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Background: Estimates of the severity of the SARS-CoV-2 omicron variant (B.1.1.529) are crucial to assess the public health impact associated with its rapid global dissemination. We estimated the risk of SARS-CoV-2-related hospitalisations after infection with omicron compared with the delta variant (B.1.617.2) in Denmark, a country with high mRNA vaccination coverage and extensive free-of-charge PCR testing capacity. Methods: In this observational cohort study, we included all RT-PCR-confirmed cases of SARS-CoV-2 infection in Denmark, with samples taken between Nov 21 (date of first omicron-positive sample) and Dec 19, 2021. Individuals were identified in the national COVID-19 surveillance system database, which included results of a variant-specific RT-PCR that detected omicron cases, and data on SARS-CoV-2-related hospitalisations (primary outcome of the study). We calculated the risk ratio (RR) of hospitalisation after infection with omicron compared with delta, overall and stratified by vaccination status, in a Poisson regression model with robust SEs, adjusted a priori for reinfection status, sex, age, region, comorbidities, and time period. Findings: Between Nov 21 and Dec 19, 2021, among the 188 980 individuals with SARS-CoV-2 infection, 38 669 (20·5%) had the omicron variant. SARS-CoV-2-related hospitalisations and omicron cases increased during the study period. Overall, 124 313 (65·8%) of 188 980 individuals were vaccinated, and vaccination was associated with a lower risk of hospitalisation (adjusted RR 0·24, 95% CI 0·22–0·26) compared with cases with no doses or only one dose of vaccine. Compared with delta infection, omicron infection was associated with an adjusted RR of hospitalisation of 0·64 (95% CI 0·56–0·75; 222 [0·6%] of 38 669 omicron cases admitted to hospital vs 2213 [1·5%] of 150 311 delta cases). For a similar comparison by vaccination status, the RR of hospitalisation was 0·57 (0·44–0·75) among cases with no or only one dose of vaccine, 0·71 (0·60–0·86) among those who received two doses, and 0·50 (0·32–0·76) among those who received three doses. Interpretation: We found a significantly lower risk of hospitalisation with omicron infection compared with delta infection among both vaccinated and unvaccinated individuals, suggesting an inherent reduced severity of omicron. Our results could guide modelling of the effect of the ongoing global omicron wave and thus health-care system preparedness. Funding: None.

Polymerase chain reaction (PCR) and antigen tests have been used extensively for screening during the severe acute respiratory syndrome coronavirus 2 pandemics. However, the real-world sensitivity and specificity of the two testing procedures in the field have not yet been estimated without assuming that the PCR constitutes a gold standard test. We use latent class models to estimate the in situ performance of both tests using data from the Danish national registries. We find that the specificity of both tests is very high (>99.7%), while the sensitivities are 95.7% (95% confidence interval [CI]: 92.8%–98.4%) and 53.8% (95% CI: 49.8%–57.9%) for the PCR and antigen tests, respectively. These findings have implications for the use of confirmatory PCR tests following a positive antigen test result: we estimate that serial testing is counterproductive at higher prevalence levels.

The world has seen numerous infectious disease outbreaks in the past decade. In many cases these outbreaks have had considerable perinatal health consequences including increased risk of preterm delivery (e.g., influenza, measles, and COVID-19), and the delivery of low birth weight or small for gestational age babies (e.g., influenza, COVID-19). Furthermore, severe perinatal outcomes including perinatal and infant death are a known consequence of multiple infectious diseases (e.g., Ebola virus disease, Zika virus disease, pertussis, and measles). In addition to vaccination during pregnancy (where possible), pregnant women, are provided some level of protection from the adverse effects of infection through community-level application of evidence-based transmission-control methods. This review demonstrates that it takes almost 2 years for the perinatal impacts of an infectious disease outbreak to be reported. However, many infectious disease outbreaks between 2010 and 2020 have no associated pregnancy data reported in the scientific literature, or pregnancy data is reported in the form of case-studies only. This lack of systematic data collection and reporting has a negative impact on our understanding of these diseases and the implications they may have for pregnant women and their unborn infants. Monitoring perinatal health is an essential aspect of national and global healthcare strategies as perinatal life has a critical impact on early life mortality as well as possible effects on later life health. The unpredictable nature of emerging infections and the potential for adverse perinatal outcomes necessitate that we thoroughly assess pregnancy and perinatal health implications of disease outbreaks and their public health interventions in tandem with outbreak response efforts. Disease surveillance programs should incorporate perinatal health monitoring and health systems around the world should endeavor to continuously collect perinatal health data in order to quickly update pregnancy care protocols as needed.

BackgroundStaphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes.MethodsFirst-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB >48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis.ResultsWe identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86–2.41]). No difference in mortality was observed with 0–40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI, .83–1.37]), while with 41–365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI, .53–.95]).ConclusionsCommunity-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality. Community-acquired Staphylococcus aureus bacteremia (SAB) was associated with twice the odds for infective endocarditis (IE), as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated S aureus IE.Background Staphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes. Methods First-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB >48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis. Results We identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86-2.41]). No difference in mortality was observed with 0-40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI, .83-1.37]), while with 41-365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI, .53-.95]). Conclusions Community-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality.

Background Monitoring of microbiological cause of infective endocarditis (IE) remains key in the understanding of IE; however, data from large, unselected cohorts are sparse. We aimed to examine temporal changes, patient characteristics, and in‐hospital and long‐term mortality, according to microbiological cause in patients with IE from 2010 to 2017. Methods and Results Linking Danish nationwide registries, we identified all patients with first‐time IE. In‐hospital and long‐term mortality rates were assessed according to microbiological cause and compared using multivariable adjusted logistic regression analysis and Cox proportional hazard analysis, respectively. A total of 4123 patients were included. Staphylococcus aureus was the most frequent cause (28.1%), followed by Streptococcus species (26.0%), Enterococcus species (15.5%), coagulase‐negative staphylococci (6.2%), and “other microbiological causes” (5.3%). Blood culture–negative IE was registered in 18.9%. The proportion of blood culture–negative IE declined during the study period, whereas no significant changes were seen for any microbiological cause. Patients with Enterococcus species were older and more often had a prosthetic heart valve compared with other causes. For Streptococcus species IE, in‐hospital and long‐term mortality (median follow‐up, 2.3 years) were 11.1% and 58.5%, respectively. Compared with Streptococcus species IE, the following causes were associated with a higher in‐hospital mortality: S aureus IE (odds ratio [OR], 3.48 [95% CI, 2.74–4.42]), Enterococcus species IE (OR, 1.48 [95% CI, 1.11–1.97]), coagulase‐negative staphylococci IE (OR, 1.79 [95% CI, 1.21–2.65]), “other microbiological cause” (OR, 1.47 [95% CI, 0.95–2.27]), and blood culture–negative IE (OR, 1.99 [95% CI, 1.52–2.61]); and the following causes were associated with higher mortality following discharge (median follow‐up, 2.9 years): S aureus IE (hazard ratio [HR], 1.39 [95% CI, 1.19–1.62]), Enterococcus species IE (HR, 1.31 [95% CI, 1.11–1.54]), coagulase‐negative staphylococci IE (HR, 1.07 [95% CI, 0.85–1.36]), “other microbiological cause” (HR, 1.45 [95% CI, 1.13–1.85]), and blood culture–negative IE (HR, 1.05 [95% CI, 0.89–1.25]). Conclusions This nationwide study showed that S aureus was the most frequent microbiological cause of IE, followed by Streptococcus species and Enterococcus species. Patients with S aureus IE had the highest in‐hospital mortality .

