Despite a well-described symptomatology, treatment delay and sequelae are common in patients with Lyme neuroborreliosis (LNB). The aim of this study was to contribute to the knowledge about the ...symptomatology and epidemiology of LNB.
We conducted a retrospective study of all LNB cases verified by a positive Borrelia intrathecal antibody index test performed at the Department of Microbiology, Odense University Hospital, Denmark, from 1995 through 2014.
The study included 431 patients; 126 were children. The mean incidence was 4.7 per 100 000 inhabitants per year. The median delay from neurological symptom debut to first hospital contact was 20 days and significantly longer for patients with symptom debut in the winter/early spring. The most common clinical symptoms were painful radiculitis (65.9%), cranial nerve palsy (43.4%), and headache (28.3%). A total of 30.6% were seen in >1 hospital department, and 85.6% were admitted during their course of treatment. Serum Borrelia immunoglobulin M and immunoglobulin G at the time of positive Borrelia intrathecal antibody index test were negative in 67 patients (15.5%). We found a median treatment delay of 24 days, with no improvement in our 20-year study period. Residual symptoms following treatment were found in 28.1% of patients, and risk of residual symptoms was significantly associated with delay from symptom debut to initiation of treatment.
The association between treatment delay and residual symptoms and the lack of improvement in treatment delay during the study period highlight the need for standardized diagnostic routines and a better follow-up for LNB patients. Our findings disprove that all patients with LNB develop positive serum Borrelia antibodies within 6 weeks after infection.
We sought to investigate whether hypoalbuminaemia was mainly caused by acute or chronic factors in patients with community-acquired bacteraemia. In this population-based study, we considered 1844 ...adult cases of community-acquired bacteraemia that occurred in Funen, Denmark between 2000 and 2008. We used a stepwise prognostic predisposition-insult-response-organ dysfunction (PIRO) logistic regression model by initially including age and comorbidity, then added bacterial species, and finally sepsis severity. The models were furthermore analysed using receiver operating characteristic (ROC) curves. Outcomes comprised mortality incidence on days 0-30 and 31-365 after the bacteraemia episode. Each step was performed with and without baseline albumin level measured on the date of bacteraemia. In 422 patients, their latest albumin measurement taken 8-30 days before the date of bacteraemia was also used in the analysis together with the baseline albumin level. For each decrease of 1g/L in plasma albumin level, the odds ratios (95% confidence intervals) of mortality in the period of 0-30 days after bacteraemia were 0.86 (0.84-0.88) in both predisposition (P) and predisposition-insult (PI) models and 0.87 (0.85-0.89) in the full PIRO-model. The AUC values were 0.78 and 0.66 for mortality in the period of 0-30 days in the model comprising only predisposition factors with and without albumin levels added as a factor, respectively. The AUC values in the full PIRO-model were 0.81 and 0.73 with and without consideration of albumin levels, respectively. A higher proportion of patients died within 30 days if there was a decrease in the albumin level between days 8 and 30 before bacteraemia and the actual bacteraemia date. A single plasma albumin measurement on the bacteraemia date was a better prognostic predictor of short-term mortality than the sepsis severity score.
The Danish national SARS-CoV-2 mass test system was among the most ambitious worldwide. We describe its set-up and analyse differences in patterns of testing per demography and time period in ...relation to the three waves of SARS-CoV-2 transmission in Denmark.
We included all reported PCR- and rapid antigen-tests performed between 27 February 2020 and 10 March 2022 among all residents aged 2 years or above. Descriptive statistics and Poisson regression models were used to analyse characteristics of individuals tested for SARS-CoV-2 using a national cohort study design.
A total of 63.7 million PCR-tests and 60.0 million rapid antigen-tests were performed in the study period, testing 90.9% and 78.8% of the Danish population at least once by PCR or antigen, respectively. Female sex, younger age, Danish heritage and living in the capital area were all factors positively associated with the frequency of PCR-testing. The association between COVID-19 vaccination and PCR-testing changed from negative to positive over time.
We provide details of the widely available, free-of-charge, national SARS-CoV-2 test system, which served to identify infected individuals, assist isolation of infectious individuals and contact tracing, and thereby mitigating the spread of SARS-CoV-2 in the Danish population. The test system was utilized by nearly the entire population at least once, and widely accepted across different demographic groups. However, demographic differences in the test uptake did exist and should be considered in order not to cause biases in studies related to SARS-CoV-2, e.g., studies of transmission and vaccine effectiveness.
•No association between symptom delay and presence of CSF B.burgdorferi IgM and/or IgG.•Most of LNB patients do not convert from B.burgdorferi IgM to IgG antibodies in CSF.•Type of CSF antibodies ...associated with different LNB symptom presentations.•B.burgdorferi CSF antibody type cannot be used to interpret stage of disease in LNB.
