Simulating the impacts of mass vaccination with live attenuated human rotavirus vaccine in a developing country

Worldwide, rotavirus infection annually claims the lives of 527,000 children under five years of age, with the vast majority of these deaths occurring in the developing world. Vaccination is widely viewed as the most promising means of reducing this mortality. With this work, I examine the public health and economic impact of mass vaccination with Live Attenuated Human Rotavirus Vaccine (RIX4414) in a developing world setting where rotavirus mortality is high, strain diversity is great, and resources are scarce. In Aim 1, a method for estimating setting-specific vaccine efficacy is developed and validated. In Aim 2, an individual-based static Markov model of rotavirus infection, natural history, and utilization in a developing country is developed and analyzed. This static model serves as a comparator for the final model developed in Aim 3, a dynamic discrete event simulation of the same system which simulates an open population of individuals transmitting rotavirus infection between one another and gaining immunity through previous natural infections as well as through vaccination. Like compartmental epidemiological models, this final model captures indirect vaccination effects, yet it offers greater flexibility and serves as a framework for more complex models involving, for example, multiple pathogen strains. This work offers timely insight into a number of critical but unanswered questions which public health decision-makers will need to consider when making investments in this and other vaccines against rotavirus. In addition, it achieves methodologic advances in rotavirus vaccination modeling.