Josephine van Dongen

Chapter 4 104 Discussion In this prospective multicenter study, we evaluated VE and the impact of HRV among 1,482 infants with MRC and prolonged care using the quasi-experimental design of a step-wedge before-after cohor t study.We found VE after at least one dose of the HRV to be substantially lower than previously estimated for healthy infants.We were unable to demonstrate statistically significant reductions in any of the pre-specified rotavirus confirmed outcomes. The point estimate for VE against severe rotavirus AGE was 30% in ATP analysis. The IRR for rotavirus AGE of any severity was 1.02 (95%CI 0.69;1.50), suggesting no effect. In subgroup analyses, we observed a trend towards lower VE with lower gestational age, although differences were non-significant. If protection against rotavirus AGE is desired for these MRC infants, herd immunity (indirect protection via universal vaccination of healthy infants) might be the best alternative. Prevention by indirect effectiveness against rotavirus hospitalizations estimated by meta-analysis (48%, 95%CI 39;55%) was higher than our direct VE estimate. 20 This lowVE after at least one dose of HRV among infants with MRC is unexpected and deserves fur ther discussion.We hypothesize that cer tain host and pathogen factors could be of influence. For instance prematurity, lower GA is known to be associated with poorer vaccine responses for some, but not all vaccines. 23 In a trial, HRV immune responses in premature infants were found to be of protective levels in 85·7% of 147 infants, although this propor tion declined with younger GA. 22 Figure 3. Posterior probability per vaccine effectiveness threshold