Infectious Disease Commons^™

Epidemiology Crucial To Cracking Elizabethkingia Crisis, Angela Tonozzi

Journal of Patient-Centered Research and Reviews

The author explains the epidemiological methods, tools and personnel required to pinpoint the source of Wisconsin’s 2016 outbreak of Elizabethkingia infections.

The Role Of Mathematical Modeling In Designing And Evaluating Antimicrobial Stewardship Programs, Lester Caudill, Joanna R. Wares

Department of Math & Statistics Faculty Publications

Antimicrobial agent effectiveness continues to be threatened by the rise and spread of pathogen strains that exhibit drug resistance. This challenge is most acute in healthcare facilities where the well-established connection between resistance and sub-optimal antimicrobial use has prompted the creation of antimicrobial stewardship programs (ASPs). Mathematical models offer tremendous potential for serving as an alternative to controlled human experimentation for assessing the effectiveness of ASPs. Models can simulate controlled randomized experiments between groups of virtual patients, some treated with the ASP measure under investigation, and some without. By removing the limitations inherent in human experimentation, including health risks, study …

Treatment And Prevention Of Human Rotavirus (Hrv) In Developing Countries: The Potential Of Avian Immunoglobulin Y, Christa Brown

Senior Honors Theses

Rotavirus gastroenteritis is a leading cause of childhood mortality, killing ~1400 children younger than five daily, primarily through severe diarrheal dehydration. Eighty-five percent of this mortality occurs in developing countries where rotavirus vaccines are not widely implemented and are only partially effective. In those countries, it has proven difficult to implement the recommended supportive therapies like oral rehydration therapy (ORT) on a wide scale due to lack of both medical infrastructure and private economic investment combined with cultural bias against ORT. IgY targeting human rotavirus (anti-HRV IgY) shows potential as a passive immunotherapy that reduces rotavirus-associated morbidity and mortality, augments …

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …

Proteome And Protein Network Analyses Of Memory T Cells Find Altered Translation And Cell Stress Signaling In Treated Human Immunodeficiency Virus Patients Exhibiting Poor Cd4 Recovery, Sausan Azzam, Daniela M. Schlatzer, Sean Maxwell, Xiaolin Li, Douglas Bazdar, Yanwen Chen, Robert Asaad, Jill S. Barnholtz-Sloan, Mark R. Chance, Scott F. Sieg

Faculty Scholarship

Background. Human immunodeficiency virus (HIV) patients who experience poor CD4 T-cell recovery despite viral suppression during antiretroviral therapy (ART) are known as immunological nonresponders. The molecular mechanism(s) underlying incomplete immune restoration during ART is not fully understood. Methods. Label-free quantitative proteomics on single-cell type central memory T cells were used to reveal relative protein abundance changes between nonresponder, responder (good CD4 recovery during ART), and healthy individuals. Proteome changes were analyzed by protein pathway and network analyses and verified by selected reaction monitoring mass spectrometry. Results. Proteomic analysis across groups detected 155 significant proteins from 1500 nonredundant proteins. Pathway and …

Toward Earlier Inclusion Of Pregnant And Postpartum Women In Tuberculosis Drug Trials: Consensus Statements From An International Expert Panel., Amita Gupta, Jyoti S. Mathad, Susan M. Abdel-Rahman, Jessica D. Albano, Radu Botgros, Vikki Brown, Renee S. Browning, Liza Dawson, Kelly E. Dooley, Devasena Gnanashanmugam, Beatriz Grinsztejn, Sonia Hernandez-Diaz, Patrick Jean-Philippe, Peter Kim, Anne D. Lyerly, Mark Mirochnick, Lynne M. Mofenson, Grace Montepiedra, Jeanna Piper, Leyla Sahin, Radojka Savic, Betsy Smith, Hans Spiegel, Soumya Swaminathan, D Heather Watts, Amina White

Manuscripts, Articles, Book Chapters and Other Papers

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human …

Expression Of Complement And Toll-Like Receptor Pathway Genes Is Associated With Malaria Severity In Mali: A Pilot Case Control Study, Rafal S. Sobota, Antoine Dara, Jessica E. Manning, Amadou Niangaly

Dartmouth Scholarship

Background: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood.

Methods: To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression …

Decrease In Driveline Infections With Change In Driveline Management Protocol, Saima Aslam, Jennifer Dan, Amanda Topik, Michael Belyk, Francesca Torriani, Randy Taplitz, Jorge Silva-Enciso, Denise Barnard, Barry Greenberg, Jack Copeland, Victor Pretorius, Eric Adler

The VAD Journal

Background: Driveline infections (DLI) are a significant cause of morbidity and mortality in ventricular assist device (VAD) recipients. We compared driveline infection (DLI) rate after an institutional change in driveline management protocol.

