Bacterial Infections and Mycoses Commons^™

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman

Neal Silverman

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur …

Use Of Urine Antigen Testing For Blastomyces In An Integrated Health System, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Purpose: Blastomycosis, an endemic fungal infection, mimics many other diseases. We explored the use of Blastomyces urine antigen (BuAg), reportedly the most sensitive noninvasive test, in clinical practice and compared it to other noninvasive tests.

Methods: A total of 836 BuAg tests performed on unique patients (first test only) at one large integrated health system from June 2013 to May 2016 were retrospectively reviewed to examine test characteristics and demographic features. Of these, 100 cases from 2015, a year containing a large local blastomycosis outbreak, were randomly selected for detailed analysis.

Results: Demographics for the BuAg-tested population: mean age 54.9 …

Fmt Placed By Colonoscopy: Systematic Review And Meta-Analysis, Nadia Huq, Veena Kumaravel, Aboud Affi, Maharaj Singh

Aurora Gastroenterology Faculty

Background: Fecal transplants are successful in the treatment of recurrent or refractory Clostridium difficile infections (CDI), but there is no consensus on the best method of instillation. Studies have shown greater success with lower gastrointestinal tract placement, but technical aspects of placement are not validated.

Purpose: This review aims to identify common traits and procedural techniques of successful fecal microbiota transplant (FMT) therapy via colonoscopy.

Methods: An electronic search was conducted using OVID Medline and PubMed for articles published from January 2010 to January 2016. The primary outcome of interest was cure by FMT placed via colonoscopy.

Results: Of the …

Superbugs Versus Outsourced Cleaners: Employment Arrangements And The Spread Of Health Care-Associated Infections, Adam Seth Litwin, Ariel C. Avgar, Edmund R. Becker

Adam Seth Litwin

On any given day, about one in 25 hospital patients in the United States has a health care–associated infection (HAI) that the patient contracts as a direct result of his or her treatment. Fortunately, the spread of most HAIs can be halted through proper disinfection of surfaces and equipment. Consequently, cleaners—“environmental services” (EVS) in hospital parlance—must take on the important task of defending hospital patients (as well as staff and the broader community) from the spread of HAIs. Despite the importance of this task, hospitals frequently outsource this function, increasing the likelihood that these workers are under-rewarded, undertrained, and detached …

Burkholderia Pseudomallei Enters The Brain And Spinal Cord Via The Trigeminal Nerve, Heidi Walkden, James St John, Lynn Nazareth, Jenny Ekberg

Jenny Ekberg

Background

The trigeminal nerve is the largest cranial nerve responsible for sensation in the face and motor functions such as chewing. It constitutes a direct route from the nasal cavity into the brain (Fig. 1). Despite this, only a handful of microorganisms are thought to infect the brain via this route.

The tropical disease melioidosis caused by Burkholderia pseudomallei is endemic to the northern Australia and south-east Asia. The main route of transmission is via inhalation of droplets and soil. The Australian variant can result in brain infection, but the mechanism of infection is unknown.

Here, we investigated whether …

Fungal Infections From Human And Animal Contact, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Fungal infections in humans resulting from human or animal contact are relatively uncommon, but they include a significant proportion of dermatophyte infections. Some of the most commonly encountered diseases of the integument are dermatomycoses. Human or animal contact may be the source of all types of tinea infections, occasional candidal infections, and some other types of superficial or deep fungal infections. This narrative review focuses on the epidemiology, clinical features, diagnosis and treatment of anthropophilic dermatophyte infections primarily found in North America. Other human-acquired and zoonotic fungal infections also are discussed in brief.

Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz

Christian Mueller

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with …

Type I Interferon Induction By Neisseria Gonorrhoeae: Dual Requirement Of Cyclic Gmp-Amp Synthase And Toll-Like Receptor 4, Warrison A. Andrade, Sarika Agarwal, Shunyan Mo, Scott A. Shaffer, Joseph P. Dillard, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Douglas T. Golenbock

Katherine A. Fitzgerald

The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression. Here, we reveal a cytosolic response to GC DNA that also contributes to type I IFN induction. We demonstrate that …

Structural And Molecular Analysis Of A Protective Epitope Of Lyme Disease Antigen Ospa And Antibody Interactions, Shivender Shandilya, Nese Kurt Yilmaz, Ejemel Monir, Andrew Sadowski, William D. Thomas, Mark S. Klempner, Celia A. Schiffer, Yan Wang

