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

Very little influenza in the WHO European Region during the 2020/21 season, weeks 40 2020 to 8 2021

Between weeks 40 2020 and 8 2021, the World Health Organization European Region experienced a 99.8% reduction in sentinel influenza virus positive detections (33/25,606 tested; 0.1%) relative to an average of 14,966/39,407 (38.0%; p < 0.001) over the same time in the previous six seasons. COVID-19 pandemic public health and physical distancing measures may have extinguished the 2020/21 European seasonal influenza epidemic with just a few sporadic detections of all viral subtypes. This might possibly continue during the remainder of the influenza season.ECDC and WHO internal fundsS

No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination

OBJECTIVES: To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy.METHODS: Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts. Controls, selected from the total population register, were matched to cases on age, gender, MSLT-referral date and county of residence. Disease history (prescriptions and diagnoses) and vaccination history was collected through telephone interviews and population-based healthcare registers. Conditional logistic regression was used to investigate disease history before A(H1N1)pdm09 vaccination as a risk-factor for narcolepsy.RESULTS: In total, 72 narcolepsy cases and 251 controls were included (range 3-69 years mean19-years). Risk of narcolepsy was increased in individuals with a disease history of nervous system disorders (OR range = 3.6-8.8) and mental and behavioural disorders (OR = 3.8, 95% CI 1.6-8.8) before referral. In a second analysis of vaccinated individuals only, nearly all initial associations were no longer statistically significant and effect sizes were smaller (OR range = 1.3-2.6). A significant effect for antibiotics (OR = 0.4, 95% CI 0.2-0.8) and a marginally significant effect for nervous system disorders was observed. In a third case-only analysis, comparing cases referred before vaccination to those referred after; prescriptions for nervous system disorders (OR = 26.0 95% CI 4.0-170.2) and ADHD (OR = 35.3 95% CI 3.4-369.9) were statistically significant during the vaccination period, suggesting initial associations were due to confounding by indication.CONCLUSION: The findings of this study do not support disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy

Systematic review of outbreaks of COVID-19 within households in the European region when the child is the index case

ObjectivesThis systematic review aims to identify the secondary attack rates (SAR) to adults and other children when children are the index cases within household settings.MethodsThis literature review assessed European-based studies published in Medline and Embase between January 2020 and January 2022 that assessed the secondary transmission of SARS-CoV-2 within household settings. The inclusion criteria were based on the Population, Exposure, Outcome framework for systematic reviews. Thus, the study population was restricted to humans within the household setting in Europe (population), in contact with paediatric index cases 1-17 years old (exposure) that led to the transmission of SARS-CoV-2 reported as either an SAR or the probability of onward infection (outcome).ResultsOf 1819 studies originally identified, 19 met the inclusion criteria. Overall, the SAR ranged from 13% to 75% in 15 studies, while there was no evidence of secondary transmission from children to other household members in one study. Evidence indicated that asymptomatic SARS-CoV-2 index cases also have a lower SAR than those with symptoms and that younger children may have a lower SAR than adolescents (>12 years old) within household settings.ConclusionsSARS-CoV-2 secondary transmission from paediatric index cases ranged from 0% to 75%, within household settings between January 2020 and January 2022, with differences noted by age and by symptomatic/asymptomatic status of the index case. Given the anticipated endemic circulation of SARS-CoV-2, continued monitoring and assessment of household transmission is necessary

A systematic review on outbreaks of COVID-19 among children within households in the European region

Objectives This systematic review aims to identify the secondary attack rates (SAR) to adults and other children when children are the index cases within household settings.Methods This literature review assessed European-based studies published in Medline and Embase between January 2020 and January 2022 that assessed the secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within household settings. The inclusion criteria were based on the PEO framework (P-Population, E-Exposure, O-Outcome) for systematic reviews. Thus, the study population was restricted to humans within the household setting in Europe (population), in contact with pediatric index cases 1–17 years old (exposure) that led to the transmission of SARS-CoV-2 reported as either a SAR or the probability of onward infection (outcome).Results Of 1,819 studies originally identified, 25 met the inclusion criteria. Overall, the SAR ranged from 13% to 75% in 23 studies, while there was no evidence of secondary transmission from children to other household members in two studies. Evidence indicated that asymptomatic SARS-CoV-2 index cases also have a lower SAR than those with symptoms and that younger children may have a lower SAR than adolescents (>12 years old) within household settings.Conclusions SARS-CoV-2 secondary transmission from paediatric index cases ranged from 0% to 75%, within household settings between January 2020 and January 2022, with differences noted by age and by symptomatic/asymptomatic status of the index case. Given the anticipated endemic circulation of SARS-CoV-2, continued monitoring and assessment of household transmission is necessary

