have a bearing on pandemic risk. The authors are Richard Webby, PhD, with St. Jude Children's Research Hospital in Memphis, and Zifeng Yang, MD, PhD, with State Key Laboratory of Respiratory Disease in China.

They said so far, there is little to suggest that H7N9 viruses on their own have become a greater threat. The two noted, however, that the most worrisome finding is the shift from urban to semi-urban and rural areas.

"If one considers human beings the canaries in the coal mine, these findings imply that the virus is more widespread in poultry," Webby and Yang wrote. They added that another possible explanation might be that the genetic shift might make the virus more infectious for waterfowl, though no evidence suggests that has happened.

Spread of the virus to provinces such as Guangxi that have extensive water bodies increases the chance of waterfowl exposure, they noted. "But how much of the above is speculation and how much is likely to be true? Herein lies the biggest unknown in the A H7N9 story."

True prevalence of H7N9 in Chinese birds isn't known, and other factors, even ones at the provincial level, might explain some of the features of the unprecedented fifth wave, they wrote.

See also:

Jun 2 Lancet Infect Dis abstract

Jun 2 Lancet Infect Dis commentary

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