From Evidence to Implementation: The Added Value of Health Economics for RSV Immunisation Implementation in Low- and Middle-Income Countries

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in young children. In 2019, RSV was estimated to cause approximately 33 million acute lower respiratory infections, 3.6 million hospitalisations and more than 101,000 deaths among children under five years of age, with more than 97% of deaths occurring in low- and middle-income countries (LMICs). The recent availability of a maternal RSV vaccine and long-acting monoclonal antibodies (mAbs) provides new opportunities to prevent severe disease during early infancy. This thesis investigates how epidemiological and health economic evidence can support the implementation of RSV immunisation strategies, with particular emphasis on LMICs.

Epidemiological studies first examined RSV burden, seasonality and the age distribution of severe disease. In the Netherlands, RSV circulation was substantially disrupted during the COVID-19 pandemic, including an unusual summer epidemic in 2021, but subsequently returned towards its pre-pandemic winter pattern. Severe disease remained concentrated in young infants. Importantly, 6% of RSV-related hospitalisations among infants aged <1 year occurred within the first 14 days of life, highlighting the importance of timely protection after birth.

The RSV GOLD III–ICU Network Study subsequently investigated severe respiratory infections among children aged <2 years across ten LMICs. During local RSV seasons, 29.0% of children admitted with severe respiratory illness tested positive for RSV. Most life-threatening RSV infections occurred among infants aged <6 months, with almost half occurring during the first three months of life, demonstrating the potential for early-life immunisation to prevent severe disease.

Cost-of-illness studies in Mozambique and Nepal demonstrated that RSV also imposes a substantial economic burden. In Mozambique, mean costs increased from USD 612 for severe hospitalised disease to USD 1,161 for life-threatening disease requiring intensive care. Household costs represented approximately 43–145% of the monthly minimum wage. In Nepal, mean total costs were USD 312 for hospitalised cases and USD 664 for intensive-care cases, with substantial out-of-pocket expenditure relative to the monthly minimum wage.

Cost-effectiveness analyses evaluated maternal vaccination and long-acting mAbs over 2025–2034. In Nepal, maternal vaccination at USD 5 per dose was estimated to prevent approximately 2,500 deaths and 50,000 hospitalisations, with an incremental cost-effectiveness ratio of USD 387 per disability-adjusted life year (DALY) averted. A mAb at the same price could prevent approximately 2,400 deaths and 54,000 hospitalisations at USD 486 per DALY averted. Seasonal delivery could further improve dose efficiency. Analyses in Mozambique similarly demonstrated substantial potential health gains, although cost-effectiveness remained strongly dependent on intervention price and the cost-effectiveness threshold used.

Overall, this thesis demonstrates that new RSV immunisation strategies could substantially reduce clinical and economic burden, but their value and feasibility are context-dependent. Integrating local epidemiology, healthcare utilisation, costs and implementation characteristics into economic evaluations can make estimates more relevant for national decision-making. Health economic evidence can thereby support priority setting and resource allocation, while successful and equitable implementation ultimately also depends on affordable pricing, sustainable financing and health-system readiness.