BACKGROUND: Superinfection following viral infection is a known complication, which may lead to longer hospitalisation and worse outcome. Empirical antibiotic therapy may prevent bacterial superinfections, but may also lead to overuse, adverse effects and development of resistant pathogens. Knowledge about the incidence of superinfections in intensive care unit (ICU) patients with severe Coronavirus Disease 2019 (COVID-19) is limited.METHODS: We will conduct a nationwide cohort study comparing the incidence of superinfections in patients with severe COVID-19 admitted to the ICU compared with ICU patients with influenza A/B in Denmark. We will include approximately 1000 patients in each group from the time period of 1 October 2014 to 30 April 2019 and from 10 March 2020 to 1 March 2021 for patients with influenza and COVID-19, respectively. The primary outcome is any superinfection within 90 days of admission to the ICU. We will use logistic regression analysis comparing COVID-19 with influenza A/B after adjustment for relevant predefined confounders. Secondarily, we will use unadjusted and adjusted logistic regression analyses to assess six potential risk factors (sex, age, cancer [including haematological], immunosuppression and use of life support on day 1 in the ICU) for superinfections and compare outcomes in patients with COVID-19 with/without superinfections, and present descriptive data regarding the superinfections.CONCLUSION: This study will provide important knowledge about superinfections in ICU patients with severe COVID-19.

Background Proton-pump inhibitors (PPIs) have been reported to increase the risk of community-associated Clostridium difficile infection (CDI), but the association remains disputed. Methods A nationwide cohort study among adults in Denmark, 2010–2013, linking register data on C. difficile testing, filled prescriptions, and patient characteristics. All incident episodes of community-associated CDI (ie, positive culture, molecular assay, or toxin test in individuals without previous hospitalization in the prior 12 weeks and without a positive test for C. difficile in the prior 8 weeks) were identified in the Danish National Microbiological Database. Self-controlled case-series analyses were used to estimate incidence rate ratios (IRRs) for community-associated CDI, comparing periods with and without exposure to PPIs. By design, models took fixed confounders such as chronic disease, genetics, and socioeconomic status into account; further, time-varying confounders, including hospital stay and antibiotic and corticosteroid use were adjusted for. Results 3583 episodes of community-associated CDI were identified, of which 964 occurred during current use of PPIs, 324 occurred 0–6 months after treatment cessation, 123 occurred 6–12 months after treatment cessation, and 2172 occurred during time periods without use of PPIs. The adjusted IRR was 2.03 (95% confidence interval, 1.74–2.36), comparing use of PPI with nonuse. The increased risk remained elevated in later time periods: 1.54 (1.31–1.80) for 0–6 months, 1.24 (1.00–1.53) for 6–12 months after current use. Conclusions Use of PPIs was associated with moderately increased risk of community-associated CDI. The risk remained elevated up to 1 year after PPI treatment had ended.

Background To facilitate research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a prospective cohort of all Danish residents tested for SARS-CoV-2 in Denmark is established. Data structure All Danish residents tested by reverse transcriptase polymerase chain reactions (RT-PCR) for SARS-CoV-2 in Denmark are included. The cohort is identified using the Danish Microbiology Database. Individual-level record linkage between administrative and health-care registries is facilitated by the Danish Civil Registration System. Information on outcomes related to SARS-CoV-2 infection includes hospital admission, intensive care unit admission, mechanical ventilation, and death and is retrieved from the five administrative Danish regions, the Danish National Patient Registry, and the Danish Register of Causes of Death. The Patient Registry further provides a complete hospital contact history of somatic and psychiatric conditions and procedures. Data on all prescriptions filled at community pharmacies are available from the Danish National Prescription Registry. Health-care authorization status is obtained from the Danish Register of Healthcare Professionals. Finally, selected laboratory values are obtained from the Register of Laboratory Results for Research. The cohort is governed by a steering committee with representatives from the Danish Medicines Agency, Statens Serum Institut, the Danish Health Authority, the Danish Health Data Authority, Danish Patients, the Faculties of Health Sciences at the Danish universities, and Danish regions. The steering committee welcomes suggestions for research studies and collaborations. Research proposals will be prioritized based on timeliness and potential clinical and public health implications. All research protocols assessing specific hypotheses for medicines will be made publicly available using the European Union electronic Register of Post-Authorisation Studies. Conclusion The Danish COVID-19 cohort includes all Danish residents with an RT-PCR test for SARS-CoV-2. Through individual-level linkage with existing Danish health and administrative registries, this is a valuable data source for epidemiological research on SARS-CoV-2.

Background: The more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages. Methods: We did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion. Findings: Between Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72–0·87; p

Background In Denmark, influenza surveillance is ensured by data capturing from existing population-based registers. Since 2017, point-of-care (POC) testing has been implemented outside the regional clinical microbiology departments (CMD). Aim We aimed to assess influenza laboratory results in view of the introduction of POC testing. Methods We retrospectively observed routine surveillance data on national influenza tests before and after the introduction of POC testing as available in the Danish Microbiological Database. Also, we conducted a questionnaire study among Danish CMD about influenza diagnostics. Results Between the seasons 2014/15 and 2018/19, 199,744 influenza tests were performed in Denmark of which 44,161 were positive (22%). After the introduction of POC testing, the overall percentage of positive influenza tests per season did not decrease. The seasonal influenza test incidence was higher in all observed age groups. The number of operating testing platforms placed outside a CMD and with an instrument analytical time ≤ 3 h increased after 2017. Regionally, the number of tests registered as POC in the Danish Microbiological Database and the number of tests performed with an instrument analytical time ≤ 3 h or outside a CMD partially differed. Where comparable (71% of tests), the relative proportion of POC tests out of all tests increased from season 2017/18 to 2018/19. In both seasons, the percentage of positive POC tests resulted slightly lower than for non-POC tests. Conclusion POC testing integrated seamlessly into national influenza surveillance. We propose the use of POC results in the routine surveillance of seasonal influenza.

