Comparative epidemiology of bacteraemia in two ageing populations: Singapore and Denmark.

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. Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus 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.

Inhaled corticosteroids and Stenotrophomonas maltophilia in outpatients with chronic obstructive pulmonary disease: a retrospective cohort study.

OBJECTIVES: Inhaled corticosteroids (ICS) are widely used in patients with chronic obstructive pulmonary disease (COPD). However, ICS are associated with an increased risk of adverse effects.We aimed to determine whether an association between a lower respiratory tract culture with Stenotrophomonas maltophilia and increasing ICS dosing in patients with COPD exists. DESIGN: An observational cohort study of outpatients with COPD in Denmark between 2010 and 2018.ICS exposure was categorised into four groups based on average daily consumption 1 year prior to inclusion: no use, low ICS dose (≤400 µg), moderate ICS dose (400-800 µg) and high ICS dose (>800 µg). Dose-response relationship was investigated by a multivariable Cox proportional hazards regression. RESULTS: Of the total 22 689 patients, 459 had lower respiratory tract cultures positive for S. maltophilia. The HR of S. maltophilia increased with increasing daily ICS dose: low ICS dose HR 2.6 (95% CI 1.6 to 4.0), moderate ICS dose HR 3.0 (95% CI 1.9 to 4.6) and high ICS dose HR 5.7 (95% CI 3.8 to 8.5). CONCLUSIONS: We found that ICS was associated with a high, dose-dependent increased hazard of S. maltophilia in outpatients with COPD. High dose users had a nearly six times increased hazard compared with non-users of ICS. When appropriate, attempts at de-escalating ICS treatment should be made.

Detection of infections by computerized capture of peaks in longitudinally measured C-reactive protein levels.

We developed four algorithms for the automatic capture of C-reactive protein (CRP) peaks in 296 adult patients with acute myeloid leukemia who had bloodstream infection (BSI) episodes, negative blood cultures (BCs) or possible infections where no BCs were performed. The algorithms detected CRP peaks for 418-446 of the 586 documented BSI episodes (71.3-76.1%) and 2714-3118 of the 4382 negative BCs (61.9-71.2%). The four algorithms captured 382-789 CRP peaks in which there were neither BSI episodes nor negative BCs. We conclude that automatic capture of CRP peaks is a tool for the monitoring of BSI episodes and possibly other infections in patients with acute myeloid leukemia.

Mortality and exacerbations associated with Stenotrophomonas maltophilia in chronic obstructive pulmonary disease. A regional cohort study of 22,689 outpatients.

OBJECTIVES: The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture positive for S. maltophilia in COPD patients was independently associated with increased risk of death and hospitalisation for exacerbation of COPD. METHODS: An observational cohort study following outpatients with COPD in Eastern Denmark between 2010 and 2018, with a follow-up period of five years. Presence of S. maltophilia was treated as a time-varying exposure, where patients were considered exposed at the time of the first isolation of S. maltophilia from the lower respiratory tract. The hazard ratio (HR) of death and hospitalisation for acute exacerbations of COPD was assessed using a Cox proportional hazards regression. RESULTS: Of the total 22,689 patients 459 (2.0%) had a lower respiratory sample positive for S. maltophilia. A total of 7,649 deaths (S. maltophilia positive: 243 (52.9%) and S. maltophilia negative: 7,406 (34.4%)) and 24,912 hospitalisations for exacerbation of COPD (S. maltophilia positive: 1,100 in 459 patients and S. maltophilia negative: 23,821 in 22,230 patients) were registered during the study period. We found that a lower respiratory tract culture positive for S. maltophilia was associated with both increased mortality: HR 3.3 (95% CI 2.6-4.3), and hospitalisation for exacerbation of COPD: HR 3.4 (95% CI 2.8-4.1). CONCLUSIONS: A lower respiratory tract culture positive for S. maltophilia in COPD patients was associated with a substantially increased mortality and hospitalisation for exacerbation of COPD. Randomised controlled trials are proposed to determine whether S. maltophilia should be the target of antibiotic treatment.

