Anthrax toxin component, Protective Antigen, protects insects from bacterial infections.

Anthrax is a major zoonotic disease of wildlife, and in places like West Africa, it can be caused by Bacillus anthracis in arid nonsylvatic savannahs, and by B. cereus biovar anthracis (Bcbva) in sylvatic rainforests. Bcbva-caused anthrax has been implicated in as much as 38% of mortality in rainforest ecosystems, where insects can enhance the transmission of anthrax-causing bacteria. While anthrax is well-characterized in mammals, its transmission by insects points to an unidentified anthrax-resistance mechanism in its vectors. In mammals, a secreted anthrax toxin component, 83 kDa Protective Antigen (PA83), binds to cell-surface receptors and is cleaved by furin into an evolutionary-conserved PA20 and a pore-forming PA63 subunits. We show that PA20 increases the resistance of Drosophila flies and Culex mosquitoes to bacterial challenges, without directly affecting the bacterial growth. We further show that the PA83 loop known to be cleaved by furin to release PA20 from PA63 is, in part, responsible for the PA20-mediated protection. We found that PA20 binds directly to the Toll activating peptidoglycan-recognition protein-SA (PGRP-SA) and that the Toll/NF-κB pathway is necessary for the PA20-mediated protection of infected flies. This effect of PA20 on innate immunity may also exist in mammals: we show that PA20 binds to human PGRP-SA ortholog. Moreover, the constitutive activity of Imd/NF-κB pathway in MAPKK Dsor1 mutant flies is sufficient to confer the protection from bacterial infections in a manner that is independent of PA20 treatment. Lastly, Clostridium septicum alpha toxin protects flies from anthrax-causing bacteria, showing that other pathogens may help insects resist anthrax. The mechanism of anthrax resistance in insects has direct implications on insect-mediated anthrax transmission for wildlife management, and with potential for applications, such as reducing the sensitivity of pollinating insects to bacterial pathogens.

Investigation of the immunogenicity of Zika glycan loop.

BACKGROUND: Zika virus (ZIKV) is a major human pathogen and member of the Flavivirus genus. Previous studies have identified neutralizing antibodies from Zika patients that bind to quaternary epitopes across neighboring envelope (E) proteins, called E dimer epitopes (EDE). An asparagine-linked glycan on the "glycan loop" (GL) of the ZIKV envelope protein protects the functionally important "fusion loop" on the opposite E subunit in the dimer, and EDE antibodies have been shown to bind to both of these loops. Human EDE antibodies have been divided into two subclasses based on how they bind to the glycan loop region: EDE1 antibodies do not require glycosylation for binding, while EDE2 antibodies strongly rely on the glycan for binding. METHODS: ZIKV GL was expressed on tobacco mosaic virus nanoparticles. Mice were immunized with GL or full-length monomeric E and the immune response was analyzed by testing the ability of sera and monoclonal antibodies to bind to GL and to neutralize ZIKV in in vitro cellular assay. RESULTS: We report here the existence of ZIKV moderately neutralizing antibodies that bind to E monomers through epitopes that include the glycan loop. We show that sera from human Zika patients contain antibodies capable of binding to the unglycosylated glycan loop in the absence of the rest of the envelope protein. Furthermore, mice were inoculated with recombinant E monomers and produced neutralizing antibodies that either recognize unglycosylated glycan loop or require glycan for their binding to monomeric E. We demonstrate that both types of antibodies neutralize ZIKV to some extent in a cellular virus neutralization assay. CONCLUSIONS: Analogous to the existing EDE antibody nomenclature, we propose a new classification for antibodies that bind to E monomer epitopes (EME): EME1 and EME2 for those that do not require and those that do require glycan for binding to E, respectively.

Attributable costs and length of stay of hospital-acquired Clostridioides difficile: A population-based matched cohort study in Alberta, Canada.