The COVID-19 pandemic has led to an unprecedented demand for real-time surveillance data in order to inform critical decision makers regarding the management of the pandemic. The aim of this review was to describe how the Danish national microbiology database, MiBa, served as a cornerstone for providing data to the real-time surveillance system by linkage to other nationwide health registries. The surveillance system was established on an existing IT health infrastructure and a close network between clinical microbiologists, information technology experts, and public health officials. In 2020, testing capacity for SARS-CoV-2 was ramped up from none to over 10,000 weekly PCR tests per 100,000 population. The crude incidence data mirrored this increase in testing. Real-time access to denominator data and patient registries enabled adjustments for fluctuations testing activity, providing robust data on crude SARS-CoV-2 incidence during the changing diagnostic and management strategies. The use of the same data for different purposes, for example, final laboratory reports, information to the public, contact tracing, public health, and science, has been a critical asset for the pandemic response. It has also raised issues concerning data protection and critical capacity of the underlying technical systems and key resources. However, even with these limitations, the setup has enabled decision makers to adopt timely interventions. The experiences from COVID-19 may motivate a transformation from traditional indicator-based public health surveillance to an all-encompassing information system based on access to a comprehensive set of data sources, including diagnostic and reference microbiology.

1AbstractAimThe aim of this study was to estimate the household transmissibility of SARS-CoV-2 for lineage B.1.1.7 compared with other lineages, by age and viral load. Further-more, we wanted to estimate whether there is a multiplicative or additive effect of the increased transmissibility of B.1.1.7 compared with other lineages.BackgroundNew lineages of SARS-CoV-2 are of potential concern due to higher transmissibility, risk of severe outcomes, and/or escape from neutralizing antibodies. Lineage B.1.1.7 has been estimated to be more transmissible than other previously known lineages, but the association between transmissibility and risk factors, such as age of primary case and viral load is still unknown.MethodsWe used comprehensive administrative data from Denmark, comprising the full population, all SARS-CoV-2 RT-PCR tests, and all WGS lineage data (January 11 to February 7, 2021), to estimate household transmissibility stratified by lineage B.1.1.7 and other lineages.ResultsWe included 5,241 households with primary cases; 808 were infected with SARS-CoV-2 lineage B.1.1.7 and 4,433 were infected with other lineages. The attack rate was 38% in households with a primary case infected with B.1.1.7 and 27% in households with a primary case infected with other lineages. Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load.ConclusionsThe results found in this study add new knowledge that can be used to mitigate the further spread of SARS-CoV-2 lineage B.1.1.7, which is becoming increasingly widespread in numerous countries. Our results clarify that the transmissibility of B.1.1.7 should be included as a multiplicative effect in mathematical models used as a tool for decision makers. The results may have important public health implications, as household transmission may serve as a bridge between otherwise separate transmission domains, such as schools and physical workplaces, despite implemented non-pharmaceutical interventions.

AimThe objective of this nationwide study was to investigate the association between SARS-CoV-2 transmissibility, viral load, and age of primary cases in Danish households.BackgroundSpread in households represents a major mode of transmission of SARS-CoV-2. In order to take proper action against the spread of the disease, it is important to have a better understanding of transmission in the household domain—including the role of viral load of primary cases.MethodsThe study was designed as an observational cohort study, using detailed administrative register data. We included the full population of Denmark and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021) to estimate transmissibility in house-holds comprising 2-6 people. RT-PCR Cycle threshold (Ct) values were used as a proxy for viral load.ResultsWe identified 63,657 primary cases and 139,882 household members of which 21% tested positive by RT-PCR within a 1-14 day period after the primary case. There was an approximately linear association between Ct value of the sample and transmissibility, implying that cases with samples having a higher viral load were more transmissible than cases with samples having a lower viral load. However, even for primary cases with relatively high sample Ct values, the transmissibility was not negligible, e.g., for primary cases with a sample Ct value of 38, we found that 13% of the primary cases had at least one secondary household case. Moreover, 34% of all secondary cases were found in households with primary cases having sample Ct values >30. An increasing transmissibility with age of the primary cases for adults (≥20 years) and a decreasing transmissibility with age for children (ConclusionsAlthough primary cases with sample high viral loads (low Ct values) were associated with higher SARS-CoV-2 transmissibility, we found no obvious cut-off for sample Ct values to eliminate transmissibility and a substantial amount of household transmission occurred in households where the primary cases had high sample Ct values (low viral load), The study further showed that transmissibility increases with age. These results have important public health implications, as they suggest that contact tracing should prioritize cases according to Ct values and age, and underline the importance of quick identification and isolation of cases. Furthermore, the study highlights that households can serve as a transmission bridge by creating connections between otherwise separate domains.

Background Infective endocarditis (IE) remains a life-threatening disease, yet substantial variation in reported incidences of the disease exist. We aimed to conduct a contemporary, nationwide study of the temporal changes in incidence of IE. Methods We included all Danish cases of first-time IE (1997–2017) using nationwide registries. Patients were grouped into three seven-year intervals (1997–2003, 2004–2010, 2011–2017). Crude annual incidence rates (IR) per 100,000 person-years (PY) were examined overall and per subgroups: age, sex, patients without prior prosthetic heart valve or a cardiac implantable electronic device (CIED). Incidence rate ratios (IRR) were calculated adjusting for age-group, sex and diabetes. Results We identified 8675 patients with IE. Over time, patients were older at diagnosis with a median age of 66.2 years (interquartile range, IQR: 51.5–76.5) and 72.2 years (IQR 62.2–79.9) in 1997–2003 and 2011–2017, respectively. The overall IR increased from 5.0/100,000 PY (95% CI: 4.4–5.6) to 10.5/100,000 PY (95% CI: 9.6–11.3) from 1997 to 2017. IR for patients without prior prosthetic heart valve or a CIED increased from 4.9/100,000 PY (95% CI: 4.3–5.5) to 6.4/100,000 PY (95% CI: 5.8–7.1) (P ≤ 0.0001 for interaction). The IR in males increased from 5.6/100,000 PY (95% CI: 4.7–6.5) to 14.2/100,000 PY (95% CI: 12.9–15.6). The IR in females increased from 4.3/100,000 PY (95% CI: 3.6–5.2) to 6.7/100,000 PY (95% CI: 5.8–7.7). IRR (adjusted for age-groups, sex and diabetes) increased over time (IRR = 1.60 (1.39–1.85) in 2017 vs 1997). Conclusion The incidence of IE more than doubled during the study period. The increase was mainly seen among men and elderly patients only partly explained by the increase in patients with prior heart valve prosthesis or a CIED.

