Digital Commons Network^™

Controversies Regarding Management Of Helicobacter Pylori Infections, Alyssa Price, David Y Graham, Mimi C Tan

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The recognition that Helicobacter pylori should be considered and treated as an infectious disease has yet to fundamentally change diagnostic and treatment practices and has resulted in many controversies.

RECENT FINDINGS: We discuss the following controversies: whether the current 'per-patient' approach to H. pylori testing based on symptoms should be expanded to include achieving population-level H. pylori eradication, whether H. pylori should be approached as an infectious gastrointestinal disease similar to that of other infectious diseases of similar severity and outcome, whether treatment of H. pylori should be primarily empiric or based on antibiotic susceptibility and locally …

Early Antibody Treatment, Inflammation, And Risk Of Post-Covid Conditions, Kelly A Gebo, Sonya L Heath, Yuriko Fukuta, Xianming Zhu, Sheriza Baksh, Allison G Abraham, Feben Habtehyimer, David Shade, Jessica Ruff, Malathi Ram, Oliver Laeyendecker, Reinaldo E Fernandez, Eshan U Patel, Owen R Baker, Shmuel Shoham, Edward R Cachay, Judith S Currier, Jonathan M Gerber, Barry Meisenberg, Donald N Forthal, Laura L Hammitt, Moises A Huaman, Adam Levine, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Shweta Anjan, Thomas Gniadek, Seble Kassaye, Janis E Blair, Karen Lane, Nichol A Mcbee, Amy L Gawad, Piyali Das, Sabra L Klein, Andrew Pekosz, Evan M Bloch, Daniel Hanley, Arturo Casadevall, Aaron A R Tobian, David J Sullivan, Cssc-004 Consortium

Faculty, Staff and Students Publications

Post-COVID conditions (PCCs) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about treatment, inflammation, and PCC. Among 882 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of COVID-19 convalescent plasma (CCP) vs control plasma with available biospecimens and symptom data, the association between early CCP treatment, cytokine levels, and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14, and day 90 using a multiplexed sandwich immunoassay (Meso Scale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. …

Returning Incidentally Discovered Hepatitis C Rna-Seq Results To Copdgene Study Participants, Edwin K Silverman, Arthur Y Kim, Barry J Make, Elizabeth A Regan, Jarrett D Morrow, Craig P Hersh, James O'Brien, James D Crapo, Nadia N Hansel, Gerard Criner, Eric L Flenaugh, Douglas Conrad, Richard Casaburi, Russell P Bowler, Nicola A Hanania, R Graham Barr, Surya P Bhatt, Frank C Sciurba, Antonio Anzueto, Meilan K Han, Charlene E Mcevoy, Alejandro P Comellas, Dawn L Demeo, Richard Rosiello, Jeffrey L Curtis, Tricia Uchida, Carla Wilson, P Pearl O'Rourke

Faculty, Staff and Students Publications

The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed …

Localized Cardiac Small Molecule Trajectories And Persistent Chemical Sequelae In Experimental Chagas Disease, Zongyuan Liu, Rebecca Ulrich Vonbargen, April L Kendricks, Kate Wheeler, Ana Carolina Leão, Krithivasan Sankaranarayanan, Danya A Dean, Shelley S Kane, Ekram Hossain, Jeroen Pollet, Maria Elena Bottazzi, Peter J Hotez, Kathryn M Jones, Laura-Isobel Mccall

Faculty, Staff and Students Publications

Post-infectious conditions present major health burdens but remain poorly understood. In Chagas disease (CD), caused by Trypanosoma cruzi parasites, antiparasitic agents that successfully clear T. cruzi do not always improve clinical outcomes. In this study, we reveal differential small molecule trajectories between cardiac regions during chronic T. cruzi infection, matching with characteristic CD apical aneurysm sites. Incomplete, region-specific, cardiac small molecule restoration is observed in animals treated with the antiparasitic benznidazole. In contrast, superior restoration of the cardiac small molecule profile is observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy, even with less parasite burden reduction. Overall, …

