Josephine van Dongen

Chapter 8 196 could protect medical risk infants. Herd effect is achieved via decreased transmission in the population if a sufficient fraction has been vaccinated. This prevents disease occurring among unvaccinated individuals, and occurs in a setting with universal vaccination. Estimates of herd effect from universal rotavirus vaccination varied between two and 77% per season in a Nor th- American study, 28 a meta-analysis repor ted 48% (95%CI 39;55%) overall indirect effectiveness among children below five years of age. 63 In addition, the population with underlying medical conditions or perinatal morbidity is mostly affected by nosocomial rotavirus infection early in life. 3 Due to frequent hospitalization and prolonged admission duration, their risk of in-hospital rotavirus acquisition increases. Universal rotavirus vaccination was repor ted to reduce 72% of nosocomial rotavirus infections per year compared to no vaccination. 64 For future research, I propose that the following five suggestions are taken into consideration: a)The (changing) epidemiology of rotavirus.Two studies underlined the need for studying rotavirus strain diversity and continuation of genotype surveillance. 29,65 Surveillance of rotavirus epidemiology and corresponding vaccine effectiveness is advised in order to monitor changes in circulating strains and its effect on vaccine performance. b)Vaccine performance should be separately assessed for specific medical risk populations as evidence from general or trial populations may not necessarily be generalizable.This thesis demonstrated that separate studies in specific at-risk populations can provide valuable information in order to guide policy on vaccine administration, programs and implementation. c)Given the poor vaccine effectiveness in our study population, alternative types of rotavirus vaccines, which are currently still in development ( figure 2 ), should be considered. 50 Parental subunit vaccines or inactivated vaccines could improve immune responses in medical risk infants and hopefully deliver sufficient protection. d)The microbiome association with rotavirus immune response.This should be verified in infants as there are several hypotheses from animal and human studies that immunity is influenced by the gut microbiota. 66–69 The microbiota is a potential stimulant, 45 and a potential target for interventions to promote the immune response needed for (mucosal) rotavirus vaccination in infants with MRC. e)Rotavirus serum IgA levels in medical risk infants after vaccination. Serum IgA antibody titer is considered the best correlate of protection, and rotavirus vaccine performance as reported by a meta-analysis of efficacy trials. 49 A lower rotavirus serum IgA titer in our population would corroborate the hypothesis of an altered immune response in infants with MRC.