Background: The more infectious SARS-CoV-2 virus lineage B.1.1.7, rapidly spread in Europe after December 2020, and a concern of B.1.1.7 causing more severe disease has been raised. Denmark has one of Europe´s highest capacities per capita of SARS-CoV-2 reverse transcription polymerase chain reaction (RT PCR) test and whole genome sequencing (WGS). We used national health register-data to explore whether B.1.1.7 increases the risk of COVID-19 hospitalisation. Methods and Findings: In an observational cohort study we included all SARS-CoV-2 RT PCR test-positive individuals in Denmark sampled between the 1st January and until the 9th February, 2021, identified in the national COVID-19 surveillance system. The surveillance system includes national individual RT PCR test results and viral WGS analyses and data from national health registers including COVID-19 related hospital admissions defined as first admission within 14 days of the test-positive swab. The odds ratio (OR) of admission according to infection with B.1.1.7, vs other co-existing lineages, was calculated in a logistic regression model adjusted for sex, age, period, follow-up time less than 14 days, region, and comorbidities. A total of 35,887 test-positive individuals were identified, 23,057 (64%) had WGS performed, of whom 18,499 (80%) resulted in a viral genome and a total of 2,155 of these were lineage B.1.1.7. The proportion of individuals with B.1.1.7 increased from 4% in early January to 45% in early February. Among the individuals with viral genome data, B.1.1.7 was associated with a crude OR of admission of 0.87 (95%CI, 0.72-1.05) and an adjusted OR of 1.64 (95%CI, 1.32-2.04) based on 128 admissions after B.1.1.7 infection and 1,107 admissions after infection with other lineages. The adjusted OR was increased in all strata of age and calendar time - the two most important confounders of the crude OR. Conclusions: Infection with lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with other lineages. This finding may have serious public health impact in countries with spread of B.1.1.7 and can support hospital preparedness and modelling of projected impact of the epidemic. Funding Statement: The authors received no specific funding for this work. Declaration of Interests: The authors declare that they have no competing interest. Ethics Approval Statement: This study was conducted on administrative register data. According to Danish law, ethics approval is not needed for such research.

ObjectiveTo examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes.MethodsThis nationwide case-control and cohort study included all individuals in Denmark tested for SARS-CoV-2 RNA with PCR from 27 February 2020 to 26 July 2020. We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use.ResultsThe study included 13 501 SARS-CoV-2 PCR-positive and 1 088 695 PCR-negative individuals. Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09).Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). The associations were similar when ACE-I/ARB users were compared with non-users.ConclusionsACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic.Trial registration numberEUPAS34887

Key Points Question Is exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) associated with increased risk of intensive care unit admission or death among patients hospitalized with influenza? Findings In this Danish nationwide cohort study that included 7747 adults aged 40 years or older, no association of NSAID use with intensive care unit admission or 30-day mortality was found. Meaning The findings of this study suggest that among patients hospitalized with influenza, those who use NSAIDs do not have worse prognosis than those with no NSAID use., This cohort study examines the association of nonsteroidal anti-inflammatory drugs (NSAIDs) with adverse outcomes in patients hospitalized with influenza or influenza pneumonia., Importance During the ongoing coronavirus disease 2019 pandemic, case reports have suggested that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes. Objective To study the association of NSAID use with adverse outcomes in patients hospitalized with influenza or influenza pneumonia. Design, Setting, and Participants This cohort study used propensity score matching among 7747 individuals aged 40 years or older who were hospitalized with influenza, confirmed by polymerase chain reaction or antigen testing, between 2010 and 2018. Data were collected using Danish nationwide registers. All analyses reported were performed on May 29, 2020. Exposures Prescription fill of an NSAID within 60 days before admission. Main Outcomes and Measures Risk ratio (RR) and risk difference (RD) with 95% CIs for intensive care unit admission and death within 30 days of admission. Results A total of 7747 patients (median [interquartile range] age, 71 [59-80] years, 3980 [51.4%] men) with confirmed influenza were identified. Of these, 520 (6.7%) were exposed to NSAIDs. In the unmatched cohorts, 104 of 520 patients (20.0%) who used NSAIDs and 958 of 7227 patients (13.3%) who did not use NSAIDs were admitted to the intensive care unit. For death within 30 days of admission, we observed 37 events (7.1%) among those who used NSAIDs compared with 563 events (7.8%) among those who did not. Current NSAID use was associated with intensive care unit admission (RR, 1.51; 95% CI, 1.26 to 1.81; RD, 6.7%; 95% CI, 3.2% to 10.3%), while NSAID use was not associated with death (RR, 0.91; 95% CI, 0.66 to 1.26; RD, –0.7%; 95% CI, –3.0% to 1.6%). In the matched cohorts, risks were unchanged for patients who used NSAIDs, while 83 ICU admissions (16.0%) and 36 deaths (6.9%) were observed among matched individuals who did not use NSAIDs. Matched (ie, adjusted) analyses yielded attenuated risk estimates for intensive care unit admission (RR, 1.25; 95% CI, 0.95 to 1.63; RD, 4.0%; 95% CI, –0.6% to 8.7%) and death (RR, 1.03; 95% CI, 0.66 to 1.60; RD, 0.2%; 95% CI, –2.9% to 3.3%). Associations were more pronounced among patients who used NSAIDs for a longer period (eg, for intensive care unit admission: RR, 1.90; 95% CI, 1.19 to 3.06; RD, 13.4%; 95% CI, 4.0% to 22.8%). Conclusions and Relevance In this cohort study of adult patients hospitalized with influenza, the use of NSAIDs was not associated with 30-day intensive care unit admission or death in adjusted analyses. There was an association between long-term use of NSAIDs and intensive care unit admission.

ObjectiveTo provide population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) in order to inform targeted protection strategies in the general population and appropriate triage of hospital contacts.Design, Setting, and ParticipantsNationwide population-based cohort of all 228.677 consecutive Danish individuals tested (positive or negative) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from the identification of the first COVID-19 case on February 27th, 2020 until April 30th, 2020.Main Outcomes and MeasuresWe examined characteristics and predictors of inpatient hospitalization versus community-management, and death versus survival, adjusted for age-, sex- and number of comorbidities.ResultsWe identified 9,519 SARS-CoV-2 PCR-positive cases of whom 78% were community-managed, 22% were hospitalized (3.2% at an intensive care unit) and 5.5% had died within 30 days. Median age varied from 45 years (interquartile range (IQR) 31-57) among community-managed cases to 82 years (IQR 7589) among those who died. Age was a strong predictor of fatal disease (odds ratio (OR) 14 for 70-79-year old, OR 26 for 80-89-year old, and OR 82 for cases older than 90 years, when compared to 50-59-year old and adjusted for sex and number of comorbidities). Similarly, the number of comorbidities was strongly associated with fatal disease (OR 5.2, for cases with ≥4 comorbidities versus no comorbidities), and 82% of fatal cases had at least 2 comorbidities. A wide range of major chronic diseases were associated with hospitalization with ORs ranging from 1.3-1.4 (e.g. stroke, ischemic heart disease) to 2.2-2.7 (e.g. heart failure, hospital-diagnosed kidney disease, chronic liver disease). Similarly, chronic diseases were associated with mortality with ORs ranging from 1.2-1.3 (e.g. ischemic heart disease, hypertension) to 2.4-2.7 (e.g. major psychiatric disorder, organ transplantation). In the absence of comorbidities, mortality was relatively low (5% or less) in persons aged up to 80 years.Conclusions and RelevanceIn this first nationwide population-based study, increasing age and number of comorbidities were strongly associated with hospitalization requirement and death in COVID-19. In the absence of comorbidities, the mortality was, however, lowest until the age of 80 years. These results may help in accurate identification, triage and protection of high-risk groups in general populations, i.e. when reopening societies.

