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As a follow-up to a previous study, we investigated vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) among 1,254,498 persons >65 years of age as part of a vaccination program in Denmark during April 2020–January 2023. We assessed VE by using a Cox regression model and adjusted for age, sex, and underlying conditions. Using nationwide data, we estimated a VE of PPSV23 against all-type IPD of 32% and against PPSV23-serotype IPD of 41%. Because this follow-up study had more statistical power than the original study, we also estimated VE against IPD caused by PPSV23-serotypes excluding serotype 3; serotype 3; serotype 8; serotype 22F; PPSV23 non-PCV15 serotypes; PPSV23 non-PCV20 serotypes; and IPD over time. Our findings suggest PPSV23 vaccination can protect persons >65 years of age against IPD caused by all serotypes or serotype groupings, except serotype 3.

Abstract Background Pneumonia is among the main causes of illness and death in children Methods From July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay. Results We identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (rs = 0.40, P = 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (rs = 0.55, P = 0.0005). Conclusion Respiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.

Summary: SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection.The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [95% CI] for BA.2: 0.83 [0.73–0.95], p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR [95% CI] for BA.2 spike-specific IgG: 0.65 [0.48–0.88], p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 [0.30–0.69], p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males.High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.

Objective: To compare the vaccine prices per vaccinated child under 18 and vaccine funding and procurement systems in the national vaccination programmes (NVPs) in Europe. Methods: The on-line survey targeted to NVP managers collected data referred to the information available on 31 December 2016. The prices of vaccines were categorised into three groups. The price per child 1) fully vaccinated comprised all vaccines and doses offered in the NVP; 2) vaccinated with standard vaccines comprised the vaccines included in the NVP in all countries; 3) vaccinated with recent vaccines comprised the pneumococcal conjugate, human papillomavirus and rotavirus vaccines. Results: In the 23 out of 32 countries that answered the survey, 17 funded the vaccines by taxes and six by social insurance. 18 countries procured the vaccines through public tenders or negotiations. Five countries purchased the vaccines by healthcare providers and reimbursed from the health insurance system.In the countries with vaccine procurement through public tenders the price per child vaccinated with standard vaccines ranged from €59 to €117 when using pentavalent and from €98 to €220 when using hexavalent vaccines. The mean price per child vaccinated with recent vaccines was €130 for the countries that offered pneumococcal conjugate and human papillomavirus vaccines and €142 for the countries that in addition included rotavirus vaccine.In the countries that purchased the vaccines by healthcare providers and reimbursed from the health insurance system the price per child vaccinated with standard vaccines ranged from €136 to €427. Conclusions: The vaccine prices differ notably in Europe. Prices were lower in countries where vaccines in the NVP were tax-funded and nationally or regionally procured. Improved procurement systems could lead to substantial savings or possibilities to introduce more vaccines into the NVP.

Abstract Background Covid-19 vaccination is the main strategy to reduce SARS-CoV-2 transmission, mortality and morbidity. This study aimed to examine sociodemographic differences in Covid-19 vaccine uptake among all individuals invited for Covid-19 vaccination in Denmark. Methods This study was designed as a nationwide register-based cohort study. The study population included all Danish residents aged 12 years or above in Denmark between December 27, 2020 and October 20, 2021. Individuals who died during the study period before receiving an invitation for Covid-19 vaccination were excluded. Associations between sociodemographic factors and Covid-19 vaccination uptake were analyzed using logistic regression models adjusting for age, sex, immigration status, educational level, disposable income and history of SARS-CoV-2 infection. Results The study population included 5,164,558 individuals. The overall vaccination coverage was 87.1% by October 20, 2021. In the full adjusted logistic regression models, the highest ORs for non-vaccination were observed among individuals aged 12–24 years (OR: 8.99 (95% CI: 8.76–9.23)), descendants of non-western immigrants (OR: 5.26 (95% CI: 5.18–5.33)), individuals who never had a PCR-test performed (OR: 2.93 (95% CI: 2.90–2.96)), individuals with primary school as highest completed educational level (OR: 2.87 (95% CI: 2.83–2.91)) and individuals with disposable income

