Clinical Features of Patients Hospitalized for All Routes of Anthrax, 1880-2018: A Systematic Review.

Background: Anthrax is a toxin-mediated zoonotic disease caused by Bacillus anthracis, with a worldwide distribution recognized for millennia. Bacillus anthracis is considered a potential biowarfare agent.

Methods: We completed a systematic review for clinical and demographic characteristics of adults and children hospitalized with anthrax (cutaneous, inhalation, ingestion, injection [from contaminated heroin], primary meningitis) abstracted from published case reports, case series, and line lists in English from 1880 through 2018, assessing treatment impact by type and severity of disease.

The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides.

During infection, Bacillus anthracis bacilli encounter potent antimicrobial peptides (AMPs) such as defensins. We examined the role that B. anthracis capsule plays in protecting bacilli from defensins and other cationic AMPs by comparing their effects on a fully virulent encapsulated wild type (WT) strain and an isogenic capsule-deficient capA mutant strain.

Engineering an Fc-Fusion of a Capsule Degrading Enzyme for the Treatment of Anthrax.

Polymers of d-glutamic acid (PDGA) form the capsule of the highly virulent Ames strain of . PDGA is antiphagocytic and weakly immunogenic; it enables the bacteria to evade the innate immune responses. CapD is an enzyme that catalyzes the covalent anchoring of PDGA.

Burkholderia pseudomallei JW270 Is Lethal in the Madagascar Hissing Cockroach Infection Model and Can Be Utilized at Biosafety Level 2 to Identify Putative Virulence Factors.

Burkholderia pseudomallei, the causative agent of melioidosis, is classified by the CDC as a tier 1 select agent, and work involving it must be performed in a biosafety level 3 (BSL-3) laboratory. Three BSL-2 surrogate strains derived from B. pseudomallei 1026b, a virulent clinical isolate, have been removed from the CDC select agent list.

Treatment of experimental anthrax with pegylated circularly permuted capsule depolymerase.

Anthrax is considered one of the most dangerous bioweapon agents, and concern about multidrug-resistant strains has led to the development of alternative therapeutic approaches that target the antiphagocytic capsule, an essential virulence determinant of , the causative agent. Capsule depolymerase is a γ-glutamyltransferase that anchors the capsule to the cell wall of . Encapsulated strains of can be treated with recombinant capsule depolymerase to enzymatically remove the capsule and promote phagocytosis and killing by human neutrophils.

Panoramic imaged carotid atheromas are associated with increased neutrophil count: both validated, independent predictors of near-term myocardial infarction.

Objectives: Panoramic images (PXs) demonstrating calcified carotid artery atheromas (CCAAs) are associated with heightened risk of near-term myocardial infarction (MI). Elevated neutrophil counts (NC) within normal range 2,500-6,000 per mm are likewise associated with future MI signaling the role neutrophils play in the chronic inflammation process underlying coronary artery atherogenesis. We determined if CCAAs on PXs are associated with increased NC.

Poly-γ-Glutamic Acid Encapsulation of Inhibits Human Dendritic Cell Responses.

The capsule of is composed of a d isomer poly-γ-glutamic acid polymer, which is especially nonstimulatory to dendritic cells, even more so than similar mixed d, l isomer polymers from nonpathogenic species. Capsule is an essential virulence factor for , protecting the bacilli from phagocytosis by innate immune cells. In this study, we demonstrate that encapsulation provides a further pathogenic advantage by shielding more inflammatory Ags on the bacillus surface, thereby reducing dendritic cell responses.

Elevated White Blood Cell Count Resultant Atherogenesis is Associated With Panoramic-Imaged Carotid Plaque.

Purpose: Atherosclerotic plaques develop as a result of a low-grade, chronic, systemic inflammatory response to the injury of endothelial cells arising from lipid deposition within the intima. Increased white blood cell count (WBCC) is both a validated "biologic marker" of the extent of this inflammatory process and a key participant in the development of subsequent atherosclerotic ischemic heart disease manifesting as myocardial infarction. We sought to determine if calcified carotid artery plaque (CCAP) on a panoramic image (PI), also a validated risk indicator of future myocardial infarction, is associated with increased WBCC.

Red Cell Distribution Width, Unlike Neutrophil Lymphocyte Ratio Is Unable to Accurately Gauge Enhanced Systemic Inflammation Associated With Panoramic Imaged Carotid Plaque.

Introduction: We have previously shown that panoramic X-rays (PXs) demonstrating calcified carotid artery atheromas (CCAA) are associated with increased systemic inflammation demonstrating increased neutrophil lymphocyte ratios (NLRs), a validated risk indicator of fatal myocardial infarctions arising from coronary artery atherosclerosis. Using this same cohort of patients (with minor adjustments because of missing data), we sought to determine if a like association existed between PXs evidencing CCAA and elevated red blood cell distribution width (RDW) given conflicting data as its reliability relative to NLR as a biologic marker of system inflammation. We hypothesized that CCAAs on PXs would simultaneously be associated with both increased NLR and RDW.