Standardization Of An Antiviral Pipeline For Human Norovirus In Human Intestinal Enteroids Demonstrates Nitazoxanide Has No To Weak Antiviral Activity, Miranda A Lewis, Nicolás W Cortés-Penfield, Khalil Ettayebi, Ketki Patil, Gurpreet Kaur, Frederick H Neill, Robert L Atmar, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis. In immunocompetent hosts, symptoms usually resolve within 3 days; however, in immunocompromised persons, HuNoV infection can become persistent, debilitating, and sometimes life-threatening. There are no licensed therapeutics for HuNoV due to a near half-century delay in its cultivation. Treatment for chronic HuNoV infection in immunosuppressed patients anecdotally includes nitazoxanide, a broad-spectrum antimicrobial licensed for treatment of parasite-induced gastroenteritis. Despite its off-label use for chronic HuNoV infection, nitazoxanide has not been clearly demonstrated to be an effective treatment. In this study, we standardized a pipeline for antiviral testing using multiple human …

A Single Nanobody Neutralizes Multiple Epochally Evolving Human Noroviruses By Modulating Capsid Plasticity, Wilhelm Salmen, Liya Hu, Marina Bok, Natthawan Chaimongkol, Khalil Ettayebi, Stanislav V Sosnovtsev, Kaundal Soni, B Vijayalakshmi Ayyar, Sreejesh Shanker, Frederick H Neill, Banumathi Sankaran, Robert L Atmar, Mary K Estes, Kim Y Green, Viviana Parreño, B V Venkataram Prasad

Faculty, Staff and Students Publications

Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed …

A Retrospective, Observational Study Of 12 Cases Of Expanded-Access Customized Phage Therapy: Production, Characteristics, And Clinical Outcomes, Sabrina I Green, Justin R Clark, Haroldo H Santos, Kyle E Weesner, Keiko C Salazar, Saima Aslam, J William Campbell, Sarah B Doernberg, Emily Blodget, Michele I Morris, Gina A Suh, Karam Obeid, Fernanda P Silveira, Andrey A Filippov, Katrine L Whiteson, Barbara W Trautner, Austen L Terwilliger, Anthony Maresso

Faculty, Staff and Students Publications

BACKGROUND: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections.

METHODS: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related …

Polygenic Prediction Across Populations Is Influenced By Ancestry, Genetic Architecture, And Methodology, Ying Wang, Masahiro Kanai, Taotao Tan, Mireille Kamariza, Kristin Tsuo, Kai Yuan, Wei Zhou, Yukinori Okada, Biobank Japan Project, Hailiang Huang, Patrick Turley, Elizabeth G Atkinson, Alicia R Martin

Faculty, Staff and Students Publications

Polygenic risk scores (PRSs) developed from multi-ancestry genome-wide association studies (GWASs), PRSmulti, hold promise for improving PRS accuracy and generalizability across populations. To establish best practices for leveraging the increasing diversity of genomic studies, we investigated how various factors affect the performance of PRSmulti compared with PRSs constructed from single-ancestry GWASs (PRSsingle). Through extensive simulations and empirical analyses, we showed that PRSmulti overall outperformed PRSsingle in understudied populations, except when the understudied population represented a small proportion of the multi-ancestry GWAS. Furthermore, integrating PRSs based on local ancestry-informed GWASs and large-scale, European-based PRSs improved predictive performance in understudied African populations, …

Bacillus Calmette-Guérin Vaccination As Defense Against Sars-Cov-2 (Badas): A Randomized Controlled Trial To Protect Healthcare Workers In The Usa By Enhanced Trained Immune Responses, Andrew R Dinardo, Moshe Arditi, Ashish M Kamat, Kent J Koster, Santiago Carrero, Tomoki Nishiguchi, Maxim Lebedev, Aaron B Benjamin, Pablo Avalos, Marisa Lozano, Madeleine G Moule, Brittany Mccune, Baysia Herron, Malik Ladki, Daanish Sheikh, Matthew Spears, Ivan A Herrejon, Courtney Dodge, Sathish Kumar, Robert W Hutchison, Theresa U Ofili, Lynne A Opperman, Jessica A Bernard, Seth P Lerner, George Udeani, Gabriel Neal, Mihai G Netea, Jeffrey D Cirillo

Faculty, Staff and Students Publications

BACKGROUND: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.

METHODS: This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at …

Report Of The Assay Guidance Workshop On 3-Dimensional Tissue Models For Antiviral Drug Development, Robert Jordan, Stephanie L Ford-Scheimer, Rodolfo M Alarcon, Anthony Atala, Jeffrey T Borenstein, Kyle R Brimacombe, Sara Cherry, Hans Clevers, Mindy I Davis, Simon G P Funnell, Lee Gehrke, Linda G Griffith, Abigail C Grossman, Thomas Hartung, Donald E Ingber, Nicole C Kleinstreuer, Calvin J Kuo, Emily M Lee, Christine L Mummery, Thames E Pickett, Sasirekha Ramani, Edwin A Rosado-Olivieri, Evi B Struble, Zhengpeng Wan, Mark S Williams, Matthew D Hall, Marc Ferrer, Sarine Markossian

Faculty, Staff and Students Publications

The National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM) Workshop on 3D Tissue Models for Antiviral Drug Development, held virtually on 7-8 June 2022, provided comprehensive coverage of critical concepts intended to help scientists establish robust, reproducible, and scalable 3D tissue models to study viruses with pandemic potential. This workshop was organized by NCATS, the National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation. During the workshop, scientific experts from academia, industry, and government provided an overview of 3D tissue models' utility and limitations, use of existing 3D tissue models for antiviral …

Safety And Immunogenicity Of Live Viral Vaccines In A Multicenter Cohort Of Pediatric Transplant Recipients, Amy G Feldman, Brenda L Beaty, Jose A Ferrolino, Gabriela Maron, Hillary K Weidner, Saira A Ali, Leandra Bitterfeld, Mary Alice Boulware, Kathleen M Campbell, Emily Carr, Shelley Chapman, Yeh-Chung Chang, Ryan Cunningham, Ronald H Dallas, Keerti L Dantuluri, Bryanna N Domenick, Noelle H Ebel, Scott Elisofon, Rima Fawaz, Marc Foca, Hayley A Gans, Vani V Gopalareddy, Cindy Gu, Nitika A Gupta, Katherine Harmann, Jessica Hollenbeck, Anna R Huppler, Catalina Jaramillo, Nagraj Kasi, Nanda Kerkar, Stacee Lerret, Steven J Lobritto, Maclovio J Lopez, Elizabeth Marini, Alisha Mavis, Sonia Mehra, Lynnette Moats, Sindhu Mohandas, Flor M Munoz, Krupa R Mysore, Ceren Onsan, Nadia Ovchinsky, Kerrigan Perkins, Stacy Postma, Lauren Pratscher, Elizabeth B Rand, Regina K Rowe, Danielle Schultz, Katherine Sear, Megan L Sell, Tanvi Sharma, Janis Stoll, Mychoua Vang, Dominique Villarin, Carly Weaver, Phoebe Wood, Olivia Woodford-Berry, George Yanni, Lara A Danziger-Isakov

Faculty, Staff and Students Publications

IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.

OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody …

Review Of Toxocariasis At A Children's Hospital Prompting Need For Public Health Interventions, Mary B Fortini, Timothy A Erickson, Lauren M Leining, Karina M Robinson, Megan N Carey, Sarah J Smith, Brendan Sullivan, Alisa R Nelson, Sarah M Gunter, Jill E Weatherhead

Faculty, Staff and Students Publications

BACKGROUND: Toxocariasis, caused the by dog and cat roundworm, is one of the most common zoonotic helminth infections in the United States and can lead to severe lifelong morbidity in children. Although historical seroprevalence studies have identified a high frequency of toxocariasis regionally in the United States, there are few studies linking epidemiology and clinical disease in children. The study objective was to examine the contemporary epidemiology of pediatric toxocariasis within an endemic US region.

METHODS: We conducted an epidemiologic study analyzing children diagnosed with toxocariasis presenting to a tertiary pediatric hospital in Texas from 2010 to 2021. We examined …

Human Glp1r Variants Affecting Glp1r Cell Surface Expression Are Associated With Impaired Glucose Control And Increased Adiposity, Wenwen Gao, Lei Liu, Eunna Huh, Florence Gbahou, Erika Cecon, Masaya Oshima, Ludivine Houzé, Panagiotis Katsonis, Alan Hegron, Zhiran Fan, Guofei Hou, Guillaume Charpentier, Mathilde Boissel, Mehdi Derhourhi, Michel Marre, Beverley Balkau, Philippe Froguel, Raphael Scharfmann, Olivier Lichtarge, Julie Dam, Amélie Bonnefond, Jianfeng Liu, Ralf Jockers

