Digital Commons Network^™

Dosing Recommendations For Ampicillin And Ceftriaxone In The Treatment Of Pediatric Community-Acquired Pneumonia Using Monte Carlo- And Physiologic-Based Pharmacokinetic Simulations, Norint Tung, Dustin Huynh, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Tyler H Do, Amartya Setty, Lana Hoang, John S Bradley, Jennifer Le

Faculty, Staff and Students Publications

Objective: Since 2011, Ampicillin (AMP) has been recommended as the parenteral antibiotic of choice for pediatric community-acquired pneumonia (CAP), but ceftriaxone (CRO) is recommended for unvaccinated children and those with complicated CAP. Using penicillin and CRO susceptibility data for pneumococcus, we evaluated the adequacy of currently recommended doses of AMP and CRO.

Methods: With nonlinear mixed-effects modeling v7.3, Monte Carlo simulations (MCS, N = 10,000) for AMP and CRO were conducted for 6 virtual patients aged 3 months, 1, 2, 5, 10, and 15 years. PK-Sim v9.0 was used to develop physiologic-based pharmacokinetic (PBPK) models for AMP (N = 4000) …

40 Years After The Discovery Of Helicobacter Pylori: Performing Optimized “Subtraction” For Clinical Eradication, Yi Hu, Ren-Chun Du, Yong-Kang Lai, Yu-Xin Hu, Yu-Chen Zhu, Yan-An Zhou, Chun-Xi Shu, Bo Zhou, Li-Xiang Ling, Xu Shu, Yong Xie, James Y W Lau, Yin Zhu, David Y Graham, Nong-Hua Lu

Faculty, Staff and Students Publications

It has been 40 years since the first discovery of the important human pathogen, Helicobacter pylori (H. pylori). Eradication of the infection continues to pose significant challenges in part because of the global increase in antibiotic resistance. Generally, the “addition” strategy has failed to deliver the desired results for more than a short period and often contributed to the increase in the prevalence of resistant strains. As such, optimization of each component of the treatment strategy has become an increasingly critical focus of research. In this study, we summarized the evolution of H. pylori eradication regimens and the …

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

Turning Analysis Into Action: Opportunities And Challenges In Implementing Wastewater Science For Public Health Decision-Making, Anna Gitter, Valeria Ruvalcaba, Katelyn Clark, Theresa Tran Carapucci, Fuqing Wu, Blake M Hanson, Jennifer Deegan, John Balliew, Eric Boerwinkle, Anthony W Maresso, Kristina D Mena

Faculty, Staff and Students Publications

In the 5 years since the emergence of the COVID-19 pandemic, the field of wastewater-based epidemiology (WBE) has dramatically expanded with programs implemented across the globe to monitor for SARS-CoV-2 and other viruses of public health concern. However, the best way to use wastewater surveillance data and inform local communities of the utility of wastewater science remains limited and sporadically discussed. Specifically, there is vague guidance regarding interpreting varying levels of viral loads in wastewater for public health significance. While collaborative efforts are key to implementing these community-specific wastewater surveillance programs, effectively using the data for public health decision-making still …

Let-7 Restrains An Epigenetic Circuit In At2 Cells To Prevent Fibrogenic Intermediates In Pulmonary Fibrosis, Matthew J Seasock, Md Shafiquzzaman, Maria E Ruiz-Echartea, Rupa S Kanchi, Brandon T Tran, Lukas M Simon, Matthew D Meyer, Phillip A Erice, Shivani L Lotlikar, Stephanie C Wenlock, Scott A Ochsner, Anton Enright, Alex F Carisey, Freddy Romero, Ivan O Rosas, Katherine Y King, Neil J Mckenna, Cristian Coarfa, Antony Rodriguez

Faculty, Staff and Students Publications

MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses …

Three Cases Of Adolescent Orf Virus Skin And Soft Tissue Infection In Southeast Texas, Margaret Taylor Danner, Caroline A Schrodt, Alexandra Tuttle, Victoria Shelus, Brendan Sullivan, Ankhi Dutta, Claire Bocchini, Denver Niles

Faculty, Staff and Students Publications

We report 3 adolescents who presented to a tertiary care hospital in Houston, Texas, with cutaneous skin lesions after contact with sheep and/or goats. The cases presented a diagnostic challenge initially but were later suspected or confirmed as orf virus infection after consultation with infectious diseases specialists.