OBJECTIVE: To determine the attributable cost and length of stay of hospital-acquired Clostridioides difficile infection (HA-CDI) from the healthcare payer perspective using linked clinical, administrative, and microcosting data. DESIGN: A retrospective, population-based, propensity-score-matched cohort study. SETTING: Acute-care facilities in Alberta, Canada. PATIENTS: Admitted adult (≥18 years) patients with incident HA-CDI and without CDI between April 1, 2012, and March 31, 2016. METHODS: Incident cases of HA-CDI were identified using a clinical surveillance definition. Cases were matched to noncases of CDI (those without a positive C. difficile test or without clinical CDI) on propensity score and exposure time. The outcomes were attributable costs and length of stay of the hospitalization where the CDI was identified. Costs were expressed in 2018 Canadian dollars. RESULTS: Of the 2,916 HA-CDI cases at facilities with microcosting data available, 98.4% were matched to 13,024 noncases of CDI. The total adjusted cost among HA-CDI cases was 27% greater than noncases of CDI (ratio, 1.27; 95% confidence interval [CI], 1.21-1.33). The mean attributable cost was $18,386 (CAD 2018; USD $14,190; 95% CI, $14,312-$22,460; USD $11,046-$17,334). The adjusted length of stay among HA-CDI cases was 13% greater than for noncases of CDI (ratio, 1.13; 95% CI, 1.07-1.19), which corresponds to an extra 5.6 days (95% CI, 3.10-8.06) in length of hospital stay per HA-CDI case. CONCLUSIONS: In this population-based, propensity score matched analysis using microcosting data, HA-CDI was associated with substantial attributable cost.

Cost-Effectiveness Analysis of the Use of Probiotics for the Prevention of Clostridium difficile-Associated Diarrhea in a Provincial Healthcare System.

OBJECTIVE To conduct a full economic evaluation assessing the costs and consequences related to probiotic use for the primary prevention of Clostridium difficile-associated diarrhea (CDAD). DESIGN Cost-effectiveness analysis using decision analytic modeling. METHODS A cost-effectiveness analysis was used to evaluate the risk of CDAD and the costs of receiving oral probiotics versus not over a time horizon of 30 days. The target population modeled was all adult inpatients receiving any therapeutic course of antibiotics from a publicly funded healthcare system perspective. Effectiveness estimates were based on a recent systematic review of probiotics for the primary prevention of CDAD. Additional estimates came from local data and the literature. Sensitivity analyses were conducted to assess how plausible changes in variables impacted the results. RESULTS Treatment with oral probiotics led to direct costs of CDN $24 per course of treatment per patient. On average, patients treated with oral probiotics had a lower overall cost compared with usual care (CDN $327 vs $845). The risk of CDAD was reduced from 5.5% in those not receiving oral probiotics to 2% in those receiving oral probiotics. These results were robust to plausible variation in all estimates. CONCLUSIONS Oral probiotics as a preventive strategy for CDAD resulted in a lower risk of CDAD as well as cost-savings. The cost-savings may be greater in other healthcare systems that experience a higher incidence and cost associated with CDAD. Infect Control Hosp Epidemiol 2016;37:1079-1086.

The Validation of a Novel Surveillance System for Monitoring Bloodstream Infections in the Calgary Zone.

Background. Electronic surveillance systems (ESSs) that utilize existing information in databases are more efficient than conventional infection surveillance methods. The objective was to assess an ESS for bloodstream infections (BSIs) in the Calgary Zone for its agreement with traditional medical record review. Methods. The ESS was developed by linking related data from regional laboratory and hospital administrative databases and using set definitions for excluding contaminants and duplicate isolates. Infections were classified as hospital-acquired (HA), healthcare-associated community-onset (HCA), or community-acquired (CA). A random sample of patients from the ESS was then compared with independent medical record review. Results. Among the 308 patients selected for comparative review, the ESS identified 318 episodes of BSI of which 130 (40.9%) were CA, 98 (30.8%) were HCA, and 90 (28.3%) were HA. Medical record review identified 313 episodes of which 136 (43.4%) were CA, 97 (30.9%) were HCA, and 80 (25.6%) were HA. Episodes of BSI were concordant in 304 (97%) cases. Overall, there was 85.5% agreement between ESS and medical record review for the classification of where BSIs were acquired (kappa = 0.78, 95% Confidence Interval: 0.75-0.80). Conclusion. This novel ESS identified and classified BSIs with a high degree of accuracy. This system requires additional linkages with other related databases.

Mapping the core: chlamydia and gonorrhea infections in Calgary, Alberta.

