Infectious Disease Commons^™

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.

The Effectiveness Of Antibiotic Treatment In Lyme Neuroborreliosis, Lane Lindeman

Physician Assistant Scholarly Project Posters

• Lyme disease is caused by human infection with Borrelia burgdorferi, a spirochete transmitted by the Ixodes tick which is indigenous primarily to an increasingly large area of the Northeast and Midwest United States.

• Manifestations of Lyme disease vary greatly, and can result in significant neurologic symptoms associated with complications of neuroborreliosis or neurologic Lyme disease.

• Diagnosis and treatment of Lyme disease and its complications has been a source of debate and confusion for providers and patients alike.

• The purpose of this study was to investigate the effectiveness and efficacy of antibiotic therapy in patients with symptoms …

Lineage-Specific Differences In The Gp120 Inner Domain Layer 3 Of Human And Simian Immunodeficiency Viruses, Shilei Ding, Halima Medjahed, Jérémie Prévost, Mathieu Coutu, Shi-Hua Xiang, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

Binding of HIV-1 and SIV gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological Layers (Layer 1, Layer 2 and Layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to Layer 1 of HIV-1 gp120, the SIVmac239 gp120 Layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could …

Hiv/Aids Care And Prevention Infrastructure In The U.S. Deep South, Susan S. Reif, Kristen Sullivan, Elena Wilson, Miriam Berger, Carolyn Mcallaster

Faculty Scholarship

No abstract provided.

Giant Chloroviruses: Five Easy Questions, James L. Van Etten, David Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large, icosahedral, dsDNA-containing viruses that replicate in certain unicellular, chlorella-like green algae [1,2]. They exist in freshwater throughout the world with titers as high as thousands of plaque-forming units (PFU) per ml of indigenous water although titers are typically 1–100 PFU/ml. Titers fluctuate during the year with the highest titers typically occurring in the spring and late fall. Known chlorovirus hosts, which are normally symbionts and are often referred to as zoochlorellae, are associated with either the protozoan Paramecium bursaria (Fig 1A), the coelenterate Hydra viridis, or the heliozoan Acanthocystis turfacea. Zoochlorellae are resistant to viruses …

Genetic Barrier To Direct Acting Antivirals In Hcv Sequences Deposited In The European Databank, Dimas Alexandre Kliemann, Cristiane Valle Tovo, Ana Beatriz Gorini Da Veiga, André Luiz Machado, John T. West

Nebraska Center for Virology: Faculty Publications

Background & Aims: Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs.

Methods: The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzed 789 NS3 sequences, 708 sequences and 536 NS5B …

Kaposi’S Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (Myd88) Expression Via Modulation Of Its Rna, Amy Lingel, Erica Ehlers, Qianli Wang, Mingxia Cao, Charles Wood, Rongtuan Lin, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of …

Nf45 And Nf90 Bind Hiv-1 Rna And Modulate Hiv Gene Expression, Yan Li, Michael Belshan

Nebraska Center for Virology: Faculty Publications

A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 …

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. …

Comparing Short Versus Long Term Antibiotics For Reducing Persistent Lyme Symptoms, Joe Webster

Physician Assistant Scholarly Project Posters

• Lyme disease is the most common tick borne illness in the United States with over 300,000 cases annually.

• Two main organizations called the Infectious Disease Society of America and the International Lyme and Associated Diseases Society differ on their opinions in the treatment duration of Lyme disease.

• A review of the literature explored studies that compared the effectiveness of short term versus long term antibiotics in the treatment of Lyme. Determining the most effective treatment method duration for reducing the long term risk of persistent symptoms of Lyme will be important for the improvement of the delivery …

Recapitulating Cross-Species Transmission Of Sivcpz To Humans Using Humanized-Blt Mice, Zhe Yuan, Guobin Kang, Fangrui Ma, Wuxun Lu, Wenjin Fan, Christine M. Fennessey, Brandon F. Keele, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The origins of HIV-1 have been widely accepted to be the consequence of simian immunodeficiency viruses from wild chimpanzees (SIVcpz) crossing over to humans. However, there has not been any in vivo study of SIVcpz infection of humans. Also, it remains largely unknown why only specific SIVcpz strains have achieved cross-species transmission and what transmission risk might exist for those SIVcpz strains that have not been found to infect humans. Closing this knowledge gap is essential for better understanding cross-species transmission and predicting the likelihood of additional cross-species transmissions of SIV into humans. Here we show hu-BLT mice are susceptible …

