Publications by authors named "Palle Valentiner-Branth"

72 Publications

Recent increase in incidence of invasive serogroup W meningococcal disease. A retrospective observational study.

Int J Infect Dis 2021 Jun 5. Epub 2021 Jun 5.

Center of Research & Disruption of Infectious Diseases (CREDID), Department of Infectious Diseases, Hvidovre Hospital, Kettegaard Alle 30, 2650 Hvidovre, Denmark; Faculty of Human Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark. Electronic address:

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 to all previous time periods. Similarly, younger (<20 years) and older age (≥60 years) was associated with an increased risk of serogroup W infection compared to being 20-39-year-old. Crude case fatality was 12.0%, 11.9%, 9.2%, and 7.9% for serogroups W, Y, C, and B, respectively. After adjustment for age, sex, and manifestation 30-day mortality was comparable for serogroups. Older age and manifestation with sepsis independently predicted risk of death.

Conclusions: Invasive meningococcal disease caused by serogroup W has increased but serogroup per se was not associated with an increased risk of 30-day mortality.
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http://dx.doi.org/10.1016/j.ijid.2021.05.086DOI Listing
June 2021

Molecular characterization and epidemiology of Streptococcus pneumoniae serotype 8 in Denmark.

BMC Infect Dis 2021 May 5;21(1):421. Epub 2021 May 5.

Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.

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 < 0.05) for the age groups above 15 years after the introduction of PCV13, primarily affecting the elderly (65+). All isolates were phenotypically susceptible to penicillin, erythromycin and clindamycin. Molecular characterization revealed seven different MLST profiles with ST53 as the most prevalent lineage (87.5%) among the analyzed serotype 8 isolates. The genes covering the cell-surface proteins: lytA, rspB, pspA, psaA & Xisco and the pneumococcal toxin pneumolysin = ply were present in all isolates, while genes for the membrane transporter proteins: piaA/piaB/piaC; the capsular genes: cpsA (wzg) & psrP; the metallo-binding proteins zmpB & zmpC; and the neuroamidase proteins: nanA/nanB were variably present. Surprisingly, the putative transcriptional regulator gene SP2020 was not present in all isolates (98%). Susceptibility to penicillin, erythromycin and clindamycin was molecularly confirmed.

Conclusion: The observed serotype 8 replacement was not significantly reflected with a change in the MLST profile or changes in antibiotic resistance- or virulence determinants.
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http://dx.doi.org/10.1186/s12879-021-06103-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097992PMC
May 2021

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Microorganisms 2021 Apr 2;9(4). Epub 2021 Apr 2.

National Public Health Organisation, 15123 Athens, Greece.

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.
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http://dx.doi.org/10.3390/microorganisms9040742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066045PMC
April 2021

Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

Microorganisms 2021 Apr 1;9(4). Epub 2021 Apr 1.

Department of Clinical Microbiology, Landspitali-The National University Hospital, Hringbraut, 101 Reykjavik, Iceland.

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 ( = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites ( = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.
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http://dx.doi.org/10.3390/microorganisms9040738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066874PMC
April 2021

Human papillomavirus vaccination and all-cause morbidity in adolescent girls: a cohort study of absence from school due to illness.

Int J Epidemiol 2021 May;50(2):518-526

Division of Infectious Diseases Preparedness, Statens Serum Institut, Copenhagen, Denmark.

Background: A growing body of evidence supports the safety of the human papillomavirus (HPV) vaccines. However, concerns about autonomic dysfunction syndromes and non-specific symptoms continue to linger. These conditions are not easily captured by traditional diagnostic classification schemes and call for innovative approaches to the study of vaccine safety which take more general measures of all-cause morbidity into account.

Methods: Taking advantage of the unique Danish registers, including regional registration of absence from school, we conducted a cohort study of 14 068 adolescent Danish girls attending 5th through 9th grade in public schools in the municipality of Copenhagen during 1 August 2013-23 January 2018. We obtained time-varying HPV vaccination status and demographic information from nationwide registers. Using Poisson regression with random effects, we estimated rate ratios (RRs) of absence due to illness, comparing HPV-vaccinated girls with unvaccinated girls with adjustment for grade, season, calendar period, demographic factors and random effects at the individual, class and school levels.

Results: Our study included 6 206 188 school days with 213 221 days of absence from school due to illness (absence rate, 3.4%). Comparing absence rates due to illness in HPV-vaccinated and unvaccinated girls yielded an adjusted RR of 1.00 (95% confidence interval [CI], 0.98-1.03).

Conclusions: Our study provides an important and novel contribution to HPV vaccine safety. Using absence from school records, we were able to address important safety concerns without relying on medical diagnoses. We conclude that HPV vaccination does not increase the risk of morbidity in any manner that manifests as absence from school due to illness.
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http://dx.doi.org/10.1093/ije/dyab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128452PMC
May 2021

Underreporting of the 5-year tetanus, diphtheria, pertussis and polio booster vaccination in the Danish Vaccination Register.

BMC Public Health 2020 Nov 10;20(1):1681. Epub 2020 Nov 10.

Infectious Disease Epidemiology and Prevention, Statens Serum Institut, 2300, Copenhagen S, Artillerivej 5, Denmark.

