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.
Lyme neuroborreliosis is the most severe clinical manifestation of Lyme borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme borreliosis seems to be stabilising. This is ...not the case on the island of Funen, Denmark, where the number of human Lyme neuroborreliosis cases has markedly declined throughout the last decade. We propose the reason for the decline is a major epidemic among roe deer, killing almost half of their population, resulting in a reduction in the tick population which make it less likely to get a tick bite and therefore to contract Lyme neuroborreliosis. This is the first time such a relationship is described as a naturally occurring phenomenon in Europe.
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 messages
The 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.
Summary Objectives To characterize patients presenting with community-acquired bacteremia and a low C-reactive protein (CRP) plasma level at date of bacteremia. Methods Population-based cohort study. ...Patient characteristics were compared for three CRP groups (≤20 mg/L, 21–100 mg/L and >100 mg/L) using chi-square test and oneway anova. The 30-day mortality rates were compared using logistic regression analyses. Results Of the 2017 patients included, 193 (9.6%) had a CRP ≤20 mg/L. These patients were younger, more likely to be male, overrepresented in the intensive care unit and had more comorbidities. In blood cultures from the low CRP group hemolytic streptococci and coagulase-negative staphylococci were found relatively more common, whereas Streptococcus pneumoniae or Staphylococcus aureus were found relatively less common compared to the other CRP groups. The majority of patients with an initial low CRP mounted a CRP response the following days. The 30-day mortality rate was lower in the low CRP group (13.5%) than in the group with CRP >100 mg/L (20.6%). Conclusions A considerable proportion of patients with community-acquired bacteremia has a normal or low initial CRP level. The plasma CRP level should not be used to rule out serious infection or withhold antibiotic therapy.
We examined whether specific time windows after hospital admission reflected a sharp transition between community and hospital acquisition of bacteremia. We further examined whether different time ...windows to distinguish between community acquisition, healthcare association (HCA), and hospital acquisition influenced the results of prognostic models.
Population-based cohort study.
Hospitals in 3 areas of Denmark (2.3 million inhabitants) during 2000-2011.
We computed graphs depicting proportions of males, absence of comorbidity, microorganisms, and 30-day mortality pertaining to bacteremia 0, 1, 2, …, 30, and 31 days and later after admission. Next, we assessed whether different admission (0-1, 0-2, 0-3, 0-7 days) and HCA (30, 90 days) time windows were associated with changes in odds ratio (OR) and area under the receiver operating characteristic (ROC) curve for 30-day mortality, adjusting for sex, age, comorbidity, and microorganisms.
For 56,606 bacteremic episodes, no sharp transitions were detected on a specific day after admission. Among the 8 combined time windows, ORs for 30-day mortality varied from 1.30 (95% confidence interval CI, 1.23-1.37) to 1.99 (95% CI, 1.48-2.67) for HCA and from 1.36 (95% CI, 1.24-1.50) to 2.53 (95% CI, 2.01-3.20) for hospital acquisition compared with community acquisition. Area under the ROC curve changed marginally from 0.684 (95% CI, 0.679-0.689) to 0.700 (95% CI, 0.695-0.705).
No time transitions unanimously distinguished between community and hospital acquisition with regard to sex, comorbidity, or microorganisms, and no difference in 30-day mortality was seen for HCA patients in relation to a 30- or 90-day time window. ORs decreased consistently in the order of hospital acquisition, HCA, and community acquisition, regardless of time window combination, and differences in area under the ROC curve were immaterial.
No study has evaluated C-reactive protein (CRP) and plasma albumin (PA) levels longitudinally in patients with acute myeloid leukaemia (AML).
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).
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.
PA decrease is an important biomarker for imminent bacteraemia in adult patients with AML.
Molecular methods for diagnosing Lyme neuroborreliosis (LNB) have shown suboptimal diagnostic sensitivities. The objective of this study was to improve the clinical sensitivity of PCR detection of ...Borrelia burgdorferi sensu lato spirochetes by inoculating cerebrospinal fluid (CSF) from patients suspected of LNB directly into culture medium at the time of lumbar puncture, with this pursuing enrichment of Borrelia spirochetes before PCR analysis. Adult patients with symptoms suggestive of LNB were prospectively enrolled at two hospitals in the Region of Southern Denmark. The CSF-culture samples were incubated for at least eight weeks. During this period, culture sample aliquots were analysed for the presence of Borrelia DNA by separate PCR protocols in two independent clinical laboratories. The included patients were diagnosed with definite (n=12) or possible (n=2) LNB, and non-LNB (n=171) based on clinical and paraclinical findings. Patients in the LNB and the non-LNB group had a median duration from symptom onset to lumbar puncture of 40 days (IQR 23–90 days) and 120 days (IQR 32–365 days), respectively. Pre-enrichment growth of Borrelia spirochetes was accomplished from three patients (21 %) in the LNB group. The positive culture samples were confirmed by both the digital droplet PCR and the real-time PCR methods employed. All CSF samples were PCR negative in the non-LNB group. The results of this study do not support the use of Borrelia-specific PCR as a general routine diagnostic tool in adults. Still, they suggest it may prove of additional value in selected patients with a limited time from symptom onset to sample collection.
Matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) is a widely used method for bacterial species identification. Incomplete databases and mass spectral ...quality (MSQ) still represent major challenges. Important proxies for MSQ are the number of detected marker masses, reproducibility, and measurement precision. We aimed to assess MSQs across diagnostic laboratories and the potential of simple workflow adaptations to improve it.
For baseline MSQ assessment, 47 diverse bacterial strains, which are challenging to identify by MALDI-TOF MS, were routinely measured in 36 laboratories from 12 countries, and well-defined MSQ features were used. After an intervention consisting of detailed reported feedback and instructions on how to acquire MALDI-TOF mass spectra, measurements were repeated and MSQs were compared.
At baseline, we observed heterogeneous MSQ between the devices, considering the median number of marker masses detected (range = 2–25), reproducibility between technical replicates (range = 55%–86%), and measurement error (range = 147 parts per million (ppm)–588 ppm). As a general trend, the spectral quality was improved after the intervention for devices, which yielded low MSQs in the baseline assessment as follows: for four out of five devices with a high measurement error, the measurement precision was improved (p-values <0.001, paired Wilcoxon test); for six out of ten devices, which detected a low number of marker masses, the number of detected marker masses increased (p-values <0.001, paired Wilcoxon test).
We have identified simple workflow adaptations, which, to some extent, improve MSQ of poorly performing devices and should be considered by laboratories yielding a low MSQ. Improving MALDI-TOF MSQ in routine diagnostics is essential for increasing the resolution of bacterial identification by MALDI-TOF MS, which is dependent on the reproducible detection of marker masses. The heterogeneity identified in this external quality assessment (EQA) requires further study.
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