Impact of COVID-19 Restrictions on Incidence of Enteropathogenic Bacteria, Virus, and Parasites in Denmark: A National, Register-Based Study.

Diarrheal diseases caused by enteric pathogens are a significant public health concern. It is widely considered that close contact between persons, poor hygiene, and consumption of contaminated food are the primary causes of gastroenteritis. Clinical microbiology laboratory observations indicate that the incidence of enteropathogenic microorganisms may have been reduced in Denmark during the COVID-19 pandemic. All Departments of Clinical Microbiology in Denmark provided data on the monthly incidence of Salmonella spp., Escherichia coli, Campylobacter spp., Clostridioides difficile, Norovirus GI+GII, Giardia duodenalis, and Cryptosporidium from March 2018 to February 2021. The data were divided into three periods as follows: Control Period 1 (March 2018 to February 2019); Control Period 2 (March 2019 to February 2020); and the Restriction (pandemic) Period (March 2020 to February 2021). The incidences of pathogenic Salmonella spp.-, Escherichia coli-, and Campylobacter spp.-positive samples decreased by 57.3%, 48.1%, and 32.9%, respectively, during the restriction period. No decrease in C. difficile was observed. Norovirus GI+GII-positive samples decreased by 85.6%. Giardia duodenalis-positive samples decreased by 66.2%. Cryptosporidium species decreased by 59.6%. This study demonstrates a clear decrease in the incidence of enteropathogenic bacteria (except for C. difficile), viruses, and parasites during the SARS-CoV-2 restriction period in Denmark.

Impact of COVID-19 Restrictions on Acute Gastroenteritis in Children: A Regional, Danish, Register-Based Study.

This study aimed to evaluate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) restrictions such as social distancing on the occurrence of acute gastroenteritis (AGE) among children. This study is a register-based study, including every child seen in the departments of paediatrics with the initial diagnosis of AGE in three neighbouring hospitals in Denmark, from March 2018 through February 2021. The study also included every positive stool sample for AGE-causing pathogens analysed in these three hospitals from children during the same period. The Wilcoxon rank-sum test was used to determine differences between the period during the SARS-CoV-2 restrictions and before. In all, 222,157 children were seen in the three paediatric departments during this period. Of these, 3917 children were diagnosed with AGE. We found a decrease of 46.6% in AGE-related visits per month after the SARS-CoV-2 restrictions were introduced compared to before (p-value < 0.001). Positive stool samples decreased by 38.2% (p-value = 0.008) during the restrictions. This study found that cases of paediatric AGE decreased significantly the during COVID-19 restrictions, suggesting that studies should be conducted to determine whether this reduction was a result of good hand hygiene and social distancing or just a result of altered health-seeking behaviour among children.

The incidence of laboratory-confirmed cases of enteric pathogens in Denmark 2018: a national observational study.

BACKGROUND: Only a subset of enteric pathogens is under surveillance in Denmark, and knowledge on the remaining pathogens detected in acute gastroenteritis is limited. Here, we present the one-year incidence of all enteric pathogens diagnosed in Denmark, a high-income country, in 2018 and an overview of diagnostic methods used for detection. METHODS: All 10 departments of clinical microbiology completed a questionnaire on test methods and provided 2018-data of persons with positive stool samples with Salmonella species, Campylobacter jejuni/coli, Yersinia enterocolitica, Aeromonas species, diarrheagenic Escherichia coli (Enteroinvasive (EIEC), Shiga toxin-producing (STEC), Enterotoxigenic (ETEC), Enteropathogenic (EPEC), and intimin-producing/attaching and effacing (AEEC)), Shigella species., Vibrio cholerae, norovirus, rotavirus, sapovirus, adenovirus, Giardia intestinalis, Cryptosporidium species, and Entamoeba histolytica. RESULTS: Enteric bacterial infections were diagnosed with an incidence of 229.9 cases/100,000 inhabitants, virus had an incidence of 86/100,000 and enteropathogenic parasites of 12.5/100,000. Viruses constituted more than half of diagnosed enteropathogens for children below 2 years and elderly above 80 years. Diagnostic methods and algorithms differed across the country and in general PCR testing resulted in higher incidences compared to culture (bacteria), antigen-test (viruses), or microscopy (parasites) for most pathogens. CONCLUSIONS: In Denmark, the majority of detected infections are bacterial with viral agents primarily detected in the extremes of ages and with few intestinal protozoal infections. Incidence rates were affected by age, clinical setting and local test methods with PCR leading to increased detection rates. The latter needs to be taken into account when interpreting epidemiological data across the country.

