title: The 24-Form Tai Chi Improves Anxiety and Depression and Upregulates miR-17-92 in Coronary Heart Disease Patients After Percutaneous Coronary Intervention

text: BACKGROUND: Anxiety and depression are common symptoms in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). The 24-form Tai Chi may exert a protective function for CHD patients after PCI by improving anxiety and depression. METHODS: Patients who received PCI after 1–4 days were randomly assigned to the 24-form Tai Chi group (TG) and the control group (CG). The differences in anxiety and depression, using the Medical Outcomes Study 36−item Short−Form Health Survey (SF-36), before and after an average of 10 months of Tai Chi intervention were compared in both groups to analyze the effects of Tai Chi on the emotion and the life quality of CHD patients. Meanwhile, the relative levels of miR-17-92 were measured by using real-time qPCR. The association between the relative levels of miR-17-92 and the anxiety and the depression of CHD patients after PCI was analyzed. Adjusted Cox models were used to explore the effect of Tai Chi exercise in CHD patients. RESULTS: After 10 months of intervention, the changes in the anxiety subscale (P = 0.002), in the depression subscale (P = 0.008), and in the stress (P = 0.015) scores were higher in the TG group when compared to those of the CG group. The proportion of anxious (P = 0.045) and depressed subjects (P = 0.042) in the TG group was lower than that in the CG group. On the other hand, the increase in the SF-36 scores and in the relative levels of miR-17-92 was significantly higher in the TG group when compared with that of the CG group (P < 0.05). The serum level of miR-17-92 had a negative correlation with the anxiety, the depression, and the stress scores (P < 0.01). CONCLUSION: The 24-form Tai Chi improved the anxiety and the depression symptoms and upregulated the miR-17-92 levels in CHD patients after PCI.


Authors’ correction for Euro Surveill. 2020;25(9)


Updated rapid risk assessment from ECDC on the novel coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK


title: Two‐pore channels regulate Tat endolysosome escape and Tat‐mediated HIV‐1 LTR transactivation

text: HIV‐1 Tat is essential for HIV‐1 replication and appears to play an important role in the pathogenesis of HIV‐associated neurological complications. Secreted from infected or transfected cells, Tat has the extraordinary ability to cross the plasma membrane. In the brain, Tat can be taken up by CNS cells via receptor‐mediated endocytosis. Following endocytosis and its internalization into endolysosomes, Tat must be released in order for it to activate the HIV‐1 LTR promoter and facilitate HIV‐1 viral replication in the nucleus. However, the underlying mechanisms whereby Tat escapes endolysosomes remain unclear. Because Tat disrupts intracellular calcium homeostasis, we investigated the involvement of calcium in Tat endolysosome escape and subsequent LTR transactivation. We demonstrated that chelating endolysosome calcium with high‐affinity rhodamine‐dextran or chelating cytosolic calcium with BAPTA‐AM attenuated Tat endolysosome escape and LTR transactivation. Significantly, we demonstrated that pharmacologically blocking and knocking down the endolysosome‐resident two‐pore channels (TPCs) attenuated Tat endolysosome escape and LTR transactivation. This calcium‐mediated effect appears to be selective for TPCs because knocking down TRPML1 calcium channels was without effect. Our findings suggest that calcium released from TPCs is involved in Tat endolysosome escape and subsequent LTR transactivation. TPCs might represent a novel therapeutic target against HIV‐1 infection and HIV‐associated neurological complications.


title: Protocol for TRAUMADORNASE: a prospective, randomized, multicentre, double-blinded, placebo-controlled clinical trial of aerosolized dornase alfa to reduce the incidence of moderate-to-severe hypoxaemia in ventilated trauma patients

text: BACKGROUND: Acute respiratory distress syndrome continues to drive significant morbidity and mortality after severe trauma. The incidence of trauma-induced, moderate-to-severe hypoxaemia, according to the Berlin definition, could be as high as 45%. Its pathophysiology includes the release of damage-associated molecular patterns (DAMPs), which propagate tissue injuries by triggering neutrophil extracellular traps (NETs). NETs include a DNA backbone coated with cytoplasmic proteins, which drive pulmonary cytotoxic effects. The structure of NETs and many DAMPs includes double-stranded DNA, which prevents their neutralization by plasma. Dornase alfa is a US Food and Drug Administration-approved recombinant DNase, which cleaves extracellular DNA and may therefore break up the backbone of NETs and DAMPs. Aerosolized dornase alfa was shown to reduce trauma-induced lung injury in experimental models and to improve arterial oxygenation in ventilated patients. METHODS: TRAUMADORNASE will be an institution-led, multicentre, double-blinded, placebo-controlled randomized trial in ventilated trauma patients. The primary trial objective is to demonstrate a reduction in the incidence of moderate-to-severe hypoxaemia in severe trauma patients during the first 7 days from 45% to 30% by providing aerosolized dornase alfa as compared to placebo. The secondary objectives are to demonstrate an improvement in lung function and a reduction in morbidity and mortality. Randomization of 250 patients per treatment arm will be carried out through a secure, web-based system. Statistical analyses will include a descriptive step and an inferential step using fully Bayesian techniques. The study was approved by both the Agence Nationale de la Sécurité du Médicament et des Produits de Santé (ANSM, on 5 October 2018) and a National Institutional Review Board (CPP, on 6 November 2018). Participant recruitment began in March 2019. Results will be published in international peer-reviewed medical journals. DISCUSSION: If early administration of inhaled dornase alfa actually reduces the incidence of moderate-to-severe hypoxaemia in patients with severe trauma, this new therapeutic strategy may be easily implemented in many clinical trauma care settings. This treatment may facilitate ventilator weaning, reduce the burden of trauma-induced lung inflammation and facilitate recovery and rehabilitation in severe trauma patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03368092. Registered on 11 December 2017.


title: Trends, risk factors and outcomes of healthcare-associated infections in a neonatal intensive care unit in Italy during 2013–2017

text: BACKGROUND: Healthcare-associated infections (HAIs) occur frequently in intensive care units (NICUs). The aim of this study was to analyze the results of surveillance of HAIs in a III level NICU in Naples, Italy during 2013–2017 and to compare with those obtained during 2006–2010. METHODS: The surveillance included 1265 neonates of all birth weight (BW) classes with > 2 days NICU stay. Infections were defined using standard Centers for Disease Control and Prevention definitions adapted to neonatal pathology. RESULTS: A total of 125 HAIs were registered during 2013–2017 with a frequency of 9.9% and an incidence density of 3.2 per 1000 patient days. HAIs occurred in all BW classes with a decreasing trend from the lowest to the highest BW classes (p = < 0.001). Central line-associated blood stream infection (CLABSI) was the most frequent infection (69.6%), followed by ventilator associated pneumonia (VAP) (20%), urinary tract infection (UTI) (8.8%) and necrotizing enterocolitis (NEC) (1.6%). Also, CLABSI and VAP incidence density decreased from lower to highest BW classes showing a significant trend (p = 0.007). Most frequent pathogens responsible for CLABSI were: Coagulase-negative staphylococci (CONS) (25.3%), Candida parapsilosis (21.8%), Pseudomonas aeruginosa (5.7), Escherichia coli and Klebsiella pneumoniae (6.8%). No microbiological diagnosis was achieved for 20.7% of CLABSI. Pseudomonas aeruginosa (28%), Stenotrophomonas maltophilia (20%), and CONS (20%) were the most frequent pathogens responsible for VAP. CLABSI incidence density showed no differences between 2006 and 2010 and 2013–2017, while VAP incidence density for the 751–100 g BW class was higher during 2006–2010 than during 2013–2017 (p = 0.006). A higher incidence of the CLABSI caused by Gram positive bacteria (p = 0.002) or by undetermined etiology (p = 0.01) was observed during 2013–2017 than during 2006–2010, while a significant lower incidence of VAP caused by Gram-negative bacteria was found during 2013–2017 than during 2006–2010 (p = 0.007). CONCLUSION: HAIs in the NICU developed in all BW classes with a decreasing trend from the lowest to the highest BW classes in both study periods. Differences in the aetiology of CLABSI and VAP were found between the two study periods. This reinforces the importance of HAIs surveillance protocol in the NICU, which monitors microbiological isolates and use of medical devices for all BW classes of neonates.


Amtilche Mitteilungen


title: DNA vaccines: are they still just a powerful tool for the future?

text: Vaccination is historically one of the most successful strategies for the prevention of infectious diseases. For safety reasons, modern vaccinology tends toward the usage of inactivated or attenuated microorganisms and uses predominantly subunit vaccines. The antigens need to be clearly defined, pure, stable, appropriately composed, and properly presented to the immune system of the host. Differing ratios of various proportions between specific CD4(+) and CD8(+) T cell responses are essential for conferring the required protection in the case of individual vaccines. To stimulate both CD4(+) and CD8(+) T cells, the antigens must be processed and presented to both antigen-presentation pathways, MHC I and MHC II. Protein antigens delivered by vaccination are processed as extracellular antigens. However, extracellularly delivered antigen can be directed towards intracellular presentation pathways in conjugation with molecules involved in antigen cross-presentation, e.g. heat shock proteins, or by genomic-DNA vaccination. In this overview, current knowledge of the host immune response to DNA vaccines is summarized in the introduction. The subsequent sections discuss techniques for enhancing DNA vaccine efficacy, such as DNA delivery to specific tissues, delivery of DNA to the cell cytoplasm or nucleus, and enhancement of the immune response using molecular adjuvants. Finally, the prospects of DNA vaccination and ongoing clinical trials with various DNA vaccines are discussed.