BACKGROUND Concern of transfusion-transmitted bacterial infections has been the major hurdle to extend shelf life of platelet (PLT) concentrates. We aimed to investigate the association between storage time and risk of positive blood cultures at different times after transfusion. STUDY DESIGN AND METHODS We performed a nationwide cohort study among PLT transfusion recipients in Denmark between 2010 and 2012, as recorded in the Scandinavian Donations and Transfusions (SCANDAT2) database. Linking with a nationwide database on blood cultures (MiBa), we compared the incidence of a positive blood culture among recipients of PLTs stored 6 to 7 days (old) to those receiving fresh PLTs (1-5 days), using Poisson regression models. We considered cumulative exposures in windows of 1, 3, 5, and 7 days. RESULTS A total of 9776 patients received 66,101 PLT transfusions. The incidence rate ratio (IRR) of a positive blood culture the day after transfusion of at least one old PLT concentrate was 0.77 (95% confidence interval [CI], 0.54-1.09) compared to transfusion of fresh PLT concentrates. The incidence rate of a positive blood culture was lower the day after receiving one old compared to one fresh PLT concentrate (IRR, 0.57; 95% CI, 0.37-0.87). Three, 5, or 7 days after transfusion, storage time was not associated with the risk of a positive blood culture. CONCLUSION Storage of buffy coat-derived PLT concentrates in PAS-C up to 7 days seems safe regarding the risk of a positive blood culture. If anything, transfusion of a single old PLT concentrate may decrease this risk the following day.

BACKGROUND: Revision of infected knee arthroplasties is associated with high failure rates (30-40%). An understanding of the microbiology is important to optimize treatment and outcome. We describe microbiological diagnostic practice and diagnosis in revision of infected knee arthroplasties.METHODS: One hundred and two partial revisions (open debridement and exchange of tibial insert) and 213 two-stage procedures performed due to infection in 275 patients from 1 July 2011 to 30 June 2013 were included and analysed by linkage to data from a nationwide registry on microbiological test results.RESULTS: 78 (24.8%) revisions were culture negative, 192 (60.9%) showed monomicrobial growth and 43 (14.3%) polymicrobial growth. Staphylococcus aureus was the most frequent isolate in mono-culture in 70 (22.2%) revisions and in polymicrobial culture in 15 revisions with a total frequency of 27.0%. Only one case (1.4%) of methicillin-resistance was registered. Coagulase-negative staphylococci (CoNS) were frequent, sole pathogen in 65 revisions and in polymicrobial cultures in 28 revisions with a total frequency of 29.5%. A pre-operative knee aspiration was performed in 50% and preoperative blood cultures were performed in 22% of cases. In 73% of the preoperative knee-aspirations bacteriological findings were fully or partially in accordance with intraoperative cultures. In 54% of the later re-revisions due to infection (treatment-failures) the cultured species differed from or was not detected at index revision surgery.CONCLUSIONS: The 25% culture negative cases in combination with only 50% preoperative knee aspirations and prevailing high failure rates confirm the need for improvement of diagnostic practice and treatment of infected knee arthroplasties.

Background Although the timely isolation of patients is an essential intervention to limit spread of drug-resistant bacteria, information about the colonization status is often unavailable or lost when patients are readmitted or transferred between hospitals. Therefore, carriers of drug resistant bacteria are not recognized sufficiently early, and proper and timely isolation precautions are not taken. Consequently, resistant bacteria of public health concerns including vancomycin resistant enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA) can spread epidemically. To ensure timely identification and proper isolation of such patients we developed an automatic real-time alert of carriers of drug resistant bacteria. Objectives The aim of this paper is to describe the system, called MiBAlert, and share the initial experiences in connection with an outbreak of VRE in the greater Copenhagen area (the Capital region), Denmark. Methods We obtained data on cases of VRE from hospitals in Copenhagen during the period when the first version of MiBAlert was implemented and log-data on the use of MiBAlert. Furthermore, a survey was conducted among 88 staff members to investigate their experiences of MiBAlert. Results The alert is a tool directed toward healthcare personnel accessing the electronic health record (EHR) and those further involved in the care and treatment of the patient. It is based on a web service using data from the national microbiological database, MiBa. MiBAlert is a real-time electronic non-intrusive alert generated automatically in the header of the EHR each time record is accessed. On February 15, 2015 a pilot version of MiBAlert was launched. All positive tests for VRE throughout 1year were shown with alert status by MiBAlert visible to all medical staff with access to EHR. The alert system was automatically updated directly in the EHR across the five hospitals in the Capital region. We found that the system performed satisfactorily, being operational 24/7 all 135 trial days, apart from 72min, for all the hospitals. Of the staff who responded to the survey, 82% considered that MiBAlert overall improved compliance with isolation precautions regarding VRE-positive patients. We found a marked decline of new patients infected or colonized with VRE concomitant with the implementation of MiBAlert and the survey results. Conclusion We found that MiBAlert was a valuable tool in a bundle approach to counter a multiple hospital outbreak of VRE, and that it has a great potential to improve the control of other drug-resistant bacteria.

Background: Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSI). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. We aimed to investigate the prevalence of IE in BSIs with bacteria typically associated with IE. Methods: By crosslinking nationwide registries from 2010-2016, we identified patients with BSIs typically associated with IE: Enterococcus faecalis (E. faecalis), Staphylococcus aureus (S. aureus), Streptococcus spp., and coagulase negative staphylococci (CoNS) and examined the concurrent IE prevalence. A trend test was used to examine temporal changes in the prevalence of IE. Findings: In total 60,119, distributed with 15,407, 16,790, and 27,922 BSIs were identified in the periods of 2010-2011, 2012-2013, and 2014-2016, respectively. Patients with E. faecalis had the highest prevalence of IE (16.3%) followed by S. aureus (10.2%), Streptococcus spp. (7.3%), and CoNS (1.6%). Throughout the study period, the prevalence of IE among patients with E. faecalis increased significantly (p=0.003). Male patients had a higher prevalence of IE for all microorganisms investigated compared with females. A significant increase in the prevalence of IE was seen for E. faecalis, Streptococcus spp., and CoNS with increasing age. Interpretation: For E. faecalis BSI, 1 in 6 had IE, for S. aureus BSI 1 in 10 had IE, and for Streptococcus spp. 1 in 14 had IE. Our results suggest that screening for IE seems reasonable in patients with E. faecalis BSI, S. aureus BSI, or Streptococcus spp. BSI. Funding Statement: The authors state: "No funding." Declaration of Interests: Lauge Ostergaard: no competing interest. Niels Eske Bruun: no competing interest. Marianne Voldstedlund: no competing interest. Magnus Arpi: no competing interest. Christian Ostergaard Andersen: no competing interest. Henrik C Schonheyder: no competing interest. Lars Lemming: reports grants from Merck Sharp & Dohme (MSD) outside the submitted work. Flemming Rosenvinge: no competing interest. Nana Valeur: no competing interest. Peter Sogaard: no competing interest. Paal Skytt Andersen: no competing interest. Robert Skov: no competing interest. Ming Chen: no competing interest. Kasper Iversen: no competing interest. Sabine Gill: no competing interest. Trine Kiilerich Lauridsen: no competing interest. Anders Dahl: no competing interest. Louise Bruun Oestergaard: no competing interest. Jonas Agerlund Povlsen: no competing interest. Claus Moser: no competing interest. Henning Bundgaard: no competing interest. Lars Kober: no competing interest. Emil Loldrup Fosbol: no competing interest. Ethics Approval Statement: This study was approved by the Danish Data Protection Agency. Register-based studies do not require ethical approval in Denmark.

