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Objectives: To investigate if receipt of measles-mumps-rubella (MMR) vaccine following the third dose of diphtheria-tetanus-acellular pertussis (DTaP3) is associated with reduced rates of non-targeted infectious disease hospitalisations., Methods: Register based cohort study following 1,397,027 children born in Denmark, Finland, Norway, and Sweden until 2 years of age. Rates of infectious disease hospitalisations with minimum one overnight stay according to time-varying vaccination status were compared using Cox proportional hazards regression analysis with age as the underlying timescale and including multiple covariates. Summary estimates were calculated using random-effects meta-analysis., Results: Compared with DTaP3 and no MMR vaccine, MMR after DTaP3 was associated with reduced rates of infectious disease hospitalisations: aHR was 0.86 (0.83-0.89) in Denmark, 0.70 (0.64-0.75) in Finland, 0.71 (0.68-0.74) in Norway, and 0.71 (0.65-0.77) in Sweden: summary estimate was 0.75 (0.65 to 0.84). A beneficial association was also seen in a negative control exposure analysis (3 vs. 2 DTaP doses): summary estimate aHR was 0.81 (0.75-0.87)., Conclusions: Having MMR as the most recent vaccine was consistently associated with reduced rates of infectious disease hospitalisation. However, bias may account for at least some of the observed association. Randomised controlled trials are warranted to inform the optimal timing of MMR for both its specific and potential non-specific effects., Competing Interests: Declaration of Competing Interest All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/http://www.icmje.org/disclosure-of-interest/ and declare: All authors had financial support from NordForsk (grant number: 83839) and LG had financial support from Odense University Hospital Research fund (A-number: 2519) and the faculty scholarship from the University of Southern Denmark for the submitted work; Finnish Institute for Health and Welfare (THL) has conducted Public-Private Partnership with vaccine manufacturers and has received research funding from Sanofi Inc., Pfizer Inc., and GlaxoSmithKline Biologicals SA. HN, ML, and AAP have been investigators in these studies, but they have received no personal remuneration; no other relationships or activities that could appear to have influenced the submitted work. Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, receives institutional research funding from public and private entities for studies of medicines and vaccines, to and administered by Aarhus University. None of these are relevant to the current study. SS is a salaried employee of Department of Clinical Epidemiology., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

It has been suggested that non-live vaccines may increase susceptibility to non-targeted infections and that such deleterious non-specific effects are more pronounced in girls. We investigated whether receipt of non-live vaccine against human papillomavirus (HPV) was associated with increased risk of infectious disease hospitalization. A nationwide cohort study based on detailed individual-level data from national registries was performed in Denmark, Finland, Norway, and Sweden. The cohort consisted of girls aged 11-14 years in Denmark, Finland, and Norway, and 10-14 years in Sweden. Cox regression, with extensive control for potential confounders, was used to assess whether risk of infectious disease hospitalization with at least one overnight stay differed according to time-varying HPV vaccination status. In total, 754 458 girls were included in the analysis. The infectious disease hospitalization rate (per 10 000 person years) was 44.1 in Denmark, 35.7 in Finland, 37.1 in Norway, and 28.5 in Sweden. Comparing HPV-vaccinated with HPV-unvaccinated person time, the adjusted hazard ratio (95% confidence interval) was 0.81 (0.72, 0.90) in Denmark, 0.69 (0.60, 0.80) in Finland, 0.76 (0.66, 0.88) in Norway, and 0.59 (0.49, 0.71) in Sweden. Decreased risk was observed regardless of number of doses, except in Norway, where risk among girls with only one dose did not differ from risk among unvaccinated girls. Receipt of HPV vaccine was consistently associated with decreased risk of infectious disease hospitalization among girls in the Nordic countries. Our study does not support that HPV vaccines have deleterious non-specific effects., Competing Interests: Declarations. Ethics approval: Ethical approval is not required for registry-based studies in Denmark or Finland. However, the study was approved by the Danish Data Protection Agency and by the Institutional Review Board of the Finnish Institute for Health and Welfare. Study approval was obtained from the Regional Ethics Committee, South-East, in Norway and from the Regional Ethical Review Board, Stockholm, in Sweden. Competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HN and ML are investigators in vaccine-related studies for which the Finnish Institute for Health and Welfare has received funding from GSK, Pfizer and Sanofi Pasteur. Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, the employer of SS, receives institutional research funding from public and private entities for studies of medicines and vaccines, to and administered by Aarhus University. None of these are relevant to the current study. The remaining authors report no relation that could be construed as a conflict of interest. Consent to participate: Informed consent was not obtained from the individuals included in the study, as data were obtained from nationwide health registries to which reporting is mandatory., (© 2024. The Author(s).)

Objectives: Previous studies have shown that vaccination against measles, mumps, and rubella (MMR) may have beneficial non-specific effects, reducing the risk of infections not targeted by the vaccine. We investigated if MMR vaccine given after the third dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP3), was associated with reduced rates of antibiotic treatments., Methods: Register-based cohort study following children from the age of recommended MMR vaccination until age 2 years. We included 831,287 children born in Denmark, Finland, Norway, and Sweden who had received DTaP3 but not yet MMR vaccine. Cox proportional hazards regression with age as the underlying timescale and vaccination status as a time-varying exposure was used to estimate covariate-adjusted Hazard Ratios (aHRs) and inverse probability of treatment weighted (IPTW) HRs of antibiotic treatments. Summary estimates were calculated using random-effects meta-analysis., Results: Compared with only having received DTaP3, receipt of MMR vaccine after DTaP3 was associated with reduced rates of antibiotic treatments in all countries: the aHR was 0.92 (0.91-0.93) in Denmark, 0.92 (0.90-0.94) in Finland, 0.84 (0.82-0.85) in Norway, and 0.87 (0.85-0.90) in Sweden, yielding a summary estimate of 0.89 (0.85-0.93). A stronger beneficial association was seen in a negative control exposure analysis comparing children vaccinated with DTaP3 vs two doses of DTaP., Conclusions: Across the Nordic countries, receipt of MMR vaccine after DTaP3 was associated with an 11% lower rate of antibiotic treatments. The negative control analysis suggests that the findings are affected by residual confounding. Findings suggest that potential non-specific effects of MMR vaccine are of limited clinical and public health importance for the milder infections treated out-of-hospital in the Nordic setting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HN and ML are investigators in vaccine-related studies for which THL has received funding from GSK, Pfizer and Sanofi Pasteur. The remaining authors report no relation that could be construed as a conflict of interest. Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, receives institutional research funding from public and private entities for studies of medicines and vaccines, to and administered by Aarhus University. None of these are relevant to the current study. SS is a salaried employee of Department of Clinical Epidemiology., (Copyright © 2024 The Authors. Published by Elsevier India Pvt Ltd. All rights reserved.)

Background: In a previous cohort study of 4-year-old Danish children, revaccination with the live measles-mumps-rubella vaccine (MMR) was associated with a 16% reduction in the rate of hospitalization lasting two days or longer for non-measles-mumps-rubella infections., Aim: To examine if the introduction of revaccination with MMR at 4 years of age in Denmark (spring 2008) and at 7-9 years of age in Sweden (autumn 2009), at a time when there was virtually no measles, mumps or rubella cases, was associated with a reduction in the rate of hospitalization-for-infection lasting two days or longer at the population level., Methods: We included 4-year-olds in Denmark and 7-9-year-olds in Sweden. We obtained the number of hospitalization-for-infection lasting two days or longer from nationwide hospital registers. Person-years at risk were approximated from population statistics for each season and year. We performed an interrupted time series analysis using Poisson regression to estimate the change in hospitalization incidence rates following the introduction of MMR revaccination, adjusting for seasonality. We also performed analyses with control series (3-year-olds in Denmark and 4-year-olds in Sweden)., Results: Comparing the incidence of hospitalization-for-infection lasting two days or longer after the introduction of MMR revaccination with the expected level without an introduction of MMR revaccination resulted in an incidence rate ratio of 1.07 (95% confidence interval [CI] = 0.89-1.28) for 4-year-olds in Denmark and 0.89 (95% CI = 0.77-1.02) for 7-9-year-olds in Sweden in analyses without controls. Analyses with controls gave similar results., Conclusion: This population-level study of the introduction of MMR revaccination in Denmark and Sweden had inadequate power to confirm or refute the findings from an individual-level Danish study of an association between MMR revaccination and a lower incidence rate of hospitalization-for-infection lasting two days or longer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HN is an employee of the Finnish Institute for Health and Welfare, which has received research funding from GlaxoSmithKline, Sanofi-Pasteur and Pfizer for clinical trials. All other authors report no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)