Clindamycin Protects Nonhuman Primates Against Inhalational Anthrax But Does Not Enhance Reduction of Circulating Toxin Levels When Combined With Ciprofloxacin.

Background: Inhalational anthrax is rare and clinical experience limited. Expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking.

Methods: Rhesus macaques exposed to an aerosol of Bacillus anthracis spores were treated with ciprofloxacin, clindamycin, or ciprofloxacin + clindamycin after becoming bacteremic.

Opsono-Adherence Assay to Evaluate Functional Antibodies in Vaccine Development Against Bacillus anthracis and Other Encapsulated Pathogens.

The opsono-adherence assay is a functional assay that enumerates the attachment of bacterial pathogens to professional phagocytes. Because adherence is requisite to phagocytosis and killing, the assay is an alternative method to opsono-phagocytic killing assays. An advantage of the opsono-adherence assay is the option of using inactivated pathogens and mammalian cell lines, which allows standardization across multiple experiments.

Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2019.

This report updates the 2009 recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) regarding use of anthrax vaccine in the United States (Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP)], 2009. MMWR Recomm Rep 2010;59[No.

Severe Sleep Apnea Associated With Increased Systemic Inflammation and Decreased Serum Bilirubin.

Purpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) among older men has been associated with increased systemic inflammation, as evidenced by an increased neutrophil/lymphocyte ratio (NLR) and provocation of coronary artery atherosclerosis, potentially resulting in myocardial infarction (MI). The total serum bilirubin levels (TSBLs; formed primarily from senescent red blood cells via the catabolic pathway in the reticuloendothelial system) at the higher end of the normal reference range are anti-inflammatory. However, at the lower end of the physiologic range, they have been associated with increased adverse vascular events.

Relationship between symptomatic lower limb peripheral artery disease and calcified carotid artery plaque detected on panoramic images of neurologically asymptomatic males.

Objective: Males with peripheral arterial disease (PAD) are at high risk of ischaemic stroke given that atherogenic risk factors for both diseases are similar. We hypothesized that neurologically asymptomatic males diagnosed with PAD would demonstrate calcified carotid artery plaques (CCAP) on panoramic images (PI) significantly more often than similarly aged males not having PAD.

Methods: Investigators implemented a retrospective cross-sectional study.

Severe Obstructive Sleep Apnea With Imaged Carotid Plaque Is Significantly Associated With Systemic Inflammation.

Purpose: Persons with obstructive sleep apnea (OSA) are at heightened risk of myocardial infarction (MI) and stroke caused by adiposity and intermittent hypoxia, which provoke proinflammatory cytokines to induce systemic and vascular inflammation, resulting in endothelial dysfunction and development of atherosclerotic plaque. This study compared levels of systemic inflammation, as indexed by the neutrophil-to-lymphocyte ratio (NLR), between groups of patients with severe OSA with and without carotid artery calcified plaque (CACP and CACP, respectively) on their panoramic image (PI).

Materials And Methods: This study had a retrospective cross-sectional study design.

Formaldehyde and Glutaraldehyde Inactivation of Bacterial Tier 1 Select Agents in Tissues.

For safety, designated Select Agents in tissues must be inactivated and viability tested before the tissue undergoes further processing and analysis. In response to the shipping of samples of "inactivated" Bacillus anthracis that inadvertently contained live spores to nonregulated entities and partners worldwide, the Federal Register now mandates in-house validation of inactivation procedures and standardization of viability testing to detect live organisms in samples containing Select Agents that have undergone an inactivation process. We tested and validated formaldehyde and glutaraldehyde inactivation procedures for animal tissues infected with virulent B.

Positive Association Between Neutrophil-Lymphocyte Ratio and Presence of Panoramically Imaged Carotid Atheromas Among Men.

Purpose: Heightened levels of systemic inflammation documented by increased neutrophil-to-lymphocyte ratios (NLRs) characterize a robust atherosclerosis processes evidenced by carotid and coronary artery plaques at ultrasound and angiography with associated strokes and myocardial infarctions (MIs). Therefore, this study investigated whether calcified carotid artery plaques (CCAPs) on panoramic images (PIs), known to herald future stroke and MI, are associated with increased NLRs.

Materials And Methods: Using a cross-sectional study design, electronic medical records and PIs of non-Hispanic white men at least 55 years old who were treated by the dental service (January 1, 2017 to December 31, 2017) were retrieved.