Background: In Denmark, vaccination coverage is measured using the Danish Vaccination Register (DDV). In general, the vaccination coverage is high, but for some vaccinations, the coverage is suboptimal with geographical variation. This study aims to validate the vaccination coverage of the 5-year booster and identify overall reasons for non-vaccination in Copenhagen.

Methods: We validated the coverage of the 5-year tetanus, diphtheria, pertussis and polio booster for children born in 2010 and living in Copenhagen municipality in 2018, an area with low coverage (current estimate: 89%). We identified all children born in 2010 in the Civil Registration System and sent an electronic questionnaire to parents of children without a record of the 5-year booster in the DDV.

Results: Parents of 692 children were contacted and 49% participated. Of those, 186 (55%) reported that the child was vaccinated: 61% by their general practitioner and 34% abroad. The most common reason for non-vaccination was forgetfulness (31%), 26% did not want their child vaccinated and 17% had migrated from abroad and were not aware of the vaccination schedule. Considering only children with documentation for the vaccination, the corrected vaccination coverage was 91%.

Conclusions: We conclude that the coverage of the 5-year booster in Copenhagen is currently underestimated and should be adjusted by 2%. We recommend increased awareness from general practitioners and tailored communication about the vaccination programme targeting immigrants in Denmark.
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http://dx.doi.org/10.1186/s12889-020-09816-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654036PMC
November 2020

Association between quadrivalent human papillomavirus vaccination and selected syndromes with autonomic dysfunction in Danish females: population based, self-controlled, case series analysis.

BMJ 2020 09 2;370:m2930. Epub 2020 Sep 2.

Division of Infectious Diseases Preparedness, Statens Serum Institut, Copenhagen, Denmark.

Objective: To evaluate the association between quadrivalent human papillomavirus vaccination and syndromes with autonomic dysfunction, such as chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome.

Design: Population-based self-controlled case series.

Setting: Information on human papillomavirus vaccinations and selected syndromes with autonomic dysfunction (chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome) identified using ICD-10 (international classification of diseases, revision 10) diagnostic codes from Danish nationwide registers.

Participants: 869 patients with autonomic dysfunction syndromes from a cohort of 1 375 737 Danish born female participants aged 10 to 44 years during 2007-16.

Main Outcome Measures: Self-controlled case series rate ratios (95% confidence intervals) of the composite outcome of chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome, adjusted for age and season, comparing female participants vaccinated and unvaccinated with the quadrivalent human papillomavirus vaccine. Chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome were also considered separately in secondary analyses.

Results: During 10 581 902 person years of follow-up, 869 female participants with syndromes of autonomic dysfunction (136 with chronic fatigue syndrome, 535 with complex regional pain syndrome, and 198 with postural orthostatic tachycardia syndrome) were identified. Quadrivalent human papillomavirus vaccination did not statistically significantly increase the rate of a composite outcome of all syndromes with autonomic dysfunction in a 365 day risk period following vaccination (rate ratio 0.99, 95% confidence interval 0.74 to 1.32) or the rate of any individual syndrome in the risk period (chronic fatigue syndrome (0.38, 0.13 to 1.09), complex regional pain syndrome (1.31, 0.91 to 1.90), or postural orthostatic tachycardia syndrome (0.86, 0.48 to 1.54)).

Conclusions: When vaccination is introduced, adverse events could occur in close temporal relation to the vaccine purely by chance. These results do not support a causal association between quadrivalent human papillomavirus vaccination and chronic fatigue syndrome, complex regional pain syndrome, or postural orthostatic tachycardia syndrome, either individually or as a composite outcome. An increased risk of up to 32% cannot be formally excluded, but the statistical power of the study suggests that a larger increase in the rate of any syndrome associated with vaccination is unlikely.
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http://dx.doi.org/10.1136/bmj.m2930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463169PMC
September 2020

Laboratory Diagnostics of Infections in Denmark 2008-2015.

Biology (Basel) 2020 Jun 19;9(6). Epub 2020 Jun 19.

Department of Bacteria, Parasites and Fungi, Statens Serum Institut (SSI), 2300 Copenhagen, Denmark.

Rickettsiosis is a vector-borne disease caused by bacterial species in the genus . Ticks in Scandinavia are reported to be infected with , yet only a few Scandinavian human cases are described, and rickettsiosis is poorly understood. The aim of this study was to determine the prevalence of rickettsiosis in Denmark based on laboratory findings. We found that in the Danish individuals who tested positive for by serology, the majority (86%; 484/561) of the infections belonged to the spotted fever group. In contrast, we could confirm 13 of 41 (32%) PCR-positive individuals by sequencing and identified all of these as , indicating infections after travel exposure. These 13 samples were collected from wound/skin material. In Denmark, approximately 85 individuals test positive for spp. annually, giving an estimated 26% (561/2147) annual prevalence among those suspected of rickettsiosis after tick bites. However, without clinical data and a history of travel exposure, a true estimation of rickettsiosis acquired endemically by tick bites cannot be made. Therefore, we recommend that both clinical data and specific travel exposure be included in a surveillance system of infections.
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http://dx.doi.org/10.3390/biology9060133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345066PMC
June 2020

Acute myocardial infarctions and stroke triggered by laboratory-confirmed respiratory infections in Denmark, 2010 to 2016.

