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ARCHIVED - Canada Communicable Disease Report

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Volume 37 • ACS-7
November 2011

An Advisory Committee Statement (ACS)
National Advisory Committee on Immunization (NACI)†

Recommendations on the use of live, attenuated influenza vaccine (FluMist®): Supplemental Statement on Seasonal Influenza Vaccine for 2011-2012


V. Recommendations

Based on the available evidence NACI makes the following recommendations with respect to the use of LAIV. These recommendations are intended to be considered in combination with NACI's existing recommendations regarding recommended recipients of influenza vaccine. For a detailed list of recommended recipients of influenza
vaccine, refer to NACI's Statement on Seasonal Influenza Vaccine for 2011-2012.

Children

V.1 Healthy Children and Adolescents 2 to 17 years of age
Healthy Children 2-17 years of age
  • Based on effectiveness, efficacy, and immunogenicity data, NACI recommends LAIV for use in healthy children and adolescents 2-17 years of age. Available data indicates that LAIV would be preferred over TIV in this population, although NACI recognizes that other programmatic considerations will impact the implementation of this recommendation in publiclyfunded programs (NACI Recommendation Grade A)

Numerous randomized placebo controlled studies in children have demonstrated efficacy, immunogenicity and safety of LAIV in the prevention of culture-confirmed influenza in children. These studies assessed reactogenicity and side effects of the vaccine, which demonstrated minimal side effects. Any reactogenicity events (e.g. runny/stuffy nose; headache, tiredness) that were experienced after the first dose of LAIV were reduced with successive dosing. In these studies, LAIV consistently demonstrated superior efficacy against culture-confirmed influenza as compared to placebo or TIV in children. In a 2009 meta-analysis of placebo controlled studies (comprising over 25,000 children), LAIV efficacy in vaccine-naïve children was 77% (95% CI: 72,80) against culture-confirmed influenza for antigenically similar subtypes for all strains, and 72% (P<0.001) against cultureconfirmed influenza for subtypes regardless of antigenic similarity13.

The same meta-analysis13 examined the relative efficacy of LAIV compared to TIV in children. All studies examined in the meta-analysis (comprising over 13,000 children) showed a lower risk of contracting influenza among children given LAIV than among those given TIV for matched and mismatched strains.

Based on the absolute efficacy of LAIV and relative efficacy of LAIV versus TIV in controlled studies and post-marketing safety data, NACI considers LAIV to be safe, efficacious, and immunogenic in children. The decision to include LAIV among the influenza vaccine products available to children aged 2 to 17 years of age as part of publicly funded Provincial/Territorial programs will depend on multiple factors such as cost-benefit evaluation and other local programmatic and operational factors such as increased cost, shorter shelf-life and the development of implementation strategies. Factors to consider include that administration of LAIV is well received by children and caregivers in clinical trials. Young children would require minimal cooperation or very brief restraint to allow administration of the vaccine intranasally52. Research has shown that even a single dose of LAIV is efficacious and offers protection in children who often are non-compliant with the more optimal two-dose regime7,11 , an issue noted by Jackson et al in evaluating compliance to two-dose recommendations for influenza vaccines.83

V.2 Children with Immune Compromising Conditions
  • NACI recommends against LAIV for individuals with immune compromising conditions. (NACI Recommendation Grade D)

Live vaccines have generally been contraindicated in people with immune compromising conditions, with some exceptions.. NACI concludes that there is insufficient evidence supporting the use of LAIV in those with immune compromising conditions in terms of both safety and effectiveness. LAIV has been administered to approximately 170 children and adults with mild to moderate immune suppression due to HIV infections and 10 children with mild to moderate immune suppression due to cancer. Although these small studies demonstrated a similar safety profile as in healthy individuals, based on expert opinion, NACI concludes that the use of LAIV in this population is contraindicated.

