Infectious Disease Commons^™

Immunogenicity And Protective Efficacy Of The Dar-901 Booster Vaccine In A Murine Model Of Tuberculosis, Timothy Lahey, Dominick Laddy, Krystal Hill, Jacqueline Schaeffer

Dartmouth Scholarship

The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.

Applying Multiple Data Collection Tools To Quantify Human Papillomavirus Vaccine Communication On Twitter., Philip M. Massey, Amy Leader, Elad Yom-Tov, Alexandra Budenz, Kara Fisher, Ann C. Klassen

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. There are several vaccines that protect against strains of HPV most associated with cervical and other cancers. Thus, HPV vaccination has become an important component of adolescent preventive health care. As media evolves, more information about HPV vaccination is shifting to social media platforms such as Twitter. Health information consumed on social media may be especially influential for segments of society such as younger populations, as well as ethnic and racial minorities.

OBJECTIVE: The objectives of our study were to quantify HPV vaccine communication on …

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Gene-Based Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …

Intravenous Versus Oral Antibiotics For Postdischarge Treatment Of Complicated Pneumonia., Samir S. Shah, Rajendu Srivastava, Susan Wu, Jeffrey D. Colvin, Derek J. Williams, Shawn J. Rangel, Waheeda Samady, Suchitra Rao, Christopher Miller, Cynthia Cross, Caitlin Clohessy, Matthew Hall, Russell Localio, Matthew Bryan, Gong Wu, Ron Keren, Pediatric Research In Inpatient Settings Network

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Postdischarge treatment of complicated pneumonia includes antibiotics administered intravenously via a peripherally inserted central venous catheter (PICC) or orally. Antibiotics administered via PICC, although effective, may result in serious complications. We compared the effectiveness and treatment-related complications of postdischarge antibiotics delivered by these 2 routes.

METHODS: This multicenter retrospective cohort study included children ≥2 months andadministration, classified as PICC or oral. The primary outcome was treatment failure. Secondary outcomes included PICC complications, adverse drug reactions, other related revisits, and a composite of all 4 outcomes, termed "all related revisits."

RESULTS: Among 2123 children, 281 (13.2%) received antibiotics …

A 9-Year-Old Boy With A Chest Mass And Eosinophilia., Laura E. Norton, Sean N. Curtis, Jennifer L. Goldman

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Update From The Advisory Committee On Immunization Practices., Jennifer E. Schuster, Sean O'Leary, David W. Kimberlin

Manuscripts, Articles, Book Chapters and Other Papers

The Advisory Committee on Immunization Practices (ACIP) consists of medical and public health experts who develop recommendations on vaccine use in the United States. The ACIP meets 3 times per year, and members and Centers for Disease Control (CDC) staff present findings and discuss vaccine research, vaccine effectiveness (VE) and safety, clinical trial results, and labeling/package insert information. Outbreaks of vaccine-preventable diseases and vaccine shortages are also discussed. Nonvoting representatives from the American Academy of Pediatrics and the Pediatric Infectious Diseases Society are present. The ACIP met on June 22-23, 2016 to discuss proposed recommendations for influenza vaccination, for human …

Bilateral Moyamoya Disease In A 2-Year-Old Pakistani Male Treated With Bilateral Encephaloduroarteriosynangiosis: A Positive Outcome., Shahvaiz Magsi, Adeel Khoja, Mansoor Ali Merchant Rameez, Ariba Khan, Noman Ishaque

Department of Medicine

Background. We present a rare case of bilateral moyamoya disease presenting as multiple strokes and neurological deficits, treated with the neurosurgical procedure, encephaloduroarteriosynangiosis (EDAS), in a 2-year-old male Pakistani minor. A positive outcome was achieved and the patient recovered fully. Case Summary. Our patient presented with a history of seizures and multiple episodes of hemiparesis (on and off weakness) at the age of 2 years. He had a delayed speech development and could not speak more than a few words. He had a slight slurring of speech too. He was diagnosed with bilateral moyamoya disease on Computed Tomography Angiography (CTA). …

Epidemiology And Impact Of Campylobacter Infection In Children In 8 Low-Resource Settings: Results From The Mal-Ed Study, Shahida Qureshi, Aneeta Hotwani, Sadia Shakoor, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Zulfiqar Ahmed Bhutta, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life.
Methods: Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter Stool and blood samples were assayed for markers of intestinal permeability and inflammation.
Results: A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter We describe a high …

Proceedings Of 2016 Aurora Scientific Day

Journal of Patient-Centered Research and Reviews

This supplement includes select abstracts presented at the 42nd annual Aurora Scientific Day research symposium, held May 25, 2016, in Milwaukee, Wisconsin. Aurora Scientific Day provides a forum for original research conducted by faculty, fellows, residents, students and other allied health professionals affiliated with Aurora Health Care, a not-for-profit health system comprised of integrated hospitals and clinics across eastern Wisconsin and northeastern Illinois.

