Using BCG Vaccine to Enhance Nonspecific Protection of Health Care Workers During the COVID-19 Pandemic: A Randomized Controlled Trial.

BACKGROUND: The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes. RESULTS: There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98-1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07-5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI, .09-.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI, .96-1.24). CONCLUSIONS: In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes. CLINICAL TRIALS REGISTRATION: NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90).

Travel demographics, patterns, and plans among adult Nordic travelers.

Background: Despite the high frequency of international travel from Nordic countries annually, data describing demographics, patterns, and plans of travel among Nordic inhabitants are scarce. Methods: In 2018, an online questionnaire covering travel patterns, plans, and knowledge about travel-related diseases was sent to Nordic inhabitants 18-74 years of age. At-risk travelers were defined as those who had traveled outside Europe and North America during the previous 2 years. Results: Of the 5407 respondents included, 4371 (80.8%) had traveled abroad within the past 2 years. Among the respondents, 37.0% (n = 1999) were at-risk travelers. The most frequent travel destinations were Europe (n = 3907, 89.4%) and Asia (n = 1019, 23.3%). Russia/Eurasia was a more common destination for Finnish travelers than the other travelers (10.6% vs 2.3-4.1%). Most at-risk travelers had traveled for leisure/tourism (n = 1329, 66.5%). Visiting friends and relatives was more frequent among Norwegian and Swedish travelers (n = 105, 22.0% and n = 98, 19.4%, respectively) than Finnish travelers (n = 74, 12.7%). The elderly traveled often and made up 21.4% of at-risk travelers. Conclusions: Travel demographics, destinations, and future travel plans were similar across the Nordic countries. More than one third had traveled outside Europe/North America. One third were either elderly or visiting friends or relatives.

The efficacy of midline catheters-a prospective, randomized, active-controlled study.

OBJECTIVES: This study was performed to investigate whether an intravenous (IV) strategy based on new-generation midline catheters is an efficacious alternative to a conventional IV strategy consisting of peripheral venous catheters and central venous catheters, for patients needing IV therapy exceeding 5 days. METHODS: This was a prospective, randomized, controlled study. Patients requiring more than 5 days of IV treatment were randomized to either a midline catheter-based IV strategy or a conventional strategy. The primary endpoint was the composite of the insertion of a central venous catheter (CVC) or the need for four or more peripheral venous catheter (PVC) insertions. The secondary outcomes included catheter dwell times and reasons for premature removal. RESULTS: One hundred and twenty patients were included. The fraction of patients receiving four or more PVCs or having a CVC inserted was 12/58 (21%) in the midline group versus 38/58 (66%) in the conventional group (p < 0.001); the number needed to treat was 2.2. The median overall catheter dwell time was 7 days (range 0-60 days) in the midline group and 4 days (range 0-84 days) in the conventional group (p = 0.002). CONCLUSION: In patients requiring more than 5 days of IV therapy, a midline catheter strategy reduced the need for insertion of a CVC or four or more PVCs.

Using BCG vaccine to enhance non-specific protection of health care workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark.

OBJECTIVES: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism.The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. HYPOTHESIS: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. TRIAL DESIGN: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. PARTICIPANTS: The trial will recruit 1,500 HCW at Danish hospitals.To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week.A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. MAIN OUTCOMES: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation.Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation.Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1.Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference.The physicians administering the treatment are not blinded.Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group.Trial Status: Current protocol version 5.1, from July 6, 2020.Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. TRIAL REGISTRATION: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291.Full protocol: The full protocol is attached as an additional file, accessible from the Trialswebsite (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

[Spondylodiscitis caused by Brucella melitensis after consumption of unpasteurised camel milk].

This is a case report of a 76-year-old man with spondylodiscitis caused by Brucella melitensis. He was admitted to hospital due to backpain, weight loss and elevated C-reactive protein level. MRI showed signs of multifocal spondylodiscitis, and blood cultures yielded B. melitensis. The patient was most likely infected through consumption of unpasteurised camel milk. Antibiotic treatment was initiated with good effect. Although bru-cellosis is rare in Denmark, correct diagnosis is important due to the high morbidity, the specific antibiotic treatment needed and the necessary laboratory precautions.