Abstract Background High-dose influenza vaccines provide better protection against influenza infection than standard-dose in persons aged 65 years and above; however, in most countries, high-dose vaccines are not widely implemented. Assessing the relative effectiveness of high-dose compared to standard-dose vaccines on hospitalizations and mortality would enable more robust public health and cost-effectiveness estimates. This study aims to investigate the feasibility of conducting a pragmatic randomized clinical trial in Denmark comparing high-dose to standard-dose vaccines utilizing existing vaccination infrastructure and the Danish nationwide health registries for data collection. Methods The DANFLU-1 trial (NCT05048589) is a pragmatic, open-label, active-controlled randomized trial randomizing Danish citizens aged 65–79 years to either high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine. The study utilizes the infrastructure of a private vaccination provider (Danske Lægers Vaccinations Service) for recruitment, inclusion, randomization, and vaccination. All collection of baseline and follow-up data including safety monitoring is performed centrally by the Department of Cardiology at Herlev and Gentofte Hospital, Copenhagen, Denmark using the Danish nationwide health registries. The study aims to include 40,000 participants during the 2021/2022 influenza season. The primary endpoints address feasibility and include the number of participants enrolled, randomization balance, and representativeness compared to the Danish general population. Relative vaccine effectiveness will also be assessed, however, this feasibility study is not powered for clinical outcomes and may be affected by the COVID-19 pandemic. Discussion The DANFLU-1 study is investigating the feasibility of conducting a large-scale pragmatic clinical trial in Denmark utilizing existing infrastructure and the Danish nationwide registries. This will provide valuable insight, especially for potential future fully powered vaccine trials, but also for trials wishing to investigate other interventions. Trial registration Clinicaltrials.gov : NCT05048589 , registered September 17, 2021.

Abstract Background Invasive meningococcal disease (IMD) is a rare but severe bacterial infection, of which a high proportion of survivors are affected by sequelae. In Denmark, IMD is a notifiable disease and data collection on sequelae information has been automated, enabling studies of sequelae due to IMD diagnosed after discharge. The aim of this study was to examine possible determinants for sequelae after IMD and to describe the distribution of sequelae by age, serogroup and clinical presentation, for all cases in Denmark from 2005–2020. Methods Data from The National Database for Notifiable Infectious Diseases was linked to data from The Danish National Patient Register and the Civil Registration System. Logistic regression models were used to study whether age, serogroup and/or clinical presentation were associated with sequelae. A descriptive analysis of the proportion of different types of sequelae across age groups, serogroups and clinical presentations was performed. Results In total, 25% of IMD survivors experienced one or more sequelae. We found no significant association between sequelae and age. The five most common sequelae in decreasing order of incidence were hearing loss, epilepsy, learning disabilities, headache and visual defects/loss of vision, with rates ranging from 8.2 to 2.8% of IMD survivors. The proportion of survivors with hearing loss and visual defects/loss of vision was not significantly different between clinical presentations. Conclusions We suggest revising IMD treatment guidelines, to include routine referral to hearing and vision tests, irrespective of clinical presentation. Furthermore, it is important to increase the awareness among parents of children who have had IMD of possible future learning disabilities to make sure that necessary measures are taken in a timely manner.

