Josephine van Dongen

5 Safety and Tolerability of Human Rotavirus Vaccination 121 Figure 1. Study design and primary series NIP schedule. Abbreviations: HRV = human rotavirus vaccine, NIP = national immunization program, DTaP-IPV-Hib-HepB = hexavalent diphtheria-tetanus toxoids- accelular per tussis-inactivated polio-Haemophilus influenzae type B-hepatitis B vaccine, PCV10 = 10-valent pneumococcal vaccine. Outcomes 1) The outcome for safety was defined as the number of vaccine related SAE per 100 vaccine doses in high-risk premature infants. 2) For tolerability, we compared the occurrence of at least one solicited AE in the seven days following receipt of either NIP vaccines (DTaP-IPV-Hib-HepB and/or PCV10), concomitant NIP+HRV or, HRV only. We estimated the relative risk of AE per vaccine administration with NIP only as reference. The number of solicited AE per vaccine administration was compared using incidence rate ratio (IRR). Comparisons were performed for the subgroup of fever and gastrointestinal AE (vomiting, bloody and/or, looser stools) and, for AE related healthcare attendance. In secondary analysis of tolerability we repor ted the cumulative incidence of solicited AE that infants experienced during completion of the primary series of either NIP or NIP+HRV. In addition, occurrence of fever, gastrointestinal solicited AE and, AE related healthcare attendance were described. Analysis 1) Each vaccine related SAE was described in terms of diagnosis, infant characteristics, timing in relation to HRV vaccination and, where applicable, results of faecal testing. Rotavirus positive faecal samples were additionally genotyped, RNA was extracted from faecal samples using the MagnaPure96 nucleic acid extraction system. The purified RNA was subsequently subjected to PCR amplification and sequencing of theVP4 andVP7 genes according to Simmonds