Path To Resistance: Risk Factors Associated With Carbapenem-Resistant Pseudomonas Aeruginosa, Kushal Patel, Jessica J.F. Kram, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Background: An estimated 51,000 health care-associated Pseudomonas aeruginosa infections occur in the United States annually. More than 13% are secondary to non-carbapenem multidrug-resistant strains, which result in 400 yearly deaths. Traditional risk factors for resistance include ICU stay, mechanical ventilation, previous hospitalization and major comorbidities. As microbes evolve, risk factors also may evolve.

Purpose: To determine if traditional and/or new risk factors for P. aeruginosa resistance are valid and predictive of infection with carbapenem-resistant P. aeruginosa.

Methods: We retrospectively studied inpatients and outpatients ≥ 18 years old who presented to an Aurora Health Care facility with a positive P. …

Losing Ground: Awareness Of Congenital Cytomegalovirus In The United States, Sara M. Doutre, Tyson S. Barrett, Janelle Greenlee, Karl R. White

Journal of Early Hearing Detection and Intervention

One in 150 infants is born with cytomegalovirus (CMV) and one in 750 will have lifelong disabilities due to CMV. Even though congenital CMV is the leading viral cause of congenital disabilities and the leading non-genetic cause of childhood hearing loss, most adults have never heard of it. Data from the 2015 and 2016 HealthStyles^TM surveys were analyzed and compared to data from similar studies and show an awareness rate of 7% for US adults (5% for men and 9% for women), a statistically significant decrease from 2005 and 2010 studies. Predictors of awareness include gender and education level. …

A 5-Year-Old With Fever, Headache, Neck Stiffness, And Leg Pain., Joy L. Solano, Grace Winningham, Duha Al Zubeidi, Angela Myers

Manuscripts, Articles, Book Chapters and Other Papers

A 5-year-old boy presented with fever, headache, fatigue, neck stiffness, and 2 episodes of nocturnal urinary incontinence, prompting a visit to the emergency department. He had experienced intermittent frontal headaches and leg and buttock pain for several months, which had worsened over the previous 2 weeks. His history was notable for a spinal hemangioma with vascular tract, but he was otherwise healthy. On examination, he was febrile and tachycardic. He held his neck slightly rotated to the right with limited range of motion in all directions due to pain. No focal neurologic deficits were noted, and sensation and deep tendon …

An Unusual Case Of Escherichia Coli Meningitis And Bacteremia In An Elderly Woman Presenting With Intractable Low Back Pain, Andrea M. Lauffer, Mahmoud Shorman, Carl Mccomas

Marshall Journal of Medicine

Abstract

Introduction:

We report an unusual case of E. coli meningitis in an elderly woman who presented to the emergency room with a chief complaint of intractable low back pain.

Case Description:

A 67 year old woman presented to the emergency room for a chief complaint of intractable low back pain. After admission, the patient developed delirium. Blood cultures were drawn. Patient underwent a lumbar puncture which revealed purulent cerebrospinal fluid. Results of the cerebrospinal fluid and blood cultures revealed pan-sensitive E. coli.

Conclusion:

In the geriatric population, delayed presentation of meningitis can occur for various reasons. With the older …

Sociodemographic Factors Associated With Igg And Igm Seroprevalence For Human Cytomegalovirus Infection In Adult Populations Of Pakistan: A Seroprevalence Survey, Saira Ibrahim, Anwar Ali Siddiqui, Amna Siddiqui, Waquaruddin Ahmed, Paul A. H. Moss, El Nasir Lalani

Department of Biological & Biomedical Sciences

Background: The seroprevalence of human cytomegalovirus (HCMV) infection ranges from 30 to 90 % in developed countries. Reliable estimates of HCMV seroprevalence are not available for Pakistan. This study determined the seroprevalence and sociodemographic factors associated with HCMV infection in adult populations of Karachi, Pakistan.
Methods: A seroprevalence survey was conducted on 1000 adults, including residents of two semi-urban communities, and visitors to a government and a private hospital. Questionnaire-based interviews were conducted. Sera were analysed for HCMV-specific IgG and IgM. Chi-square or Fisher’s exact test was used for comparing sociodemographic variables against seropositivity of HCMV-IgG or IgM. Multiple logistic …

