Purpose: To accelerate the control of hepatitis B virus (HBV) infection in the U.S., augmenting the current main strategy of infant vaccination with a ‘catch-up' vaccination program targeting high-risk adults is being considered. Our objectives were to predict the potential long-term impact of various vaccination scenarios and to quantify the portion of the program's benefits that may be represented by externalities to unvaccinated individuals.

Methods: We developed a dynamic (deterministic, compartmental) model to simulate the transmission dynamics of HBV in the U.S. population, incorporating heterogeneity in sex, age, and risk behaviors (sexual activity and drug use), and calibrated the model using empirical data. Based on model simulations of various hepatitis B vaccination scenarios, we computed total benefits as the difference in the cumulative numbers of HBV infections with and without vaccination; and direct benefits as the number of HBV infections averted among vaccinated persons only. The externalities of a given vaccination program were calculated as the difference between its total and direct benefits. We performed univariate and multivariate sensitivity analyses and also examined the distribution of the externalities across subpopulations.

Results: Implementation of catch-up vaccination targeting high-risk U.S. adults aged 15-39 (70% effective coverage) would prevent 163,000 additional cases of HBV infection compared to an infant-only vaccination scenario over the period 2005-2090. About 25% of the total benefits were estimated to come from externalities, and a majority of these would accrue among unvaccinated low-risk individuals. When expressed as the indirectly prevented cases of HBV infection per effectively immunized person, the externality due to the selective adult vaccination program (0.008 cases per person) was a bit higher than that of the infant vaccination (0.007 cases per person). The externalities increased non-linearly with increasing vaccine coverage and were sensitive to sexual mixing patterns among subpopulations.

Conclusions: A selective adult hepatitis B vaccination program would significantly reduce HBV incidence among high-risk groups and provide positive externalities for the society, lowering incidence even among unvaccinated low-risk individuals. However, the findings imply that, to eliminate HBV in the U.S., a comprehensive strategy should be considered, including an optimal combination of infant and adult vaccination programs and interventions to reduce risk behaviors.