BackgroundIndividuals with a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection have a moderate to high degree of protection against reinfection, though seemingly less so when the Omicron variant of SARS-CoV-2 started to circulate. The aim of this study was to evaluate the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, Coronavirus Disease 2019 (COVID-19)-related hospitalization, and COVID-19-related death, in individuals with prior SARS-CoV-2 infection, and to assess the effect of time since vaccination during periods with different dominant SARS-CoV-2 variants.Methods and findingsThis study used a nationwide cohort design including all individuals with a confirmed SARS-CoV-2 infection, who were alive, and residing in Denmark between 1 January 2020 and 31 January 2022. Using Danish nationwide registries, we obtained information on SARS-CoV-2 infections, COVID-19 vaccination, age, sex, comorbidity, staying at hospital, and country of origin. The study population included were individuals with prior SARS-CoV-2 infection. Estimates of VE against SARS-CoV-2 reinfection with 95% confidence intervals (CIs) were calculated using a Poisson regression model and adjusted for age, sex, country of origin, comorbidity, staying at hospital, calendar time, and test incidence using a Cox regression model. The VE estimates were calculated separately for three periods with different dominant SARS-CoV-2 variants (Alpha (B.1.1.7), Delta (B.1.617.2), or Omicron (B.1.1.529)) and by time since vaccination using unvaccinated as the reference. In total, 148,527 person-years and 44,192 SARS-CoV-2 infections were included for the analysis regarding reinfections. The study population comprised of 209,814 individuals infected before or during the Alpha period, 292,978 before or during the Delta period, and 245,530 before or during the Omicron period. Of these, 40,281 individuals had completed their primary vaccination series during the Alpha period (19.2%), 190,026 during the Delta period (64.9%), and 158,563 during the Omicron period (64.6%). VE against reinfection following any COVID-19 vaccine type administered in Denmark, peaked at 71% (95% CI: -Inf to 100%) at 104 days or more after vaccination during the Alpha period, 94% (95% CI: 92% to 96%) 14 to 43 days after vaccination during the Delta period, and 60% (95% CI: 58% to 62%) 14 to 43 days after vaccination during the Omicron period. Waning immunity following vaccination was observed and was most pronounced during the Omicron period. Due to too few events, it was not possible to estimate VE for hospitalization and death. Study limitations include potentially undetected reinfections, differences in health-seeking behavior, or risk behavior between the compared groups.ConclusionsThis study shows that in previously infected individuals, completing a primary vaccination series was associated with a significant protection against SARS-CoV-2 reinfection compared with no vaccination. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods.

Objectives: Neisseria meningitidis serogroup W incidence has increased. Mortality associated with serogroup W has been higher than for other serogroups. Here we report epidemiological characteristics and risks of poor outcomes associated with invasive meningococcal disease in Denmark since 1980. Methods: All cases of invasive meningococcal disease reported from 1980–2018 were analyzed. Incidence rates by age, sex, manifestation, and serogroup were calculated. Poisson regression was used to analyze the rise in serogroup W, and multivariate logistic analysis was used to analyze risk factors for mortality. Results: A total of 5825 cases were analyzed. Risk of serogroup W infection increased after 2015 compared with all previous periods. Younger (

