Publications by authors named "Jens Möller"

194 Publications

Proteome Adaptation to Cell Culture Medium and Serum.

Proteomes 2021 Mar 13;9(1). Epub 2021 Mar 13.

Microbiology Division, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.

Host-pathogen interactions are often studied in vitro using primary or immortal cell lines. This set-up avoids ethical problems of animal testing and has the additional advantage of lower costs. However, the influence of cell culture media on bacterial growth and metabolism is not considered or investigated in most cases. To address this question growth and proteome adaptation of strain ISS3319 were investigated in this study. Bacteria were cultured in standard growth medium, cell culture medium, and fetal calf serum. Mass spectrometric analyses and label-free protein quantification hint at an increased bacterial pathogenicity when grown in cell culture medium as well as an influence of the growth medium on the cell envelope.
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http://dx.doi.org/10.3390/proteomes9010014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005964PMC
March 2021

Newly Isolated Animal Pathogen Is Cytotoxic to Human Epithelial Cells.

Int J Mol Sci 2021 Mar 29;22(7). Epub 2021 Mar 29.

Microbiology Division, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

is a newly identified animal pathogen of forest animals such as roe deer and wild boars. The species is closely related to the emerging human pathogen and the widely distributed animal pathogen . In this study, strain W25 was characterized with respect to its interaction with human cell lines. Microscopy, measurement of transepithelial electric resistance and cytotoxicity assays revealed detrimental effects of to different human epithelial cell lines and to an invertebrate animal model, larvae, comparable to diphtheria toxin-secreting Furthermore, the results obtained may indicate a considerable zoonotic potential of this newly identified species.
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http://dx.doi.org/10.3390/ijms22073549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037504PMC
March 2021

Prediction of risk of acquiring urinary tract infection during hospital stay based on machine-learning: A retrospective cohort study.

PLoS One 2021 31;16(3):e0248636. Epub 2021 Mar 31.

SAS Institute A/S, Aarhus, Denmark.

Background: Healthcare associated infections (HAI) are a major burden for the healthcare system and associated with prolonged hospital stay, increased morbidity, mortality and costs. Healthcare associated urinary tract infections (HA-UTI) accounts for about 20-30% of all HAI's, and with the emergence of multi-resistant urinary tract pathogens, the total burden of HA-UTI will most likely increase.

Objective: The aim of the current study was to develop two predictive models, using data from the index admission as well as historic data on a patient, to predict the development of UTI at the time of entry to the hospital and after 48 hours of admission (HA-UTI). The ultimate goal is to predict the individual patient risk of acquiring HA-UTI before it occurs so that health care professionals may take proper actions to prevent it.

Methods: Retrospective cohort analysis of approx. 300 000 adult admissions in a Danish region was performed. We developed models for UTI prediction with five machine-learning algorithms using demographic information, laboratory results, data on antibiotic treatment, past medical history (ICD10 codes), and clinical data by transformation of unstructured narrative text in Electronic Medical Records to structured data by Natural Language Processing.

Results: The five machine-learning algorithms have been evaluated by the performance measures average squared error, cumulative lift, and area under the curve (ROC-index). The algorithms had an area under the curve (ROC-index) ranging from 0.82 to 0.84 for the entry model (T = 0 hours after admission) and from 0.71 to 0.77 for the HA-UTI model (T = 48 hours after admission).

Conclusion: The study is proof of concept that it is possible to create machine-learning models that can serve as early warning systems to predict patients at risk of acquiring urinary tract infections during admission. The entry model and the HA-UTI models perform with a high ROC-index indicating a sufficient sensitivity and specificity, which may make both models instrumental in individualized prevention of UTI in hospitalized patients. The favored machine-learning methodology is Decision Trees to ensure the most transparent results and to increase clinical understanding and implementation of the models.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248636PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011767PMC
March 2021

Characterisation of advanced Parkinson's disease: OBSERVE-PD observational study - results of the Swiss subgroup.

Swiss Med Wkly 2021 Mar 6;151:w20419. Epub 2021 Mar 6.

Neurocenter, Lucerne Kantonsspital, Lucerne, Switzerland.

Aims Of The Study: Currently, the characterisation of advanced Parkinson’s disease (APD) does not follow standardised diagnostic criteria, which complicates the evaluation of ongoing care and treatment strategies, such as eligibility for device-aided treatment (DAT). Therefore, this study aimed to determine the proportion of APD and non-advanced Parkinson’s disease (non-APD) patients treated at specialised movement disorder centres in Switzerland, to compare clinical characteristics of APD versus non-APD patients and to assess eligibility for and use of DAT. Furthermore, potential differences between the Swiss and international situation should be uncovered.

Methods: OBSERVE-PD was a cross-sectional, international, observational study including 2615 patients from 128 movement disorder centres in 18 countries. For the Swiss subgroup of the study analysed here, which included 134 patients from 5 movement disorder centres, motor and non-motor symptoms, activities of daily living and quality of life were assessed as endpoints. The correlation between physician’s judgement of APD and the Delphi criteria for APD, which were developed by an international expert group, as well as the clinical burden in APD and non-APD patients and eligibility for and use of DAT were evaluated. The results for the Swiss subgroup were subsequently compared with the international full analysis set of the OBSERVE-PD study.