High Glucose Induces Reactivation Of Latent Kaposi’S Sarcoma-Associated Herpesvirus, Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou-Jiang Gao

Nebraska Center for Virology: Faculty Publications

High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29

grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high …

Persistent Low-Level Replication Of Sivδnef Drives Maturation Of Antibody And Cd8 T Cell Responses To Induce Protective Immunity Against Vaginal Siv Infection, Sama Adnan, R. Keith Reeves, Jacqueline Gillis, Fay E. Wong, Yi Yu, Jeremy V. Camp, Qingsheng Li, Michelle Connole, Yuan Li, Michael Piatak Jr., Jeffrey D. Lifson, Wenjun Li, Brandon F. Keele, Pamela A. Kozlowski, Ronald C. Desrosiers, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef …

Putting Prep Into Practice: Lessons Learned From Early-Adopting U.S. Providers’ Firsthand Experiences Providing Hiv Pre-Exposure Prophylaxis And Associated Care, Sarah K. Calabrese, Manya Magnus, Kenneth H. Mayer, Douglas S. Krakower, Adam I. Eldahan, Lauren A. Gaston Hawkins, Nathan B. Hansen, Trace S. Kershaw, Kristen Underhill, Joseph R. Betancourt, John F. Dovidio

Faculty Scholarship

Optimizing access to HIV pre-exposure prophylaxis (PrEP), an evidence-based HIV prevention resource, requires expanding healthcare providers’ adoption of PrEP into clinical practice. This qualitative study explored PrEP providers’ firsthand experiences relative to six commonly-cited barriers to prescription – financial coverage, implementation logistics, eligibility determination, adherence concerns, side effects, and anticipated behavior change (risk compensation) – as well as their recommendations for training PrEP-inexperienced providers. U.S.-based PrEP providers were recruited via direct outreach and referral from colleagues and other participants (2014-2015). One-on-one interviews were conducted in person or by phone, transcribed, and analyzed. The sample (n = 18) primarily practiced …

We Have The Tools To End Hiv: Benefits, Barriers, And Solutions To Expanded Utilization Of Pre-Exposure Prophylaxis (Prep) In The Us Deep South, Jason Ervin, Allison Weller Tikare, Carolyn Mcallaster

Faculty Scholarship

No abstract provided.

Reducing Overutilization Of Testing For Clostridium Difficile Infection In A Pediatric Hospital System: A Quality Improvement Initiative., J Michael Klatte, Rangaraj Selvarangan, Mary Anne Jackson, Angela Myers

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Study objectives included addressing overuse of Clostridium difficile laboratory testing by decreasing submission rates of nondiarrheal stool specimens and specimens from children ≤12 months of age and determining resultant patient and laboratory cost savings associated with decreased testing.

METHODS: A multifaceted initiative was developed, and components included multiple provider education methods, computerized order entry modifications, and automatic declination from laboratory on testing stool specimens of nondiarrheal consistency and from children ≤12 months old. A run chart, demonstrating numbers of nondiarrheal plus infant stool specimens submitted over time, was developed to analyze the initiative's impact on clinicians' test-ordering practices. A …

Complete Genome Sequence Of Highly Virulent Porcine Reproductive And Respiratory Syndrome Virus Variants That Recently Emerged In The United States, Aspen M. Workman, Timothy P.L. Smith, Fernando A. Osorio, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

A recent outbreak of particularly virulent disease caused by porcine reproductive and respiratory syndrome virus has occurred in swine herds across the United States. We report here the complete genome sequence of eight viral isolates from four Nebraska herds experiencing an outbreak of severe disease in 2016.

A Healthy Herd: Addressing The Justifications For Vaccine Denial And Applying The Health Belief Model To The Current Anti-Vaccination Movement, Sarah L. Mchugh

Honors Program Theses

The purpose of this thesis is to explore and analyze the existing literature regarding the refusal to receive vaccinations designed specifically to prevent Measles-Mumps-Rubella (MMR), which has spurred a serious public health issue that puts every unvaccinated person at risk. It will investigate the reasons people refuse to get vaccinations for themselves or their children. The analysis of the current situation and the application of the Health Belief Model to the related factors will provide potential explanations regarding how the decision-making process may strengthen efforts towards increasing vaccination rates.

