It is time to get your influenza shot

November 2006

It’s that time of year again. People are starting to line up to receive their annual flu shot. This year there should be adequate supplies of vaccine with approximately 100 million doses available.

Individuals who should receive the flu vaccine include: children aged 6 months to 59 months; women who will be pregnant during the influenza season; adults aged 50 years and older; adults and children with chronic disorders of the pulmonary or cardiovascular systems, chronic metabolic diseases, renal dysfunction, hemoglobinopathies or immunodeficiency caused by medications or HIV, or conditions that can compromise respiratory function or the handling or respiratory secretions. Residents of nursing homes and other chronic-care facilities and people who live with or care for people at high risk for influenza-related complications should also receive the influenza vaccine.

Health care workers have also been targeted for annual influenza vaccination. Influenza vaccine should be offered to health care workers at no cost to protect the staff, patients and family members and to decrease absenteeism. Recommendations suggest that levels of health care personnel influenza vaccination coverage be used as a measure in patient safety and quality programs.

Two types

Two types of influenza vaccine are licensed for use in the United States and both vaccines contain the same viral subunits. The trivalent inactivated vaccine (TIV) is the most widely used influenza vaccine. It is administered by intramuscular injection and is approved for use in all age groups and risk populations. In contrast, the live-attenuated influenza vaccine is approved for use in healthy individuals aged 5 years to 49 years and is administered intranasally.

The live-attenuated influenza vaccine, LAIV, (FluMist, MedImmune) was approved by the FDA in 2003 and was available for use during the 2003-2004 influenza season. LAIV contains master donor strains of influenza that are cold-adapted and temperature-sensitive. The master donor strains grow efficiently at 25°C, but are unable to grow efficiently at 37°C to 39°C, the temperature in which most wild type influenza grow efficiently. The master donor strain is genetically and phenotypically stable. Each year antigen updating is accomplished by replacing the two hemagglutinin and neuraminidase genes of the master donor strain with those genes of the recommended updated vaccine. The immune response elicited by LAIV is multifaceted. Following intranasal administration of LAIV, influenza specific IgA nasal antibodies, serum antibodies and T-cell responses are elicited. This gives both a local mucosal immune response as well as a systemic response to the vaccine.

The intranasal administration of LAIV makes this an attractive method for vaccinating children or other people who are frightened by vaccines. However, there is concern regarding the risk of using LAIV in children with underlying respiratory disorders. The licensing studies showed a trend toward an increase in exacerbations of asthma requiring medical attention. Recently published studies may alleviate some of these concerns.

Comparison

Fleming and colleagues compared an investigational refrigerator stable formulation of LAIV with TIV in 2,229 children aged 6 to 17 with documented asthma. Participants were randomly assigned to one of two study groups. The children were vaccinated at the beginning of influenza season and followed for approximately eight months to determine the vaccine’s effectiveness in preventing influenza and its effect on asthma symptoms. The LAIV group had significantly fewer cases of culture-proven community-acquired influenza than the TIV group. There were no significant differences between the groups in the number of asthma exacerbations, asthma symptom scores or nighttime awakening scores.

Ashkenazi and colleagues studied 2,187 young children, aged 6 months to 71 months, with recurrent respiratory tract infections. Children were randomized to receive LAIV or TIV at the beginning of influenza season and were followed for approximately eight months. The children receiving LAIV had fewer cases of culture-confirmed influenza compared with the TIV group. Additionally, the LAIV group had fewer visits to health care providers for respiratory tract complaints and fewer missed days from school or day care than the TIV group.

Both of these studies demonstrated superior relative efficacy of LAIV and helped to alleviate concerns regarding use of LAIV in children with underlying respiratory problems. As expected in both studies, children in the LAIV groups had more complaints of nasal congestion and rhinorrhea for up to five days following vaccination, and the TIV groups had complaints of injection site reactions.

Further concerns

Another concern in using LAIV has been the theoretical potential of secondary transmission of influenza. There is a low probability of this occurring since the virus would need to be shed in sufficient quantities to infect another person, lose its temperature sensitivity to efficiently replicate at 36°C, and cause infection. Vesikari and colleagues studied the secondary transmission of LAIV in the ‘worst case scenario’: children aged 9 months to 36 months attending day care. One hundred ninety-seven healthy children regularly attending day care were randomly assigned to receive LAIV or placebo. Nasal swabs were taken at regular intervals to determine post-vaccination viral shedding, genotype and phenotype of shed viruses and the probability of secondary transmission of the vaccine influenza strains.

Of the 98 vaccine recipients, 80% shed at least one vaccine influenza strain. All of the vaccine virus isolates retained their cold adaptation and temperature sensitivity characteristics. There was one confirmed transmission of a vaccine strain to a placebo recipient, but the child did not exhibit any signs or symptoms of clinically significant influenza. The probability of secondary transmission of influenza from one vaccinated child is approximately 0.58%. This study demonstrates that even in the worst conditions, despite the high rate of viral shedding following LAIV vaccination, there is a low potential for secondary transmission of influenza. This is similar to other live virus vaccines such as MMR, which have high rates of viral shedding but not in sufficient quantities to cause an infection.

LAIV is an attractive alternative to TIV in healthy children and those who are afraid of shots. Recent literature demonstrates that LAIV is more effective in preventing influenza than TIV and is safe to use in most children. LAIV should be used when possible to divert some of the pressure on use of TIV. This would help preserve TIV for use in high risk populations.

For more information:

• Marianne Billeter, PharmD, BCPS, is a Clinical Pharmacology Specialist of Infectious Diseases at Ochsner Clinic Foundation in New Orleans.
• Ashkenazi S, Vertruyen A, Aristegui J, et al. Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections. Pediatr Infect Dis J. 2006;25:870-879.
• Belshe RB. Current status of live attenuated influenza virus vaccine in the US. Virus Res. 2004;103:177-185.
• CDC. Influenza vaccination of health-care personnel: recommendations of the health care Infection Control practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP). MMWR. 2006;55 (RR-2):1-15.
• CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2006;55 (RR-10):1-41.