Pediatric Norovirus Vaccination: Modeling the Influence of Schedule on Population Health

Abstract

AbstractIntroductionNoroviruses cause approximately 20 million cases of acute gastroenteritis (AGE) annually in the United States, with children under 5 years of age experiencing the highest incidence. With promising norovirus vaccines moving into pivotal trials in children, an important next step in norovirus vaccine evaluation is comparing benefits of various pediatric vaccination schedules.MethodsWe developed an age-structured deterministic compartmental model for norovirus transmission and fit it to norovirus case incidence data representative of the United States population. The model accounted for immunity accrued across multiple infections and potential maternal antibody interference with vaccine performance. Using this model, we simulated five pediatric vaccination schedules (at 0/2/4m, 2/4/6m, 6/12m, 12/24m, and 48m) with 70% and 90% vaccination coverage, with and without maternal antibody interference. We evaluated the impacts of vaccination on clinical outcomes, including acute gastroenteritis cases, outpatient visits, hospitalization, and death due to norovirus.ResultsVaccination impacts were primarily concentrated in the pediatric age group, with modest indirect effects to unvaccinated age groups. Comparing scenarios, the 2/4/6m schedule was more impactful, with a 43% (95% uncertainty interval (UI): 29 – 62%) reduction in pediatric AGE cases (<5 years old) and 19% (95% UI: 7 – 54%) reduction in total population cases (including pediatric cases) with 70% vaccination coverage and no maternal antibody interference. This scenario was estimated to avert 12,200 (95% US: 7,100 – 21,500) AGE cases, 2,100 (900 – 4,500) outpatient visits, and 50 (30 – 90) hospitalizations per 100,000 young children. In the total population, 3.72 million (95% UI: 2.06 – 7.07 million) AGE cases, 526,000 (24,800 – 1,092,000) outpatient visits, 18,000 (9,500 – 41,600) hospitalizations, and 152 (52-602) deaths were estimated to be averted across the population, with 38% of the overall impact conferred by indirect effects. While the 0/2/4m schedule had the greatest overall impact when assuming no interference from maternal antibody, the 2/4/6m schedule was less affected by interference from maternal antibodies. Assuming maternal antibody interference does compromise vaccine efficacy, the 2/4/6m schedule was comparable to the most impactful vaccination schedule with maternal antibody interference (6/12m schedule, 16% [95% UI: 7 – 29%] of pediatric cases and 6% [95% UI: 1 – 26%] of total cases averted, 2/4/6m schedule: 14% [95% UI: 7 – 25%] of pediatric cases and 6% [95% UI: 2 -21%] of total cases averted). Thus, while the total vaccination impact was highly sensitive to assumptions regarding maternal antibody interference, the 2/4/6m schedule impacts were robust across assumptions.SignificancePediatric norovirus vaccination scheduled at 2/4/6m and similar schedules have the potential to substantially reduce norovirus burden in high incidence age groups and avert healthcare utilization, likely with modest benefits to unvaccinated individuals.