Faculty, Staff and Students Publications

The glucagon-like peptide 1 receptor (GLP1R) is a major drug target with several agonists being prescribed in patients with type 2 diabetes (T2D) and obesity 1, 2. The impact of genetic variability of GLP1R on receptor function and its association with metabolic traits are unclear with conflicting reports. Here, we performed a functional profiling of 60 GLP1R variants across four signaling pathways and revealed an unexpected diversity of phenotypes ranging from defective cell surface expression to complete or pathway-specific gain- (GoF) and loss-of-functions (LoF). The defective insulin secretion of GLP1R LoF variants was rescued by allosteric GLP1R ligands …

Structural Biology Of Mcr-1-Mediated Resistance To Polymyxin Antibiotics, Isabel Cristina Materon, Timothy Palzkill

Faculty, Staff and Students Publications

Polymyxins, a last resort antibiotic, target the outer membrane of pathogens and are used to address the increasing prevalence of multidrug-resistant Gram-negative bacteria. The plasmid-encoded enzyme MCR-1 confers polymyxin resistance to bacteria by modifying the outer membrane. Transferable resistance to polymyxins is a major concern; therefore, MCR-1 is an important drug target. In this review, we discuss recent structural and mechanistic aspects of MCR-1 function, its variants and homologs, and how they are relevant to polymyxin resistance. Specifically, we discuss work on polymyxin-mediated disruption of the outer and inner membranes, computational studies on the catalytic mechanism of MCR-1, mutagenesis and …

Understanding The Gap Between Nursing Workforce In The United States And Population Needs-A Policy Brief, Mayar Al Mohajer

Faculty, Staff and Students Publications

Purpose  This report is intended to analyze the root causes for the current gap between the nursing workforce and population needs in the United States. It aims to consolidate what is known about these contributing reasons and provide evidence-based recommendations for action.

Methods  The report utilized the Sample, Phenomenon of Interest, Design, Evaluation, Research type framework to develop the research question and the 5 Whys methodology for the root cause analysis.

Results  This report highlighted six major causative problems, including workforce market mismatch, poor financing design, inadequate governance, flawed technologies, insufficient research, and suboptimal service delivery. A detailed evaluation of …

Best Practices For Effective Management Of Point Of Care Testing, Anil K Chokkalla, Brandy D Recio, Sridevi Devaraj

Faculty, Staff and Students Publications

With the recent COVID-19 pandemic, point-of-care testing has gained tremendous attention, particularly in acute care settings. The point-of-care testing landscape is rapidly expanding and being contemplated for any crucial test with a central laboratory turnaround time >25% of the clinical decision time. A typical point-of-care testing program within a large hospital system encompasses a multitude of operators utilizing a wide range of devices across multiple testing sites. Thus, managing a large point-of-care testing network remains a daunting task with challenges related to staffing, standardization, quality management, training and competency assessment, and data management. This review will focus on understanding the …

Time To Establish An International Vaccine Candidate Pool For Potential Highly Infectious Respiratory Disease: A Community’S View, Lan Yao, Hiam Chemaitelly, Emanuel Goldman, Esayas Kebede Gudina, Asma Khalil, Rahaman Ahmed, Ayorinde Babatunde James, Anna Roca, Mosoka Papa Fallah, Andrew Macnab, William C Cho, John Eikelboom, Farah Naz Qamar, Peter Kremsner, Miquel Oliu-Barton, Ivan Sisa, Birkneh Tilahun Tadesse, Florian Marks, Lishi Wang, Jerome H Kim, Xia Meng, Yongjun Wang, Alyce D Fly, Cong-Yi Wang, Sara W Day, Scott C Howard, J Carolyn Graff, Marcello Maida, Kunal Ray, Carlos Franco-Paredes, Tapfumanei Mashe, Ngashi Ngongo, Jean Kaseya, Nicaise Ndembi, Yu Hu, Maria Elena Bottazzi, Peter J Hotez, Ken J Ishii, Gang Wang, Dianjun Sun, Lotfi Aleya, Weikuan Gu

Faculty, Staff and Students Publications

In counteracting highly infectious and disruptive respiratory diseases such as COVID-19, vaccination remains the primary and safest way to prevent disease, reduce the severity of illness, and save lives. Unfortunately, vaccination is often not the first intervention deployed for a new pandemic, as it takes time to develop and test vaccines, and confirmation of safety requires a period of observation after vaccination to detect potential late-onset vaccine-associated adverse events. In the meantime, nonpharmacologic public health interventions such as mask-wearing and social distancing can provide some degree of protection. As climate change, with its environmental impacts on pathogen evolution and international …