Development Of A Risk Score To Aid With The Diagnosis Of Infections After Spinal Cord Injury: Protocol For A Retrospective Cohort Study, Felicia Skelton, Larissa Grigoryan, Joann Pan, Ashley Collazo, Barbara Trautner

Faculty, Staff and Students Publications

Background: Patients with spinal cord injury (SCI) who develop urinary tract infection (UTI) present differently than the non-SCI population. UTIs can cause loss of quality of life and even lead to life-threatening complications including urosepsis. Challenges in SCI management include distinguishing symptomatic UTI from asymptomatic bacteriuria (ASB), which occurs often in patients with SCI, and the lack of standardization in UTI diagnosis in SCI.

Objective: This study aims to set the foundation for the development of a risk score to improve diagnostic accuracy of UTI after SCI.

Methods: This study will use data from the Veterans Health Administration Corporate Data …

Artificial Intelligence-Based Virtual Staining Platform For Identifying Tumor-Associated Macrophages From Hematoxylin And Eosin-Stained Images, Arpit Aggarwal, Mayukhmala Jana, Amritpal Singh, Tanmoy Dam, Himanshu Maurya, Tilak Pathak, Sandra Orsulic, Kailin Yang, Deborah Chute, Justin A Bishop, Farhoud Faraji, Wade M Thorstad, Shlomo Koyfman, Scott Steward, Qiuying Shi, Vlad Sandulache, Nabil F Saba, James S Lewis, Germán Corredor, Anant Madabhushi

Faculty, Staff and Students Publications

Background: Virtual staining is an artificial intelligence-based approach that transforms pathology images between stain types, such as hematoxylin and eosin (H&E) to immunohistochemistry (IHC), providing a tissue-preserving and efficient alternative to traditional IHC staining. However, existing methods for translating H&E to virtual IHC often fail to generate images of sufficient quality for accurately delineating cell nuclei and IHC+ regions. To address these limitations, we introduce VISTA, an artificial intelligence-based virtual staining platform designed to translate H&E into virtual IHC.

Methods: We applied VISTA to identify M2-subtype tumor-associated macrophages (M2-TAMs) in H&E images from 968 patients with HPV+ oropharyngeal squamous cell …

Cdc’S Core Elements To Promote Diagnostic Excellence, Daniel J Morgan, Hardeep Singh, Arjun Srinivasan, Andrea Bradford, L Clifford Mcdonald, Preeta K Kutty

Faculty, Staff and Students Publications

Nearly a decade after the National Academy of Medicine released the "Improving Diagnosis in Health Care" report, diagnostic errors remain common, often leading to physical, psychological, emotional, and financial harm. Despite a robust body of research on potential solutions and next steps, the translation of these efforts to patient care has been limited. Improvement initiatives are still narrowly focused on selective themes such as diagnostic stewardship, preventing overdiagnosis, and enhancing clinical reasoning without comprehensively addressing vulnerable systems and processes surrounding diagnosis. To close this implementation gap, the US Centers for Disease Control and Prevention (CDC) released the Core Elements of …

Evaluating The Test-Negative Design For Covid-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis Of 5 Randomized Clinical Trials, Leah I B Andrews, M Elizabeth Halloran, Kathleen M Neuzil, Lars Van Der Laan, Yunda Huang, Jessica Andriesen, Mayur Patel, Leigh H Fisher, Holly Janes, Nadine Rouphael, Stephen R Walsh, Deborah A Theodore, Hong-Van Tieu, Magdalena Sobieszczyk, Hana M El Sahly, Lindsey R Baden, Ann R Falsey, Thomas B Campbell, Colleen F Kelley, Catherine Mary Healy, Lilly Immergluck, Benjamin Luft, Ian Hirsch, Guy De Bruyn, Carla Truyers, Frances Priddy, Kelsey M Sumner, Brendan Flannery, Dean Follmann, Peter B Gilbert, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

Design, setting, and participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults …

Clinical, Immunologic, And Genetic Characteristics Of 148 Patients With Natural Killer Cell Deficiency, Manar Abdalgani, Evelyn R Hernandez, Luis A Pedroza, Ivan K Chinn, Lisa R Forbes Satter, Nicholas L Rider, Pinaki P Banerjee, M Cecilia Poli, Sanjana Mahapatra, Debra Canter, Tram Cao, Linda M Shawver, Sarada L Nandiwada, James R Lupski, Jennifer E Posey, Rajasekhar Ramakrishnan, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Background: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.