Celia A. Schiffer

The murine monoclonal antibody LA-2 recognizes a clinically protective epitope on outer surface protein (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease in North America. Human antibody equivalence to LA-2 is the best serologic correlate of protective antibody responses following OspA vaccination. Understanding the structural and functional basis of the LA-2 protective epitope is important for developing OspA-based vaccines and discovering prophylactic antibodies against Lyme disease. Here, we present a detailed structure-based analysis of the LA-2/OspA interaction interface and identification of residues mediating antibody recognition. Mutations were introduced into both OspA and LA-2 based on computational predictions on …

Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss,, Daniel R. Caffrey, Neal S. Silverman, Adam R. Wespiser, Catherine A. Hill

Neal Silverman

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing approximately 57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, …

Blastomyces: Why Be Dimorphic?, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

In introducing the infectious disease focus for this edition of the Journal of Patient-Centered Research and Reviews, the author describes the unsolved mysteries surrounding the dimorphic fungus Blastomyces and the related pathogenesis of pulmonary blastomycosis.

Clinical Approach To Nonresponsive Pneumonia In Adults Diagnosed By A Primary Care Clinician: A Retrospective Study, Kiley B. Vander Wyst, Jessica J. F. Kram, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Purpose

Community-acquired pneumonia (CAP) is commonly diagnosed in the primary care setting. Management of nonresponsive pneumonia (NRP), i.e. failure to respond to CAP treatment, is not clearly understood. The purpose of this study was to describe the initial work-up and treatment of CAP in the ambulatory primary care setting and to determine relative proportion of, diagnostic approach to and treatment of NRP.

Methods

We retrospectively studied adult patients diagnosed with CAP within our large, integrated health care system from October 2006 through July 2013. Cases were defined as patients with CAP who worsened after 4 days, or did not improve …

Geodemographic Features Of Human Blastomycosis In Eastern Wisconsin, Megan E. Huber, Dennis J. Baumgardner, Jessica J. F. Kram, Melissa A. Lemke

Dennis J. Baumgardner, MD

Purpose

Blastomycosis is an endemic fungal infection. In rural northern Wisconsin, blastomycosis cases are associated with certain environmental features including close proximity to waterways. Other studies have associated blastomycosis with particular soil chemicals. However, blastomycosis also occurs in urban and suburban regions. We explored the geodemographic associations of blastomycosis cases in the more urban/suburban landscape of eastern Wisconsin.

Methods

We conducted a retrospective study of 193 laboratory-identified blastomycosis cases in a single eastern Wisconsin health system, 2007–2015. Controls were 250 randomly selected cases of community-diagnosed pneumonia from a similar time period. Geographic features of home addresses were explored using Google …

Disease-Causing Fungi In Homes And Yards In The Midwestern United States, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

A number of fungal pathogens that may result in a variety of human diseases are found in residential homes and yards. The growth of these microscopic fungi is often favored by particular characteristics of the dwelling and nearby outdoor environment. Evolved virulence factors or increased ability of specific fungi to grow in diverse, and sometimes harsh, microenvironments presented by the domestic environment may promote growth and pathogenesis. Infection may occur by inhalation or direct inoculation and include endemic fungi in addition to opportunistic or emerging species. Systemic or locally aggressive fungal infections are particularly likely and may be life-threatening in …

Geographic Distribution Of Maternal Group B Streptococcus Colonization And Infant Death During Birth Hospitalization: Eastern Wisconsin, Jessica J. F. Kram, Dennis J. Baumgardner, Kiley B. Vander Wyst, Melissa A. Lemke

Dennis J. Baumgardner, MD

Purpose

Maternal group B Streptococcus (GBS) can be transmitted from a colonized mother to newborn during vaginal delivery and may or may not contribute to infant death. This study aimed to explore the geographic distribution and risk factors of maternal GBS colonization and infant death during birth hospitalization.

Methods

We retrospectively studied mothers with live birth(s) in a large eastern Wisconsin hospital system from 2007 through 2013. Associations between maternal and neonatal variables, GBS colonization and infant death were examined using chi-squared, Mann-Whitney U and t-tests. Multivariable logistic regression models also were developed.