Euro Surveill 2020 04;25(17)

Statens Serum Institut, Copenhagen, Denmark.

BackgroundSeveral studies have investigated a possible association between respiratory infection and acute myocardial infarction (MI). As both influenza and pneumococcal infections are vaccine preventable, understanding the populations affected by virus-induced cardiovascular complications is important to guide public health and clinical practice.AimThis observational study aimed to quantify the association between laboratory-confirmed respiratory bacteria or virus infections and risk of first MI or stroke, by using self-controlled case series (SCCS) analysis of anonymised linked electronic Danish health records.MethodsThe SCCS method was used to determine the relative incidence of the first event of MI and stroke occurring within 28 days after laboratory-confirmed respiratory infections compared with the baseline time period.ResultsIn the age and season adjusted analyses for first acute MI, the incidence ratios (IR) of a MI event occurring during the risk period were significantly elevated following a infection with values of 20.1, 11.0 and 4.9 during 1-3, 4-7 and 8-14 days, respectively and following respiratory virus infection with values of 15.2, 4.5 and 4.4 during 1-3, 8-14 and 15-28 days, respectively. The significantly elevated IRs for stroke following an infection were 25.5 and 6.3 during 1-3 and 8-14 days, respectively and following respiratory virus infection 8.3, 7.8 and 6.2 during 1-3, 4-7 and 8-14 days, respectively.ConclusionThis study suggested a significant cardiovascular event triggering effect following infection with and respiratory viruses (mainly influenza), indicating the importance of protection against vaccine-preventable respiratory infections.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.17.1900199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201950PMC
April 2020

A Systematic Review of Studies Published between 2016 and 2019 on the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease in an Elderly Population.

Pathogens 2020 Apr 3;9(4). Epub 2020 Apr 3.

Unit for Vaccination Programmes, Public Health Agency of Sweden, 171 82 Solna, Sweden.

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.
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http://dx.doi.org/10.3390/pathogens9040259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238108PMC
April 2020

A cluster analysis of serious adverse event reports after human papillomavirus (HPV) vaccination in Danish girls and young women, September 2009 to August 2017.

Euro Surveill 2019 May;24(19)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

BackgroundSuspected adverse events (AE) after human papillomavirus (HPV) vaccines include postural orthostatic tachycardia syndrome (POTS), chronic fatigue syndrome (CFS), complex regional pain syndrome (CRPS) and symptoms including headache and orthostatic intolerance.AimWe aimed to identify phenotypes of AEs after HPV vaccination, defined as patterns of AE terms (signs, symptoms, diagnoses), and to evaluate if identified phenotypes reflected previously suspected symptomatology or heightened public concerns over HPV vaccine safety since 1 January 2015.MethodsWe conducted a retrospective observational study using latent class cluster analysis of all serious AE reports (n = 963) reported by females residing in Denmark between September 2009 and August 2017. Resulting clusters were characterised according to AE terms associated with POTS, CFS and CRPS before (September 2009-December 2014) and during (January 2015-August 2017) a time of heightened media activity regarding HPV vaccines.ResultsFour clusters of AE reports were distinguished. The most common symptoms were fatigue, dizziness and headache but their frequency varied among clusters. The majority of reports in one cluster were submitted during a period of heightened media activity, including an anomalous spike in submissions in December 2015; a high proportion of these reports included the symptoms cognitive disorder (78%), abdominal pain (77%), dysuria (60%) and sleep disorder (60%).ConclusionsNon-specific symptoms including headache, fatigue and dizziness feature prominently in serious AE reports from females in Denmark. Our analysis identified a cluster of reports, likely media stimulated, with a focus on symptoms of CFS and POTS.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.19.1800380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518966PMC
May 2019

Decline in HPV-vaccination uptake in Denmark - the association between HPV-related media coverage and HPV-vaccination.

BMC Public Health 2018 Dec 10;18(1):1360. Epub 2018 Dec 10.

Division of Infectious Disease Preparedness, Statens Serum Institut, 2300, Copenhagen, Artillerivej 5, Denmark.

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.
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http://dx.doi.org/10.1186/s12889-018-6268-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288961PMC
December 2018

Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination.

Thorax 2019 05 24;74(5):473-482. Epub 2018 Oct 24.

EpiConcept, Paris, France.

Background: Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies.

Methods: For each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011-2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 - IRR)*100.

Results: After five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI -4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI -8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20-29% and 32-53% of IPD cases in PCV13 and PCV10 sites, respectively.

Conclusion: Overall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative.
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http://dx.doi.org/10.1136/thoraxjnl-2018-211767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484683PMC
May 2019

Differences in the Impact of Pneumococcal Serotype Replacement in Individuals With and Without Underlying Medical Conditions.

Clin Infect Dis 2019 06;69(1):100-106

Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.

Background: Pneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD). However, declines in IPD due to vaccine-targeted serotypes have been partially offset by increases in IPD due to nonvaccine serotypes (NVTs). The goal of this study was to quantify serotype-specific changes in the incidence of IPD that occurred in different age groups, with or without certain comorbidities, following the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the childhood vaccination program in Denmark.