title: Dipyrithione inhibits IFN-γ-induced JAK/STAT1 signaling pathway activation and IP-10/CXCL10 expression in RAW264.7 cells

text: OBJECTIVE: This study investigates the effects of dipyrithione (PTS2) on the expression of IP-10/CXCL10, which has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions. METHODS: RAW264.7 cells (a murine macrophage-like cell line) were cultured in the absence or in the presence of PTS2 (3–10 μM) together with or without IFN-γ (10 ng/ml). IP-10/CXCL10 expression was measured by specific enzyme-amplified immunoassays and reverse transcriptase-PCR (RT-PCR). Phosphorylation of JAK1, JAK2 and STAT1 were detected by Western blot analysis. RESULTS: We found that PTS2 inhibited IFN-γ-induced up-regulation of IP-10/CXCL10 protein level in a dose- and time-dependent manner in RAW264.7 cells. RT-PCR experiments showed that PTS2 suppressed IFN-γ-induced IP-10/CXCL10 expression at mRNA levels. Mechanistically, PTS2 prevented phosphorylation of JAK1, JAK2 and STAT1, but did not interfere with the p38 pathway. Furthermore, the inhibitory effect of PTS2 on IP-10/CXCL10 up-regulation was slightly stronger than JAK2 inhibitor AG490. CONCLUSION: PTS2 inhibits IFN-γ-induced IP-10/CXCL10 expression in RAW264.7 cells by targeting the JAK/STAT1 signaling pathway, suggesting that PTS2 could exert anti-inflammatory effects through attenuating the formation of chemokine IP-10/CXCL10.


title: Nuclear functions of heterogeneous nuclear ribonucleoproteins A/B

text: The hnRNP A/B proteins are among the most abundant RNA-binding proteins, forming the core of the ribonucleoprotein complex that associates with nascent transcripts in eukaryotic cells. There are several paralogs in this subfamily, each of which is subject to alternative transcript splicing and post-translational modifications. The structural diversity of these proteins generates a multitude of functions that involve interactions with DNA or, more commonly, RNA. They also recruit regulatory proteins associated with pathways related to DNA and RNA metabolism, and appear to accompany transcripts throughout the life of the mRNA. We have highlighted here recent progress in elucidation of molecular mechanisms underlying the roles of these hnRNPs in a wide range of nuclear processes, including DNA replication and repair, telomere maintenance, transcription, pre-mRNA splicing, and mRNA nucleo-cytoplasmic export.


title: Membrane traffic in the secretory pathway: Take the ’A’ train: on fast tracks to the cell surface

text: Cholesterol, certain lipids, membrane-bound and soluble proteins, as well as viruses that are synthesized in the endoplasmic reticulum (ER), reach the plasma membrane (PM) via non-classical pathway(s) that remain poorly understood. Typical for this transport is (i) its insensitivity to brefeldin A (BFA), which dissociates selected coat complexes from membranes, resulting in the disassembly of the Golgi apparatus; (ii) its rapid kinetics as compared to the classical secretory pathway; and (iii) its role in the trafficking of lipid raft components. Based on results showing that the intermediate compartment (IC) at the ER-Golgi boundary constitutes a stable tubular network that maintains its dynamics in the presence of BFA, we propose that two bidirectional Golgi-bypass pathways to the PM exist, a direct route from early IC elements, and another, reminescent of the yeast secretory pathway, from late IC elements via the endosomal system. These pathways have implications for the organization of the secretory processes in different cell types. (Part of a Multi-author Review)


title: Biological weapons: Development of a matrix to evaluate the threat of biological agents used for bioterrorism

text: Adequate public health preparedness for bioterrorism includes the elaboration of an agreed list of biological and chemical agents that might be used in an attack or as threats of deliberate release. In the absence of counterterrorism intelligence information, public health authorities can also base their preparedness on the agents for which the national health structures would be most vulnerable. This article aims to describe a logical method and the characteristics of the variables to be brought in a weighing process to reach a priority list for preparedness. The European Union, in the aftermath of the anthrax events of October 2001 in the United States, set up a task force of experts from multiple member states to elaborate and implement a health security programme. One of the first tasks of this task force was to come up with a list of priority threats. The model, presented here, allows Web-based updates for newly identified agents and for the changes occurring in preventive measures for agents already listed. The same model also allows the identification of priority protection action areas.


title: Molecular mechanisms underlying Th1-like Treg generation and function

text: Since their ‘re-discovery’ more than two decades ago, FOXP3(+) regulatory T cells (Tregs) have been an important subject of investigation in the biomedical field and our understanding of the mechanisms that drive their phenotype and function in health and disease has advanced tremendously. During the past few years it has become clear that Tregs are not a terminally differentiated population but show some degree of plasticity, and can, under specific environmental conditions, acquire the phenotype of effector T cells. In particular, recent works have highlighted the acquisition of a Th1-like phenotype by Tregs in several pathological environments. In this review we give an update on the concept of Treg plasticity and the advances in defining the molecular mechanisms that underlie the generation of Th1-like Tregs during an immune response and in different disease settings.


title: Sumoylation regulates diverse biological processes

text: Ten years after its discovery, the small ubiquitin-like protein modifier (SUMO) has emerged as a key regulator of proteins. While early studies indicated that sumoylation takes place mainly in the nucleus, an increasing number of non-nuclear substrates have recently been identified, suggesting a wider stage for sumoylation in the cell. Unlike ubiquitylation, which primarily targets a substrate for degradation, sumoylation regulates a substrate’s functions mainly by altering the intracellular localization, protein-protein interactions or other types of post-translational modifications. These changes in turn affect gene expression, genomic and chromosomal stability and integrity, and signal transduction. Sumoylation is counter-balanced by desumoylation, and well-balanced sumoylation is essential for normal cellular behaviors. Loss of the balance has been associated with a number of diseases. This paper reviews recent progress in the study of SUMO pathways, substrates, and cellular functions and highlights important findings that have accelerated advances in this study field and link sumoylation to human diseases.


title: Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines

text: In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies). We report here that injection of naked β-globin untranslated region (UTR)-stabilized mRNA coding for β-galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the requirement of antiviral, antibacterial or antitumor immunity.


title: Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane

text: Alphavirus budding is driven by interactions between nucleocapsids assembled in the cytoplasm and envelope proteins present at the plasma membrane. So far, the expression of capsid and envelope proteins in infected cells has been considered an absolute requirement for alphavirus budding and propagation. In the present study, we show that Semliki Forest virus and Sindbis virus lacking the capsid gene can propagate in mammalian and insect cells. This propagation is mediated by the release of infectious microvesicles (iMVs), which are pleomorphic and have a larger size and density than wild-type virus. iMVs, which contain viral RNA inside and viral envelope proteins on their surface, are released at the plasma membrane and infect cells using the endocytic pathway in a similar way to wild-type virus. iMVs are not pathogenic in immunocompetent mice when injected intravenously, but can infect different organs like lungs and heart. Finally, we also show that alphavirus genomes without capsid can mediate the propagation of heterologous genes, making these vectors potentially interesting for gene therapy or vaccination studies. The minimalist infectious system described in this study shows that a self-replicating RNA able to express membrane proteins with binding and fusion properties is able to propagate, providing some insights into virus evolution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-016-2230-1) contains supplementary material, which is available to authorized users.


Infektionen und Impfungen in der Gynäkologie und Geburtshilfe


title: Caliciviren Virale Auslöser akuter Gastroenteritiden: Virale Auslöser akuter Gastroenteritiden

text: Human caliciviruses are highly infectious and co-circulate worldwide. They are responsible for many individual cases and extensive outbreaks of acute gastroenteritis. The ability of the viruses to survive in the environment facilitates the fecal-oral spread through water, food, aerosols, and person-to-person contact. Therefore, they are an important global public health problem. Despite the lack of a cell culture or animal model system to grow caliciviruses, great advances in our understanding of these pathogens, especially of the NLVs, have been made by using molecular methods. More and more information about the viral genome is being accumulated in data bases. This information will be used to develop sensitive molecular methods for the better understanding of the viral biology and epidemiology and will assist in developing strategies to prevent and control infections.


Abstracts 2017 der GNPI und DGPI


Corticosteroids for H1N1 associated acute lung injury: is it just wishful thinking?


title: Ethische Aspekte eines Influenzapandemiemanagements und Schlussfolgerungen für die Gesundheitspolitik: Ein Überblick

text: Infectious diseases are among the major global health threats. Although associated with these diseases there are vast ethical challenges, ethics has more focused on other health related issues – e.g. associated with rare diseases, embryo research, genetic diagnosis. Nowadays we are facing a possible influenza pandemic caused by a new human influenza virus subtype. This article presents issues and ethical challenges of the pandemic threat. The authors argue that it is necessary to consider ethical implications of pandemic influenza preparedness early on and to include ethical reasoning when deciding on the measures for the pandemic management.