The cost of the COVID-19 pandemic vs the cost-effectiveness of mitigation strategies in EU/UK/OECD: a systematic review

Objectives: The economic burden of COVID-19 pandemic is substantial, with both direct and indirect costs playing a significant role. Design: A systematic literature review was conducted to estimate the cost of the COVID-19 pandemic and the cost-effectiveness of pharmaceutical or non-pharmaceutical interventions. All cost data were adjusted to the 2021 Euro, and interventions compared with null.Data Sources: Ovid Medline and EMBASE were searched from January 2020 through 22nd of April 2021. Eligibility Criteria: Studies regarding COVID-19 outbreak or public health preparedness measures or interventions with outcome measures related to the direct and indirect costs for disease and preparedness and/or response for the EU/EEA/UK and OECD countries of all relevant epidemiological designs which estimate cost within the selected timeframe.Data extraction and synthesis: Studies were searched, screened, and coded independently by two reviewers with high measure of inter-rater agreement. Data were extracted to a predefined data extraction sheet. The risk of bias was assessed using the Consensus on Health Economic Criteria checklist.Results: We included data from 41 economic studies. Ten studies evaluated the cost of the COVID-19 pandemic, while 31 assessed the cost-benefit of public health surveillance, preparedness, and response measures. Overall, the economic burden of the COVID-19 pandemic was found to be substantial. Community screening, bed provision policies, investing in personal-protective-equipment and vaccination strategies were cost-effective. Physical distancing measures were associated with health benefits; however, their cost-effectiveness was dependent on the duration, compliance and the phase of the epidemic in which it was implemented. Conclusions: COVID-19 pandemic is associated with substantial short-term and long-term economic costs to healthcare systems, payers, and societies, while interventions including testing and screening policies, vaccination and physical distancing policies were identified as those presenting cost-effective options to deal with the pandemic, dependent on population vaccination and the Re at the stage of the pandemic

Increasing risk of breakthrough COVID-19 in outbreaks with high attack rates in European long-term care facilities, July to October 2021

We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July-October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8-52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.S

Is there an increasing trend in domestic Salmonella infection in Sweden between 1997-2008.

An analysis of the recorded cases of Salmonella in Sweden indicates that there was no significant increase between 1997-2008, including or excluding outbreaks. The most common serotypes of Salmonella in Sweden were found to be S. Typhimurium and S. Enteritidis, with only the incidence of S. Typhimurium significantly increasing between 1997-2008. The most common phage types identified were S. Typhimurium 40, 104, NST and NT, with both S. Typhimurium NST and NT found to be significantly increasing. The season that has the greatest incidence of salmonellosis is the summer, from June to August. The number of Salmonella outbreaks occurring each year was found to be statistically increasing, this was however almost certainly due to a change in cluster detection techniques introduced in 2008, since a re-analysis excluding this year found no significant increase between 1997-2007. The most common serotypes that caused outbreaks during the study period were found to be S. Typhimurium, S Enteritidis, S. Saintpaul, S. Stanley and S. Hadar. There was no relationship found between the serotypes, with the number of cases not being proportional to the number of outbreaks. Despite these positive results, it should be of concern that evidence was found indicating that the sources of Salmonella infection appear to be changing, with an increase in the presence of ‘non-domestic’ serotypes.

Very little influenze in the WHO European Region during the 2020/21 season, weeks 40 2020 to 8 2021

Between weeks 40 2020 and 8 2021, the World Health Organization European Region experienced a 99.8% reduction in sentinel influenza virus positive detections (33/25,606 tested; 0.1%) relative to an average of 14,966/39,407 (38.0%; p < 0.001) over the same time in the previous six seasons. COVID-19 pandemic public health and physical distancing measures may have extinguished the 2020/21 European seasonal influenza epidemic with just a few sporadic detections of all viral subtypes. This might possibly continue during the remainder of the influenza season

Very little influenza in the WHO European Region during the 2020/21 season, weeks40 2020 to 8 2021

Between weeks40 2020 and 8 2021, the World Health Organization European Region experienced a 99.8% reduction in sentinel influenza virus positive detec-tions (33/25,606 tested; 0.1%) relative to an average of 14,966/39,407 (38.0%; p<0.001) over the same time in the previous six seasons. COVID-19 pandemic public health and physical distancing measures may have extinguished the 2020/21 European seasonal influenza epidemic with just a few sporadic detections of all viral subtypes. This might possibly continue dur-ing the remainder of the influenza season. We study features of influenza epidemiology in the World Health Organization (WHO) European Region from week40 2020 to week8 2021, a period when in usual seasons the highest influenza activity (peak of seasonal epidemic) would be expected. Results are compared to those of the previous six seasons (2014/15-2019/20)