Hexenfieber im Erzgebirge - Die Annaberger Krankheit 1712 - 1720

Die Arbeit untersucht das seuchenartige Auftreten von Besessenheitsfällen in Annaberg (Erzgebirge) in den Jahren 1713-1720, die Auslöser der letzten Hexenprozesse in Kursachsen waren. Zeitgenössische Beobachter stritten intensiv, ob diese sogenannte „Annaberger Krankheit“ durch Zauberei verursacht oder eine psychosomatisch bedingte Massenerkrankung war. In Abkehr von dem Vorurteil, alle Betroffenen einer solchen Massenhysterie litten an derselben Erkrankung, werden diverse Krankengeschichten rekonstruiert. Indem sich dabei Elemente von Rollenspielen (Kinderhexen, Hysterie) und Betrug (Almosenerschleichung, Denunziationen, politisch motivierte Inszenierungen) finden, zeigt sich die wundersame „Krankheit“ als nicht pathologischer sondern sozialer Vorgang. rnAm dessen Beginn stand die Geburt der Interpretation, es gäbe eine außergewöhnliche Krankheit in der Stadt, wozu akzidentielle Ereignisse mehr beitrugen als auffällige Krankheitsfälle. Gerüchtbildung und politische Instrumentalisierung bildeten den Rahmen für den Einstieg von Nachahmern, die das fiktive Krankheitsbild in die Realität eines demonstrativen Schauspiel umsetzten. Dieser Mechanismus eines selbsterfüllenden Menetekels wird vor dem Hintergrund seiner kulturellen, sozialen, ökonomischen und historischen Bedingungen detailliert rekonstruiert.

Disseminazioni in reti peer-to-peer attraverso algoritmi di gossip a due fasi

Gli algoritmi di gossip sono utilizzati per la disseminazione di messaggi in una rete peer-to-peer. La tesi tratta lo sviluppo, l'implementazione e l'analisi di quattro nuovi algoritmi di gossip "a due fasi". Gli algoritmi sono stati sviluppati e testati con il simulatore LUNES per poi essere analizzati in vari confronti con gli algoritmi classici dell'ambito, ovvero Fixed Probability e Conditional Broadcast. Le prove sono state effettuate su varie tipologie di grafi, ovvero Random, Scale-free, Small-world e K-Regular.

Tackling of unhealthy diets, physical inactivity, and obesity: health effects and cost-effectiveness

The obesity epidemic is spreading to low-income and middle-income countries as a result of new dietary habits and sedentary ways of life, fuelling chronic diseases and premature mortality. In this report we present an assessment of public health strategies designed to tackle behavioural risk factors for chronic diseases that are closely linked with obesity, including aspects of diet and physical inactivity, in Brazil, China, India, Mexico, Russia, and South Africa. England was included for comparative purposes. Several population-based prevention policies can be expected to generate substantial health gains while entirely or largely paying for themselves through future reductions of health-care expenditures. These strategies include health information and communication strategies that improve population awareness about the benefits of healthy eating and physical activity; fiscal measures that increase the price of unhealthy food content or reduce the cost of healthy foods rich in fibre; and regulatory measures that improve nutritional information or restrict the marketing of unhealthy foods to children. A package of measures for the prevention of chronic diseases would deliver substantial health gains, with a very favourable cost-effectiveness profile.

Impact of obesity on stroke outcome after intravenous thrombolysis

Obesity is an established risk factor for stroke and has reached epidemic proportions. However, its impact on intravenous thrombolysis applied for acute ischemic stroke is not well known. We aimed to compare the clinical outcome and safety after intravenous thrombolysis in obese (body mass index ≥30 kg/m²) and nonobese (body mass index <30 kg/m²) patients with ischemic stroke.

