Assessing direct and indirect effects of pediatric influenza vaccination in Germany by individual-based simulations

Abstract

Children have a high burden of influenza and play a central role in spreading influenza. Routinely vaccinating children against influenza may, thus, not only reduce their disease burden, but also that of the general population, including the elderly who frequently suffer severe complications. Using the published individual-based tool 4Flu, we simulated how pediatric vaccination would change infection incidence in Germany. Transmission of four influenza strains was simulated in 100,000 individuals with German demography and contact structure. After initialization with the recorded trivalent influenza vaccination coverage for 20 years (1997-2016), all vaccinations were switched to quadrivalent influenza vaccine (QIV). Scenarios where vaccination coverage of children (0.5-17-year-old) was increased from the current value (4.3%) to a maximum of 10-60% were compared to baseline with unchanged coverage, averaging results of 1,000 pairs of simulations over a 20-year evaluation period (2017-2036). Pediatric vaccination coverage of 10-60% annually prevented 218-1,732 (6.3-50.5%) infections in children, 204-1,961 (2.9-28.2%) in young adults and 95-868 (3.1-28.9%) in the elderly in a population of 100,000 inhabitants; overall, 34.1% of infections in the total population (3.7 million infections per year in Germany) can be prevented if 60% of all children are vaccinated annually. 4.4-4.6 vaccinations were needed to prevent one infection among children; 1.7-1.8 were needed to prevent one in the population. Enhanced pediatric vaccination prevents many infections in children and even more in young adults and the elderly.

Keywords: Influenza; mathematical model; pediatric; simulation; vaccination.

Figure 1.

Increased QIV vaccination of children from 6 months to 4 years of age (a) or 6 months to 17 years of age (b). Average annual number of influenza infections prevented among children (black; 0–17 years), young adults (dark gray; 18–59 years) and elderly (light gray; 60+ years) compared to QIV vaccination at baseline coverage. Infections prevented (%) show the overall reduction of infection in the population. Averages of 1,000 pairs of simulations for each combination of target age-group and coverage; population size 100,000; evaluation period 20 years. NNV = number needed to vaccinate; yoa = years of age.

Figure 2.

Prevented influenza infections in the German population by annually applying a number of QIV doses to pre-school children (0.5–4 years, squares with dashed regression line) or to all children (0.5–17 years, circles with full regression line) or to at-risk children (0.5–17 years; asterisk). The percentages next to the dots indicate what annual coverage of the respective group of children can be reached with the given number of doses. The origin of the curves indicates that no additional vaccinations are performed, i.e. the pediatric vaccination coverage in both simulation branches is equal to 4.1% (i.e. 7.7% for risk children, 3.8% for others). The figure also takes into account that children below 9 years of age are given two doses when they are vaccinated for the first time in their life. Averages of 1,000 pairs of simulations for each dot, using an evaluation period of 20 years; results are based on a simulated population size of 100,000 individuals and were extrapolated to the total population of Germany.

Figure 3.

Univariate sensitivity analyses for the number of prevented infections when vaccinating 40% of children from 6 months to 17 years of age with QIV in a population of 100,000 individuals with German demography (annually prevented infections; black: children 0–17 years, dark gray: young adults 18–59 years, light gray: elderly 60+ years; averages of 1,000 pairs of simulations for each parameter setting, using an evaluation period of 20 years).

Figure 4.

Average numbers of secondary infections per infected individual in 5-year age groups (starting with 0–4 years, 5–9 years, etc.). During the 20-year evaluation period of branch 1 (QIV vaccination with unchanged vaccination coverage) of a randomly picked simulation with 100,000 individuals, the numbers of secondary infections were recorded for all infected individuals. These numbers were then averaged for each 5-year age group (black: children 0–17 years, dark gray: young adults 18–59 years, light gray: elderly 60+ years).

Figure 5.

Time course of the annual number of prevented influenza infections during the 20-year evaluation period. Comparison between QIV vaccination at baseline coverage and extended QIV vaccination of up to 40% (reached after four years, using a linear increase) of vaccination of children from 0.5 to 17 years of age. The results show averages of 1,000 stochastic simulations with a population of 100,000 individuals (black: children 0–17 years, dark gray: young adults 18–59 years, light gray: elderly 60+ years). The numbers above the bars show the percentages of prevented infections in all age categories. Averaged over all 20 years, 3,066 infections (22.71%) are prevented annually.