Methods: We retrospectively reviewed records of left VAD recipients at our institution, based on driveline management. Group 1: daily driveline dressing change consisting of chlorhexidine cleansing, sterile 4x4 gauze, and use of an abdominal binder. Group 2: Dressing change every 3 days consisting of chlorhexidine cleansing, non-sterile silver-impregnated foam with overlying clear dressing, and use of a driveline anchor. Follow-up was censored at first DLI, device removal, transplant …

The Association Between Vitamin A Status Or Supplementation And Hiv/Aids, Mikaela Kathleen Curtis

Food Science and Nutrition

The human immunodeficiency virus (HIV) has infected millions of people since the start of the epidemic in the early 1980s. HIV is the etiologic agent of the acquired immunodeficiency syndrome (AIDS), which has taken millions of lives. It is extremely difficult for particular populations to receive medication to treat HIV infection and prevent the progression of HIV to AIDS. Multiple studies have examined the effect of vitamin A on HIV infection, due to its immune stimulating effects. It is unclear whether an association exists between vitamin A and different aspects of HIV. This review examined the effect of vitamin A …

Micro-Rna And Mrna Profiles Associated With Ectopic Germinal Center Formation In Thymus Samples Of Patients With Autoimmune Myas, Manjistha Sengupta, Bi-Dar Wang, Norman H. Lee, Gary Cutter, Linda Louise Kusner, Henry J. Kaminski

GW Research Days 2016 - 2020

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction (NMJ). A characteristic pathology of patients with early onset MG is thymic hyperplasia with ectopic germinal centers (GC). However, mechanisms that trigger and maintain thymic hyperplasia are poorly characterized. Micro-RNAs (miRNA) are small, non-coding RNAs that are increasingly appreciated to be involved in the pathology of several autoimmune diseases. In order to determine the central mechanisms involved in the pathology, thymus samples from MG patients were assessed by histology and grouped based on appearance of GC compared to …

Use Of Concomitant Antibiotics During Treatment For Clostridium Difficile Infection (Cdi) In Pediatric Inpatients: An Observational Cohort Study., Vanessa W. Stevens, Cary Thurm, Elyse M. Schwab, Matthew P. Kronman, Jeffrey S. Gerber, Samir S. Shah, Jason G. Newland, Joshua Courter, Sarah Parker, Thomas V. Brogan, Adam L. Hersh

Manuscripts, Articles, Book Chapters and Other Papers

Concomitant antibiotic use during treatment for Clostridium difficile infection (CDI) increases the risk of recurrence. Across a network of children's hospitals, 46% of patients treated for CDI received concomitant antibiotics for a median of 7 days. Concomitant antibiotic use was more common among patients with malignancies, and solid organ or bone marrow transplant. Unnecessary concomitant antibiotic use in CDI patients is a potential target for pediatric antimicrobial stewardship.

Antimicrobial Stewardship Barriers And Goals In Pediatric Oncology And Bone Marrow Transplantation: A Survey Of Antimicrobial Stewardship Practitioners., Joshua Wolf, Yilun Sun, Li Tang, Jason G. Newland, Jeffrey S. Gerber, Christie J. Van Dyke, Saul R. Hymes, Diana Yu, Delia C. Carias, Penelope A. Bryant, Pediatric Hematology/Oncology Antimicrobial Stewardship Interest Group

Manuscripts, Articles, Book Chapters and Other Papers

We undertook a cross-sectional survey of antimicrobial stewardship clinicians in North America and Australasia regarding practices, goals, and barriers to implementation of stewardship for pediatric oncology patients. Goals and barriers were similar regardless of clinician or institutional characteristics and geographic location. Strategies addressing these factors could help optimize antimicrobial use.

Multi-Level Correlates Of Safer Conception Methods Awareness And Attitudes Among Ugandan Hiv Clients With Fertility Intentions., Glenn J. Wagner, Mahlet A. Woldetsadik, Jolly Beyeza-Kashesya, Kathy Goggin, Deborah Mindry, Sarah Finocchario-Kessler, Sarah Khanakwa, Rhoda K. Wanyenze

Manuscripts, Articles, Book Chapters and Other Papers

Many people living with HIV desire childbearing, but low cost safer conception methods (SCM) such as timed unprotected intercourse (TUI) and manual self-insemination (MSI) are rarely used. We examined awareness and attitudes towards SCM, and the correlates of these constructs among 400 HIV clients with fertility intentions in Uganda. Measures included awareness, self-efficacy, and motivation regarding SCM, as well as demographics, health management, partner and provider characteristics. Just over half knew that MSI (53%) and TUI (51%) reduced transmission risk during conception, and 15% knew of sperm washing and pre-exposure prophylaxis. In separate regression models for SCM awareness, motivation, and …

Sepsis Management: An Evidence-Based Approach., Muhammad Akbar Baig, Hira Shahzad, Bushra Jamil, Erfan Hussain

Department of Medicine

The Surviving Sepsis Campaign (SSC) guidelines have outlined an early goal directed therapy (EGDT) which demonstrates a standardized approach to ensure prompt and effective management of sepsis. Having said that, there are barriers associated with the application of evidence-based practice, which often lead to an overall poorer adherence to guidelines. Considering the global burden of disease, data from low- to middle-income countries is scarce. Asia is the largest continent but most Asian countries do not have a well-developed healthcare system and compliance rates to resuscitation and management bundles are as low as 7.6% and 3.5%, respectively. Intensive care units are …