Combining spatial-temporal and phylogenetic analysis approaches for improved understanding on global H5N1 transmission

Background Since late 2003, the highly pathogenic influenza A H5N1 had initiated several outbreak waves that swept across the Eurasia and Africa continents. Getting prepared for reassortment or mutation of H5N1 viruses has become a global priority. Although the spreading mechanism of H5N1 has been studied from different perspectives, its main transmission agents and spread route problems remain unsolved. Methodology/Principal Findings Based on a compilation of the time and location of global H5N1 outbreaks from November 2003 to December 2006, we report an interdisciplinary effort that combines the geospatial informatics approach with a bioinformatics approach to form an improved understanding on the transmission mechanisms of H5N1 virus. Through a spherical coordinate based analysis, which is not conventionally done in geographical analyses, we reveal obvious spatial and temporal clusters of global H5N1 cases on different scales, which we consider to be associated with two different transmission modes of H5N1 viruses. Then through an interdisciplinary study of both geographic and phylogenetic analysis, we obtain a H5N1 spreading route map. Our results provide insight on competing hypotheses as to which avian hosts are responsible for the spread of H5N1. Conclusions/Significance We found that although South China and Southeast Asia may be the virus pool of avian flu, East Siberia may be the source of the H5N1 epidemic. The concentration of migratory birds from different places increases the possibility of gene mutation. Special attention should be paid to East Siberia, Middle Siberia and South China for improved surveillance of H5N1 viruses and monitoring of migratory birds.

Adjunctive dexamethasone affects the expression of genes related to inflammation, neurogenesis and apoptosis in infant rat pneumococcal meningitis

Streptococcus pneumoniae is the most common pathogen causing non-epidemic bacterial meningitis worldwide. The immune response and inflammatory processes contribute to the pathophysiology. Hence, the anti-inflammatory dexamethasone is advocated as adjuvant treatment although its clinical efficacy remains a question at issue. In experimental models of pneumococcal meningitis, dexamethasone increased neuronal damage in the dentate gyrus. Here, we investigated expressional changes in the hippocampus and cortex at 72 h after infection when dexamethasone was given to infant rats with pneumococcal meningitis. Nursing Wistar rats were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis or were sham-infected with pyrogen-free saline. Besides antibiotics, animals were either treated with dexamethasone or saline. Expressional changes were assessed by the use of GeneChip® Rat Exon 1.0 ST Arrays and quantitative real-time PCR. Protein levels of brain-derived neurotrophic factor, cytokines and chemokines were evaluated in immunoassays using Luminex xMAP® technology. In infected animals, 213 and 264 genes were significantly regulated by dexamethasone in the hippocampus and cortex respectively. Separately for the cortex and the hippocampus, Gene Ontology analysis identified clusters of biological processes which were assigned to the predefined categories "inflammation", "growth", "apoptosis" and others. Dexamethasone affected the expression of genes and protein levels of chemokines reflecting diminished activation of microglia. Dexamethasone-induced changes of genes related to apoptosis suggest the downregulation of the Akt-survival pathway and the induction of caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as transforming growth factor pathway was reduced by dexamethasone resulting in a lack of pro-survival triggers. The anti-inflammatory properties of dexamethasone were observed on gene and protein level in experimental pneumococcal meningitis. Further dexamethasone-induced expressional changes reflect an increase of pro-apoptotic signals and a decrease of pro-neurogenic processes. The findings may help to identify potential mechanisms leading to apoptosis by dexamethasone in experimental pneumococcal meningitis.

Twelve years' detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay

Background Direct immunofluorescence assays (DFA) are a rapid and inexpensive method for the detection of respiratory viruses and may therefore be used for surveillance. Few epidemiological studies have been published based solely on DFA and none included respiratory picornaviruses and human metapneumovirus (hMPV). We wished to evaluate the use of DFA for epidemiological studies with a long-term observation of respiratory viruses that includes both respiratory picornaviruses and hMPV. Methods Since 1998 all children hospitalized with respiratory illness at the University Hospital Bern have been screened with DFA for common respiratory viruses including adenovirus, respiratory syncytial virus (RSV), influenza A and B, and parainfluenza virus 1-3. In 2006 assays for respiratory picornaviruses and hMPV were added. Here we describe the epidemiological pattern for these respiratory viruses detected by DFA in 10'629 nasopharyngeal aspirates collected from 8'285 patients during a 12-year period (1998-2010). Results Addition of assays for respiratory picornaviruses and hMPV raised the proportion of positive DFA results from 35% to 58% (p < 0.0001). Respiratory picornaviruses were the most common viruses detected among patients ≥1 year old. The seasonal patterns and age distribution for the studied viruses agreed well with those reported in the literature. In 2010, an hMPV epidemic of unexpected size was observed. Conclusions DFA is a valid, rapid, flexible and inexpensive method. The addition of assays for respiratory picornaviruses and hMPV broadens its range of viral detection. DFA is, even in the "PCR era", a particularly adapted method for the long term surveillance of respiratory viruses in a pediatric population.