Background Increasing attention has been given to patients with blood stream infection (BSI) and the concurrent prevalence of infective endocarditis (IE). However, there exist a gap in knowledge on the prevalence of IE among patients with a left-sided heart valve prosthesis and BSI. Purpose To examine the prevalence between different BSI and IE in patients with a left-sided heart valve prosthesis. Methods By linking Danish nationwide registries, we were able to identify patients with a left-sided prosthetic heart valve and first-time BSI of interest (Enterococcus faecalis, Staphylococcsus aureus, streptococci species (spp.), and coagulase negative staphylococci [CoNS]) in the period of 2010–2016. Concurrent admission for IE was identified from the Danish National Patient Registry in a period of up to 14 days after the BSI. Results A total of 1,465 patients with BSI were included (1,319 patients with an aortic valve prosthesis [82.6% bioprosthetic] and 146 patients with a mitral valve prosthesis [48.6% bioprosthetic]). Among the included patients, 244 had E. faecalis (median age: 78.3 years, 77.0% male), 301 had S. aureus (median age: 76.9 years, 69.1% male), 401 had streptococci spp. (median age: 78.0 years, 69.1% male) and 519 had CoNS (median age: 76.4 years, 64.2% male). The percentage of patients with a diagnosis of IE in relation to the BSI was 44.3%, 33.6%, 34.4%, and 7.9% for E. faecalis, S. aureus, streptococci spp., and CoNS, respectively. No difference in the overall results was seen by type of valve prosthesis, sex, or age group. Percentage of patients with endocarditis Conclusion In patients with a left-sided heart valve prosthesis, IE was diagnosed in almost half of the patients with E. faecalis, in 1/3 with S. aureus or streptococci spp. and in 1 in 12 with CoNS BSI. Future studies may try to explain why some microbes are more likely to cause prosthetic heart valve endocarditis, than others are.

Background Infective endocarditis (IE) is frequently caused by streptococcal species. However, there is limited knowledge about the relationship between different streptococcal species and IE, and their associated outcomes. Purpose To examine the prevalence of streptococci at species level in IE, and to relate these different species to outcomes. Methods From 2002–2012 we prospectively collected consecutive patients with IE admitted to two tertiary heart centres covering a catchment area of 2.4 million people. The registry comprises 915 IE patients, 366 (40%) with streptococcal IE. Based on phylogenetic relationship, streptococcal species were classified into seven main groups: Mitis, Bovis, Mutans, Anginosus, Salivarius, Pyogenic and Nutritionally Variant Streptococcus (NVS). Classification at species level was not possible in 51 patients, who were excluded. Complications and prognosis of streptococcal IE were compared between the subgroups, and at species level. Results We included 315 patients with streptococcal IE. Mean age was 63 (IQR 52–76) years, and most were men (67%). A total of 115 patients (37%) had a previous heart valve disease, 58 (18%) had a prosthetic valve, 22 (7%) had previously had IE and 29 (9%) had a cardiac electronic device. With 148 episodes (47%) the Mitis group was the most common cause of IE. Other frequent groups were the Pyogenic group and the Bovis group, accounting for 66 (21%) and 51 (16%) of the cases, respectively. Surgery was carried out in 55% (n=173) of all cases. Patients infected with S. pneumoniae or S. agalactiae had a significantly higher rate of surgery, 72.2% (n=13) and 71.9% (n=23) respectively, whereas the Bovis group had a significantly lower rate, 35.5% (n=18) (p=0.048). The aortic valve was infected in 137 patients (43.5%), mitral valve in 105 patients (33.3%) and both valves were infected in 53 patients (16.8%). Twenty patients (6.3%) had right-sided IE, including pacemaker lead IE. There was no significant difference between the species subgroups regarding type of infected valve. Embolization and osteitis were observed in 76 (24.1%) and 30 (9.5%) patients, respectively. There was no significant difference between the species groups, as was the case with mortality: 23 patients (7.3%) died in-hospital and the one-year mortality was 16% (n=50). Distribution of streptococcal IE Conclusion Species of the Mitis group were the most frequent Streptococci causing IE. Patients infected with S. pneumonia or S. agalactiae had significantly higher rate of surgery, and patients infected with S. bovis group had lower rate of surgery. There was no significant difference in rate of complications such as abscesses, embolization, osteitis or mortality between the streptococcal species. Acknowledgement/Funding Supported by grants from Herlev-Gentofte University Hospital Research Foundation

Background Infective Endocarditis (IE) is a disease with high mortality. Previous studies have shown considerable differences and contradicting trends in overall incidence and mortality why data from an unselected nationwide cohort is needed. Purpose We investigated temporal trends in the incidence rate and in-hospital mortality of IE in Denmark in the period of 1997–2016. Methods We included cases of first-time IE (1997–2016) using Danish nationwide registries. Crude incidence rates were given for each calendar year. Further, incidence rates were reported for subgroups of age and sex. For the analysis of patient characteristics and in-hospital mortality, the study cohort was grouped into four 5-year intervals (1997–2001, 2002–2006, 2007–2011, 2012–2016). Multivariable adjusted Cox proportional hazard model was used to compare in-hospital mortality between groups. Results A total of 8,147 patients with IE were identified in the period of 1997–2016. The median age and proportion of males increased from 64.3 years (P25-P75: 48–75.5) and 59.1% to 71.8 years (P25-P75: 62.1–79.9) and 67.1% in 1997–2001 and 2012–2016, respectively. The overall incidence rate (Figure 1) increased from 4.68/100.000-person-years (PY) (CI95: 4.17–5.26) to 8.23/100.000 PY (CI95: 7.53–8.99) in 1997 and 2016, respectively. Male incidence increased from 5.35/100.000 PY (CI95: 4.59–6.23) to 11.03/100.000 PY (CI95: 9.9–12.29) and female incidence increased from 4.03/100.000 PY (CI95: 3.38–4.8) to 5.44/100.000 PY (CI95: 4.67–6.35) in 1997 and 2016 respectively. Incidence rates increased more than seven-fold for the oldest age group (≥80 years) from 1997 to 2016 (6.95/100.000 PY [CI95: 5.32–9.08] to 51.19/100.000 PY [CI95: 43.41–60.38], respectively). In-hospital mortality was significantly lower for patients with IE in the period of 2011–2016 compared with 1997–2001 HR: 0.8 (CI95: 0.69–0.92). Figure 1 Conclusion Infective endocarditis incidences are increasing mostly among men and elderly patients. In order to prevent this disease as best as possible, we need more knowledge on causes for this increasing incidence.