Year in review in intensive care medicine, 2004. I. Respiratory failure, infection, and sepsis


ESPR 2004 - Oral Presentations


Abstract


Virus diseases in ICU patients: a long time underestimated; but be aware of overestimation


title: Viren im Trinkwasser

text: Viruses in drinking water can cause infectious diseases. In the past, hepatitis A and E were the most frequently observed drinking- water-borne viral infections, but in recent years several small- and large-scale norovirus epidemics have been described, even in Europe. All virus species spread via drinking water are of fecal origin. They are regularly identified in waste water even after conventional multi-stage water treatment. The approved disinfection methods can cope with these viruses if they are not integrated in larger particles. For this reason particle separation is particularly important in water treatment. Virological tests are not reliable enough to ensure that drinking water is sufficiently virus-free. The examination of 100 mL of water for E. coli and coliform bacteria is not adequate proof either. If potentially contaminated raw water is used, consumer safety must be ensured by calculating the performance of water treatment plants on a case-by-case basis. Such a calculation takes into account the virus load of the raw water, the efficiency of the physical and chemical particle elimination steps and the effect of disinfection. Those factors which determine the effectiveness of disinfection, namely concentration and exposure time or UV radiation strength, must be adjusted according to the risk of viral infection, and calculated settings must be adhered to, even if favorable E. coli levels may make them seem excessive.


title: Helicase-dependent isothermal amplification: a novel tool in the development of molecular-based analytical systems for rapid pathogen detection

text: Highly sensitive testing of nucleic acids is essential to improve the detection of pathogens, which pose a major threat for public health worldwide. Currently available molecular assays, mainly based on PCR, have a limited utility in point-of-need control or resource-limited settings. Consequently, there is a strong interest in developing cost-effective, robust, and portable platforms for early detection of these harmful microorganisms. Since its description in 2004, isothermal helicase-dependent amplification (HDA) has been successfully applied in the development of novel molecular-based technologies for rapid, sensitive, and selective detection of viruses and bacteria. In this review, we highlight relevant analytical systems using this simple nucleic acid amplification methodology that takes place at a constant temperature and that is readily compatible with microfluidic technologies. Different strategies for monitoring HDA amplification products are described. In addition, we present technological advances for integrating sample preparation, HDA amplification, and detection. Future perspectives and challenges toward point-of-need use not only for clinical diagnosis but also in food safety testing and environmental monitoring are also discussed. [Figure: see text]


title: Aufgaben und Funktion der Ständigen Arbeitsgemeinschaft der Kompetenz- und Behandlungszentren für hochkontagiöse, lebensbedrohliche Erkrankungen

text: The introduction of tropical diseases into Germany is becoming a more and more frequent public health problem due to increasing long distance travel and the globalization of economic activities. A network of centers of excellence for imported, highly contagious diseases has proven efficient and shown that the linking of public health service, clinical care, laboratory-based special diagnostics, ambulance service, and hospital hygiene can react quickly and professionally in even unexpected situations in clinical infectiology. These networks joined forces in the “Permanent Working Group of the Medical Competence and Treatment Centers“ (Ständigen Arbeitsgemeinschaft der Kompetenz- und Behandlungszentren, StAKoB). Not only in Germany but also worldwide, the StAKoB is a unique system for the treatment of imported highly contagious diseases. The goals and structure of the StAKoB are presented in this article.


title: Neues zur Pathophysiologie der Pneumonie

text: Pneumonia can lead to the critical impairment of gas exchange in the lung. Due to the great variability of pneumonia causing pathogens, a large variety of diverse virulence factors act on the lung. Besides stimulation of unspecific defense mechanisms, activation of receptor-dependent cell-mediated innate immune defense mechanisms are critical for the pulmonary immune defense. Pathogen-associated molecules are detected via transmembraneous and cytosolic receptors of the host. This interaction stimulates the expression of immunomodulatory molecules via signal cascades. Of particular importance, in addition to direct pathogen-caused lung damage, is the overwhelming activation of the inflammatory response which can result in lung barrier failure and impairment of pulmonary gas exchange. In addition to the design of new antibiotics, innovative therapeutic strategies should therefore concentrate on the enhancement of antimicrobial mechanisms by concurrent limitation of inflammation.


title: Chapter 2. Surge capacity and infrastructure considerations for mass critical care

text: PURPOSE: To provide recommendations and standard operating procedures for intensive care unit (ICU) and hospital preparations for a mass disaster or influenza epidemic with a specific focus on surge capacity and infrastructure considerations. METHODS: Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including surge capacity and infrastructure considerations. RESULTS: Key recommendations include: (1) hospitals should increase their ICU beds to the maximal extent by expanding ICU capacity and expanding ICUs into other areas; (2) hospitals should have appropriate beds and monitors for these expansion areas; hospitals should develop contingency plans at the facility and government (local, state, provincial, national) levels to provide additional ventilators; (3) hospitals should develop a phased staffing plan (nursing and physician) for ICUs that provides sufficient patient care supervision during contingency and crisis situations; (4) hospitals should provide expert input to the emergency management personnel at the hospital both during planning for surge capacity as well as during response; (5) hospitals should assure that adequate infrastructure support is present to support critical care activities; (6) hospitals should prioritize locations for expansion by expanding existing ICUs, using postanesthesia care units and emergency departments to capacity, then step-down units, large procedure suites, telemetry units and finally hospital wards. CONCLUSIONS: Judicious planning and adoption of protocols for surge capacity and infrastructure considerations are necessary to optimize outcomes during a pandemic.


title: Public-Health-Ethik: Bedarf und Diskurs in Deutschland

text: The international discourse about public health ethics is becoming more intensive and complex. The starting point is bioethics. The debate about public health ethics is simultaneously a debate about an adequate identity of public health, its goals, tasks and standards. In Germany there is a tremendous need to take part in this discourse. German experiences within the traditions of social medicine, social hygiene and medical ethics could significantly contribute to the international discussion. Unfortunately the German speaking public health community has hardly acknowledged the topic of ethics. The reasons for this are not explicitly known. The Angloamerican discourse is much more developed, but the concepts, terms and paradigms should not simply be transferred. They should critically be proven.


title: The synthetic and therapeutic expedition of isoxazole and its analogs

text: Isoxazole, constituting an important family of five-membered heterocycles with one oxygen atom and one nitrogen atom at adjacent positions is of immense importance because of its wide spectrum of biological activities and therapeutic potential. It is, therefore, of prime importance that the development of new synthetic strategies and designing of new isoxazole derivatives should be based on the most recent knowledge emerging from the latest research. This review is an endeavor to highlight the progress in the chemistry and biological activity of isoxazole derivatives which could provide a low-height flying bird’s eye view of isoxazole derivatives to the medicinal chemists for the development of clinically viable drugs using this information.


Was man von Viren lernen kann


ACUTE LEUKEMIAS XV: Biology and Treatment Strategies Munich, Germany, February 22– 25, 2015


title: Die telefonische infektionsepidemiologische Bund-Länder-Lagekonferenz in Deutschland: Eine Zwischenbilanz nach drei Quartalen 2009

text: Public health threats are increasingly triggered by events which span across international, national and state level jurisdictions. Innovative surveillance methods are needed to ensure adequate and timely response to such threats. In January 2009 the Department of Infectious Disease Epidemiology at the Robert Koch Institute (RKI) established a system of weekly telephone conferences with all competent authorities of the German federal states to identify, discuss and respond to infectious disease events in real-time. A regular and structured platform was developed for use between participants from state level public health authorities, the military and the RKI. During the first three quarters, 46 infectious diseases were covered, including mandatory reports of measles and meningococcal meningitis and outbreaks of cowpox, which does not have to be notified in Germany. Results of a targeted evaluation and a consistently high attendance rate both indicate that the teleconference has met additional needs for supplemental information exchange among participants. The telephone conference has proven to be a useful resource for rapid and direct communication, coordination and evaluation of signals for public health events in Germany.


title: Ausbildungsprogramme für angewandte Epidemiologie in Deutschland und Europa: Eine lohnende Investition für die Zukunft

text: Outbreaks of infectious diseases such as SARS and influenza can have a profound impact on society. Therefore, training epidemiologists in infectious diseases control is of crucial importance. The German Postgraduate training in Applied Epidemiology (PAE) at the Robert Koch Institute (RKI) and the European Programme for Intervention Epidemiology Training (EPIET) are striving to meet these challenges. Currently, 27 and 12 persons of German origin have joined PAE and EPIET, respectively. A total of 17 out of the 36 alumni started working at the RKI, regional or local German health authorities after completing their training. Since 2006, the number of yearly admitted fellows increased from 3 to 6 in PAE, and 9 to 19 in EPIET and 5 state health departments have been added as training sites. The collaboration between EPIET and PAE has been strengthened and diversified in recent years. Alumni of these programs will play a key role in the control of infectious diseases in Germany and Europe.


Stellungnahme zur Gewinnung und Nutzung von Rekonvaleszentenplasma (RKP) als Therapieoption bei Ausbrüchen schwerer Infektionen


title: Infektionskrankheiten und ihre Codierung: Was kann sich durch die ICD-11 verbessern?

text: The revision of the International Classification of Diseases (ICD) could change morbidity and mortality statistics significantly, which also affects the area of infectious diseases. Infectious diseases are classified according to their etiology, affected body system or the life period during which the episode occurs. Specific challenges arise from emerging pathogens and the respective necessary adaptation. For epidemiologic analysis ICD-10 does not always offer enough additional information. ICD provides the basis for international comparison of infectious disease morbidity and mortality statistics, but it is also used to collect data for surveillance and research purposes, e. g. the notification system for infectious diseases, syndromic surveillance systems and the evaluation of data quality by using secondary data sources. ICD-11 offers the chance to better represent epidemiological concepts of infectious diseases by adding more relevant information as affected body system or manifestation. Due to the complexity of coding, ensuring continuity of morbidity and mortality statistics could be challenging.


title: Epidemien und Pandemien in der hausärztlichen Praxis: Was können wir aus dem Schweinegrippe (H1N1)- und EHEC-Ausbruch lernen?

text: BACKGROUND: As primary care givers with a coordinating function, general practitioners (GP) play a key role in dealing with epidemics and pandemics. As of yet, there are no studies in Germany describing the difficulties experienced by GPs in patient care during epidemics/pandemics. OBJECTIVES: This study aimed at identifying the problem areas in GPs’ patient care during the H1N1 and EHEC (enterohemorrhagic strain of Escherichia coli) outbreaks. With this information, recommendations for guaranteeing proper patient care during future epidemics/pandemics can be derived. MATERIALS AND METHODS: In all, 12 qualitative, semi-structured, open guideline interviews with GPs in Hamburg and Lübeck were conducted, transcribed, and evaluated with qualitative content analysis. RESULTS: Five areas in ambulatory patient care were identified in which changes are needed from the primary care perspective: provision of information for GPs, workload, financing of epidemic-related measures, organization of the practices, care of those taken ill. CONCLUSIONS: The workload of GPs in particular can and should be reduced through successful, centralized information distribution during epidemics/pandemics. The GP’s function as a coordinator should be supported and consolidated, in order to relieve the in-patient sector in cases of an epidemic/pandemic. Secured financing of epidemic-associated measures can help ensure patient care.