Results: Based on physician’s judgement, 69.4% of patients included in the Swiss study suffered from APD. A moderate correlation between physician’s judgement and the Delphi criteria for APD was observed (Κ = 0.480, 95% confidence interval 0.317–0.642). Clinical burden was higher for APD patients, as shown by worse scores for activities of daily living, motor symptom severity, dyskinesia duration/disability, duration of “off” time, non-motor symptoms and quality of life as compared with non-APD patients (p <0.0001 for all). The Swiss data for disease burden were comparable to the international findings, except that the Swiss patients showed less “off” time. Amongst APD patients eligible for DAT, the main reason for no DAT in Switzerland was patient refusal, whereas patients needing more time to decide about it was the most frequent reason in the international analysis.

Conclusions: The study shows that the burden of APD in tertiary care centres in Switzerland is comparable to the international situation. Patient refusal is the main reason for no DAT amongst eligible APD patients in such centres. The identification of standard APD classification parameters and evaluation of the reasons for no DAT are relevant for optimising treatment strategies and the transition to DAT.
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http://dx.doi.org/10.4414/smw.2021.20419DOI Listing
March 2021

Risk-based screening and intrapartum group B streptococcus polymerase chain reactionresults reduce use of antibiotics during labour.

Dan Med J 2020 Oct 20;67(11). Epub 2020 Oct 20.

Introduction: This study investigated the feasibility of a risk-based screening approach combined with testing of Group B streptococcus (GBS) by polymerase chain reaction (PCR), the effect on use of intrapartum antibiotic prophylaxis (IAP) and the impact on the incidence of early-onset GBS infection (EOGBS).

Methods: During one year, 551 women giving birth at Lillebaelt Hospital, Denmark, having one or more risk factors for EOGBS (previous birth of infant with EOGBS, GBS bacteriuria during current pregnancy, gestational age less than 37 weeks, rupture of membranes greater than 18 hours, and temperature ≥ 38 °C) were tested by a GBS PCR assay intrapartum. IAP was administered when the woman tested positive.

Results: Among 2,889 women in labour, 19.1% (n = 551) had one or more risk factors for EOGBS, and 5.1% (n = 146) had both risk factors for EOGBS and a positive intrapartum GBS PCR test. In total, 185 women with risk factors for EOGBS received IAP. If the former risk-based approach had been applied, 551 women giving birth would have received IAP. Implementing IAP based on the GBS PCR results produced a two-thirds reduction of IAP. No children were diagnosed with EOGBS.

Conclusions: The GBS PCR assay was easy to perform and provided test results within 50 minutes. Implementation of risk-based screening combined with intrapartum GBS PCR testing reduces the use of IAP by two thirds compared with risk-based screening alone, thus minimising antibiotic resistance. The study material was too small to evaluate the effect on the incidence of EOGBS. Since EOGBS is a rare disease, more studies are required.

Funding: The study was supported by Forskningsraadet Lillebaelt Hospital, Udviklingsraadet Lillebaelt Hospital, Johs. M. Klein og Hustrus Mindelegat, the Region of Southern Denmark, Farusa Emballage A/S.

Trial Registration: not relevant.
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October 2020

The Parkinson disease pain classification system: results from an international mechanism-based classification approach.

Pain 2021 Apr;162(4):1201-1210

Pain Center, LIM-62, Departamento de Neurologia da Faculdade de Medicina da Universidade de Sao Paulo, Hospital das Clínicas, Sao Paulo, Brazil.

Abstract: Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 ± 7.6 years) and 37 healthy controls were recruited in 4 centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.
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http://dx.doi.org/10.1097/j.pain.0000000000002107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977616PMC
April 2021

Assessment of the Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication Among Patients With Lyme Neuroborreliosis in Denmark.

JAMA Psychiatry 2021 Feb;78(2):177-186

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Importance: The association of Lyme neuroborreliosis with the development of psychiatric disease is unknown and remains a subject of debate.

Objective: To investigate the risk of psychiatric disease, the percentage of psychiatric hospital inpatient and outpatient contacts, and the receipt of prescribed psychiatric medications among patients with Lyme neuroborreliosis compared with individuals in a matched comparison cohort.

Design, Setting, And Participants: This nationwide population-based matched cohort study included all residents of Denmark who received a positive result on an intrathecal antibody index test for Borrelia burgdorferi (patient cohort) between January 1, 1995, and December 31, 2015. Patients were matched by age and sex to a comparison cohort of individuals without Lyme neuroborreliosis from the general population of Denmark. Data were analyzed from February 2019 to March 2020.

Exposures: Diagnosis of Lyme neuroborreliosis, defined as a positive result on an intrathecal antibody index test for B burgdorferi.

Main Outcomes And Measures: The 0- to 15-year hazard ratios for the assignment of psychiatric diagnostic codes, the difference in the percentage of psychiatric inpatient and outpatient hospital contacts, and the difference in the percentage of prescribed psychiatric medications received among the patient cohort vs the comparison cohort.

