Adverse SARS-CoV-2-associated outcomes among people experiencing social marginalisation and psychiatric vulnerability: A population-based cohort study among 4,4 million people.

Background: Knowledge of the adverse problems related to SARS-CoV-2 infection in marginalised and deprived groups may help to prioritise more preventive efforts in these groups. We examined adverse outcomes associated with SARS-CoV-2 infection among vulnerable segments of society. Methods: Using health and administrative registers, a population-based cohort study of 4.4 million Danes aged at least 15 years from 27 February 2020 to 15 October 2021 was performed. People with 1) low educational level, 2) homelessness, 3) imprisonment, 4) substance abuse, 5) supported psychiatric housing, 6) psychiatric admission, and 7) severe mental illness were main exposure groups. Chronic medical conditions were included for comparison. COVID-19-related outcomes were: 1) hospitalisation, 2) intensive care, 3) 60-day mortality, and 4) overall mortality. PCR-confirmed SARS-CoV-2 infection and PCR-testing were also studied. Poisson regression analysis was used to compute adjusted incidence and mortality rate ratios (IRRs, MRRs). Findings: Using health and administrative registers, we performed a population-based cohort study of 4,412,382 individuals (mean age 48 years; 51% females). In all, 257,450 (5·8%) individuals had a PCR-confirmed SARS-CoV-2 infection. After adjustment for age, calendar time, and sex, we found that especially people experiencing homelessness had high risk of hospitalisation (IRR 4·36, 95% CI, 3·09-6·14), intensive care (IRR 3·12, 95% CI 1·29-7·52), and death (MRR 8·17, 95% CI, 3·66-18·25) compared with people without such experiences, but increased risk was found for all studied groups. Furthermore, after full adjustment, including for status of vaccination against SARS-CoV-2 infection, individuals with experiences of homelessness and a PCR-confirmed SARS-CoV-2 infection had 41-times (95% CI, 24·84-68·44) higher risk of all-cause death during the study period compared with individuals without. Supported psychiatric housing was linked to almost 3-times higher risk of hospitalisation and 60-day mortality following SARS-CoV-2 infection compared with the general population with other living circumstances. Interpretation: Socially marginalised and psychiatrically vulnerable individuals had substantially elevated risks of adverse health outcomes following SARS-CoV-2 infection. The results highlight that pandemic preparedness should address inequalities in health, including infection prevention and vaccination of vulnerable groups. Funding: Novo Nordisk Foundation.

Electronic reporting of diagnostic laboratory test results from all healthcare sectors is a cornerstone of national preparedness and control of COVID-19 in Denmark.

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.

Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study.

BACKGROUND: The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10·6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2. METHODS: In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 - RR. FINDINGS: During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% [95% CI 0·51-0·82]) tested positive again during the second surge compared with 16 819 (3·27% [3·22-3·32]) of 514 271 who tested negative during the first surge (adjusted RR 0·195 [95% CI 0·155-0·246]). Protection against repeat infection was 80·5% (95% CI 75·4-84·5). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 [0·179-0·251], estimated protection 78·8% [74·9-82·1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% CI 24·7-62·8). We found no difference in estimated protection against repeat infection by sex (male 78·4% [72·1-83·2] vs female 79·1% [73·9-83·3]) or evidence of waning protection over time (3-6 months of follow-up 79·3% [74·4-83·3] vs ≥7 months of follow-up 77·7% [70·9-82·9]). INTERPRETATION: Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on. FUNDING: None.

The Economic Burden of Clostridioides difficile in Denmark: A Retrospective Cohort Study.

Objectives: The aim of this study was to make a comprehensive economic assessment of the costs of hospital-acquired C. difficile infections (CDI). Methods: We carried out a retrospective matched cohort study utilizing Danish registry data with national coverage to identify CDI cases and matched reference patients without CDI (controls) for economic burden assessment in Denmark covering 2011-2014. Health care costs and public transfer costs were obtained from national registries, and calculated for 1 year prior to, and 2 years after index admission using descriptive statistics and regression analysis. Results: The study included 12,768 CDI patients and 23,272 matched controls. The total health care cost was significantly larger for CDI cases than controls throughout all periods. During the index admission period, cost was €12,867 per CDI case compared to €4,522 (p < 0.001) for controls, which increased to an average of €31,388 and €19,512 (p < 0.001) in Year 1 for the two groups, respectively. Excess costs were found both among infections with onset in hospitals and in the community. Diagnosis compatible with complications increased costs to on average >€91,000 per case. The regression analysis showed that CDI adds a substantial economic burden, but only explains about 1/3 of the crude difference observed in the matched analysis. Discussion: The major economic impact of hospital-acquired CDI with complications underlines the importance of preventing complications in these patients. Our study provides an informed estimate of the potential economic gain per patient by successful intervention, which is likely to be relatively comparable across countries.

