Publications by authors named "Luise Müller"

31 Publications

LAG-3-Expressing Tumor-Infiltrating T Cells Are Associated with Reduced Disease-Free Survival in Pancreatic Cancer.

Cancers (Basel) 2021 Mar 15;13(6). Epub 2021 Mar 15.

Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.

T cells are the predominant immune cell population in the pancreatic tumor microenvironment. High CD8 and Th1-polarized CD4 T cell infiltration is associated with prolonged survival in human pancreatic ductal adenocarcinoma (PDAC). However, the expression pattern of co-stimulatory and inhibitory receptors by PDAC-infiltrating T cells and their prognostic significance are not well defined. In this study, we employed multiplex immunofluorescence to investigate the intratumoral expression of the co-stimulatory receptor inducible T-cell co-stimulator (ICOS), the inhibitory receptors lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1), and V-domain immunoglobulin suppressor of T cell activation (VISTA) by tumor-infiltrating T cells (CD3) in a cohort of 69 patients with resected PDAC. T cells were enriched particularly within the stromal area and were highly heterogeneous across tumors. Further, T cells were associated with prolonged disease-free survival (DFS). However, LAG-3 expression by PDAC-infiltrating T cells was correlated with reduced DFS. Our study highlights the biological importance of LAG-3 expression by tumor-infiltrating T cells. LAG-3 T cells may represent a novel prognostic marker and a particularly attractive target for immunotherapeutic strategies in PDAC.
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http://dx.doi.org/10.3390/cancers13061297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998134PMC
March 2021

Tumor-infiltrating plasmacytoid dendritic cells are associated with survival in human colon cancer.

J Immunother Cancer 2021 Mar;9(3)

Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany

Background: Plasmacytoid dendritic cells (pDCs) play a key role in the induction and maintenance of antitumor immunity. Conversely, they can act as tolerogenic DCs by inhibiting tumor-directed immune responses. Therefore, pDCs may profoundly influence tumor progression. To gain novel insights into the role of pDCs in colon cancer, we investigated the frequency and clinical relevance of pDCs in primary tumor tissues from patients with colon cancer with different clinicopathological characteristics.

Methods: Immunohistochemical stainings were performed to explore the frequency of tumor-infiltrating BDCA-2 pDCs in patients with colon cancer. Statistical analyses were conducted to determine an association between the pDC density and clinicopathological characteristics of the patients. Furthermore, we used multiplex immunofluorescence stainings to evaluate the localization and phenotype of pDCs in stroma and tertiary lymphoid structures (TLS) of colon cancer tissues.

Results: An increased density of infiltrating pDCs was associated with lower Union for International Cancer Control (UICC) stages. Furthermore, a higher pDC frequency was significantly correlated with increased progression-free and overall survival of patients with colon cancer. Moreover, a lower number of coloncancer-infiltrating pDCs was significantly and independently linked to worse prognosis. In addition, we found that a proportion of pDCs shows a nuclear expression of the transcription factor interferon regulatory factor 7 (IRF7), which is characteristic for an activated phenotype. In various tumor stroma regions, IRF7 pDCs were located in the neighborhood of granzyme B-expressing CD8 T cells. Moreover, pDCs were identified as a novel component of the T cell zone of colon cancer-associated TLS, which are major regulators of adaptive antitumor immunity. A proportion of TLS-associated pDCs displayed a nuclear IRF7 expression and was preferentially located close to CD4 T cells.

Conclusions: These results indicate that higher densities of tumor-infiltrating pDCs are associated with prolonged survival of patients with colon cancer. Moreover, colon cancer-infiltrating pDCs may represent a novel prognostic factor. The colocalization of activated pDCs and T cells in tumor stroma and within TLS may contribute to the correlation between higher pDC densities and better prognosis. In addition, our findings may have implications for the design of novel immunotherapeutic strategies that are based on targeting colon cancer-infiltrating pDCs.
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http://dx.doi.org/10.1136/jitc-2020-001813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993360PMC
March 2021

Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update.

Front Cell Dev Biol 2021 9;9:637725. Epub 2021 Feb 9.

Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.

Mesenchymal stromal cells (MSCs) are characterized by an extraordinary capacity to modulate the phenotype and functional properties of various immune cells that play an essential role in the pathogenesis of inflammatory disorders. Thus, MSCs efficiently impair the phagocytic and antigen-presenting capacity of monocytes/macrophages and promote the expression of immunosuppressive molecules such as interleukin (IL)-10 and programmed cell death 1 ligand 1 by these cells. They also effectively inhibit the maturation of dendritic cells and their ability to produce proinflammatory cytokines and to stimulate potent T-cell responses. Furthermore, MSCs inhibit the generation and proinflammatory properties of CD4 T helper (Th)1 and Th17 cells, while they promote the proliferation of regulatory T cells and their inhibitory capabilities. MSCs also impair the expansion, cytokine secretion, and cytotoxic activity of proinflammatory CD8 T cells. Moreover, MSCs inhibit the differentiation, proliferation, and antibody secretion of B cells, and foster the generation of IL-10-producing regulatory B cells. Various cell membrane-associated and soluble molecules essentially contribute to these MSC-mediated effects on important cellular components of innate and adaptive immunity. Due to their immunosuppressive properties, MSCs have emerged as promising tools for the treatment of inflammatory disorders such as acute graft-versus-host disease, graft rejection in patients undergoing organ/cell transplantation, and autoimmune diseases.
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http://dx.doi.org/10.3389/fcell.2021.637725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900158PMC
February 2021

DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial.

Genome Med 2020 Nov 16;12(1):97. Epub 2020 Nov 16.

Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.Box 653, 84105, Beer Sheva, Israel.