Results: Among 2897 patients with Lyme neuroborreliosis (1646 men [56.8%]) and 28 970 individuals in the matched comparison cohort (16 460 men [56.8%]), the median age was 45.7 years (interquartile range [IQR], 11.5-62.0 years) for both groups. The risk of a psychiatric disease diagnosis and the percentage of hospital contacts for psychiatric disease were not higher among patients with Lyme neuroborreliosis compared with individuals in the comparison cohort. A higher percentage of patients with Lyme neuroborreliosis compared with individuals in the comparison cohort received anxiolytic (7.2% vs 4.7%; difference, 2.6%; 95% CI, 1.6%-3.5%), hypnotic and sedative (11.0% vs 5.3%; difference, 5.7%; 95% CI, 4.5%-6.8%), and antidepressant (11.4% vs 6.0%; difference, 5.4%; 95% CI, 4.3%-6.6%) medications within the first year after diagnosis, after which the receipt of psychiatric medication returned to the same level as the comparison cohort.

Conclusions And Relevance: In this population-based matched cohort study, patients with Lyme neuroborreliosis did not have an increased risk of developing psychiatric diseases that required hospital care or treatment with prescription medication. The increased receipt of psychiatric medication among patients with Lyme neuroborreliosis within the first year after diagnosis, but not thereafter, suggests that most symptoms associated with the diagnosis subside within a short period.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542530PMC
February 2021

Changes in Lyme neuroborreliosis incidence in Denmark, 1996 to 2015.

Ticks Tick Borne Dis 2020 11 25;11(6):101549. Epub 2020 Aug 25.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Lyme neuroborreliosis (LNB) has recently been added to the list of diseases under the European Union epidemiological surveillance in order to obtain updated information on incidence. The goal of this study was to identify temporal (yearly) variation, high risk geographical regions and risk groups, and seasonal variation for LNB in Denmark. This cohort-study investigated Danish patients (n = 2791) diagnosed with LNB (defined as a positive Borrelia burgdorferi sensu lato (s.l.) intrathecal antibody test) between 1996-2015. We calculated incidence and incidence ratios of LNB by comparing 4-yr groups of calendar-years, area of residency, sex and age, income and education groups, and the number of new LNB cases per month. The incidence of LNB was 2.2 per 100,000 individuals and year in 1996-1999, 2.7 in 2004-2007 and 1.1 per 100,000 individuals in 2012-2015. Yearly variations in LNB incidence were similar for most calendar-year groups. LNB incidence was highest in Eastern Denmark and among males and individuals who were 0-14 yrs old, who had a yearly income of >449,000 DKK, and who had a Master's degree or higher education. The number of LNB cases was highest from July to November (p < 0.001). In conclusion, based on Danish nationwide data of patients with positive B. burgdorferi s.l. intrathecal antibody index (1996-2015) the incidence of LNB was found to increase until 2004-2007 but thereafter to decline. European surveillance studies of Lyme borreliosis should be encouraged to monitor the incidence trend.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101549DOI Listing
November 2020

Challenging diagnostics in familial transmission from an asymptomatic COVID-19 carrier: Should we group SARS-CoV-2 samples from households?

Int J Infect Dis 2020 12 28;101:203-204. Epub 2020 Sep 28.

Department of Clinical Microbiology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark; Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Vejle, Denmark.

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http://dx.doi.org/10.1016/j.ijid.2020.09.1442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521898PMC
December 2020

Cellular and Extracellular Proteome of the Animal Pathogen , a Close Relative of Zoonotic and .

Proteomes 2020 Aug 12;8(3). Epub 2020 Aug 12.

Microbiology Division, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany.

is a newly described animal pathogen, closely related to the emerging human pathogen and , a major pathogen of small ruminants. In this study, proteins of a whole cell and a shaving fraction and the exoproteome of strain W25 were analyzed as a first proteome study of this species. In total, 1305 proteins were identified out of 2013 proteins encoded by the W25 genome sequence and number of putative virulence factors were detected already under standard growth conditions including phospholipase D and sialidase. An up to now uncharacterized trypsin-like protease is by far the most secreted protein in this species, indicating a putative role in pathogenicity. Furthermore, the proteome analyses carried out in this study support the recently published taxonomical delineation of from the closely related zoonotic species.
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http://dx.doi.org/10.3390/proteomes8030019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564913PMC
August 2020

Improvement of selection of pregnant women for intrapartum polymerase chain reaction screening for vaginal Group B Streptococci (GBS) colonization by adding GBS urine screening at 35-37 weeks of pregnancy.

Int J Gynaecol Obstet 2020 Oct 9;151(1):124-127. Epub 2020 Jul 9.

Department of Clinical Microbiology, University Hospital of Southern Denmark, Vejle Hospital, Vejle, Denmark.

Objective: To evaluate whether systematic antepartum screening for Group B Streptococci (GBS) by urine culture improves the risk factor-based selection of pregnant women for intrapartum GBS screening with a rapid polymerase chain reaction (PCR) assay.

Methods: A prospective observational study was conducted between April 2013 and June 2014. GBS colonization judged by urine culture at 35-37 weeks of gestation was compared with the result of a vaginal GBS PCR test at labor as outcome. The results of urine culture were used as exposure variable. The PCR test was performed on intrapartum vaginal samples.

Results: Screening for urine GBS in 902 unselected pregnant Danish women at 35-37 weeks of gestation predicted intrapartum PCR GBS status with a sensitivity of 33.6%. A positive predictive value of 41.2% was seen among women with low GBS counts (<104 CFU/mL) and 83.3% among women with high GBS counts (≥104 CFU/mL). Systematic GBS screening of urine at 35-37 weeks of gestation added 30.9% extra women for intrapartum GBS PCR screening in the study group.

Conclusion: Systematic antepartum GBS screening of urine should be implemented in order to improve risk stratification for early onset GBS by offering laboring women an intrapartum GBS PCR test.
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http://dx.doi.org/10.1002/ijgo.13267DOI Listing
October 2020

Phylogenomic characterisation of a novel corynebacterial species pathogenic to animals.

Antonie Van Leeuwenhoek 2020 Aug 4;113(8):1225-1239. Epub 2020 Jun 4.

Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.

The genus Corynebacterium includes species of biotechnological, medical and veterinary importance. An atypical C. ulcerans strain, W25, was recently isolated from a case of necrotizing lymphadenitis in a wild boar. In this study, we have analysed the genome sequence of this strain and compared the phenotypic and virulence properties with other corynebacterial pathogens. Phylogenomic analyses revealed that strain W25 belongs to a novel species along with PO100/5 and KL1196. The latter strains were isolated from a pig and a roe deer, respectively; hence, this species appears to be associated to animals. The isolate W25 is likely a non-toxigenic tox gene bearing strain and may have compromised abilities to adhere to pharyngeal and laryngeal epithelial cells due to potential loss of the gene functions in spaBC and spaDEF pilus gene clusters. A number of corynebacterial virulence genes are present including pld encoding phospholipase D. Therefore, this strain may be able to cause severe invasive infections in animals and zoonotic infections in humans.
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http://dx.doi.org/10.1007/s10482-020-01430-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334274PMC
August 2020

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

BMC Cancer 2020 Mar 24;20(1):249. Epub 2020 Mar 24.

Department of Haematology, Odense University Hospital, and Research Unit of Haematology, Department of Clinical Research, University of Southern Denmark, Kløvervænget 6, entrance 93, 12th floor, 5000, Odense C, Denmark.

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.
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http://dx.doi.org/10.1186/s12885-020-06754-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092519PMC
March 2020

A Chlamydia trachomatis 23S rRNA G1523A variant escaping detection in the Aptima Combo 2 assay (Hologic) was widespread across Denmark in July-September 2019.

APMIS 2020 Jun 4;128(6):440-444. Epub 2020 May 4.

Department for Bacteria, Parasites and Fungi, Infectious Diseases Preparedness, Statens Serum Institut, Copenhagen, Denmark.

Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection globally, and nucleic acid amplification tests (NAATs) are recommended for highly sensitive and specific diagnosis. In early 2019, the Finnish new variant of Chlamydia trachomatis (FI-nvCT) was identified. The FI-nvCT has a C1515T mutation in the 23S rRNA gene, making it escaping detection in the Aptima Combo 2 (AC2; Hologic) NAAT, and the FI-nvCT has been subsequently reported in Sweden and Norway. In the present study, we investigated the presence of the FI-nvCT and other AC2 diagnostic-escape CT mutants in July-September 2019 in Denmark. The FI-nvCT was present but rare in Denmark. However, another AC2 diagnostic-escape CT mutant (with a 23S rRNA G1523A mutation) was found to be widespread across Denmark, accounting for 95% (76/80) of AC2 diagnostic-escape nvCT samples from five Danish CT-diagnostic laboratories. This nvCT-G1523A has previously only been detected in one single sample in the United Kingdom and Norway, respectively. It is vital to monitor the continued stability of the NAAT targets in local, national and international settings and monitor as well as appropriately analyse incidence, unexplained shifts in diagnostics rates and/or annual collections of samples diagnosed as negative/equivocal using NAATs with different target(s). Furthermore, diagnostic CT NAATs with dual target sequences are crucial, and fortunately, an updated Hologic AC2 assay including one additional target sequence is in advanced development.
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http://dx.doi.org/10.1111/apm.13043DOI Listing
June 2020

Two-year outcome data suggest that less invasive surfactant administration (LISA) is safe. Results from the follow-up of the randomized controlled AMV (avoid mechanical ventilation) study.

Eur J Pediatr 2020 Aug 18;179(8):1309-1313. Epub 2020 Feb 18.

Department of Paediatrics, University Hospital of Schleswig-Holstein, University of Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany.

Less invasive surfactant administration (LISA) is a method to deliver surfactant to spontaneously breathing premature infants via a thin catheter. Here we report the two-year outcome from the AMV (avoid mechanical ventilation) study, the first randomized controlled trial on this mode of surfactant delivery. No statistically significant differences in weight, length or neurodevelopmental outcome (Bayley II scores) were found between the LISA intervention group (n = 95) and the control group (n = 84) that received standard treatment.Conclusion: No differences in outcome were observed at 2 years. LISA seems safe in that aspect. What is Known: • LISA is a method that is in increasing use for surfactant delivery to spontaneously breathing infants. LISA reduces the need for mechanical ventilation. What is New: • Outcome data at 2 years from the first randomized study with LISA raise no safety concerns in comparison to a group of infants that received standard treatment.
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http://dx.doi.org/10.1007/s00431-020-03572-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351829PMC
August 2020

Urine dipstick for predicting intrapartum recto-vaginal colonisation by group B streptococci.

