Disproportionality analysis of reported drug adverse events to assess a potential safety signal for pentavalent vaccine in 2019 in El Salvador

Detection and surveillance of vaccine safety hazards is a public health staple. In the post-marketing phase, when vaccines are used in mass, it is crucial to monitor potential signals of adverse reactions that may have been missed in the pre-marketing phase. We analysed spontaneous reports of drug adverse events in El Salvador to assess a potential safety signal related to an increase in febrile seizures following the pentavalent (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae Type B) vaccine in 2019. This was a retrospective observational study of adverse event notifications in the national electronic drug safety database from 2011 to 2019. We performed standard disproportionality analysis computing Proportional Reporting Risk (PRR), Reporting Odds Ratio (ROR), Relative Reporting Ratio (RRR), Chi-squared, and Information Component (IC), comparing the pairing of febrile seizures and pentavalent vaccine to all other drugs and adverse events recorded in 2019. The occurrence of febrile seizures following pentavalent vaccination exceeded the WHO expected rate of six cases × 100 000 doses administered from April 2019, with a maximum of 9.2 in September. IC was 4.3, ORR 421.9 (95% Confidence Interval, CI: 123.8–1437.7), PRR 223.5 (95 %CI: 70.2–710.9), RRR was 19.5. The first booster presented the highest rate (14.6 per 100,000 doses) of febrile seizures, more than double than expected. Rates for 2018 remained below expected. Reports of febrile seizures following pentavalent vaccine were also on the increase globally since 2014, with highest rates in 2018 and 2019. There was a disproportion of febrile seizures notifications following pentavalent in El Salvador in 2019, suggesting the existence of a safety signal. This may be due to the change in provider. Further studies should assess the causes of the increase and compute costs and benefits of this vaccination to determine if switching to a less reactogenic vaccine formulation is indicated.