Mortality benefits and intussusception risks of rotavirus vaccination in low- and middle-income countries

Infant rotavirus vaccines have led to substantial reductions in rotavirus gastroenteritis (RVGE) hospital admissions and costs, but some studies have reported an elevated risk of intussusception, a rare bowel disorder, in vaccinated infants. The aim of this thesis is to quantify the potential mortality benefits and intussusception risks of alternative rotavirus vaccination schedules in 135 low- and middle-income countries (LMICs). The thesis begins with an introduction to the topic and background to the literature and concludes with some final reflections on the research and its relevance for informing national decisions about vaccine safety and optimal scheduling of rotavirus vaccines. The main body of the thesis includes a series of research papers which address specific topics relevant to the estimation of mortality benefits and intussusception risks. These include methods for estimating: RVGE deaths <5 years of age; RVGE age distributions <5 years; vaccine coverage and timeliness; rotavirus vaccine efficacy and waning; and, intussusception incidence, age distributions, and case fatality ratios in children <5 years of age. The final research paper brings together this evidence and uses a national-level vaccine decision support model to estimate the potential rotavirus mortality benefits (averted RVGE deaths <5 years of age) and risks (excess intussusception deaths <5 years of age) of 18 possible vaccination schedules in 135 LMICs. Scenarios with and without age restrictions are evaluated. Rotavirus vaccines are found to have a favourable benefit-risk profile in LMICs. Mortality benefits and intussusception risks are estimated to vary considerably by country and choice of rotavirus vaccination schedule. Schedules involving birth and booster doses could further increase benefits and reduce risks, but more research is needed to assess their feasibility, safety and impact.