Model-based estimation of the impact on rotavirus disease of RV3-BB vaccine administered in a neonatal or infant schedule

Abstract

Rotavirus infection is a common cause of severe diarrheal disease and a major cause of deaths and hospitalizations among young children. Incidence of rotavirus has declined globally with increasing vaccine coverage. However, it remains a significant cause of morbidity and mortality in low-income countries where vaccine access is limited and efficacy is lower. The oral human neonatal vaccine RV3-BB can be safely administered earlier than other vaccines, and recent trials in Indonesia have demonstrated high efficacy. In this study, we use a stochastic individual-based model of rotavirus transmission and disease to estimate the anticipated population-level impact of RV3-BB following delivery according to either an infant (2, 4, 6 months) and neonatal (0, 2, 4 months) schedule. Using our model, which incorporated an age- and household-structured population and estimates of vaccine efficacy derived from trial data, we found both delivery schedules to be effective at reducing infection and disease. We estimated 95-96% reductions in infection and disease in children under 12 months of age when vaccine coverage is 85%. We also estimate high levels of indirect protection from vaccination, including 78% reductions in infection in adults over 17 years of age. Even for lower vaccine coverage of 55%, we estimate reductions of 84% in infection and disease in children under 12 months of age. While open questions remain about the drivers of observed lower efficacy in low-income settings, our model suggests RV3-BB could be effective at reducing infection and preventing disease in young infants at the population level.

Keywords: Indonesia; RV3-BB vaccine; Rotavirus; individual-based model; neonatal schedule.

Figure 1.

Schematic of the rotavirus infection and disease model to epidemiological data. Infants may be born with maternal immunity (M) or susceptible (S). Following contact and transmission with an infectious individual, susceptible individuals become exposed (E) and then infectious (I). Recovered individuals (R) are protected from further infection until their immunity wanes, and they once again become susceptible (S). Following successive exposures (denoted as subscripts 1, 2 and 3) individuals have different levels of susceptibility, infectiousness, and protection against disease (see Table 1). Black arrows denote transitions occurring due to infection and loss of immunity. Red arrows denote transitions occurring due to vaccination.

Figure 2.

Annual incidence of all rotavirus infections, including asymptomatic infections, by age in the baseline, infant schedule and neonatal schedule scenarios. Incidence values are calculated over a five-year period, five years after the introduction of vaccination. Each boxplot shows the median, IQR and range over 10 simulation runs.

Figure 3.

Impact of lower vaccine coverage. Annual incidence of all rotavirus infections, including asymptomatic infections, by age for baseline assumption of 85% vaccine coverage, and alternative moderate (55%) and low (25%) vaccine coverage scenarios. Incidence values are calculated over a five-year period, five years after the introduction of vaccination. Each boxplot shows the median, IQR and range over 10 simulation runs.

Figure 4.

Impact of reduced maternal immunity on annual incidence when the probability of acquiring maternal immunity is halved. Annual incidence of all rotavirus infections, any disease, and severe disease only are shown for the baseline (no vaccination), infant schedule, and neonatal schedule scenarios. Incidence values are calculated over a five-year period, five years after the introduction of vaccination. Each error bar shows the median, 95% CIs over 10 simulation runs.