Last year Australia experienced the most severe influenza season since the 2009 pandemic year. There was some variation throughout the country, with the most significant impact seen in the eastern states. The 2017 influenza season started approximately one month earlier than usual, and activity at the peak was prolonged. A total of 249,868 laboratory-confirmed cases of influenza were reported to the National Notifiable Diseases Surveillance System. This was a considerable increase from the 90,853 cases reported in the preceding year.
Influenza is caused by the influenza virus. Humans can be infected with influenza types A, B, or C, although only types A and B tend to cause severe disease. Influenza A can be further classified into subtypes based on differences in surface antigens. Transmission of the influenza virus occurs by aerosol or direct contact with the respiratory secretions of an infected individual. While good health habits can limit the spread of influenza, annual vaccination remains the best way to prevent transmission and the development of severe disease.
It is recommended that all people over six months of age who would like to prevent contracting influenza consult their healthcare professional regarding vaccination. However, certain groups of people are at higher risk of developing influenza-related complications and are encouraged to get an influenza vaccine annually. To improve vaccine uptake, the National Immunisation Program (NIP) provides free influenza vaccinations to the following groups:
- People 65 years of age and over;
- People six months and over with medical risk factors (e.g. heart disease, Down syndrome, lung disease, diabetes, liver disease, kidney disease);
- Aboriginal and Torres Strait Islander children between six months and five years, or over 15 years of age; and
- Pregnant women (may be given at any trimester and should be considered during each pregnancy).
The elderly are particularly susceptible to influenza-related morbidity and mortality. However, while it is expected that the elderly will be over-represented in influenza statistics, last year was particularly severe. Of the influenza-related deaths reported in notified cases, more than 91% occurred in people over 65 years of age with a median age of 86 years.
The reason for this high proportion of mortality in elderly patients is multi-factorial. There is evidence to suggest that influenza vaccination is less effective in the elderly compared to younger populations. Meta-analyses of cohort studies demonstrate an overall vaccine efficacy of 24% to 56% in elderly populations. In addition, the predominant circulating strain in 2017 was Influenza A (H3N2) which can cause particularly severe illness in the elderly. The H3N2 strain also tends to mutate more rapidly than H1N1 or influenza B. The result is antigenic variability which may contribute to reduced vaccine efficacy.
In response to the significant morbidity and mortality seen during last year’s influenza season, the Minister for Health recently announced the addition of two new influenza vaccines for the elderly. These new trivalent vaccines are indicated for active immunisation against influenza disease in people aged 65 years and older. They are designed to produce a more robust immune response and, hence, provide greater protection for the elderly. These vaccines, Fluzone® High-Dose and Fluad®, will be available on the NIP from April 2018.
Fluzone® High-Dose contains four times the amount of influenza antigen compared to a standard influenza vaccine. The efficacy of Fluzone® High-Dose in adults 65 years and older was compared against standard-dose Fluzone® (not registered in Australia) in a randomised, double-blind trial. The results demonstrate that around a quarter of all cases of laboratory-confirmed influenza occurring in patients vaccinated with the standard dose preparation could be prevented if the high-dose formulation was used. This figure increased to more than a third of all cases of breakthrough influenza if only vaccine-similar strains were considered. This study was conducted over two influenza seasons. The first season had low influenza activity and a moderate-to-good match between the vaccine and circulating strains, while the second season had high influenza activity and mismatch between the vaccine and circulating strains. However, the high-dose vaccine showed superior efficacy against infection due to influenza A and B in each season despite significantly different conditions.
The Fluad® vaccine employs a different technique to increase efficacy. While this vaccine contains the standard antigen dose, it is formulated with the adjuvant MF59C to improve the antibody response. MF59C is an oil-in-water emulsion containing squalene in the oil phase. Squalene is a readily metabolised oil that occurs naturally in humans as a component of cell membranes and as a metabolite of cholesterol. While the action of MF59C is not fully understood, it is thought to involve local induction of chemokines required for antigen presenting cell (APC) recruitment and pro-inflammatory cytokines involved in antigen presentation, APC differentiation, and cell migration to the draining lymph node. Since its first approval in 1997, MF59C has been widely used internationally, including extensive use during the 2009 pandemic. There is, therefore, solid evidence to support the safety and efficacy of this adjuvant.
Non-inferiority between MF59C-adjuvanted trivalent influenza vaccine and non-adjuvanted trivalent vaccine has been demonstrated in clinical trials. A phase III study conducted on people over 65 years of age revealed a significantly higher antibody response against all homologous and heterologous strains in participants receiving the adjuvanted vaccine. Interestingly, the most significant difference between the two groups was seen in the persistence of antibody response against H3N2. It is hoped that this translates into long-term efficacy in this patient group. The incidence of adverse effects was similar between the two groups, although reactogenicity was moderately higher with the adjuvanted vaccine. Adverse reactions were mostly transient and of mild to moderate intensity.
While vaccination against influenza is the best defence, it is estimated that only around 70% of eligible Australians receive their annual vaccine under the NIP. Barriers to vaccination may include misconceptions about the risk of vaccination, underestimation of the severity of influenza, and doubts about the efficacy of the vaccine. Greater education of the public can address these issues and may help to improve the level of protection in the community.
A summary of the key differences between the influenza vaccinations that will be available this year is shown in Table 1. For more specific information, please consult the appropriate product information.
Table 1. Comparison of 2018 influenza vaccines
|Product||Vaccine type||Intended population|
|FluQuadri™ Junior||QuadrivalentSplit virion||Children 6-35 months of age|
|FluQuadri™||QuadrivalentSplit virion||People ≥3 years of age|
|Fluarix® Tetra||QuadrivalentSplit virion||People ≥3 years of age and older|
|Fluvax®||TrivalentSplit virion||People ≥5 years of age|
|Afluria® Quad||QuadrivalentSplit virion||People ≥18 years of age|
|Influvac® Tetra||QuadrivalentSurface antigen||People ≥ 18 years of age|
|Fluad®||TrivalentSurface antigen||People ≥65 years of age|
|Fluzone® High-Dose||TrivalentSplit virion||People ≥65 years of age|
- Department of Health. National Notifiable Diseases Surveillance System. Canberra: Australian Government; 2018.
- DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014; 371(7): 635-45.
- Fluad® (inactivated influenza vaccine) Australian approved product information. Parkville: Seqirus Pty Ltd. Approved November 2017.
- Fluzone® High-Dose (inactivated trivalent influenza vaccine) Australian approved product information. Macquarie Park: Sanofi-Aventis Australia. Approved January 2018.
- Frey SE, Reyes MR, Reynales H, Bermal NN, Uwe N, Narasimhan V, et al. Comparison of the safety and immunogenicity of an MF59®-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine 2014; 32(39): 5027-34.