Background: One of the major challenges in obesity treatment is to explain the high variability in the individual's response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss.

Methods: We conducted an explorative genome-wide DNA methylation analysis in blood samples from 120 subjects (90% men, mean ± SD age = 49 ± 9 years, body mass-index (BMI) = 30.2 ± 3.3 kg/m) from the 18-month CENTRAL randomized controlled trial who underwent either Mediterranean/low-carbohydrate or low-fat diet with or without physical activity.

Results: Analyses comparing male subjects with the most prominent body weight-loss (responders, mean weight change - 16%) vs. non-responders (+ 2.4%) (N = 10 each) revealed significant variation in DNA methylation of several genes including LRRC27, CRISP2, and SLFN12 (all adj. P < 1 × 10). Gene ontology analysis indicated that biological processes such as cell adhesion and molecular functions such as calcium ion binding could have an important role in determining the success of interventional therapies in obesity. Epigenome-wide association for relative weight-loss (%) identified 15 CpGs being negatively correlated with weight change after intervention (all combined P < 1 × 10) including new and also known obesity candidates such as NUDT3 and NCOR2. A baseline DNA methylation score better predicted successful weight-loss [area under the curve (AUC) receiver operating characteristic (ROC) = 0.95-1.0] than predictors such as age and BMI (AUC ROC = 0.56).

Conclusions: Body weight-loss following 18-month lifestyle intervention is associated with specific methylation signatures. Moreover, methylation differences in the identified genes could serve as prognostic biomarkers to predict a successful weight-loss therapy and thus contribute to advances in patient-tailored obesity treatment.
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http://dx.doi.org/10.1186/s13073-020-00794-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670623PMC
November 2020

Application of an Optimized Direct Lysis Method for Viral RNA Extraction Linking Contaminated Dates to Infection With Hepatitis A Virus.

Front Microbiol 2020 15;11:516445. Epub 2020 Sep 15.

Division of Microbiology and Production, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.

Consumption of dates has not been considered a common risk of hepatitis A virus (HAV) infection. In January 2018, an outbreak of hepatitis was identified with cases resident in all regions of Denmark. All the detected strains belonged to HAV genotype 3A. Epidemiological investigations through patients' interviews, case-control and trace-back studies pointed toward different batches of dates from a single producer as the vehicle of infection. Boxes of dates from suspected batches were collected from homes of patients and healthy families and analyzed using a recently reported optimized direct lysis method, consisting of simultaneous viral RNA elution and extraction from dates followed by purification of the nucleic acids. Extracts were analyzed for HAV and norovirus (NoV) RNA using RT-qPCR, while detected HAV were genotyped by Sanger sequencing. Among 20 nucleic acid extracts representing eight batches of dates, RNA of HAV (9.3 × 10 genome copies/g) and NoV genogroup (G)II (trace amounts) were detected in one batch, while NoV GII RNA (trace amounts) was detected in another. Average extraction efficiency of spiked process control murine norovirus was 20 ± 13% and the inhibitions of RT-qPCR detection of NoV GI, NoV GII, and HAV were 31 ± 34, 9 ± 9, and 3 ± 7%, respectively. The HAV genome detected in the dates matched by sequence 100% to the HAV genotype 3A detected in stool samples from cases implicated in the outbreak. This confirmed, to our knowledge, for the first time a sequence link between HAV infection and consumption of contaminated dates, suggesting dates to be an important vehicle of HAV transmission.
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http://dx.doi.org/10.3389/fmicb.2020.516445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522280PMC
September 2020

Are gamers better laparoscopic surgeons? Impact of gaming skills on laparoscopic performance in "Generation Y" students.

PLoS One 2020 26;15(8):e0232341. Epub 2020 Aug 26.

Department of General, Visceral, Cancer, and Transplant Surgery, University Hospital of Cologne, Cologne, Germany.

Background: Both laparoscopic surgery and computer games make similar demands on eye-hand coordination and visuospatial cognitive ability. A possible connection between both areas could be used for the recruitment and training of future surgery residents.

Aim: The goal of this study was to investigate whether gaming skills are associated with better laparoscopic performance in medical students.

Methods: 135 medical students (55 males, 80 females) participated in an experimental study. Students completed three laparoscopic tasks (rope pass, paper cut, and peg transfer) and played two custom-designed video games (2D and 3D game) that had been previously validated in a group of casual and professional gamers.

Results: There was a small significant correlation between performance on the rope pass task and the 3D game, Kendall's τ(111) = -.151, P = .019. There was also a small significant correlation between the paper cut task and points in the 2D game, Kendall's τ(102) = -.180, P = .008. Overall laparoscopic performance was also significantly correlated with both the 3D game, Kendall's τ(112) = -.134, P = .036, and points in the 2D game, Kendall's τ(113) = -.163, P = .011. However, there was no significant correlation between the peg transfer task and both games (2D and 3D game), P = n.s..

Conclusion: This study provides further evidence that gaming skills may be an advantage when learning laparoscopic surgery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232341PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449406PMC
October 2020

Veterinary Students Have a Higher Risk of Contracting Cryptosporidiosis when Calves with High Fecal Loads Are Used for Fetotomy Exercises.

Appl Environ Microbiol 2020 09 17;86(19). Epub 2020 Sep 17.

Laboratory of Parasitology, Department of Bacteria, Parasites & Fungi, Infectious Disease Preparedness, Statens Serum Institut, Copenhagen, Denmark.

