H7-subtype Influenza Infections: Pandemic Potential?
By Amesh A. Adalja, MD, June 5, 2009
Among the myriad subtypes of influenza A that circulate in waterfowl, only a few strains have made the species jump to humans; those that have are limited to 4 hemagglutinin types: H5, H7, H9, and H10 (see table below). Of the four, H5N1 receives the most attention because it causes fulminant illness. However, the pandemic potential of the H7 viruses cannot be overlooked. While they are not nearly as lethal as H5N1, a pandemic need not cause mass lethality to have a significant impact around the globe. A team from the Centers for Disease Control and Prevention (CDC) recently published a review of H7 infections in humans in Emerging Infectious Diseases.
Avian influenza subtypes
H7 Infections Rare Prior to 2003
Prior to 2003, H7 infections were usually the result of occupational accidents or laboratory exposures. Most cases involved ocular exposure with resultant conjunctivitis. During the last decade, outbreaks of H7 infection in humans have become more common. The largest, which infected 89 people—3 through person-to-person contact—occurred in 2003 on poultry farms in the Netherlands. The only known fatality from H7 infection occurred during that outbreak. Follow-up serologic studies indicated more widespread exposure than the number of known infections indicated.1
There also have been documented infections with H7N3 strains in Italy (2002-03), Canada (2004), and the United Kingdom (2006). In the United States, H7N2 strains caused human infections in 2002 and 2003. H7N2 has also caused infections in the United Kingdom (2007).1
Infections Predominantly Result in Conjunctival Symptoms
Almost all cases of H7 influenza have resulted in conjunctivitis, but lower respiratory disease with severe presentations has also occurred. The mechanism for conjunctival tropism has not been identified.1
Adamantane Resistance Has Been Detected
H7 viruses have been found to harbor adamantine resistance in some instances. Resistance to neuraminidase inhibitors, however, has not been detected to date.1
H9 and H10 Influenza A Viruses Also Have Infected Humans
In both 1999 and 2003, H9N2 subtype infections were found in Hong Kong in at least 3 patients. All cases were mild; poultry was the suspected source. In 2004, Egypt reported mild cases of H10N7 infection in 2 children, one of whose father was a poultry merchant.2
Does H7 Have Pandemic Potential?
H7 viruses are characterized by several features that suggest pandemic potential (see also CBN Report, June 6, 2008):
North American lineage H7 viruses are highly pathogenic; they have a polybasic amino acid HA cleavage site that is a marker for virulence.
North American lineage H7 viruses have partially adapted to bind to the α2–6 linked sialic acid receptors found in the human upper respiratory tract, a property thought necessary for human-to-human transmission.
The disease caused by European lineage H7 viruses in mammalian models resembles H5N1 infections; limited human-to-human transmission has occurred.
H7 viruses with 3 different neuraminidase (N) subtypes (N2, N3, N7) have infected humans, suggesting greater compatibility with human infections (as opposed to H5 viruses, which only infect humans in the H5N1 form).1
Taken together, these facts suggest another influenza virus with the potential for pandemic spread. Vaccine development for H7 viruses is under way, but none are available commercially at this time.1 As the current 2009 H1N1 influenza outbreak has illustrated, increased surveillance for novel influenza viruses is a necessary and a crucial step in pandemic mitigation.
Belser JA, Bridges CB, Katz JM, Tumpey TM. Past, present, and possible future human infection with influenza virus A subtype H7. Emerg Infect Dis 2009;15:859-865. http://www.cdc.gov/EID/content/15/6/859.htm. Accessed June 2, 2009.
National Institute of Allergy and Infectious Diseases. Timeline of Human Flu Pandemics. http://www3.niaid.nih.gov/topics/Flu/Research/Pandemic/
TimelineHumanPandemics.htm. Accessed June 2, 2009.