Immediate Blood Draw For Cd4+ Cell Count Is Associated With Linkage To Care In Durban, South Africa: Findings From Pathways To Engagement In Hiv Care, Susie Hoffman, Theresa M. Exner, Naomi Lince-Deroche, Cheng-Shiun Leu, Jessica L. Phillip, Elizabeth A. Kelvin, Anisha D. Gandhi, Bruce Levin, Dinesh Singh, Joanne E. Mantell, Kelly Blanchard, Gita Ramjee

Publications and Research

Background Timely linkage to care by newly-diagnosed HIV+ individuals remains a significant challenge to achieving UNAIDS 90-90-90 goals. Current World Health Organization (WHO) guidelines recommend initiating anti-retroviral treatment (ART) regardless of CD4+ count, with priority given to those with CD4+/μl. We evaluated the impact of not having a day-of-diagnosis CD4+ count blood draw, as recommended by South African guidelines, on time to linkage, using data from a prospective cohort study.

Methods Individuals (N = 2773) were interviewed prior to HIV counseling and testing at three public sector primary care clinics in the greater Durban area; 785 were newly-diagnosed and eligible …

Use Of A Multiplex Transcript Method For Analysis Of Pseudomonas Aeruginosa Gene Expression Profiles In The Cystic Fibrosis Lung, Alex H. Gifford, Sven D. Willger, Emily L. Dolben, Lisa A. Moulton, Dana Dorman, Heather Bean, Jane Hill, Thomas Hampton, Alix Ashare, Deborah Hogan

Dartmouth Scholarship

The discovery of therapies that modulate Pseudomonas aeruginosa virulence or that can eradicate chronic P. aeruginosa lung infections associated with cystic fibrosis (CF) will be advanced by an improved understanding of P. aeruginosa behavior in vivo We demonstrate the use of multiplexed Nanostring technology to monitor relative abundances of P. aeruginosa transcripts across clinical isolates, in serial samples, and for the purposes of comparing microbial physiology in vitro and in vivo The expression of 75 transcripts encoded by genes implicated in CF lung disease was measured in a variety of P. aeruginosa strains as well as RNA serial sputum samples …

Pyrimidine Pathway-Dependent And -Independent Functions Of The Toxoplasma Gondii Mitochondrial Dihydroorotate Dehydrogenase, Miryam Andrea Hortua Triana, Daniela Cajiao Herrera, Barbara H. Zimmermann, Barbara A. Fox, David Bzik

Dartmouth Scholarship

Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of de novo pyrimidine biosynthesis and is a proven drug target for inducing immunosuppression in therapy of human disease as well as a rapidly emerging drug target for treatment of malaria. In Toxoplasma gondii, disruption of the first, fifth, or sixth step of de novo pyrimidine biosynthesis induced uracil aux- otrophy. However, previous attempts to generate uracil auxotrophy by genetically deleting the mitochondrion-associated DHODH of T. gondii (Tg DHODH) failed. To further address the essentiality of Tg DHODH, mutant gene alleles deficient in Tg DHODH activity were designed to ablate the enzyme activity. …

Performance Of Point-Of-Care Cd4 Testing Technologies In Resource-Constrained Settings: A Systematic Review And Meta-Analysis, Minh D. Pham, Paul A. Agius, Lorena Romero, Peter Mcglynn, David Anderson, Suzanne M. Crowe, Stanley Luchters

Population Health, East Africa

Background: Point-of-care (POC) CD4 testing increases patient accessibility to assessment of antiretroviral therapy eligibility. This review evaluates field performance in low and middle-income countries (LMICs) of currently available POC CD4 technologies.

Methods: Eight electronic databases were searched for field studies published between January 2005 and January 2015 of six POC CD4 platforms: PointCare NOW™, Alere Pima™ CD4, Daktari™ CD4 Counter, CyFlow® CD4 miniPOC, BD FACSPresto™, and MyT4™ CD4. Due to limited data availability, meta-analysis was conducted only for diagnostic performance of Pima at a threshold of 350 cells/μl, applying a bivariate multi-level random-effects modelling approach. A covariate extended model was …

An Unusual Pathogen Causing Native Valve Endocarditis., Aneela Hussain, Nosheen Nasir, Bushra Jamil

Department of Medicine

No abstract provided.