An outbreak of cryptosporidiosis among veterinary students performing fetotomy exercises on euthanized calves took place in September 2018 in Denmark. A prospective cohort investigation was performed to identify risk factors and provide guidance for preventing outbreaks of cryptosporidiosis in this setting. Ninety-seven students attended the fetotomy exercises and completed a questionnaire about symptoms and potential risk behavior. Real-time PCR was used to detect spp. in stool samples from students and to quantify the fecal parasite load in the calves used for the exercises. subtyping was carried out for the -positive samples. Our case definition was based on participation in a fetotomy exercise, reported symptoms, and laboratory results. Eleven laboratory-confirmed or probable cases (11%) were identified in two outbreaks during the prospective study period, with attack rates of 4/10 (40%) and 7/9 (78%), respectively. The risk factors for cryptosporidiosis we identified were performing the exercise on a diarrheic calf, reporting visible fecal contamination on the personal protective equipment (PPE), and reporting problems with PPE during the exercise. IIaA15G2R1 was detected in both cases and calves. A significantly higher proportion of the calves aged 7 days old and above were positive compared with younger calves. Furthermore, a high fecal load in a calf was associated with a higher probability of an outbreak among the students. Based on our results, using noninfected calves for the exercises, appropriate use of PPE, and thorough hand hygiene are recommended to reduce the risk of contracting cryptosporidiosis in connection with fetotomy exercises. spp. can cause severe diarrhea in infected individuals. is zoonotic, and cattle are the main reservoir. In several countries, outbreaks of cryptosporidiosis have occurred in veterinary students after handling calves. We carried out a 1-year-long prospective study to investigate the occurrence of these recurrent cryptosporidiosis outbreaks in Denmark. Our investigation used a One Health approach and combined comprehensive epidemiological approaches and laboratory methods applied to both students and calves in the setting of the fetotomy exercises. Two outbreaks took place during the study period; additionally, we retrospectively identified two more suspected outbreaks prior to the study period. The results illustrated a high risk of contracting cryptosporidiosis among veterinary students in the setting of the fetotomy exercises, especially when using calves with high fecal loads. Our data can be used to inform future efforts to prevent transmission of to students during fetotomy exercises.
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http://dx.doi.org/10.1128/AEM.01250-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499042PMC
September 2020

Developmentally Driven Changes in Adipogenesis in Different Fat Depots Are Related to Obesity.

Front Endocrinol (Lausanne) 2020 26;11:138. Epub 2020 Mar 26.

University of Leipzig Medical Center, IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.

Subcutaneous (sc) and visceral (vis) adipose tissue (AT) contribute to the variability in pathophysiological consequences of obesity and adverse fat distribution. To gain insights into the molecular mechanisms distinguishing vis and sc fat, we compared the transcriptome during differentiation of immortalized adipocytes from murine epididymal (epi) and inguinal (ing) AT. RNA was extracted on different days of adipogenesis (-2, 0, 2, 4, 6, 8) and analyzed using Clariom™ D mouse assays (Affymetrix) covering >214,900 transcripts in >66,100 genes. Transcript Time Course Analysis revealed 137 differentially expressed genes. The top genes with most divergent expression dynamics included developmental genes like , and . According to pathway analysis the majority of the genes were enriched in pathways related to AT development. Finally, in paired samples of human vis and sc AT ( = 63), several of these genes exhibited depot-specific variability in expression which correlated closely with body mass index and/or waist-to-hip ratio. In conclusion, intrinsically programmed differences in gene expression patterns during adipogenesis suggest that fat depot specific regulation of adipogenesis contributes to individual risk of obesity.
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http://dx.doi.org/10.3389/fendo.2020.00138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115744PMC
February 2021

Characteristics of Tumor-Infiltrating Lymphocytes Prior to and During Immune Checkpoint Inhibitor Therapy.

Front Immunol 2020 4;11:364. Epub 2020 Mar 4.

Faculty of Medicine Carl Gustav Carus, Institute of Immunology, TU Dresden, Dresden, Germany.

The tumor immune contexture plays a major role for the clinical outcome of patients. High densities of CD45RO T helper 1 cells and CD8 T cells are associated with improved survival of patients with various cancer entities. In contrast, a higher frequency of tumor-infiltrating M2 macrophages is correlated with poor prognosis. Recent studies provide evidence that the tumor immune architecture also essentially contributes to the clinical efficacy of immune checkpoint inhibitor (CPI) therapy in patients. Pretreatment melanoma samples from patients who experienced a clinical response to anti-programmed cell death protein 1 (PD-1) treatment show higher densities of infiltrating CD8 T cells compared to samples from patients that progressed during therapy. Anti-PD-1 therapy results in an increased density of tumor-infiltrating T lymphocytes in treatment responders. In addition, elevated frequencies of melanoma-infiltrating TCF7CD8 T cells are correlated with beneficial clinical outcome of anti-PD-1-treated patients. In contrast, a high density of tumor-infiltrating, dysfunctional PD-1CD38 CD8 cells in melanoma patients is associated with anti-PD-1 resistance. Such findings indicate that comprehensive tumor immune contexture profiling prior to and during CPI therapy may lead to the identification of underlying mechanisms for treatment response or resistance, and the design of improved immunotherapeutic strategies. Here, we focus on studies exploring the impact of intratumoral T and B cells at baseline on the clinical outcome of CPI-treated cancer patients. In addition, recent findings demonstrating the influence of CPIs on tumor-infiltrating lymphocytes are summarized.
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http://dx.doi.org/10.3389/fimmu.2020.00364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064638PMC
March 2021

Bidirectional Crosstalk Between Cancer Stem Cells and Immune Cell Subsets.

Front Immunol 2020 5;11:140. Epub 2020 Feb 5.

Faculty of Medicine Carl Gustav Carus, Institute of Immunology, TU Dresden, Dresden, Germany.