Results

Study population (N = 99,305) had …

Isoniazid Completion Rates For Latent Tuberculosis Infection Among College Students Managed By A Community Pharmacist, Karl Hess, Jeffery Goad, Joanne Wu, Kathleen Johnson

Jeff Goad

Objective: The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy oil a college Campus. and to describe patient characteristics. Participants: Participants were university Students diagnosed with LTBI. Methods: The authors conducted a retrospective review, of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken. characteristics of completers versus noncompleters. average time to treatment completion, and reported adverse drug events. Results: The 9-month completion rate was 59%, and the …

A Comparison Of Pharmacist Travel-Health Specialists' Versus Primary Care Providers' Recommendations For Travel-Related Medications, Vaccinations, And Patient Compliance In A College Health Setting, Melissa J. Durham, Jeffery A. Goad, Lawrence S. Neinstein, Mimi Lou

Jeff Goad

Background. Pretravel medication and vaccination recommendations and receipt were compared between primary care providers (PCPs) without special training and clinical pharmacists specializing in pretravel health. Methods. A retrospective chart review of patients seen for pretravel health services in a pharmacist-run travel clinic (PTC) compared to PCPs at a University Student Health Center. Vaccine/medication recommendations were assessed for consistency with national/international guidelines. Medical/pharmacy records were queried to determine the receipt of medications/vaccinations. Results. The PTC recommended antibiotics for travelers' diarrhea were given more often when indicated (96% vs 50%, p < 0.0001), and patients seen in the PTC received their medications more …

Vaccine-Preventable Diseases In Travelers, Edith Mirzaian, Jeffery Goad, Ani Amloian, Fady Makar

Jeff Goad

Travel to the developing world is increasing among those from developed countries, placing them at risk for vaccine preventable and non-vaccine preventable diseases. From 2007-2011, the GeoSentinel Network reported 737 returned travelers with a vaccine preventable disease. While it is essential that clinicians use vaccines when available for a disease of risk, they should also be aware that the vast majority of diseases acquired by travelers are non-vaccine preventable. The vaccine preventable diseases can be divided into routine travel vaccines, special travel vaccines and routine vaccines used for travel. The routine travel vaccines include Hepatitis A and B, typhoid; special …

Malaria-Induced Nlrp12/Nlrp3-Dependent Caspase-1 Activation Mediates Inflammation And Hypersensitivity To Bacterial Superinfection, Marco A. Ataide, Warrison A. Andrade, Dario S. Zamboni, Donghai Wang, Maria Do Carmo Souza, Bernardo S. Franklin, Samir Elian, Flaviano S. Martins, Dhelio Pereira, George W. Reed, Katherine A. Fitzgerald, Douglas T. Golenbock, Ricardo T. Gazzinelli

Katherine A. Fitzgerald

Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1beta. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-gamma-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1beta expression required a second stimulation with LPS and was also dependent on IFN-gamma-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1beta upon a second …

Treating Methicillin-Resistant Staphylococcus Aureus With The Drug Vancomycin In A Home Infusion Therapy Setting, Joshua Webb, Alberto Coustasse, Dennis Emmett

Dennis Emmett

The basic purpose of this paper is to examine the effects the home infusion therapy has on the cost, duration of, and effectiveness of treatment between those individuals under 60 and those 60 and over. The results show that those 60 and over had a slightly higher cost/day. The older age group had slightly smaller treatment duration, then the younger group. The number of adverse effects was small. The results suggest that home infusion therapy appears to be a viable alternative to hospitalization.

Treating Methicillin-Resistant Staphylococcus Aureus With The Drug Vancomycin In A Home Infusion Therapy Setting, Joshua L. Webb, Alberto Coustasse, Dennis Emmett

Alberto Coustasse, DrPH, MD, MBA, MPH

The basic purpose of this paper is to examine the effects the home infusion therapy has on the cost, duration of, and effectiveness of treatment between those individuals under 60 and those 60 and over. The results show that those 60 and over had a slightly higher cost/day. The older age group had slightly smaller treatment duration, then the younger group. The number of adverse effects was small. The results suggest that home infusion therapy appears to be a viable alternative to hospitalization.

