20 YEARS OF OUTPATIENT RESPIRATORY SYNCYTIAL VIRUS-INFECTION - A FRAMEWORK FOR VACCINE EFFICACY TRIALS

Background. Respiratory syncytial virus (RSV) is the most important vi ral respiratory pathogen of infancy and childhood. Much has been writt en about inpatients with severe disease. Inpatients, however, represen t only a minority of RSV-infected children. We studied the characteris tics of symptomatic outpatient RSV infection in healthy children to ga in a better understanding of RSV disease and to provide a background f or the testing of intervention strategies in children without high-ris k conditions. Methods. A total of 1113 children were followed during 2 0 consecutive RSV seasons. Signs and symptoms of respiratory infection were monitored. Cultures were obtained for febrile upper respiratory infection, acute otitis media, and lower respiratory infection (LRI). Rates of febrile upper respiratory infection, acute otitis media, LRI, and hospitalization were calculated. Given those rates, numbers of ch ildren needed to demonstrate efficacy of a vaccine product were calcul ated. Results. Mild disease from RSV infection lacked some of the clas sic features of RSV infection seen in hospitalized children. Involveme nt of the lower respiratory tract was, however, noted to be much highe r in RSV infection than it was in infection with other viral respirato ry pathogens. LRI was, therefore, considered the best candidate endpoi nt for vaccine trials. A product with 60% efficacy could be proven, wi th a power of 0.8, to be efficacious with as few as 1500 infants. Conc lusions. RSV infection is common and often involves the lower respirat ory tract, even in outpatients. Our 20-year study of RSV infection pro vides a basis for calculation of sample sizes to be used in trials of vaccine candidates.