Exploring the dynamics of Borrelia burgdorferi sensu lato antibodies-a registry-based study on laboratory data from Sweden and Denmark.

OBJECTIVES: Lyme borreliosis (LB) is the most common tick-transmitted infection in the northern hemisphere and is caused by bacteria in the Borrelia burgdorferi sensu lato (Bbsl)-complex. The diagnosis is partially based on serology, and clinicians often take follow-up serum samples to look for seroconversion or an increase in IgG-antibody levels. In this registry-based study, we proposed a method for determining actual changes in IgG and examined antibody reactivity and decay. METHODS: Serological data from the departments of clinical microbiology at Karlstad Hospital, Sweden, and Slagelse Hospital, Denmark, were used to calculate a seroreactivity cut-off (SCOFF), above which changes between two samples from the patient cannot be explained by random variation. Increases in IgG reactivity as well as IgG and IgM decay were illustrated using time-to-event analysis and the SCOFF. RESULTS: A total of 44,861 serum samples from 34,157 patients were tested for Bbsl-antibodies. Of the 4301 patients with follow-up samples taken within 100 days, 201 (4.67%) were above the SCOFF of 1.42 with a median time to follow-up sample of 36 days (interquartile range: 21). IgG demonstrated longer median time for all antibody levels (indeterminate: 4.6 years, low: 7.0 years, moderate-high: 8.8 years) than IgM antibodies (indeterminate: 2.1 years, low: 3.9 years, moderate-high: 6.8 years) and higher initial antibody levels persisted significantly longer for both IgG and IgM antibodies (p < 0.001). Of the 7868 patients with follow-up samples, isolated IgM reactivity preceded an increase in IgG reactivity in 18 patients (0.23%). DISCUSSION: The SCOFF indicated little biological and random variation for Bbsl-specific IgG antibodies on the platforms used during the study. In most follow-up samples, both IgG and IgM antibodies persisted for years, with longer seropositivity associated with high initial antibody levels and IgG-type antibodies. The diagnostic value of isolated IgM reactivity was limited.

Inhaled corticosteroids and risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease.

BACKGROUND: Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia. Moraxella catarrhalis is one of the most common bacterial causes of infectious exacerbation in COPD. Currently, to our knowledge, no studies have investigated if ICS increases the risk of lower respiratory tract infection with M. catarrhalis in patients with COPD. OBJECTIVE: To investigate if accumulated ICS use in patients with COPD, is associated with a dose-dependent risk of infection with M. catarrhalis. METHODS: This observational cohort study included 18 870 persons with COPD who were registered in The Danish Register of COPD. Linkage to several nationwide registries was performed.Exposure to ICS was determined by identifying all prescriptions for ICS, redeemed within 365 days prior to study entry. Main outcome was a lower respiratory tract sample positive for M. catarrhalis. For the main analysis, a Cox multivariate regression model was used.We defined clinical infection as admission to hospital and/or a redeemed prescription for a relevant antibiotic, within 7 days prior to 14 days after the sample was obtained. RESULTS: We found an increased, dose-dependent, risk of a lower respiratory tract sample with M. catarrhalis among patients who used ICS, compared with non-users. For low and moderate doses of ICS HR was 1.65 (95% CI 1.19 to 2.30, p=0.003) and 1.82 (95% CI 1.32 to 2.51, p=0.0002), respectively. In the group of patients with highest ICS exposure, the HR of M. catarrhalis was 2.80 (95% CI 2.06 to 3.82, p<0.0001). Results remained stable in sensitivity analyses. 87% of patients fulfilled the criteria for clinical infection, and results remained unchanged in this population. CONCLUSION: Our study shows a dose-dependent increased risk of infection with M. catarrhalis associated to ICS exposure.

Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease and Risk of Acquiring Streptococcus pneumoniae Infection. A Multiregional Epidemiological Study.