Cancer stem cells (CSCs), also known as tumor-initiating cells, are characterized by an increased capacity for self-renewal, multipotency, and tumor initiation. While CSCs represent only a small proportion of the tumor mass, they significantly account for metastatic dissemination and tumor recurrence, thus making them attractive targets for therapy. Due to their ability to sustain in dormancy, chemo- and radiotherapy often fail to eliminate cancer cells with stemness properties. Recent advances in the understanding of the tumor microenvironment (TME) illustrated the importance of the immune contexture, determining the response to therapy and clinical outcome of patients. In this context, CSCs exhibit special properties to escape the recognition by innate and adaptive immunity and shape the TME into an immunosuppressive, pro-tumorigenic landscape. As CSCs sculpt the immune contexture, the phenotype and functional properties of the tumor-infiltrating immune cells in turn influence the differentiation and phenotype of tumor cells. In this review, we summarize recent studies investigating main immunomodulatory properties of CSCs and their underlying molecular mechanisms as well as the impact of immune cells on cancer cells with stemness properties. A deeper understanding of this bidirectional crosstalk shaping the immunological landscape and determining therapeutic responses will facilitate the improvement of current treatment modalities and the design of innovative strategies to precisely target CSCs.
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http://dx.doi.org/10.3389/fimmu.2020.00140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013084PMC
March 2021

A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer.

J Immunother Cancer 2019 11 15;7(1):307. Epub 2019 Nov 15.

Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany.

Background: We previously showed that the bacterial lipopeptide PamCys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8 T cells in mice, when covalently coupled to a synthetic peptide.

Case Presentation: We now designed a new water-soluble synthetic PamCys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8 T and NK cells by 6-sulfo LacNAc monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging. XS15 induced strong ex vivo CD8 and T1 CD4 responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide™ ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4 and CD8 effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 10 in the granuloma and 20.5 × 10 in peripheral blood.

Conclusion: Thus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.
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http://dx.doi.org/10.1186/s40425-019-0796-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858783PMC
November 2019

Cross-border outbreak of O3 associated with imported fresh spinach, Sweden and Denmark, March 2019.

Euro Surveill 2019 06;24(24)

Public Health Agency of Sweden, Solna, Sweden.

In April 2019, a cross-border outbreak of O3 was identified in Sweden and Denmark and confirmed using whole genome sequencing. Close cross-border collaboration with representatives from human and food authorities helped direct resources and investigations. Combined epidemiological and trace-back investigations pointed to imported fresh spinach as the outbreak vehicle and highlight that other vehicles of outbreaks than pork should be considered.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.24.1900368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582516PMC
June 2019

An international outbreak of Salmonella enterica serotype Enteritidis linked to eggs from Poland: a microbiological and epidemiological study.

Lancet Infect Dis 2019 07 24;19(7):778-786. Epub 2019 May 24.

National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Bilthoven, Netherlands.

Background: Salmonella spp are a major cause of food-borne outbreaks in Europe. We investigated a large multi-country outbreak of Salmonella enterica serotype Enteritidis in the EU and European Economic Area (EEA).

Methods: A confirmed case was defined as a laboratory-confirmed infection with the outbreak strains of S Enteritidis based on whole-genome sequencing (WGS), occurring between May 1, 2015, and Oct 31, 2018. A probable case was defined as laboratory-confirmed infection with S Enteritidis with the multiple-locus variable-number tandem repeat analysis outbreak profile. Multi-country epidemiological, trace-back, trace-forward, and environmental investigations were done. We did a case-control study including confirmed and probable cases and controls randomly sampled from the population registry (frequency matched by age, sex, and postal code). Odds ratios (ORs) for exposure rates between cases and controls were calculated with unmatched univariable and multivariable logistic regression.

Findings: 18 EU and EEA countries reported 838 confirmed and 371 probable cases. 509 (42%) cases were reported in 2016, after which the number of cases steadily increased. The case-control study results showed that cases more often ate in food establishments than did controls (OR 3·4 [95% CI 1·6-7·3]), but no specific food item was identified. Recipe-based food trace-back investigations among cases who ate in food establishments identified eggs from Poland as the vehicle of infection in October, 2016. Phylogenetic analysis identified two strains of S Enteritidis in human cases that were subsequently identified in salmonella-positive eggs and primary production premises in Poland, confirming the source of the outbreak. After control measures were implemented, the number of cases decreased, but increased again in March, 2017, and the increase continued into 2018.

Interpretation: This outbreak highlights the public health value of multi-country sharing of epidemiological, trace-back, and microbiological data. The re-emergence of cases suggests that outbreak strains have continued to enter the food chain, although changes in strain population dynamics and fewer cases indicate that control measures had some effect. Routine use of WGS in salmonella surveillance and outbreak response promises to identify and stop outbreaks in the future.

Funding: European Centre for Disease Prevention and Control; Directorate General for Health and Food Safety, European Commission; and National Public Health and Food Safety Institutes of the authors' countries (see Acknowledgments for full list).
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http://dx.doi.org/10.1016/S1473-3099(19)30047-7DOI Listing
July 2019

Evaluating pathogenicity of SLC34A3-Ser192Leu, a frequent European missense variant in disorders of renal phosphate wasting.

Urolithiasis 2019 Dec 23;47(6):511-519. Epub 2019 Feb 23.

Division of Nephrology, Department of Internal Medicine, University Hospital Leipzig, Liebigstr. 20, 04103, Leipzig, Germany.

