Being a daddy and homeowner (maintenance, repairs) have taken priority over writing entries for this blog, but I'm not complaining!
I've been interested in the H7N9 epidemic in China since is began two months ago. I had considered writing a post on H7N9 for several weeks. I've been asked to write an article for a health department newsletter, which will cover the basics of what clinicians should know about H7N9, but I'd like to go into more detail here.
Influenza A H7N9 was first detected on March 30th in specimens from three people in China who died from severe respiratory disease. Within a month there were 128 cases and 24 deaths from H7N9 in China. As of May 31st, there have been 132 cases and 37 deaths. Most of cases and deaths were older adults and most had recently had contact with live chickens or had been in live bird markets. One cases of H7N9 influenza was detected outside of China, but he had recently traveled to China.
H7N9 is the first H7 influenza detected in human in Asia and the first N9 subtype virus ever detected in humans.
It occurred to me that I haven't written a post on avian influenza. In my previous post, what are H and N? I briefly discussed the diversity of hemagglutinin and neuraminidase, the glycoproteins on the surface of influenza viruses. I also mentioned that the ability of influenza viruses to infect humans depends upon how well the hemagglutinin on the virus surface is adapted to receptors in our respiratory tract. There are a couple of things I didn't discuss in that post that I think are important to understand about influenza A viruses.
As I mentioned in my previous post, there are 16 hemagglutinins and 9 neuraminidases. Hemagglutinin is the molecule on the surface of influenza viruses that attaches to the cell membrane and allows the virus to enter the cell. The virus then uses the cell's protein synthesis mechanisms to create new copies of itself. Neuraminidase is the molecule on the surface of the virus that allows the newly created viruses to escape the infected cell.
Influenza A viruses have a segmented genome. The gene segments can reassort in a cell infected with two viruses. This can result in the creation of new (novel) influenza viruses. The danger of reassortment is that a pandemic virus can be created that is easily spread from person-to-person and to which most people have little or no immunity.
Like 2009 H1N1, H7N9 is a triple reassortant; that is, it has genes from three different influenza viruses. Unlike 2009 H1N1, there is no conclusive evidence that H7N9 is transmitted from person-to-person.
For sustained human-to-human transmission to occur, an influenza virus must be adapted to α2-6 linked sialic acid receptors on cells in the upper part of the human respiratory tract. Avian influenza viruses are adapted to α2-3 linked sialic acid receptors found in birds. Humans have α2-3 linked sialic acid receptors in the lower part of our airway, so humans can be infected with avian influenza viruses, but they are not easily transmitted from one person to another. Pigs have both α2-6 linked and α2-3 linked sialic acid receptors, so pigs are often the intermediate host for avian influenza viruses that become human influenza viruses, but H7N9 has not been found in pigs. Genetic analysis of the hemagglutinin gene in H7N9 suggests that it may be better adapted to human sialic acid receptors.
Avian influenza viruses circulate widely in poultry and are frequently responsible for economic losses when infected birds either die or are culled. H7 avian influenza viruses have sporadically infected poultry workers or people who are involved with culling infected flocks in North America and Europe. The most frequent clinical manifestation of human H7 influenza virus infection is conjunctivitis (pinkeye). Mild respiratory illness is also common. Although a few mild H7N9 infections have been identified, the most cases have been associated with severe respiratory disease requiring hospitalization and admission to an intensive care unit (ICU).
Before the H7N9 epidemic in China, the largest outbreak of an H7 virus was in The Netherlands in 2003. Eighty three people were found to be infected with H7N7. Seventy eight of them had conjunctivitis, seven had mild respiratory disease, and one 57-year-old veterinarian died from acute respiratory distress syndrome (ARDS).
In contrast to H5N1, which is a highly pathogenic avian influenza virus (HPAI), H7N9 is a low pathogenic avian influenza virus (LPAI). In this case, pathogenicity refers to the viruses' ability to cause disease in bird, not humans. It's easy to tell when a flock is infected with an HPAI like H5N1 because there are a lot of sick and dead birds. H7N9 appears to cause very mild or no illness in birds. This makes H7N9 more dangerous because humans can be exposed to infected birds without any easily recognizable indication that the birds are infected.
