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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. |
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. |
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. |
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. |
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. |
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. |
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] |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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] |
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. |
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. |
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. |
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). |
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. |
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. |
Prevention of infectious diseases is targeted at individuals, specific risk groups or communities. Vaccines are one of the most cost-effective medical interventions and protect the individual and the community against vaccine preventable diseases. Immunization programs aim to control, eliminate or eradicate infectious pathogens. In industrialized countries several vaccine preventable diseases are almost eliminated. Strict implementation of recommendations for influenza and pneumococcal immunization is crucial to reduce morbidity and mortality. Hence, uptake of recommended immunization among adults and elderly people is often low. Internal specialists are demanded to improve vaccine coverage in those age groups. |
This paper summarizes the features and performances of optical detection systems currently applied in order to monitor separations on microchip devices. Fluorescence detection, which delivers very high sensitivity and selectivity, is still the most widely applied method of detection. Instruments utilizing laser-induced fluorescence (LIF) and lamp-based fluorescence along with recent applications of light-emitting diodes (LED) as excitation sources are also covered in this paper. Since chemiluminescence detection can be achieved using extremely simple devices which no longer require light sources and optical components for focusing and collimation, interesting approaches based on this technique are presented, too. Although UV/vis absorbance is a detection method that is commonly used in standard desktop electrophoresis and liquid chromatography instruments, it has not yet reached the same level of popularity for microchip applications. Current applications of UV/vis absorbance detection to microchip separations and innovative approaches that increase sensitivity are described. This article, which contains 85 references, focuses on developments and applications published within the last three years, points out exciting new approaches, and provides future perspectives on this field. |
This paper is concerned with a stochastic model, describing outbreaks of infectious diseases that have potentially great animal or human health consequences, and which can result in such severe economic losses that immediate sets of measures need to be taken to curb the spread. During an outbreak of such a disease, the environment that the infectious agent experiences is therefore changing due to the subsequent control measures taken. In our model, we introduce a general branching process in a changing (but not random) environment. With this branching process, we estimate the probability of extinction and the expected number of infected individuals for different control measures. We also use this branching process to calculate the generating function of the number of infected individuals at any given moment. The model and methods are designed using important infections of farmed animals, such as classical swine fever, foot-and-mouth disease and avian influenza as motivating examples, but have a wider application, for example to emerging human infections that lead to strict quarantine of cases and suspected cases (e.g. SARS) and contact and movement restrictions. |
Significant progress regarding hygiene, nutrition, and antimicrobial treatment as well as immunizations have lead to a significant decline of morbidity and mortality of infectious diseases in the recent past. Furthermore, immunizations are one of the most cost-effective tools for prevention. However, lack of perception of the substantial risks of complications associated with infectious diseases cause doubts about the necessity of immunizations today. This development is highly worrisome and needs to be adequately addressed by informing physicians and the public about the risks of vaccine-preventable diseases, efficiency, safety and benefits of available vaccines, as well as providing convincing arguments justifying current immunization recommendations. These activities are indispensable for successful implementation and continuation of current immunization programs. |
ABSTRACT: Quantitative structure–activity relationship (QSAR) parameters are good indicators for the reactivity of direct-acting antiviral drugs. Since molecular structure is related to molecular function, careful selection of molecular substitutions will result in more drugs that are potent. In this work, QSAR parameters are selected in order to compare the four drugs used as nucleotide inhibitors (NIs) for non-structural 5B (NS5B) RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV). These drugs are: ribavirin (widely used over the last 20 years), sofosbuvir (approved on December 2013 by FDA), and finally IDX-184 and R7128 (phase IIb of clinical trial drugs). The nucleotide analogues uracil (U), guanine (G), and cytosine (C) from which these drugs are fabricated are also compared to that group of drugs. QSAR parameters suggested that the drug IDX-184 is the best among all of the studied NIs. It also shows that NIs are always more reactive than their parent nucleotide. GRAPHICAL ABSTRACT: The active site environment of 12 amino acids coordinated with IDX-184 through two Mg(2+). The interaction with HCV subtypes 1a, 2b, and 3b is better than 4a subtype. [Image: see text] |
Heterogeneities in behaviours of individuals may underpin important processes in evolutionary biology and ecology, including the spread of disease. Modelling approaches can sometimes fail to predict disease spread, which may partly be due to the number of unknown sources of variation in host behaviour. The European badger is a wildlife reservoir for bovine tuberculosis (bTB) in Britain and Ireland, and individual behaviour has been demonstrated to be an important factor in the spread of bTB among badgers and to cattle. Radio-telemetry devices were deployed on 40 badgers from eight groups to investigate patterns of den (sett) use in a high-density population, where each group had one or two main and three to eight outlier setts in their territory. Badgers were located at their setts for 28 days per season for 1 year to investigate how patterns differed between individuals. Denning behaviour may have a strong influence on contact patterns and the transmission of disease. We found significant heterogeneity, influenced by season, sex and age. Also, when controlling for these, bTB infection status interacting with season was highly correlated with sett use. Test-positive badgers spent more time away from their main sett than those that tested negative. We speculate that wider-ranging behaviour of test-positive animals may result in them contacting sources of infection more frequently and/or that their behaviour may be influenced by their disease status. Measures to control infectious diseases might be improved by targeting functional groups, specific areas or times of year that may contribute disproportionately to disease spread. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00265-012-1467-4) contains supplementary material, which is available to authorized users. |
Infections play a crucial role in organ transplantations as possible complications. Viruses, bacteria, fungi and parasites are potential agents. The relevance of individual diseases depends on the organ transplanted. Morphology of the inflammatory reaction is given by the agent involved, but often several reactions can be caused by the same agent and different agents can also lead to the same reaction. Histology therefore provides concrete identification of the causal agent only in some cases, such that additional microbiological diagnostics are necessary. Results from these investigations should be transferred to the pathologist to distinguish between infection-associated changes and transplant rejection. |
Random networks with specified degree distributions have been proposed as realistic models of population structure, yet the problem of dynamically modeling SIR-type epidemics in random networks remains complex. I resolve this dilemma by showing how the SIR dynamics can be modeled with a system of three nonlinear ODE’s. The method makes use of the probability generating function (PGF) formalism for representing the degree distribution of a random network and makes use of network-centric quantities such as the number of edges in a well-defined category rather than node-centric quantities such as the number of infecteds or susceptibles. The PGF provides a simple means of translating between network and node-centric variables and determining the epidemic incidence at any time. The theory also provides a simple means of tracking the evolution of the degree distribution among susceptibles or infecteds. The equations are used to demonstrate the dramatic effects that the degree distribution plays on the final size of an epidemic as well as the speed with which it spreads through the population. Power law degree distributions are observed to generate an almost immediate expansion phase yet have a smaller final size compared to homogeneous degree distributions such as the Poisson. The equations are compared to stochastic simulations, which show good agreement with the theory. Finally, the dynamic equations provide an alternative way of determining the epidemic threshold where large-scale epidemics are expected to occur, and below which epidemic behavior is limited to finite-sized outbreaks. |
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