Background:\ud Infectious mononucleosis (IM) is a common adverse presentation of primary infection with Epstein-Barr virus (EBV) in adolescence and later, but is rarely recognized in early childhood where primary EBV infection commonly occurs. It is not known what triggers IM, and also not why IM risk upon primary EBV infection (IM attack rate) seemingly varies between children and adolescents. IM symptoms may be severe and persist for a long time. IM also markedly elevates the risk of Hodgkin lymphoma and multiple sclerosis for unknown reasons. The way IM occurrence depends on age and sex is incompletely described and hard to interpret etiologically, because it depends on three quantities that are not readily observable: the prevalence of EBV-naϊve persons, the hazard rate of seroconverting and the attack rate, i.e. the fraction of primary EBV infections that is accompanied by IM. We therefore aimed to provide these quantities indirectly, to obtain epidemiologically interpretable measures of the dynamics of IM occurrence to provide etiological clues.\ud \ud Methods and findings:\ud We used joint modeling of EBV prevalence and IM occurrence data to provide detailed sex- and age-specific EBV infection rates and IM attack rates and derivatives thereof for a target population of all Danes age 0–29 years in 2006–2011. We demonstrate for the first time that IM attack rates increase dramatically rather precisely in conjunction to typical ages of puberty onset. The shape of the seroconversion hazard rate for children and teenagers confirmed a priori expectations and underlined the importance of what happens at age 0–2 years. The cumulative risk of IM before age 30 years was 13.3% for males and 22.4% for females. IM is likely to become more common through delaying EBV infection in years to come.\ud \ud Conclusions:\ud The change in attack rate at typical ages of puberty onset suggests that the immunologic response to EBV drastically changes over a relatively short age-span. We speculate that these changes are an integrated part of normal sexual maturation. Our findings may inform further etiologic research into EBV-related diseases and vaccine design. Our methodology is applicable to the epidemiological study of any infectious agent that establishes a persistent infection in the host and the sequelae thereof.

Fusobacterium necrophorum findings in Denmark and estimation of the incidence of F. necrophorum bacteraemia was described using data from the nationwide Danish microbiology database (MiBa). All microbiological reports on any Fusobacterium species in Denmark were extracted for a period of 5 years from 2010 to 2014 from MiBa and from the local department of clinical microbiology. The overall incidence of F. necrophorum bacteraemia from 2010 to 2014 was 2.8 cases per million/year vs 9.4 in the age group 15-24 years. F. necrophorum was rare in blood cultures from children and middle-aged patients and then raised again. However, 48 of 232 cases of Fusobacterium bacteraemia were not identified to species level, so the incidences of F. necrophorum bacteraemia may be underestimated in our study. F. necrophorum was found in throat swabs in the age group between 13 and 40 years and in otitis media in children below 2 years in those departments which performed anaerobic culture. The incidence of F. necrophorum bacteraemia found was comparable to earlier reported figures for Lemierre's syndrome. Fusobacterium bacteraemia should always be identified to species level.

Objectives: Bacteria with common microbiological and clinical characteristics are often recognized as a particular group. The acronym HACEK stands for five fastidious genera associated with infective endocarditis (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella). Data on the epidemiology of HACEK are sparse. This article reports a 6-year nationwide study of HACEK bacteraemia in Denmark. Methods: Cases of HACEK bacteraemia occurring during the years 2010–2015 were retrieved from the national Danish microbiology database, covering an average surveillance population of 5.6 million per year. Results: A total of 147 cases of HACEK bacteraemia were identified, corresponding to an annual incidence of 0.44 per 100 000 population. The annual incidence for males was 0.56 per 100 000 and for females was 0.31 per 100 000. The median age was 56 years (range 0–97 years), with variation among the genera. One hundred and forty-three isolates were identified to the species level and six to the genus level: Haemophilus spp, n = 55; Aggregatibacter spp, n = 37; Cardiobacterium spp, n = 9; Eikenella corrodens n = 21; and Kingella spp, n = 27. Conclusions: This is the first study on the incidence of HACEK bacteraemia in a large surveillance population and may inspire further studies on the HACEK group. Haemophilus spp other than Haemophilus influenzae accounted for most cases of HACEK bacteraemia in Denmark, with Aggregatibacter spp in second place. Keywords: Epidemiology, Incidence, Age, Sex, Haemophilus, Aggregatibacter

For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual RSV-associated admissions in children

SUMMARYThe surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010–2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.

Concern of transfusion-transmitted bacterial infections has been the major hurdle to extend shelf life of platelet (PLT) concentrates. We aimed to investigate the association between storage time and risk of positive blood cultures at different times after transfusion.We performed a nationwide cohort study among PLT transfusion recipients in Denmark between 2010 and 2012, as recorded in the Scandinavian Donations and Transfusions (SCANDAT2) database. Linking with a nationwide database on blood cultures (MiBa), we compared the incidence of a positive blood culture among recipients of PLTs stored 6 to 7 days (old) to those receiving fresh PLTs (1-5 days), using Poisson regression models. We considered cumulative exposures in windows of 1, 3, 5, and 7 days.A total of 9776 patients received 66,101 PLT transfusions. The incidence rate ratio (IRR) of a positive blood culture the day after transfusion of at least one old PLT concentrate was 0.77 (95% confidence interval [CI], 0.54-1.09) compared to transfusion of fresh PLT concentrates. The incidence rate of a positive blood culture was lower the day after receiving one old compared to one fresh PLT concentrate (IRR, 0.57; 95% CI, 0.37-0.87). Three, 5, or 7 days after transfusion, storage time was not associated with the risk of a positive blood culture.Storage of buffy coat-derived PLT concentrates in PAS-C up to 7 days seems safe regarding the risk of a positive blood culture. If anything, transfusion of a single old PLT concentrate may decrease this risk the following day.

