Acute Disseminated Encephalomyelitis Onset: Evaluation Based on Vaccine Adverse Events Reporting Systems

Paolo Pellegrino,Carla Carnovale,Valentina Perrone,Marco Pozzi,Sonia Radice,Stefania Antoniazzi,Emilio Clementi,Tobias Derfuss

doi:10.1371/journal.pone.0077766

Abstract

ObjectiveTo evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM) by considering data from different pharmacovigilance surveillance systems.MethodsThe Vaccine Adverse Event Reporting System (VAERS) database and the EudraVigilance post-authorisation module (EVPM) were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed.ResultsWe retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40±21.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines.ConclusionsThis study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reaction.

Highlights

Acute disseminated encephalomyelitis (ADEM) is an immune mediated inflammatory disorder of the central nervous system (CNS) that commonly occurs within one month from antigenic challenge [1]
By grouping together vaccinations against Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B (DTaP+IPV+HiB), we found that this was the vaccine group most frequently associated with ADEM development in the Vaccine Adverse Event Reporting System (VAERS) database (21%)
In this study we report the first characterisation of epidemiologic data regarding ADEM following vaccination considering a large number of reports arising from the two largest PV safety databases, covering more than 1 billion persons in the US and European Union (EU)

Summary

Introduction

Acute disseminated encephalomyelitis (ADEM) is an immune mediated inflammatory disorder of the central nervous system (CNS) that commonly occurs within one month from antigenic challenge [1]. Post vaccine aetiology was described for 5% of all ADEM cases [2] and several vaccines have been described to be related to this condition [2,3]. The incidence of ADEM onset ranges from 1/106 to 1/105 and may change between different vaccine formulations [3]. Epidemiological data about this adverse event are still missing; this may be due to the rarity of post vaccine ADEM. Several PV programmes have aimed at identifying the onset of adverse reactions to drugs and vaccines. These programmes are valuable as they collect spontaneous reports on large populations

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