Molecular Evolution And Intraclade Recombination Of Enterovirus D68 During The 2014 Outbreak In The United States., Yi Tan, Ferdaus Hassan, Jennifer E. Schuster, Ari Simenauer, Rangaraj Selvarangan, Rebecca A. Halpin, Xudong Lin, Nadia Fedorova, Timothy B. Stockwell, Tommy Tsan-Yuk Lam, James D. Chappell, Tina V. Hartert, Edward C. Holmes, Suman R. Das

Manuscripts, Articles, Book Chapters and Other Papers

In August 2014, an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data, there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipeline for EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, MO, collected during the 2014 …

Safety And Immunogenicity Of Sequential Rotavirus Vaccine Schedules., Romina Libster, Monica Mcneal, Emmanuel B. Walter, Andi L. Shane, Patricia Winokur, Gretchen Cress, Andrea A. Berry, Karen L. Kotloff, Kwabena Sarpong, Christine B. Turley, Christopher J. Harrison, Barbara A. Pahud, Jyothi Marbin, John Dunn, Jill El-Khorazaty, Jill Barrett, Kathryn M. Edwards, Vteu Rotavirus Vaccine Study Work Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone.

METHODS: Randomized, multicenter, open-label study. Healthy infants (6-14 weeks of age) were randomized to receive rotavirus vaccines in 1 of 5 different schedules (2 using a single vaccine for all doses, and 3 using mixed schedules). The group receiving …

The Gras Sensor In Staphylococcus Aureus Mediates Resistance To Host Defense Peptides Differing In Mechanisms Of Action, Siyang Chaili, Ambrose L. L. Cheung, Arnold S. Bayer, Yan Q. Xiong, Alan Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

Staphylococcus aureus uses the two-component regulatory system GraRS to sense and respond to host defense peptides (HDPs). However, the mechanistic impact of GraS or its extracellular sensing loop (EL) on HDP resistance is essentially unexplored. Strains with null mutations in the GraS holoprotein (ΔgraS) or its EL (ΔEL) were compared for mechanisms of resistance to HDPs of relevant immune sources: neutrophil α-defensin (human neutrophil peptide 1 [hNP-1]), cutaneous β-defensin (human β-defensin 2 [hBD-2]), or the platelet kinocidin congener RP-1. Actions studied by flow cytometry included energetics (ENR); membrane permeabilization (PRM); annexin V binding (ANX), and cell death protease activation (CDP). …

Multilevel Analysis Of Individual, Neighborhood, And Health Care Facility Characteristics Associated With Achievement And Maintenance Of Hiv Viral Suppression Among Persons Newly Diagnosed With Hiv In New York City, Ellen W. Wiewel

Dissertations, Theses, and Capstone Projects

Objective

To investigate the effect of individual, health care facility, and neighborhood characteristics on achievement and maintenance of HIV viral suppression, among New York City residents aged 13 years and older diagnosed with HIV between 2006 and 2012.

Methods

I used individual-level data from the New York City HIV surveillance registry and Case Surveillance-Based Sampling, facility-level data from the surveillance registry, and neighborhood-level data from the U.S. Census and American Community Survey. The outcomes of interest were first viral suppression after diagnosis (Aims 1 and 3; ≤400 copies/mL) and virologic failure after first suppression among persons who achieved suppression (Aim …

Case Report: Recurrent Staphylococcal Scalded Skin Syndrome In Healthy Term Neonate Despite Full Course Of Antibiotic Therapy, Indira Bhavsar, Rebecca Hayes, Amy Vaughan

Marshall Journal of Medicine

Background

Staphylococcal scalded skin syndrome (SSSS) describes a blistering skin infection caused by the exfoliative toxin in the bacterium Staphylococcus aureus. It more commonly affects the infant population and is characterized by large blistering bullae that rupture upon application of pressure.

Case description

We describe a case of recurrent SSSS in a healthy term neonate who initially presented with a perioral rash on day of life (DOL) 11 that quickly became vesicular with new lesions on the sternum and extremities. The patient’s rash began to resolve upon administration of culture-specific IV antibiotics. She was appropriately treated with a 14-day …

First Described Case Of Group B Streptococcus Pelvic Abscess In A Patient With No Medical Comorbidities, Paul Tyan, Elias Abi-Khalil, Karthik Dwarki, Gaby N. Moawad

Obstetrics and Gynecology Faculty Publications

Background. Group B Streptococcus is an organism that commonly infects a wide range of hosts including infants in the first week of life, pregnant women, and older age adults as well as adults with underlying medical comorbidities.

Case. Large pelvic abscess in a nonpregnant patient found to be caused by Group B Streptococcuswas treated successfully with IR guided drainage and antibiotics.

Conclusion. Though rare, GBS can still be a cause of invasive infection even in individuals who are nonpregnant and have no underlying comorbidities. Empiric antibiotic coverage for this organism should be kept in mind when treating an abscess.