Towards global prevention of severe pediatric RSV infection

Abstract

Respiratory syncytial virus (RSV) is the major cause of respiratory infections in young children. Globally, RSV infection presents a significant health problem with over 100,000 deaths annually among children <5 years. The majority of these deaths occur in low- and lower-middle-income countries (LMICs) due to lack of high-quality healthcare. Unequal distribution of RSV mortality calls for equitable distribution of RSV vaccines, prioritizing regions with the highest disease burden. Unfortunately, there are no RSV vaccines available in LMICs. An important aim of this thesis was to enhance our understanding of RSV mortality in LMICs to support equitable RSV vaccine distribution. Using a global database, subgroups with RSV mortality are described: children with Down syndrome, children who die outside the hospital, and children who acquire RSV infection in the hospital. A prospective study among children admitted to intensive care units across 10 LMICs revealed RSV in nearly one-third of all children with life-threatening respiratory infection. This thesis also includes the results of a phase 1/2b randomized placebo-controlled clinical trial: intranasal palivizumab to prevent RSV infection. Palivizumab has long been available but not in LMICs due to high costs. Administered as nasal drops, costs could be significantly reduced. Although safe, the trial showed inefficacy. Over time, access to RSV vaccines for LMICs can be enhanced by drug development reform. By prioritizing impact (lives-saved) over profit (return-on-investment), vaccine development can be aligned with mortality burden. Finally, in this thesis I advocate for equitable future RSV research through co-creation, equitable partnership and authorship policy, and sustainable capacity strengthening.