title: Strukturelle Erfordernisse für das Management von Patienten mit hochkontagiösen, lebensbedrohlichen Erkrankungen – Update 2015

text: The care of highly contagious life-threatening infectious diseases (HLID) requires specialized treatment facilities that are capable of strict isolation measures and appropriate medical treatment. The German approach to the management of these diseases, which is maintained by the Permanent Working Group of Medical Competence and Treatment Centers for Highly Contagious and Life-Threatening Diseases (STAKOB) is adjusted in the present publication with regards to recent experiences and upcoming needs. Clear synergies in using infrastructures and bundling of resources have led to similar efforts at the European level. The German concept, therefore, has a pioneering role. This update is intended to improve professional patient care and also minimize the risk of disease spread and transmission.


title: Infektiöse Lungenerkrankungen

text: Infectious pulmonary diseases and pneumonias are important causes of death within the group of infectious diseases in Germany. Most cases are triggered by bacteria. The morphology of the inflammation is often determined by the agent involved but several histopathological types of reaction are possible. Histology alone is only rarely able to identify the causal agent; therefore additional microbiological diagnostics are necessary in most cases. Clinically cases are classified as community acquired and nosocomial pneumonia, pneumonia under immunosuppression and mycobacterial infections. Histologically, alveolar and interstitial as well as lobar and focal pneumonia can be differentiated.


title: Zoonotische Infektionen beim Menschen: Übersicht über die epidemiologische Situation in Deutschland

text: Zoonoses are infectious diseases that can be transmitted from vertebrate animals to humans. Their significance lies in the large number of cases that occur, the high case fatality ratio of certain zoonoses, and the potential for some pathogens as yet restricted to animal hosts to cross the species barrier and infect humans. Changing habits in food production (for example, intensive animal husbandry) and food consumption as well as demographic, climatic, and ecological factors contribute to the spread of zoonotic pathogens. Several zoonoses are notifiable in Germany according to the Protection Against Infection Act enacted 1 January 2001. The European Commission issued a new directive on the monitoring of zoonoses and zoonotic agents on 17 November 2003. There is ongoing need to develop further measures to prevent and control zoonotic diseases on a national as well as international basis.


title: Surveillance gemäß den Internationalen Gesundheitsvorschriften (2005)

text: The International Health Regulations (IHR 2005) are a legally binding agreement that was adopted by all WHO Member States and which entered into force in June 2007. While taking the challenges of a globalized world into consideration, the purpose of the IHR (2005) is to provide a framework for international efforts to contain or reduce the risk from public health threats that may spread between countries. To this end, the IHR (2005) contain rights and obligations for the States and for WHO concerning national and international surveillance, assessment and public health response. With respect to surveillance, States are required to notify WHO of all events “that may constitute a public health emergency of international concern” according to agreed criteria. This obligation applies to novel or evolving public health risks, taking into account the context in which the event occurs. The IHR (2005) also contain obligations regarding global preparedness to address public health threats which include the establishment of national capacity to both detect and respond to events by June 2012.


An overview on severe infections in Europe


title: Kommunen, Länder, Bund und Europäische Gemeinschaft: Zuständigkeiten und Aufgaben bei Seuchennotfällen im Kontext der neuen Internationalen Gesundheitsvorschriften

text: Pandemic preparedness has become a catch phrase for politicians, government agencies and communities, both nationally and internationally. This is due to the increasing number of infectious diseases emergencies that are important challenges for health protection authorities, which was shown impressively when SARS emerged as the first pandemic in this millennium. In Germany, effective and efficient infection control is complex, with local health protection authorities having their own responsibilities. In the case of an emergency epidemic, regional health departments are responsible. Having authority over these are authorities on the federal state level as well as on the federal level. For the European Community, the European Centre for Disease Prevention and Control (ECDC) was established. The mission of this agency is to identify, assess and communicate current and emerging threats to human health posed by infectious diseases.


Das schwere akute Atemwegssyndrom


9th EBSA European Biophysics Congress, 13-17 July 2013, Lisbon, Portugal - Abstracts


Virusinfektionen in der Schwangerschaft und im Wochenbett


Antiinfektive Therapie/Neue antiinfektive Substanzen


title: Evidence for a prokaryotic insertion-sequence contamination in eukaryotic sequences registered in different databases

text: An insertion-sequence of prokaryotic origin was detected in a genomic clone obtained from a Phaseolus vulgaris bacterial artificial chromosome (BAC) library. This BAC clone, characterized as part of a contig constructed near a virus resistance gene, exhibited restriction fragment length polymorphism with an overlapping clone of the contig. Restriction analysis of DNA obtained from individual colonies of the stock culture indicated the presence of a mixed population of wild-type and insertional mutants. Sequence analysis of both members of the population revealed the presence of IS10R, an insertion-sequence from Escherichia coli. A BLAST search for IS10-like sequences detected unexpected homologies with a large number of eukaryotic sequences from Homo sapiens, Arabidopsis thaliana, Drosophila melanogaster and Caenorhabditis elegans. Southern analysis of a random sample of BAC clones failed to detect IS10 in the BAC DNA. However, prolonged sub-culturing of a set of 15 clones resulted in transposition into the BAC DNA. Eventually, all cultures acquired a 2.3-kb fragment that hybridized strongly with IS10. Sequence analysis revealed the presence of a preferred site for transposition in the BAC vector. These results indicate that a large number, if not all, of the BAC libraries from different organisms are contaminated with IS10R. The source of this element has been identified as the DH10B strain of E. coli used as the host for BAC libraries.


title: Early diagnosis and treatment of steroid-induced osteonecrosis of the femoral head

text: OBJECTIVE: This study aims to investigate the early diagnosis and treatment of steroid-induced osteonecrosis of the femoral head. PATIENTS AND METHODS: From January 2010 to January 2014, a total of 350 patients, who required the use of large amounts of hormones, were enrolled into the study. These patients were followed up every three months after starting the hormone therapy. A total of 62 cases were screened, among which nine cases were asymptomatic. Furthermore, 38 patients were diagnosed as stage I and were given low-molecular weight heparin (LMWH) and vasodilator drugs. Moreover, 22 cases were diagnosed as stage IIa/b and underwent core decompression. In addition, two cases were diagnosed as stage IIc and underwent pedicled bone transplantation. During the follow-up period, ARCO staging was used for radiological evaluation, the HHS score was applied to evaluate for clinical efficacy, and SPSS 22.0 statistical software was used for the data analysis. RESULTS: A total of 60 patients were followed up for 24 months. Among these patients, 38 patients were diagnosed with ARCO stage I and underwent systematic therapy. No progress was found in 29 cases (76.3%). Furthermore, three cases progressed to stage IIb (7.8%), four cases progressed to stage IIc (10.5%), two cases progressed to stage III and IV, respectively (2.6%), and 16 cases (80%) did not progress after core decompression. In the 16 cases at stage IIa and four cases at stage IIb, and four cases (20%) progressed in stage III. The HHS score of stage I was 80.42 ± 3.25 before follow-up, while the HHS score was 86.46 ± 8.54 after follow-up, and the difference was statistically significant (P < 0.05). Furthermore, the HHS score of patients with stage IIa/b was 70.38 ± 4.62 before follow-up, while the HHS score was 80.28 ± 6.72 after follow-up, and the difference was statistically significant (P < 0.01). CONCLUSION: MRI remains as the most effective method for the non-invasive diagnosis of osteonecrosis, at present. Enhanced MRI may be able to detect early osteonecrosis, but further research is needed. Drug treatment and core decompression can achieve satisfactory results at the early stage.


title: Innovationen in der Leberchirurgie durch die Transplantation mit Lebendspende

text: Living-donor liver transplantation was introduced into clinical practice in the early 1990s. At first the results were unsatisfactory, but today's results after living donation are as good as those obtained after conventional liver transplantation with full-sized organs. With minimally invasive diagnostic methods, it is now possible to determine the quality of potential donor livers and exclude focal lesions and anatomical variants which influence the strategy of organ retrieval procedures. Donor liver resection is done without hilar occlusion after determining the anatomical variants of the bile system (especially for right lobes) and localizing of the course of the middle hepatic vein. Microsurgical techniques are used for reconstruction of the biliary system and hepatic vessels. Living-donor liver transplantation allows us to investigate the complex changes after liver resection. The surgical techniques and pathophysiological postoperative changes can be adapted unconventionally to complex oncological liver resections. Therapeutic optimization and better risk management are becoming possible for liver resections.


