In the present study we evaluated the tolerability of the newly introduced MenACWY-TT vaccine in the NIP in toddlers. Our results show that solicited systemic AEs like listlessness, fever and sleeping problems frequently occur, although most of them recovered within 4 days. The frequency of rash was much lower, but the majority of the children had not recovered after 4 days. However, rashes are also a known adverse event of MMR vaccination which usually occurs 5–21 days after vaccination. Therefore, overlapping frequencies of this adverse event from both vaccines may explain the longer duration. A follow-up questionnaire showed that only 2 children experiencing rash within 4 days after vaccination, did not recover within 30 days after vaccination (data not shown). The impact for most of the systemic AEs was mild to moderate, but parents reported on a high impact of sleeping problems and the vomiting, while hardly mentioning problems with local reactions.
The tolerability of MenACWY-TT observed in our study was in line with that observed in Lareb’s MenC-TT study conducted a few years earlier in a similar group of young children in the Netherlands. Only for fever a higher risk after MenACWY-TT vaccination was found within 4 days after vaccination.
The frequencies of local reactions we found in our study are remarkable lower compared with the results from post-licensure trials. In our study, redness was the most reported local reaction (2.9%), whereas in other studies percentages up to 45% were found for local reactions (10, 12, 19–21). In the clinical trials, irritability was one of the most mentioned solicited general symptoms with frequencies between 15 and 45% (10, 12, 19, 20), whereas in our study, listlessness was the most reported systemic AE (22.4%). Unfortunately, we did not include irritability in our questionnaire, whereas the trials did not describe listlessness. Drowsiness was another frequently mentioned systemic AE in the trials (15–35%), whereas in our study somnolence was hardly reported (2.7%). On the other hand, the results for loss of appetite (10.5% in our study vs. 10–25% in the trials) and fever (13.4% vs. 5–30%) were more consistent. Differences in study design (cross-section vs RCTs, data collection, age distribution) may contribute to the differences in our results and the results from clinical trials. This is underlined by the fact that our results are very similar to the results of Lareb’s MenC-TT study, which had the same study design. Only for fever a significant difference was found between these studies (13.4% for MenACWY vaccination and 8.2% for MenC-TT vaccination), although our result is in line with what is reported in the SMPC of this vaccine (≥ 1:10) (4).
There were a few number of limitations to this study. Compared to Lareb’s MenC-TT study, significant differences were identified in baseline characteristics for comorbidity, attending daycare and seasonality. Although this may influence the frequency of for example fever, no different risk estimations were found between the adjusted and unadjusted analyses. Confounding by any of the covariates is therefore unlikely.
Data from the MenACWY-TT and Lareb’s MenC-TT study were collected in different years. As the circulation of infectious agents differs between years, this may have influenced the frequency of some systemic events, like fever, diarrhea and vomiting. Since many of these events in our study recovered within 4 days, we assume that this effect is limited. However, the actual effect is unknown.
The non-response in both studies was high. A low response rate can give rise to sampling bias if the nonresponse is unequal among the participants regarding exposure and/or outcome. It is not clear to what extent this has occurred in this study. But since they have the same study design, it may be assumed that the reasons for non-response is similar for the MenACWY-TT and MenC-TT study. Therefore it is unlikely that the comparison of these studies is biased.