Age-targeted vaccination for reducing Clostridioides difficile infection in England: a coupled mathematical-economic modelling analysis

Background: Clostridioides difficile infection (CDI) is associated with high morbidity and mortality, emphasising the need for prophylaxis. The lead vaccine candidate recently demonstrated promising reductions in medically attended cases. Methods: Key risk factors for CDI were incorporated into a hospital-level mathematical model used to simulate the impact of the vaccine on reducing disease burden in England. Model outputs of interest included medically attended cases, intensive care admissions and deaths associated with CDI, as well as costs and quality-adjusted life years (QALYs). Hospital costs and costs of years of life lost due to premature mortality averted per vaccine course were computed for a 10-year time horizon. Results: The epidemiological model demonstrated considerable benefits to targeting older age groups whereby vaccinating only those over the age of 74 years old (i.e. 9% of England’s population) more than halved CDI cases and intensive care unit (ICU) admissions. Simulations also showed that this could be expected to reduce deaths by almost two-thirds and that around 20% of lives saved would be achieved through indirect benefits, i.e. due to reduced transmission to unvaccinated as well as vaccinated individuals. Issuing around 5 million vaccine courses in both the first and second year to protect the eldest, and 0.4 million annual courses thereafter to maintain effective coverage of all those over 64 years old, can be expected to avert £378 in costs (2023£) and gain 0.046 QALYs per vaccine course by the fourth year of rollout. Conclusions: Should a safe and efficacious C. difficile vaccine be licensed, it could be positioned very well for providing considerable economical and health benefits. This work guides how these gains could be maximised for England’s population.