Methods: We used nationwide surveillance data for IPD and a hierarchical Bayesian regression framework to estimate changes in the incidence of IPD associated with the introduction of PCV7 (2007) and PCV13 (2010) while controlling for serotype-specific epidemic cycles and unrelated secular trends.

Results: Following the introduction of PCV7 and PCV13 in children, the net impact of serotype replacement varied considerably by age group and comorbidities. Differences in the magnitude of serotype replacement were due to variations in the incidence of NVTs in the different risk groups before the introduction of PCVs. The relative increases in the incidence of IPD caused by specific NVTs did not differ appreciably between risk groups in the postvaccination period. Serotype replacement offset a greater proportion of the benefit of PCVs in strata in which the NVTs comprised a larger proportion of cases prior to the introduction of the vaccines.

Conclusions: These findings could help to predict the impact of next-generation PCVs in specific risk groups.
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http://dx.doi.org/10.1093/cid/ciy875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579958PMC
June 2019

Examining determinants for reporting suspected adverse events following HPV vaccination in Denmark.

Vaccine 2018 10 7;36(41):6158-6162. Epub 2018 Sep 7.

Infectious Disease Preparedness, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Electronic address:

HPV vaccination has been offered to 12-year-old girls as part of the Danish Childhood Vaccination Programme since 2009. From 2013, an increasing number of suspected severe adverse events (AE) without a documented causal link to the vaccine was observed, resulting in public concerns about vaccine safety and a decline in uptake. This study aimed at describing the group of females reporting AE and comparing them to vaccinated peers not reporting AE. A questionnaire focusing on demographics, lifestyle, and health-related issues was distributed to 251 female cases who had reported severe AE and 1,003 female controls randomly selected from the population-based Danish Vaccination Registry. All had been HPV-vaccinated. There were no significant differences on measures of self-reported psychiatric or somatic conditions before vaccination. More cases reported being physically very active prior to first HPV vaccination (OR 4.2) whereas fewer cases than controls sometimes (OR 0.31) or often/always (OR 0.36) felt sad. This is unexpected because two recent Danish registry-based case-control studies concluded that females reporting severe AE were more likely to consult a psychologist/psychiatrist and to have pre-existing psychiatric conditions before first HPV vaccination. One of these studies also showed that cases had increased health-care seeking regarding a number of somatic conditions prior to first vaccination. Our study adds value when seeking to understand the lifeworld of the affected females and their interpretations of their everyday lives pre- and post-HPV vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2018.08.061DOI Listing
October 2018

Identification of determinants associated with uptake of the first dose of the human papillomavirus vaccine in Denmark.

Vaccine 2018 09 12;36(38):5747-5753. Epub 2018 Aug 12.

Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark.

Background: The human papillomavirus vaccine (HPV vaccine) was introduced into the Danish Childhood Vaccination Programme in 2009. Following a national debate questioning the safety of the vaccine, the coverage decreased from an uptake of >90% for the first dose of the HPV vaccine to an uptake of 52% in girls born in 2003. The aim of this study was to identify changes in determinants for HPV vaccine hesitancy in the period when the debate spiraled and to identify determinants for specific hesitancy towards the HPV vaccine among girls who received the second dose of the measles, mumps and rubella vaccine.

Methods: We included girls born in the period 1999-2003 who were residing in Denmark between their 12th and 13th birthday (n = 161,528). Data from the Danish Vaccination Register were linked with demographic data from the Danish Civil Registration System. We used multiple logistic regression models to identify associations between determinants and the uptake of the first dose of the HPV vaccine (HPV1).

Results: For girls born in 1999-2000, low uptake was seen in children of increasing birth order, young or old age of mother, non-Danish origin, low uptake of other childhood vaccines, and in girls living with one parent. For girls born in 2001-2003, most of these determinants of low uptake became less significant. Birth order and origin showed different tendencies when comparing birth cohorts 1999-2000 with birth cohorts 2001-2003.

Conclusions: We found demographic disparities in the uptake of HPV1 that were generally in line with existing literature. More importantly, the results indicate that determinants for hesitancy towards the HPV vaccines changed during a period of intense public debate regarding the safety of the HPV vaccine. This may indicate that the public concerns over safety disproportionally affect those who trusted vaccines prior to the debate.
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http://dx.doi.org/10.1016/j.vaccine.2018.08.006DOI Listing
September 2018

Sociodemographic predictors are associated with compliance to a vaccination-reminder in 9692 girls age 14, Denmark 2014-2015.

Prev Med Rep 2018 Jun 23;10:93-99. Epub 2018 Feb 23.

Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark.