Summary: Background: The level of protection after a SARS-CoV-2 infection against reinfection and COVID-19 disease remains important with much of the world still unvaccinated. Methods: Analysing nationwide, individually referable, Danish register data including RT-PCR-test results, we conducted a cohort study using Cox regression to compare SARS-CoV-2 infection rates before and after a primary infection among still unvaccinated individuals, adjusting for sex, age, comorbidity and residency region. Estimates of protection against infection were calculated as 1 minus the hazard ratio. Estimates of protection against symptomatic infections and infections leading to hospitalisation were also calculated. The prevalence of infections classified as symptomatic or asymptomatic was compared for primary infections and reinfections. The study also assessed protection against each of the main viral variants after a primary infection with an earlier variant by restricting follow-up time to distinct, mutually exclusive periods during which each variant dominated. Findings: Until 1 July 2021 the estimated protection against reinfection was 83.4% (95%CI: 82.2–84.6%); but lower for the 65+ year-olds (72.2%; 95%CI: 53.2–81.0%). Moderately higher estimates were found for protection against symptomatic disease, 88.3% overall (95%CI: 85.9–90.3%). First-time cases who reported no symptoms were more likely to experience a reinfection (odds ratio: 1.48; 95%CI: 1.35–1.62). By autumn 2021, when infections were almost exclusively caused by the Delta variant, the estimated protection following a recent first infection was 91.3% (95%CI: 89.7–92.7%) compared to 71.4% (95%CI: 66.9–75.3%) after a first infection over a year earlier. With Omicron, a first infection with an earlier variant in the past 3-6 months gave an estimated 51.0% (95%CI: 50.1–52.0%) protection, whereas a first infection longer than 12 months earlier provided only 19.0% (95%CI: 17.2–20.5%) protection. Protection by an earlier variant-infection against hospitalisation due to a new infection was estimated at: 86.6% (95%CI: 46.3–96.7%) for Alpha, 97.2% (95%CI: 89.0–99.3%) for Delta, and 69.8% (95%CI: 51.5–81.2%) for the Omicron variant. Interpretation: SARS-CoV-2 infection offered a high level of sustained protection against reinfection, comparable with that offered by vaccines, but decreased with the introduction of new main virus variants; dramatically so when Omicron appeared. Protection was lower among the elderly but appeared more pronounced following symptomatic compared to asymptomatic infections. The level of estimated protection against serious disease was somewhat higher than that against infection and possibly longer lasting. Decreases in protection against reinfection, seemed primarily to be driven by viral evolution. Funding: None.

BackgroundThe continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period.Methods and findingsA Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: -0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals.ConclusionsTwo vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds.

Abstract Background Streptococcus pneumoniae serotype 8 incidence has increased in Denmark after the introduction of pneumococcal conjugated vaccines (PCV). The mechanism behind the serotype 8 replacement is not well understood. In this study, we aimed to present epidemiological data on invasive pneumococcal disease (IPD) and molecular characterization of 96 serotype 8 clinical isolates. Methods IPD data from 1999 to 2019 were used to calculate the incidence and age distribution. Whole-genome sequencing (WGS) analysis was performed on 96 isolates (6.8% of the total serotype 8 IPD isolates in the period) to characterize the isolates with respect to pneumococcal lineage traits, a range of genes with potential species discrimination, presence of colonization and virulence factors, and molecular resistance pattern. Results The serotype 8 IPD incidence increased significantly (P

BackgroundThe recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different Coronavirus Disease 2019 (COVID-19) vaccine types, which necessitates knowledge on vaccine effectiveness (VE) of heterologous vaccine schedules. The aim of this Danish nationwide population-based cohort study was therefore to estimate the VE against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and death following the first dose of the ChAdOx1 vaccine and the combination of the ChAdOx1/mRNA vaccines.Methods and findingsAll individuals alive in or immigrating to Denmark from 9 February 2021 to 23 June 2021 were identified in the Danish Civil Registration System. Information on exposure, outcomes, and covariates was obtained from Danish national registries. Poisson and Cox regression models were used to calculate crude and adjusted VE, respectively, along with 95% confidence intervals (CIs) against SARS-CoV-2 infection and COVID-19-related hospitalization or death comparing vaccinated versus unvaccinated individuals. The VE estimates were adjusted for calendar time as underlying time and for sex, age, comorbidity, country of origin, and hospital admission. The analyses included 5,542,079 individuals (97.6% of the total Danish population). A total of 144,360 individuals were vaccinated with the ChAdOx1 vaccine as the first dose, and of these, 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 SARS-CoV-2 infections were included. The individuals vaccinated with the first dose of the ChAdOx1 vaccine dose had a median age of 45 years. The study population was characterized by an equal distribution of males and females; 6.7% and 9.2% originated from high-income and other countries, respectively. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% CI: 83; 92) 14 days after the second dose and onwards. There were no COVID-19-related hospitalizations or deaths among the individuals vaccinated with the combined vaccine schedule during the study period. Study limitations including unmeasured confounders such as risk behavior and increasing overall vaccine coverage in the general population creating herd immunity are important to take into consideration when interpreting the results.ConclusionsIn this study, we observed a large reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals.