Dan Med J 2020 Feb;67(2)

Introduction: In pregnant women, bacteriuria with group B streptococci (GBS) may be associated with a high degree of recto-vaginal GBS colonisation and therefore an increased risk of early-onset GBS disease. The aim of this study was to assess the performance of routine use of dipstick urine analysis during pregnancy for prediction of recto-vaginal GBS colonisation at the time of labour.

Methods: Among 902 unselected Danish pregnant women, we obtained results from 1) dipstick urine analysis, 2) urine culture carried out during pregnancy, if indicated, and 3) recto-vaginal culture at labour. The inclusion criteria were age > 18 years and gestational age ≥ 37 weeks.

Results: Intrapartum recto-vaginal GBS colonisation was predicted by a positive urine dipstick with 5% sensitivity only.

Conclusion: Dipstick urine analysis had a low sensitivity for predicting intrapartum recto-vaginal colonisation with GBS.

Funding: none.

Trial Registration: not relevant.
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February 2020

Comparison between optical coherence tomography imaging and histological sections of peripheral nerves.

J Neurosurg 2019 Nov 22:1-8. Epub 2019 Nov 22.

1Department of Neurosurgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum.

Objective: Optical coherence tomography (OCT) is an imaging technique that uses the light-backscattering properties of different tissue types to generate an image. In an earlier feasibility study the authors showed that it can be applied to visualize human peripheral nerves. As a follow-up, this paper focuses on the interpretation of the images obtained.

Methods: Ten different short peripheral nerve specimens were retained following surgery. In a first step they were examined by OCT during, or directly after, surgery. In a second step the nerve specimens were subjected to histological examination. Various steps of image processing were applied to the OCT raw data acquired. The improved OCT images were compared with the sections stained by H & E. The authors assigned the structures in the images to the various nerve components including perineurium, fascicles, and intrafascicular microstructures.

Results: The results show that OCT is able to resolve the myelinated axons. A weighted averaging filter helps in identifying the borders of structural features and reduces artifacts at the same time. Tissue-remodeling processes due to injury (perineural fibrosis or neuroma) led to more homogeneous light backscattering. Anterograde axonal degeneration due to sharp injury led to a loss of visible axons and to an increase of light-backscattering tissue as well. However, the depth of light penetration is too small to allow generation of a complete picture of the nerve.

Conclusions: OCT is the first in vivo imaging technique that is able to resolve a nerve's structures down to the level of myelinated axons. It can yield information about focal and segmental pathologies.
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http://dx.doi.org/10.3171/2019.8.JNS191278DOI Listing
November 2019

Genome sequence of a pathogenic Corynebacterium ulcerans strain isolated from a wild boar with necrotizing lymphadenitis.

BMC Res Notes 2019 Oct 25;12(1):692. Epub 2019 Oct 25.

Institut für Bakterielle Infektionen und Zoonosen, Friedrich-Loeffler-Institut, Bundesforschungsinstitut für Tiergesundheit, Jena, Germany.

Objectives: Corynebacterium ulcerans can colonize a wide variety of animals and also humans are infected, typically by zoonotic transmission. Symptoms range from skin ulcers or systemic infections to diphtheria-like illness. In contrast, Corynebacterium pseudotuberculosis is widely distributed among herds of sheep, goats and other farm animals, where it causes high economic losses due to caseous lymphadenitis. Here we describe the genome sequence of an atypical C. ulcerans strain isolated from a wild boar with necrotizing lymphadenitis. This strain has similarities to C. pseudotuberculosis.

Data Description: Genome sequence data of C. ulcerans isolate W25 were generated, analyzed and taxonomical relationship to other Corynebacterium species as well as growth properties of the isolate were characterized. The genome of C. ulcerans W25 comprises 2,550,924 bp with a G+C content of 54.41% and a total of 2376 genes.
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http://dx.doi.org/10.1186/s13104-019-4704-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815020PMC
October 2019

International travel as source of a hospital outbreak with an unusual meticillin-resistant clonal complex 398, Denmark, 2016.

Euro Surveill 2019 10;24(42)

Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.

In May 2016, an unusual outbreak with the Panton-Valentine leukocidin-positive human variant of meticillin-resistant (MRSA) clonal complex 398 occurred among mothers and infants in the maternity unit of a Danish hospital. MRSA sharing genotypic and phenotypic characteristics was confirmed in 36 cases, including 26 patients, nine household members and a healthcare worker (HCW) who had contact with all the patients. The national MRSA database contained 37 seemingly unlinked MRSA cases whose isolates shared the same genotypic and phenotypic characteristics as the outbreak strain. Whole genome sequencing showed that three of these isolates clustered together with the 36 outbreak isolates, suggesting spread outside the hospital. The HCW and 21 of 37 cases from the national MRSA database had links to south-eastern Asia, where the outbreak strain is endemic. These findings suggest that the HCW acquired the outbreak strain while travelling in south-eastern Asia and then introduced it into the hospital; from there, it spread within the patients' households and into the community. Screening of travellers returning from countries with high levels of MRSA could be an important intervention to prevent spread of these bacteria into hospitals via patients or HCWs.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.42.1800680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807253PMC
October 2019

Clinical experiences with a new system for automated hand hygiene monitoring: A prospective observational study.