V.3 Children with Asthma
  • NACI recommends that LAIV can be used in children 24 months and older with stable, non-severe asthma. (NACI Recommendation Grade B)
    • LAIV should not be used in those with severe asthma (as defined as currently on oral or high dose inhaled glucocorticosteriods or active wheezing) and those with medically attended wheezing in the 7 days prior to vaccination

A study of LAIV found increased rates of wheezing in children 6-23 months of age when compared to TIV. Children 2 years of age and older and adolescents with asthma who received LAIV in clinical trials showed there was no significant difference between LAIV and TIV in the exacerbation of asthma post-vaccination. Several studies demonstrated that LAIV is well tolerated in asthmatics, and it has been demonstrated to have a higher relative efficacy versus TIV with matched and mismatched strains. NACI's review of current evidence on the use of LAIV in children 2 years of age and over with asthma and wheezing supports the use of LAIV in stable, non-severe asthmatics; however, NACI recommends against LAIV in those with severe asthma or medically attended wheezing in the previous seven days.

V.4 Children with other chronic health conditions
  • NACI recommends that LAIV can be used in children with chronic health conditions (excluding those with immune compromising conditions and severe asthma, as defined above). (NACI Recommendation Grade B)
    • A limited number of immunogenicity and efficacy studies have been conducted in this population as a result of these conditions being fairly limited in this age group. Based on expert review, it is expected that LAIV should be as immunogenic and efficacious in immune competent children with chronic health conditions as it is in healthy children.

At this time there is insufficient evidence to recommend LAIV preferentially over TIV in children with chronic health conditions.

ADULTS

V.5 Healthy Adults 18 to 59 years of age
    • NACI recommends that LAIV can be used for the prevention of influenza in healthy adults 18 to 59 years of age. (NACI recommendation Grade A)
    • There is some evidence that TIV may provide better efficacy than LAIV in healthy adults, although not all studies are consistent on this point.

The combined data from LAIV trials in over 10,000 people confirmed evidence of immunogenicity, efficacy and effectiveness in adults 18 to 59 years of age.

There are limited data from randomized controlled trials in adults on relative efficacy of LAIV versus TIV, and those that are available show that LAIV and TIV were similarly efficacious or that TIV was more efficacious. Most studies demonstrated that LAIV was less effective than TIV in the adult population; however in one large observational study, LAIV was shown to be more protective than TIV in a cohort of new military recruits (who are generally a younger adult population and are likely to be vaccine-naïve).29 Pre-existing immunity to the virus from infection or vaccine, which may interfere with the LAIV response, may also be a contributing factor.22

V.6 Adults with Immune Compromising Conditions
  • NACI recommends against LAIV for individuals with immune compromising conditions. (NACI Recommendation Grade D)

Live vaccines have generally been contraindicated in people with immune compromising conditions, with some exceptions. NACI concludes that there is insufficient evidence supporting the use of LAIV in those with immune compromising conditions in terms of both safety and effectiveness. LAIV has been administered to approximately 170 children and adults with mild to moderate immune suppression due to HIV infections and 10 children with mild to moderate immune suppression due to cancer. Although these small studies demonstrated a similar safety profile as in healthy individuals, based on expert opinion, NACI concludes that the use of LAIV in this population is contraindicated.

V.7 Adults with other chronic health conditions
  • At this time NACI concludes that there is insufficient evidence to recommend LAIV in adults with chronic health conditions. (NACI Recommendation Grade I)
  • The potentially better immune response following TIV compared to LAIV in healthy adults in some studies should be considered when the choice of an influenza vaccine for adults at high risk for complications is made.

Data on the use of LAIV in adults 18 to 59 years of age with chronic underlying medical conditions are limited; however some research has been done on older adults (age 60 and older) with chronic conditions. Although not an indicated age group, the studies in older adults demonstrate a similar safety profile of LAIV in these individuals to individuals without these conditions but the absolute efficacy of LAIV or relative efficacy of LAIV compared to TIV, as in the healthy adult population, remains questionable.