OBJECTIVES: To examine the spatial patterning of the individuals with gonorrhea or chlamydia infection in the Calgary Health Region (CHR) to target prevention and control activities. METHODS: A Geographic Information System was used to map the prevalence rates of gonorrhea and chlamydia infection in the CHR to 2001 Census Tracts in the CHR. Data from the 2001 Canadian Census were used to describe the socioeconomic status (SES) of these areas. RESULTS: Low SES indicators correlated with each other (low median household income, lower education, single mothers) as did high SES indicators (married, owning a dwelling, high median income, university education). A correlation was detected between areas of low SES and areas of high prevalence rates for gonorrhea and for chlamydia. These areas clustered primarily downtown and in the northeast part of the city. CONCLUSIONS: Nodes and corridors of activity in Calgary were detected in correlation studies of the 2001 Census variables used. The core (high prevalence) areas should be the areas targeted for sexually transmitted infection prevention and control. This can be done at the community level through measures such as more sexually transmitted infection clinics operating with longer hours in areas identified from this mapping.

Ventilator-associated pneumonia in severe traumatic brain injury.

INTRODUCTION: Pneumonia is an important cause of morbidity following severe traumatic brain injury (TBI). However, previous studies have been limited by inclusion of specific patient subgroups or by selection bias. The primary objective of this study was to describe the incidence, risk factors for, and outcome of ventilator-associated pneumonia in an unselected population-based cohort of patients with severe TBI. An additional goal was to define the relationship of ventilator-associated pneumonia (VAP) with nonneurological organ dysfunction. METHODS: A prospective, observational cohort study was performed at Foothills Medical Centre, the sole adult tertiary-care trauma center servicing southern Alberta. All patients with severe TBI requiring ventilation for more than 48 hours between May 1, 2000 and December 30, 2002 were included. RESULTS: A total of 60 patients (45%) acquired VAP for an incidence density of 42.7/1000 ventilator days. Patients with polytrauma were at higher risk (risk ratio 1.7, 95% confidence interval, 0.9-3.1) for development of VAP than those with isolated head injury. Development of VAP was associated with a significantly greater degree of nonneurological organ system dysfunction. Although VAP was not associated with increased hospital mortality, patients who developed VAP had a longer duration of mechanical ventilation (15 versus 8 days, p < 0.0001), longer intensive care unit (17 versus 9 days, p < 0.0001) and hospital (60 versus 28 days, p = 0.003) lengths of stay, and more often required tracheostomy (35 versus 18%, p = 0.003). CONCLUSIONS: VAP occurs frequently and is associated with significant morbidity in patients with severe TBI.

The measurement of influenza vaccine coverage among health care workers.

BACKGROUND: Annual influenza vaccination is recommended for health care workers in both the United States and Canada. Estimations of vaccine coverage are commonly used to evaluate these vaccination programs. PURPOSE: We identify, discuss, and illustrate challenges including definitions of health care worker (HCW), selection of indicators, and data sources in the estimation of staff influenza vaccination coverage rates. METHODS: To illustrate the impact of the factors we discuss, we created a database of a simulated pool of HCWs that included varying proportions of permanent, casual, and contract staff under differing scenarios of staff turnover and differing probabilities of individuals being vaccinated. The Excel 97 random number generator (Microsoft) was used to randomly allocate the HCW to different strata under differing staff turnover rates and to designate individuals as being vaccinated. RESULTS: The nature of the staff targeted in the program policy has a large impact on the estimations of vaccine coverage. Different indicators provide data that might be useful for different purposes. The counts in the numerator and denominator of a period prevalence may be useful for estimation of the total workload required of the vaccination program. An incidence density might be useful as an indicator of the efficiency of the program in "capturing" staff for vaccination. The indicator that may be easiest is the point prevalence. CONCLUSION: Program evaluators must think carefully when planning to estimate staff vaccination coverage to avoid invalid comparisons of estimates over time and place. State or province-wide targets for health care worker (HCW) vaccination may be meaningless unless appropriate criteria for the calculation of influenza vaccination rates are developed and specified.

Theory and models for planning and evaluating institutional influenza prevention and control programs.

BACKGROUND: Low rates of staff influenza vaccine coverage occur in many health care facilities. Many programs do not offer vaccination to physicians or to volunteers, and some programs do not measure coverage or do so only for a subset of staff. The use of theory in planning and evaluation may prevent these problems and lead to more effective programs. METHOD: We discuss the use of theory in the planning and evaluation of health programs and demonstrate how it can be used for the evaluation and planning of a hospital or nursing home influenza control program. RESULTS: The application of theory required explicit statement of the goals of the program and examination of the assumptions underlying potential program activities. This indicated that staff should probably be considered as employees, volunteers, physicians, and contractors of the facility. It also directed attention to evidence-based strategies for increasing vaccination rates. CONCLUSION: The application of a program planning model to a problem of institutional influenza prevention may prevent planners from excluding important target populations and failing to monitor the important indicators of program success.