Am J Infect Control 2020 05 18;48(5):527-533. Epub 2019 Oct 18.

Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark.

Background: Hand hygiene compliance (HHC) among health care workers remains suboptimal, and good monitoring systems are lacking. We aimed to evaluate HHC using an automated monitoring system.

Methods: A prospective, observational study was conducted at 2 Danish university hospitals employing a new monitoring system (Sani nudge). Sensors were located on alcohol-based sanitizers, health care worker name tags, and patient beds measuring hand hygiene opportunities and sanitations.

Results: In total, 42 nurses were included with an average HHC of 52% and 36% in hospitals A and B, respectively. HHC was lowest in patient rooms (hospital A: 45%; hospital B: 29%) and highest in staff toilets (hospital A: 72%; hospital B: 91%). Nurses sanitized after patient contact more often than before, and sanitizers located closest to room exits and in hallways were used most frequently. There was no association found between HHC level and the number of beds in patient rooms. The HHC level of each nurse was consistent over time, and showed a positive correlation between the number of sanitations and HHC levels (hospital A: r = 0.69; hospital B: r = 0.58).

Conclusions: The Sani nudge system can be used to monitor HHC at individual and group levels, which increases the understanding of compliance behavior.
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http://dx.doi.org/10.1016/j.ajic.2019.09.003DOI Listing
May 2020

Risk of Neurological Disorders in Patients With European Lyme Neuroborreliosis: A Nationwide, Population-Based Cohort Study.

Clin Infect Dis 2020 09;71(6):1511-1516

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: Lyme neuroborreliosis (LNB), caused by the tick-borne spirochetes of the Borrelia burgdorferi sensu lato species complex, has been suggested to be associated with a range of neurological disorders. In a nationwide, population-based cohort study, we examined the associations between LNB and dementia, Alzheimer's disease, Parkinson's disease, motor neuron disease, epilepsy, and Guillain-Barré syndrome.

Methods: We used national registers to identify all Danish residents diagnosed during 1986-2016 with LNB (n = 2067), created a gender- and age-matched comparison cohort from the general population (n = 20 670), and calculated risk estimates and hazard ratios.

Results: We observed no long-term increased risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, or epilepsy. However, within the first year, 8 (0.4%) of the LNB patients developed epilepsy, compared with 20 (0.1%) of the comparison cohort (difference, 0.3%; 95% confidence interval, .02-.6%). In the LNB group, 11 (0.5%) patients were diagnosed with Guillain-Barré syndrome within the first year after LNB diagnosis, compared with 0 (0.0%) in the comparison cohort. After the first year, the risk of Guillain-Barré was not increased.

Conclusions: LNB patients did not have increased long-term risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, epilepsy, or Guillain-Barré. Although the absolute risk is low, LNB patients might have an increased short-term risk of epilepsy and Guillain-Barré syndrome.
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http://dx.doi.org/10.1093/cid/ciz997DOI Listing
September 2020

Association between risk factors and testicular microlithiasis.

Acta Radiol Open 2019 Sep 10;8(9):2058460119870297. Epub 2019 Sep 10.

Research Unit for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark.

Background: Testicular microlithiasis and its clinical significance are not fully understood. Testicular microlithiasis and risk factors have been associated with testicular cancer. The role of testicular microlithiasis is investigated.

Purpose: To investigate the association between testicular microlithiasis and socioeconomic and other pre-diagnostic factors.

Material And Methods: All men who had a scrotal ultrasound examination at the Department of Radiology, Vejle Hospital, during 2001-2013 were included. They were categorized as patients with and without testicular microlithiasis and compared with pre-diagnostic data from a nationwide registry. A total of 2404 men (283 [11.8%] with testicular microlithiasis and 2121 [88.2%] without testicular microlithiasis) were included. The association between testicular microlithiasis and pre-diagnostic conditions was investigated with logistic regression.

Results: Overall, we found no statistically significant differences in demographics, socioeconomic characteristics, or testicular diseases in men with and without testicular microlithiasis. Men with testicular microlithiasis had more often been treated for infertility (odds ratio [OR] 2.09, 95% confidence interval [CI] 0.84-5.24) and testicular torsion (OR 1.58, 95% CI 0.34-7.36) compared to men without testicular microlithiasis. We found no association between sexually transmitted diseases and testicular microlithiasis.

Conclusion: Treatment for infertility and torsion was non-significantly associated with testicular microlithiasis and no other association was found. These data do not suggest early exposure is related to testicular microlithiasis.
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http://dx.doi.org/10.1177/2058460119870297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740053PMC
September 2019

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

Eur J Clin Microbiol Infect Dis 2019 Dec 22;38(12):2305-2310. Epub 2019 Aug 22.

Department of Infectious Disease, Aalborg University Hospital, Mølleparkvej 4, DK-9000, Aalborg, Denmark.

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.
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http://dx.doi.org/10.1007/s10096-019-03678-wDOI Listing
December 2019

Active perinatal care of preterm infants in the German Neonatal Network.