Prevalence and Mortality of Infective Endocarditis in Community-Acquired and Healthcare-Associated Staphylococcus aureus Bacteremia: A Danish Nationwide Registry-Based Cohort Study.

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.

Temporal Changes, Patient Characteristics, and Mortality, According to Microbiological Cause of Infective Endocarditis: A Nationwide Study.

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.

Azole resistance in Aspergillus fumigatus. The first 2-year's Data from the Danish National Surveillance Study, 2018-2020.

BACKGROUND: Azole resistance complicates treatment of patients with invasive aspergillosis with an increased mortality. Azole resistance in Aspergillus fumigatus is a growing problem and associated with human and environmental azole use. Denmark has a considerable and highly efficient agricultural sector. Following reports on environmental azole resistance in A. fumigatus from Danish patients, the ministry of health requested a prospective national surveillance of azole-resistant A. fumigatus and particularly that of environmental origin. OBJECTIVES: To present the data from the first 2 years of the surveillance programme. METHODS: Unique isolates regarded as clinically relevant and any A. fumigatus isolated on a preferred weekday (background samples) were included. EUCAST susceptibility testing was performed and azole-resistant isolates underwent cyp51A gene sequencing. RESULTS: The azole resistance prevalence was 6.1% (66/1083) at patient level. The TR34 /L98H prevalence was 3.6% (39/1083) and included the variants TR34 /L98H, TR34 3 /L98H and TR34 /L98H/S297T/F495I. Resistance caused by other Cyp51A variants accounted for 1.3% (14/1083) and included G54R, P216S, F219L, G54W, M220I, M220K, M220R, G432S, G448S and Y121F alterations. Non-Cyp51A-mediated resistance accounted for 1.2% (13/1083). Proportionally, TR34 /L98H, other Cyp51A variants and non-Cyp51A-mediated resistance accounted for 59.1% (39/66), 21.2% (14/66) and 19.7% (13/66), respectively, of all resistance. Azole resistance was detected in all five regions in Denmark, and TR34 /L98H specifically, in four of five regions during the surveillance period. CONCLUSION: The azole resistance prevalence does not lead to a change in the initial treatment of aspergillosis at this point, but causes concern and leads to therapeutic challenges in the affected patients.

Sentinel surveillance and epidemiology of Clostridioides difficile in Denmark, 2016 to 2019.

BackgroundSince 2008, Danish national surveillance of Clostridioides difficile has focused on binary toxin-positive strains in order to monitor epidemic types such as PCR ribotype (RT) 027 and 078. Additional surveillance is needed to provide a more unbiased representation of all strains from the clinical reservoir.AimSetting up a new sentinel surveillance scheme for an improved understanding of type distribution relative to time, geography and epidemiology, here presenting data from 2016 to 2019.MethodsFor 2─4 weeks in spring and autumn each year between 2016 and 2019, all 10 Danish Departments of Clinical Microbiology collected faecal samples containing toxigenic C. difficile. Isolates were typed at the national reference laboratory at Statens Serum Institut. The typing method in 2016-17 used tandem-repeat-sequence typing, while the typing method in 2018-19 was whole genome sequencing.ResultsDuring the study period, the sentinel surveillance scheme included ca 14-15% of all Danish cases of C. difficile infections. Binary toxin-negative strains accounted for 75% and 16 of the 20 most prevalent types. The most common sequence types (ST) were ST2/13 (RT014/020) (19.5%), ST1 (RT027) (10.8%), ST11 (RT078) (6.7%), ST8 (RT002) (6.6%) and ST6 (RT005/117) (5.1%). The data also highlighted geographical differences, mostly related to ST1 and temporal decline of ST1 (p = 0.0008) and the increase of ST103 (p = 0.002), ST17 (p = 0.004) and ST37 (p = 0.003), the latter three binary toxin-negative.ConclusionSentinel surveillance allowed nationwide monitoring of geographical differences and temporal changes in C. difficile infections in Denmark, including emerging types, regardless of binary toxin status.