V.8 Health Care Workers providing care to individuals with immune compromising conditions
  • NACI recommends that TIV, instead of LAIV, should be used for health care workers providing care to those with immune compromising conditions, unless the individual will only accept LAIV. (NACI Recommendation Grade B)
  • NACI recommends that if a health care worker, or another caregiver, receives LAIV and is providing care to individuals with severe immune compromising conditions (defined as hospitalized and requiring care in a protected environment), they should wait 2 weeks following receipt of LAIV before continuing to provide care to such individuals. (NACI Recommendation Grade D)

The rationale for these recommendations is two-fold. First, although limited, the existing evidence suggests that TIV may be more efficacious in adults than LAIV. Secondly, there is a theoretical concern that shed vaccine virus could be transmitted to a person with an immune compromising condition who could theoretically develop serious illness. However, shedding is generally below the levels needed to transmit infection and the duration of shedding after receipt of LAIV is shorter in adults than in children. This transmission of vaccine viruses from vaccine recipients to unvaccinated persons has occurred in rare instances, although serious illnesses have not been reported among unvaccinated persons who have been inadvertently infected with vaccine viruses. No transmission has ever been reported in a health care setting.84

Table 6: SUMMARY OF INFORMATION CONTAINED IN THIS NACI STATEMENT

The following table highlights key information for immunization providers. Please refer to the remainder of the Statement for details.

1. What

  1. Basic information about the Disease (e.g. agent, symptoms, epidemiology)
  2. Basic information about the Vaccine (e.g. efficacy, safety)

Influenza is a respiratory infection caused by influenza A and B viruses and occurs in Canada every year, generally during late fall and the winter months. Infection typically starts with a headache, chills and cough, followed rapidly by fever, loss of appetite, muscle aches and fatigue, running nose, sneezing, watery eyes and throat irritation. Nausea, vomiting and diarrhea may also occur, especially in children.

Most people will recover from influenza within a week or ten days, but some - including those 65 years of age and older and adults and children with chronic conditions, such as diabetes and cancer - are at greater risk of more severe complications, such as pneumonia. Additional information about influenza can be accessed at: healthycanadians.gc.ca - Flu (influenza)

FluMist® is a live, attenuated, trivalent influenza vaccine administered by the intranasal route as a spray. There is a single dosing formula available containing 106.5-7.5 fluorescent focus units of each influenza strain in a 0.2 mL dose (administered as 0.1 mL dose in each nostril).

FluMist® was approved in Canada in 2010, and as been available for use in the United States since 2003. Efficacy and safety studies have demonstrated that FluMist® is safe and well tolerated.

2. Who

Groups recommended to immunize

NACI recommends that FluMist® can be used for the prevention of influenza in:

  • Healthy children and adolescents 2-17 years of age (NACI Recommendation Grade A).
  • Children 24 months and older with stable, non-severe asthma (NACI Recommendation Grade B)
  • Children with chronic health conditions (excluding severe asthma and immune compromising conditions) (NACI Recommendation Grade B)
  • Healthy adults 18-59 years of age (NACI Recommendation Grade A)

3. How

  • Dose, schedule
  • Precautions, contraindications
  • Co-administration

The recommended vaccine dosage per administration is 0.2 mL (0.1 mL per nostril) for individuals 2-59 years of age.

  • Children 2-8 years of age inclusive who have not previously received seasonal influenza vaccine are recommended to receive a two dose schedule. An initial dose of 0.2 mL (0.1 mL in each nostril) is followed by a second 0.2 mL dose (0.1 mL in each nostril) administered at least 4 weeks later.
  • For all other individuals, including children 2-8 years of age who have previously received seasonal influenza vaccine, the recommended schedule is one 0.2 mL dose (0.1 mL in each nostril).

The use of FluMist® should be carefully evaluated in individuals:

  • Persons with serious acute febrile illness should not be vaccinated until their symptoms have abated. If nasal congestion is present that might impede delivery of the vaccine, deferral of FluMist® or administration of TIV should be considered instead.