Loss-of-function mutations of SLC34A3 represent an established cause of a distinct renal phosphate wasting disorder termed hereditary hypophosphatemic rickets with hypercalciuria (HHRH). SLC34A3 encodes the renal phosphate transporter NaPi2c expressed at the apical brush border of proximal renal tubules. Substitution of p.Ser192Leu is one of the most frequent genetic changes among HHRH patients in Europe, but has never been systematically evaluated, clinically or on a cellular level. Identification of a 32-year-old female with a homozgyous c.575C>T, p.Ser192Leu substitution enabled a more comprehensive assessment of the impact of this missense variant. Clinically, the patient showed renal phosphate wasting and nephrocalcinosis without any bone abnormalities. Heterozygous carriers of deleterious SLC34A3 variants were previously described to harbor an increased risk of kidney stone formation and renal calcification. We hence examined the frequency of p.Ser192Leu variants in our adult kidney stone cohort and compared the results to clinical findings of previously published cases of both mono- and biallelic p.Ser192Leu changes. On a cellular level, p.Ser192Leu-mutated transporters localize to the plasma membrane in different cellular systems, but lead to significantly reduced transport activity of inorganic phosphate upon overexpression in Xenopus oocytes. Despite the reduced function in ectopic cellular systems, the clinical consequences of p.Ser192Leu may appear relatively mild, at least in our index patient, and can potentially be missed in clinical practice.
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http://dx.doi.org/10.1007/s00240-019-01116-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825645PMC
December 2019

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017.

Euro Surveill 2018 08;23(33)

European Centre for Disease Prevention and Control, Solna, Sweden.

Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.
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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.33.1700641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205254PMC
August 2018

Two concurrent outbreaks of hepatitis A highlight the risk of infection for non-immune travellers to Morocco, January to June 2018.

Euro Surveill 2018 07;23(27)

Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark.

From January to June 2018, two ongoing hepatitis A outbreaks affected travellers returning from Morocco and cases in Europe without travel history, resulting in 163 patients in eight European countries. Most interviewed travel-related cases were unaware of the hepatitis A risk in Morocco. Molecular analysis revealed two distinct hepatitis A virus (HAV) strains (subgenotype IA DK2018_231; subgenotype IB V18-16428). Vaccination recommendations should be emphasised to increase awareness among non-immune travellers to Morocco and HAV-endemic countries.
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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.27.1800329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152161PMC
July 2018

Travel-associated hepatitis A in Europe, 2009 to 2015.

Euro Surveill 2018 05;23(22)

Karolinska Institutet, Stockholm, Sweden.

BackgroundTravel to countries with high or intermediate hepatitis A virus (HAV) endemicity is a risk factor for infection in residents of countries with low HAV endemicity. The objective of this study was to estimate the risk for hepatitis A among European travellers using surveillance and travel denominator data. We retrieved hepatitis A surveillance data from 13 European Union (EU)/ European Economic Area (EEA) countries with comprehensive surveillance systems and travel denominator data from the Statistical Office of the European Union. A travel-associated case of hepatitis A was defined as any case reported as imported. From 2009 to 2015, the 13 countries reported 18,839 confirmed cases of hepatitis A, of which 5,233 (27.8%) were travel-associated. Of these, 39.8% were among children younger than 15 years. The overall risk associated with travel abroad decreased over the period at an annual rate of 3.7% (95% confidence interval (CI): 0.7-2.7) from 0.70 cases per million nights in 2009 to 0.51 in 2015. The highest risk was observed in travellers to Africa (2.11 cases per million nights). Cases more likely to be reported as travel-associated were male and of younger age (< 25 years). Travel is still a major risk factor for HAV infection in the EU/EEA, although the risk of infection may have slightly decreased in recent years. Children younger than 15 years accounted for a large proportion of cases and should be prioritised for vaccination.
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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.22.1700583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152172PMC
May 2018

Update on Hereditary Kidney Stone Disease and Introduction of a New Clinical Patient Registry in Germany.

Front Pediatr 2018 7;6:47. Epub 2018 Mar 7.

Division of Pediatric Nephrology, University Children's Hospital, Bonn, Germany.

Kidney stone disease is an increasingly prevalent condition with remarkable clinical heterogeneity, with regards to stone composition, age of manifestation, rate of recurrence, and impairment of kidney function. Calcium-based kidney stones account for the vast majority of cases, but their etiology is poorly understood, notably their genetic drivers. As recent studies indicate, hereditary conditions are most likely underestimated in prevalence, and new disease genes are constantly being identified. As a consequence, there is an urgent need of a more efficient documentation and collection of cases with underlying hereditary conditions, to better understand shared phenotypic presentation and common molecular mechanisms. By implementation of a centralized patient registry on hereditary kidney stone disease in Germany, we aim to help closing the vast knowledge gap on genetics of kidney stone disease. In this context, clinical registries are indispensable for several reasons: first, delineating better phenotype-genotype associations will allow more precise patient stratification in future clinical research studies. Second, identifying new disease genes and new mechanisms will further reduce the rate of unknown nephrolithiasis/nephrocalcinosis etiology; and third, deciphering new molecular targets will pave the way to develop drugs for recurrence prevention in severely affected families.
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http://dx.doi.org/10.3389/fped.2018.00047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850730PMC
March 2018

Cross-border outbreak of listeriosis caused by cold-smoked salmon, revealed by integrated surveillance and whole genome sequencing (WGS), Denmark and France, 2015 to 2017.

Euro Surveill 2017 Dec;22(50)

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

In August 2017, an outbreak of six listeriosis cases in Denmark was traced to cold-smoked salmon, using epidemiological investigations and whole-genome sequencing (WGS) analyses. Exchange of genome sequences allowed identification in France of a food isolate from a salmon-derived product and a human isolate from 2016 within the same cgMLST cluster as the Danish isolates (L2-SL8-ST8-CT771). The salmon product came from a third European Union country. WGS can rapidly link human cases and food isolates across Europe.
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http://dx.doi.org/10.2807/1560-7917.ES.2017.22.50.17-00762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743096PMC
December 2017

Infant botulism in Denmark from 1995 to 2015.