ABSTRACT Respiratory viruses cause a substantial proportion of respiratory tract infections in children but are underrecognized as a cause of severe pneumonia hospitalization in low-income settings. We employed 22 real-time PCR assays and retrospectively reanalyzed 610 nasopharyngeal aspirate specimens from children aged 2 to 35 months with severe pneumonia (WHO definition) admitted to Kanti Childrens’ Hospital in Kathmandu, Nepal, from January 2006 through June 2008. Previously, ≥1 of 7 viruses had been detected by multiplex reverse transcription-PCR in 30% (188/627) of cases. Reanalyzing the stored specimens, we detected ≥1 pathogens, including 18 respiratory viruses and 3 atypical bacteria, in 98.7% (602/610) of cases. Rhinovirus (RV) and respiratory syncytial virus (RSV) were the most common, detected in 318 (52.1%) and 299 (49%) cases, respectively, followed by adenovirus (AdV) (10.6%), human metapneumovirus (hMPV) (9.7%), parainfluenza virus type 3 (8.4%), and enterovirus (7.7%). The remaining pathogens were each detected in less than 5%. Mycoplasma pneumoniae was most common among the atypical bacteria (3.7%). Codetections were observed in 53.3% of cases. Single-virus detection was more common for hMPV (46%) and RSV (41%) than for RV (22%) and AdV (6%). The mean cycle threshold value for detection of each pathogen tended to be lower in single-pathogen detections than in codetections. This finding was significant for RSV, RV, and AdV. RSV outbreaks occurred at the end of the monsoon or during winter. An expanded diagnostic PCR panel substantially increased the detection of respiratory viruses in young Nepalese children hospitalized with severe pneumonia. IMPORTANCE Respiratory viruses are an important cause of respiratory tract infections in children but are underrecognized as a cause of pneumonia hospitalization in low-income settings. Previously, we detected at least one of seven respiratory viruses by PCR in 30% of young Nepalese children hospitalized with severe pneumonia over a period of 36 months. Using updated PCR assays detecting 21 different viruses and atypical bacteria, we reanalyzed 610 stored upper-respiratory specimens from these children. Respiratory viruses were detected in nearly all children hospitalized for pneumonia. RSV and rhinovirus were the predominant pathogens detected. Detection of two or more pathogens was observed in more than 50% of the pneumonia cases. Single-virus detection was more common for human metapneumovirus and RSV than for rhinovirus and adenovirus. The concentration of virus was higher (low cycle threshold [CT] value) for single detected pathogens, hinting at a high viral load as a marker of clinical significance.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011–2014 but increased during 2015–2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children 65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. Serotypes included in the 15-valent PCV represented one third of cases and those in the 20-valent PCVs two thirds of cases in children 65 years of age in 2018. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

BackgroundGlobally, solid fuels are used by about 3 billion people for cooking. These fuels have been associated with many health effects, including acute lower respiratory infection (ALRI) in young children. Nepal has a high prevalence of use of biomass for cooking and heating.ObjectiveThis case-control study was conducted among a population in the Bhaktapur municipality, Nepal, to investigate the relationship of cookfuel type to ALRI in young children.MethodsCases with ALRI and age-matched controls were enrolled from an open cohort of children 2-35 months old, under active monthly surveillance for ALRI. A questionnaire was used to obtain information on family characteristics, including household cooking and heating appliances and fuels. The main analysis was carried out using conditional logistic regression. Population-attributable fractions (PAF) for stove types were calculated.ResultsA total of 917 children (452 cases and 465 controls) were recruited into the study. Relative to use of electricity for cooking, ALRI was increased in association with any use of biomass stoves [odds ratio (OR) = 1.93; 95% CI: 1.24, 2.98], kerosene stoves (OR = 1.87; 95% CI: 1.24, 2.83), and gas stoves (OR = 1.62; 95% CI: 1.05, 2.50). Use of wood, kerosene, or coal heating was also associated with ALRI (OR = 1.45; 95% CI: 0.97, 2.14), compared with no heating or electricity or gas heating. PAFs for ALRI were 18.0% (95% CI: 8.1, 26.9%) and 18.7% (95% CI: 8.4%-27.8%), for biomass and kerosene stoves, respectively.ConclusionsThe study supports previous reports indicating that use of biomass as a household fuel is a risk factor for ALRI, and provides new evidence that use of kerosene for cooking may also be a risk factor for ALRI in young children.

Abstract Background In 2014, Denmark experienced a rapid decline in vaccination uptake for the human papillomavirus (HPV) vaccine after a successful introduction of the vaccine in 2009. Before the decline, the uptake of the first HPV vaccine was around 90% for girls born in the period 1998 to 2000, while it dropped to 54% for girls born in 2003. The decline followed negative public attention from 2013 coinciding with increasing suspected adverse-event reporting to the Danish Medicines Agency. The aim of this study is to describe the HPV-vaccination uptake, to quantify relevant HPV-related media coverage, and analyse the relation between media coverage and HPV-vaccination acceptance in Denmark in year 2009–2016. Methods Three types of data were used for the analysis: Immunisation data from 243,415 girls, media coverage (8524 news items) and Google search activity. We used changes in the correlation between media coverage and vaccination uptake to identify a changing point in their relationship. The relationship before and after the changing point was analysed determined on the interactions between vaccination uptake, media and search activity, with search activity as a proxy for public attention. Results We identified July 2013 as a changing point in the relationship between media coverage and vaccination uptake. We found no significant relationship between media coverage and vaccination uptake in the first part of the time series (June 2009 to June 2013), whereas from July 2013 and onwards there was a negative Pearson’s correlation of − 0.52. The changing point coincides with both an increase in Google searches for “HPV side effects” and media coverage with negative content. Conclusions Following a successful launch of the HPV-vaccination programme, concerns about vaccine safety shifted the public opinion and the coverage by the media. The noticeable shift in correlation between vaccination uptake and media coverage before and after July 2013 could indicate that increased media coverage influenced the decline in vaccination uptake. Media monitoring may represent an important tool in future monitoring and assessment of confidence in vaccination programmes.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5–7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases N = 32; cases = 4503), PCV13 types caused 14% in

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the evidence base for vaccine efficacy and effectiveness of PPV23 and PCV13 against invasive pneumococcal disease and pneumonia among an unselected elderly population. We systematically searched for clinical trials and observational studies published between January 1 2016 and April 17 2019 in Pubmed, Embase, Cinahl, Web of Science, Epistemonikos and Cochrane databases. Risk of bias was assessed using Cochrane Risk of Bias tool for and the Newcastle–Ottawa Scale. Results were stratified by vaccine type and outcome. We identified nine studies on PCV13 and six on PPV23. No new randomized clinical trials were identified. Due to different outcomes, it was not possible to do a meta-analysis. New high-quality observational studies indicate protective vaccine effectiveness for both vaccines against vaccine type pneumonia. Our estimates for the protective vaccine efficacy and effectiveness (VE) of PPV23 on pneumonia and pneumococcal pneumonia overlap with results from previously published reviews. Some of the results indicate that the effectiveness of the PPV23 is best in younger age groups, and that it decreases over time.