Plasmodium cynomolgi as Cause of Malaria in Tourist to Southeast Asia, 2018.

We report human infection with simian Plasmodium cynomolgi in a tourist from Denmark who had visited forested areas in peninsular Malaysia and Thailand in August and September 2018. Because P. cynomolgi may go unnoticed by standard malaria diagnostics, this malaria species may be more common in humans than was previously thought.

Comparative evaluation of the CerTest VIASURE flu A, B & RSV real time RT-PCR detection kit on the BD MAX system versus a routine in-house assay for detection of influenza A and B virus during the 2016/17 influenza season.

BACKGROUND: Diagnosing of influenza rapidly and accurately helps clinicians to initiate appropriate treatment options and isolation protocols. Unnecessary antimicrobial treatment and laboratory testing can also be reduced. Assess commercial alternatives to in-house assays that may not only reduce laboratory technician "hands on" time but also the laboratory turnaround time is of interest. OBJECTIVES: We evaluated the performance of the VIASURE Flu A, B & RSV Real Time RT-PCR Detection Kit (CerTest Biotec) for detecting Influenza A and B viruses. STUDY DESIGN: During the 2016/17 influenza season 532 clinical samples were tested with the VIASURE assay on the BD MAX™ system versus an in-house real time RT-PCR assay with discrepant results resolved by a real time RT-PCR assay at a national reference laboratory. RESULTS: The VIASURE assay on the BD MAX showed a sensitivity of 99.5% (95% CI: 97.3-100) and a specificity of 99.1% (95% CI: 97.4-99.8) for detection of Influenza A virus. The positive predictive and negative predictive values were 98.5% (95% CI: 95.8-99.7) and 99.7% (95% CI: 98.3-100) respectively. Influenza B virus detection could not be evaluated due to a low positivity rate. The BD MAX platform offered the flexibility of several daily runs, shorter hands-on-time and shorter turnaround time than the in-house assay. CONCLUSIONS: The VIASURE assay on the BD MAX performed well and is now implemented in our clinical laboratory.

[Rat bite fever in a three-year-old child].

Rat bite fever (RBF) is rare in Denmark. It can be very difficult to diagnose, as the causative agent is an extremely fastidious organism which needs microaerophilic conditions to grow. We report a case of arthritis in the right ankle due to Streptobacillus moniliformis in a three-year-old girl who fully recovered after 14-day treatment of intravenous administrated penicillin followed by four weeks of orally administrated amoxicillin. Social history revealed the presence of two domestic rats living in the child's home. As rodents are becoming more popular as pets, RBF must be considered in patients with a history of relevant exposure.

Bacteremia with the bovis group streptococci: species identification and association with infective endocarditis and with gastrointestinal disease.

DNA sequencing of the intergenic spacer (ITS) region was used to identify 53 blood culture isolates that had previously been designated to the bovis group streptococci and clinical data was collected retrospectively from patients' records using a standardized protocol. ITS sequencing identified 19 (35.8%) isolates as Streptococcus gallolyticus subsp. gallolyticus, 12 (22.6%) as S. gallolyticus subsp. pasteurianus, two (3.8%) as S. gallolyticus subsp. macedonicus, seven (13.2%) as S. infantarius subsp. infantarius, 12 (22.6%) as S. lutetiensis and one (1.9%) as S. equinus. The association of S. gallolyticus subsp. gallolyticus with colorectal neoplasia and with infective endocarditis and the association between S. gallolyticus subsp. pasteurianus and pancreatic cancer were found to be clinically important. Also, a very high 1-year mortality rate with S. lutetiensis (66.7%) and S. gallolyticus subsp. pasteurianus (58.7%) bacteremia calls for intensive investigation for underlying disease focusing on the pancreas and the hepatobiliary system.