In Europe, a definite diagnosis of Lyme neuroborreliosis (LNB) requires intrathecally produced Borrelia-specific antibodies. We aimed to examine if the time from symptom debut to lumbar puncture (LP) correlated with findings of intrathecal production of Borrelia-specific IgM and/or IgG antibodies in LNB
A retrospective study of 544 patients with a positive Borrelia burgdorferi antibody index (Bb-AI) analysed at the Department of Clinical Microbiology, Odense University Hospital, Denmark, between 01.01.1995 and 31.12.2020
The delay from symptom onset to LP for patients with positive Bb-AI IgM was 30 days (IQR 14–95 days), IgG 24 days (IQR 11–62), IgM+IgG 24 days (IQR 14–48), P = 0.098. Ninety-three patients had a second LP after median 125 days (IQR 28–432) and 25 had a third LP after median 282 days (IQR 64–539). Most patients (66.7%) did not convert from their initial intrathecal antibody finding. The prevalence of different clinical manifestations differed significantly between the three Bb-AI groups.
Intrathecal Borrelia-specific antibody production did not follow the typical immune response of initial IgM production followed by IgG production. Diagnosis of LNB stage should not be based on the type of antibodies found in the cerebrospinal fluid.
Burden of bacteraemia is rising due to increased average life expectancy in developed countries. This study aimed to compare the epidemiology and outcomes of bacteraemia in two similarly ageing ...populations with different ethnicities in Singapore and Denmark. Historical cohorts from the second largest acute-care hospital in Singapore and in the hospitals of two Danish regions included patients aged 15 and above who were admitted from 1 January 2006 to 31 December 2016 with at least 1 day of hospital stay and a pathogenic organism identified. Among 13 144 and 39 073 bacteraemia patients from Singapore and Denmark, similar 30-day mortality rates (16.5%; 20.3%), length of hospital stay (median 14 (IQR: 9-28) days; 11 (6-21)), and admission rate to ICU (15.5%; 15.6%) were observed, respectively.
,
, and
ranked among the top four in both countries. However, Singaporeans had a higher proportion of patients with diabetes (46.8%) and renal disease (29.5%) than the Danes (28.0% and 13.7%, respectively), whilst the Danes had a higher proportion of patients with chronic pulmonary disease (18.0%) and malignancy (35.3%) than Singaporeans (9.7% and 16.2%, respectively). Our study showed that top four causative organisms and clinical outcomes were similar between the two cohorts despite pre-existing comorbidities differed.
•Lateral flow tests with low sensitivity are unsuited to diagnose and monitor SARS-CoV-2.•Sensitive anti-SARS-CoV-2 ELISAs are suitable for COVID-19 diagnosis in mild cases.•IgG ELISA assays with ...high specificity would be appropriate for seroprevalence studies.
Evaluate six commercial serological assays for detection of IgA, IgM or IgG SARS-CoV-2 antibodies in different disease severities.
Three lateral flow tests (LFTs) (Acro IgM/IgG, CTK IgM/IgG, Livzon IgM/IgG) and three ELISA assays (Euroimmun IgA and IgG, Wantai IgM) were included. Application was evaluated using samples from 57 patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction, stratified according to disease severity. Specificity was assessed using historical samples from 200 blood donors.
While IgM LFTs failed to detect SARS-CoV-2 antibodies in 37–84% of non-hospitalised patients, the Wantai IgM ELISA detected antibodies in 79%. The Euroimmun IgG ELISA detected antibodies in 95% of non-hospitalised patients. IgA, IgM and IgG ELISA levels were initially low, increased over time, and correlated with disease severity. LFT sensitivity declined in samples taken >28 days after symptom onset/resolution. The Livzon IgG LFT had the highest specificity (98.5%), followed by the Euroimmun IgG ELISA (96.2%). The specificity for Euroimmun IgA ELISA improved (≥97.5%) using a custom cut-off value (4.0).
The sensitive and semi-quantitative ELISA assays are most appropriate for serologic detection of SARS-CoV-2 infection in mild cases. Livzon LFT and Euroimmun ELISA had the highest specificity among the IgG assays, making them most suitable for seroprevalence studies.
Abstract
Background
Our objectives were to improve the following outcomes in patients with Lyme borreliosis (LB) through an educational intervention in general practice: (i) increase the number of ...hospital referrals on suspicion of LB, (ii) increase the number of cerebrospinal fluid (CSF) tests examined for Borrelia burgdorferi antibody index, (iii) decrease the number of serum-B. burgdorferi antibody tests ordered, (iv) shorten delay from symptom onset to hospital in Lyme neuroborreliosis (LNB) patients, (v) increase LB knowledge among general practitioners.
