Nature
Volume 496 Number 7446 pp397-542 25 April 2013
http://www.nature.com/nature/current_issue.html
Nature | Editorial
The fight against bird flu
China’s well-handled response to outbreaks of H7N9 avian influenza belies the country’s bad reputation from its past dealings with disease. But there are still improvements to be made.
24 April 2013
China deserves credit for its rapid response to the outbreaks of H7N9 avian influenza, and its early openness in the reporting and sharing of data.
A bad reputation is difficult to shake. A decade ago, China failed to report early cases of severe acute respiratory syndrome (SARS) and fumbled its initial response to the threat. Today, some commentators view its reaction to H7N9 with mistrust. But from all the evidence so far, China’s response to the virus, which had caused 104 confirmed human cases and 21 deaths as Nature went to press, is next to exemplary.
China reported the H7N9 outbreak to the World Health Organization (WHO) on 31 March, just six weeks after the first known person fell ill. On the same day, it published the genomic sequences of viruses from the three human cases then identified on the database of the Global Initiative on Sharing Avian Influenza Data (GISAID). It has also shared all the sequences with the WHO, and live virus with the WHO and other laboratories. This has allowed scientists to identify the virus’s mutations, trace its origins and develop crucial diagnostic tests. China continues to report new cases daily, and its media discusses H7N9 fairly openly. Chinese and other researchers have quickly published detailed analyses of the virus in journals (R. Gao N. Engl. J. Med. http://doi.org/k7r; 2013). Chinese President Xi Jinping added political clout last week when he called for an effective response, and said that the government must ensure the release of accurate information about the outbreaks.
China’s response to the epidemic has also been brisk. Diagnostic tests have been distributed to hospitals and research labs across the country. The response, spearheaded by the Chinese Center for Disease Control and Prevention in Beijing, has united clinicians, virologists, and epidemiologists. Live-bird markets at which H7N9 has been found have been shut down, and birds culled. The agriculture ministry has tested tens of thousands of birds and other animals for the virus, to try to pin down the sources of human infections and explain their occurrence in cities hundreds of kilometres apart — no mean task given that China has some 6 billion domestic fowl and half a billion pigs, which can also carry the virus. So far, however, apart from birds at the live markets, the sources of infection remain elusive. To help track them down, and to collaborate in efforts to control H7N9, China has invited a team of WHO scientists and international flu experts to the country. They arrived last week, and are expected to report their preliminary conclusions this week.
Yet suspicions linger. Some critics have questioned, for example, the time between the first person falling ill on 19 February and China’s first announcement about the virus, and have asked whether the announcement was deliberately delayed. This is unfair. With just a handful of severe pneumonia cases caused by the virus by mid-March, it is impressive that China realized as quickly as it did that something was amiss. It took the United States, which has one of the world’s most advanced disease-surveillance systems, an almost identical amount of time to identify a novel H3N2 swine virus that caused serious illness in a child in 2011.
“China has made a good start, but it is crucial for the country to continue its openness over the H7N9 outbreaks.”
China has made a good start, but it is crucial for the country to continue its openness over the H7N9 outbreaks. In particular, it must promptly report any evidence of human-to-human spread. There are also areas for improvement: data made public on human cases are often limited to basic facts such as age, sex, date of onset of illness and location. Epidemiologists also need more detailed data, including possible exposures to infection and underlying medical conditions. Case reports should be published in full in journals or online as quickly as possible.
It is also important that sequences from as many cases as possible are submitted to publicly accessible databases, because sequence data are important in tracking evolutionary changes such as new mutations that could allow the virus to spread between humans more easily. They can also provide clues to the source of infection (see page 399).
Even as the Chinese authorities are being open and transparent on H7N9, some scientists are hoarding epidemiological and other data, because of intense competition to be the first to publish. Competition can be healthy, but in the face of a virus that has the potential to cause a pandemic, researchers have a duty above all else to share important data. Journals must be ready and willing, as in any public-health emergency, to fast-track peer review of H7N9 papers, and not let rapid publication of preprints stand in the way of considering papers for publication. Meanwhile, observers should continue to scrutinize China’s response to H7N9, but they should also give credit where credit is due. It is time to recognize that China has changed.
http://www.nature.com/news/the-fight-against-bird-flu-1.12850
Nature | Column: World View
H7N9 is a virus worth worrying about
Warnings about the emergence of another influenza virus may elicit skepticism, but we should not be complacent, cautions Peter Horby.
24 April 2013
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.
So far, extensive monitoring of contacts has not found evidence that the virus has spread efficiently between people. Limited human-to-human transmission may have occurred but, as we saw with H5N1 and H7N7, this does not necessarily represent the early stages of a trajectory towards full human adaptation. However, H7N9 viruses isolated from patients possess some genetic signatures that are associated with effective replication and transmission, and with high virulence in mammals. The regions of China where H7N9 seems to be circulating have large populations of pigs as well as humans, providing opportunities for further adaptation to mammals and for re-assortment with human- or pig-adapted viruses.
The clinical epidemiology of H7N9 cases has some similarities to human seasonal influenza. Unlike the H7N7 cases in 2003, which usually took the form of conjunctivitis, the H7N9 infections so far detected have caused respiratory illness, with cases in all ages but being most severe in the elderly and people with underlying illnesses. However, the fact that the average age of people infected is high — around 60 years — and that most reported infections have been severe suggests that the virus is not yet well adapted to humans. Only further clinical and epidemiological data will reveal the full spectrum of infection and severity.
Standardized collection and sharing of clinical data would aid risk assessment and treatment. A clinical protocol and case-record and informed-consent forms developed by the International Severe Acute Respiratory and Emerging Infection Consortium and the World Health Organization are available online (see go.nature.com/fpsiog).
If H7N9 were to stably adapt to humans, it would probably meet with little or no human immunity. Detecting and tracking a partially human-adapted H7N9 virus in a city as vast as Shanghai or Beijing would be difficult; tracking a fully adapted virus would be impossible. And it could easily spread nationally and internationally. Eastern China is now one of the most ‘connected’ population centres in the world. Seventy per cent of the global population outside China lives within two hours of an airport linked to the outbreak regions by a direct flight or a single connection (see go.nature.com/tvfev8). Travel restrictions or border screening will not contain pandemic influenza for long.
If there was an overreaction to H1N1, we should not compound the error by under-reacting to H7N9. Hopefully H7N9 will remain an animal virus, and maybe the fact that it has circulated for at least two months without stably adapting to humans indicates that the species barrier is too great for it; but maybe not. The first human case of H7N9 outside mainland China is perhaps only a matter of time. Then the public-health and clinical community will need to assess, carefully and quickly, whether it represents a single imported case of animal-to-human transmission, an animal epidemic that has spread abroad, or the international spread of a partially or fully human-adapted virus.
http://www.nature.com/news/h7n9-is-a-virus-worth-worrying-about-1.12853
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