Species differentiation of Bacteroides dorei from Bacteroides vulgatus and Bacteroides ovatus from Bacteroides xylanisolvens - back to basics.

We present the results from 16S sequencing and phenotypic tests for differentiation of Bacteroides dorei from Bacteroides vulgatus and Bacteroides ovatus from Bacteroides xylanisolvens, which was not possible with MALDI-TOF MS. Testing with ß-glucosidase could differentiate B. dorei from B. vulgatus and a negative catalase reaction could identify B. xylanisolvens.

Better treatment of outpatients with type 1 diabetes after introduction of continuous subcutaneous insulin infusion.

INTRODUCTION: Continuous subcutaneous insulin infusion (CSII) was introduced in the outpatient diabetes clinic in Fredericia, Denmark, in 2005. The aim of this study was to evaluate the quality of metabolic control and patient satisfaction in type 1 diabetic patients treated with CSII. MATERIAL AND METHODS: In 2009-2010, a database with registration of metabolic variables and patient satisfaction was established. The collected material is a combination of retrospective and prospective data. Patient satisfaction was measured by use of the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and change (DTSQc) versions. RESULTS: By 31 December 2010, the database contained data from 68 active patients. Compared with before the initiation of CSII, glycohaemoglobin (HbA1c) had decreased significantly from 8.0% (5.8-13.7%) to 7.6% (6.1-9.5%). The improved glycaemic control was maintained each year until ≤ 4 years after initiation of CSII (p < 0.01).The fraction of patients with an HbA1c ≤ 7% had increased from 13% to 24%, the fraction of patients with an HbA1c > 9% had decreased from 18% to 3%, and the number of serious attacks of hypoglycaemia had decreased (p < 0.05). Only three episodes of ketoacidosis were observed. The DTSQs and DTSQc showed a higher patient satisfaction during CSII treatment (p < 0.01) than before its introduction. Compared with before the introduction of CSII, the patient satisfaction score had increased from 19 (12-33) to 34.5 (27-36) (p < 0.01). CONCLUSION: Type 1 diabetes patients who were changed from treatment with multi-injection therapy to CSII showed improved glycaemic control, a reduced number of hypoglycaemic attacks and improved and very high levels of patient satisfaction.

[Therapeutic consequences of lung scintigraphy in patients with intermediate probability of pulmonary embolism]. / Terapeutiske konsekvenser ved lungeskintigrafi med intermediaer sandsynlighed for lungeemboli.

INTRODUCTION: Pulmonary embolism has a high mortality and is difficult to diagnose. Lung scintigraphy is widely used. However, a significant number of patients receive an inconclusive result. The aim of this study was to determine how patients with an intermediate result were handled. MATERIAL AND METHODS: Case notes from 321 (77%) of a total of 416 consecutive patients who underwent lung scintigraphy at Odense University Hospital in 2004 were examined retrospectively. RESULTS: We found 98 (30%) patients with an intermediate probability of pulmonary embolism, among whom 14 (14%) underwent further investigation, 28 (29%) received treatment, and in 29 (30%) cases, the result was interpreted as negative for pulmonary embolism. We found no significant difference in demographic data or results of investigations performed before the scintigraphy between those who received treatment and those who did not, nor was there any difference between those who were interpreted as negative and those who were not. CONCLUSION: Few patients with intermediate probability underwent further investigation and one third was interpreted as negative for pulmonary embolism, contrary to the recommendations of several guidelines. In patients with intermediate probability of pulmonary embolism we demonstrated no differences in patient history or clinical presentation between those who received treatment and those who did not.