The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study

Abstract

Background: Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany.

Methods: A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion.

Results: In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children.

Conclusions: Our results demonstrate that vaccinating children 2-17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany.

Figure 1

Model structure. Individuals are either born susceptible (S) or with maternal protection (M), which prevents infection and successful vaccination. Only susceptible individuals can successfully be vaccinated (V_LAIV and V_TIV) or infected. When infected, they pass through a latent period (E) before becoming infectious (I) and finally become immune (R). Individuals can completely lose their immunity (derived by infection or vaccination) and become susceptible again.

Figure 2

Excess consultations per 100,000 per year. Grey bars represent outpatient physician visits simulated by the model, dots with 95% confidence intervals are estimates of influenza-associated excess consultations published by the RKI.

Figure 3

Simulated seasonal fluctuation in influenza infections. The light grey solid curve shows influenza A and B infections in scenario 1 where only TIV is used, the dark grey dashed curve shows those in scenario 2 where TIV immunisation of children 2 to 17 years old is replaced in 2012 by LAIV immunisation and where childhood vaccination coverage with LAIV is subsequently increased up to 50% in three annual steps.

Figure 4

Annual average number of symptomatic influenza cases. The left bar of each pair shows symptomatic influenza cases in scenario 1 where only TIV is used, the right bar of each pair represents those in scenario 2 where TIV immunisation of children 2 to 17 years old is replaced in 2012 by LAIV immunisation and where childhood vaccination coverage with LAIV is subsequently increased up to 50% in three annual steps. The lower parts of the bars correspond to the number of paediatric cases, the upper parts of the bars indicate the number of cases in adults aged 18 years and above.

Figure 5

Results of one-way sensitivity analyses. Each of the horizontal bars of this tornado chart shows the impact of varying a single parameter of the model across a given range on the number of symptomatic influenza cases prevented while keeping all other parameters at their base values. The dark grey bars represent the upper bound of the range, the light grey bars represent the lower bound. The prevented cases are the difference of symptomatic influenza cases between scenario 1 and scenario 2 during the 10-year evaluation period. TIV is used constantly in scenario 1, whereas TIV immunisation in children 2 to 17 years of age is replaced by LAIV immunisation in scenario 2, with coverage increasing up to 50% in three annual steps.

Figure 6

Results of two-way sensitivity analyses varying the vaccination coverage and the maximum vaccination age. These charts show how many additional symptomatic influenza cases are prevented in scenario 2 during the 10-year evaluation period in Germany when compared to scenario 1. In scenario 1, TIV is used for all age classes with constant age-specific vaccination coverage, as reported for Germany. Scenario 1 remains unchanged in all analyses presented by these graphs. Scenario 2 assumes that annual vaccination of children up to a given maximum age (see numbers on the right hand side) is recommended in Germany, starting in 2012. In scenario 2, the vaccination coverage of children from 2 years up to the recommended age is increased in three annual steps, starting from the baseline value and finally reaching the coverage given on the horizontal axis; the vaccination coverage of children in other age groups and of adults is kept at the baseline value (which is also used in scenario 1). (a) TIV is used for all children and adults in scenario 2; (b) LAIV is used for all children from 2 years up to the recommended maximum age of childhood vaccination, and TIV is used for all others; (c) LAIV is used for all children from 2 years up to the recommended maximum age of childhood vaccination (with increasing coverage) and for all older children up to 17 years (with constant coverage); TIV is used for all others.