Susan is a health care aide. Her grandfather, who is 86, has been fairly healthy and lives independently. He receives some support for instrumental ADL from his daughter and Susan. He has type 2 diabetes, hypertension and chronic obstructive pulmonary disease (COPD). For this he takes metformin, gliclazide, losartan and tiotropium. He has salbutamol that he uses only occasionally. Susan has heard that this flu season will be a “bad one” and wonders if he should be getting a flu shot.
Issue: What is the efficacy and what are the risks of the influenza vaccine?
Bottom Line: It remains uncertain but better efficacy is demonstrated when the vaccine matches circulating viral strains. Influenza vaccines are safe with a low risk for severe adverse effects.
Influenza is a viral respiratory disease caused by a virus from the Orthomyxoviridae family. It has three subtypes: A, B and C. Symptoms of influenza infection include acute onset of a febrile illness, myalgias, headache and cough. Median duration is three days, though cough and malaise may persist. Complications of influenza include pneumonia, secondary bacterial pneumonia and exacerbations of COPD. Influenza viruses cause between 7% and 15% of viral respiratory disease, with the remainder caused by a number of different agents.[i]
While influenza infection occurs across the globe, seasonal influenza is seen in temperate zones. In North America, outbreaks typically begin in late November and peak by early March. Transmission is by droplet and by contact with infected surfaces. The incubation period is from one-to-four days, and infected individuals are contagious from one day before until five days after symptom onset.[ii]
Early on, the dominant strains are A-strain viruses, with type B following and becoming more dominant towards the end of the season. Two A-strain viruses are more commonly recognized, including H3N2 and H1N1. In healthy adults, H3N2 produces the most severe illness, followed by type B and then H1N1. In both older adults and younger adults with underlying chronic conditions, H3N2 has been the type most associated with complications leading to hospitalization and death. In addition, frequency of infection has been shown to fall more rapidly with increasing age for both H1N1 and type B, with H3N2 being the more likely infection in older adults. In the United States, H3N2 accounts for an estimated 36,000 deaths annually, with the majority of those occurring over age 65, followed by those between ages 50-64 with underlying chronic conditions.[iii]
Inactivated influenza vaccine is typically one of three types:
- Whole virion: comprises killed or inactivated whole viruses
- Subunit virion: comprises surface antigens only
- Split-virion: comprises viruses whose viral structure has been broken by a disrupting agent
These vaccines are administered via the intramuscular route. Live attenuated vaccines, which are unable to replicate in cells but are still antigenic, are administered by the intranasal route. They are not currently licensed for use in older adults.
Influenza viruses have an ability to change their antigenic configuration and regularly do so. Due to this drift, year-to-year protection from vaccination is therefore not seen. On an annual basis, the World Health Organization meets to identify circulating influenza strains and predict those most likely to be responsible for illness during the upcoming influenza season. Typically three or four strains are included, including an H3N2, H1N1 and at least one B strain. Depending on the lead time for vaccination production, antigenic drift may occur after the components of the vaccine have been determined. This leads to a less effective vaccine for that season.
Benefits of the vaccine have been widely promoted, but questions have been raised about the efficacy of the vaccine, and the degree of match to the circulating strains of influenza is important in this regard. Recent Cochrane Reviews have demonstrated that in younger adults, an overall effectiveness of 16% is demonstrated with inactivated vaccines.[iv] One study has demonstrated a 42% reduction in frequency of physician visits for those receiving vaccination where there is a match to circulating strains versus no significant difference for those where the degree of match was unknown.[v] For older adults, a second Cochrane Review has suggested that no firm conclusions can be drawn around efficacy because of the differences in the types of vaccines used and the trial designs.[vi] This conclusion, though widely quoted, has been challenged in a series of articles and rebuttals, which essentially revolve around how the data is interpreted.[vii][viii][ix]
Risks were also assessed, and were classified as either local or systemic. Local side effects included tenderness/sore arm, swelling/induration and erythema. Systemic side effects included malaise, fever, headache, nausea and respiratory tract symptoms. While all side effects were seen more frequently than with placebo, none reached statistical significance other than local tenderness in the injected arm. Guillian Barre Syndrome (GBS) was strongly associated with the 1976 vaccine which contained A/New Jersey/76 but this was not confirmed in subsequent seasons not containing this strain. The conclusion on safety was that the public health safety profile of vaccines is acceptable.[x] The Centers for Disease Control and Prevention estimate that the risk for development of GBS is 1-2/million persons vaccinated. There is also a risk of an anaphylactic reaction in individuals with a severe egg allergy.[xi]
[i] Demicheli V, Jefferson T, Al-Ansary LA, Ferroni E, Rivetti A, Di Pietrantonj C. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD001269.
[ii] Jefferson T Clinical Evidence 2009;93:911.
[iii] Monto AS. Epidemiology of Influenza. Vaccine 2008;26S:D45-48.
[iv] Demicheli V, Jefferson T, Al-Ansary LA, Ferroni E, Rivetti A, Di Pietrantonj C. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD001269.
[v] Buxton Bridges C, Thompson V, et al. Effectiveness and cost benefit of influenza vaccination of healthy working adults, a randomized controlled trial. JAMA 2000;284(13):1655-63
[vi] Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S, Thomas RE. Vaccines for preventing influenza in the elderly. Cochrane Database of Systematic Reviews 2010, Issue 2. Art. No.: CD004876.
[vii] Beyer WEP, McElhaney J, et al. Cochrane re-arranged: support for policies to vaccinate elderly people against influenza. Vaccine 2013;31(50):6030–3.
[viii] Osterholm M, Kelley N et al. Reply: Letter to the Editor, Cochrane Rearranged Vaccine 2015;33:12.
[ix] Beyer WEP, McElhaney J, et al. Reply: Letter to the Editor, Cochrane Rearranged Vaccine 2015;33:13-14.
[x] Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S, Thomas RE. Vaccines for preventing influenza in the elderly. Cochrane Database of Systematic Reviews 2010, Issue 2. Art. No.: CD004876.