Anthrax Toxins Inhibit Neutrophil Signaling Pathways in Brain Endothelium and Contribute to the Pathogenesis of Meningitis

Anthrax meningitis is the main neurological complication of systemic infection with Bacillus anthracis approaching 100% mortality. The presence of bacilli in brain autopsies indicates that vegetative bacteria are able to breach the blood-brain barrier (BBB). The BBB represents not only a physical barrier but has been shown to play an active role in initiating a specific innate immune response that recruits neutrophils to the site of infection. Currently, the basic pathogenic mechanisms by which B. anthracis penetrates the BBB and causes anthrax meningitis are poorly understood.Using an in vitro BBB model, we show for the first time that B. anthracis efficiently invades human brain microvascular endothelial cells (hBMEC), the single cell layer that comprises the BBB. Furthermore, transcriptional profiling of hBMEC during infection with B. anthracis revealed downregulation of 270 (87%) genes, specifically key neutrophil chemoattractants IL-8, CXCL1 (Gro alpha) and CXCL2 (Gro beta), thereby strongly contrasting hBMEC responses observed with other meningeal pathogens. Further studies using specific anthrax toxin-mutants, quantitative RT-PCR, ELISA and in vivo assays indicated that anthrax toxins actively suppress chemokine production and neutrophil recruitment during infection, allowing unrestricted proliferation and dissemination of the bacteria. Finally, mice challenged with B. anthracis Sterne, but not the toxin-deficient strain, developed meningitis.These results suggest a significant role for anthrax toxins in thwarting the BBB innate defense response promoting penetration of bacteria into the central nervous system. Furthermore, establishment of a mouse model for anthrax meningitis will aid in our understanding of disease pathogenesis and development of more effective treatment strategies

Encephalomyocarditis virus infection in a splenectomised calf

Background Encephalomyocarditis (EMC) caused by EMC virus (EMCV) was diagnosed in a 5-month-old splenectomised calf, which died suddenly on an experimental farm that had a high infestation of rodents. Results At postmortem examination, the lungs were dark purple and diffusely congested. On histological examination, the calf had severe necrotising myocarditis. EMCV was isolated from the heart. The polyprotein gene of the EMCV isolate was amplified by PCR and had 85–91% identity with published EMCV sequences, including 89% identity with isolates from Queensland. On phylogenetic analysis, the polyprotein gene had highest sequence identity with South Korean EMCV strain, CBNU. Conclusion This is the first report of naturally occurring EMC in cattle in Australia and the first report of naturally occurring bovine EMC from which EMCV has been isolated

Quality of Medication Ordering at a Large Teaching Hospital

Objectives: To identify and quantify deficiencies in the prescribing/ordering of inpatient and discharge medications and determine strategies to address them. Design and setting: A descriptive study in medical and surgical wards at a tertiary referral teaching hospital. Patients: All available inpatients in 12 medical and 2 surgical wards on two consecutive days and all discharges on a single day. Results: Medication orders for 230 inpatients and 68 discharge patients were audited. A total of 2978 inpatient orders were reviewed including 634 'once only' doses, 1840 regular and 504 'as required' medications. Errors in physician prescribing occurred at a frequency of 25/1000 prescriptions and included 48 (1.6%) incorrect, ambiguous or unspecified doses and four prescriptions where the specific oral form was not stated. In 14 (0.5%) cases, the dosing frequency specified was wrong, unclear or absent and there were three cases of duplication. Two patients were prescribed drugs to which they had a documented allergy. Details of previous adverse drug reactions were complete in only 14 of 62 (23%) patients. Of the 68 discharge prescriptions audited, orders for 49 of 329 regular medications (15%) had been unintentionally omitted (range 1-8 medications per patient). Conclusions: The audit identified limitations in the quality of prescribing/ordering which were in part due to deficiencies in the current medication chart and discharge summary. To address these limitations, the medication ordering system has been revised and a multidisciplinary educational program implemented to promote safe and explicit prescribing

Progress testing of information literacy versus information literacy self-efficay in medical students

Progress testing is a common assessment tool within medical schools. A similar assessment tool, the “Progress Test of Information Literacy” (PTIL) has been created. To become an information literate person, information literacy selfefficacy (ILSE) is a meaningful part and important to evaluate. In this study, every PTIL-item has been mapped with an item of the 38-ILSE scale. Even though the mapping turned out to be delicate and context related, the results of this study suggests a relation between PTIL and specific ILSE items. Students of the first two medical years scored better for certain PTIL questions compared to students in the last years. In addition, students from year 1 were less certain about their answers. Once extra-integrated IL courses were organized, students were much more certain about their answers. Integrated and repeated IL-courses are necessary throughout the whole curriculum

CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.

BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts 350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed