Josephine van Dongen

5 Safety and Tolerability of Human Rotavirus Vaccination 127 generally well tolerated, although risk of AE increased by seven percent when HRV was added. Gastrointestinal AE were repor ted in one in four infants who received HRV. Reassuringly, this increased rate of (gastrointestinal) AE did not result in more frequent healthcare attendance for AE among NIP versus NIP+HRV vaccinated infants, ten versus nine percent, respectively. For HRV only vaccine administration fever as AE is less commonly repor ted (5.2%) compared to NIP vaccines (17.3%). Rotavirus vaccines have been available worldwide since 2006, and over 100 countries have implemented a globally licensed vaccine in their infant immunization program. 16 In Cochrane systematic reviews on safety of these vaccines, SAE were repor ted in 2.3-7.6% of healthy term infants following vaccination, no increased risk compared to placebo. 17,18 Gastrointestinal SAE occur in 0.1-0.6% of HRV vaccinated term infants, but this is without mention of possible relatedness to vaccination. 19–21 A prior study, among infants generally healthy and on average of older gestational age, identified two vaccine related SAE among 670 HRV vaccinated premature infants, 6 which is lower than in our study. Given the clinical vulnerability of the infants in our study receiving rotavirus vaccination, an active approach and systematic screening of all medical records was chosen to guarantee complete case finding. However, it makes it difficult to interpret our finding of 0.25 vaccine related SAE per 100 vaccine doses in the context of existing evidence. It is well known that rates of (vaccine related) SAE following vaccination are generally higher in premature infants, 8 but to what extend this also applies to HRV is uncer tain. Our findings indicate that clinicians should be vigilant about the possibility of vaccine related SAE when vaccinating against rotavirus in infants with prematurity and clinical vulnerability. In line with results of prior HRV tolerability studies in premature and term infants, 6,19–21 HRV seemed well tolerated among high-risk premature infants and was associated with only a small increase in AE when combined with NIP vaccines. The observed frequency of AEs in 45-55% of our study population is even slightly lower than the 60% repor ted in a Dutch study of healthy term infants receiving NIP vaccines. 22 Gastrointestinal AE appear a class effect of oral rotavirus vaccines and occur in up to 25% of premature infants in our and other studies, but they rarely require medical attention. 6,7,23 Although symptoms may be mild, it is impor tant to counsel parents about this possible side effect prior to vaccination. Because infants with GA < 27 weeks were excluded from the pre-licensure trials of HRV, administration of HRV to these infants is off-label. In our study, fewer solicited AE among infants of GA < 27 weeks were repor ted to those among premature infants ≥ 27 weeks. No vaccine related SAE was documented. Although the numbers are small, these findings are reassuring. The Netherlands currently has no national rotavirus vaccine policy and uptake in private market is very low. 24,25 We recently showed that vaccine effectiveness of at least one dose HRV among our study population of medical risk infants was substantially lower than expected at 30%