The Interaction Between Autophagy, Helicobacter Pylori, And Gut Microbiota In Gastric Carcinogenesis, Ali Nabavi-Rad, Abbas Yadegar, Amir Sadeghi, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali, Daniel J Klionsky, Yoshio Yamaoka

Faculty, Staff and Students Publications

Chronic infection with Helicobacter pylori is the primary risk factor for the development of gastric cancer. Hindering our ability to comprehend the precise role of autophagy during H. pylori infection is the complexity of context-dependent autophagy signaling pathways. Recent and ongoing progress in understanding H. pylori virulence allows new frontiers of research for the crosstalk between autophagy and H. pylori. Novel approaches toward discovering autophagy signaling networks have further revealed their critical influence on the structure of gut microbiota and the metabolome. Here we intend to present a holistic view of the perplexing role of autophagy in H. pylori pathogenesis …

Texas Developmental Center For Aids Research Cfar Diversity, Equity, And Inclusion Pathway Initiative Program, Fred A Pereira, Alana D Newell, Andrew P Rice

Faculty, Staff and Students Publications

BACKGROUND: The Texas Developmental Center for AIDS Research (D-CFAR) diversity program, termed the CFAR Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI), was created in 2021 to engage high school students and graduate students from Underrepresented Minorities/Black, Indigenous, and People of Color populations.

SETTING: The Texas D-CFAR CDEIPI has partnered with 2 Texas high schools with predominantly economically disadvantaged and minority student populations-Michael E. DeBakey High School for Health Professions in Houston, TX, and the South Texas Independent School District Medical Professions High School in Olmito, TX in the Rio Grande Valley.

METHODS: A total of 370 high school student learners …

Tuberculosis Incidence In Foreign-Born People Residing In European Countries In 2020, Anca Vasiliu, Niklas Köhler, Ekkehardt Altpeter, Tinna Rán Ægisdóttir, Marina Amerali, Wouter Arrazola De Oñate, Ágnes Bakos, Stefania D'Amato, Daniela Maria Cirillo, Reinout Van Crevel, Edita Davidaviciene, Irène Demuth, Jose Domínguez, Raquel Duarte, Gunar Günther, Jean-Paul Guthmann, Sophia Hatzianastasiou, Louise Hedevang Holm, Zaida Herrador, Urška Hribar, Conny Huberty, Elmira Ibraim, Sarah Jackson, Mogens Jensenius, Kamilla Sigridur Josefsdottir, Anders Koch, Maria Korzeniewska-Kosela, Liga Kuksa, Heinke Kunst, Christian Lienhardt, Beatrice Mahler, Mateja Janković Makek, Inge Muylle, Johan Normark, Analita Pace-Asciak, Goranka Petrović, Despo Pieridou, Giulia Russo, Olena Rzhepishevska, Helmut J F Salzer, Marta Sá Marques, Daniela Schmid, Ivan Solovic, Mariya Sukholytka, Petra Svetina, Mariya Tyufekchieva, Tuula Vasankari, Piret Viiklepp, Kersti Villand, Jiri Wallenfels, Stefan Wesolowski, Anna-Maria Mandalakas, Leonardo Martinez, Dominik Zenner, Christoph Lange, Tbnet

Faculty, Staff and Students Publications

Background

European-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.

Aim

We aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.

Methods

The Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries …

Supplemental Issue Of The Journal Of The Acquired Immune Deficiency Syndromes (Jaids): The Centers For Aids Research (Cfar) Diversity, Equity, And Inclusion Pathway Initiative (Cdeipi), Alan E Greenberg, Anthony K Wutoh, Lisa Bowleg, Manya Magnus, Brandi Robinson, Lorena Segarra, Eric Refsland

Faculty, Staff and Students Publications

No abstract provided.