Erweiterte Reanimationsmaßnahmen für Erwachsene (ALS)


title: Adaptive evolution of virus-sensing toll-like receptor 8 in bats

text: Recently, bats have gained attention as potential reservoir hosts for emerging zoonotic single-stranded (ssRNA) viruses that may prove fatal for humans and other mammals. It has been hypothesized that some features of their innate immune system may enable bats to trigger an efficient early immune response. Toll-like receptors (TLRs) represent a first line defense within the innate immune system and lie directly at the host–pathogen interface in targeting specific microbe-molecular patterns. However, the direction and strength of selection acting on TLRs are largely unknown for bats. Here, we studied the selection on viral ssRNA sensing TLR8 based on sequence data of 21 bat species. The major part (63 %) of the TLR8 gene evolved under purifying selection, likely due to functional constraints. We also found evidence for persistent positive selection acting on specific amino acid sites (7 %), especially when compared to viral TLR evolution of other mammals. All of these putatively positively selected codons were located in the ligand-binding ectodomain, some coincidenced or were in close proximity to functional sites, as suggested by the crystallographic structure of the human TLR8. This might contribute to the inter-species variation in the ability to recognize molecular patterns of viruses. TLR8 evolution within bats revealed that branches leading to ancestral and recent lineages evolved under episodic positive selection, indicating selective selection pressures in restricted bat lineages. Altogether, we found that the TLR8 displays extensive sequence variation within bats and that unique features separate them from humans and other mammals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00251-016-0940-z) contains supplementary material, which is available to authorized users.


title: Microfluidics in macro-biomolecules analysis: macro inside in a nano world

text: Use of microfluidic devices in the life sciences and medicine has created the possibility of performing investigations at the molecular level. Moreover, microfluidic devices are also part of the technological framework that has enabled a new type of scientific information to be revealed, i.e. that based on intensive screening of complete sets of gene and protein sequences. A deeper bioanalytical perspective may provide quantitative and qualitative tools, enabling study of various diseases and, eventually, may offer support for the development of accurate and reliable methods for clinical assessment. This would open the way to molecule-based diagnostics, i.e. establish accurate diagnosis and disease prognosis based on identification and/or quantification of biomacromolecules, for example proteins or nucleic acids. Finally, the development of disposable and portable devices for molecule-based diagnosis would provide the perfect translation of the science behind life-science research into practical applications dedicated to patients and health practitioners. This review provides an analytical perspective of the impact of microfluidics on the detection and characterization of bio-macromolecules involved in pathological processes. The main features of molecule-based diagnostics and the specific requirements for the diagnostic devices are discussed. Further, the techniques currently used for testing bio-macromolecules for potential diagnostic purposes are identified, emphasizing the newest developments. Subsequently, the challenges of this type of application and the status of commercially available devices are highlighted, and future trends are noted.


Aufrechterhaltung der Versorgung mit Blutprodukten im Falle einer Influenza-Pandemie


Mitteilungen der DGKJ und ÖGKJHK


title: Pandemic risk prevention in European countries: role of the ECDC in preparing for pandemics: Development and experience with a national self-assessment procedure, 2005–2008

text: To be effective risk prevention work takes place well before pandemics through the three Ps: Planning, Preparedness and Practise. Between 2005 and 2008 the European Centre for Disease Prevention and Control (ECDC) worked with the European Commission (EC) and the WHO Regional Office for Europe (WHO-Euro) to assist European countries in preparing themselves for a future influenza pandemic. All eligible countries in the European Union and European Economic Area participated with energy and commitment. Indicators of preparedness were developed based on WHO planning guidance and these were set within a simple assessment which included a formal country visit. The procedure evolved considerably with field experience. As the complexity of pandemic preparedness was appreciated it changed from being a classical short external assessment to longer national self-assessments with demonstrable impact, especially when self-assessments were published. There were essential supporting activities undertaken including a series of pan-European pandemic preparedness workshops organised by EC, WHO-Euro, ECDC and countries holding the European Union Presidency. The self-assessments highlighted additional work and documentation that was needed by national authorities from the ECDC. This work was undertaken and the document produced. The benefits of the self-assessments were seen in the 2009 pandemic in that EU/EEA countries performed better than some others. A number of the guidance documents were updated to fit the specific features of the pandemic. However the pandemic revealed many weaknesses and brought new challenges for European countries, notably over communication and vaccines, the need to prepare for a variety of scenarios and to factor severity estimates into preparedness, to improve surveillance for severe disease and to deliver seroepidemiology. Any revised self-assessment procedure will need to respond to these challenges.


title: Chapter 1. Introduction

text: BACKGROUND: In December 2007, the European Society of Intensive Care Medicine established a Task Force to develop standard operating procedures (SOPs) for operating intensive care units (ICU) during an influenza epidemic or mass disaster. PURPOSE: To provide direction for health care professionals in the preparation and management of emergency ICU situations during an influenza epidemic or mass disaster, standardize activities, and promote coordination and communication among the medical teams. METHODS: Based on a literature review and contributions of content experts, a list of essential categories for managing emergency situations in the ICU were identified. Based on three cycles of a modified Delphi process, consensus was achieved regarding the categories. A primary author along with an expert group drafted SOPs for each category. RESULTS: Based on the Delphi cycles, the following key topics were found to be important for emergency preparedness: triage, infrastructure, essential equipment, manpower, protection of staff and patients, medical procedures, hospital policy, coordination and collaboration with interface units, registration and reporting, administrative policies and education. CONCLUSIONS: The draft SOPs serve as benchmarks for emergency preparedness and response of ICUs to emergencies or outbreak of pandemics.


title: Das Auftreten alter und neuer Seuchen als Konsequenz menschlichen Handelns

text: In the era of antibiotics and vaccines and prior to the appearance of AIDS, well-known infectious diseases received decreasing clinical attention. Occasionally, the opinion was also expressed that new types of infectious diseases could no longer be expected. However, a more detailed analysis of the state of infectious diseases yields quite a different picture. A variety of new infectious diseases has clinically been defined over the last few decades. New viruses, bacteria, and parasites with pathogenic potential for humans have been detected and well-known microorganisms have spread beyond their original geographic areas. Infectious agents, in particular viruses, permanently alter their genomes and may thus gain new clinical relevance. This article demonstrates that primarily the behavior of man influenced the nature and distribution of infectious diseases in the past and will affect the spread of infectious diseases in the future.


title: Das Renin–Angiotensin–Aldosteron–System – komplexer als bisher gedacht

text: BACKGROUND: Angiotensin II (ANG II) is an important factor for the progression of renal diseases. ANG II has many pleiotropic effects on the kidney such as pro–inflammatory and profibrotic actions besides the well–known blood pressure–increasing effect. NOVEL KNOWLEDGE: Organs have local ANG II–generating systems that work independently from their classic systemic counterpart. Renal proximal tubular cells could generate and secrete ANG II into the urine in concentrations that are 10,000 times higher than those found in serum. These local systems are only incompletely blocked by currently used doses of ACE inhibitors or AT(1) antagonists. There are other enzyme systems besides ACE that contribute to the formation of ANG II. Alternative pathways generate peptides such as angiotensin 1–7 that have antagonistic effect compared with ANG II. Degradation products of ANG II such as angiotensin IV bind at separate receptors and could mediate fibrosis. The discovery of AT(1) receptor dimers and agonistic antibodies against AT(1) receptors contributes to the complexity of the system. CLINICAL RELEVANCE: The complexity of the renin–angiotensin–aldosterone system (RAAS) implies that dual blockade with ACE inhibitors and AT(1) receptor antagonists makes sense for pathophysiological reasons. First clinical studies have shown that such as dual therapy reduces progression of chronic renal disease more efficiently that the respective monotherapies in certain risk populations. This shows that novel pathophysiological data could lead to innovative clinical treatment strategies.


title: Design and application of GB virus C (GBV-C) peptide microarrays for diagnosis of GBV-C/HIV-1 co-infection

text: The main objectives of the design of GB virus C (GBV-C) peptide microarrays are the miniaturisation of antigen–antibody interaction assays, the simultaneous analysis of several peptide sequences and the reduction in the volume of serum required from patients since this always represents a limiting factor in studies to develop new systems for diagnosing human diseases. We herein report the design of a microarray immunoassay based on synthetic peptides derived from the GBV-C E2 protein to evaluate their diagnostic value in detecting anti-E2 antibodies in HIV-1 patients. To this end, peptide microarrays were initially prepared to identify the most relevant epitopes in the GBV-C E2 protein. Thus, 124 peptides composed of 18 amino acids covering the whole E2-protein sequence, with 15 residue overlaps, were spotted in triplicate onto γ-aminopropyl silane-functionalised adsorbent binding slides. The procedure to select the E2 protein epitopes was carried out using serum samples from HIV-1-infected patients. The samples had previously been tested for the presence or absence of GBV-C anti-E2 antibodies by means of the Abbott test. Thus, 11 specific epitopes in the GBV-C E2 protein were identified. Subsequently, peptide antigen microarrays were constructed using the E2 epitopes identified to detect GBV-C anti-E2 antibodies in the serum of HIV-1-infected patients with no known GBV-C co-infection. The 11 peptides selected identified anti-E2 GBV-C antibodies among HIV-1-infected patients, and a reactivity of 47 % was established. The potential antigenic peptides selected could be considered a useful tool for designing a new diagnostic system based on peptide microarrays to determine anti-GBV-C E2 antibodies in the serum of HIV-1-infected patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00216-012-6585-3) contains supplementary material, which is available to authorized users.


Influenzapandemieplanung: Nationaler Influenzapandemieplan


title: Haben HIV-Positive eine besondere Verantwortung?: Ein Diskussionsbeitrag

text: In the 1980s, most Western countries decided to opt for a new public health approach based on learning strategies to fight HIV/AIDS. Within the new public health paradigm, every sexually active person protects him-/herself, whereas it is the infected people that bear the burden of prevention according to old public health. The paper begins with a clear statement for the new public health approach that includes self-protection and the protection of civil rights. It argues that this approach is still valid under the changing circumstances due to combination therapies and the developments related to them, such as the introduction of routine HIV screening in some countries. On this background, the paper examines from an ethical perspective to what extent people with HIV have a responsibility in HIV prevention. The paper argues that a person with HIV has a responsibility to protect his/her partner in the case of a relationship of love. On the other hand, in the case of "purely" sexual encounters, each person is responsible for his/her own security and should not rely on the other. This position also helps to clarify prevention messages. In conclusion, the paper shows how morality evolves into ethical positions and then translates into the law. It finally claims for stronger obligations for sex businesses to support HIV prevention.