Background: Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users. Methods: The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010-2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses. Findings: A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with S. pneumoniae during follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk of S. pneumoniae as follows: low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results. Interpretation: Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring S. pneumoniae, but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk.

Discriminating between Lyme neuroborreliosis and other central nervous system infections by use of biomarkers CXCL13 and IL-6.

CXCL13 in cerebrospinal fluid has gradually become an established biomarker for Lyme neuroborreliosis (LNB), however the diagnostic performance of CXCL13 may be improved by the addition of IL-6, a non-specific infection biomarker. The aim of this study was to measure the concentrations of CXCL13 and IL-6 in cerebrospinal fluid, in the attempt to evaluate the diagnostic performance of these two biomarkers, in the differentiation between definite and possible LNB, as well as between LNB and other neuroinfections. This study used a cross-sectional design to quantify the levels of CXCL13 and IL-6 in cerebrospinal fluid (CSF) specimens from consecutive patients examined for central nervous system (CNS) infections at Lillebaelt Hospital in the Region of Southern Denmark. CXCL13 and IL-6 were measured simultaneously using the Bio-Plex 200 multiplex Cytokine Immunoassay System (Bio-Rad). Based on clinical and paraclinical findings, we grouped patients into six separate groups: definite LNB, possible LNB, Viral CNS infection, non-Borrelia Bacterial CNS infection, Other CNS disease (with pleocytosis) and Negative (without pleocytosis). A combined interpretation of four variables (leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF) is presented using principal component cluster analysis. We included by chart review 390 patients discharged with definite LNB (n = 31), possible LNB (n = 10), confirmed Viral or non-Borrelia Bacterial CNS infection (n = 34), Other CNS disease (n = 58), and Negative (n = 257) for CXCL13 and IL-6 analysis. Principal component analysis (PCA) revealed three distinct clusters based on leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF from 380 included patients (10 possible LNB patients excluded). The clusters clearly differentiate the groups: definite LNB, non-Borrelia Bacterial CNS infection and Negative (without pleocytosis). A receiver operating characteristic (ROC) curve comparing LNB patients (n = 31) and all non-LNB conditions with CSF pleocytosis (n = 99) indicated an optimal CXCL13 cut-off value of 50.7 pg/mL, resulting in a sensitivity and a specificity of 93.6 and 91.1%, respectively. The ROC analysis comparing patients with confirmed non-LNB CNS infection (n = 34) and all others with CSF pleocytosis (n = 97) resulted in an optimal IL-6 cut-off value of 111.5 pg/mL, yielding a sensitivity and a specificity of 78.8% and 82.5% respectively. Of the ten possible LNB patients, three cases (with CXCL13 levels above cut-off) fall within the LNB cluster, and one case is just outside, providing some laboratory support for the diagnosis of LNB. The remaining six possible LNB patients (with CXCL13 levels below the 50.7 cut-off) had little support for the diagnosis of LNB in the PCA-plot. The results of this study confirm that CXCL13 is a valuable supplement for diagnosis of LNB, and that the combination of CXCL13 and IL-6 may be used to differentiate cases of LNB from other CNS infections. Furthermore, IL-6 can be of differential diagnostic value when evaluating patients with possible LNB.

Impact of C-reactive protein and albumin levels on short, medium, and long term mortality in patients with diffuse large B-cell lymphoma.

Objectives and study design: In this population-based study of 602 patients, we amended C-reactive protein (CRP) and plasma albumin (PA) levels around the diagnosis of diffuse large B-cell lymphoma (DLBCL) to the International Prognostic Index (IPI) and assessed 0-90, 91-365, and +365-day survival.Results: The CRP did not contribute to the IPI's prognostic or discriminatory ability, regardless of time period, particularly not in models with PA. In contrast, the PA was an important contributor, especially in the 0-90 day period, but also up to one year after the diagnosis. For day 0-90, the model with the IPI only had an Area Under the Receiver Operating Characteristics (AUROC) of 0.742, whereas the IPI with PA as a continuous variable rendered an AUROC of 0.841. Especially the lower PA quartile (18-32 g/L) contributed to the worse prognosis.Conclusions: The amendment of PA to the IPI may significantly improve the short-term prognostic and discriminative ability.Key messagesThe amendment of the plasma albumin (PA) level to the International Prognostic Index significantly improved the prediction of mortality up to one year after the diagnosis of diffuse large B-cell lymphoma.It was especially the lower quartile of the PA level (18-32 g/L) that contributed to the worse prognosis.