Dan Med J 2017 Sep;64(9)

Introduction: Infant botulism is a rare, probably underdiagnosed, life-threatening disease caused by the toxin-producing bacterium Clostridium botulinum.

Methods: We investigated reported cases of infant botulism in Denmark from 1995 to 2015, and compared the incidence with that of other western countries.

Results: We found nine cases of infant botulism in Denmark from 1995 to 2015. The incidence of infant botulism in Denmark was similar to that seen in other western countries, but likely underestimated. The source of infection was only confirmed in a single case. Four cases received botulism immune globulin, intravenous (BIG-IV), which was administered within 7-10 days from admission.

Conclusions: Infant botulism is probably underdiagnosed. Increased awareness is crucial to be able to recognise the condition. The time delay from hospital admission to administration of BIG-IV is challenging. Studies have shown that BIG-IV reduces both mean duration of intensive care and mean length of hospital stay; however, this was not confirmed in our work due to the limited number of patients.

Funding: none.

Trial Registration: not relevant.
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September 2017

Multinational outbreak of travel-related Salmonella Chester infections in Europe, summers 2014 and 2015.

Euro Surveill 2017 Feb;22(7)

Institut Pasteur, French National Reference Center for E. coli, Shigella and Salmonella, Paris, France.

Between 2014 and 2015, the European Centre for Disease Prevention and Control was informed of an increase in numbers of Salmonella enterica serotype Chester cases with travel to Morocco occurring in six European countries. Epidemiological and microbiological investigations were conducted. In addition to gathering information on the characteristics of cases from the different countries in 2014, the epidemiological investigation comprised a matched case-case study involving French patients with salmonellosis who travelled to Morocco that year. A univariate conditional logistic regression was performed to quantify associations. The microbiological study included a whole genome sequencing (WGS) analysis of clinical and non-human isolates of S. Chester of varied place and year of isolation. A total of 162 cases, mostly from France, followed by Belgium, the Netherlands, Spain, Denmark and Sweden were reported, including 86 (53%) women. The median age per country ranged from 3 to 38 years. Cases of S. Chester were more likely to have eaten in a restaurant and visited the coast of Morocco. The results of WGS showed five multilocus sequence types (ST), with 96 of 153 isolates analysed clustering into a tight group that corresponded to a novel ST, ST1954. Of these 96 isolates, 46 (48%) were derived from food or patients returning from Morocco and carried two types of plasmids containing either qnrS1 or qnrB19 genes. This European-wide outbreak associated with travel to Morocco was likely a multi-source outbreak with several food vehicles contaminated by multidrug-resistant S. Chester strains.
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http://dx.doi.org/10.2807/1560-7917.ES.2017.22.7.30463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322187PMC
February 2017

Series of Norovirus Outbreaks Caused by Consumption of Green Coral Lettuce, Denmark, April 2016.

PLoS Curr 2016 Oct 4;8. Epub 2016 Oct 4.

Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark.

Introduction: In early April 2016, an unusual high number of point-source outbreaks of gastrointestinal disease were reported to occur in Denmark.

Methods: Outbreaks were individually investigated. Two analytical studies were performed. Patient stool samples collected and analysed; positive stool samples were sequenced over the polymerase and/or capsid gene areas. Implicated lettuce heads were collected and analysed for the presence of norovirus. Foods were traced-back and traced-forward and international alert systems applied.

Results: A total of 23 linked point-source outbreaks occurred over the course of one week. Fresh green coral lettuce (Lollo Bionda lettuce) had been consumed in all settings. In a cohort study including 234 participants a dish containing green lettuce was associated with illness. Norovirus of Genogroup I (GI) was detected in samples from 28 patients comprising eight of the outbreaks. Sequencing showed GI.P2-GI.2. GI norovirus was detected in one of 20 examined lettuce heads. All lettuce consumed was supplied by the same packer who in turn had bought the lettuce from a wholesaler in France. The two lots of lettuce came from two different growers in different parts of France.

Discussion: Green coral lettuce produced in France was found to have caused a large series of linked norovirus outbreaks in Denmark as established by a number of lines of evidence. A similar incidence occurred in 2010. Fresh lettuce increasingly appear to be a risk food for norovirus infections.
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http://dx.doi.org/10.1371/currents.outbreaks.115761d5d6de6a8bc7dd4b41f0f5f142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074700PMC
October 2016

Whole-genome Sequencing Used to Investigate a Nationwide Outbreak of Listeriosis Caused by Ready-to-eat Delicatessen Meat, Denmark, 2014.

Clin Infect Dis 2016 07 29;63(1):64-70. Epub 2016 Mar 29.

Department of Infectious Disease Epidemiology Department of Microbiology and Infection Control, Statens Serum Institut.

Background: Listeriosis is a serious foodborne infection. Outbreaks of listeriosis occur rarely, but have often proved difficult to solve. In June 2014, we detected and investigated a listeriosis outbreak in Denmark using patient interviews and whole-genome sequencing (WGS).

Methods: We performed WGS on Listeria monocytogenes isolates from patients and available isolates from ready-to-eat foods and compared them using single-nucleotide polymorphism (SNP) analysis. Case patients had L. monocytogenes with ≤3 SNPs (the outbreak strain) isolated in September 2013-December 2014. Through interviews, we established case patients' food and clinical histories. Food production facilities were inspected and sampled, and we performed trace-back/trace-forward of food delivery chains.