Objective: We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice.

Methods: During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.

Results: NK cell abnormalities consistent with …

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

A Case Of Persistently Positive Mpox Pcr For 1 Year In A Patient With Advanced Hiv, Haitham Alaithan, Neha Venkatesh, Prathit A Kulkarni, Richard J Hamill, Maria C Rodriguez-Barradas

Faculty, Staff and Students Publications

Mpox (previously called monkeypox) is a self-limited vesiculopustular skin disease caused by the monkeypox virus. Symptoms and skin findings typically resolve within 4 weeks in immunocompetent patients. This report describes a case of persistent Mpox infection with polymerase chain reaction positivity lasting greater than 1 year after initial infection in a patient with advanced HIV.

The Impact Of Epac2-Associated Junction Plakoglobin On Respiratory Syncytial Virus Infection, Chaitra A Takle, Eun-Jin Choi, Eun Seok Choi, Devang Deepak, Kashish Khatkar, Jong Min Choi, Ke Zhang, Sung Yun Jung, Tian Wang, Wenzhe Wu, Xiaoyong Bao

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants, young children, and immunocompromised individuals. Currently, FDA-approved monoclonal antibody therapies are limited to infants and young children with severe RSV disease. As a result, there is an urgent need for comprehensive studies of RSV pathogenesis to support the development of new therapeutic strategies. Exchange proteins directly activated by cAMP (EPAC) have recently emerged as key regulators in various viral infections. Our previous work identified EPAC isoform 2 (EPAC2) as a critical factor in RSV replication and host innate immune responses. However, …

Parapneumonic Empyema Complicating Community-Acquired Pneumonia: Etiology In The Era Of Pneumococcal Vaccination And Role Of Molecular Diagnosis, Antonio C Arrieta, Stephanie Osborne, Lindsay R Grant, Bradford D Gessner, Anne J Blaschke, Kristina G Hulten, Delma J Nieves, Ashley Miller, Cody Bender, Raul Isturiz, Ronika Alexander, Shannon M Nielsen, Linda B Lamberth, Alejandro Cane, Adriano Arguedas

Faculty, Staff and Students Publications

Background: Impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease is well described; pneumococcus is infrequently identified by culture in pneumonia. Yield is higher when pleural fluid is cultured. Polymerase chain reaction (PCR) in pleural fluid samples improves pathogen identification, particularly in the case of S. pneumoniae.

Methods: Healthy children with empyema who underwent pleural fluid drainage were eligible. Demographics and PCV immunization status were collected. Blood/pleural fluid cultures were obtained. Pleural fluid samples were sent for PCR for pathogen. Serotyping was done by Neufeld-Quellung reaction on pneumococcus isolates, and PCR in culture negative cases.

Results: From December 2018 to …

Distinguishing Multisystem Inflammatory Syndrome In Children From Typhus Using Artificial Intelligence: Mis-C Versus Endemic Typhus (Ai-Met), Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M De Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

Faculty, Staff and Students Publications

Background: The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus endemic typhus (MET).

Methods: Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the 2-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features …

A Hitchhiker’S Guide To Long-Read Genomic Analysis, Medhat Mahmoud, Daniel P Agustinho, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Over the past decade, long-read sequencing has evolved into a pivotal technology for uncovering the hidden and complex regions of the genome. Significant cost efficiency, scalability, and accuracy advancements have driven this evolution. Concurrently, novel analytical methods have emerged to harness the full potential of long reads. These advancements have enabled milestones such as the first fully completed human genome, enhanced identification and understanding of complex genomic variants, and deeper insights into the interplay between epigenetics and genomic variation. This mini-review provides a comprehensive overview of the latest developments in long-read DNA sequencing analysis, encompassing reference-based and de novo assembly …

Epidemiologic Investigation Of Protozoa And Soil-Transmitted Helminths In Starr County, Texas, Lauren M Leining, Timothy A Erickson, Craig L Hanis, Cici Bauer, Maya D Murry, Eric L Brown, Rojelio Mejia, Sarah M Gunter

Faculty, Staff and Students Publications

The burden of pathogenic enteric protozoa and soil-transmitted helminths among impoverished populations living on the Texas-Mexico border is unclear. We conducted a cross-sectional study on an ongoing longitudinal cohort of 616 adults residing in Starr County, Texas. A total of 359 adults were screened for four protozoa and five soil-transmitted helminths by using real-time polymerase chain reaction. This analysis identified 48 (13.4%) participants who tested positive for Blastocystis sp., three (0.8%) who tested positive for Giardia intestinalis, and one (0.3%) who tested positive for Strongyloides stercoralis and was also coinfected with Blastocystis sp. Infection was significantly associated with age, a …

Insights Into Protection Against Mycobacterium Tuberculosis Infection: Time To Officially Confirm Another Phenotype?, Todia P Setiabudiawan, Philip C Hill, Andrew R Dinardo, Reinout Van Crevel

Faculty, Staff and Students Publications

Immune correlates of protection against infection with Mycobacterium tuberculosis (Mtb) remain elusive. In this issue of the JCI, Dallmann-Sauer and authors demonstrate that lack of tuberculin skin test (TST) and interferon γ release assay (IGRA) conversion among people with HIV despite years-long Mtb exposure is associated with alveolar lymphocytosis, including specific poly-cytotoxic T cells, and M1-type alveolar macrophages with a stronger ex vivo response to the pathogen. Studies in these rare individuals, termed "TB resisters" and in tuberculosis household contacts who are repeatedly IGRA negative in the months after a specific exposure event (known as "early clearers") help elucidate manipulatable …

Statin Use Is Associated With Protection Against Acute Cholangitis In Patients With Primary Sclerosing Cholangitis: A Multicenter Retrospective Cohort Study, Chiraag Kulkarni, George Cholankeril, Touran Fardeen, Joseph Rathkey, Samir Khan, Soumya Murag, Robert Lerrigo, Ahmad Kamal, Ajitha Mannalithara, Prasun Jalal, Aijaz Ahmed, John Vierling, Aparna Goel, Sidhartha R Sinha

Faculty, Staff and Students Publications

Introduction: Patients with primary sclerosing cholangitis (PSC) are at increased risk of acute cholangitis. The epidemiological risks of cholangitis are poorly studied despite the high morbidity associated with this infection. The aim of this study was to understand the impact of statins on acute cholangitis in PSC.

Methods: This multicenter, retrospective cohort study assessed data from 294 patients with PSC at Stanford Medical Center, Baylor Medical Center, and Valley Medical Center. Clinical factors associated with the development of cholangitis were identified using multivariable Cox regression.

Results: The patients were predominantly male (68.7%) with a median age at enrollment of 48 …

Postvaccination Immunogenicity Among Pediatric Solid Organ Transplant Recipients, Amy G Feldman, Brenda L Beaty, Jose A Ferrolino, Gabriela Maron, Saira A Ali, Leandra Bitterfeld, Adam Blatt, Mary Alice Boulware, Kathleen M Campbell, Emily Carr, Benhur Cetin, 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, Nitika A Gupta, Katherine Harmann, Jessica Hollenbeck, Anna R Huppler, Catalina Jaramillo, Nagraj Kasi, Nanda Kerkar, Stacee Lerret, Steven J Lobritto, M James Lopez, Alisha Mavis, Sonia Mehra, Sindhu Mohandas, Flor M Munoz, Krupa R Mysore, Nadia Ovchinsky, Kerrigan Perkins, Stacy Postma, Lauren Pratscher, Elizabeth B Rand, Regina K Rowe, Daniel Ruderfer, Danielle Schultz, Katherine Sear, Megan L Sell, Tanvi S Sharma, Janis Stoll, Jerry Turner, Kristen G Valencia Deray, Dominique Villarin, Carly Weaver, Phoebe Wood, Olivia Woodford-Berry, George Yanni, Lara A Danziger-Isakov

Faculty, Staff and Students Publications

This cohort study assesses the protection provided by live attenuated viral vaccines among a pediatric population of solid organ transplant recipients 1 year after vaccination.