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

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

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.

Toward rubella elimination in Europe: an epidemiological assessment.

BACKGROUND: The elimination of rubella and prevention of congenital rubella syndrome (CRS) by 2015 are established goals for Europe. Our aim was to review the epidemiology of rubella in relation to this goal. MATERIAL AND METHODS: National surveillance institutions from 32 European countries provided information on rubella and CRS surveillance systems and data for 2000-08. We reported the number of notified rubella cases by year for countries with a national mandatory notification system for rubella covering total country population consistently throughout 2000-08 and analysed rubella surveillance data for 2008. RESULTS: Throughout 2000-08, 24 countries conducted passive routine surveillance based on mandatory reporting rubella covering total country population. Altogether these countries reported 526,751 rubella cases. The median incidence per million inhabitants declined from 7.2 in 2000 to 0.3 in 2008. By 2008, the number of countries with mandatory notification systems for rubella increased to 28. These countries reported 21,475 rubella cases of which 1.5% (n=317) were laboratory-confirmed. Most cases (n=21,075; 98%) were reported from Poland, Italy and Romania. Ten countries reported zero rubella cases and five others reported an incidence of <1 per million inhabitants. In 2008, 20 CRS cases were reported from five countries. CONCLUSION: The overall decline in rubella incidence and increase in the number of countries conducting rubella surveillance through a mandatory notification system are notable achievements toward the goal of rubella elimination in Europe. However, in a few countries with high rubella incidence the risk for CRS still exists. Achievement and maintenance of the required high vaccination coverage and high-quality surveillance of rubella and CRS including laboratory testing of all suspected cases are fundamental to eliminate rubella and prevent CRS in Europe.

Uptake of the human papillomavirus-vaccination within the free-of-charge childhood vaccination programme in Denmark.

BACKGROUND: Persistent infection with human papillomavirus (HPV) is a prerequisite for cervical cancer, which causes 175 yearly deaths and substantial morbidity in Denmark. In January 2009, HPV-vaccination for 12 year-old girls was introduced into the free-of-charge childhood vaccination programme. Due to concerns about potential poor compliance we determined the uptake and identified determinants for vaccination after the first year of the programme. METHODS: All vaccinations given within the vaccination programme are reported to a central register, which we linked to demographic information found in the Danish civil register. We calculated vaccination uptake and used Cox regression survival analysis to compare the uptake rates between demographic subgroups in the population, e.g. by number of siblings, age of mother (at the daughter's birth) and place of origin. RESULTS: The uptake among the 33,838 eligible girls was 80%, 75% and 62% respectively for the three HPV-doses. All subgroups had uptake above 68% for the first HPV-vaccination. Girls with mothers younger or older than the reference group of 25-34 years had a lower uptake rate (adjHR 0.94, 95% CI 0.91-0.97 and adjHR 0.91, 95% CI 0.88-0.94 respectively). Girls with 5 or more siblings had lower uptake rate than girls without siblings (adjHR 0.79, 95% CI 0.71-0.87). Girls born in other EU/EFTA-countries had lower uptake rate than Danish-born girls with Danish-born parents (adjHR 0.74, 95% CI 0.67-0.82). CONCLUSIONS: The introduction of routine HPV-vaccination in Denmark resulted in a relatively high uptake, indicating little reason for major concern about barriers towards the vaccination in Denmark. Population groups with reduced uptake were identified, but as they were small in number their effect on the overall vaccination coverage was marginal. Nonetheless, these groups should be targeted in future acceptance studies and vaccination awareness campaigns.

Burden of illness of the 2009 pandemic of influenza A (H1N1) in Denmark.

