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Novel H7N9 Outbreak in China

By Eric Toner, MD, April 5, 2013

According to media reports and official announcements from the WHO,1 CDC,2 and ECDC,3 as of 8 AM on April 5, 2013, there have been 14 confirmed human cases of infection with a novel H7N9 influenza A virus in the eastern part of China. Six of the 14 people have died. The first report of this virus was issued on April 1, 2013, but the earliest cases had dates of onset of illness in February, and the latest case had onset of illness less than 1 week ago.

Epidemiology Unclear

The source of the outbreak has not been confirmed, but there have been reports of pigeons in a Shanghai agricultural market that have tested positive for the H7N9 virus. There is as yet no obvious epidemiological links among the people, who come from at least 3 different provinces. So far, there has been no confirmation of person-to-person transmission, although mild upper respiratory illnesses have been reported in a few contacts of the confirmed cases. There also may have been a small family cluster of severe disease around the first reported case.  

H7N9 Viruses Are Not New

Low pathogenic H7N9 viruses have been found previously in poultry, but H7N9 viruses have not been known to cause human infection before. However, other H7 viruses, including H7N7, H7N3 and H7N2, have caused human infections. The most notable occurred in the Netherlands in 2003, when there was a relatively large outbreak of H7N7, with 89 confirmed cases. In that outbreak, limited person-to-person spread was confirmed. Most of the cases were clinically mild, many consisting only of conjunctivitis. There was, however, one death associated with a specific mutation, E627K, in the PB2 gene.4

Sequencing Providing Some Insights

Sequencing of the virus indicates that this novel H7N9 virus is the product of reassortment of several avian influenza viruses. In addition, it has acquired certain gene sequences that suggest an intermediate mammalian host. The virus does carry certain amino acid substitutions previously associated with pathogenicity in humans, including the E627K mutation in the PB2 gene. However, it does not appear to have the poly-basic amino acid sequence at the hemagglutinin cleavage site that is the hallmark of highly pathogenic avian influenza viruses such as H5N1.5

Uncertain CFR

Although the case fatality rate (CFR) of confirmed cases is currently over 40%, experience suggests that this figure is mostly likely much higher than the true CFR and that, as more testing is done and milder cases are discovered, the CFR will drop. However, even if the CFR drops several-fold, it appears that this virus is much more lethal than most flu viruses that infect humans. For comparison, the CFR of seasonal influenza is typically about 0.01%, and the CFR of the 1918 pandemic virus was estimated to be 2.5%. Preliminary evidence indicates that the virus is susceptible to neuraminidase inhibitors such as oseltamivir.

What Does This Mean?

The fact that human cases have occurred in a large geographic areas suggests that either the virus is widespread in the environment or that it is spreading person-to-person. From previous experience with avian influenza outbreaks, we can suspect that the most likely source of the outbreaks is domestic poultry. Since many of the cases occurred in cities, the live poultry markets are very likely sources. This does not preclude some human-to-human transmission. The degree of human-to-human transmission is key. If the virus spreads as readily as seasonal influenza, then control of the outbreak would be extraordinarily difficult and in fact unlikely. This does not yet appear to be the case because there have not been reports of widespread influenza-like illness. On the other hand, if there is little or no human-to-human transmission, then control of the outbreak is much more likely and would be accomplished by identifying and then stamping out the source.  

See also: H7-subtype Influenza Infections: Pandemic Potential? (Amesh Adalja, MD, CBN, June 5, 2009)

References

  1. WHO. Human infection with influenza A(H7N9) virus in China–update. April 4, 2013. http://www.who.int/csr/don/2013_04_04/en/index.html. Accessed April 5, 2013.
  2. CDC. Avian Influenza A (H7N9) Virus. http://www.cdc.gov/flu/avianflu/h7n9-virus.htm. Accessed April 5, 2013.
  3. European CDC. Severe respiratory disease associated with a novel influenza A virus, A(H7N9)–China, 3 April 2013. http://ecdc.europa.eu/en/publications/Publications/AH7N9-China-rapid-risk-assessment.pdf. Accessed April 5, 2013.
  4. CDC. Human Cases of Avian Influenza A (H7N7) Infection–The Netherlands, 2003 http://www.cdc.gov/flu/avian/h7n7-netherlands.htm. Accessed April 5, 2013.
  5. CIDRAP. Two more H7N9 cases cited; virus may be adapting to mammals. April 3, 2013. http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/apr0313virus.html. Accessed April 5, 2013.