Quality Improvement Initiative To Improve Time And Adherence To Revaccination After Hematopoietic Cell Transplantation: Implementation Of A Revaccination Clinic Within The Transplantation Program, Caitlin Elgarten, Anne Wohlschlaeger, Ellen Levy, Katharine Tadley, Lei Wang, Megan Atkinson, Houston Roberson, Timothy Olson, Nancy Bunin, Jennifer Heimall, Brian Fisher, Stephan Grupp, Jason Freedman

Faculty, Staff and Students Publications

Background:

Revaccination after hematopoietic cell transplantation (HCT) is critical to prevent morbidity and mortality from vaccine preventable illnesses. While earlier re-vaccination after HCT is desirable, they may be ineffective if deployed before partial reconstitution of adaptive immunity. Increasingly, personalized approaches to re-vaccination after HCT have replaced time-based protocols in order to minimize unvaccinated time and enhance vaccine effectiveness. Furthermore, for revaccination to be maximally beneficial, compliance with, and timely delivery of the complete revaccination schedule is imperative, but rare, and there is little data on strategies to optimize vaccine delivery.

Objectives:

The global aim of our quality improvement initiative was …

Human Intestinal Organoids As Models To Study Enteric Bacteria And Viruses, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sasirekha Ramani

Faculty, Staff and Students Publications

Laboratory studies of host-microbe interactions have historically been carried out using transformed cell lines and animal models. Although much has been learned from these models, recent advances in the development of multicellular, physiologically active, human intestinal organoid (HIO) cultures are allowing unprecedented discoveries of host-microbe interactions. Here, we review recent literature using HIOs as models to investigate the pathogenesis of clinically important enteric bacteria and viruses and study commensal intestinal microbes. We also discuss limitations of current HIO culture systems and how technical advances and innovative engineering approaches are providing new directions to improve the model. The studies discussed here …

Adjunctive Diagnostic Studies Completed Following Detection Of Candidemia In Children: Secondary Analysis Of Observed Practice From A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Rachel L Wattier, Robert F T Bucayu, Craig L K Boge, Rachael K Ross, Inci Yildirim, Theoklis E Zaoutis, Debra L Palazzi, Surabhi B Vora, Elio Castagnola, Martha Avilés-Robles, Lara Danziger-Isakov, Alison C Tribble, Tanvi S Sharma, Antonio C Arrieta, Gabriela Maron, David M Berman, Dwight E Yin, Lillian Sung, Michael Green, Emmanuel Roilides, Kiran Belani, José Romero, Pere Soler-Palacin, Eduardo López-Medina, Dawn Nolt, Ibrahim Zaid Bin Hussain, William J Muller, Sarmistha B Hauger, Natasha Halasa, Daniel Dulek, Alice Pong, Blanca E Gonzalez, Mark J Abzug, Fabianne Carlesse, Anna R Huppler, Sujatha Rajan, Catherine Aftandilian, Monica I Ardura, Arunaloke Chakrabarti, Benjamin Hanisch, Christine M Salvatore, Lena Klingspor, Elizabeth D Knackstedt, Irja Lutsar, Maria E Santolaya, Sydney Shuster, Sarah K Johnson, William J Steinbach, Brian T Fisher

Faculty, Staff and Students Publications

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown.

METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics …

Blockade Of Interferon Signaling Decreases Gut Barrier Integrity And Promotes Severe West Nile Virus Disease, Shih-Ching Lin, Fang R Zhao, Hana Janova, Adrian Gervais, Summer Rucknagel, Kristy O Murray, Jean-Laurent Casanova, Michael S Diamond

Faculty, Staff and Students Publications

The determinants of severe disease caused by West Nile virus (WNV) and why only ~1% of individuals progress to encephalitis remain poorly understood. Here, we use human and mouse enteroids, and a mouse model of pathogenesis, to explore the capacity of WNV to directly infect gastrointestinal (GI) tract cells and contribute to disease severity. At baseline, WNV poorly infects human and mouse enteroid cultures and enterocytes in mice. However, when STAT1 or type I interferon (IFN) responses are absent, GI tract cells become infected, and this is associated with augmented GI tract and blood-brain barrier (BBB) permeability, accumulation of gut-derived …

Specific Polysaccharide Antibody Deficiency, Daniel M Musher

Faculty, Staff and Students Publications

No abstract provided.

