2012–2013 Influenza update: Hitting a rapidly moving target

THE 2009 H1N1 PANDEMIC KILLED MORE PEOPLE THAN WE THOUGHT

The fourth flu pandemic of the last 100 years occurred in 2009. (The other three were in 1918, 1957, and 1968.) It was caused by a novel strain, H1N1 of swine origin.²² This 2009 pandemic strain had six genes from the North American swine flu virus and two genes from the Eurasian swine flu virus. The pandemic affected more children and young people (who completely lacked prior immunity to this virus), while older people, who had cross-reacting antibodies, were less affected.

Worldwide, 18,500 people were reported initially to have died in this pandemic from April 2009 to August 2010.²³ However, a recent modeling study estimated the number of respiratory and cardiovascular deaths associated with this pandemic at 283,500—about 15 times higher.²⁴

AN AUSTRALIAN OUTBREAK OF OSELTAMIVIR-RESISTANT H1N1

Many strains of influenza A virus are resistant to amantadine and rimantadine, owing to amino acid substitutions in the M2 protein.²⁵ In contrast, resistance to the neuraminidase inhibitors oseltamivir and zanamivir has been reported only occasionally.²⁶

Until recently, most oseltamivir-resistant viruses were isolated from immunocompromised hosts treated with oseltamivir.^27–29 All the resistant viral isolates contained an amino acid substitution of histidine (H) to tyrosine (Y) at position 275 of the viral neuraminidase.³⁰ In general, transmission of these oseltamivir-resistant strains has been limited and unsustained, but it can occur in settings of close contact, such as hospitals, school camps, or long train rides.^31–35 Oseltamivir-resistant strains were detected in fewer than 1% of isolates from the community during the 2010–2011 influenza season in the Northern Hemisphere and most countries in the Southern Hemisphere during the 2011 flu season.^36,37

However, an outbreak of oseltamivir-resistant H1N1 occurred in Australia between June and August 2011.³⁸ In that outbreak, the isolates from only 15% of the 191 people infected with this virus, designated H1N1pdm09, carried the H257Y neuraminidase substitution.³⁹ Further, only 1 of the 191 patients had received oseltamivir before. More importantly, genetic analysis suggested that the infection spread from a single source.

This was the first reported sustained community transmission of oseltamivir-resistant H1N1 in a community previously unexposed to this drug. As such, it is a warning sign of the potential for a widespread outbreak of this virus. In the event of such an outbreak, inhaled zanamivir would be the only effective treatment available.

THIS SEASON’S TRIVALENT INACTIVATED VACCINE

The trivalent inactivated influenza vaccine for the 2012–2013 season contains three inactivated viruses⁴⁰:

• Influenza A/California/7/2009(H1N1)-like
• Influenza A/Victoria/361/2011(H3N2)-like
• Influenza B/Wisconsin/1/2010-like (Yamagata lineage).

The influenza A H3N2 and influenza B antigens are different from those in the 2011–2012 vaccine.⁴¹ The H1N1 strain is derived from H1N1pdm09, which had been contained in the 2011–2012 seasonal vaccine. This vaccine will not protect against H3N2v or H5N1.

LATEST RECOMMENDATIONS ON VACCINATION

Since 2010, the Advisory Committee on Immunization Practices (ACIP) has recommended annual flu shots for all people older than 6 months in the United States.⁴²

Vaccination should be done before the onset of influenza activity in the community as soon as vaccine is available for the season. However, one should continue offering vaccination throughout the influenza season as long as influenza viruses are circulating in the community.

Children ages 6 months through 8 years not previously vaccinated against influenza should receive two doses of influenza vaccine at least 4 weeks apart for an optimal immune response. The US-licensed Afluria vaccine (CSL Biotherapies, King of Prussia, PA), a trivalent inactivated vaccine, is not recommended for children under 9 years of age because of concern about febrile seizures.^43,44

There is no contraindication to giving inactivated trivalent influenza vaccine to immunosuppressed people.

The live-attenuated influenza vaccine is indicated only for healthy, nonpregnant people age 2 through 49 years and not for people who care for severely immunosuppressed patients who require a protective environment.

For indications for and details about the different available influenza vaccines, see the ACIP’s current recommendations (www.cdc.gov/mmwr/pdf/wk/mm6132.pdf).⁴⁰

Updated recommendations for people allergic to eggs

All currently available influenza vaccines are made by growing the virus in chicken eggs. Therefore, severe allergic and anaphylactic reactions can occur in people with egg allergy. The ACIP recommends that if people experienced only hives after egg exposure, they should still receive the trivalent inactivated vaccine. Recently, the ACIP reviewed data from the Vaccine Adverse Event Reporting System⁴⁵ and issued the following recommendations for the 2012–2013 influenza season⁴⁰:

• In people who are allergic to eggs, only trivalent inactivated vaccine should be used, not the live-attenuated vaccine, because of lack of data for use of the latter in this group.
• Vaccine should be given by providers who are familiar with the signs of egg allergy.
• Patients with a history of egg allergy who have experienced only hives after exposure to eggs should be observed for a minimum of 30 minutes after vaccination.
• Patients who experience lightheadedness, respiratory distress, angioedema, or recurrent emesis or who require epinephrine or emergency medical attention after egg exposure should be referred before vaccination to a physician who has expertise in managing allergic conditions.
• Tolerance to egg-containing foods does not exclude the possibility of egg allergy. Egg allergy can be confirmed by a consistent medical history of adverse reactions to eggs or egg-containing foods, plus skin or blood testing for immunoglobulin E antibodies to egg proteins.

A high-dose vaccine is available for people 65 years and older

The rates of hospitalization and death due to seasonal flu in elderly people have increased significantly in the last 20 years despite rising rates of vaccination.^46–48 This is largely due to lower serologic response rates and vaccine efficacy in older adults with weaker immune systems.

Several studies have shown that the development of protective antibody titers depends on the dose of antigen.^49–53 A randomized, controlled clinical trial compared the immunogenicity of a high-dose vaccine and a standard-dose vaccine in older adults and found that the level of antibody response was significantly higher with the high-dose vaccine, and that the rate of adverse reactions was the same.⁵⁴

In December 2009, the US Food and Drug Administration (FDA) licensed a new trivalent inactivated influenza vaccine with high doses of hemagglutinin antigens for adults over the age of 65.⁵⁵ Postlicensure safety surveillance in 2010 revealed no serious safety concerns.⁵⁶

At present, the ACIP expresses no preference for standard-dose or high-dose vaccine for adults 65 years of age and older.⁴⁰ Importantly, if only the standard-dose vaccine is at hand, the opportunity for influenza vaccination should not be missed with the intention of giving high-dose vaccine at a later date.