Incidence and mortality of herpes simplex encephalitis in Denmark: A nationwide registry-based cohort study.

OBJECTIVES: We aimed to investigate the incidence and mortality of herpes simplex encephalitis (HSE) in a nationwide cohort. METHODS: From the Danish National Patient Registry, we identified all adults hospitalised with a first-time diagnosis of HSE in Denmark during 2004-2014. The HSE diagnoses were verified using medical records and microbiological data. Patients were followed for mortality through the Danish Civil Registry System. We estimated age-standardised incidence rates of HSE and 30-day, 60-day, and 1-year cumulative mortality. Furthermore, we assessed whether calendar year, age, gender, level of comorbidity, virus type, and department type was associated with HSE mortality. RESULTS: We identified a total of 230 cases of HSE. Median age was 60.7 years (interquartile range: 49.3-71.6). The overall incidence rate was 4.64 cases per million population per year (95% confidence interval: 4.06-5.28). The cumulative mortality within 30 days, 60 days, and 1 year of the HSE admission was 8.3%, 11.3%, and 18.6%, respectively. Advanced age and presence of comorbidity were associated with increased 60-day and 1-year mortality. CONCLUSIONS: This nationwide study of verified HSE found a higher incidence than reported in previous nationwide studies. Presence of comorbidity was identified as a novel adverse prognostic factor. Mortality rates following HSE remain high.

Infective endocarditis in patients receiving chronic hemodialysis: A 21-year observational cohort study in Denmark.

BACKGROUND: Chronic hemodialysis is a risk factor for invasive bacterial infections. We conducted a nationwide study of risk and mortality of infective endocarditis (IE) among patients undergoing chronic hemodialysis. METHODS: In this observational cohort study, patients with end-stage renal disease who initiated hemodialysis in Denmark during 1990 to 2010 were matched on age, gender, and municipality with up to 19 population controls. We extracted information on first admissions with IE, comorbidity, and arteriovenous fistula surgery from medical administrative databases. Incidence rates (IRs) of IE were compared between patients undergoing hemodialysis and population controls using Poisson regression. Risk factors for IE were assessed by Cox regression. RESULTS: IE was diagnosed in 150 of 9392 patients undergoing hemodialysis (IR: 6.83 per 1000 person-years, 95% confidence interval [CI]; 5.82-8.01) and 250 of 176,369 population controls (IR: 0.18 per 1000 person-years, 95% CI; 0.16-0.20) yielding an incidence rate-ratio of 38.1 (95% CI; 31.2-46.7). Among patients undergoing hemodialysis, absence of arteriovenous fistula surgery was associated with increased risk of IE (hazard ratio [HR] = 1.57; 95% CI; 1.09-2.27) after adjusting for age, sex, valvular disease, diabetes and period of first hemodialysis. Age ≥70 years was associated with a lower risk of IE (HR = 0.59; 95% CI 0.37-0.93). The 90-day all-cause mortality following diagnose of IE was 27% (95% CI; 20-35) for patients undergoing hemodialysis and 23% (95% CI; 18-29) for controls. CONCLUSIONS: Patients undergoing hemodialysis have markedly elevated risk of IE compared to the general population. Future challenges will be to develop strategies to prevent IE, to reduce IE-related morbidity and mortality in this vulnerable population.

Risk and outcome of pyelonephritis among renal transplant recipients.