Human Metapneumovirus Induces Reorganization Of The Actin Cytoskeleton For Direct Cell-To-Cell Spread, Farah El Najjar, Nicolás Cifuentes-Muñoz, Jing Chen, Haining Zhu, Ursula J. Buchholz, Carole L. Moncman, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. …

Immune- And Nonimmune-Compartment-Specific Interferon Responses Are Critical Determinants Of Herpes Simplex Virus-Induced Generalized Infections And Acute Liver Failure, Zachary M. Parker, Tracy Jo Pasieka, George A. Parker, David A. Leib

Dartmouth Scholarship

The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex virus 1 (HSV-1) infections, usually from encephalitis. Although rare, HSV-1 can also cause fulminant hepatic failure, which is often fatal. Although herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFN-αβγR-/- mice are exquisitely susceptible to liver infection following corneal infection with HSV-1. In this study, we used bone marrow chimeras of IFN-αβγR-/- (AG129) and wild-type (WT; 129SvEv) mice …

Early Haart Should Be Used For Treatment-Naive Hiv Patients With Pneumocystis Pneumonia, Maxwell L. Winkler

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Manzardo C, Esteve A, Ortega N, et al. Optimal timing for initiation of highly active antiretroviral therapy in treatment-naïve human immunodeficiency virus-1-infected individuals presenting with AIDS-defining diseases: the experience of the PISCIS Cohort. Clin. Microbiol. Infect. 2013 July;19(7):646-653. doi: 10.1111/j.1469-0691.2012.03991.x

Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher

Theses & Dissertations

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

Effects Of Tcpb Mutations On Biogenesis And Function Of The Toxin-Coregulated Pilus, The Type Ivb Pilus Of Vibrio Cholerae, Yang Gao, Caitlyn A. Hauke, Jarrad M. Marles, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae is the etiological agent of the acute intestinal disorder cholera. The toxin-coregulated pilus (TCP), a type IVb pilus, is an essential virulence factor of V. cholerae. Recent work has shown TcpB is a large minor pilin encoded within the tcp operon. TcpB contributes to efficient pilus formation and is essential for all TCP functions. Here we have initiated a detailed, targeted mutagenesis approach to further characterize this salient TCP component. We have identified (thus far) 20 residues of TcpB, which affect either the steady state level of TcpB or alter one or more TCP functions. This study …

Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5-fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. Ad5-R3 …

Two Cases Of Vibrio Infection And Sepsis In The Delaware Estuary, René Daniel, Md, Joseph Yoo, Md, Roberto Fratamico, Md, Robert Measley, Md

The Medicine Forum

INTRODUCTION

Vibrio is a genus of Gram-negative motile rods. Several species are pathogenic, including Vibrio vulnificus and Vibrio parahaemolyticus. The interest in this genus is due to its extreme virulence and often fatal outcomes. In healthy patients, these infections are typically self-limited; however, in immunocompromised and cirrhotic patients, infections can result in bacteremia, which has a high fatality rate1. Both pathogens may cause acute gastroenteritis, necrotizing wound infections, and if severe, subsequent bacteremia. In this report, we present two cases of Vibrio infections recently identified in the Delaware River Estuary that resulted in severe sepsis and, in one case, death.

Unexplained Recurrent Fevers And The Importance Of Inquiring About Occupation: A Case Report, Zachary Reese, Ms4, Poonam Maru, Do

The Medicine Forum

INTRODUCTION

Many different tick-borne diseases are identified in various geographical areas throughout the United States. Ixodes scapularis tick-borne diseases can present unique diagnostic challenges because of their constellation of vague symptoms. The Ixodes scapularis tick, more commonly known as the blacklegged tick, is responsible for three specific tick-borne infections: Lyme disease (Borellia burgdorferii), Babesiosis (Babesia microti), and Anaplasmosis (Anaplasma phagocytophilum) also known as human granulocytic anaplasmosis. Although these three tick-borne diseases are characteristically found in the New England area, the geographical distribution of the Ixodes tick has expanded to encompass much of the northeastern United States and even states in …

Oral Cryptococcosis In A Patient With Chronic Lymphocytic Leukemia, Sachin Patel, Maria Navas, Courtney Batt, Robin L.P. Jump

Faculty Scholarship

No abstract provided.

Cyclic Di-Gmp-Regulated Periplasmic Proteolysis Of A Pseudomonas Aeruginosa Type Vb Secretion System Substrate, Richard B. Cooley, T. Jarrod Smith, Wilfred Leung, Valerie Tierney, Bradley Borlee, George A. O'Toole, Holger Sondermann

Dartmouth Scholarship

We previously identified a second-messenger-regulated signaling system in the environmental bacterium Pseudomonas fluorescens which controls biofilm formation in response to levels of environmental inorganic phosphate. This system contains the transmembrane cyclic di-GMP (c-di-GMP) receptor LapD and the periplasmic protease LapG. LapD regulates LapG and controls the ability of this protease to process a large cell surface adhesin protein, LapA. While LapDG orthologs can be identified in diverse