Abstracts der 112. Jahrestagung der Deutschen Gesellschaft für Kinder- und Jugendmedizin (DGKJ). Gemeinsam mit der 68. Jahrestagung der Deutschen Gesellschaft für Sozialpädiatrie (DGSPJ), 54. Herbsttagung der Deutschen Gesellschaft für Kinderchirurgie (DGKCH), 38. Jahrestagung des Berufsverbandes Kinderkrankenpflege Deutschland (BeKD) und 31. Jahrestagung der Gesellschaft für Pädiatrische Gastroenterologie und Ernährung (GPGE)


title: Exact epidemic models on graphs using graph-automorphism driven lumping

text: The dynamics of disease transmission strongly depends on the properties of the population contact network. Pair-approximation models and individual-based network simulation have been used extensively to model contact networks with non-trivial properties. In this paper, using a continuous time Markov chain, we start from the exact formulation of a simple epidemic model on an arbitrary contact network and rigorously derive and prove some known results that were previously mainly justified based on some biological hypotheses. The main result of the paper is the illustration of the link between graph automorphisms and the process of lumping whereby the number of equations in a system of linear differential equations can be significantly reduced. The main advantage of lumping is that the simplified lumped system is not an approximation of the original system but rather an exact version of this. For a special class of graphs, we show how the lumped system can be obtained by using graph automorphisms. Finally, we discuss the advantages and possible applications of exact epidemic models and lumping.


title: Role of environmental persistence in pathogen transmission: a mathematical modeling approach

text: Although diseases such as influenza, tuberculosis and SARS are transmitted through an environmentally mediated mechanism, most modeling work on these topics is based on the concepts of infectious contact and direct transmission. In this paper we use a paradigm model to show that environmental transmission appears like direct transmission in the case where the pathogen persists little time in the environment. Furthermore, we formulate conditions for the validity of this modeling approximation and we illustrate them numerically for the cases of cholera and influenza. According to our results based on recently published parameter estimates, the direct transmission approximation fails for both cholera and influenza. While environmental transmission is typically chosen over direct transmission in modeling cholera, this is not the case for influenza.


Abstracts der ÖGKJ zur 47. Jahrestagung


Händehygiene in Einrichtungen des Gesundheitswesens: Empfehlung der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut (RKI)


title: Angst essen Impfbereitschaft auf?: Der Einfluss kognitiver und affektiver Faktoren auf die Risikowahrnehmung im Ausbruchsgeschehen

text: During the influenza pandemic in 2009 individuals had the choice of either receiving a vaccination or running the risk of becoming infected with the pandemic influenza virus A (H1N1). For many individuals knowledge of a likely infection and possibly serious health consequences stood in contrast to a vague fear of the vaccination itself. What has a stronger influence on the decision to be vaccinated: the cognitive estimation of risk or the feeling of risk? Based on data collected during the 2009 influenza A (H1N1) pandemic we tested the relative influence of the cognitive and affective aspects of risk on estimation of the individual willingness to be vaccinated. In doing so we also focused on fear. The results indicate that the feeling of risk had a significant effect on the willingness to be vaccinated. In contrast, the classic, cognitive estimation of a risk was no longer a significant predictor when the feeling of risk was also used to predict the willingness to be vaccinated. A highly felt risk to become infected with influenza A (H1N1) substantially increased the willingness to be vaccinated. A highly felt risk regarding the vaccination, on the other hand, decreased the willingness to be vaccinated. Fear of the vaccination significantly decreased the willingness to be vaccinated even when fear of the spreading disease was also very high. The implications of the results for crisis communications will also be discussed.


Empfehlungen zur intensivmedizinischen Therapie von Patienten mit COVID-19


title: Evolutionary dynamics of HIV at multiple spatial and temporal scales

text: Infectious diseases remain a formidable challenge to human health, and understanding pathogen evolution is crucial to designing effective therapeutics and control strategies. Here, we review important evolutionary aspects of HIV infection, highlighting the concept of selection at multiple spatial and temporal scales. At the smallest scale, a single cell may be infected by multiple virions competing for intracellular resources. Recombination and phenotypic mixing introduce novel evolutionary dynamics. As the virus spreads between cells in an infected individual, it continually evolves to circumvent the immune system. We discuss evolutionary mechanisms of HIV pathogenesis and progression to AIDS. Viral spread throughout the human population can lead to changes in virulence and the transmission of immune-evading variation. HIV emerged as a human pathogen due to selection occurring between different species, adapting from related viruses of primates. HIV also evolves resistance to antiretroviral drugs within a single infected host, and we explore the possibility for the spread of these strains between hosts, leading to a drug-resistant epidemic. We investigate the role of latency, drug-protected compartments, and direct cell-to-cell transmission on viral evolution. The introduction of an HIV vaccine may select for viral variants that escape vaccine control, both within an individual and throughout the population. Due to the strong selective pressure exerted by HIV-induced morbidity and mortality in many parts of the world, the human population itself may be co-evolving in response to the HIV pandemic. Throughout the paper, we focus on trade-offs between costs and benefits that constrain viral evolution and accentuate how selection pressures differ at different levels of selection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-012-0892-1) contains supplementary material, which is available to authorized users.


title: Infektionsprävention durch Hygiene zu Hause und in der Öffentlichkeit: Die Notwendigkeit für eine familienzentrierte Strategie

text: Over the past 20 years, infectious disease has moved back up the health agenda, prompting new emphasis on developing strategies for prevention and control, including reduction of spread of infection within the family at home and in their social and work lives outside the home. This paper reviews the various issues that have contributed to this trend. In response to the need for a science-based approach to home hygiene, the International Scientific Forum on Home Hygiene has developed an approach based on risk management which involves identifying the critical control points for preventing the spread of infectious diseases in the home. If we are to be successful in achieving behaviour change in the community, we need to develop a family-centred approach which ensures an understanding of infectious disease agents and their mechanism of spread.


Abstracts: 8th EBSA European Biophysics Congress, August 23rd–27th 2011, Budapest, Hungary


title: Erster Erfahrungsaustausch zur H1N1-Pandemie in Deutschland 2009/2010: Bericht über einen Workshop am 22. und 23. März 2010 in Berlin

text: In April 2009 the first pandemic of the 21st century developed within a few weeks starting from Mexico. Its first wave reached Germany in autumn 2009 and was responsible for 1.8–3.5 million additional medical consultations. For the public health sector, this pandemic was one of the largest challenges of the last few decades. As a contribution to broader evaluations on national and international level, the Robert Koch Institute invited representatives from different professions involved in the pandemic response to participate in a workshop on 22–23 March 2010. This workshop was structured in short presentations, group work, and plenary discussions. Main experiences were that (a) pandemic preparedness was helpful, (b) the early warning systems were reliable, (c) vaccines were available within a few months, however, in limited amounts. Need for improvement was discussed for (a) effectiveness of vaccination logistics, (b) mechanisms for the reimbursement of the cost of vaccination, (c) availability of surveillance and monitoring systems, (d) integration of physicians in decision-making processes and health education, and (e) proactive communication strategies. Investments in the above mentioned areas can help to improve public health protection in the future.


Empfehlung zur Prävention nosokomialer Infektionen bei neonatologischen Intensivpflegepatienten mit einem Geburtsgewicht unter 1500 g: Mitteilung der Kommission für Krankenhaushygiene und Infektionsprävention beim Robert Koch-Institut


title: Lage – Krise – Katastrophe. Eine Konzeptualisierung biologischer Gefahrenlagen

text: Unusual biological threats demand adequate preparedness efforts, as demonstrated, for example, by the Ebola virus disease outbreak in West Africa in 2014/2015 and pandemic influenza in 2009/2010. In Germany, responsibilities for such efforts are located in different governmental authorities and differ from state to state. As a result, there are many different preparedness approaches using divergent core terminology. In this article a common definition for the term “unusual biological incident” is proposed. To do so, a literature review as well as semi-structured expert interviews with representatives of central actors in Germany were conducted. The understanding of “unusual biological incident” was not consistent among experts; four approaches to qualify a biological incident as “unusual” were identified. These were merged in a comprehensive system-oriented approach that focuses on the health system’s resilience and on shortages of knowledge and material resources during incidents. Based on this approach, we suggest a stage model for the categorization of biological threats as “incident,” “crisis,” “severe crisis,” or “disaster.” The need for central coordination is a defining characteristic to qualify a biological incident as “unusual.” Based on the identified shortages, the necessary response strategies can be derived.


title: Bacterial survival in evaporating deposited droplets on a teflon-coated surface

text: Understanding of bacterial survival in aerosols is crucial for controlling infection transmission via airborne aerosols and/or large droplets routes. The cell viability changes of four bacteria species (Escherichia coli K12 JM109; Acinetobacter sp. 5A5; Pseudomonas oleovorans X5; and Staphylococcus aureus X8), three Gram-negative and one Gram-positive, in a large evaporating droplet of size 1,800 μm in diameter on teflon-coated slides were measured using the LIVE/DEAD BacLight solution and a microscope. Droplets of three levels of salinity (0, 0.9, and 36% w/v) were tested. All four species survived well during the droplet evaporation process, but died mostly at the time when droplets were dried out at 40–45 min. The final bacteria survival rate after droplets were completely dried was dependent on bacteria species and the salinity of the suspension solution. Droplet evaporation over the first 35–40 min had no adverse effect on bacterial survival for the droplets tested. The lethal effect of desiccation was found to be the most important death mechanism.


title: Systemische Infektionen in der Geburtshilfe

text: The importance of systemic infections in pregnancy is often underestimated. This is primarily due to the fact that pregnant women, in the majority of cases, do not notice any complaints or only have unspecific flu-like symptoms (e.g. toxoplasmosis). Serological screening within the framework of German maternity care is often insufficient to diagnose existing or emerging infections in time. However, the long-term consequences for the affected children and their parents can be immense. A serological TORCH analysis should be performed if a pregnant woman complains about any typical or unspecific symptoms on suspicion of an infection.