In response to the H7N9 epidemic, local and national authorities in China closed live bird markets in the affected provinces. The number of cases has decreased since then and emergency responses ended May 28th. The reservoir for the virus has not been identified, but the virus has not been detected in poultry farms.
Whatever happened to H5N1 that we heard so much about ten years ago? It's still out there and still killing people. So far this year there have been 20 cases and 15 deaths caused by avian influenza A H5N1.
Another one to watch: H9 avian influenzas.
Centers for Disease Control and Prevention
Center for Infectious Disease Research & Policy
World Health Organization
Belser, J. A., Bridges, C. B., Katz, J. M., & Tumpey, T. M. (2009). Past, present, and possible future human infection with influenza virus A subtype H7. Emerging Infectious Diseases, 15(6), 859-865. http://wwwnc.cdc.gov/eid/article/15/6/09-0072_article.htm.
Fouchier, R. A. M., Schneeberger, P. M., Rozendaal, F. W., Broekman, J. M., Kemink, S. A. G., Munster, V. et al. (2004). Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. PNAS, 101(5), 1356-1361. http://www.pnas.org/content/101/5/1356.full.
Gao, H-V., Lu, H-Z., Cao, B., Du, B., Shang, H., Gan, J-H. et al. (2013). Clinical findings in 111 cases of influenza A (H7N9) virus infection. New England Journal of Medicine, DOI: 10.1056/NEJMoa1305584. http://www.nejm.org/doi/full/10.1056/NEJMoa1305584.
Gao, R., Cao, B., Hu, Y., Feng, Z., Wang, D. et al. (2013). Human infection with a novel avian-origin influenza A (H7N9) virus. New England Journal of Medicine, 368(20), 1888-1897. http://www.nejm.org/doi/full/10.1056/NEJMoa1304459.
Hu, Y., Lu, S., Song, Z., Wang, W., Hao, P., Li, J. et al. (2013). Association between adverse clinical outcome in human disease caused by novel influenza, A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet, DOI: 10.1016/S0140-6736(13)61125-3. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61125-3/abstract.
Li, Q., Zhou, L., Zhou, M., Chen, Z., Li, F., Wu, H. et al. (2013). Preliminary report: epidemiology of the avian influenza A (H7N9) outbreak in China. New England Journal of Medicine, DOI: 10.1056/NEJMoa1304617. http://www.nejm.org/doi/full/10.1056/NEJMoa1304617.
Murhekar, M., Arima, Y., Horby, P., Vandemaele, K. A. H., Vong, S., Zijian, F. et al. (2013). Avian influenza A (H7N9) and the closure of live bird markets. Western Pacific Surveillance and Response Journal, 4(2), doi: 10.5365/wpsar.2013.4.2.008. http://www.wpro.who.int/wpsar/volumes/04/2/2013_PE_EMT_Murhekar/en/index.html.
Osterholm, M. T., Ballering, K. S., & Kelley, N. S. (2013) Major challenges in providing an effective and timely pandemic vaccine for influenza A (H7N9). JAMA, doi:10.1001/jama.2013.6589. http://jama.jamanetwork.com/article.aspx?articleid=1686871.
Treanor, J. J. (2009). Influenza viruses, including avian influenza and swine flu. In G. L. Mandell, J. E. Bennett, & R. Dolin (Eds.). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. (7th Ed.) [Electronic version].
Uyeki, T. M. & Cox, N. J. (2013). Global concerns regarding novel influenza A (H7N9) virus infections. New England Journal of Medicine, 368(20), 1862-1864. http://www.nejm.org/doi/full/10.1056/NEJMp1304661.
Xu, C., Havers, F., Wang, L., Chen, T., Shi, J, Wang, J. et al. (2013). Monitoring avian influenza A (H7N9) virus through national influenza-like illness surveillance, China. Emerging Infectious Diseases, 19(8), DOI: 10.3201/eid1908.130662. http://wwwnc.cdc.gov/eid/article/19/8/13-0662_article.htm.