We aimed to identify sociodemographic predictors of compliance after receiving a personalised reminder on lacking vaccinations against MMR (Measles, Mumps, Rubella) and/or HPV (Human Papilloma Virus) among parents of Danish adolescent girls. A nationwide register-based study, including all 14-year-old girls (15 May 2014-14 May 2015) lacking either MMR, HPV-vaccination or both. Vaccination-compliance following a postal reminder was modelled using multivariable logistic regression and included the following socio-demographic predictors: maternal age, education, employment and ethnicity. Birth order, number of siblings, family-structure, location of residence, and household income. The parents of 9692 girls received a reminder. Out of 4940 exclusively lacking an HPV-vaccine, 15.3% were subsequently vaccinated. Among 2026 only lacking an MMR vaccination, 8.5% were vaccinated. Among 2726 girls lacking both, 5% received an HPV, 4.4% an MMR and 5.4% received both vaccinations. We identified sociodemographic differences between reminderletter-compliers and non-compliers, also according to vaccination types. Non-western descendants were more likely to receive HPV-vaccination, although the association was only significant for those who only lacked HPV (OR 2.02, 95% 1.57-2.59). For girls only lacking an MMR, regional differences were identified. Among girls lacking both vaccines, girls of mothers with intermediate (OR 0.63, 0.42-0.95) or basic education (OR 0.43, 0.24-0.75) were less likely to be vaccinated compared to girls of higher educated mothers. Reminders were in particular effective in increasing HPV uptake among immigrants of non-Western ethnicity. We found reminders to be less effective among less educated mothers whose daughters lacked both vaccines. To increase the coverage in this group, additional interventions are needed.
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http://dx.doi.org/10.1016/j.pmedr.2018.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984205PMC
June 2018

Quadrivalent human papillomavirus vaccination in boys and risk of autoimmune diseases, neurological diseases and venous thromboembolism.

Int J Epidemiol 2018 04;47(2):634-641

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

Background: In recent years, human papillomavirus (HPV) vaccination of boys has been added to childhood vaccination programmes in several countries but, so far, no systematic population-based assessment with long-term follow-up has been undertaken of the relative incidence of adverse outcomes following HPV vaccination in this group. We investigated if quadrivalent HPV (qHPV) vaccination of 10-17-year-old boys is associated with any unusual risk of autoimmune diseases, neurological diseases or venous thromboembolism.

Methods: We conducted a national cohort study of 568 410 boys born in Denmark 1988-2006 and followed for 4 million person-years during 2006-16, using nationwide registers to obtain individual-level information about received doses of the qHPV vaccine and hospital records for 39 autoimmune diseases, 12 neurological diseases and venous thromboembolism. For each outcome, we estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) according to qHPV vaccination status.

Results: Altogether 7384 boys received at least one dose of the qHPV vaccine at age 10-17 years. Overall, RRs were close to unity for the combined groups of autoimmune diseases (RR = 0.96; 95% CI: 0.71-1.28, n = 46 cases in qHPV-vaccinated boys) and neurological diseases (RR = 0.67; 0.41-1.10, n = 16), as well as for venous thromboembolism (RR = 0.88; 0.33-2.35, n = 4). After taking multiple testing into account, none of the 52 individual outcomes studied appeared to occur in excess among qHPV-vaccinated boys.

Conclusions: Although additional large-scale epidemiological studies are warranted, our findings provide population-based reassurance that qHPV vaccination of 10-17-year-old boys is unlikely to be associated with an elevated risk of autoimmune diseases, neurological diseases or venous thromboembolism.
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http://dx.doi.org/10.1093/ije/dyx273DOI Listing
April 2018

Kitchen PM concentrations and child acute lower respiratory infection in Bhaktapur, Nepal: The importance of fuel type.

Environ Res 2018 02;161:546-553

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720-7360, USA.

Background: Globally, solid fuels are used by about 3 billion people for cooking and a smaller number use kerosene. These fuels have been associated with acute lower respiratory infection (ALRI) in children. Previous work in Bhaktapur, Nepal, showed comparable relationships of biomass and kerosene cooking fuels with ALRI in young children, compared to those using electricity for cooking. We examine the relationship of kitchen PM concentrations to ALRI in those households.

Methods: ALRI cases and age-matched controls were enrolled from a cohort of children 2-35 months old. 24-h PM was measured once in each participant's kitchen. The main analysis was carried out with conditional logistic regression, with PM measures specified both continuously and as quartiles.

Results: In the kitchens of 393 cases and 431 controls, quartiles of increasing PM concentration were associated with a monotonic increase in odds ratios (OR): 1.51 (95% CI: 1.00, 2.27), 2.22 (1.47, 3.34), 2.48 (1.63, 3.77), for the 3 highest exposure quartiles. The general kitchen concentration-response shape across all stoves was supralinear. There was evidence for increased risk with biomass stoves, but the slope for kerosene stoves was steeper, the highest quartile OR being 5.36 (1.35, 21.3). Evidence for increased risk was also found for gas stoves.

Conclusion: Results support previous reports that biomass and kerosene cooking fuels are both ALRI risk factors, but suggests that PM from kerosene is more potent on a unit mass basis. Further studies with larger sample sizes and preferably using electricity as the baseline fuel are needed.
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http://dx.doi.org/10.1016/j.envres.2017.11.056DOI Listing
February 2018

Modelling stunting in LiST: the effect of applying smoothing to linear growth data.

BMC Public Health 2017 Nov 7;17(Suppl 4):778. Epub 2017 Nov 7.

Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Background: The Lives Saved Tool (LiST) is a widely used resource for evidence-based decision-making regarding health program scale-up in low- and middle-income countries. LiST estimates the impact of specified changes in intervention coverage on mortality and stunting among children under 5 years of age. We aimed to improve the estimates of the parameters in LiST that determine the rate at which the effects of interventions to prevent stunting attenuate as children get older.