Arch Dis Child Fetal Neonatal Ed 2020 Mar 27;105(2):190-195. Epub 2019 Jun 27.

Department of Neonatology and Pediatric Intensive Care, University Hospital Carl Gustav Carus, Dresden, Germany.

Objective: To determine if survival rates of preterm infants receiving active perinatal care improve over time.

Design: The German Neonatal Network is a cohort study of preterm infants with birth weight <1500 g. All eligible infants receiving active perinatal care are registered. We analysed data of patients discharged between 2011 and 2016.

Setting: 43 German level III neonatal intensive care units (NICUs).

Patients: 8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care.

Interventions: Participating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25-P75) and low (
Main Outcome Measures: Death by any cause before discharge.

Results: Total survival increased from 85.8% in 2011-2013 to 87.4% in 2014-2016. This increase was due to reduced mortality of NICUs with low survival rates in 2011-2013. Survival increased in these centres from 53% to 64% in the 22-24 weeks strata and from 73% to 84% in the 25-26 weeks strata.

Conclusions: Our data support previous reports that active perinatal care of very immature infants improves outcomes at the border of viability and survival rates at higher gestational ages. The high total number of surviving infants below 24 weeks of gestation challenges national recommendations exclusively referring to gestational age as the single criterion for providing active care. However, more data are needed before recommendations for parental counselling should be reconsidered.

Trial Registration: Approval by the local institutional review board for research in human subjects of the University of Lübeck (file number 08-022) and by the local ethic committees of all participating centres has been given.
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http://dx.doi.org/10.1136/archdischild-2018-316770DOI Listing
March 2020

Proteomics of Bordetella pertussis whole-cell and acellular vaccines.

BMC Res Notes 2019 Jun 10;12(1):329. Epub 2019 Jun 10.

Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.

Objectives: Bordetella pertussis is the etiological agent of whooping cough, a bacterial infection of especially children, which may be fatal without treatment. In frame of studies to investigate putative effects of vaccination on host-pathogen interaction and clonal distribution of strains, in addition to Corynebacterium diphtheriae and Clostridium tetani toxoid vaccines, also whole-cell and acellular pertussis vaccines were analyzed by mass spectrometry.

Data Description: LC-MS/MS spectra were generated and analyzed using B. pertussis genome data and proteins present in whole-cell and acellular pertussis vaccines were identified. Subcellular localization of proteins and presence of signal peptides was determined bioinformatically.
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http://dx.doi.org/10.1186/s13104-019-4373-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558669PMC
June 2019

Beyond diphtheria toxin: cytotoxic proteins of Corynebacterium ulcerans and Corynebacterium diphtheriae.

Microbiology (Reading) 2019 08 4;165(8):876-890. Epub 2019 Jun 4.

> Microbiology Division, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.

Diphtheria toxin is one of the best investigated bacterial toxins and the major virulence factor of toxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans strains. However, also diphtheria toxin-free strains of these two species can cause severe infections in animals and humans, indicating the presence of additional virulence factors. In this study, we present a first characterization of two proteins with cytotoxic effect in corynebacteria. A putative ribosome-binding protein (AEG80717, CULC809_00177), first annotated in a genome sequencing project of C. ulcerans strain 809, was investigated in detail together with a homologous protein identified in C. diphtheriae strain HC04 (AEX80148, CDHC04_0155) in this study. The corresponding proteins show striking structural similarity to Shiga-like toxins. Interaction of wild-type, mutant and complementation as well as overexpression strains with invertebrate model systems and cell lines were investigated. Depending on the presence of the corresponding genes, detrimental effects were observed in vivo in two invertebrate model systems, Caenorhabditis elegans and Galleria mellonella, and on various animal and human epithelial and macrophage cell lines in vitro. Taken together, our results support the idea that pathogenicity of corynebacteria is a multifactorial process and that new virulence factors may influence the outcome of potentially fatal corynebacterial infections.
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http://dx.doi.org/10.1099/mic.0.000820DOI Listing
August 2019

Proteomics of diphtheria toxoid vaccines reveals multiple proteins that are immunogenic and may contribute to protection of humans against Corynebacterium diphtheriae.

Vaccine 2019 05 26;37(23):3061-3070. Epub 2019 Apr 26.

Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. Electronic address:

Introduced for mass immunization in the 1920s, vaccines against diphtheria are among the oldest and safest vaccines known. The basic principle of their production is the inactivation of purified diphtheria toxin by formaldehyde cross-linking, which converts the potentially fatal toxin in a completely harmless protein aggregate, which is still immunogenic. Since in addition to diphtheria toxin also other proteins may be secreted by Corynebacterium diphtheriae during cultivation, we assumed that diphtheria toxoid might not be the only component present in the vaccine. To address this question, we established a protocol to reverse formaldehyde cross-linking and carried out mass spectrometric analyses. Different secreted, membrane-associated and cytoplasmic proteins of C. diphtheriae were detected in several vaccine preparations from across the world. Based on these results, bioinformatics and Western blot analyses were applied to characterize if these proteins are immunogenic and may therefore support protection against C. diphtheriae. In frame of this study, we could show that the C. diphtheriae toxoid vaccines induce antibodies against different C. diphtheriae proteins and against diphtheria toxin secreted by Corynebacterium ulcerans, an emerging pathogen which is outnumbering C. diphtheriae as cause of diphtheria-like illness in Western Europe.
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http://dx.doi.org/10.1016/j.vaccine.2019.04.059DOI Listing
May 2019

[Formula: see text] Limb apraxia profiles in different clinical samples.