BACKGROUND: Urinary tract infection is the most common infectious disease requiring hospitalisation following renal transplantation. However, the risk and outcome of post-transplant pyelonephritis remains unclear. METHODS: This population-based cohort study was conducted from 1 January 1990 to 31 December 2009. Each member of a Danish population-based, nationwide cohort of first-time renal transplant recipients was matched by age and gender with up to 19 population controls. Information on hospital discharge diagnosis, emigration, and mortality was obtained from nationwide administrative databases. Individuals were observed from the date of first renal transplantation and until graft loss, emigration, or death. Risk factors were assessed by Poisson regression. RESULTS: The incidence rate (IR) of first-time hospitalisation for pyelonephritis was 18.5 (95 % confidence interval [CI]: 16.4-20.9) per 1,000 person-years of follow-up (PYFU) among renal transplant recipients (N = 2,656) and 0.26 (CI: 0.21-0.31) per 1,000 PYFU among population controls (N = 49,226) yielding an incidence rate-ratio (IRR) of 72.0 (95 % CI: 57.8-89.7). Among renal transplant recipients, the risk of pyelonephritis decreased during the entire study period and was lowest in 2005-09 (IRR = 0.46, CI: 0.31-0.68). The highest risk of pyelonephritis was observed within the first six months post-transplantation (IR = 69.9 per 1,000 PYFU; CI: 56.4-86.7). Other risk factors for post-transplant pyelonephritis included female gender, high Charlson comorbidity index score, HLA-DR mismatch, cause of renal failure, and calendar period. Interestingly, we found that the combined risk of graft loss and death was 45 %, (CI: 19-77 %) higher in renal transplant recipients following post-transplant pyelonephritis compared to those who had no admission due to pyelonephritis. CONCLUSIONS: The risk of first-time hospitalisation for pyelonephritis among renal transplant recipients is high. Further, post-transplant pyelonephritis was associated with excess risk of graft loss and death; this indicates that strategies aimed at reducing upper urinary tract infections are likely to enhance renal graft survival.

Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry.

BACKGROUND: Large health care databases are a valuable source of infectious disease epidemiology if diagnoses are valid. The aim of this study was to investigate the accuracy of the recorded diagnosis coding of herpes simplex encephalitis (HSE) in the Danish National Patient Registry (DNPR). METHODS: The DNPR was used to identify all hospitalized patients, aged ≥15 years, with a first-time diagnosis of HSE according to the International Classification of Diseases, tenth revision (ICD-10), from 2004 to 2014. To validate the coding of HSE, we collected data from the Danish Microbiology Database, from departments of clinical microbiology, and from patient medical records. Cases were classified as confirmed, probable, or no evidence of HSE. We estimated the positive predictive value (PPV) of the HSE diagnosis coding stratified by diagnosis type, study period, and department type. Furthermore, we estimated the proportion of HSE cases coded with nonspecific ICD-10 codes of viral encephalitis and also the sensitivity of the HSE diagnosis coding. RESULTS: We were able to validate 398 (94.3%) of the 422 HSE diagnoses identified via the DNPR. Hereof, 202 (50.8%) were classified as confirmed cases and 29 (7.3%) as probable cases providing an overall PPV of 58.0% (95% confidence interval [CI]: 53.0-62.9). For "Encephalitis due to herpes simplex virus" (ICD-10 code B00.4), the PPV was 56.6% (95% CI: 51.1-62.0). Similarly, the PPV for "Meningoencephalitis due to herpes simplex virus" (ICD-10 code B00.4A) was 56.8% (95% CI: 39.5-72.9). "Herpes viral encephalitis" (ICD-10 code G05.1E) had a PPV of 75.9% (95% CI: 56.5-89.7), thereby representing the highest PPV. The estimated sensitivity was 95.5%. CONCLUSION: The PPVs of the ICD-10 diagnosis coding for adult HSE in the DNPR were relatively low. Hence, the DNPR should be used with caution when studying patients with encephalitis caused by herpes simplex virus.

Risk and Prognosis of Bacteremia and Fungemia Among Peritoneal Dialysis Patients: A Population-Based Cohort Study.