Methods: We identified datasets with serial measurements of children's lengths or heights and used random effects models and restricted cubic splines to model the growth trajectories of children with at least six serial length/height measurements. We applied WHO growth standards to both measured and modelled (smoothed) lengths/heights to determine children's stunting status at multiple ages (1, 6, 12, 24 months). We then calculated the odds ratios for the association of stunting at one age point with stunting at the next ("stunting-to-stunting ORs") using both measured and smoothed data points. We ran analyses in LiST to compare the impact on intervention effect attenuation of using smoothed rather than measured stunting-to-stunting ORs.

Results: A total of 21,786 children with 178,786 length/height measurements between them contributed to our analysis. The odds of stunting at a given age were strongly related to whether a child is stunted at an earlier age, using both measured and smoothed lengths/heights, although the relationship was stronger for smoothed than measured lengths/heights. Using smoothed lengths/heights, we estimated that children stunted at 1 month have 45 times the odds of being stunted at 6 months, with corresponding odds ratios of 362 for the period 6 to 12 months and 175 for the period 12 to 24 months. Using the odds ratios derived from the smoothed data in LiST resulted in a somewhat slower attenuation of intervention effects over time, but substantial attenuation was still observed in the LiST outputs. For example, in Mali the effect of effectively eliminating SGA births reduced prevalence of stunting at age 59 months from 44.4% to 43.7% when using odds ratios derived from measured lengths/heights and from 44.4% to 41.9% when using odds ratios derived from smoothed lengths/heights.

Conclusions: Smoothing of children's measured lengths/heights increased the strength of the association between stunting at a given age and stunting at an earlier age. Using odds ratios based on smoothed lengths/heights in LiST resulted in a small reduction in the attenuation of intervention effects with age and thus some increase in the estimated benefits, and may better reflect the true benefits of early nutritional interventions.
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http://dx.doi.org/10.1186/s12889-017-4744-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688407PMC
November 2017

Ethnic background and human papillomavirus vaccine uptake in Denmark: A countrywide retrospective cohort study including 274,154 women aged 19-28 years.

Papillomavirus Res 2016 12 14;2:78-84. Epub 2016 Apr 14.

Infectious Disease Epidemiology, Statens Serum Institut, Artillerivej 5 2300 København S, Copenhagen, Denmark. Electronic address:

Aim: We examined ethnicity-related differences in the uptake of a temporary free-of-charge HPV vaccine (HPVV) catch-up programme offered in Denmark from August 2012 to December 2013 to women born from 1985-1992 and compared it with the previous self-payment system in place.

Methods: We conducted a nationwide retrospective cohort study. We performed logistic regression analyses to examine the relationship between ethnic background and HPV vaccine (HPVV) programme initiation.

Results: The free programme increased the vaccination uptake from 16% to 75%. Descendants (Denmark-born women with both parents of foreign origin) and immigrants in Denmark for more than 5 years were less likely to initiate the free HPVV programme than Denmark-born women ((aOR=0.56; 95% CI: 0.54-0.59) and (aOR=0.39; 95% CI: 0.38-0.40), respectively). The likelihood of HPVV programme initiation among immigrants increased with time in Denmark ((aOR=2.28; 95% CI: 2.11-2.48) for immigrants living in Denmark for 16-20 years compared to 6-10 years)).

Conclusion: The initiation of the free-of-charge HPVV programme was satisfactory. However, large differences in uptake were demonstrated, indicating that some target groups are harder to reach than others. The integration process (as related to use of health services) occurs over many years where differences between the different population groups seem to vanish.
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http://dx.doi.org/10.1016/j.pvr.2016.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886896PMC
December 2016

A nationwide study on the impact of pneumococcal conjugate vaccination on antibiotic use and ventilation tube insertion in Denmark 2000-2014.

Vaccine 2017 10 18;35(43):5858-5863. Epub 2017 Sep 18.

Epidemiology, Biostatistics and Biodemography, University of Southern Denmark, J.B. Winsløws Vej 9 B, 5000 Odense C, Denmark; Department of ENT Head & Neck Surgery, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark.

Introduction of Pneumococcal Conjugated Vaccines (PCV) in national immunization programs have been successful in reducing the number of invasive and lower respiratory pneumococcal infections. The impact of the vaccines on upper respiratory infections caused by pneumococci is less clear although these account for most pneumococcal infections. In this study, we used likely proxies for respiratory infections in children, such as antibiotic use and ventilation tube insertions (VTI), to estimate the impact of the vaccine on a national level. The study was designed as a population-based retrospective observational study, comparing trends in the incidence rate of antibiotic prescriptions and VTIs in the period 2000-2014, where PCV7 was introduced in 2007 and PCV13 in 2010. The introduction of PCV7 and PCV13 correlated with changes in the incidence rate from an almost steady increase in prescription of antibiotics in the pre-PCV period to a decreasing incidence for all children age 0-15years. The 2.4 DDD per person year in 2014 was at almost the same level of antibiotic use as in 2000 at 2.3 DDD per person year. Similar patterns were observed in the mostly vaccinated age groups below 5years of age. For VTI we observed a decreasing incidence rate in the years following introduction of PCV13 ending with a slightly higher incidence at 35 per 1000 person years in 2014 compared to 31 in year 2000. We conclude that the steady increase in antibiotic use and VTI in the pre-PCV period have been partially reversed to near year 2000 levels after the introduction of PCV. This indicates that implementation of pneumococcal vaccines in the Childhood Vaccination Programme has likely reduced the incidence of upper respiratory diseases due to pneumococci in Denmark.
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http://dx.doi.org/10.1016/j.vaccine.2017.09.006DOI Listing
October 2017

[Acute meningococcal disease in children and adolescents].

