Vaccine safety, vaccine effectiveness and other determinants for successful immunisation programmes

The studies in this thesis examined several key determinants for successful uptake of vaccinations in the Nordic countries, with focus on vaccine safety and vaccine effectiveness. In study I, we investigated whether disease history is a risk factor for narcolepsy after vaccination with the pandemic influenza vaccine, Pandemrix, which was circulated between 2009 and 2010. The results showed that there was no association between disease history and narcolepsy. We also found evidence for confounding by indication, with a larger number of prescriptions/diagnoses for nervous system disorders and mental and behavioural disorders when we did not adjust for the timing of vaccination or vaccination status. This could suggest that early cases of narcolepsy were initially misdiagnosed prior to narcolepsy diagnosis.

In study II, we investigated the effect of the quadrivalent humanpapillomavirus (qHPV) vaccine on genital condyloma by the number of doses and time between doses. This cohort study followed young Swedish girls ages 10-27 for HPV vaccination and condyloma. The results showed that the greatest protection against condyloma was seen after two doses of qHPV vaccine with 4-7 months between dose one and two. We also found that girls, who initiated vaccination at a younger age, had a greater protection against condyloma.

The results from these studies show just how complex the improvement of vaccination programmes can be. On one hand, we see the difficulties in assessing what went wrong following the introduction of a vaccine into a population– it is not always possible to predict a rare outcome from a mass vaccination campaign, so vaccine safety becomes a paramount concern from a societal perspective. We also see what happens when a vaccine proves its effectiveness in a population-based setting to the point where the number of doses can be reduced without compromising its effectiveness. Improving the vaccination programmes is, therefore, a complex multifactorial problem with many key determinants that can change depending on the vaccine in question e.g. mass vaccination versus routine vaccination.

List of scientific papers

I. Lamb F, Ploner A, Fink K, et al. No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination. PLoS ONE. 2016;11(4):e0154296.
https://doi.org/10.1371/journal.pone.0154296

II. Lamb F, Herweijer E, Ploner A, et al. Timing of two versus three doses of quadrivalent HPV vaccine and associated effectiveness against condyloma in Sweden: a nationwide cohort study. BMJ Open. 2017;7:e015021.
https://doi.org/10.1136/bmjopen-2016-015021