Influenza (Flu)
Types
Avian (A/H5N1 subtype) Canine Equine Swine (A/H1N1 subtype)
Vaccines
2009 pandemic (Pandemrix) ACAM-FLU-A Fluzone Influvac Live attenuated (FluMist) Optaflu
Treatment
Amantadine Arbidol Laninamivir Oseltamivir Peramivir Rimantadine Vitamin D Zanamivir
Pandemics
2009 Swine 1968–1969 Hong Kong 1918
Outbreaks
2008 West Bengal 2007 Bernard Matthews H5N1 2007 Australian equine 2006 H5N1 India 1976 swine flu
See also
Flu season Influenza evolution Influenza research Influenza-like illness
v t e

Influenza A virus subtype H3N2 (also H3N2) is a subtype of viruses that causes influenza (flu). H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. H3N2 is increasingly abundant in seasonal influenza, which kills an estimated 36,000 people in the United States each year. In the last half of 2011, a dozen human cases of a new variant of the disease have been found in the U.S.A. This new variant is called H3N2v. It appears to be transmissible among humans.^[1]

Classification[link]

H3N2 is a subtype of the viral genus Influenzavirus A, which is an important cause of human influenza. Its name derives from the forms of the two kinds of proteins on the surface of its coat, hemagglutinin (H) and neuraminidase (N). By reassortment, H3N2 exchanges genes for internal proteins with other influenza subtypes.

Seasonal H3N2 flu[link]

Seasonal influenza kills an estimated 36,000 people in the United States each year. Flu vaccines are based on predicting which mutants of H1N1, H3N2, H1N2, and influenza B will proliferate in the next season. Separate vaccines are developed for the northern and southern hemispheres in preparation for their annual epidemics. In the tropics, influenza shows no clear seasonality. In the past ten years, H3N2 has tended to dominate in prevalence over H1N1, H1N2, and influenza B. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005.^[2][3]

Seasonal H3N2 flu is a human flu from H3N2 that is slightly different from one of last year's flu season H3N2 variants. Seasonal influenza viruses flow out of overlapping epidemics in East and Southeast Asia, then trickle around the globe before dying off. Identifying the source of the viruses allows global health officials to better predict which viruses are most likely to cause the most disease over the next year. An analysis of 13,000 samples of influenza A/H3N2 virus that were collected across six continents from 2002 to 2007 by the WHO's Global Influenza Surveillance Network showed that newly emerging strains of H3N2 appeared in East and Southeast Asian countries about 6 to 9 months earlier than anywhere else. The strains generally reached Australia and New Zealand next, followed by North America and Europe. The new variants typically reached South America after an additional 6 to 9 months, the group reported.^[4]

Swine flu[link]

Pigs can harbor influenza viruses adapted to humans and others that are adapted to birds, allowing the viruses to exchange genes and create a pandemic strain.

"In swine, 3 influenza A virus subtypes (H1N1, H3N2, and H1N2) are circulating throughout the world. In the United States, the classic H1N1 subtype was exclusively prevalent among swine populations before 1998; however, since late August 1998, H3N2 subtypes have been isolated from pigs. Most H3N2 virus isolates are triple reassortants, containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages. [...] Present vaccination strategies for SIV control and prevention in swine farms typically include the use of 1 of several bivalent SIV vaccines commercially available in the United States. Of the 97 recent H3N2 isolates examined, only 41 isolates had strong serologic cross-reactions with antiserum to 3 commercial SIV vaccines. Since the protective ability of influenza vaccines depends primarily on the closeness of the match between the vaccine virus and the epidemic virus, the presence of nonreactive H3N2 SIV variants suggests that current commercial vaccines might not effectively protect pigs from infection with a majority of H3N2 viruses."^[5]

Avian influenza virus H3N2 is endemic in pigs in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. Health experts say pigs can carry human influenza viruses, which can combine (i.e. exchange homologous genome sub-units by genetic reassortment) with H5N1, passing genes and mutating into a form which can pass easily among humans. H3N2 evolved from H2N2 by antigenic shift and caused the Hong Kong Flu pandemic of 1968 and 1969 that killed up to 750,000 humans. The dominant strain of annual flu in humans in January 2006 is H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 in humans has increased to 91% in 2005. In August 2004, researchers in China found H5N1 in pigs.^[6] 11/10/2010 The Centers for Disease Control and Prevention (CDC) has issued the following alert: Influenza A (H3N2) virus infections have been recently detected in people in a number of states across the U.S., including two small localized outbreaks. Sporadic cases of influenza and localized summer outbreaks from seasonal influenza viruses are detected each summer.^[7]

Flu spread, by season[link]

Hong Kong Flu (1968–1969)[link]

The influenza viruses that caused Hong Kong flu. (magnified approximately 100,000 times)

The Hong Kong Flu was a category 2 flu pandemic caused by a strain of H3N2 descended from H2N2 by antigenic shift, in which genes from multiple subtypes reassorted to form a new virus. This pandemic of 1968 and 1969 killed an estimated one million people worldwide.^[8][9][10] The pandemic infected an estimated 500,000 Hong Kong residents, 15% of the population, with a low death rate.^[11] In the United States, approximately 33,800 people died.^[12]

