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International Society for Infectious Diseases
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Date: Tue 2 Tue 2003
Source: Nature, Breaking News [edited]
http://www.nature.com/news/novel-bird-flu-kills-2-in-china-1.12728
Scientists and public health officials worldwide are on alert after China announced on 31 Mar 2013 that 2 people had died and a 3rd had been seriously sickened from infections with a new avian flu virus, H7N9, that has never been seen before in humans. The emerging, if preliminary, analyses of the virus's genome point to the possible spectre of a pathogen that might spread silently in poultry without causing serious disease. That would make the virus difficult to monitor even as it causes serious disease in humans. Should the virus become established in birds [poultry], regular human infections might then occur, providing opportunities for it to adapt better to humans, and ultimately spread between them, potentially sparking a pandemic.
Scientists stress that it is far too early to make a full risk assessment of the potential pandemic threat. But the initial analysis of viral sequences is "worrisome" because they show several features suggestive of adaptation to humans, says Masato Tashiro, a virologist at the Influenza Virus Research Center in Tokyo, the World Health Organisation (WHO)'s influenza reference centre in Japan.
The epidemiological picture is troubling too, says Malik Peiris, a flu virologist at Hong Kong University. "Any time an animal influenza virus crosses to humans, it is a cause for concern, and with 3 severe cases [of disease] over a short period of time, we certainly have to take it seriously," he says. "There's no obvious indication of human to human spread, so we should not overreact, but neither should we be complacent."
The cases
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The 1st case of the novel H7N9 was an 87-year-old man in Shanghai who became ill on 19 Feb 2013 and died on 4 Mar 2013. A 27-year-old man in the same city fell ill on 27 Feb 2013 and died on 10 Mar 2013. A 35-year-old woman in Chuzhou City in Anhui province, several hundred km west of Shanghai, fell ill on 9 Mar 2013 and remains seriously ill. All 3 developed flu-like symptoms before developing severe pneumonia. The cases were announced on 31 Mar 2013 by China's health ministry, the China Health and Family Planning Commission, which informed the WHO on the same day.
So far, there appears to be no sustained spread between people. Chinese authorities tracked dozens of contacts of the 3 cases and reported that none showed relevant symptoms or tested positive for the virus. Some uncertainty hangs over whether family members of the 1st case -- who were hospitalized with severe pneumonia just before their father -- might have passed on the virus to the elderly, housebound man. Though the family members reportedly tested negative for the virus, these might have been false negatives. Still, for the moment, experts say that if any human spread is occurring, it is not happening easily.
Chinese researchers have moved swiftly to decipher the new virus. The WHO Chinese National Influenza Center in Beijing has sequenced isolates from each of the 3 cases and on 31 Mar 2013 published them on the GISAID flu sequence database. Researchers around the world have since been racing to discover what clues the genome might hold as to the source of the virus and to its pathogenicity and potential to infect and spread between humans. Analyses suggest the virus is a new one that has been generated by reassortment, which occurs when different virus strains infect a host at the same time and swap genes with each other.
Flu viruses have 8 genes, including 2 that carry codes for the haemagglutinin (H) and neuraminidase (N) proteins that stud the surface of the virus, and 6 that code for internal proteins. Analyses so far suggest that in the new human cases, the genes coding for the internal proteins appear to come from H9N2 viruses, a class that is endemic in birds, including poultry, in Asia and elsewhere. More specifically, the sequences appear similar to recent H9N2 viruses found in China and South Korea.
The gene for the N protein, says Tashiro, appears similar to avian H11N9 viruses that were found in South Korea in 2011; in Hongze, Jiangsu, in 2010; and the Czech Republic in 2005. The gene for the H protein is especially critical, because this protein allows the virus to bind to host cells and seems to belong to a Eurasian group of H7 avian flu viruses.
The new virus, in other words, seems to stem from reassortment of 3 virus strains that purely infect birds, in contrast with the 2009 H1N1 pandemic virus, which was a mix of viruses that infect birds, pigs and humans. Most of the genetic analyses are still being carried out confidentially within WHO's global flu research networks. But some researchers, such as a team at the University of Edinburgh, have also started posting their preliminary analyses online athttp://epidemic.bio.ed.ac.uk/. - Mod.CP]
Does not sicken birds
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A striking feature of the novel virus is that its H protein is structurally similar to that of viruses that don't cause severe sickness in birds and different from those that do, such as the H5N1 virus that has been ravaging poultry flocks in Asia since late 2002. Flu viruses that don't sicken birds can, however, cause severe disease in humans simply because we lack any immunity to them. They also may be more lethal in people depending on how they bind to receptors in the human airways.
Though analysis is in the early days, scientists say it seems clear from the sequence that the novel virus has acquired key mutations that permit the H protein to latch onto receptors on mammalian cells in the airways instead of avian receptors. The virus also contains several other genetic variations that are known from past studies in mice and other animals to cause severe disease.
Initial data suggest, too, that the virus is affecting cells deep in the lung, which would fit with a picture of a virus, much like that of the novel coronavirus, that can cause severe disease. But it may also indicate a virus that doesn't spread as easily as one that affects the nose and throat and can thus be coughed and sneezed out more readily. Still, the full pattern of receptor binding has yet to be worked out, cautions Peiris.
Public health implications
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The fact that the virus appears not to sicken birds has potential epidemiological and possibly public health implications, Peiris adds. It could be spreading in poultry undetected and thus could create a reservoir of infection that would lead to frequent sporadic human infections that crop up without warning. A highly pathogenic virus like H5N1 is easy to spot as it wipes out flocks, and can then be controlled by extended culling. But it might be next to impossible to control a virus in birds that offers few visible symptoms, says Peiris. "That really would be quite a problem," he says. "The question is whether it's already too late to stamp out or not." Indeed, China has not reported any recent H7 flu infections in birds, perhaps because such infections would not show up as serious disease, or maybe because of shortcomings in surveillance or reporting. A key need now, Peiris says, is to track down from which birds or animals the affected humans caught the virus.
Though H7 viruses are common in wild birds, but much less so in poultry, it seems highly unlikely that 3 human cases [now 9 - Mod.CP] in such a short time could result from contact with wild birds, he says. Domestic fowl are the most likely alternative. But given that the virus has mutations that are adapted to infection of mammals, a source might also be pigs, says Tashiro.
Flu experts say that other urgent needs include testing any human cases of serious pneumonia for traces of the virus and tracking down contacts of any new human cases. Among researchers and public health officials, says Peiris, "It's not an atmosphere of alarm, but an atmosphere of concern."
[Byline: Declan Butler]
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Communicated by:
ProMED-mail Rapporteur Kunihiko Iizuka
[The initial analysis of viral sequences is showing several features suggestive of adaptation to humans. The H7N9 virus seems to originate from reassortment of 3 virus strains that only infect birds, in contrast to the 2009 H1N1 pandemic virus, which was a mix of viruses that infect birds, pigs and humans. Some sequence information is already becoming available. Readers interested in data as distinct from comment should visit the University of Edinburgh at:http://epidemic.bio.ed.ac.uk/(http://epidemic.bio.ed.ac.uk/influenza_H7N9_analysisandhttp://epidemic.bio.ed.ac.uk/influenza_H7N9_mutations).
The sequence data available so far suggest that the H7N9 virus may have acquired key mutations that permit the haemagglutinin protein to latch onto receptors in mammalian airways instead of avian-type receptors. The virus also contains several other genetic variations that are known from past studies in mice and other animals to cause severe disease. - Mod.CP http://www.promedmail.org/direct.php?id=20130403.1619096