Ugeskr Laeger 2017 Sep;179(36)

Meningococcal disease is a rapidly progressing infection, which continues to cause deaths among children and adolescents. In this review, clinical signs and initial treatment of acute childhood meningococcal disease is described. Operational flow charts have been developed for assessment of non-blanching rash and initial treatment of meningococcal disease.
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September 2017

Vitamin D status is associated with treatment failure and duration of illness in Nepalese children with severe pneumonia.

Pediatr Res 2017 Dec 16;82(6):986-993. Epub 2017 Aug 16.

Centre for Intervention Science in Maternal and Child Health, Centre for International Health, Department of Medicine and Odontology, University of Bergen, Bergen, Norway.

BackgroundThere is no consensus on optimal Vitamin D status. The objective of this study was to estimate the extent to which vitamin D status predicts illness duration and treatment failure in children with severe pneumonia by using different cutoffs for vitamin D concentration.MethodsWe measured the plasma concentration of 25(OH)D in 568 children hospitalized with World Health Organization-defined severe pneumonia. The associations between vitamin D status, using the most frequently used cutoffs for vitamin D insufficiency (25(OH)D<50 and <75 nmol/l), and risk for treatment failure and time until recovery were analyzed in multiple logistic regression and Cox proportional hazards models, respectively.ResultsOf the 568 children, 322 (56.7%) had plasma 25(OH)D levels ≥75 nmol/l, 179 (31.5%) had levels of 50-74.9 nmol/l, and 67 (%) had levels <50 nmol/l. Plasma 25(OH)D <50 nmol/l was associated with increased risk for treatment failure and longer time until recovery.ConclusionOur findings indicate that low vitamin D status (25(OH)D<50 nmol/l) is an independent risk factor for treatment failure and delayed recovery from severe lower respiratory infections in children.
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http://dx.doi.org/10.1038/pr.2017.71DOI Listing
December 2017

Written reminders increase vaccine coverage in Danish children - evaluation of a nationwide intervention using The Danish Vaccination Register, 2014 to 2015.

Euro Surveill 2017 Apr;22(17)

Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark.

We evaluated a national intervention of sending written reminders to parents of children lacking childhood vaccinations, using the Danish Vaccination Register (DDV). The intervention cohort included the full birth cohort of 124,189 children born in Denmark who reached the age of 2 and 6.5 years from 15 May 2014 to 14 May 2015. The reference cohort comprised 124,427 children who reached the age of 2 and 6.5 years from 15 May 2013 to 14 May 2014. Vaccination coverage was higher in the intervention cohort at 2.5 and 7 years of age. The differences were most pronounced for the second dose of the measles-mumps-rubella vaccine (MMR2) and the diphtheria-tetanus-pertussis-polio vaccine DTaP-IPV4 among the 7-year-olds, with 5.0 percentage points (95% confidence interval (CI): 4.5-5.4) and 6.4 percentage points (95% CI: 6.0-6.9), respectively. Among the 2.5 and 7-year-olds, the proportion of vaccinations in the preceding 6 months was 46% and three times higher, respectively, in the intervention cohort than the reference cohort. This study indicates a marked effect of personalised written reminders, highest for the vaccines given later in the schedule in the older cohort. In addition, the reminders increased awareness about correct registration of vaccinations in DDV.
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http://dx.doi.org/10.2807/1560-7917.ES.2017.22.17.30522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434886PMC
April 2017

25-Hydroxy-Vitamin D Concentration Is Not Affected by Severe or Non-Severe Pneumonia, or Inflammation, in Young Children.

Nutrients 2017 Jan 17;9(1). Epub 2017 Jan 17.

Innlandet Hospital Trust, Lillehammer, Anders Sandvigs gt. 17, 2609 Lillehammer, Norway.

Poor vitamin D status has been associated with increased risk and severity of respiratory tract infections. Whether or not inflammation and infection affects 25-hydroxy vitamin D (25(OH)D) concentration is controversial and is important in the interpretation of observational studies using plasma-25(OH)D as a biomarker for status. Our objectives were to measure whether 25(OH)D concentration was altered by an episode of acute lower respiratory tract infection and whether markers of inflammation predicted the 25(OH)D concentration. Children aged 2-35 months with severe ( 43) and non-severe ( 387) community-acquired, WHO-defined pneumonia were included. 25(OH)D concentration and inflammatory markers (cytokines, chemokines, and growth factors) were measured in plasma during the acute phase and 14, 45, and 90 days later. Predictors for 25(OH)D concentrations were identified in multiple linear regression models. Mean 25(OH)D concentration during the acute phase and after recovery (14, 45, and 90 days) was 84.4 nmol/L ± 33.6, and 80.6 ± 35.4, respectively. None of the inflammatory markers predicted 25(OH)D concentration in the multiple regression models. Age was the most important predictor for 25(OH)D concentration, and there were no differences in 25(OH)D concentrations during illness and after 14, 45, and 90 days when adjusting for age. Infection and inflammation did not alter the 25(OH)D concentration in young children with acute lower respiratory tract infections.
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http://dx.doi.org/10.3390/nu9010052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295096PMC
January 2017

The incidence of invasive pneumococcal serotype 3 disease in the Danish population is not reduced by PCV-13 vaccination.

