2012 Antigen Review for the New Zealand National Immunisation Schedule: Influenza

Abstract

Epidemiolology The impact of influenza in New Zealand (NZ) over the past 20 seasons, since the sentinel surveillance systems commenced, has been substantial in terms of General Practitioner (GP) consultations, hospitalisations and deaths. The 1997 policy change offering influenza vaccination free to all ≥ 65 years was associated with a significant reduction of influenza mortality in the elderly population. High influenza-like-illness consultation rates and high hospitalisations particularly among young children under five and in particular, the under one year olds continue to be reported. New measures to prevent influenza-related hospitalisations particularly among young children are needed. Since 2002, influenza virus strain surveillance in NZ has frequently recorded co-circulation of four antigenically distinct viruses: A (H1N1), A (H3N2), B/Yamagata lineage and B/Victoria lineage virus. NZ influenza virus circulation pattern supports the introduction of quadravalent vaccines which contains these four antigenically distinct influenza viruses. Safety Overall the traditional trivalent inactivated influenza vaccines (TIV) have an extensive and excellent safety record around their use in all populations including pregnant women. However, several issues for safety have arisen over the past two years, largely as an indirect result of the 2009 pandemic: 1. The finding that seasonal trivalent inactivated influenza vaccines can cause significant febrile events in children. This is primarily associated with CSL’s TIV influenza vaccine that contained the pandemic H1N1 strain; however other brands were also associated with higher rates of febrile events. There was also a slightly higher risk for febrile convulsions associated with the co-administration of TIV and pneumococcal vaccine. This has highlighted the importance of safety monitoring annual antigenic changes, and monitoring/comparing the behaviours of different brands of TIV. 2. Theoretical safety concerns around the use of repeat annual vaccination with TIVs for children. 3. There appears to be a small excess in risk for Guillain-Barre Syndrome (GBS) following TIV vaccination (less than one additional case per million persons), so the risk from influenza infection is much greater. 4. The use of the live attenuated influenza vaccines (LAIV) increases risk for wheezing events in recipients less than two years of age. This has led to the exclusion of this age group in the recommendations for use of the vaccine. While more recent data has suggested this may be less of a problem than originally considered, further research is required to clarify the risks for this group. There are no issues identified around the use of LAIV in mild to moderately immunocompromised children despite cautions remaining for this group. 5. An association has been shown for one adjuvanted H1N1 pandemic vaccine with narcolepsy. This does not extend to non-adjuvanted vaccines. It is possible that the onset of narcolepsy may be confounded by other factors, therefore the incidence of narcolepsy with influenza is unknown currently, and further data is required to confirm a causal link. Immunogenicity/efficacy TIVs are generally recognised as effective for healthy adults, particularly when the vaccine and circulating virus are antigenically similar. Traditionally, the TIVs generate poor immune responses in the elderly, the very young and some high risk groups, particularly the immunocompromised. These groups tend to be those at higher risk of disease and there are no randomised control trials (RCT) of TIV in adults over the age of 65 years to confirm the efficacy. There remains a need for more high quality studies in young children, older adults and those with a variety of co-morbidities. Adjuvanted vaccines are more immunogenic than unadjuvanted vaccines. However, there is no efficacy or effectiveness data on adjuvanted vaccines. Intradermal (ID) vaccines do not generate higher antibody titres than IM vaccines in healthy adults although higher doses of ID vaccine can improve immunogenicity in the elderly. LAIV vaccines generate a different immune response to TIV therefore immunogenicity data is not directly comparable. While LAIV vaccines appear to provide superior protection in children compared with TIV, the TIVs appear better in healthy adults compared to children. There is some evidence to suggest herd immunity, particularly via vaccinating children, can be achieved providing coverage is very high. Vaccinating healthcare workers to protect the highly vulnerable is likely to be an effective strategy, though data is limited. The duration of immunity provided by influenza vaccines is difficult to study due to the continual strain shifts. However in the years when strains have remained the same vaccination in a previous year appears to confer immunity in the next year. Protection from LAIV has been demonstrated to persist beyond a year. The additional of ‘B’ strain in seasonal influenza vaccines is likely to moderately improve effectiveness. Options for Vaccine Schedules Current international recommendations are conflicting as to whether annual vaccination of healthy adults with TIV is cost saving. The options to consider improving vaccine schedules are both broad and targeted including: 1. The use of quadrivalent vaccines - A quadrivalent option for inactivated influenza vaccine is likely to modestly improve the performance of these vaccines. 2. ID vaccination for the elderly and immunosuppressed allows for antigen sparing but there is little evidence that the immune response is superior or that better protection is afforded, except in the elderly. 3. Higher antigen dose, or two dose regimes 4. In the elderly and immune supressed, generally adjuvanted vaccines provide superior responses of TIV and formulations of adjuvanted TIV with higher antigen doses generally appear more immunogenic than standard TIV. 5. Vaccination of heath care worker and other close contacts are likely to be sensible strategies, albeit based on relatively limited data. 6. For children 2 years up to 18 years LAIV vaccine provide superior performance over TIVs. There is increasing evidence that annual vaccination of children 2 years of age and older with LAIVs offer benefits both for direct protection and indirect protection to other members of the community. 7. There is a lack of data to support effectiveness of TIV in the very young. Strategies for this age group include consideration of lowering the age of delivery of LAIVs, and herd immunity strategies. For children less than two years of age the LAIV, elicits good immune responses but are currently not recommended due to possible increased risk of wheezing episodes. Emerging data suggests adjuvanted vaccines may work better in this group although there is little evidence to indicate any influenza vaccines elicit good responses in infants less than six years of age. 8. More recently identified high risk groups for targeting influenza vaccination strategies include the morbidly obese and pregnant women. Cocoon strategies sound pragmatically sensible and are advocated in some countries, but they are difficult to implement and there is not data yet to support their effectiveness in reducing influenza morbidity in infants. Implementation Issues LAIVs are contraindicated in the immunocompromised and those receiving salicylic acid, and are not to be administered to healthcare professionals who interact with high risk patients. LAIVs are recommended not to be used in infants under 12 months, individuals with severe asthma or active wheezing and individuals who are pregnant or breast-feeding. Vaccine recipients should avoid close association with severely immunocompromised individuals for 1-2 weeks following immunisation. Adjuvanted vaccines increased local reactogenicity and the potential for increased incidence of narcolepsy. ID vaccines can also have increased local reactogenicity but despite this are frequently more acceptable to recipients than intramuscular (IM). Improving Coverage Recent studies on vaccination for healthy adults highlight the advantages of onsite work vaccination clinics to improve coverage. For improving national immunisation rates overall clear leadership, effective communication about performance and methods, and financial targets to incentivise practices improved vaccine coverage of the seasonal influenza targeted programme. Improving vaccination rates for healthcare workers highlight advantages with mandatory vaccination policies such as making it a condition of employment, alongside effective senior leadership support. A key factor in improving uptake rates for elderly is the engagement of the treating physician. Use of effective integrated systems alongside provider and public education is needed to improve vaccination rates for pregnant women. Immunisation registers and effective surveillance systems are important elements of a successful national immunisation programme. International Policy Current international policies are a mixture of individual protection strategies, and herd immunity. In general the European Union (EU) countries have more conservative strategies. Different available licensed vaccines in different areas also are likely to significantly affect policy decisions.