title: Targeted rotavirus vaccination of high-risk infants; a low cost and highly cost-effective alternative to universal vaccination.
abstract: BACKGROUND
  The cost-effectiveness of universal rotavirus (RV) vaccination is controversial in developed countries. As a result, RV vaccination programs do not currently exist in most European countries. Hospitalization is the main driver of RV disease costs, and prematurity, low birth weight (LBW) and underlying medical conditions have been associated with RV hospitalization and complications. We investigated the cost-effectiveness of targeted RV vaccination of high-risk infants and universal RV vaccination versus no vaccination.
  
  
  METHODS
  Disease burden, mortality and healthcare costs of RV hospitalization for children with and without prematurity, LBW and congenital pathology were quantified in two hospital-based observational studies in the Netherlands. Cost-effectiveness analysis was based on an age-structured stochastic multi-cohort model of the Dutch population comparing universal RV vaccination and targeted vaccination of high-risk infants to no vaccination. The primary endpoint was the incremental cost-effectiveness ratio (ICER), with a threshold of €35,000/quality-adjusted life year (QALY) from the healthcare provider perspective. Sensitivity analyses included vaccine price and coverage, herd-immunity and QALY losses.
  
  
  RESULTS
  A total of 936 children with RV infection were included. Prematurity, LBW and congenital pathology were associated with increased risks of RV hospitalization (relative risks (RR) ranging from 1.6 to 4.4), ICU admission (RR ranging from 4.2 to 7.9), prolonged hospital stay (1.5 to 3.0 excess days) and higher healthcare costs (€648 to €1,533 excess costs). Seven children succumbed due to RV complications, all belonging to the high-risk population. Targeted RV vaccination was highly cost-effective and potentially cost-saving from the healthcare provider perspective with ICERs below €20,000/QALY in all scenarios with total (undiscounted) annual healthcare costs between -€0.1 and €0.5 million/year. Results were most sensitive to mortality rates, but targeted vaccination remained highly cost-effective up to reductions of 90% compared to observed mortality. Universal RV vaccination was not considered cost-effective (mean ICER: €60,200/QALY) unless herd-immunity and caretaker QALY losses were included and vaccine prices were €60 at most (mean ICER: €21,309/QALY).
  
  
  CONCLUSIONS
  We recommend targeted RV vaccination for high-risk infants in developed countries.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Huispostnummer STR,6,131, Postbus 85500, Utrecht 3508 GA, The Netherlands. P.Bruijning@umcutrecht.nl
authors.forename: Patricia
authors.initials: P
authors.lastname: Bruijning-Verhagen
authors.forename: Marie-Josée J
authors.initials: MJ
authors.lastname: Mangen
authors.forename: Mariet
authors.initials: M
authors.lastname: Felderhof
authors.forename: Nico G
authors.initials: NG
authors.lastname: Hartwig
authors.forename: Marlies
authors.initials: M
authors.lastname: van Houten
authors.forename: Léon
authors.initials: L
authors.lastname: Winkel
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: de Waal
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017281:Cost of Illness; D003362:Cost-Benefit Analysis; D005260:Female; D017048:Health Care Costs; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015233:Models, Statistical; D009426:Netherlands / Q000453:epidemiology; D012189:Retrospective Studies; D012400:Rotavirus Infections / Q000191:economics* / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000191:economics*; D016019:Survival Analysis; D014611:Vaccination / Q000191:economics* / Q000379:methods*
chemical_list: D022243:Rotavirus Vaccines