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Introduction: The aim of this study was to investigate how age and underlying medical conditions affect the risk of severe outcomes following SARS-CoV-2 infection and how they should be weighed while prioritising vaccinations against COVID-19., Methods: This population-based register study includes all SARS-CoV-2 PCR-test-positive cases until 24 Feb 2021, based on the Finnish National Infectious Diseases Register. The cases were linked to other registers to identify presence of predisposing factors and severe outcomes (hospitalisation, intensive care treatment, death). The odds of severe outcomes were compared in those with and without the pre-specified predisposing factors using logistic regression. Furthermore, population-based rates were compared between those with a given predisposing factor and those without any of the specified predisposing factors using negative binomial regression., Results: Age and various comorbidities were found to be predictors of severe COVID-19. Compared to 60-69-year-olds, the odds ratio (OR) of death was 7.1 for 70-79-year-olds, 26.7 for 80-89-year-olds, and 55.8 for ≥ 90-year-olds. Among the 20-69-year-olds, chronic renal disease (OR 9.4), malignant neoplasms (5.8), hematologic malignancy (5.6), chronic pulmonary disease (5.4), and cerebral palsy or other paralytic syndromes (4.6) were strongly associated with COVID-19 mortality; severe disorders of the immune system (8.0), organ or stem cell transplant (7.2), chronic renal disease (6.7), and diseases of myoneural junction and muscle (5.5) were strongly associated with COVID-19 hospitalisation. Type 2 diabetes and asthma, two very common comorbidities, were associated with all three outcomes, with ORs from 2.1 to 4.3. The population-based rate of SARS-CoV-2 infection decreased with age. Taking the 60-69-year-olds as reference, the rate ratio was highest (3.0) for 20-29-year-olds and < 1 for 70-79-year-olds and 80-89-year-olds., Conclusion: Comorbidities predispose for severe COVID-19 among younger ages. In vaccine prioritisation both the risk of infection and the risk of severe outcomes, if infected, should be considered., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in 9/2010. We estimated the individual-level effectiveness (VE) of PCV10 in children during eight years of vaccine implementation., Methods: Data on invasive pneumococcal disease (IPD) were collected from national, population-based surveillance, and vaccination status from the vaccination register. Vaccine-eligible children were followed from six months of age until end of 2018 (born 6/2010 or later, ages 6-102 months). VE was estimated with three parallel approaches: full cohort, nested case-control and indirect cohort designs adjusting with age-group, sex and calendar year., Results: VE against PCV10 serotype IPD was estimated at 93% (95% credible interval 87-97%), 98% (90-100%) and 100% (98-100%), and against PCV10-related serotypes at 46% (-13-72%), 51% (-24-79%), and 78% (-7-97%), with the full cohort, nested case-control, and indirect cohort designs, respectively. The estimated VE against non-PCV10-related (neither PCV10 nor PCV10-related) serotypes was negative but included zero effectiveness (full cohort VE -67%, -711-52%; nested case-control VE -77%, -929-59%). VE against all IPD was estimated with these two methods at 54% (24-71%) and 61% (26-79%). Over time, VE against PCV10 IPD remained stable but VE against all IPD decreased., Discussion: All designs provided estimates that were concordant with each other, but those with the full cohort design were usually the most precise. PCV10 offered sustained high VE against PCV10-serotype IPD on vaccinated children during the first decade after introduction into the programme., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Finnish Institute for Health and Welfare has received research funding from GlaxoSmithKline Vaccines for the conduct of a nationwide effectiveness trial of the 10-valent pneumococcal conjugate vaccine, and from Pfizer, Inc. and Sanofi Pasteur, Inc. for non-pneumococcal research. HR-K, AAP, MT, and LS are co-investigators in these studies. The other authors have no conflicts to disclose. The current study was entirely publicly funded., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pneumococcal conjugate vaccines reduce the incidence of invasive pneumococcal diseases, pneumonia, acute otitis media (AOM), and antimicrobial prescriptions in children. We investigated the effectiveness of at least one dose of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; GSK) against respiratory tract infections (RTIs) in children under two years of age., Methods: 424 children enrolled in a cluster-randomized, double-blind Finnish Invasive Pneumococcal disease (FinIP) vaccine trial during the years 2009-2010 were actively followed in a prospective cohort study (STEPS study) for RTIs from birth to two years of age. Children received the PHiD-CV10 vaccine, or a control vaccine (hepatitis A or B vaccine) according to an age-specific schedule. Data on RTIs were collected by symptom diaries, clinic visits, an electronic registry on hospitalizations, and by nasal swab samples analyzed for respiratory viruses. We estimated the vaccine effectiveness against all RTI episodes and RTI episodes with or without AOM by comparing the corresponding incidence rates between PHiD-CV10 vaccinated and control children, adjusted for presence of siblings and cluster as a random effect., Results: A total of 3193 RTI episodes were documented after the first vaccination in 368 children with all data available. The majority of the illnesses were upper RTIs caused by rhinovirus. The PHiD-CV10-vaccinated children had lower mean annual rates of all RTI episodes (6.4; 95% confidence interval [CI], 6.0-6.8) and RTI episodes with AOM (1.0; 95% CI, 0.9-1.2) as compared to the control children (7.4; 95% CI, 6.8-8.0 and 1.3; 95% CI, 1.1-1.6, respectively). The vaccine effectiveness was 12% (95% CI, 2-22%) against all RTIs, 23% (95% CI, 0-40%) against RTIs with AOM, and 10% (95% CI, 0-19%) against RTIs without AOM., Conclusions: Vaccination with PHiD-CV10 resulted in lower rates of RTIs in children under two years of age compared to children vaccinated with control vaccine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010. The impact of PCV10 vaccination against invasive pneumococcal disease (IPD) in vaccine-eligible children has been high. We evaluated the long-term impact of PCV10 vaccination against IPD in vaccine-eligible and older, unvaccinated children six years after PCV10 introduction with a special focus on cross-protection against PCV10-related serotypes (serotypes in the same serogroups as the PCV10 types)., Methods: We used data on IPD from the national, population-based surveillance. A target cohort of vaccine-eligible children (born June 2010 or later) was followed from 3 months of age until the end of 2016. For the indirect effect, another cohort of older PCV10-ineligible children was followed from 2012 through 2016. IPD rates were compared with those of season- and age-matched reference cohorts before NVP introduction., Results: Among vaccine-eligible children, the incidence of all IPD decreased by 79% (95% CI 74-83%). There was a statistically significant reduction in the incidence of 6A IPD, but for 19A, the reduction was non-significant and the incidence of 19A increased towards the end of the study period in the older vaccine-eligible children. The increase in non-PCV10 related serotypes was non-significant. In the unvaccinated older children, the incidence of all IPD decreased by 33% (95% CI 8-52%) compared to the reference cohort, and there was no impact on serotype 6A or 19A IPD., Conclusion: Overall, the impact of PCV10 vaccination on IPD was high in vaccine-eligible children, with a major reduction in vaccine-type disease, and without notable replacement by other serotype groups. Our data suggest that PCV10 results in long-lasting direct cross-protection against 6A IPD. For 19A, no net reduction was observed six years after NVP introduction in the vaccine-eligible cohort. The indirect impact on IPD in unvaccinated children sustained., (Copyright © 2018. Published by Elsevier Ltd.)

Background: In 2011, Kenya introduced the 10-valent pneumococcal conjugate vaccine together with a catch-up campaign for children aged <5years in Kilifi County. In a post-vaccination surveillance study based in Kilifi, there was a substantial decline in invasive pneumococcal disease (IPD). However, given the continued circulation of the vaccine serotypes it is possible that vaccine-serotype disease may re-emerge once the effects of the catch-up campaign wear off., Methods: We developed a compartmental, age-structured dynamic model of pneumococcal carriage and invasive disease for three serotype groups: the 10-valent vaccine serotypes and two groups of non-vaccine serotypes based on their susceptibility to mutual competition. The model was calibrated to age- and serotype-specific data on carriage and IPD in the pre-vaccination era and used to predict carriage prevalence and IPD up to ten years post-vaccination in Kilifi. The model was validated against the observed carriage prevalence after vaccine introduction., Results: The model predicts a sustained reduction in vaccine-type pneumococcal carriage prevalence from 33% to 8% in infants and from 30% to 8% in 1-5year olds over the 10-year period following vaccine introduction. The incidence of IPD is predicted to decline across all age groups resulting in an overall reduction of 56% in the population, corresponding to 10.4 cases per 100,000 per year. The vaccine-type IPD incidence is estimated to decline by 83% while non-vaccine-type IPD incidence is predicted to increase by 52%. The model's predictions of carriage prevalence agrees well with the observed data in the first five years post-vaccination., Conclusion: We predict a sustained and substantial decline in IPD through PCV vaccination and that the current regimen is insufficient to fully eliminate vaccine-serotype circulation in the model. We show that the observed impact is likely to be sustained despite waning effects of the catch-up campaign., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: We describe the current epidemiology of acute and chronic hepatitis B infections in Finland. We estimate the total incidence of chronic hepatitis B following from the current incidence of acute infections and the influx of chronic carriers of hepatitis B associated with net immigration. We evaluate the incidence of hepatitis B infections preventable by a universal vaccination programme among infants., Methods: We analysed hepatitis B cases reported to the National Infectious Disease Register during 2004-2012 and used pre-developed methods to adjust for acute asymptomatic infections. We estimated the projected incidence of chronic infection by applying age-specific risks of chronic infection to the estimated incidence of acute infection. We estimated the influx of chronic carriers associated with immigration by utilising data on immigration during 2004-2012 and the WHO regional estimates of carriage prevalence., Results: The estimated incidence of acute hepatitis B infection in Finland, adjusted for asymptomatic infections, was 1.67 per 100,000 per year (95% Crl 1.43-1.94) which is 4.2-fold to the register-based incidence. The estimated lifetime risks of acute and chronic hepatitis B infections were 0.13% and 0.01%, respectively. We estimated that annually seven new chronic infections would result from infections acquired in Finland. These new chronic infections accounted for 1.2% of the total incidence of chronic infections. We estimated that eventually three chronic infections per year would be potentially preventable by a universal infant vaccination programme., Conclusions: Partly due to the fact that hepatitis B infections in neonates and in children are rare, a very limited number of chronic hepatitis B infections resulted from infection acquired within the country. A vast majority of chronic hepatitis B infections occurred among foreign-born persons and were therefore not preventable by a universal infant immunisation programme in Finland. Even with a targeted immunisation programme, the incidence of hepatitis B infection has remained low., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Evaluation of vaccine efficacy for protection against colonisation (VEcol) with Streptococcus pneumoniae and other bacterial pathogens is often based on a cross-sectional study design, in which only one nasopharyngeal sample is obtained per study subject. Here we investigate the feasibility of this study design by investigating a number of practical design problems. Specific questions are related to the timing of colonisation measurement with respect to the time of vaccination, the adjustment for the within-host replacement of vaccine-type colonisation by the non-vaccine type pneumococci, and the impact of multiple serotype colonisation on VEcol estimation. We also discuss the issue of choosing the control vaccine, including comparison of two active pneumococcal vaccines, as well as the sample size and the statistical power of colonisation endpoint trials. In addition, the statistical design with the specific aim to include information about VEcol in the licensure process of new pneumococcal vaccine products is discussed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Evaluating vaccine efficacy for protection against colonisation (VEcol) with bacterial pathogens is an area of growing interest. In this article, we consider estimation of VEcol for colonisation with Streptococcus pneumoniae (the pneumococcus). Colonisation is a common, recurrent and multi-type endpoint that requires both careful definition of the vaccine efficacy parameter and the corresponding method of estimation. We review recent developments in the area and provide practical guidelines for choosing the estimand and the estimation method in trials with a colonisation endpoint. We concentrate on methods that are based on a cross-sectional study design, in which only one nasopharyngeal sample is obtained per study subject., (Copyright © 2013. Published by Elsevier Ltd.)

Evaluation of the effect of new conjugate vaccines on nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) has been based on simple comparisons of the prevalence of carriage in vaccinees and controls. However, the definition and measurement of vaccine efficacy should be based on knowledge of the actual mechanism of the vaccine's effect. According to current knowledge, conjugate vaccines affect acquisition. We propose a simple-to-use method to measure vaccine efficacy against serotype-specific acquisition that needs only cross-sectional measurements of carriage. We demonstrate the use of the method by application to a data set where it is also possible to estimate efficacy against acquisition from longitudinal measurements.

We first studied the immunogenicity of PRP-T and DTwP vaccines in Filipino infants given at 6, 10 and 14 weeks concomitantly with either an aluminum adjuvanted eleven-valent pneumococcal conjugate vaccine (11PncTD) or a meningococcal diphtheria-conjugated vaccine as compared to a control group that received only DTwP/PRP-T. The GMCs and proportions of infants achieving protective antibody concentrations to DTwP and PRP-T vaccine antigens were similar among the groups. In the second phase, the control group received 11PncTD at 18 weeks and the antibody concentrations were measured at 9 months in all children; 11PncTD induced a booster response to diphtheria in the control group. There was no negative interference from concomitant administration of new conjugate vaccines. In contrast, 11PncTD can boost the antibody response to the carrier proteins.

Although Haemophilus influenzae type b (Hib) conjugate vaccines, after licensure in 1987, are now recommended for world-wide use, the duration of protective immunity afforded by them is not known. We therefore assessed the immunogenity at 9-10 years of age in 37 children who had received the first Hib conjugate, PRP-D, in infancy (the Hib-conjugate group) and were now given a dose of Hib polysaccharide (PS) as a test vaccine. The anti-Hib PS antibodies (Hib-ab) were measured before and after this test vaccination, and the values compared to those in 37 control children who had not previously received any Hib vaccine and in 13 children who had received Hib PS vaccine in infancy (the Hib-PS group). Prior to the test vaccination, the Hib-ab concentrations in the Hib-conjugate group were 3.6-fold higher than in the control group. After the test vaccination, the Hib-conjugate group had higher total Hib-ab concentrations, higher proportion of IgG and higher avidity of Hib-ab than the control or the Hib-PS group, suggesting persisting immunological memory in a Hib-c group. A mathematical model, including memory, predicted accurately the Hib-ab concentrations, which are maintained through anamnestic responses to intervening stimuli (Hib or cross-reacting bacteria).