Post-marketing surveillance of adverse events following measles, mumps, rubella and varicella (MMRV) vaccine: retrospecive study in apulia region (ITALY), 2009-2017

Abstract

Since 2006, some Italian Regions introduced the active offer of measles, mumps, rubella, and varicella (MMRV) vaccine for all newborns during the second years of life. In 2011, Italian Drug Authority (AIFA) recommended the discontinuation of the MMRV use for an increased risk of febrile seizures following vaccination; furthermore, some Regions (such as Apulia, that introduced MMRV offer in 2009) chose to continue the use of MMRV and Ministry of Health recommended to guarantee supplemental monitoring of safety of the vaccine. In Italy, the surveillance of Adverse Events following immunization (AEFIs) is currently carried out by AIFA and Regional Health Authorities; this paper aims to summarize the results of MMRV-vaccine surveillance of AEFIs program carried out in Apulia. From the AIFA database, we selected MMRV AEFIs that occurred in Apulia (about 4,000,000 inhabitants) from 2009 to 2017. For serious AEFIs, we applied the WHO causality assessment algorithm, using for cases hospitalized information from individual medical records. In the 8 years of observation, 155 MMRV-AEFIs (reporting rate: 37.9×100,000 doses) occurred of which 26 were classified as serious (6.3×100,000 doses) and 22 led to hospitalization. Performing causality assessment, for 10 the classification was "consistent causal association to immunization" (reporting rate: 2.4×100000 doses), for 2 indeterminate, for 13 "inconsistent causal association to immunization" and for 1 not-classifiable. No case of febrile seizure resulted consistent to vaccination. All consistent serious AEFIs were completely resolved at subsequent follow-up.

Adverse events following measles-mumps-rubella-varicella vaccine: an independent perspective on Italian pharmacovigilance data

“…However, this calculation was obtained after discarding 3 out of 4 cases of febrile seizures by applying the WHO causality assessment algorithm. Furthermore, the data of this paper 3 are in partial conflict with a retrospective epidemiological research carried out in the same Region with passive methods of AEFI reporting 5 .…”

“…study 5 , and to the fact that in three of four cases they discarded the responsibility of the vaccine by applying the WHO causality assessment algorithm.…”

“…Case n. 9 cited in the paper of Stefanizzi et al 5 : Note: In this case, the adverse effects following immunization (AEFI) took place precisely in the time window in which the greatest number of episodes of febrile seizures normally occur, so there is a high biological plausibility and a correct time window for attributing causality to the vaccine. In the report by Stefanizzi et al 3 there is a very high incidence of serious gastrointestinal symptoms with a causality ascertained with the vaccine.…”

“…Vaccines has published a paper by researchers from the University of Bari and the Apulia Region 3 reporting and updating the main results of the 2018 report of the Apulia Region official Epidemiological Observatory on surveillance after the administration of measles-mumps-rubella-varicella (MMRV) vaccine 4 . Subsequently, Human Vaccines and Immunotherapeutics reported a retrospective study of AEFIs following MMRV vaccine during eight years of passive pharmacovigilance 5 . This vaccination has been made mandatory in Italy for all newborns from 2017 onwards.…”

“…Despite the results showing a high incidence of serious AEFIs, the authors concluded reassuringly on the safety profile of the MMRV vaccine 5 and stated that “ the active surveillance program confirmed and reinforced the safety profile of the vaccine " 3 . A specific aspect concerns the incidence of febrile seizures after vaccination with MMRV.…”