Identification Of A Human Monoclonal Antibody To Replace Equine Diphtheria Anti-Toxin For The Treatment Of Diphtheria, Leila M. Sevigny, Brian J. Booth, Kirk J. Rowley, Brett A. Leav, Peter S. Cheslock, Kerry A. Garrity, Susan Sloan, Gregory J. Babcock, William D. Thomas, Mark Klempner, Yang Wang

William D Thomas Jr

Diphtheria anti-toxin (DAT) has been used to treat Corynebacterium diphtheriae infection for over one hundred years. While the global incidence of diphtheria has declined in the 20th century, the disease remains endemic in many parts of the world and significant outbreaks still occur. Diphtheria anti-toxin is an equine polyclonal antibody with considerable side effects that is in critically short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we cloned human monoclonal antibodies (HuMabs) directly from antibody secreting cells of human volunteers immunized with Td vaccine. We isolated a diverse panel of …

Compliance With The Centers For Disease Control And Prevention Recommendations For The Diagnosis And Treatment Of Sexually Transmitted Diseases, Bryan Kane, Linda Degutis, Helen Sayward, Gail D'Onofrio

Bryan G Kane MD

No abstract provided.

Tca Cycle Inactivation In Staphylococcus Aureus Alters Nitric Oxide Production In Raw 264.7 Cells, Chandirasegaran Massilamany, Arunakumar Gangaplara, Donald Gardner, James Musser, David Steffen, Greg Somerville, Jay Reddy

Greg A. Somerville

Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts …

Not Just Full Of Hot Air: Hyperbaric Oxygen Therapy Increases Survival In Cases Of Necrotizing Soft Tissue Infections, Joshua Shaw, Charles Psoinos, Timothy Emhoff, Heena Santry

Joshua J Shaw

INTRODUCTION: The utility of hyperbaric oxygen therapy (HBOT) in the treatment for necrotizing soft tissue infections (NSTI) has not been proven. Previous studies have been subject to significant selection bias since HBOT is not universally available at all medical centers and there is often considerable delay associated with its initiation. We examined the utility of HBOT for the treatment of NSTI in the modern era by isolating centers that have their own HBOT facilities. METHODS: We queried all centers in the University Health Consortium (UHC) database from 2008 to 2010 that have their own HBOT facilities (N=14). Cases of NSTI …

Infection With Streptococcus Pneumoniae Moderately Resistant To Penicillin Does Not Alter Clinical Outcome, Todd Gress, Kevin Yingling, Ronald Stanek, Maurice Mufson

Maurice A. Mufson

Increasingly, drug-resistant Streptococcus pneumoniae is an identified pathogen causing pneumonia, sepsis, and meningitis. Our study evaluated outcome variables of patients infected with strains of S. pneumoniae moderately resistant to penicillin. We retrospectively analyzed the data on 110 Huntington, West Virginia, community patients who had types 6, 9, 14, 19, and 23 pneumococcal infections between 1982 and 1994. These strains are most likely to demonstrate resistance. Comparing patients infected with sensitive vs. moderately resistant pneumococcal strains, we found no significant difference in days in the hospital (10.9 vs. 11.1, P =.96), days of fever (2.4 vs. 2.8, P =.74), or mortality …

Infection With Streptococcus Pneumoniae Moderately Resistant To Penicillin Does Not Alter Clinical Outcome, Todd Gress, Kevin Yingling, Ronald Stanek, Maurice Mufson

Todd W. Gress

Increasingly, drug-resistant Streptococcus pneumoniae is an identified pathogen causing pneumonia, sepsis, and meningitis. Our study evaluated outcome variables of patients infected with strains of S. pneumoniae moderately resistant to penicillin. We retrospectively analyzed the data on 110 Huntington, West Virginia, community patients who had types 6, 9, 14, 19, and 23 pneumococcal infections between 1982 and 1994. These strains are most likely to demonstrate resistance. Comparing patients infected with sensitive vs. moderately resistant pneumococcal strains, we found no significant difference in days in the hospital (10.9 vs. 11.1, P =.96), days of fever (2.4 vs. 2.8, P =.74), or mortality …

Nothing To Sneeze At! A Study Into Intra-Operative Contamination, David Graham, Benjamin Parkinson, Meghan Evans, Gerben Keijzers, Petra Derrington

Gerben Keijzers

Purpose: We performed a prospective study of sneezes from orthopaedic registrars to assess the potential for intra-operative contamination from a masked surgeon, and to determine if head position can alter the potential for contamination. Type of Study: Prospective controlled trial. Methods: Four orthopaedic registrars from the Gold Coast Hospital each inhaled pepper to precipitate a sneeze. Cultures were taken with and without standard Smith & Nephew™ surgical masks, in positions directly in front and to the sides of a masked registrar. The process was repeated three times for each registrar. A control plate was left exposed to the atmosphere. A …