♦ BACKGROUND: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). ♦ OBJECTIVE: The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. ♦ METHODS: Design: Observational cohort study. SETTING: Central and North Denmark regions. PARTICIPANTS: patients who initiated PD during 1995 - 2010. For each patient we sampled up to 10 controls from the general population matched on age, sex, and municipality. ♦ MAIN OUTCOME: Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. ♦ RESULTS: Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 - 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 - 0.5) per 100 PYFU in population controls (IRR = 10.4; 95% CI, 8.1 - 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 - 31.0) and 20.7% (95% CI, 16.3 - 25.9) among PD patients and population controls, respectively. ♦ CONCLUSIONS: Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts.

Testing for hepatitis B virus and HIV in patients with chronic hepatitis C: screening performance and outcome.

BACKGROUND: Patients infected with hepatitis C virus (HCV) and co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) are at increased risk for progression of liver disease. The aim of this study was to assess HBV and HIV screening performance and outcome in HCV patients followed at a Danish university hospital and affiliated regional outpatient clinics. METHODS: HBV and HIV serology data were extracted from a quality assurance database for the assessment of screening performance in patients diagnosed with chronic HCV infection during the period 1 January 1996 to 31 December 2011. Patients with incomplete and missing serology data had complementary serology tests performed to assess the prevalence of HBV and HIV co-infection and HBV immune status. RESULTS: Among 624 HCV patients, 10 (2%) were co-infected with chronic HBV and 32 (5%) with HIV. Approximately half of the cohort were non-immune to HBV or had an unknown HBV serology status. Serology results consistent with resolved infection and HBV vaccination were found in 209 (33%) and 65 (10%) patients, respectively. During the 16-y observation period, HBV and HIV screening coverage at HCV diagnosis increased from 23% to 92% and from 38% to 80%, respectively. CONCLUSION: Despite improvements throughout the study period, HBV and HIV serology screening remained incomplete. The majority of patients were either HBV non-immune or had an unknown HBV serology status. These findings thus call for a more proactive screening approach as well as an improved HBV vaccination strategy for patients with chronic HCV infection.

Use of InfCare HIV to identify and characterize suboptimally treated HIV patients at a Danish HIV clinic: a cross-sectional cohort study.

BACKGROUND: The software program InfCare HIV is a combined clinical decision support tool and database. This study investigated the usefulness of InfCare HIV for identifying and characterizing suboptimally treated HIV-infected patients at a Danish HIV clinic. METHODS: This cross-sectional cohort study included data on all HIV-infected patients treated at the Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark on a specific date. InfCare HIV was used to identify and characterize suboptimally treated patients defined as patients with virological failure (VF) or untreated patients with a CD4 + count below 350 cells/µl. Patient characteristics were analyzed (i.e. age, sex, ethnicity, and nadir and latest CD4 + cell count). Treatment history and reasons for suboptimal treatment were also investigated. RESULTS: Among all 530 patients, 421 were receiving highly active antiretroviral therapy (HAART) and had undergone at least 48 weeks of treatment on 29 October 2010. Of these, 27 (6.4%) had ongoing VF. Four were untreated despite a CD4 + count below 350 cells/µl. Among patients on HAART, patients with VF were younger and had lower median nadir CD4 + cell counts than patients without VF. Further, 33.3% (6/18) of African Black men but only 4.1% (10/244) of Caucasian men on HAART had VF (p < 0.001). The primary reason for VF was non-adherence. Three untreated patients had refused HAART, and 1 was not treated because of concerns of non-adherence. CONCLUSIONS: InfCare HIV was successfully used to identify patients with suboptimal treatment. A surprisingly high percentage of African Black men had VF.

[Nosocomial infections--ecological niches]. / Nosokomielle infektioner--økologiske nicher.

Knowledge of ecological niches of nosocomial pathogens is used in treatment and prevention of nosocomial infections. This article offers an analysis of the ecological niches of three important nosocomial pathogens: Clostridium difficile, Staphylococcus aureus and Legionella pneumophila. Relevant terms are explained and examples of deliberate and non-deliberate manipulation of the niches and the following consequences are given. Finally, the consequences of climate changes on the pattern of nosocomial infections are discussed.