The use of FluMist® is contraindicated in:

  • Children <24 months of age
  • Individuals with a history of anaphylaxis to a previous dose of influenza vaccine or have a history of hypersensitivity to the non-medicinal ingredients contained in the vaccine, including those with egg allergy
  • Children and adolescents 2-17 years of age receiving ongoing aspirin therapy or aspirin-containing therapy. The use of aspirin-containing medications in individuals <18 years should be delayed at least four weeks after vaccination with FluMist®.
  • Pregnant women
  • Individuals with severe asthma (as defined as currently on oral or high dose inhaled glucocorticosteriods or active wheezing) and those with medically attended wheezing in the 7 days prior to vaccination
  • Individuals with occurrence of Guillain-Barré Syndrome within eight weeks of any prior influenza vaccination.
  • Individuals with immune compromising conditions
  • Health care workers providing care to individuals with severe immune compromising conditions.

FluMist® may be administered concurrently with the MMR and varicella vaccines.

  • If not administered at the same time, the administration of another live vaccine should only be administered at least four weeks prior to, or after the receipt of FluMist®.

FluMist® should not be administered until 48 hours after antiviral agents active against influenza (e.g. oseltamivir and zanamivir) are stopped, and antiviral agents should not be administered until two weeks after receipt of FluMist® unless medically indicated. If antiviral agents are administered within this time frame (from 48 hours before to two weeks after FluMist®), revaccination should take place at least 48 hours after the antivirals are stopped.

No data currently exist about the concomitant use of nasal corticosteroids or other intranasal medications.

4. Why

  • "Counseling Points” for providers to emphasize with clients when discussing these recommendations

Vaccination is the most effective way to prevent influenza.

Each year there is a new vaccine to protect against the influenza virus strains that are expected in the coming influenza season. Even if the vaccine strains have not changed, getting influenza vaccine every year reinforces optimal protection.
Annual influenza vaccination is encouraged for all Canadians, particularly those at high risk of influenza complications, those who could spread influenza to someone at risk and those who provide essential community services.

FluMist ® is administered through the intranasal route which may increase compliance during administration. It can be used in children 2-17 years of age inclusive, and in healthy adults 18-59 years of age inclusive.  Nasal congestion and rhinorrhea are the most common adverse reactions observed.

Table 7: Levels of Evidence Based on Research Design

I

Evidence from randomized controlled trial(s).

II-1

Evidence from controlled trial(s) without randomization.

II-2

Evidence from cohort or case–control analytic studies, preferably from more than one centre or research group using clinical outcome measures of vaccine efficacy.

II-3

Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.

III

Opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.


Table 8: Quality (internal validity) Rating of Evidence

Good

A study (including meta-analyses or systematic reviews) that meets all design- specific criteria* well.

Fair

A study (including meta-analyses or systematic reviews) that does not meet (or it is not clear that it meets) at least one design-specific criterion* but has no known "fatal flaw".

Poor

A study (including meta-analyses or systematic reviews) that has at least one design-specific* "fatal flaw", or an accumulation of lesser flaws to the extent that the results of the study are not deemed able to inform recommendations.


* General design specific criteria are outlined in Harris et al., 2001d

Table 9: NACI Recommendation for Immunization - Grades

A

NACI concludes that there is good evidence to recommend immunization.

B

NACI concludes that there is fair evidence to recommend immunization.

C

NACI concludes that the existing evidence is conflicting and does not allow making a recommendation for or against immunization, however other factors may influence decision-making.

D

NACI concludes that there is fair evidence to recommend against immunization.

E

NACI concludes that there is good evidence to recommend against immunization.

I

NACI concludes that there is insufficient evidence (in either quantity and/or quality) to make a recommendation, however other factors may influence decision-making.


a FluMist® has been described in clinical studies using various terminology and acronyms such as CAIV-T, LAIV, and LAIV-T. In this document, FluMist will be referred to as LAIV (live, attenuated, influenza vaccine), except in the evidence tables, where the terminology will be consistent with the study citation.

b The strength may change with the selection of the contained influenza strains for the specific season but will always be within the specification of 106.5-7.5 FFU.

c MSW defined as the presence of wheezing on a physical examination conducted by a health care provider, accompanied by at least one of the following: sign of respiratory distress: tachypnea, retractions, or dyspnea; hypoxemia (O2 saturation <95%); or a new prescription for a daily bronchodilator.

d Harris RP, Helfand M, Woolf SH, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 2001;20:21-35.

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