2008: Hygiene im Alltag


title: Seroprävalenz von Antikörpern gegen schwangerschaftsrelevante virale Infektionserreger bei Mitarbeiterinnen im Gesundheitswesen

text: Healthcare workers (HCWs) are exposed to infectious diseases throughout the course of their work. The concerns of pregnant HCWs are considerable because certain otherwise mild infections may affect fetal development. We studied 424 pregnant HCWs at the University Hospital Frankfurt between March 2007 and July 2011. Serological tests were carried out for varicella zoster virus (VZV), measles, mumps, rubella (MMR), cytomegalovirus (CMV) and parvovirus B19. Our overall seroprevalence data with regard to VZV, MMR, CMV and parvovirus B 19 corresponded to the general population. However, physicians demonstrated lower seroprevalence towards the two non-vaccine-preventable diseases (CMV: 37.5% [KI 27.4–48.5]; parvovirus B19: 69.3% [KI 58.6–78.7]) compared with nurses (CMV: 53.4% [KI 46.1–60.6], parvovirus B19: 75.1% [68.4–81.1]). It was striking that, only one in five of the study population showed IgG antibodies against all of the six pregnant-relevant viral diseases tested, of the physicians as few as one in six. A routine exclusion from the workplace due to non-immunity would mean that it would not be possible to employ the majority of pregnant staff in healthcare and childcare.


title: SUMO fusion system facilitates soluble expression and high production of bioactive human fibroblast growth factor 23 (FGF23)

text: As a key humoral regulator of phosphate homeostasis and its involvement in the pathogenesis of human disease, human fibroblast growth factor 23 (hFGF23) has become a particularly attractive therapeutic target. To prepare soluble and bioactive recombinant human FGF23 to meet the increasing demand in its pharmacological application, small ubiquitin-related modifier (SUMO)-FGF23 fusion gene and FGF23 non-fusion gene were amplified by standard PCR methods and cloned into vector pET-22b and pET-3c, then transformed into Escherichia coli Rosetta (DE3) and BL21 (DE3). The best combination of plasmid and host strain was screened, and only Rosetta (DE3)/pET-SUMO-FGF23 was screened for rhFGF23 protein expressed. The average bacterial yield and the soluble expression level of recombinant hFGF23 of three batches attained 687 ± 18 g and 30 ± 1.5%, respectively, after treatment with 0.4 mM isopropyl-thio-β-galactopyranoside for 19 h at 16 °C in a 30-L fermentor, after which it was purified by DEAE Sepharose FF and nickel nitrilotriacetic acid affinity chromatography. Once cleaved by the SUMO protease, the recombinant human FGF23 was released from the fusion protein. The purity of rFGF23 was shown by high performance liquid chromatography to be greater than 90% and the yield was 60 ± 1.5 mg/L. In vitro data showed that the purified rFGF23 can induce the phosphorylation of mitogen-activated protein kinases in the glioma U251 cell. The results of in vivo animal experiments also showed that rFGF23 could decrease the concentration in the plasma of normal rats fed with a fixed formula diet. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-011-3864-4) contains supplementary material, which is available to authorized users.


title: Fünf Jahre Empfehlungen der Kommission für Krankenhaushygiene zur Aufbereitung flexibler Endoskope: Blick zurück und Blick nach vorn(1)

text: In a short review the national and international reception of the German guidelines for reprocessing flexible endoscopes is presented. The recommendations of the guidelines are discussed in view of recent knowledge on old problems such as prion inactivation and new infectious diseases and new microorganisms such as SARS, avian influenza and C. difficile. New disinfectants and new methods for endoscope disinfection are mentioned, the importance of careful cleaning is underlined. The German guidelines of the Robert Koch Institute and the US Multi-Society guidelines, published in 2003, are compared. The discrepancies concerning recommendations for water quality for final rinsing and need of microbiological controls of endoscope reprocessing are stressed. Aspects not mentioned in the German guidelines, e.g. duration of storage after reprocessing and risk of infection transmission by the endo-washer, are discussed.


title: The role of the WHO Regional Office for Europe in response to seasonal, avian, and pandemic influenza

text: Between 2005 and 2011, the WHO Regional Office for Europe assisted the member states of the WHO European Region to prepare and respond to outbreaks of avian influenza H5N1, the 2009 pandemic, and to enhance their capacities for the prevention and control of seasonal influenza. It did this through conducting a combination of regional and subregional meetings and trainings, establishing a regional network for influenza surveillance, providing operational guidance for implementing influenza surveillance and strengthening the capacities of National Influenza Centers, and through assistance at the country-level where needed. In all, close to 60 country-missions or country-level activities were conducted. These activities were conducted in close coordination with WHO headquarters, WHO European Region Country Offices, the European Commission, the European Centre for Disease Prevention and Control, and with other partner organizations, and were in line with the implementation of the International Health Regulations (2005). The results of activities as well as guidance documents were disseminated to a wide audience through publication on the WHO Regional Office for Europe Influenza website, on the EuroFlu website, and through peer-reviewed publications.


title: Diagnosis of severe respiratory infections in immunocompromised patients

text: An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05906-5) contains supplementary material, which is available to authorized users.


title: Wie groß sind die Differenzen zwischen den europäischen Pandemieplänen, sind sie relevant und woher stammen sie?

text: The coordination of influenza pandemic preparedness planning within Europe is especially important for Germany with 10 out of 16 Länder (regions) bordering neighbouring countries. The language barrier presents only one of the challenges to overcome. Creating a European early warning system by linking national surveillance structures and the development of a communication network are important initial achievements. Several instruments have been designed and the European Centre for Disease Prevention and Control has already played a major role in the coordination of this process. It has also led the assessment of preparedness and planning by Member States. The speed of the European Member States in preparing for and the foci they have chosen when dealing with an influenza outbreak are heterogeneous. The simultaneous analysis presented here from European, national and regional points of view aims to identify both opportunities and risks of this diversity in Europe for coping with a new pandemic. Regional and local initiatives for cross-border measures and crisis management will play a central role in achieving successful influenza pandemic preparedness in Europe.


title: Recent advances and safety issues of transgenic plant-derived vaccines

text: Transgenic plant-derived vaccines comprise a new type of bioreactor that combines plant genetic engineering technology with an organism's immunological response. This combination can be considered as a bioreactor that is produced by introducing foreign genes into plants that elicit special immunogenicity when introduced into animals or human beings. In comparison with traditional vaccines, plant vaccines have some significant advantages, such as low cost, greater safety, and greater effectiveness. In a number of recent studies, antigen-specific proteins have been successfully expressed in various plant tissues and have even been tested in animals and human beings. Therefore, edible vaccines of transgenic plants have a bright future. This review begins with a discussion of the immune mechanism and expression systems for transgenic plant vaccines. Then, current advances in different transgenic plant vaccines will be analyzed, including vaccines against pathogenic viruses, bacteria, and eukaryotic parasites. In view of the low expression levels for antigens in plants, high-level expression strategies of foreign protein in transgenic plants are recommended. Finally, the existing safety problems in transgenic plant vaccines were put forward will be discussed along with a number of appropriate solutions that will hopefully lead to future clinical application of edible plant vaccines.


title: Infektionsprävention bei der Narkosebeatmung durch Einsatz von Atemsystemfiltern: Gemeinsame Empfehlung der Deutschen Gesellschaft für Krankenhaushygiene e.V. (DGKH) und der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V. (DGAI)

text: An interdisciplinary working group from the German Society of Hospital Hygiene (DGKH) and the German Society for Anesthesiology and Intensive Care (DGAI) worked out the following recommendations for infection prevention during anesthesia by using breathing system filters (BSF). The BSF shall be changed after each patient. The filter retention efficiency for airborne particles is recommended to be >99% (II). The retention performance of BSF for liquids is recommended to be at pressures of at least 60 hPa (=60 mbar) or 20 hPa above the selected maximum ventilation pressure in the anesthetic system. The anesthesia breathing system may be used for a period of up to 7 days provided that the functional requirements of the system remain unchanged and the manufacturer states this in the instructions for use. The breathing system and the manual ventilation bag are changed immediately after the respective anesthesia if the following situation has occurred or it is suspected to have occurred: Notifiable infectious disease involving the risk of transmission via the breathing system and the manual bag, e.g. tuberculosis, acute viral hepatitis, measles, influenza virus, infection and/or colonization with a multi-resistant pathogen or upper or lower respiratory tract infections. In case of visible contamination e.g. by blood or in case of defect, it is required that the BSF and also the anesthesia breathing system is changed and the breathing gas conducting parts of the anesthesia ventilator are hygienically reprocessed. Observing of the appropriate hand disinfection is very important. All surfaces of the anesthesia equipment exposed to hand contact must be disinfected after each case.


title: Wirksamkeit von Pflanzenprodukten gegen Herpesinfektionen

text: Essential oils from various aromatic medicinal plants are highly active against some viral infections, e.g. labial herpes caused by herpes simplex virus type 1. Balm oil, tea tree oil and peppermint oil demonstrate in vitro a significant antiherpetic activity, mainly related to a direct drug-virus particle interaction, some essential oils also act directly virucidal. Interestingly, these essential oils are also highly active against acyclovir-resistant herpes simplex virus strains. In clinical studies, tea tree oil has been shown to possess antiherpetic, anti-inflammatory and pain-relieving properties, as well as to accelerate the healing process of herpes labialis. Applying diluted essential oils three to four times daily for the antiherpetic treatment of affected areas is recommended. Some companies have marketed plant products, e.g. from Melissa, for the treatment of recurrent herpetic infections.