Variability In Treatment Of Utis In Children With Genitourinary Anomalies In Children's Hospitals, Catherine S Forster, Alexis C Wood, Stephanie Davis-Rodriguez, Sanyukta Desai, Pearl W Chang, Michael J Tchou, John M Morrison, Rana F Hamdy, Vijaya Vemulakonda, Patrick W Brady, Cynthia Abou Zeid, Sowdhamini S Wallace, Uti In Children With Cakut Study Group

Faculty, Staff and Students Publications

Objective: In children with urinary tract anomalies, febrile urinary tract infections (UTIs) are associated with increased risks of sepsis, hospitalization, and kidney injury. However, the best treatment strategies are unknown. We aimed to describe antibiotic treatment practices and outcomes for UTIs in children with urinary tract anomalies and evaluate whether variability in UTI treatment exists between hospitals.

Methods: We conducted a multicenter retrospective cohort study of children seen in emergency departments (EDs) in 6 free-standing US children's hospitals from January 1, 2017, through December 31, 2018. We included children aged 0-17 years with an anatomic or functional urinary tract anomaly …

Inborn Errors Of Immunity Reveal Molecular Requirements For Generation And Maintenance Of Human Cd4+ Il-9-Expressing Cells, Geetha Rao, Corinne D Mack, Tina Nguyen, Natalie Wong, Kathryn Payne, Lisa Worley, Paul E Gray, Melanie Wong, Peter Hsu, Michael O Stormon, Kahn Preece, Daniel Suan, Michael O'Sullivan, Annaliesse K Blincoe, Jan Sinclair, Satoshi Okada, Sophie Hambleton, Peter D Arkwright, Kaan Boztug, Polina Stepensky, Megan A Cooper, Liliana Bezrodnik, Kari C Nadeau, Hassan Abolhassani, Roshini S Abraham, Mikko R J Seppänen, Vivien Béziat, Jacinta Bustamante, Lisa R Forbes Satter, Jennifer W Leiding, Isabelle Meyts, Emmanuelle Jouanguy, Stéphanie Boisson-Dupuis, Gulbu Uzel, Anne Puel, Jean-Laurent Casanova, Stuart G Tangye, Cindy S Ma

Faculty, Staff and Students Publications

Background: CD4+ T cells play essential roles in adaptive immunity. Distinct CD4+ T-cell subsets-TH1, TH2, TH17, TH22, T follicular helper, and regulatory T cells-have been identified, and their contributions to host defense and immune regulation are increasingly well defined. IL-9-producing TH9 cells were first described in 2008 and appear to play both protective and pathogenic roles in human immunity. However, key requirements for generating human TH9 cells remain incompletely defined.

Objective: We sought to define signaling pathways that regulate IL-9 production by human CD4+ T cells.

Methods: Human naive and memory CD4+ T cells were cultured under different conditions, and …

Rapid Diagnostic Sequencing Of Stool Dna Using Targeted Nanopore Sequencing In Patients With A Pulmonary Tuberculosis Diagnosis, Tara Ness, Nontobeko Maphalala, Wethusonkhe Khumalo, Doctor Sibandze, Abigail Seeger, Maia Madison, Anca Vasiliu, Durbin Mulengwa, Clement Gascua, Mangaliso Ziyane, Sindisiwe Dlamini, Gugu Maphalala, Eric Bortz, Alexander Kay, Christoph Lange, Viola Dreyer, Tanja Niemann, Stefan Niemann, Andrew Dinardo, Anna Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

Background: Approximately 1.25 million individuals died of tuberculosis in 2023, in part due to ineffective treatment. In patients with paucibacillary tuberculosis, microbiologic confirmation and drug resistance testing via respiratory specimens is challenging; hence, stool samples are increasingly used for microbiologic confirmation. Targeted next-generation sequencing (tNGS) of stool DNA may improve detection of drug-resistant (DR) tuberculosis, helping patients receive appropriate treatments.

Methods: We assessed the ability of a nanopore tNGS approach using stool to detect drug resistance in a prospective, nested cohort of consecutive participants in Eswatini with pulmonary tuberculosis confirmed via sputum culture or sputum GeneXpert Ultra from 2020 to …

Who And Its Enduring Commitment To Global Pediatrics, Peter J Hotez

Faculty, Staff and Students Publications

No abstract provided.