Clin Neuropsychol 2020 01 19;34(1):217-242. Epub 2019 Apr 19.

University of Konstanz, Konstanz, Germany.

: Limb apraxia is a motor cognitive disorder that has been mainly studied in patients with dementia or left hemisphere stroke (LHS). However, limb apraxia has also been reported in patients with right hemisphere stroke (RHS), multiple sclerosis (MS) or traumatic brain injury (TBI). This study's aim was to report detailed praxis performance profiles in samples suffering from these different neurological disorders by use of the Diagnostic Instrument for Limb Apraxia (DILA-S).: 44 LHS patients, 36 RHS patients, 27 patients with dementia, 26 MS and 44 TBI patients participated. The diagnostics included the imitation of meaningless and meaningful hand gestures, pantomime of tool-use, single real tool-use as well as a multistep naturalistic action task (preparing breakfast).: Apraxia occurred in all tested samples but to a varying degree and with dissimilar profiles. LHS patients demonstrated most severe deficits in pantomime, but they were also vulnerable to deficits in real tool-use. Dementia patients showed high incidence rates of apraxia in almost all subscales of the DILA-S. RHS patients demonstrated difficulties in imitation and pantomime of tool-use, but they did not show severe difficulties with real tool-use. TBI patients appeared challenged by multistep naturalistic actions. The tested MS sample did not show clinically relevant symptoms in the DILA-S.: Different types of patients display varying limb apraxic symptoms detectable by the DILA-S. In these limb apraxia susceptible populations, testing should be warranted as standard. Prospectively, individual error profiles may be helpful for shaping motor cognitive training.
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http://dx.doi.org/10.1080/13854046.2019.1585575DOI Listing
January 2020

More than a Toxin: Protein Inventory of Toxoid Vaccines.

Proteomes 2019 Apr 16;7(2). Epub 2019 Apr 16.

Microbiology Division, Department of Biology, Friedrich-Alexander University Erlangen-Nuremberg, Staudtstr. 5, 91058 Erlangen, Germany.

is the etiological agent of tetanus, a life-threatening bacterial infection. The most efficient protection strategy against tetanus is a vaccination with the neurotoxin, which is inactivated by formaldehyde-crosslinking. Since we assumed that besides the tetanus toxin, other proteins of may also be present in toxoid preparations, we analyzed commercially available vaccines from different countries in respect to their protein content using mass spectrometry. In total 991 proteins could be identified in all five analyzed vaccines, 206 proteins were common in all analyzed vaccines and 54 proteins from the 206 proteins were potential antigens. The additionally present proteins may contribute at least partially to protection against infection by supporting the function of the vaccine against the devastating effects of the tetanus toxin indirectly. Two different label-free protein quantification methods were applied for an estimation of protein contents. Similar results were obtained with a Total Protein Approach (TPA)-based method and Protein Discoverer 2.2 software package based on the minora algorithm. Depending on the tetanus toxoid vaccine and the quantification method used, tetanus neurotoxin contributes between 14 and 76 % to the total protein content and varying numbers of other proteins were detected.
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http://dx.doi.org/10.3390/proteomes7020015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631180PMC
April 2019

Risk-based approach versus culture-based screening for identification of group B streptococci among women in labor.

Int J Gynaecol Obstet 2019 Feb 6;144(2):187-191. Epub 2018 Dec 6.

Department of Clinical Microbiology, Lillebaelt Hospital, Vejle, Denmark.

Objective: To compare a risk-based and culture-based screening approach for identification of group B streptococci (GBS) vaginal colonization using an intrapartum rectovaginal culture as the reference standard.

Methods: Pregnant women attending the prenatal clinic at Lillebaelt Hospital, Kolding, Denmark, between April 1, 2013, and June 30, 2014, were invited to participate in a prospective observational study. For prepartum culture-based screening, vaginal and rectal culture samples were obtained and, for reference, standard, paired vaginal and rectal culture samples were collected during labor. Risk factors for risk-based screening were previous early-onset GBS, GBS bacteriuria during pregnancy, maternal temperature ≥38.0°C intrapartum, and rupture of membranes for more than 18 hours.

Results: The intrapartum rectovaginal GBS colonization rate was 30% (32/108) among participants with risk factors and 15% (123/794) among participants without risk factors. Culture-based screening demonstrated a sensitivity, specificity, positive predictive value, negative predictive value, and positive likelihood ratio in predicting intrapartum GBS carriage of 78% (95% confidence interval [CI] 71-84), 95% (94-97), 78% (70-84), 95% (94-97), and 17 (12-23), respectively; for risk-based screening, these values were 21% (15-28), 90% (87-92), 30% (22-38), 85% (83-86), and 2 (1-3), respectively.

Conclusions: Culture-based screening performed considerably better than a risk-based approach in identifying intrapartum GBS colonization.
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http://dx.doi.org/10.1002/ijgo.12721DOI Listing
February 2019