Heliyon 2016 Nov 29;2(11):e00198. Epub 2016 Nov 29.

Neisseria and Streptococcus Reference Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.

Since 2010, Denmark has included the 13-valent pneumococcal conjugated vaccine (PCV-13) in the childhood immunization programme. However, serotype 3 remains as an important cause of invasive pneumococcal disease (IPD) in Denmark. IPD surveillance data (1999-2016) was used to calculate the incidence and age-distribution of serotype 3 IPD, and the effect of PCV-13 on serotype 3 IPD incidence was examined. The incidence of serotype 3 IPD in the age group below 65 years was 0.51/100,000 pre PCV-13, and 0.45/100,000 post PCV-13. In the group 0-4 years, serotype 3 IPD incidence was 0.28/100,000 pre PCV-13, and 0.16/100,000 post PCV-13. Serotype 3 IPD incidence in the elderly showed a mean of 4.27/100,000 pre PCV-13, and 4.32/100,000 post PCV-13. PCV-13 childhood immunization in Denmark has not lead to a reduction of the incidence of IPD caused by serotype 3. The reason behind this missing effect needs to be investigated further.
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http://dx.doi.org/10.1016/j.heliyon.2016.e00198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133732PMC
November 2016

Pre-Vaccination Care-Seeking in Females Reporting Severe Adverse Reactions to HPV Vaccine. A Registry Based Case-Control Study.

PLoS One 2016 9;11(9):e0162520. Epub 2016 Sep 9.

Department of Infectious Diseases Epidemiology, Statens Serum Institut, Copenhagen, Denmark.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162520PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017678PMC
August 2017

Meticillin-resistant Staphylococcus aureus CC398 is an increasing cause of disease in people with no livestock contact in Denmark, 1999 to 2011.

Euro Surveill 2015 ;20(37)

Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.

Livestock constitutes a potential reservoir of meticillin-resistant Staphylococcus aureus isolates belonging to a recently derived lineage within clonal complex 398 (MRSA CC398-IIa). Since its discovery in the early 2000s, this lineage has become a major cause of human disease in Europe, posing a serious public health challenge in countries with intensive livestock production. To retrace the history of human colonisation and infection with MRSA CC398-IIa in Denmark, we conducted a nationwide, retrospective study of MRSA isolates collected from 1999 to 2011. Among 7,429 MRSA isolates screened, we identified 416 MRSA CC398-IIa isolates. Of these, 148 were from people with infections, including 51 from patients reporting no livestock exposure. The first cases of MRSA CC398-IIa infection in Denmark occurred in 2004. Subsequently, the incidence of MRSA CC398-IIa infection showed a linear annual increase of 66% from 2004 to 2011 (from 0.09 to 1.1 per 100,000 person-years). There were clear temporal and spatial relationships between MRSA CC398-IIa-infected patients with and without livestock exposure. These findings suggest substantial dissemination of MRSA CC398-IIa from livestock or livestock workers into the Danish community and underscore the need for strategies to control its spread both on and off the farm.
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http://dx.doi.org/10.2807/1560-7917.ES.2015.20.37.30021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902279PMC
April 2016

Cytokine Concentrations in Plasma from Children with Severe and Non-Severe Community Acquired Pneumonia.

PLoS One 2015 25;10(9):e0138978. Epub 2015 Sep 25.

Department of Medical Microbiology, Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway.

Background: Children in low and middle-income countries have a high burden of pneumonia. Measuring the cytokine responses may be useful to identify novel markers for diagnosing, monitoring, and treating pneumonia.

Objective: To describe and compare a wide range of inflammatory mediators in plasma from children with WHO-defined severe and non-severe community acquired pneumonia (CAP), and explore to what extent certain mediators are associated with severity and viral detection.

Methods: We collected blood samples from 430 children with severe (n = 43) and non-severe (n = 387) CAP. Plasma from these children were analysed for 27 different cytokines, and we measured the association with age, disease severity and viral detection.

Results: There were generally higher plasma concentrations of several cytokines with both pro-inflammatory and anti-inflammatory effects among children with severe CAP than in children with non-severe CAP. We found significantly higher concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-9, IL-15, eotaxin, basic fibroblast growth factor (b-FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-α) in the group of severe CAP. Most of these associations persisted when adjusting for age in linear regression analyses. The cytokine response was strongly associated with age but to a lesser extent with viral etiology.

Conclusion: The plasma concentrations of several cytokines, both with pro-inflammatory and anti-inflammatory effects, were higher among children with severe illness. In particular G-CSF and IL-6 reflected severity and might provide complementary information on the severity of the infection.

Trial Registration: ClinicalTrials.gov NCT00148733.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138978PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583304PMC
June 2016