Postnatal Zika And Dengue Infection And Their Effects On Neurodevelopment Among Children Living In Rural Guatemala, Edwin J Asturias, Amy K Connery, Daniel Olson, Molly M Lamb, Alejandra Paniagua-Avila, Evan J Anderson, Chris Focht, Alison M Colbert, Muktha Natrajan, Jesse J Waggoner, Erin Scherer, D Mirella Calvimontes, Guillermo A Bolaños, Desirée Bauer, Paola Arroyave, Sara Hernández, Maria A Martinez, Aida V Ralda, Neudy Rojop, Edgar E Barrios, Andrea Chacon, Walla Dempsey, Kay M Tomashek, Wendy A Keitel, Hana M El Sahly, Flor M Muñoz

Faculty, Staff and Students Publications

Background: Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic.

Methods: A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by …

Limosilactobacillus Reuteri Promotes The Expression And Secretion Of Enteroendocrine- And Enterocyte-Derived Hormones, Sara C Di Rienzi, Heather A Danhof, Micah D Forshee, Ari Roberts, Robert A Britton

Faculty, Staff and Students Publications

Intestinal microbes can beneficially impact host physiology, prompting investigations into the therapeutic usage of such microbes in a range of diseases. For example, human intestinal microbe Limosilactobacillus reuteri strains ATCC PTA 6475 and DSM 17938 are being considered for use for intestinal ailments, including colic, infection, and inflammation, as well as for non-intestinal ailments, including osteoporosis, wound healing, and autism spectrum disorder. While many of their beneficial properties are attributed to suppressing inflammatory responses, we postulated that L. reuteri may also regulate intestinal hormones to affect physiology within and outside of the gut. To determine if L. reuteri secreted factors …

Liver Transplantation In 3 Cholestatic Infants With History Of Covid Exposure, Shruti Sakhuja, Kalyani R Patel, Matthew Goss, Flor M Munoz, Garrett Wortham, Megan Crawford, John A Goss, Nhu Thao Galvan

Faculty, Staff and Students Publications

The COVID-19 pandemic presents several challenges during pregnancy including thromboembolic complications, direct placental infection, transplacental transmission, and systemic hyperinflammatory state. The liver is the second most commonly affected organ in SARS-CoV-2 infection after the lungs. Mechanisms of liver injury in COVID-19 patients can include: direct viral cytopathic effect, worsening of underlying liver disease, cytokine storm, hypoxic ischemic injury, and cholangiopathy leading to persistent marked cholestasis. Here we describe 3 infants at Texas Children's Hospital with perinatal SARS-CoV-2 exposure with persistent cholestasis and histologic evidence of extrahepatic biliary obstruction suggesting underlying biliary atresia (BA) with some atypical features possibly exacerbated by …

The Influence Of Improved Access To Alcohol-Based Hand Rub And Hand Hygiene Training In Healthcare Facilities On Hand Hygiene Adherence In Belize During Covid-19: June 2021-August 2022., Kelsey Mcdavid, Anh N Ly, Nicholas Bivens, Francis Morey, Gerhaldine Morazan, Russell Manzanero, Melissa Musa-Diaz, Alexandra Medley, Kristy O Murray, Matthew J Lozier

Faculty, Staff and Students Publications

Access to hand hygiene (HH) resources in clinical settings is important to prevent healthcare-associated infections, including COVID-19. However, many countries, including Belize, have limited national data on the availability of HH resources and healthcare worker (HCW) hand hygiene adherence (HHA) in healthcare facilities (HCFs). We conducted a study in the 11 largest public HCFs across Belize to evaluate access to HH resources and HHA before and after an intervention (provision of alcohol-based hand rub (ABHR) wall mounts and HH training). Descriptive statistics and multilevel logistic regressions were used to assess changes in HH resources and HHA from baseline to follow-up …

Antimicrobial Performance Of A Novel Drug-Eluting Bioenvelope, Zerelda Esquer Garrigos, Sunil Kapur, Michelle Leroux Williams, M Rizwan Sohail

Faculty, Staff and Students Publications

No abstract provided.