Description Of A New Pavlovskyella Species (Acari: Argasidae) From Chile, Sebastián Muñoz-Leal, José M Venzal, Alexander R Kneubehl, Job E Lopez, Thiago F Martins, Marcelo B Labruna

Faculty, Staff and Students Publications

Soft ticks (Argasidae) of the Pavlovskyella Pospelova-Shtrom subgenus are important vectors of relapsing fever spirochetes, which are agents of disease globally. South American representatives of the Pavlovskyella subgenus include 3 species: Ornithodoros (Pavlovskyella) brasiliensis Aragão, Ornithodoros (Pavlovskyella) furcosus Neumann, and Ornithodoros (Pavlovskyella) rostratus Aragão. Here, we describe a fourth species based on morphological and mitogenomic evidence of ticks collected in burrows of unknown hosts in central Chile. The larva of the new species separates from other South American soft ticks by the following combination of characters: 13 pairs of dorsolateral setae, dorsal plate hexagonal, hypostome blunt with denticles from apex …

Acculturation And Subjective Norms Impact Non-Prescription Antibiotic Use Among Hispanic Patients In The United States, Lindsey A Laytner, Kiara Olmeda, Juanita Salinas, Osvaldo Alquicira, Susan Nash, Roger Zoorob, Michael K Paasche-Orlow, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Using antibiotics without medical guidance (non-prescription antibiotic use) may contribute to antimicrobial resistance. Hispanic individuals are a growing demographic group in the United States (US) with a high prevalence of non-prescription antibiotic use. We investigated the effects of acculturation and subjective norms on Hispanic individuals’ intentions to use antibiotics without a prescription from the following sources: (1) markets in the United States (not legal), (2) other countries (abroad), (3) leftovers from previous prescriptions, and (4) friends/relatives. We surveyed self-identified Hispanic outpatients in eight clinics from January 2020 to June 2021 using the previously validated Short Acculturation Scale for Hispanics (SASH). …

Autoantibodies Neutralizing Type I Ifns Underlie West Nile Virus Encephalitis In ∼40% Of Patients, Adrian Gervais, Francesca Rovida, Maria Antonietta Avanzini, Stefania Croce, Astrid Marchal, Shih-Ching Lin, Alessandro Ferrari, Christian W Thorball, Orianne Constant, Tom Le Voyer, Quentin Philippot, Jérémie Rosain, Micol Angelini, Malena Pérez Lorenzo, Lucy Bizien, Cristian Achille, Francesca Trespidi, Elisa Burdino, Irene Cassaniti, Daniele Lilleri, Chiara Fornara, José Camilla Sammartino, Danilo Cereda, Chiara Marrocu, Antonio Piralla, Chiara Valsecchi, Stefano Ricagno, Paola Cogo, Olaf Neth, Inés Marín-Cruz, Monia Pacenti, Alessandro Sinigaglia, Marta Trevisan, Andrea Volpe, Antonio Marzollo, Francesca Conti, Tiziana Lazzarotto, Andrea Pession, Pierluigi Viale, Jacques Fellay, Stefano Ghirardello, Mélodie Aubart, Valeria Ghisetti, Alessandro Aiuti, Emmanuelle Jouanguy, Paul Bastard, Elena Percivalle, Fausto Baldanti, Anne Puel, Margaret R Macdonald, Charles M Rice, Giada Rossini, Kristy O Murray, Yannick Simonin, Anna Nagy, Luisa Barzon, Laurent Abel, Michael S Diamond, Aurélie Cobat, Shen-Ying Zhang, Jean-Laurent Casanova, Alessandro Borghesi

Faculty, Staff and Students Publications

Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0–24.0, P value <10–15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1–186.4, P value <10–15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.

Equine Bronchial Epithelial Cells Are Susceptible To Cell Entry With A Sars-Cov-2 Pseudovirus But Reveal Low Replication Efficiency, Rebecca M Legere, Angelica R Allegro, Yvonne Affram, Bibiana Petri Da Silveira, Jennifer L Fridley, Kelsey M Wells, Numan Oezguen, Robert C Burghardt, Gus A Wright, Jeroen Pollet, Angela I Bordin, Paul De Figueiredo, Julian L Leibowitz, Noah D Cohen

Faculty, Staff and Students Publications

Objective: To examine the susceptibility of cultured primary equine bronchial epithelial cells (EBECs) to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus relative to human bronchial epithelial cells (HBECs).

Sample: Primary EBEC cultures established from healthy adult horses and commercially sourced human bronchial epithelial cells (HBECs) were used as a positive control.

Methods: Angiotensin-converting enzyme 2 (ACE2) expression by EBECs was demonstrated using immunofluorescence, western immunoblot, and flow cytometry. EBECs were transduced with a lentivirus pseudotyped with the SARS-CoV-2 spike protein that binds to ACE2 and expresses the enhanced green fluorescent protein (eGFP) as a reporter. Cells were transduced …