We analysed Danish surveillance data to estimate influenza-associated morbidity and mortality in 2009. To obtain population-based estimates of the clinical attack rate, we combined data from two different primary health care surveillance systems, national numbers of the proportion of positive influenza tests, and data from a web-based interview on health care seeking behaviour during the pandemic. From a national registry, we obtained data on hospital admissions (ICD-10 codes) for influenza related conditions. Admission to intensive care was monitored by a dedicated surveillance scheme. Mortality was estimated among laboratory confirmed cases but was also expressed as excess all-cause mortality attributed to influenza-like illness in a multivariable time series analysis. In total, we estimated that 274,000 individuals (5%) in Denmark experienced clinical illness. The highest attack rate was found in children 5-14 years (15%). Compared with the expected number of hospital admissions, there was an 80% increase in number of influenza related hospital admissions in this age group. The numbers of patients admitted to intensive care approached 5% of the national capacity. Estimates of the number of deaths ranged from 30 to 312 (0.5-5.7 per 100,000 population) depending on the methodology. In conclusion, the pandemic was characterised by high morbidity and unprecedented high rates of admissions to hospitals for a range of influenza-related conditions affecting mainly children. Nonetheless, the burden of illness was lower than assumed in planning scenarios, and the present pandemic compares favourable with the 20th century pandemics.

Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions.

OBJECTIVES: Evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains debatable in part due to misclassification of exposure levels. In a registry-based case-control study, the authors applied a risk-based classification of surgical interventions to determine the association between a history of surgery and sCJD. DESIGN: Case-control study, allowing for detailed analysis according to time since exposure. SETTING: National populations of Denmark and Sweden. PARTICIPANTS: From national registries of Denmark and Sweden, the authors included 167 definite and probable sCJD cases with onset during the period 1987-2003, 835 age-, sex- and residence-matched controls and 2224 unmatched. Surgical procedures were categorised by anatomical structure and presumed risk of transmission level. The authors used logistic regression to determine the odds ratio (OR) for sCJD by surgical interventions in specified time-windows before disease-onset. RESULTS: From comparisons with matched controls, procedures involving retina and optic nerve were associated with an increased risk at a latency of ≥1 year OR (95% CI) 5.53 (1.08 to 28.0). At latencies of 10 to 19 years, interventions on peripheral nerves 4.41 (1.17 to 16.6) and skeletal muscle 1.58 (1.01 to 2.48) were directly associated. Interventions on blood vessels 4.54 (1.01 to 20.0), peritoneum 2.38 (1.14 to 4.96) and skeletal muscle 2.04 (1.06 to 3.92), interventions conducted by vaginal approach 2.26 (1.14 to 4.47) and a pooled category of lower-risk procedures 2.81 (1.62 to 4.88) had an increased risk after ≥20 years. Similar results were found when comparing with unmatched controls. INTERPRETATION: This observation is in concordance with animal models of prion neuroinvasion and is likely to represent a causal relation of surgery with a non-negligible proportion of sCJD cases.

Measles in Europe: an epidemiological assessment.

BACKGROUND: Measles persists in Europe despite the incorporation of the measles vaccine into routine childhood vaccination programmes more than 20 years ago. Our aim was therefore to review the epidemiology of measles in relation to the goal of elimination by 2010. METHODS: National surveillance institutions from 32 European countries submitted data for 2006-07. Data for age-group, diagnosis confirmation, vaccination, hospital treatment, the presence of acute encephalitis as a complication of disease, and death were obtained. 30 countries also supplied data about importation of disease. Clinical, laboratory-confirmed, and epidemiologically linked cases that met the requirements for national surveillance were analysed. Cases were separated by age: younger than 1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years, and older than 20 years. Countries with indigenous measles incidence per 100 000 inhabitants per year of 0, less than 0.1, 0.1-1, and more than 1 were grouped into categories of zero, low, moderate, and high incidence, respectively. FINDINGS: For the 2 years of the study, 12 132 cases of measles were recorded with most cases (n=10 329; 85%) from five countries: Romania, Germany, UK, Switzerland, and Italy. Most cases were unvaccinated or incompletely vaccinated children; however, almost a fifth were aged 20 years or older. For the same 2 years, seven measles-related deaths were recorded. High measles incidence in some European countries revealed suboptimum vaccination coverage. Of the 210 cases that were reported as being imported, 117 (56%) came from another country within Europe and 43 (20%) from Asia. INTERPRETATION: The suboptimum vaccination coverage raises serious doubts that the goal of elimination by 2010 can be attained. Achievement and maintenance of optimum vaccination coverage and improved surveillance are the cornerstones of the measles elimination plan for Europe.

Epidemiology and aetiology of diarrhoeal diseases in adults engaged in wastewater-fed agriculture and aquaculture in Hanoi, Vietnam.

OBJECTIVES: To determine the occurrence of and risk factors for diarrhoea in an adult population exposed to wastewater used for agricultural and aquacultural productions. METHODS: An open cohort of 636 adults aged 15-70 years living in a wastewater-irrigated area in Hanoi was followed by weekly visit for 18 months. The aetiology and risk factors for diarrhoeal diseases were determined in a nested case-control study. Stool specimens and exposure information related to wastewater, hygiene, water and food consumption were collected from 163 unmatched pairs of cases and controls. RESULTS: The incidence rate of diarrhoeal diseases was 28.1 episodes per 100 person-years at risk. Of the 326 stool specimens, 47 cases and 24 controls were identified with enteric pathogens, of which diarrhoeagenic Escherichia coli and Entamoeba histolytica were the most common. Risk factors for diarrhoeal diseases included contact with wastewater [odds ratio (OR) = 1.98, attributable fraction of the population (AF) 35%], not washing hands after defecation (OR = 3.34, AF 3%), drinking water from a well (OR = 6.21, AF 6%), consumption of raw or undercooked foods (OR = 2.45, AF 6%), and contact with persons with diarrhoea (OR = 4.22, AF 5%). CONCLUSION: Wastewater contact was the principal risk factor for diarrhoea in this population. As the local economy depends on the use of wastewater for agriculture and aquaculture, it is important to find ways to mitigate the public health risks associated with this use, in addition to promotions of personal, domestic and food hygiene.

[The economic impact of an epidemic of hepatitis A among men who have sex with men]. / Hvad koster et udbrud af hepatitis A blandt maend, der har sex med maend?

INTRODUCTION: In 2004 Denmark had an epidemic of hepatitis A among men who have sex with men (MSM). We estimate the size and the economic impact of the epidemic and discuss possibilities to prevent new epidemics. MATERIALS AND METHODS: The size of the outbreak was estimated from notifications received by the Department of Epidemiology and the number of hepatitis A IgM positive specimens sent to the Department of Virology at Statens Serum Institut. The economical impact was estimated according to data on cost of illness from the National Board of Health and the results of the outbreak investigation. RESULTS: In 2004, 165 cases of hepatitis A in men > 17 years of age were reported compared with a yearly average of 25 cases in the previous 10 years. The size of the outbreak, adjusted for an estimated underreporting of 60% was 220 cases. The economical impact was EUR 650,000, or EUR 3,000 per case. CONCLUSION: Outbreaks of hepatitis A among men who have sex with men are reported from major European cities almost on an annual basis. In the case of an outbreak, we suggest the response should include a targeted information campaign in the MSM media, hygiene control at gay saunas, sex clubs and darkrooms and a free vaccination offer to MSM with frequent partners at locations frequented by MSM. Before an outbreak we propose that vaccination against hepatitis A be recommended to MSM with frequent partners.

Tissue classification for the epidemiological assessment of surgical transmission of sporadic Creutzfeldt-Jakob disease. A proposal on hypothetical risk levels.

BACKGROUND: Epidemiological studies on the potential role of surgery in Creutzfeldt-Jakob Disease transmission have disclosed associations with history of specific surgical interventions or reported negative results. METHODS: Within the context of a case-control study designed to address surgical risk of sporadic Creutzfeldt-Jakob Disease in Nordic European countries (EUROSURGYCJD Project), a strategy was adopted to categorise reported surgical procedures in terms of potential risk of Creutzfeldt-Jakob Disease acquisition. We took into account elements of biological plausibility, either clinically or experimentally demonstrated, such as tissue infectivity, PrP expression content or successful route of infection. RESULTS: We propose a classification of exposed tissues and anatomic structures, drawn up on the basis of their specific putative role as entry site for prion transmission through contact with surgical instruments that are not fully decontaminated. CONCLUSIONS: This classification can serve as a reference, both in our study and in further epidemiological research, for categorisation of surgical procedures in terms of risk level of Creutzfeldt-Jakob Disease acquisition.

Salmonella control programs in Denmark.

We describe Salmonella control programs of broiler chickens, layer hens, and pigs in Denmark. Major reductions in the incidence of foodborne human salmonellosis have occurred by integrated control of farms and food processing plants. Disease control has been achieved by monitoring the herds and flocks, eliminating infected animals, and diversifying animals (animals and products are processed differently depending on Salmonella status) and animal food products according to the determined risk. In 2001, the Danish society saved U.S.$25.5 million by controlling Salmonella. The total annual Salmonella control costs in year 2001 were U.S.$14.1 million (U.S.$0.075/kg of pork and U.S.$0.02/kg of broiler or egg). These costs are paid almost exclusively by the industry. The control principles described are applicable to most industrialized countries with modern intensive farming systems.