Legionnaires' disease - a qualitative study on Swiss physicians' approaches to the diagnosis and treatment of community-acquired pneumonia

BACKGROUND: The number of reported cases of Legionnaires' disease has increased significantly over the last decade in Switzerland and abroad. Along with the number of cases, the volume of testing has increased as well, which has been partially attributed to a change in awareness of the disease. Yet, while there are numerous guidelines and recommendations for the case management of community-acquired pneumonia, little is known about how physicians in Switzerland perceive and manage Legionnaires' disease. METHODS: This study aimed to investigate physicians' awareness of Legionnaires' disease, their information resources and their approach to the diagnosis and treatment of pneumonia (and thus Legionnaires' disease). Using a semi-structured interview guide, we conducted in-depth interviews with physicians from different levels of care and from the German-, French- and Italian-speaking regions of Switzerland. RESULTS: We conducted 46 interviews with physicians from university, cantonal and regional hospitals as well as with general practitioners (GPs) from all three language regions. Overall, the physicians working in hospitals indicated a similar level of awareness of Legionnaires' disease, and comparable diagnosis and treatment approaches. The Legionella urine antigen test (UAT) was reported to be routinely performed in inpatients. In contrast, GPs indicated lower levels of awareness, reflecting the fact that they treat pneumonia cases empirically without identification of the causative agent, in accordance with current guidelines. The value of the diagnostic tests in general and the Legionella UAT in particular was considered to be dependent on the (preferred) antibiotic treatment approach. Some physicians saw the test as redundant, as its result would not influence treatment. This was tied to concerns about the UAT's sensitivity and its limited use for the detection of Legionella pneumophila serogroup 1. Lastly, extrinsic constraints, such as financial and time considerations also affected physicians' testing and treatment preferences. CONCLUSION: Awareness of Legionnaires' disease is overall high, yet cases are mainly diagnosed and reported by hospitals. Improved diagnostic tools are needed to support physicians in reducing underestimation of Legionnaires' disease and optimise antibiotic stewardship without compromising patient health outcomes

Sonoelastography of the Common Flexor Tendon of the Elbow with Histologic Agreement: A Cadaveric Study.

Purpose To determine the correlation of the results of conventional B-mode ultrasonography (US) and compression sonoelastography with histologic results in common flexor tendons of the elbow in human cadavers. Materials and Methods Twenty-five common flexor tendons were evaluated in 16 fresh, unembalmed cadavers of 11 women with a median age of 85 years (range, 71-101 years) and five men with a median age of 78 years (range, 70-88 years). Informed consent was provided according to the last will of the donors. B-mode US results were classified as grade 1, normal tendon with homogeneous fibrillar pattern; grade 2, tendon thickening or hypoechoic areas and/or calcifications in less than 30% of the tendon; or grade 3, hypoechoic areas and/or calcifications greater than 30% of the tendon. Sonoelastographic results were grade 1, blue (hardest) to green (hard); grade 2, yellow (soft); and grade 3, red (softest). The intraclass correlation coefficient was calculated to determine agreement with histologic findings for each B-mode US, sonoelastographic, and combined B-mode US and sonoelastographic examination. Histologic results were grade 1, normal, with parallel fibrillar pattern; grade 2, mild tendinopathy, with cellular infiltration, angiogenesis, or fatty vacuoles; or grade 3, severe tendinopathy, with loss of parallel collagen structure and necrosis. Results Histologic alterations were detected in 44% (11 of 25) of biopsy specimens. Intraclass correlation with histologic results was 0.57 for B-mode US, 0.68 for sonoelastography, and 0.84 for the combination of the two approaches. Conclusion The addition of sonoelastography to B-mode US provided statistically significant improvement in correlation with histologic results compared with the use of B-mode US alone (P \u3c .02). (©) RSNA, 2016 Online supplemental material is available for this article

Vaccine hesitancy and HPV vaccine uptake among male and female youth in Switzerland: a cross-sectional study

OBJECTIVES: Identifying factors associated with human papillomavirus (HPV) vaccine uptake is essential for designing successful vaccination programmes. We aimed to examine the association between vaccine hesitancy (VH) and HPV vaccine uptake among male and female youth in Switzerland. DESIGN: With a cross-sectional study, an interview-based questionnaire was used to collect information on sociodemographic factors, vaccination records and to measure the prevalence of VH using the Youth Attitudes about Vaccines scale (YAV-5), a modified version of the Parent Attitudes about Childhood Vaccinations survey instrument. SETTING AND PARTICIPANTS: Eligible male and female participants, 15-26 years of age, were recruited through physicians' offices and military enlistment in all three language regions of Switzerland. Of 1001 participants, we included 674 participants with a vaccination record available (415 males and 259 females) in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome was uptake for HPV vaccine (having received >/=1 dose of HPV vaccine). Covariates were VH, sex, age and other sociodemographics. RESULTS: 151 (58%) female and 64 (15%) male participants received >/=1 dose of HPV vaccine. 81 (31%) female and 92 (22%) male participants were VH (YAV-5-Score >50). The odds for being unvaccinated were higher for VH women than non-VH women, adjusted OR=4.90 (95% CI 2.53 to 9.50), but similar among VH and non-VH men, OR=1.90 (95% CI 0.84 to 4.31). The odds for being unvaccinated were lower for younger men (born on or after 1 July 2002) than older men (born before 1 July 2002), OR=0.34 (95% CI 0.14 to 0.81), but we found no association between age and vaccine uptake for female youth, OR=0.97 (95% CI 0.48 to 1.97). CONCLUSIONS: VH was associated with lower HPV vaccine uptake in female youth but not male youth in our study population in Switzerland. Our findings suggest that issues other than VH contribute to HPV underimmunisation in male youth in Switzerland

Altering an Artificial Gagpolnef Polyprotein and Mode of ENV Co-Administration Affects the Immunogenicity of a Clade C HIV DNA Vaccine

HIV-1 candidate vaccines expressing an artificial polyprotein comprising Gag, Pol and Nef (GPN) and a secreted envelope protein (Env) were shown in recent Phase I/II clinical trials to induce high levels of polyfunctional T cell responses; however, Env-specific responses clearly exceeded those against Gag. Here, we assess the impact of the GPN immunogen design and variations in the formulation and vaccination regimen of a combined GPN/Env DNA vaccine on the T cell responses against the various HIV proteins. Subtle modifications were introduced into the GPN gene to increase Gag expression, modify the expression ratio of Gag to PolNef and support budding of virus-like particles. I.m. administration of the various DNA constructs into BALB/c mice resulted in an up to 10-fold increase in Gag- and Pol-specific IFNγ+ CD8+ T cells compared to GPN. Co-administering Env with Gag or GPN derivatives largely abrogated Gag-specific responses. Alterations in the molar ratio of the DNA vaccines and spatially or temporally separated administration induced more balanced T cell responses. Whereas forced co-expression of Gag and Env from one plasmid induced predominantly Env-specific T cells responses, deletion of the only H-2d T cell epitope in Env allowed increased levels of Gag-specific T cells, suggesting competition at an epitope level. Our data demonstrate that the biochemical properties of an artificial polyprotein clearly influence the levels of antigen-specific T cells, and variations in formulation and schedule can overcome competition for the induction of these responses. These results are guiding the design of ongoing pre-clinical and clinical trials

Broad Antibody Mediated Cross-Neutralization and Preclinical Immunogenicity of New Codon-Optimized HIV-1 Clade CRF02_AG and G Primary Isolates

Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary “street strain” isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA) to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G). Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G) and consensus tat (CRF02_AG and G) antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G

Differential Trends in the Codon Usage Patterns in HIV-1 Genes

Host-pathogen interactions underlie one of the most complex evolutionary phenomena resulting in continual adaptive genetic changes, where pathogens exploit the host's molecular resources for growth and survival, while hosts try to eliminate the pathogen. Deciphering the molecular basis of host–pathogen interactions is useful in understanding the factors governing pathogen evolution and disease propagation. In host-pathogen context, a balance between mutation, selection, and genetic drift is known to maintain codon bias in both organisms. Studies revealing determinants of the bias and its dynamics are central to the understanding of host-pathogen evolution. We considered the Human Immunodeficiency Virus (HIV) type 1 and its human host to search for evolutionary signatures in the viral genome. Positive selection is known to dominate intra-host evolution of HIV-1, whereas high genetic variability underlies the belief that neutral processes drive inter-host differences. In this study, we analyze the codon usage patterns of HIV-1 genomes across all subtypes and clades sequenced over a period of 23 years. We show presence of unique temporal correlations in the codon bias of three HIV-1 genes illustrating differential adaptation of the HIV-1 genes towards the host preferred codons. Our results point towards gene-specific translational selection to be an important force driving the evolution of HIV-1 at the population level

Step-wise evolution of complex chemical defenses in millipedes: a phylogenomic approach

With fossil representatives from the Silurian capable of respiring atmospheric oxygen, millipedes are among the oldest terrestrial animals, and likely the first to acquire diverse and complex chemical defenses against predators. Exploring the origin of complex adaptive traits is critical for understanding the evolution of Earth’s biological complexity, and chemical defense evolution serves as an ideal study system. The classic explanation for the evolution of complexity is by gradual increase from simple to complex, passing through intermediate “stepping stone� states. Here we present the first phylogenetic-based study of the evolution of complex chemical defenses in millipedes by generating the largest genomic-based phylogenetic dataset ever assembled for the group. Our phylogenomic results demonstrate that chemical complexity shows a clear pattern of escalation through time. New pathways are added in a stepwise pattern, leading to greater chemical complexity, independently in a number of derived lineages. This complexity gradually increased through time, leading to the advent of three distantly related chemically complex evolutionary lineages, each uniquely characteristic of each of the respective millipede groups