Results: In total, 41 cases were identified; 17 deaths occurred (41%). An isolate from a delicatessen meat (spiced meat roll) from company A was identical to the outbreak strain. Half of the patients were infected while hospitalized/institutionalized; institutions were supplied food by company A. The outbreak strain was repeatedly isolated from further samples taken within this company and within companies in its distribution chain. Products from company A were traced and recalled from >6000 food establishments, after which the outbreak ended.

Conclusions: Ready-to-eat spiced meat roll from a single production facility caused this outbreak. The product, served sliced and cold, is popular among the elderly; serving it at hospitals probably contributed to the high case-fatality rate. WGS used for patient isolates and isolates from food control inspections, coupled with routine epidemiological follow-up, was instrumental in swiftly locating the source of infections, preventing further illnesses and deaths.
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http://dx.doi.org/10.1093/cid/ciw192DOI Listing
July 2016

Associations of age and sex with the clinical outcome and incubation period of Shiga toxin-producing Escherichia coli O104:H4 infections, 2011.

Am J Epidemiol 2013 Sep 8;178(6):984-92. Epub 2013 Aug 8.

We pooled data on adults who reported diarrhea or developed life-threatening hemolytic uremic syndrome (HUS) in any of 6 closed cohorts from 4 countries (1 cohort each in Denmark, France, and Sweden and 3 in Germany) that were investigated during a large outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in 2011. Logistic regression and Weibull regression for interval censored data were used to assess the relation of age and sex with clinical outcome and with incubation period. Information on the latter was used in a nonparametric back-projection context to estimate when adult cases reported in Germany were exposed to STEC O104:H4. Overall, data from 119 persons (median age, 49 years; 80 women) were analyzed. Bloody diarrhea and HUS were recorded as the most severe outcome for 44 and 26 individuals, respectively. Older age was significantly associated with bloody diarrhea but not with HUS. Woman had nonsignificantly higher odds for bloody diarrhea (odds ratio = 1.81) and developing HUS (odds ratio = 1.83) than did men. Older participants had a statistically significantly reduced incubation period. The shortest interval that included 75% of exposures in adults spanned only 12 days and preceded outbreak detection. In conclusion, the frequency of bloody diarrhea but not of HUS and the length of the incubation period depended on the age of individuals infected with STEC O104:H4. A large number of people were exposed to STEC O104:H4 for a short period of time.
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http://dx.doi.org/10.1093/aje/kwt069DOI Listing
September 2013

Salmonella Typhimurium outbreak associated with smoked pork tenderloin in Denmark, January to March 2011.

Scand J Infect Dis 2012 Dec 17;44(12):903-8. Epub 2012 Jul 17.

European Programme for Intervention Epidemiology Training-EPIET, European Centre for Disease Prevention and Control, Stockholm, Sweden.

Background: An outbreak of salmonellosis (Salmonella Typhimurium, phage type DT120) occurred from 26 January to 15 March 2011, in Denmark, with 22 laboratory confirmed cases. Hypothesis-generating patient interviews gave rise to the suspicion that smoked pork tenderloin was the source of infection. The primary objective of this study was to identify the source of the outbreak in order to initiate appropriate control measures.

Methods: A matched (1:2) case-control study was conducted. A case was defined as a person residing in Denmark whose stool sample tested positive for S. Typhimurium, with a particular multilocus variable-number tandem repeat profile, from January to March 2011. Controls were matched to cases on age, gender, and municipality of residence.

Results: Of 21 interviewed cases, 19 (91%) indicated that they typically ate smoked pork tenderloin more than once a week, compared with 13 (33%) of 39 interviewed controls (matched odds ratio 19.6, 95% confidence interval 2.6-153). Eighteen (86%) cases indicated that they might have consumed smoked pork tenderloin the week before becoming ill, compared with 1 (4%) control who had eaten the product a week before the interview. Two cases provided the brand name of the product and the supermarket where it was purchased.

Conclusions: The results show a strong statistically significant association between the consumption of smoked pork tenderloin and S. Typhimurium infection. The European Rapid Alert System for Food and Feed was used to notify these findings to the competent authorities in the country of origin of the product. Subsequently, the smoked pork tenderloin of the brand in question, dating from 1 January to 1 May 2011, was recalled from consumers.
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http://dx.doi.org/10.3109/00365548.2012.693196DOI Listing
December 2012

Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany.

N Engl J Med 2011 Nov 22;365(19):1771-80. Epub 2011 Jun 22.

Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.

Background: We describe an outbreak of gastroenteritis and the hemolytic-uremic syndrome caused by Shiga-toxin-producing Escherichia coli in Germany in May, June, and July, 2011. The consumption of sprouts was identified as the most likely vehicle of infection.

Methods: We analyzed data from reports in Germany of Shiga-toxin-producing E. coli gastroenteritis and the hemolytic-uremic syndrome and clinical information on patients presenting to Hamburg University Medical Center (HUMC). An outbreak case was defined as a reported case of the hemolytic-uremic syndrome or of gastroenteritis in a patient infected by Shiga-toxin-producing E. coli, serogroup O104 or serogroup unknown, with an onset of disease during the period from May 1 through July 4, 2011, in Germany.

Results: A total of 3816 cases (including 54 deaths) were reported in Germany, 845 of which (22%) involved the hemolytic-uremic syndrome. The outbreak was centered in northern Germany and peaked around May 21 to 22. Most of the patients in whom the hemolytic-uremic syndrome developed were adults (88%; median age, 42 years), and women were overrepresented (68%). The estimated median incubation period was 8 days, with a median of 5 days from the onset of diarrhea to the development of the hemolytic-uremic syndrome. Among 59 patients prospectively followed at HUMC, the hemolytic-uremic syndrome developed in 12 (20%), with no significant differences according to sex or reported initial symptoms and signs. The outbreak strain was typed as an enteroaggregative Shiga-toxin-producing E. coli O104:H4, producing extended-spectrum beta-lactamase.