Patterns Of Human Herpesvirus-8 Oral Shedding Among Diverse Cohorts Of Human Herpesvirus-8 Seropositive Persons, Rachel A. Bender Ignacio, Jason D. Goldman, Amalia S. Magaret, Stacy Selke, Meei-Li Huang, Soren Gantt, Christine Johnston, Warren Phipps, Joshua Schiffer, Richard Zuckerman

Dartmouth Scholarship

Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication (“shedding”) at mucosal sites, especially the oropharynx. Patterns of HHV-8 shedding are not well understood, and require elucidation to better predict risk of HHV-8 related malignancies in those infected. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV-8 seropositive persons.

Typical Hus: Evidence Of Acute Phase Complement Activation From A Daycare Outbreak, T M. Brady, C Pruette, L F. Loeffler, Darcy Weidemann, J J. Strouse, E Gavriilaki, R A. Brodsky

Manuscripts, Articles, Book Chapters and Other Papers

The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by …

Slug Bug: Quality Improvement With Orchestrated Testing Leads To Nicu Clabsi Reduction., Anthony J. Piazza, Beverly Brozanski, Lloyd Provost, Theresa R. Grover, John Chuo, Joan R. Smith, Teresa Mingrone, Susan Moran, Lorna Morelli, Isabella Zaniletti, Eugenia K. Pallotto

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Reduce central line-associated bloodstream infection (CLABSI) rates 15% over 12 months in children's hospital NICUs. Use orchestrated testing as an approach to identify important CLABSI prevention practices.

METHODS: Literature review, expert opinion, and benchmarking were used to develop clinical practice recommendations for central line care. Four existing CLABSI prevention strategies (tubing change technique, hub care monitoring, central venous catheter access limitation, and central venous catheter removal monitoring) were identified for study. We compared the change in CLABSI rates from baseline throughout the study period in 17 participating centers. Using orchestrated testing, centers were then placed into 1 of 8 …

Domain I Of The 5′ Non-Translated Genomic Region In Coxsackievirus B3 Rna Is Not Required For Productive Replication, L. Jaramillo, S. Smithee, S. Tracy, N. M. Chapman

Nebraska Center for Virology: Faculty Publications

Domain I is a cloverleaf-like secondary structure at the 5′ termini of all enterovirus genomes, comprising part of a cis-acting replication element essential for efficient enteroviral replication. 5′ genomic terminal deletions up to as much as 55% of domain I can occur without lethality following coxsackie B virus infections. We report here that the entire CVB structural domain I can be deleted without lethality.

Reversion To Wildtype Of A Mutated And Nonfunctional Coxsackievirus B3cre(2c), Shane Smithee, Steven Tracy, Nora M. Chapman

Nebraska Center for Virology: Faculty Publications

The cis-acting replication element (CRE) in the 2C protein coding region [CRE(2C)] of enteroviruses (EV) facilitates the addition of two uridine residues (uridylylation) onto the virus-encoded protein VPg inorder for it to serve as the RNA replication primer. We demonstrated that coxsackievirus B3 (CVB3) is replication competent in the absence of a native (uridylylating) CRE(2C) and also demonstrated that lackof a functional CRE(2C) led to generation of 5’ terminal genomic deletions in the CVB3 CRE-knock-out (CVB3-CKO) population. We asked whether reversion of the mutated CRE(2C) occurred, thus permitting sustained replication, and when were 5’ terminal deletions generated during replication. Virions …

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Head-to-head comparisons of conventional influenza vaccines with ade- novirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we de- veloped “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than …

Effect Of Mobile Phone Text Messages Reminders On Uptake Of Routine Immunization Among Children In Pakistan- Study Protocol For A Randomized Clinical Trial, Abdul Momin Kazi, Murtaza Ali, Khurram Zubair, Hussain Kalimuddin, Syed Asad Ali

Department of Paediatrics and Child Health

Introduction: Routine Immunization (RI) is considered one of the best public health interventions to decrease child morbidity and mortality. The RI coverage in Pakistan is still well below the desired level, leading to continued polio transmission, large measles outbreaks and thousands of deaths from vaccine-preventable illnesses. Different innovative and cost effective strategies are required to look into for enhancement in vaccination uptake and coverage. We plan to test the effectiveness of reminders to parents/caregivers on cell phones through short messaging system (SMS) in improving vaccine uptake and on-time routine immunization for children in Pakistan.
Methods and Analysis: A parallel-randomized controlled …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …