Hybrid Immunity Improves the Immune Response after the Fourth COVID-19 Vaccine Dose in Individuals with Medical Conditions Predisposing to Severe COVID-19.

Data on immune responses following COVID-19 booster vaccinations and subsequent infections in the immunocompromised are limited. We studied antibody responses after the fourth dose and subsequent infections to define patient groups benefiting most from boosters. Fourth vaccine (booster) doses were, in Finland, first recommended for severely immunocompromised individuals, whom we invited to participate in our study in 2022. We assessed spike protein-specific IgG and neutralizing antibodies (NAb) against the ancestral and Omicron BA.1 strains one month after the fourth dose from 488 adult participants and compared them to the levels of 35 healthy controls after three doses. We used Bayesian generalized linear modeling to assess factors explaining antibody levels and assessed vaccine-induced and hybrid immunity six months after the last vaccine dose. Chronic kidney disease (CKD) and immunosuppressive therapy (IT) were identified as factors explaining sub-optimal antibody responses. The proportion of participants with a normal antibody response and NAbs was significantly lower regarding CKD patients compared to the controls. By the 6-month sampling point, one-third of the participants became infected (documented by serology and/or molecular tests), which notably enhanced antibody levels in most immunocompromised participants. Impaired antibody responses, especially NAbs against the Omicron lineage, suggest limited protection in individuals with CKD and highlight the need for alternative pharmaceutical preventive strategies. Vaccination strategies should take into account the development of robust hybrid immunity responses also among the immunocompromised.

Factors associated with parental Human Papillomavirus (HPV) vaccination intention of daughter: A national survey in Finland.

BACKGROUND: Human papillomavirus (HPV) vaccines are offered free of charge in Finland to 10-12-year-old children. Nationally about 80% of girls are vaccinated, with regional differences in first dose coverage varying from 62% to 82% in girls born in 2011. This study examined the factors associated with HPV vaccination intention. Furthermore, we assessed the realisation of HPV vaccination among the daughters of the participating parents. METHODS: A web-based survey was conducted for randomly selected parents of girls (N = 6 465) aged 10 to 14 years of age. Data was collected in February and March 2022 in five Finnish high and low coverage municipalities. The national vaccination register was employed to assess realisation of vaccination. RESULTS: Participation rate was 13.7% (n = 883 parents). Almost all parents were aware of the association between HPV and cervical cancer, but only one fifth was aware of other diseases associated with HPV. Adherence to the national vaccination programme, parents' mother tongue, and trusting in official information were associated with positive vaccination intention. The most often reported reason for non-vaccination was fear of adverse effects (22%). Overall, parental attitudes towards HPV vaccination were positive, with 83% of parents indicating their daughter had received or will receive the vaccination. Vaccination realisation was subsequently examined and 88% of the daughters were vaccinated. CONCLUSIONS: Despite low knowledge of HPV-related diseases overall, majority of parents held a positive intention to vaccinate their daughter. Realisation of intention was high in our study, higher than the national uptake. Foreign-origin parents had lower intention to vaccinate their daughters. As information on HPV and its vaccine is available in 11 languages, there is a need to re-think accessibility. In-depth interviews are needed to better explore the reasons behind non-vaccination.

Factors associated with parental intention to vaccinate their child against influenza, Finland, February to March, 2022: a web-based survey.

BackgroundInfluenza vaccination for children aged 6 months to 6 years is included in the national vaccination programme in Finland. Although all vaccines in the programme are free of charge, national coverage of influenza vaccination among children under 3 years and 3-6 years during 2020/21 was 43% and 35% respectively, with regional differences.AimTo assess factors underlying parental vaccination intention in order to increase influenza vaccine uptake among children.MethodsWe conducted a web-based survey among parents (n = 17,844) of randomly selected eligible children (aged 6 months-6 years) in February-March 2022 in five Finnish municipalities from regions of high and low coverage. Logistic regressions were used to determine associations between vaccination intention and e.g. sociodemographic factors, attitudes and knowledge. Linkage to the national vaccination register was used to confirm realisation of vaccination intention after the study.ResultsParticipation rate was 13% (n = 2,322 parents). Influenza knowledge, trust in official information, responding parent's education level, adherence to the vaccination programme, number of children and changes in attitudes towards vaccination since COVID-19 were all associated with intention to vaccinate. Vaccination intention for children was 64%, and realised vaccination 51%.ConclusionDespite the low participation rate, both vaccinated and unvaccinated children were represented. Influenza vaccine uptake is not dependent on a single factor. Our results identified the need for open dialogue between parents and healthcare professionals, as the lack of vaccine being offered by healthcare professionals was the most reported reason for not vaccinating.

Decline in varicella cases contacting primary health care after introduction of varicella vaccination in Finland - A population-based register study.

A two-dose varicella vaccination programme at the age of 18 months and 6 years started in September 2017 in Finland with catch-up vaccinations, based on earlier modelling results, for children <12 years (born in 2006 or later) with no history of varicella. Nationwide population-based register data were used to assess the age-specific vaccination coverage and the annual incidence rates of varicella cases contacting public primary health care in 2014-2020. Age-specific incidence rates after (2022) and before (2014-2016) the implementation of the vaccination programme was compared by incidence rate ratios (IRR) with 95 % confidence interval. In 2019-2022, the first-dose coverage of varicella vaccination among children following the routine vaccination programme ranged from 85 to 87 % (children born in 2016 or later). The second-dose coverage was 58 % for the children born in 2016. The coverage of the catch-up vaccinations ranged from 18 % (children born in 2006) to 82 % (children born in 2015) for the first dose and from 10 % to 64 % for the second dose in the respective birth cohorts. In 2022, compared to the pre-vaccination period (2014-2016) the annual incidence rate of varicella cases contacting public primary health care declined in all age groups. The reduction ranged from 92 % to 98 % among the children eligible for the vaccinations (born 2006 or later). The 87 % reduction in the incidence rate among the unvaccinated children < 1 year suggests the indirect effect of the vaccinations. Introducing varicella vaccinations with catch-up was associated with rapid reduction in the varicella cases contacting primary health care in all ages. However, the coverage of the routine programme needs to be improved further as presently susceptibles accumulate and enable thus further outbreaks in coming decades.

Nationwide health, socio-economic and genetic predictors of COVID-19 vaccination status in Finland.

Understanding factors associated with COVID-19 vaccination can highlight issues in public health systems. Using machine learning, we considered the effects of 2,890 health, socio-economic and demographic factors in the entire Finnish population aged 30-80 and genome-wide information from 273,765 individuals. The strongest predictors of vaccination status were labour income and medication purchase history. Mental health conditions and having unvaccinated first-degree relatives were associated with reduced vaccination. A prediction model combining all predictors achieved good discrimination (area under the receiver operating characteristic curve, 0.801; 95% confidence interval, 0.799-0.803). The 1% of individuals with the highest predicted risk of not vaccinating had an observed vaccination rate of 18.8%, compared with 90.3% in the study population. We identified eight genetic loci associated with vaccination uptake and derived a polygenic score, which was a weak predictor in an independent subset. Our results suggest that individuals at higher risk of suffering the worst consequences of COVID-19 are also less likely to vaccinate.

Efficacy and effectiveness of case isolation and quarantine during a growing phase of the COVID-19 epidemic in Finland.

Based on data collected as part of the contact tracing activity of the City of Helsinki Epidemiological Operations Unit, we evaluated the efficacy and effectiveness of isolating SARS-CoV-2 cases and quarantining their exposed contacts during a mildly growing phase of the COVID-19 epidemic in Finland in autumn 2020. Based on the observed symptom-to-symptom intervals in 1016 pairs of primary and secondary cases, we estimated that without case isolation or quarantine 40[Formula: see text] (90[Formula: see text] credible interval, CI 25-59) of transmission would have occurred on the day of or after symptom onset. One third of SARS-CoV-2 cases (N = 1521) had initially been quarantined, with a self-reported time until isolation (quarantine) of 0.8 days before symptom onset. This delay translates into an efficacy of 50[Formula: see text] (90[Formula: see text] CI 40-63) of averting secondary infections per quarantined case. Due to later isolation (mean 2.6 days after symptoms), the efficacy was smaller (24[Formula: see text]; 90[Formula: see text] CI 12-41) in those two third of the cases (N = 3101) whose isolation was prompted by their symptoms, i.e. without being previously quarantined. At the population level, we evaluated the effectiveness of case isolation and quarantine on the growth rate of the COVID-19 epidemic in the autumn of 2020. Under a wide range of underlying assumptions, the rate would have been at least 2 times higher without case isolation and quarantine. The numbers needed to isolate or quarantine to prevent one secondary case were 2 and 20, respectively.

High vaccine effectiveness against severe COVID-19 in the elderly in Finland before and after the emergence of Omicron.

BACKGROUND: The elderly are highly vulnerable to severe COVID-19. Waning immunity and emergence of Omicron have caused concerns about reduced effectiveness of COVID-19 vaccines. The objective was to estimate vaccine effectiveness (VE) against severe COVID-19 among the elderly. METHODS: This nationwide, register-based cohort analysis included all residents aged 70 years and over in Finland. The follow-up started on December 27, 2020, and ended on March 31, 2022. The outcomes of interest were COVID-19-related hospitalization and intensive care unit (ICU) admission timely associated with SARS-CoV-2 infection. VE was estimated as one minus the hazard ratio comparing the vaccinated and unvaccinated and taking into account time since vaccination. Omicron-specific VE was evaluated as the effectiveness observed since January 1, 2022. RESULTS: The cohort included 896,220 individuals. Comirnaty (BioNTech/Pfizer) VE against COVID-19-related hospitalization was 93% (95% CI 89-95%) and 85% (95% CI 82-87%) 14-90 and 91-180 days after the second dose; VE increased to 95% (95% CI 94-96%) 14-60 days after the third dose. VE of other homologous and heterologous three dose series was similar. Protection against severe COVID-19 requiring ICU treatment was even better. Since January 1, 2022, Comirnaty VE was 98% (95% CI 92-99%) and 92% (95% CI 87-95%) 14-90 and 91-180 days after the second and 98% (95% CI 95-99%) 14-60 days after the third dose. CONCLUSIONS: VE against severe COVID-19 is high among the elderly. It waned slightly after two doses, but a third restored the protection. VE against severe COVID-19 remained high even after the emergence of Omicron.

Health care costs related to hepatitis B in Finland are mostly due to chronic infections: a register-based study.

BACKGROUND: Finland is among the countries with low hepatitis B endemicity. We evaluate the hepatitis B-related disease and economic burden needed for evidence-based immunisation policy decision-making. METHODS: Hepatitis B-related cases in 2004-2012 were retrieved from population-based nationwide registers. We evaluated the incidence, health care resource use, health care costs, and life years lost due to hepatitis B-related outcomes. An episode of care was constructed from each individual's hepatitis B-related events retrieved from individually linkable registers. RESULTS: The mean health care costs per an acute hepatitis B case were €450 (SD 240), €2030 (SD 350), and €5400 (SD 3370) in those aged 0-14, 15-64, and ≥65 years, respectively. For chronic infection, the mean cost per case among Finnish-born individuals was €990 and among foreign-born €1360. The costs per case of liver cirrhosis were €15,350 and liver cancer €19,080. In addition, the annual antiviral medication costs per case receiving antiviral medication were €4710 to €5530. Annually <10% of the chronic and approximately 20% of liver cirrhosis cases received antiviral medication. We identified annually 21 acute, 264 chronic, three liver cirrhosis, and four liver cancer cases and 63.7 life years lost due to hepatitis B per 5.3 million inhabitants. The total annual health care costs were €1.2 million of which 60% were antiviral medication costs and 86% accounted for chronic hepatitis B. CONCLUSIONS: When planning prevention of hepatitis B infection, it is pivotal to notice that the overall disease and economic burden due to hepatitis B is mostly due to chronic infection.

Predictors of hospitalisation and death due to SARS-CoV-2 infection in Finland: A population-based register study with implications to vaccinations.

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.

The indirect effect of mRNA-based COVID-19 vaccination on healthcare workers' unvaccinated household members.

Mass vaccination is effective in reducing SARS-CoV-2 infections among vaccinated individuals. However, it remains unclear how effectively COVID-19 vaccines prevent people from spreading the virus to their close contacts. Using nationwide administrative datasets on SARS-CoV-2 infections, vaccination records, demographics, and unique household IDs, we conducted an observational cohort study to estimate the direct and indirect effectiveness of mRNA-based COVID-19 vaccines in reducing infections among vaccinated healthcare workers and their unvaccinated household members. Our estimates for adults imply indirect effectiveness of 39.1% (95% CI: -7.1% to 65.3%) two weeks and 39.0% (95% CI: 18.9% to 54.0%) eight weeks after the second dose. We find that the indirect effect of mRNA-based COVID-19 vaccines within households is smaller for unvaccinated children than for adults and statistically insignificant. Here, we show that mRNA-based COVID-19 vaccines are associated with a reduction in SARS-CoV-2 infections not only among vaccinated individuals but also among unvaccinated adult household members in a real-world setting.

Cohort study of Covid-19 vaccine effectiveness among healthcare workers in Finland, December 2020 - October 2021.

Recently, Covid-19 vaccine effectiveness has decreased especially against mild disease due to emergence of the Delta variant and waning protection. In this register-based study among healthcare workers in Finland, the vaccine effectiveness of two-dose mRNA vaccine series against SARS-CoV-2 infection decreased from 82% (95% CI 79-85%) 14-90 days after vaccination to 53% (43-62%) after 6 months. Similar trend was observed for other series. Waning was not observed against Covid-19 hospitalization. These results facilitate decision-making of booster doses for healthcare workers.

Effectiveness of vaccination against SARS-CoV-2 infection and Covid-19 hospitalisation among Finnish elderly and chronically ill-An interim analysis of a nationwide cohort study.

BACKGROUND: In Finland, both mRNA and adenovirus vector (AdV) Covid-19 vaccines have been used after the vaccination campaign started on December 27, 2020. Vaccination of the elderly and chronically ill was prioritized and the interval between doses set to 12 weeks. The objective of this interim analysis was to evaluate first and second dose vaccine effectiveness (VE) in a real-world setting. METHODS: During the first five months of the campaign, a register-based cohort study was conducted in the Finnish elderly aged 70+ years and those aged 16-69 years with medical conditions predisposing to severe Covid-19 (chronically ill). Using Cox regression, VE against SARS-CoV-2 infection and Covid-19 hospitalisation was estimated comparing the hazard in the vaccinated with that in the unvaccinated. RESULTS: The cohorts included 901092 elderly (89% vaccinated) and 774526 chronically ill (69% vaccinated) individuals. Three weeks after the first dose, mRNA VE against infection was 45% (95% confidence interval, 36-53%) and 40% (26-51%) in elderly and chronically ill; mRNA VE against hospitalisation was 63% (49-74%) and 82% (56-93%). In chronically ill, AdV VE was 42% (32-50) and 62% (42-75%) against infection and hospitalisation, respectively. One week after the second dose, mRNA VE against infection was 75% (65-82%) and 77% (65-85%) in elderly and chronically ill; mRNA VE against hospitalisation was 93% (70-98%) and 90% (29-99%). CONCLUSIONS: Covid-19 vaccines protect against SARS-CoV-2 infection and Covid-19 hospitalisation. A single dose provides moderate protection in elderly and chronically ill, although two doses are clearly superior.

Social Distancing and SARS-CoV-2 Transmission Potential Early in the Epidemic in Finland.

BACKGROUND: Information about social mixing patterns under heavy social distancing is needed to model the impact of nonpharmaceutical interventions on SARS-CoV-2 transmission. METHODS: We conducted a survey on daily person-to-person contacts during the early phase of the SARS-CoV-2 epidemic in Finland, one month after strong social distancing measures had been introduced nationwide. We defined a contact as exchange of at least a few words in proximity of another person. We also considered physical ("skin-to-skin") contacts separately. Based on 3,171 reported contacts by 1,320 participants of 1-79 years of age, we estimated age-stratified contact matrices essential in modeling virus transmission. RESULTS: Compared with contacts during prepandemic conditions, as learned from the Finnish part of the Polymod study, there was a 72% (95% credible interval, CI = 71, 74) reduction in the daily number of all contacts and a 69% (95% CI = 66, 73) reduction in the daily number of physical contacts in April 2020. The largest reduction, of almost 90%, occurred in physical contacts by individuals more than 70 years of age. The estimated reduction in the transmission potential of the virus attributable solely to reduced contact frequencies varied between 59% (whole population; physical contacts; 95% CI = 52, 68) and 77% (over 20-year olds; physical contacts; 95% CI = 70, 89). CONCLUSIONS: We surmise that the large reduction in the daily numbers of social contacts in the early part of the SARS-CoV-2 epidemic in Finland was likely a major contributor to the steady decline of the epidemic in the country since early April.

Success ofrotavirus vaccination in Finland, a register based study measuring impact beyond overall effectiveness.

INTRODUCTION: Even with vaccines available since 2006, rotavirus continues to be a major cause of acute gastroenteritis globally in children under 5 years old. Finland introduced the rotavirus vaccine to its national vaccination programme in 2009. Since then hospitalizations due to gastroenteritis caused by rotavirus (RVGE) and of all causes (AGE) have been reduced significantly in young children. METHODS: We performed a retrospective analysis of data from register databases consisting of over 200 000 children aged 0.5-2 years. Children born before rotavirus vaccines were available (2002, 2003) and after the implementation of rotavirus vaccination programme (2014, 2015) were followed for episodes of acute infectious gastroenteritis. We calculated the incidences of hospital outpatient and inpatient episodes and used individual vaccination records to estimate the overall, total, direct and indirect vaccine effect (VE %). RESULTS: Among children born in 2014 and 2015, there was a 96% reduction in inpatient RVGE episodes and a 78% reduction in episodes of inpatient AGE compared to the pre-vaccination era, comprising the overall VE. Direct effectiveness was 96% and 53% for RVGE and AGE respectively. Herd effect i.e. indirect protection was estimated to be 67% against inpatient RVGE and 56% against inpatient AGE. Protection acquired by the vaccinated children when compared to pre vaccination era i.e. the total VE was 99% for inpatient RVGE and 79% for inpatient AGE. CONCLUSIONS: Although overall incidences for every disease type studied were reduced, rotavirus is still circulating with seasonality and there is a slight shift of disease towards the older age groups. Together with changes observed in the distribution of rotavirus genotypes, our results indicate that continuous monitoring is still necessary.

Impact of five years of rotavirus vaccination in Finland - And the associated cost savings in secondary healthcare.

INTRODUCTION: This study aimed to estimate the impact of the national rotavirus (RV) vaccination programme, starting 2009, on the total hospital-treated acute gastroenteritis (AGE) and severe RV disease burden in Finland during the first five years of the programme. This study also evaluated the costs saved in secondary healthcare by the RV vaccination programme. METHODS: The RV related outcome definitions were based on ICD10 diagnostic codes recorded in the Care Register for Health Care. Incidences of hospitalised and hospital outpatient cases of AGE (A00-A09, R11) and RVGE (A08.0) were compared prior (1999-2005) and after (2010-2014) the start of the programme among children less than five years of age. RESULTS: The reduction in disease burden in 2014, when all children under five years of age have been eligible for RV vaccination, was 92.9% (95%CI: 91.0%-94.5%) in hospitalised RVGE and 68.5% (66.6%-70.3%) in the total hospitalised AGE among children less than five years of age. For the corresponding hospital outpatient cases, there was a reduction of 91.4% (82.4%-96.6%) in the RVGE incidence, but an increase of 6.3% (2.7%-9.9%) in the AGE incidence. The RV vaccination programme prevented 2206 secondary healthcare AGE cases costing €4.5 million annually. As the RV immunisation costs were €2.3 million, the total net savings just in secondary healthcare costs were €2.2 million, i.e. €33 per vaccinated child. DISCUSSION: The RV vaccination programme clearly controlled the severe, hospital-treated forms of RVGE. The total disease burden is a more valuable end point than mere specifically diagnosed cases as laboratory confirmation practises usually change after vaccine introduction. The RV vaccination programme annually pays for itself at least two times over.

Rotavirus Vaccination and the Risk of Celiac Disease or Type 1 Diabetes in Finnish Children at Early Life.

BACKGROUND: Rotavirus infection has been suggested as a trigger of type 1 diabetes (T1D)-related autoimmunity and celiac disease (CD)-related autoimmunity. METHODS: We carried out a nationwide, population-based cohort study evaluating whether prevention of rotavirus infection with vaccination affects the risk of CD and T1D diagnosed during 2009-2014 in Finnish children by comparing vaccinated and unvaccinated children in a cohort born in 2009-2010. Nationwide rotavirus vaccination records were collected from healthcare databases during 2009-2011 and validated for a sample of 495 children born from July 2009 to December 2009. Incident diagnoses of CD and T1D during 2009-2014 in the cohort were identified in the National Care Register. RESULTS: The adjusted relative risks (with 95% confidence intervals) were 0.91 (0.69-1.20) for T1D and 0.87 (0.65-1.17) for CD in vaccinated children compared with unvaccinated, suggesting that oral rotavirus vaccination does not alter the risk of CD or T1D during 4-6 years follow-up after vaccination. CONCLUSIONS: Our results suggest that oral rotavirus vaccination is considered safe in the individuals at risk of CD and T1D.