Effect of Influenza Vaccination on Risk of Coronavirus Disease 2019: A Prospective Cohort Study of 46†000 Healthcare Workers.

BACKGROUND: The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19). METHODS: A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination. RESULTS: The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56-1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found. CONCLUSIONS: The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.

Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia. The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD. METHODS: We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017. ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry. Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa. Propensity score matched models were used as sensitivity analyses. RESULTS: A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up. ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use). A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001). CONCLUSION: Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa. Caution should be taken when administering high doses of ICS in severely ill patients with COPD. These results should be confirmed in comparable cohorts and other settings.

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.

Longitudinal trajectory patterns of plasma albumin and C-reactive protein levels around diagnosis, relapse, bacteraemia, and death of acute myeloid leukaemia patients.

BACKGROUND: No study has evaluated C-reactive protein (CRP) and plasma albumin (PA) levels longitudinally in patients with acute myeloid leukaemia (AML). METHODS: We studied defined events in 818 adult patients with AML in relation to 60,209 CRP and PA measures. We investigated correlations between CRP and PA levels and daily CRP and PA levels in relation to AML diagnosis, AML relapse, or bacteraemia (all ±30 days), and death (─30-0 days). RESULTS: On the AML diagnosis date (D0), CRP levels increased with higher WHO performance score (PS), e.g. patients with PS 3/4 had 68.1 mg/L higher CRP compared to patients with PS 0, adjusted for relevant covariates. On D0, the PA level declined with increasing PS, e.g. PS 3/4 had 7.54 g/L lower adjusted PA compared to PS 0. CRP and PA levels were inversely correlated for the PA interval 25-55 g/L (R = - 0.51, p < 10-5), but not for ≤24 g/L (R = 0.01, p = 0.57). CRP increases and PA decreases were seen prior to bacteraemia and death, whereas no changes occurred up to AML diagnosis or relapse. CRP increases and PA decreases were also found frequently in individuals, unrelated to a pre-specified event. CONCLUSIONS: PA decrease is an important biomarker for imminent bacteraemia in adult patients with AML.

Prognostic accuracy of qSOFA in predicting 28-day mortality among infected patients in an emergency department: a prospective validation study.

BACKGROUND: Few prospective studies have evaluated the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) criteria in emergency department (ED)settings. The aim of this study was to determine the prognostic accuracy of qSOFA compared with systemic inflammatory response syndrome (SIRS) in predicting the 28-day mortality of infected patients admitted to an ED. METHODS: A prospective observational cohort study of all adult (≥18 years) infected patients admitted to the ED of Slagelse Hospital, Denmark, was conducted from 1 October 2017 to 31 March 2018. Patients were enrolled consecutively and data related to SIRS and qSOFA criteria were obtained from electronic triage record. Information regarding mortality was obtained from the Danish Civil Registration System. The original cut-off values of ≥2 was used to determine the prognostic accuracy of SIRS and qSOFA criteria for predicting 28-day mortality and was assessed by analyses of sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios and area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). RESULTS: A total of 2112 patients were included in this study. A total of 175 (8.3%) patients met at least two qSOFA criteria, while 1012 (47.9%) met at least two SIRS criteria on admission. A qSOFA criteria of at least two for predicting 28-day mortality had a sensitivity of 19.5% (95% CI 13.6% to 26.5%) and a specificity of 92.6% (95% CI 91.4% to 93.7%). A SIRS criteria of at least two for predicting 28-day mortality had a sensitivity of 52.8% (95% CI 44.8% to 60.8%) and a specificity of 52.5% (95% CI 50.2% to 54.7%). The AUROC values for qSOFA and SIRS were 0.63 (95% CI 0.59 to 0.67) and 0.52 (95% CI 0.48 to 0.57), respectively. CONCLUSION: Both SIRS and qSOFA had poor sensitivity for 28-day mortality. qSOFA improved the specificity at the expense of the sensitivity resulting in slightly higher prognostic accuracy overall.