Methods
A prospective non-blinded non-randomized intervention trial on the island of Funen, Denmark. The intervention included oral and written education about LB and was carried out in areas with an LNB incidence ≥4.7/100.000 between 22 January 2019 and 7 May 2019. Results were compared between the intervention group (49 general practices) and the remaining general practices in Funen (71 practices) 2 years before and after the intervention.
Results
In the study period, 196 patients were referred on suspicion of LB, a 28.9% increase in the intervention group post-intervention, 59.5% increase in the control group (P = 0.47). The number of CSF-Borrelia-antibody index tests increased 20.8% in the intervention group, 18.0% in the control group (P = 0.68), while ordered serum-B. burgdorferi antibody tests declined 43.1% in the intervention group, 34.5% in the control group (P = 0.30). 25.1% had the presence of serum-B. burgdorferi antibodies. We found no difference in LNB pre-hospital delay before and after intervention or between groups (P = 0.21). The intervention group performed significantly better on a follow-up questionnaire (P = 0.02).
Conclusion
We found an overall improvement in LB awareness and referrals among general practitioners but could not show any effect of the intervention on clinical outcomes of LNB.
Sepsis is a frequent cause of admission, but incidence rates based on administrative data have previously produced large differences in estimates. The aim of the study was to estimate the incidence ...of community-acquired sepsis based on patients' symptoms and clinical findings at arrival to the hospital.
Population-based survey.
Medical emergency department from September 1, 2010, to August 31, 2011.
All patients were manually reviewed using a structured protocol in order to identify the presence of infection. Vital signs and laboratory values were collected to define the presence of systemic inflammatory response syndrome and organ dysfunction.
Incidence rate of sepsis of any severity. Among 8,358 admissions to the medical emergency department, 1,713 patients presented with an incident admission of sepsis of any severity, median age 72 years (5-95%; range, 26-91 yr), 793 (46.3%) were men, 728 (42.5%) presented with a Charlson comorbidity index greater than 2,621 (36.3%) were admitted with sepsis, 1,071 (62.5%) with severe sepsis, and 21 (1.2%) with septic shock. Incidence rate was 731/100,000 person-years at risk (95% CI, 697-767) in patients with sepsis of any severity, 265/100,000 person-years at risk (95% CI, 245-287) in patients with sepsis, 457/100,000 person-years at risk (95% CI, 430-485) in patients with severe sepsis, and 9/100,000 person-years at risk (95% CI, 6-14) in patients with septic shock.
Based on symptoms and clinical findings at arrival, incidence rates of patients admitted to a medical emergency department with sepsis and severe sepsis are more frequent than previously reported based on discharge diagnoses.
Abstract Background context Information on short- and especially long-term mortality among patients with infectious spondylodiscitis is sparse. Purpose To analyze mortality, factors associated with ...death, and cause-specific mortality rates among patients with infectious nonpostoperative spondylodiscitis. Study design A case-cohort study. Patient sample We identified all patients aged 18 years or older treated for infectious spondylodiscitis from January 1994 to May 2009 at hospitals in Funen County, Denmark. Outcome measures Overall and cause-specific mortality. Methods Mortality rates among patients were compared with rates among a reference population using Kaplan-Meier plots and mortality rate ratios (MRRs). Short-term mortality was defined as deaths within first year after admission and long-term mortality was deaths thereafter. Factors associated with death were determined. Results Among 298 identified patients, 61 (20%) died within the first year. Adjusted MRRs were 16.8 (95% confidence interval: 9.9–28.5) for 0 to 90 days; 4.2 (2.5–7.0) for 91 to 365 days; 2.2 (1.6–2.9) for 1 to 4 years; and 1.7 (1.2–2.5) for 5 to 14 years. Mortality rate ratios stratified on microbiological etiology were 8.8 (3.3–22.1) for 0 to 90 days; 1.4 (0.3–5.8) for 91 to 365 days; 3.2 (2.0–5.1) for 1 to 4 years; and 1.1 (0.5–2.4) for 5 to 14 years for unknown etiology and 24.0 (13.0–44.2) for 0 to 90 days; 6.0 (3.1–11.5) for 91 to 365 days; 1.9 (1.1–3.2) for 1 to 4 years; and 2.7 (1.5–4.7) for 5 to 14 years among Staphylococcus aureus infections. The main factors associated with short-term mortality were severe neurologic deficits at the time of admission, epidural abscess, and comorbidities. Long-term mortality seemed independent of microbiological etiology. Conclusions Mortality remained high the first year after admission and thereafter decreased with time to a level close to the reference population. Short-term mortality was especially related to infection with abscess formation and neurologic deficits and long-term mortality was related to alcohol dependency.