Epidemiology of hepatitis B infection in Finland: Implications for immunisation policy.

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.

New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media.

For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2-24 months at scheduled visits and at visits during respiratory infection in 1994-97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media.

Evaluation of the Intussusception Risk after Pentavalent Rotavirus Vaccination in Finnish Infants.

BACKGROUND: An association between rotavirus immunisation and intussusception (IS) has been suggested with present rotavirus vaccines in post-licensure studies. In Finland, rotavirus vaccination programme was implemented in September 2009 using a 2, 3, and 5 months schedule with the pentavalent rotavirus vaccine. By the end of 2013, it is estimated that 719 000 rotavirus vaccine doses have been given in the national programme of which 240 000 were first doses. Nationwide register allows us to evaluate the association between rotavirus vaccination and IS. METHODS AND MATERIALS: Cases of IS diagnosed during 1999-2013 were identified from National Hospital Discharge Register. All cases under 250 days of age diagnosed during 2009-2013 were confirmed by reviewing medical charts. Self-controlled case-series method was used to assess the risk of IS during 1-21 days compared to 22-42 days post vaccination. FINDINGS: In register data the relative incidence of IS at 2 months of age between the post and pre vaccination era was 9.1 (95%CI 2.0-84.3). We identified 22 verified cases with date of admission less than 43 days after any of the three rotavirus vaccine doses. The incidence of IS in the risk period after the 1st dose relative to the control period was 2.0 (95% CI 0.5-8.4; p = 0.34.) Number of excess IS cases per 100 000 first vaccine doses was therefore estimated to be 1.04 (95% CI 0.0-2.5), i.e. one additional IS case per 96 000 first doses of rotavirus vaccine (95% CI 54 600 to ∞). There was no risk detected after 2nd and 3rd doses. CONCLUSION: The finding is in line with the recent published estimates. The benefits of rotavirus immunisation programme outweigh possible small risks of intussusception.

Perinatal survival and health after maternal influenza A(H1N1)pdm09 vaccination: A cohort study of pregnancies stratified by trimester of vaccination.

Large cohort studies demonstrated the safety of vaccination with the AS03 adjuvanted pandemic influenza vaccine, but data on first trimester vaccination safety are limited. We conducted a nationwide register-based retrospective cohort study in Finland, included singleton pregnancies present on 01 November 2009 and followed them from 01 November 2009 until delivery. Pregnancies with abortive outcome, pregnancies that started before 01 February 2009 and pregnancies of women, who received the AS03 adjuvanted pandemic influenza vaccine prior to the onset of pregnancy, were excluded. Our main outcome measures were hazard ratios comparing the risk of stillbirth, early neonatal death, moderately preterm birth, very preterm birth, moderately low birth weight, very low birth weight, and being small for gestational age between pregnancies exposed and unexposed to maternal influenza A(H1N1)pdm09 vaccination. The study population comprised 43,604 pregnancies; 34,241 (78.5%) women were vaccinated at some stage during pregnancy. The rates of stillbirth, early neonatal death, moderately preterm birth, and moderately low birth weight were similar between pregnant women exposed and unexposed to influenza A(H1N1)pdm09 vaccination. After adjusting for known risk factors, the relative rates were 0.90 (95% confidence interval 0.55-1.45) for very preterm birth, 0.84 (0.61-1.16) for very low birth weight, and 1.17 (0.98-1.40) for being small for gestational age. Also, in the subanalysis of 7839 women vaccinated during the first trimester, the rates did not indicate that maternal vaccination during the first trimester had any adverse impact on perinatal survival and health. The risk of adverse pregnancy outcomes was not associated with the exposure to the AS03 adjuvanted pandemic influenza vaccine. This study adds reassuring evidence on the safety of AS03 adjuvanted influenza vaccines when given in the first trimester and supports the recommendation of influenza vaccination to all pregnant women through all stages of pregnancy.