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Vaccination and demyelination : Is there a link? Examples with anti-hepatitis B and papillomavirus vaccines

Abstract : While vaccines represent a great achievement for public health, the risk of adverse effects is a real threat for vaccine acceptability by both the population and healthcare professionals. France still ranks as the country having the highest vaccine defiance. This often turned into poor vaccination coverages. This origin of this mistrust in vaccines is probably related to the intense polemic around anti-hepatitis B (HB) vaccination and the risk of multiple sclerosis in the 1990’s. The main aim of this thesis was to assess the putative link between vaccination and demyelinating disorders by considering two examples: anti-HB and anti-papillomavirus (HPV) vaccines. For both vaccines, methods adopted a stepwise evidence-based approach. Hypothesis generation was based on evidence regarding the biological plausibility, the published case reports, the disproportionality analyses conducted in the US Vaccine Adverse Event Reporting System (VAERS) and the analysis of signals detected by spontaneous reporting systems, if any. For the research question centered on the anti-HB vaccination, observed-to-expected analyses based on all confirmed cases reported to the French pharmacovigilance in the 1990’s were also conducted. Systematic reviews of all individual studies having assessed the possible association between demyelination and either anti-HB or HPV vaccines were then conducted while meta-analyses brought pooled risk estimates of all evidence published so far. Results were non-conclusive for both vaccines. For anti-HB vaccination, several elements could give credence to an association with central demyelination: a weak and indirect biological plausibility, the analysis of the French signal detected in the 1990’s which revealed a complete disjunction between the target and the joint populations, and the results of the disproportionality analyses in VAERS. Nevertheless, neither the meta-analysis nor the observed-to-expected analyses (although might be easily reversed by a moderate degree of underreporting), provided statistically significant findings. If the excess risk actually existed, it would be weak and would be a concern for adults only. The current recommendations which are minimizing the probability of the French population to be exposed at an adult age, are therefore more than justified. For the anti-HPV vaccination, after reviewing all materials available, the risk of central demyelination seems, at this date, unlikely. Nevertheless, a doubt remains regarding a possible excess risk of Guillain Barré Syndrome (GBS) in the follow of an anti-HPV immunization. More specific studies would be needed, although the rarity of this event renders its evaluation difficult. From the studies already conducted, it was estimated that this excess risk, if any, would be lower than 1 per 1,000,000 doses sold. To conclude, a strong association with a risk of central demyelination can be ruled out for both vaccines, making the benefit and risk balances still largely positive for both products if used in their current target populations. In that context, an independent, clear and scientifically-based communication is the key element to promote vaccination programmes and to generate the confidence and adherence of the general population. Political decisions also carry a heavy responsibility in ensuring trust towards vaccination programmes, as the suspension of national immunization campaigns which could have long-lasting deleterious consequences. The future of vaccine pharmacovigilance could rely on the implementation of a collaborative GP-patient network-based solution using SMS and smartphones, as already experimented in Australia. While collecting potential adverse effects of vaccines, it would also be a unique opportunity to place the patients at the heart of the surveillance system, giving them a voice and potentially contributing to restore their confidence in vaccines and even, in the decision-makers in the field of public health.
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Julie Mouchet Le Moal. Vaccination and demyelination : Is there a link? Examples with anti-hepatitis B and papillomavirus vaccines. Human health and pathology. Université de Bordeaux, 2019. English. ⟨NNT : 2019BORD0015⟩. ⟨tel-02134582⟩

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