Conclusions: In this outbreak, caused by an unusual E. coli strain, cases of the hemolytic-uremic syndrome occurred predominantly in adults, with a preponderance of cases occurring in women. The hemolytic-uremic syndrome developed in more than 20% of the identified cases.
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http://dx.doi.org/10.1056/NEJMoa1106483DOI Listing
November 2011

Molecular characterization of Salmonella Typhimurium highly successful outbreak strains.

Foodborne Pathog Dis 2011 Jun 7;8(6):655-61. Epub 2011 Mar 7.

Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.

Three large clusters of Salmonella Typhimurium infections in Denmark in 2008 and 2009 were defined by multilocus variable number of tandem repeat analysis (MLVA). One of these proved to be the hereto largest Danish cluster of salmonellosis with 1446 cases. Two smaller clusters with a total of 197 and 89 cases, respectively, were seen concurrently. These clusters shared epidemiological characteristics such as age distribution, geography, and time. To investigate the possible genetic relationship between the cluster strains, these were further characterized by phage typing, pulsed-field gel electrophoresis, and Optical Mapping. Although the MLVA method proved robust and well-performing in detecting and defining clusters, the employment of a second typing method detected an additional fourth cluster among the isolates. The cluster strains were stable throughout the almost 2-year period, even though we detected changes in three of five MLVA loci in a small fraction of isolates. These changes were mainly due to the gain or loss of single repeats. Optical Mapping of the large cluster strain indicated no increased content of virulence genes; however, Optical Mapping did reveal a large insert, a probable prophage, in the main cluster. This probable prophage may give the cluster strain a competitive advantage. The molecular methods employed suggested that the four clusters represented four distinct strains, although they seemed to be epidemiologically linked and shared genotypic characteristics.
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http://dx.doi.org/10.1089/fpd.2010.0683DOI Listing
June 2011

[Salmonella and campylobacter infections in 2008].

Ugeskr Laeger 2010 May;172(19):1451-5

Statens Serum Institut, Epidemiologisk Afdeling, København S, Denmark.

Introduction: Information about whether Salmonella and Campylobacter infections are acquired during foreign travel has previously been incomplete. We collected such information systematically for 2008.

Methods: Information from all laboratory-confirmed cases of Salmonella and Campylobacter-cases from three laboratory catchment areas were prospectively collected by telephone interviews.

Results: Of the overall 3,675 cases of Salmonella infection in 2008, information about recent travel was obtained in 3,152 (86%). Among these, 61% of S. Enteritidis, 6% of S. Typhimurium, and 34% of individuals infected with other serotypes were acquired abroad. Among the isolates that were tested for antimicrobial drug sensitivity, 21% of the isolates acquired during foreign travel were resistant and 9% were multidrug-resistant compared with 7% and 2%, respectively, of the indigenous strains. Nearly a quarter of the 3,455 registered Campylobacter cases were included in the survey, and information about recent travel was obtained from 82%. Among these, 33% were acquired abroad.

Discussion: The proportion of Salmonella infections acquired abroad varies by serotype. S. Enteritidis used to be the most frequent serotype, predominantly acquired from contaminated Danish egg, but S. Enteritidis is today primarily an imported infection. By contrast, S. Typhimurium is predominately acquired in Denmark. The latter observation should be interpreted on the background of the unprecedented large outbreaks of S. Typhimurium in 2008. There was a clear association between a history of foreign travel and the risk of acquiring an infection with a drug-resistant strain.
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May 2010

Complexity in estimating recent tuberculosis transmission among predominantly immigrant school children in Stockholm, Sweden 2006.

Scand J Infect Dis 2008 ;40(9):709-14

Epidemiological Department, Swedish Institute for Infectious Disease Control, Stockholm, Sweden.

In January 2006, an after-school carer in Stockholm was diagnosed with open pulmonary tuberculosis (TB) after having been symptomatic for 3 months. The aim of this paper is to illustrate the difficulties encountered in estimating recent transmission of TB among children in an immigrant school population. A tuberculin skin test was performed on 261 pupils aged 6-15 y and an additional interferon-gamma release assay was performed on 20 children. In total, 76% of the children were born in Sweden; however, 95% of the parents originated from countries with TB incidence >25/100,000. Three active TB cases were identified, 1 of whom was culture-positive with the same strain as the index case. Latent tuberculous infection (LTBI) was diagnosed in 35 children. However, the increased risk of earlier infection in this population makes it difficult to evaluate when transmission occurred. The magnitude of recent transmission from the index case will thus be uncertain and indications to treat less clear.
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http://dx.doi.org/10.1080/00365540801995352DOI Listing
January 2009

Nationwide measles epidemic in Ukraine: the effect of low vaccine effectiveness.

Vaccine 2008 Dec 19;26(52):6980-5. Epub 2008 Sep 19.

European Centre for Disease Prevention and Control, Solna, Sweden.

The WHO European Region has a measles elimination target for 2010. Between September 2005 and mid-June 2006, more than 50,000 measles cases were reported in Ukraine; many reportedly had received two doses of measles vaccine and over 60% were among persons 15-29 years old. To investigate vaccine effectiveness (VE), a case-control study was undertaken in Dnepropetrovsk region. VE for two doses of measles vaccine was 93.1%, providing insufficient population immunity for measles elimination. An additional dose of measles vaccine for these age-cohorts is required if Ukraine is to achieve measles elimination. Other republics of the former Soviet Union also need to consider a supplemental dose of measles vaccine for older age groups identified epidemiologically to be at increased risk for measles even though individuals may have already received two doses.
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http://dx.doi.org/10.1016/j.vaccine.2008.09.012DOI Listing
December 2008