Community-acquired meningitis caused by beta-haemolytic streptococci in adults: a nationwide population-based cohort study.

The objective of this study was to examine the clinical presentation of community-acquired beta-haemolytic streptococcal (BHS) meningitis in adults. This is a nationwide population-based cohort study of adults (≥ 16 years) with BHS meningitis verified by culture or polymerase chain reaction of the cerebrospinal fluid (CSF) from 1993 to 2005. We retrospectively evaluated clinical and laboratory features and assessed outcome by Glasgow Outcome Scale (GOS). We identified 54 adults (58% female) with a median age of 65 years (IQR 55-73). Mean incidence rate was 0.7 cases per 1,000,000 person-years. Alcohol abuse was noted among 11 (20%) patients. Group A streptococci (GAS) were found in 17 (32%) patients, group B (GBS) in 18 (34%), group C (GCS) in four (8%) and group G (GGS) in 14 (26%). Patients with GAS meningitis often had concomitant otitis media (47%) and mastoiditis (30%). Among patients with GBS, GCS or GGS meningitis, the most frequent concomitant focal infections were bone and soft tissue infections (19%) and endocarditis (16%). In-hospital mortality was 31% (95% CI 19-45), and 63% (95% CI 49-76) had an unfavourable outcome at discharge (GOS < 5). BHS meningitis in adults is primarily observed among the elderly and has a poor prognosis. GAS meningitis is primarily associated with concomitant ear-nose-throat infection.

The value of seroprevalence data as surveillance tool for Lyme borreliosis in the general population: the experience of Belgium.

BACKGROUND: Serological surveillance, based on the measurement of the presence of specific antibodies in a given population, can be used in addition to traditional and routine disease surveillance methods. The added value of this has been largely documented for vaccine-preventable diseases, but to a lesser extent for vector-borne diseases. This study aimed to evaluate the utility of seroprevalence data as additional source of information on the epidemiology of Lyme borreliosis in Belgium. METHODS: In total, 3215 residual blood samples collected in 2013-2015 were analysed with Liaison® Borrelia IgG kit (DiaSorin S.p.A, Saluggia, Italy). Positive and equivocal results were further examined with immunoblotting (recomLine Borrelia IgG kit, Mikrogen, Neuried, Germany). Crude prevalence estimates of equivocal and seropositive results were calculated and further adjusted accounting for clustered sampling and standardized for age, sex and population per province, according to the Belgian population structure in 2014. The effect of age, sex and region on seropositivity was assessed using log-binomial regression. RESULTS: The overall weighted national seroprevalence for Borrelia burgdorferi sensu lato, adjusted for clustered sampling, age, sex and province was 1.06% (95%CI 0.67-1.67). Although not statistically significant, the highest prevalences were observed in men and in those younger than 15 years or older than 59 years of age. At provincial level, the seroprevalence estimates do not follow the geographical distribution of tick bites and diagnoses of Lyme borreliosis as detected through other surveillance systems. CONCLUSIONS: Although the use of residual samples for seroprevalence estimates has several advantages, it seems to be a limited tool for serological surveillance of Lyme borreliosis in Belgium, other than follow-up of trends if repeated over time. A population-based sampling strategy might provide a more representative nationwide sample, but would be very time intensive and expensive. Seroprevalence studies within risk groups or risk areas in Belgium could provide a useful alternative approach to complement routine surveillance data of Lyme borreliosis.