Annual influenza vaccination is widely recommended in older adults and other high-risk groups including patients with cardiovascular disease. The real-world effectiveness of influenza vaccination is limited by suboptimal uptake and effective strategies for increasing vaccination rates are therefore needed. The purpose of this trial is to investigate whether behavioral nudges digitally delivered via the Danish nationwide mandatory governmental electronic letter system can increase influenza vaccination uptake among older adults. The NUDGE-FLU trial is a randomized implementation trial randomizing all Danish citizens aged 65 years and above without an exemption from the Danish mandatory governmental electronic letter system to receive no digitally delivered behavioral nudge (usual care arm) or to receive one of 9 electronic letters (intervention arms) each leveraging different behavioral science strategies. The trial has randomized 964,870 participants with randomization clustered at the household level (n = 691,820 households). Intervention letters were delivered on September 16, 2022, and follow-up is currently ongoing. All trial data are captured using the nationwide Danish administrative health registries. The primary end point is the receipt of an influenza vaccine on or before January 1, 2023. The secondary end point is time to vaccination. Exploratory end points include clinical events such as hospitalization for influenza or pneumonia, cardiovascular events, all-cause hospitalization, and all-cause mortality. The nationwide randomized NUDGE-FLU trial is one of the largest implementation trials ever conducted and will provide important insights into effective communication strategies to maximize vaccination uptake among high-risk groups. Clinicaltrials.gov: NCT05542004, registered September 15, 2022, https://clinicaltrials.gov/ct2/show/NCT05542004. [ABSTRACT FROM AUTHOR]

BACKGROUND:Since 2013 the number of suspected adverse reactions to the quadrivalent human papillomavirus (HPV) vaccine reported to the Danish Medicines Agency (DMA) has increased. Due to the resulting public concerns about vaccine safety, the coverage of HPV vaccinations in the childhood vaccination programme has declined. The aim of the present study was to determine health care-seeking prior to the first HPV vaccination among females who suspected adverse reactions to HPV vaccine. METHODS:In this registry-based case-control study, we included as cases vaccinated females with reports to the DMA of suspected severe adverse reactions. We selected controls without reports of adverse reactions from the Danish vaccination registry and matched by year of vaccination, age of vaccination, and municipality, and obtained from the Danish National Patient Registry and The National Health Insurance Service Register the history of health care usage two years prior to the first vaccine. We analysed the data by logistic regression while adjusting for the matching variables. RESULTS:The study included 316 cases who received first HPV vaccine between 2006 and 2014. Age range of cases was 11 to 52 years, with a peak at 12 years, corresponding to the recommended age at vaccination, and another peak at 19 to 28 years, corresponding to a catch-up programme targeting young women. Compared with 163,910 controls, cases had increased care-seeking in the two years before receiving the first HPV vaccine. A multivariable model showed higher use of telephone/email consultations (OR 1.9; 95% CI 1.2-3.2), physiotherapy (OR 2.1; 95% CI 1.6-2.8) and psychologist/psychiatrist (OR 1.9; 95% CI 1.3-2.7). Cases were more likely to have a diagnosis in the ICD-10 chapters of diseases of the digestive system (OR 1.6; 95% CI 1.0-2.4), of the musculoskeletal system (OR 1.6; 95% CI 1.1-2.2), symptoms or signs not classified elsewhere (OR 1.8; 95% CI 1.3-2.5) as well as injuries (OR 1.5; 95% CI 1.2-1.9). CONCLUSION:Before receiving the first HPV vaccination, females who suspected adverse reactions has symptoms and a health care-seeking pattern that is different from the matched population. Pre-vaccination morbidity should be taken into account in the evaluation of vaccine safety signals.

BackgroundPneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from invasive pneumococcal disease (IPD).Methods and findingsIn a nationwide population-based cohort study of IPD in Denmark during 1977-2007, 30-d mortality associated with pneumococcal serotypes was examined by multivariate logistic regression analysis after controlling for potential confounders. A total of 18,858 IPD patients were included. Overall 30-d mortality was 18%, and 3% in children younger than age 5 y. Age, male sex, meningitis, high comorbidity level, alcoholism, and early decade of diagnosis were significantly associated with mortality. Among individuals aged 5 y and older, serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A were associated with highly increased mortality as compared with serotype 1 (all: adjusted odds ratio >or=3, pConclusionsSpecific pneumococcal serotypes strongly and independently affect IPD associated mortality.