4(a)). The reason for this is that if very old adults cannot be boosted then reduction in varicella incidence (reduced exposure to VZV) will have little effect on their risk of developing zoster. Thirdly, more effective vaccines (or effective programs) against varicella will produce the greatest increases in zoster cases (Fig. Nintedanib mw 4(b)). However, in the long-term the worst vaccines will produce a higher zoster incidence as more people will be infected with varicella

and therefore will have the possibility of reactivation (Fig. 4(b)). Finally, age-specific effective mixing can largely influence the impact of varicella on zoster. If older adults have very little contact with varicella cases (e.g. low contact rates with infected children) then reduction in varicella incidence following vaccination will only have a small impact on zoster (see England and Wales mixing scenario ( Fig. 4(c)). The expected increase in zoster predicted by the model is directly related to estimates of the force of infection in adults; the force

of infection in 25–44 years olds for the base case, BMN 673 in vivo England and Wales, Finland and Germany are 0.06, 0.03, 0.04 and 0.04 per person-year, respectively. Fig. 5 shows the impact of 2-dose varicella vaccination programs on varicella and zoster. The base model predicts that a 2-dose varicella vaccination program will significantly reduce varicella incidence under the three strategies investigated (Infant, Pre-school and Grade 4 ( Fig. 5)). Of note, our results suggest that giving the second Thymidine kinase dose in Grade 4 could help avoid the predicted epidemic of varicella 10 years into the 1-dose program by acting as: (1) catch-up vaccination in those yet to be immunised with a first dose and (2) a booster dose in vaccinees whose protection

will have waned. The main benefit of the second dose is its effectiveness at reducing breakthrough varicella (Fig. 5(b)). However, the short to medium term increase in zoster incidence (Fig. 5(c)) is predicted to be slightly higher under a 2-dose program (compared to 1-dose) because of its greater effectiveness at preventing varicella. Fig. 6 illustrates the incremental benefits of adding a second dose for different vaccine efficacy, mixing matrix and boosting assumptions. The base case model (range: min; max) predicts that adding a second dose will reduce varicella and zoster cases by an additional 22% (0%; 82%) and 6% (0%; 14%) over 80-years, respectively. Importantly, although the incremental benefit of adding the second dose is highly sensitive to assumptions regarding vaccine efficacy and mixing, the overall effectiveness of a 2-dose strategy at preventing varicella is not (Fig. 6). A 2-dose infant strategy (90% coverage) is predicted to reduce varicella cases by 72%–97%.