title: HIV-Infektion – Grenzen der Präventionskonzepte: Überlegungen zur Verantwortung der Betroffenen, der Politik und der Gesellschaft*

text: Despite the introduction of campaigns to prevent the continued spread of HIV/AIDS in Germany, the number of annual firsttime HIV-diagnoses is continuing steadily. The concepts behind the current campaigns are largely based on models of New Public Health, of which social learning strategies are an essential element. The established personal and individual rights should be unimpeachable but the right not to know the status of HIV infection should be questioned for those people who spread their HIV infection intentionally and wilfully. Confronted with more than 10,000 people in Germany unconscious of their HIV infection, easy access to HIV testing and access of opportune therapy should be offered with the goal of reducing the number of new infections. Expanded strategies on the responsibility to one’s personal health and that of the partner, understandable and adapted to special groups of the society, should be established and maintained at a high level of awareness. All measures must be performed voluntarily.


title: Automated analytical microarrays: a critical review

text: Microarrays provide a powerful analytical tool for the simultaneous detection of multiple analytes in a single experiment. The specific affinity reaction of nucleic acids (hybridization) and antibodies towards antigens is the most common bioanalytical method for generating multiplexed quantitative results. Nucleic acid-based analysis is restricted to the detection of cells and viruses. Antibodies are more universal biomolecular receptors that selectively bind small molecules such as pesticides, small toxins, and pharmaceuticals and to biopolymers (e.g. toxins, allergens) and complex biological structures like bacterial cells and viruses. By producing an appropriate antibody, the corresponding antigenic analyte can be detected on a multiplexed immunoanalytical microarray. Food and water analysis along with clinical diagnostics constitute potential application fields for multiplexed analysis. Diverse fluorescence, chemiluminescence, electrochemical, and label-free microarray readout systems have been developed in the last decade. Some of them are constructed as flow-through microarrays by combination with a fluidic system. Microarrays have the potential to become widely accepted as a system for analytical applications, provided that robust and validated results on fully automated platforms are successfully generated. This review gives an overview of the current research on microarrays with the focus on automated systems and quantitative multiplexed applications. [Figure: see text]


One year with the EJNMMI


title: Behandlungseinrichtungen für hochkontagiöse, lebensbedrohliche Erkrankungen: Deutschland im Vergleich zu 15 europäischen Staaten

text: BACKGROUND: Patients suffering from highly contagious, life-threatening infections should be treated in specialized clinical facilities that follow the highest infection control standards. Consensus statements defining technical equipment and operational procedures have been published in recent years, but the level of adherence to these has not been evaluated. METHODS: Data summarized here comparing German and European isolation facilities are the partial results of a cross-sectional analysis conducted by the “European Network for Highly Infectious Diseases” that included 48 clinical care facilities in 16 European nations. Data collection was conducted using questionnaires and on-site visits, focussing on aspects of infrastructure, technical equipment, and the availability of trained personnel. RESULTS: Although all centres enrolled were listed as “isolation units”, all aspects evaluated differed broadly. Eighteen facilities fulfilled the definition of a ‘High Level Isolation Unit’, as 6/8 enrolled German facilities did. In contrast, 24 facilities could not operate independently from their co-located hospital. DISCUSSION: Within and between nations contributing data disparities regarding the fulfilment of guidelines published were seen. German isolation facilities mostly fulfilled all criteria evaluated and performed on a high technical level. However, data presented do not reflect the current situation in Germany due to the time that has elapsed since the study was conducted. Hence, longitudinal data collection and harmonisation of terminology at least on national level needs to be implemented.


title: Epidemiological implications of mobility between a large urban centre and smaller satellite cities

text: An SIR infectious disease propagation model is considered that incorporates mobility of individuals between a large urban centre and smaller satellite cities. Because of the difference in population sizes, the urban centre has standard incidence and satellite cities have mass action incidence. It is shown that the general basic reproduction number [Formula: see text] acts as a threshold between global asymptotic stability of the disease free equilibrium and disease persistence. The case of Winnipeg (MB, Canada) and some neighbouring satellite communities is then considered numerically to complement the mathematical analysis, highlighting the importance of taking into account not only [Formula: see text] but also other measures of disease severity. It is found that the large urban centre governs most of the behaviour of the general system and control of the spread is better achieved by targeting it rather than reducing movement between the units. Also, the capacity of a satellite city to affect the general system depends on its population size and its connectivity to the main urban centre.


title: Current trends in targeted therapy for drug-resistant infections

text: Escalating antibiotic resistance is now a serious menace to global public health. It may be led to the emergence of “postantibiotic age” in which most of infections are untreatable. At present, there is an essential need to explore novel therapeutic strategies as a strong and sustainable pipeline to combat antibiotic-resistant infections. This review focuses on recent advances in this area including therapeutic antibodies, antimicrobial peptides, vaccines, gene therapy, genome editing, and phage therapy for tackling drug-resistant infections.


Prüfung und Deklaration der Wirksamkeit von Desinfektionsmitteln gegen Viren: Stellungnahme des Arbeitskreises Viruzidie* beim Robert Koch-Institut (RKI) sowie des Fachausschusses „Virusdesinfektion“ der Deutschen Gesellschaft zur Bekämpfung der Viruskrankheiten (DVV) und der Desinfektionsmittelkommission der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM)


title: Studying the recovery procedure for the time-dependent transmission rate(s) in epidemic models

text: Determining the time-dependent transmission function that exactly reproduces disease incidence data can yield useful information about disease outbreaks, including a range potential values for the recovery rate of the disease and could offer a method to test the “school year” hypothesis (seasonality) for disease transmission. Recently two procedures have been developed to recover the time-dependent transmission function, β(t), for classical disease models given the disease incidence data. We first review the β(t) recovery procedures and give the resulting formulas, using both methods, for the susceptible-infected-recovered (SIR) and susceptible-exposed-infected-recovered (SEIR) models. We present a modification of one procedure, which is then shown to be identical to the other. Second, we explore several technical issues that appear when implementing the procedure for the SIR model; these are important when generating the time-dependent transmission function for real-world disease data. Third, we extend the recovery method to heterogeneous populations modeled with a certain SIR-type model with multiple time-dependent transmission functions. Finally, we apply the β(t) recovery procedure to data from the 2002–2003 influenza season and for the six seasons from 2002–2003 through 2007–2008, for both one population class and for two age classes. We discuss the consequences of the technical conditions of the procedure applied to the influenza data. We show that the method is robust in the heterogeneous cases, producing comparable results under two different hypotheses. We perform a frequency analysis, which shows a dominant 1-year period for the multi-year influenza transmission function(s).


Relapse of SARS upon tapering corticosteroid


Arboviren—durch Arthropoden übertragbare Viren: Stellungnahmen des Arbeitskreises Blut des Bundesministeriums für Gesundheit und Soziale Sicherung


title: Diagnostic workup for ARDS patients

text: Acute respiratory distress syndrome (ARDS) is defined by the association of bilateral infiltrates and hypoxaemia following an initial insult. Although a new definition has been recently proposed (Berlin definition), there are various forms of ARDS with potential differences regarding their management (ventilator settings, prone positioning use, corticosteroids). ARDS can be caused by various aetiologies, and the adequate treatment of the responsible cause is crucial to improve the outcome. It is of paramount importance to characterize the mechanisms causing lung injury to optimize both the aetiological treatment and the symptomatic treatment. If there is no obvious cause of ARDS or if a direct lung injury is suspected, bronchoalveolar lavage (BAL) should be strongly considered to identify microorganisms responsible for pneumonia. Blood samples can also help to identify microorganisms and to evaluate biomarkers of infection. If there is no infectious cause of ARDS or no other apparent aetiology is found, second-line examinations should include markers of immunologic diseases. In selected cases, open lung biopsy remains useful to identify the cause of ARDS when all other examinations remain inconclusive. CT scan is fundamental when there is a suspicion of intra-abdominal sepsis and in some cases of pneumonia. Ultrasonography is important not only in evaluating biventricular function but also in identifying pleural effusions and pneumothorax. The definition of ARDS remains clinical and the main objective of the diagnostic workup should be to be focused on identification of its aetiology, especially a treatable infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-016-4324-5) contains supplementary material, which is available to authorized users.


title: Recent advances in technology supporting biopharmaceutical production from mammalian cells

text: The demand for production of glycoproteins from mammalian cell culture continues with an increased number of approvals as biopharmaceuticals for the treatment of unmet medical needs. This is particularly the case for humanized monoclonal antibodies which are the largest and fastest growing class of therapeutic pharmaceuticals. This demand has fostered efforts to improve the efficiency of production as well as to address the quality of the final product. Chinese hamster ovary cells are the predominant hosts for stable transfection and high efficiency production on a large scale. Specific productivity of recombinant glycoproteins from these cells can be expected to be above 50 pg/cell/day giving rise to culture systems with titers of around 5 g/L if appropriate fed-batch systems are employed. Cell engineering can delay the onset of programmed cell death to ensure prolonged maintenance of productive viable cells. The clinical efficacy and quality of the final product can be improved by strategic metabolic engineering. The best example of this is the targeted production of afucosylated antibodies with enhanced antibody-dependent cell cytotoxicity, an important function for use in cancer therapies. The development of culture media from non-animal sources continues and is important to ensure products of consistent quality and without the potential danger of contamination. Process efficiencies may also be improved by employing disposable bioreactors with the associated minimization of downtime. Finally, advances in downstream processing are needed to handle the increased supply of product from the bioreactor but maintaining the high purity demanded of these biopharmaceuticals.


SARS—ein Lehrstück der Infektionsepidemiologie und ein Meisterstück moderner Infektionskontrolle