Pleural infection: a retrospective study of clinical outcome and the correlation to known etiology, co-morbidity and treatment factors.

BACKGROUND: We explored the hypothesized importance of early knowledge of microbiological etiology in patients with pleural infection, including comorbidity and treatment factors in the outcome analyses. METHODS: Data from the medical records of a large cohort of 437 consecutive patients in 9 hospitals in East-Denmark were included retrospectively. RESULTS: Microbiology, co-morbidity, therapy and outcome are described in detail. Patient groups with microbiology negative and known bacterial etiology had a similar 30-day and 90-day mortality. There were no differences in initial antibiotic treatment regimens, antibiotic treatment duration, rate of intra-pleural fibrinolysis treatment, surgical referral rate, and ICU admittance rate. Patients with microbiology negative etiology were younger (60.8 vs 64.3 years) and fewer had predisposing risk factors (59% vs 71%), but pleural drainage was more often delayed (49% vs 36%). Mortality was similar in patients treated with either of the two nationally recommended initial antibiotic regimens. However, higher 90-day mortality (22.5% vs 9.7%), disease severity (31.5% vs 6.2%), and ICU admittance rate (21.3% vs 2.9%) was observed in a sub-group with initial broad-spectrum treatment compared to patients receiving the nationally recommended initial treatments, irrespective of knowledge of etiology. Several factors correlated independently to 90-day mortality, including age, predisposing risk factors, surgical referral (Odds-Ratios > 1), drainage delay and intra-pleural fibrinolysis (ORs < 1). CONCLUSIONS: No difference was found between patients with microbiology negative and known bacterial etiology regarding outcome or treatment parameters. Treatment factors and predisposing factors independently relating to mortality were found in the cohort. Broad-spectrum antibiotics were initially used for treatment of patients with more severe illness and poorer outcome.

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) results from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the heritability of AS. METHODS: Using a candidate gene approach in this case-control study, 51 mainly functional single nucleotide polymorphisms (SNPs) in genes regulating inflammation were assessed in 709 patients with AS and 795 controls. Data on the patients with AS were obtained from the DANBIO registry where patients from all of Denmark are monitored in routine care during treatment with conventional and biologic disease modifying anti-rheumatic drugs (bDMARDs). The results were analyzed using logistic regression (adjusted for age and sex). RESULTS: Nine polymorphisms were associated with risk of AS (p < 0.05). The polymorphisms were in genes regulating a: the TNF-α pathway (TNF -308 G > A (rs1800629), and - 238 G > A (rs361525); TNFRSF1A -609 G > T (rs4149570), and PTPN22 1858 G > A (rs2476601)), b: the IL23/IL17 pathway (IL23R G > A (rs11209026), and IL18-137 G > C (rs187238)), or c: the NFkB pathway (TLR1 743 T > C (rs4833095), TLR4 T > C (rs1554973), and LY96-1625 C > G (rs11465996)). After Bonferroni correction the homozygous variant genotype of TLR1 743 T > C (rs4833095) (odds ratios (OR): 2.59, 95% confidence interval (CI): 1.48-4.51, p = 0.04), and TNFRSF1A -609 G > T (rs4149570) (OR: 1.79, 95% CI: 1.31-2.41, p = 0.01) were associated with increased risk of AS and the combined homozygous and heterozygous variant genotypes of TNF -308 G > A (rs1800629) (OR: 0.56, 95% CI: 0.44-0.72, p = 0.0002) were associated with reduced risk of AS. CONCLUSION: We replicated associations between AS and the polymorphisms in TNF (rs1800629), TNFRSF1A (rs4149570), and IL23R (rs11209026). Furthermore, we identified novel risk loci in TNF (rs361525), IL18 (rs187238), TLR1 (rs4833095), TLR4 (rs1554973), and LY96 (rs11465996) that need validation in independent cohorts. The results suggest that genetically determined high activity of the TNF-α, IL23/IL17, and NFkB pathways increase risk of AS.