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.
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CDC, 2012
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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.
More information:
Centers for Disease Control and Prevention
Center for Infectious Disease Research & Policy
World Health Organization
References:
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.
Avian influenza mainly refers to the epidemic of infectious diseases caused by influenza virus. H7N9 virus mainly exists in the lower respiratory tract.
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