Both the H2N2 and H3N2 pandemic flu strains contained genes from avian influenza viruses. The new subtypes arose in pigs coinfected with avian and human viruses and were soon transferred to humans. Swine were considered the original "intermediate host" for influenza, because they supported reassortment of divergent subtypes. However, other hosts appear capable of similar coinfection (e.g., many poultry species), and direct transmission of avian viruses to humans is possible. H1N1 may have been transmitted directly from birds to humans (Belshe 2005).^[13]

The Hong Kong flu strain shared internal genes and the neuraminidase with the 1957 Asian Flu (H2N2). Accumulated antibodies to the neuraminidase or internal proteins may have resulted in much fewer casualties than most pandemics. However, cross-immunity within and between subtypes of influenza is poorly understood.

The Hong Kong flu was the first known outbreak of the H3N2 strain, though there is serologic evidence of H3N? infections in the late 19th century. The first record of the outbreak in Hong Kong appeared on 13 July 1968 in an area with a density of about 500 people per acre in an urban setting. The outbreak reached maximum intensity in 2 weeks, lasting 6 weeks in total. The virus was isolated in Queen Mary Hospital. Flu symptoms lasted 4 to 5 days.^[11]

By July 1968, extensive outbreaks were reported in Vietnam and Singapore. By September 1968, it reached India, Philippines, northern Australia and Europe. That same month, the virus entered California from returning Vietnam War troops. It would reach Japan, Africa and South America by 1969.^[11]

"Three strains of Hong Kong influenza virus isolated from humans were compared with a strain isolated from a calf for their ability to cause disease in calves. One of the human strains. A/Aichi/2/68, was detected for five days in a calf, but all three failed to cause signs of disease. Strain A/cal/Duschanbe/55/71 could be detected for seven days and caused an influenza-like illness in calves."^[14]

Fujian flu (2003–2004)[link]

Diagram of influenza virus nomenclature.

Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus. These strains are named after Fujian, a coastal province of the People's Republic of China that is across the Taiwan strait from Taiwan.^[15]

A/Fujian (H3N2) human flu (from A/Fujian/411/2002(H3N2) -like flu virus strains) caused an unusually severe 2003–2004 flu season. This was due to a reassortment event that caused a minor clade to provide a haemagglutinin gene that later became part of the dominant strain in the 2002–2003 flu season. A/Fujian (H3N2) was made part of the trivalent influenza vaccine for the 2004–2005 flu season and its descendants are still the most common human H3N2 strain.

2004–2005 flu season[link]

The 2004–05 trivalent influenza vaccine for the United States contained A/New Caledonia/20/99-like (H1N1), A/Fujian/411/2002-like (H3N2), and B/Shanghai/361/2002-like viruses.^[16]

2005–2006 flu season[link]

The vaccines produced for the 2005–2006 season use:

• an A/New Caledonia/20/1999-like(H1N1);
• an A/California/7/2004-like(H3N2) (or the antigenically equivalent strain A/New York/55/2004);
• a B/Jiangsu/10/2003-like viruses.

2006–2007 flu season[link]

The 2006–2007 influenza vaccine composition recommended by the World Health Organization on 15 February 2006 and the U.S. FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) on 17 February 2006 use:

• an A/New Caledonia/20/99 (H1N1)-like virus;
• an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 and A/Hiroshima/52/2005 strains);
• a B/Malaysia/2506/2004-like virus from B/Malaysia/2506/2004 and B/Ohio/1/2005 strains which are of B/Victoria/2/87 lineage.^[17]

2007–2008 flu season[link]

The composition of influenza virus vaccines for use in the 2007–2008 Northern Hemisphere influenza season recommended by the World Health Organization on 14 February 2007^[18] was:

• an A/Solomon Islands/3/2006 (H1N1)-like virus;
• an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 (H3N2) and A/Hiroshima/52/2005 were used at the time);
• a B/Malaysia/2506/2004-like virus^[19][20]

"A/H3N2 has become the predominant flu subtype in the United States, and the record over the past 25 years shows that seasons dominated by H3N2 tend to be worse than those dominated by type A/H1N1 or type B." Many H3N2 viruses making people ill in this 2007–2008 flu season differ from the strains in the vaccine and may not be well covered by the vaccine strains. "The CDC has analyzed 250 viruses this season to determine how well they match up with the vaccine, the report says. Of 65 H3N2 isolates, 53 (81%) were characterized as A/Brisbane/10/2007-like, a variant that has evolved [notably] from the H3N2 strain in the vaccine—A/Wisconsin/67/2005."^[21]

2008–2009 flu season[link]

The composition of virus vaccines for use in the 2008–2009 Northern Hemisphere influenza season recommended by the World Health Organization on February 14, 2008^[22] was:

• an A/Brisbane/59/2007 (H1N1)-like virus;
• an A/Brisbane/10/2007 (H3N2)-like virus;
• a B/Florida/4/2006-like virus (B/Florida/4/2006 and B/Brisbane/3/2007 (a B/Florida/4/2006-like virus) were used at the time).^[23][24]

As of May 30, 2009: "CDC has antigenically characterized 1,567 seasonal human influenza viruses [947 influenza A (H1), 162 influenza A (H3) and 458 influenza B viruses] collected by U.S. laboratories since October 1, 2008, and 84 novel influenza A (H1N1) viruses. All 947 influenza seasonal A (H1) viruses are related to the influenza A (H1N1) component of the 2008–09 influenza vaccine (A/Brisbane/59/2007). All 162 influenza A (H3N2) viruses are related to the A (H3N2) vaccine component (A/Brisbane/10/2007). All 84 novel influenza A (H1N1) viruses are related to the A/California/07/2009 (H1N1) reference virus selected by WHO as a potential candidate for novel influenza A (H1N1) vaccine. Influenza B viruses currently circulating can be divided into two distinct lineages represented by the B/Yamagata/16/88 and B/Victoria/02/87 viruses. Sixty-one influenza B viruses tested belong to the B/Yamagata lineage and are related to the vaccine strain (B/Florida/04/2006). The remaining 397 viruses belong to the B/Victoria lineage and are not related to the vaccine strain."^[25]

2009–2010 flu season[link]

The vaccines produced for the 2009–2010 season use:

• an A/Brisbane/59/2007(H1N1)-like virus;
• an A/Brisbane/10/2007 (H3N2)-like virus;
• a B/Brisbane 60/2008-like antigens.^[26]

There also was also a separate vaccine available for Pandemic H1N1 Influenza using the A/California/7/2009-like Pandemic H1N1 Strain.^[27]

2010–2011 flu season[link]

The vaccines produced for the 2010–2011 season use:

• an A/California/7/2009-like (Pandemic H1N1)
• an A/Perth/16/2009-like (H3N2)-like virus;
• a B/Brisbane/60/2008-like antigens.^[28]

2011–2012 flu season[link]

The vaccines produced for the 2011–2012 season use:

• an A/California/07/2009 (H1N1)-like virus,
• an A/Victoria/210/2009 (an A/Perth/16/2009-like strain) (H3N2)-like virus,
• a B/Brisbane/60/2008-like virus.^[29]

Note: 2011–2012 Influenza Vaccine Composition

The viruses used in making seasonal flu vaccines are chosen each year based on information collected over the previous year about which influenza viruses are spreading and what vaccine viruses would offer the best protection against circulating viruses. Viruses gathered by 136 national influenza centers in 106 countries as well as information on disease trends are further analyzed by the five World Health Organization (WHO) Collaborating Centers for Reference and Research on Influenza located in Atlanta, Georgia, USA (Centers for Disease Control and Prevention, CDC); London, United Kingdom (National Institute for Medical Research); Melbourne, Australia (Victoria Infectious Diseases Reference Laboratory); Tokyo, Japan (National Institute for Infectious Diseases); and Beijing, China (National Institute for Viral Disease Control and Prevention). The seasonal flu vaccine is usually a trivalent vaccine (a three component vaccine) with each component selected to protect against one of the three groups of influenza viruses circulating most commonly in humans. The 2009 H1N1 vaccine that was made to protect against the pandemic virus first detected in April, 2009 was a monovalent (one-component) vaccine that only protects against the 2009 H1N1 virus. The three vaccine viruses are chosen to maximize the likelihood that the main circulating viruses during the upcoming flu season will be well covered. WHO recommends specific vaccine viruses for vaccine production, but then each individual country makes their own decision for licensing of vaccines in their country. In the United States, the US Food and Drug Administration (FDA) determines what viruses will be used in US–licensed vaccines. WHO recommended that the Northern Hemisphere’s 2011–2012 seasonal influenza vaccine contain the following three vaccine viruses:

• an A/California/7/2009 (H1N1)–like virus,
• an A/Perth/16/2009 (H3N2)–like virus, and
• a B/Brisbane/60/2008–like virus

These are the same viruses that were selected for the Northern Hemisphere for the 2010–2011 influenza vaccine. This recommended composition of the seasonal vaccine for the Northern Hemisphere, including the United States, is the same composition that was recommended for the Southern Hemisphere’s 2011–2012 influenza vaccines. ^[30]

See also[link]

• 2009 H1N1 influenza outbreak
• Bird flu
• Dog flu
• Horse flu
• Human flu
• Swine flu

References[link]

Further reading[link]

• Graphic showing H3N2 mutations, amino acid by amino acid, among 207 isolates completely sequenced by the Influenza Genome Sequencing Project.
• Influenza A (H3N2) Outbreak, Nepal
• Hot topic – Fujian-like strain A influenza
• Monitoring Antibodies for Swine Influenza H3N2 Virus
• New Scientist: Bird Flu

External links[link]

• Influenza Research Database Database of influenza sequences and related information.