Surveillance and simulation of bovine spongiform encephalopathy and scrapie in small ruminants in Switzerland

BACKGROUND: After bovine spongiform encephalopathy (BSE) emerged in European cattle livestock in 1986 a fundamental question was whether the agent established also in the small ruminants' population. In Switzerland transmissible spongiform encephalopathies (TSEs) in small ruminants have been monitored since 1990. While in the most recent TSE cases a BSE infection could be excluded, for historical cases techniques to discriminate scrapie from BSE had not been available at the time of diagnosis and thus their status remained unclear. We herein applied state-of-the-art techniques to retrospectively classify these animals and to re-analyze the affected flocks for secondary cases. These results were the basis for models, simulating the course of TSEs over a period of 70 years. The aim was to come to a statistically based overall assessment of the TSE situation in the domestic small ruminant population in Switzerland. RESULTS: In sum 16 TSE cases were identified in small ruminants in Switzerland since 1981, of which eight were atypical and six were classical scrapie. In two animals retrospective analysis did not allow any further classification due to the lack of appropriate tissue samples. We found no evidence for an infection with the BSE agent in the cases under investigation. In none of the affected flocks, secondary cases were identified. A Bayesian prevalence calculation resulted in most likely estimates of one case of BSE, five cases of classical scrapie and 21 cases of atypical scrapie per 100'000 small ruminants. According to our models none of the TSEs is considered to cause a broader epidemic in Switzerland. In a closed population, they are rather expected to fade out in the next decades or, in case of a sporadic origin, may remain at a very low level. CONCLUSIONS: In summary, these data indicate that despite a significant epidemic of BSE in cattle, there is no evidence that BSE established in the small ruminant population in Switzerland. Classical and atypical scrapie both occur at a very low level and are not expected to escalate into an epidemic. In this situation the extent of TSE surveillance in small ruminants requires reevaluation based on cost-benefit analysis.

Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study

Background Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART. Methods and Findings Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located. Conclusions HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic.

Resurgence of HIV infection among men who have sex with men in Switzerland: mathematical modelling study

Background New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. Methodology/Principal Findings The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995–1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. Conclusions/Significance The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.

Genetic variations in IL28B and allergic disease in children

Environmental changes affecting the relationship between the developing immune system and microbial exposure have been implicated in the epidemic rise of allergic disease in developed countries. While early developmental differences in T cell function are well-recognised, there is now emerging evidence that this is related to developmental differences in innate immune function. In this study we sought to examine if differences associated with innate immunity contribute to the altered immune programming recognised in allergic children. Here, we describe for the first time, the association of carriage of the T allele of the tagging single nucleotide polymorphism rs12979860 3 kb upstream of IL28B, encoding the potent innate immune modulator type III interferon lambda (IFN-λ3), and allergy in children (p = 0.004; OR 4.56). Strikingly, the association between rs12979860 genotype and allergic disease is enhanced in girls. Furthermore, carriage of the T allele at rs12979860 correlates with differences in the pro-inflammatory profile during the first five years of life suggesting this contributes to the key differences in subsequent innate immune development in children who develop allergic disease. In the context of rising rates of disease, these immunologic differences already present at birth imply very early interaction between genetic predisposition and prenatal environmental influences.

The Design and Analysis of Partner Studies of HIV Transmission

Common goals in epidemiologic studies of infectious diseases include identification of the infectious agent, description of the modes of transmission and characterization of factors that influence the probability of transmission from infected to uninfected individuals. In the case of AIDS, the agent has been identified as the Human Immunodeficiency Virus (HIV), and transmission is known to occur through a variety of contact mechanisms including unprotected sexual intercourse, transfusion of infected blood products and sharing of needles in intravenous drug use. Relatively little is known about the probability of IV transmission associated with the various modes of contact, or the role that other cofactors play in promoting or suppressing transmission. Here, transmission probability refers to the probability that the virus is transmitted to a susceptible individual following exposure consisting of a series of potentially infectious contacts. The infectivity of HIV for a given route of transmission is defined to be the per contact probability of infection. Knowledge of infectivity and its relationship to other factors is important in understanding the dynamics of the AIDS epidemic and in suggesting appropriate measures to control its spread. The primary source of empirical data about infectivity comes from sexual partners of infected individuals. Partner studies consist of a series of such partnerships, usually heterosexual and monogamous, each composed of an initially infected "index case" and a partner who may or may not be infected by the time of data collection. However, because the infection times of both partners may be unknown and the history of contacts uncertain, any quantitative characterization of infectivity is extremely difficult. Thus, most statistical analyses of partner study data involve the simplifying assumption that infectivity is a constant common to all partnerships. The major objectives of this work are to describe and discuss the design and analysis of partner studies, providing a general statistical framework for investigations of infectivity and risk factors for HIV transmission. The development is largely based on three papers: Jewell and Shiboski (1990), Kim and Lagakos (1990), and Shiboski and Jewell (1992).

Microarray based study on virulence-associated genes and resistance determinants of Staphylococcus aureus isolates from cattle

Staphylococcus aureus is a common pathogen which can colonise and infect not only man, but also domestic animals. Especially, infection of cattle is of high economic relevance as S. aureus is an important causal agent of bovine mastitis. In the present contribution, a DNA microarray was applied for the study of 144 different gene targets, including resistance genes and genes encoding exotoxins, in S. aureus isolated from cows. One hundred and twenty-eight isolates from Germany and Switzerland were tested. These isolates were assigned to 20 different strains and nine clonal complexes. The majority of isolates belonged either to apparently closely related clonal complexes 8, 25, and 97 (together 34.4%) or were related to the sequenced bovine strain RF122 (48.4%). Notable characteristics of S. aureus of bovine origin are the carriage of intact haemolysin beta (in 82% of isolates tested), the absence of staphylokinase (in 89.1%), the presence of allelic variants of several exotoxins such as toxic shock syndrome toxin and enterotoxin N, and the occurrence of the leukocidin lukF-P83/lukM (in 53.1%). Two isolates were methicillin-resistant S. aureus (MRSA). One of them was a clonal complex 8 MRSA related to the epidemic MRSA strain Irish 01. The other one belonged to ST398/spa-type 34 resembling a newly emerging MRSA strain which has been described to occur in humans as well as in domestic animals. The presence of these two strains highlights the possibility of transfers of S. aureus strains between different host species.

Human alveolar echinococcosis after fox population increase, Switzerland

We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12-0.15 during 1956-1992 and a mean of 0.10 during 1993-2000 to a mean of 0.26 during 2001-2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10-15 years later.

No temporal association between influenza outbreaks and invasive pneumococcal infections

OBJECTIVE: To assess whether the influenza peak in populations precedes the annual peak for invasive pneumococcal infections (IPI) in winter. DESIGN: Ecological study. Active surveillance data on influenza A and IPI in children up to 16 years of age collected from 1997 to 2003 were analysed. SETTING: Paediatric hospitals in Germany. Patients: Children under 16 years of age. RESULTS: In all years under study, the influenza A season did not appear to affect the IPI season (p = 0.49). Specifically, the influenza peak never preceded the IPI peak. CONCLUSION: On a population level there was no indication that the annual influenza epidemic triggered the winter increase in the IPI rate or the peak of the IPI distribution in children.