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https://www.sciencedirect.com/science/article/pii/S0264410X20308434#!
Vaccine
Available online 2 July 2020
Are unexplained adverse health events following HPV vaccination associated with infectious mononucleosis? – A Danish nationwide matched case-control study
Lene Wulff KrogsgaardaIda GlodeHelmuthbBodil HammerBechaOleguerPlana-RipollcTina HovgaardLützenaHanne ThangVestergaarddKarsten DalsgaardBjerreeReimar WernichThomsenfKåreMølbakghDorteRyttera
a
Research Unit for Epidemiology, Department of Public Health, Aarhus University, Denmark
b
Department of Infectious Diseases Epidemiology, Statens Serum Institut, Copenhagen, Denmark
c
National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus University, Denmark
d
Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark
e
Division of Infectious Disease Preparedness, Data Analysis and Integration, Statens Serum Institut, Copenhagen, Denmark
f
Department of Clinical Epidemiology, Aarhus University Hospital, Denmark
g
Division of Infectious Disease Preparedness, Statens Serum Institut, Copenhagen, Denmark
h
Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
Received 3 February 2020, Revised 12 June 2020, Accepted 18 June 2020, Available online 2 July 2020.
https://doi.org/10.1016/j.vaccine.2020.06.057
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Abstract
Background
In Denmark, the acceptance of the HPV vaccination program has been threatened by reports of suspected adverse events. Epstein Barr Virus (EBV) infection is associated with symptoms of long-lasting tiredness and may be misinterpreted as HPV vaccine adverse events. The main aim of this study was to examine if EBV infection around time of HPV vaccination was a risk factor for later suspected vaccine adverse events.
Methods
The study was a nationwide register-based matched case-control study. Cases were females vaccinated against HPV in the period 2011 throughout 2017 with suspected adverse events. For each case, five HPV vaccinated females without suspected adverse events were selected. Information about EBV infection was obtained from the Danish Microbiology Database and assessed for three time periods: (1) before first HPV vaccination, (2) around time of HPV vaccination, and (3) any time during the study period 2010–2017. Multiple logistic regression was used to estimate the association between EBV and suspected adverse events.
Results
We identified 1217 cases, matched to 6085 controls. A higher proportion of cases (38; 3.1%) than controls (31; 0.5%) were tested for EBV around time of HPV vaccination and cases had elevated odds for testing both EBV positive (OR 4.52, 95% CI 2.68–7.63) and EBV negative (OR 20.99, 95% CI 5.81–75.79). Only five females were classified with acute/recent EVB infection in this period.
Conclusion
Misinterpretation of EBV infection late symptoms is not a leading explanation for Danish females experiencing suspected adverse events after HPV vaccination. Although EBV cannot be excluded as an explanatory factor for a very small proportion of suspected adverse events, the findings are more likely explained by protopathic bias, i.e. the fact that a larger proportion of females suspecting adverse events are tested for EBV.
Keywords
HPV vaccination
Mononucleosis
Epstein Barr Virus infection
Suspected adverse events
Register-based
Case-control study