BACKGROUNDIn 2015, Denmark launched an automated surveillance system for hospital-acquired infections, the Hospital-Acquired Infections Database (HAIBA).OBJECTIVETo describe the algorithm used in HAIBA, to determine its concordance with point prevalence surveys (PPSs), and to present trends for hospital-acquired bacteremiaSETTINGPrivate and public hospitals in DenmarkMETHODSA hospital-acquired bacteremia case was defined as at least 1 positive blood culture with at least 1 pathogen (bacterium or fungus) taken between 48 hours after admission and 48 hours after discharge, using the Danish Microbiology Database and the Danish National Patient Registry. PPSs performed in 2012 and 2013 were used for comparison.RESULTSNational trends showed an increase in HA bacteremia cases between 2010 and 2014. Incidence was higher for men than women (9.6 vs 5.4 per 10,000 risk days) and was highest for those aged 61–80 years (9.5 per 10,000 risk days). The median daily prevalence was 3.1% (range, 2.1%–4.7%). Regional incidence varied from 6.1 to 8.1 per 10,000 risk days. The microorganisms identified were typical for HA bacteremia. Comparison of HAIBA with PPS showed a sensitivity of 36% and a specificity of 99%. HAIBA was less sensitive for patients in hematology departments and intensive care units. Excluding these departments improved the sensitivity of HAIBA to 44%.CONCLUSIONSAlthough the estimated sensitivity of HAIBA compared with PPS is low, a PPS is not a gold standard. Given the many advantages of automated surveillance, HAIBA allows monitoring of HA bacteremia across the healthcare system, supports prioritizing preventive measures, and holds promise for evaluating interventions.Infect Control Hosp Epidemiol 2017;38:559–566

BACKGROUND: The Danish Hospital-Acquired Infections Database (HAIBA) is an automated surveillance system using hospital administrative, microbiological, and antibiotic medication data.AIM: To define and evaluate the case definition for hospital-acquired urinary tract infection (HA-UTI) and to describe surveillance data from 2010 to 2014.METHODS: The HA-UTI algorithm defined a laboratory-diagnosed UTI as a urine culture positive for no more than two micro-organisms with at least one at ≥10(4)cfu/mL, and a probable UTI as a negative urine culture and a relevant diagnosis code or antibiotic treatment. UTI was considered hospital-acquired if a urine sample was collected ≥48h after admission and FINDINGS: HAIBA detected a national incidence rate of 42.2 laboratory-diagnosed HA-UTI per 10,000 risk-days with an increasing trend. Compared to PPS the laboratory-diagnosed HA-UTI algorithm had a sensitivity of 50.0% (26/52) and a specificity of 94.2% (1842/1955). There were several reasons for discrepancies between HAIBA and PPS, including laboratory results being unavailable at the time of the survey, the results considered clinically irrelevant by the surveyor due to an indwelling urinary catheter or lack of clinical signs of infection, and UTIs being considered HA-UTI in PPS even though the first sample was taken within 48h of admission.CONCLUSION: The HAIBA algorithm was found to give valid and valuable information and has, among others, the advantages of covering the whole population and allowing continuous standardized monitoring of HA-UTI.

The primary aim of the Danish enterovirus (EV) surveillance system is to document absence of poliovirus infection. The conflict in Syria has left many children unvaccinated and movement from areas with polio cases to Europe calls for increased awareness to detect and respond to virus-transmission in a timely manner. We evaluate the national EV laboratory surveillance, to generate recommendations for system strengthening. The system was analysed for completeness of viral typing analysis and clinical information and timeliness of specimen collection, laboratory results and reporting of clinical information. Of 23,720 specimens screened, 2,202 (9.3%) were EV-positive. Submission of cerebrospinal fluid and faecal specimens from primary diagnostic laboratories was 79.5% complete (845/1,063), and varied by laboratory and patient age. EV genotypes were determined in 68.5% (979/1,430) of laboratory-confirmed cases, clinical information was available for 63.1% (903/1,430). Primary diagnostic results were available after a median of 1.4 days, typing results after 17 days, detailed clinical information after 33 days. The large number of samples typed demonstrated continued monitoring of EV-circulation in Denmark. The system could be strengthened by increasing the collection of supplementary faecal specimens, improving communication with primary diagnostic laboratories, adapting the laboratory typing methodology and collecting clinical information with electronic forms.

Background: The degree to which the results of valve culture depend on different laboratory procedures as well as other factors is unknown. The aim of this study was to compare the results of heart valve culture at 2 different endocarditis centres in order to clarify this. Methods: The study included 223 patients with definitive endocarditis undergoing heart valve surgery at 2 Danish endocarditis centres (96 at the East centre and 127 at the West centre). The following data related to the samples were registered: transportation, time to inoculation, culture media used and duration of incubation, species distribution, and preoperative duration of appropriate antimicrobial treatment (DAAT). 16S polymerase chain reaction (PCR) of valve tissue was used to estimate the frequency of non-cultivable bacteria. Results: Valve culture was positive in 12.5% of cases at the East centre and 36.2% at the West centre (p

Our aim was to evaluate the results of automated surveillance of Lyme neuroborreliosis (LNB) in Denmark using the national microbiology database (MiBa), and to describe the epidemiology of laboratory-confirmed LNB at a national level. MiBa-based surveillance includes electronic transfer of laboratory results, in contrast to the statutory surveillance based on manually processed notifications. Antibody index (AI) testing is the recommend laboratory test to support the diagnosis of LNB in Denmark. In the period from 2010 to 2012, 217 clinical cases of LNB were notified to the statutory surveillance system, while 533 cases were reported AI positive by the MiBa system. Thirty-five unconfirmed cases (29 AI-negative and 6 not tested) were notified, but not captured by MiBa. Using MiBa, the number of reported cases was increased almost 2.5 times. Furthermore, the reporting was timelier (median lag time: 6 vs 58 days). Average annual incidence of AI-confirmed LNB in Denmark was 3.2/100,000 population and incidences stratified by municipality ranged from none to above 10/100,000. This is the first study reporting nationwide incidence of LNB using objective laboratory criteria. Laboratory-based surveillance with electronic data-transfer was more accurate, complete and timely compared to the surveillance based on manually processed notifications. We propose using AI test results for LNB surveillance instead of clinical reporting.

Aims: In vascular smooth muscle cells caveolae are important for signalling mechanisms regulating vascular contraction. In smooth muscle layer of the renal afferent arteriole juxtaglomerular cells (JG cells) are non-contractile renin producing cells that have the capacity to change their phenotype into smooth muscle cells and back again by metaplastic transformation. Signalling mechanisms in JG cells are not fully understood and we therefore investigated if caveolae were present, and thereby could be involved as integrators of cellular signalling in both of these phenotypes of smooth muscle cells. Methods: Using electron microscopy we compared the number of caveolae in JG cells and smooth muscle cells in the afferent arteriole of the rat kidney. The expression of caveolin and cav-p60 was examined using a combination of immunogold electron microscopy and immunofluorescence microscopy. Results: We found that JG cells have sixfold less caveolae per cell surface sectional length than smooth muscle cells. The expression of cavolin-1 and cav-p60 correlated with the number of caveolae. An examination of the general distribution of caveolae, cav-p60 and caveolins in the rat kidney showed that cav-p60, like caveolin-1, is a specific maker of caveolae. Conclusion: The number of caveolae in JG cells is very low, and this makes it unlikely that caveolae are of major importance for the renin secretion specific for JG cells.

The Danish microbiology database (MiBa) is a national database that automatically accumulates patient test results from all Danish Departments of Clinical Microbiology. As an example for use of MiBa, we describe the real-time surveillance of laboratory confirmed influenza established in October 2012. It functions without any extra burdens of reporting by laboratories or clinicians. This is an important improvement of the existing surveillance for influenza like illness (ILI) which includes only limited virological testing. The MiBa based surveillance adds complete national virological data which are specific for influenza, in contrast to ILI, and serves as a tool for regional and national preparedness and planning.