Digital Commons Network^™

Individual Host Variation In Single-Cell Responses To Enteroaggregative Escherichia Coli Infection Modeled With Human Colon Organoids, Ling Qiu, Tajhal D Patel, Hannah E Jones, Cristian Coarfa, Anthony W Maresso

Faculty, Staff and Students Publications

Enteroaggregative Escherichia coli (EAEC) is a leading cause of diarrhea worldwide. Interestingly, EAEC disease outcomes vary dramatically among infected individuals, ranging from asymptomatic colonization to acute and chronic diarrhea. While previous research has focused on EAEC virulence factors, emerging evidence suggests that host genetic and cellular background may be equally important in determining disease susceptibility. To understand host-driven disease heterogeneity, we performed single-cell RNA sequencing on human colon organoids (HCOs) derived from three healthy adult donors following EAEC 042 infection. Surprisingly, despite comparable EAEC adherence across donors, we observed striking donor-specific responses to infection at multiple levels. A total of …

Skin Carotenoid Scores Reflect Immune Status Among Children Living With Hiv In Tanzania, Wilbert Mbuya, Thobias Boniphace, Michael Mwagala, Peter Agrea, Nazareth M Mbilinyi, Nancy E Moran, Andrew R Dinardo, Mkunde Chachage

Children’s Nutrition Research Center Staff Publications

Many individuals living with HIV experience persistent inflammation despite antiretroviral treatment, increasing their risk for cardiovascular diseases, cognitive decline, and other noncommunicable diseases. Carotenoids can inhibit this inflammation by reducing lipid peroxidation. Carotenoid intake and plasma concentrations can be approximated using a noninvasive cutaneous spectrophotometer. This study quantified skin carotenoid levels in Tanzanian children ages 5 to 15 years old (N = 185) both with and without HIV. Over 95% had low to moderate skin carotenoid scores (< 400 units). In children living with HIV, higher viral loads were linked to lower skin carotenoid scores (rho = -0.57, P < 0.001), whereas higher CD4 counts correlated with increased skin carotenoid scores (rho = 0.52, P < 0.001). Overall, carotenoid levels were low and associated with immune status, suggesting that elevated carotenoid scores correlate with lower inflammation in children living with HIV. Future studies investigating dietary carotenoid interventions to support immune function are warranted.

Newborn Screening Reduces Survival Disparities In Scid After Stem Cell Transplant: A Pidtc Report, Lena E Winestone, Brent R Logan, Xuerong Liu, Olatundun Williams, Elizabeth A Dunn, Monica S Thakar, Sharon A Kidd, Talal Mousallem, Morna J Dorsey, Richard J O'Reilly, Neena Kapoor, Lisa Forbes Satter, Malika Kapadia, Soma C Jyonouchi, Sharat Chandra, Christen L Ebens, Deepakbabu Chellapandian, Sonali Chaudhury, Karin Chen, Blachy J Dávila Saldaña, Ahmad Rayes, Troy C Quigg, Shanmuganathan Chandrakasan, Jeffrey J Bednarski, Kenneth B Desantes, Pierre Teira, Alfred P Gillio, Hesham Eissa, Alan P Knutsen, Victor M Aquino, Evan B Shereck, Theodore B Moore, Emi H Caywood, Mark T Vander Lugt, Jacob Rozmus, Larisa Broglie, Lolie C Yu, Ami J Shah, Avni Y Joshi, Rebecca H Buckley, Jasmeen Dara, Joseph H Oved, Hisham Abdel Azim, Caridad A Martinez, Susan Prockop, Kathleen E Sullivan, Jack J Bleesing, Michael D Keller, Lisa M Madden, Suhag Parikh, Shalini Shenoy, Christine M Seroogy, Tamar Rubin, Jennifer Licata, Jeffrey R Andolina, Donald B Kohn, Lauri Burroughs, Jennifer W Leiding, Rebecca A Marsh, Luigi D Notarangelo, Sung-Yun Pai, Troy R Torgerson, Michael A Pulsipher, Jennifer Heimall, Geoffrey D E Cuvelier, Linda M Griffith, Jennifer M Puck, Christopher C Dvorak, Morton J Cowan, Elie Haddad

Faculty, Staff and Students Publications

Black race and Hispanic ethnicity are associated with higher mortality in severe combined immunodeficiency (SCID) following hematopoietic cell transplantation (HCT), though mechanisms remain unclear. We evaluated 796 children with SCID who received nonsibling HCT between 1982 and 2020 using data from the Primary Immune Deficiency Treatment Consortium. Overall survival for Black (aHR 2.47, 95%CI 1.64, 3.71) and Asian/Pacific Islander patients (aHR 1.82, 95%CI 1.00, 3.30) was significantly lower compared with non-Hispanic White patients, while Hispanic patients had lower event-free survival (aHR 1.83, 95%CI 1.27, 2.63) compared with non-Hispanic White patients. Even after adjusting for age and infection, Black patients with …

A Distinct Form Of Fat Fibrosis Is Linked To Insulin Resistance In People With Hiv, Diana L Alba, Alaa Abdellatif, Moon Kyung Choi, Stephen M Brown Mayfield, Thuy An T Pham, David I Berrios, Antonio E Rodriguez, Marin Ewing, Tony R Figueroa, Judy Gonzalez-Vargas, Ningyan Zhang, Zhiqiang An, Dawei Bu, Steven G Deeks, Philipp E Scherer, Peter W Hunt, Suneil K Koliwad

The Brown Foundation: Institute of Molecular Medicine

BACKGROUND

Despite antiretroviral therapy (ART), people with HIV (PWH) are at heightened risk for insulin resistance (IR) and type 2 diabetes (T2D). Subcutaneous adipose tissue (SAT) fibrosis contributes to metabolic disease, but its role in IR among PWH is unknown. We investigated the relationship between SAT fibrosis and IR in PWH, along with transcriptional signatures to distinguish it from SAT fibrosis due to obesity.

METHODS

We analyzed body composition and SAT fibrosis (hydroxyproline) in 46 PWH and 74 people without HIV (PWoH), excluding individuals with T2D. We examined fibrosis-related gene transcription in the SAT using a targeted panel and measured …

Function And Regulation Of Long Polar Fimbriae During Enterohemorrhagic Escherichia Coli Infection, Walter J. Galdamez

Dissertations and Theses (Open Access)

Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen that causes severe gastrointestinal disease and hemolytic uremic syndrome. EHEC employs multiple virulence factors to colonize the host intestine, including the locus of enterocyte effacement (LEE) encoded type III secretion system, intimin, and flagella, yet the role of long polar fimbriae (Lpf) in adhesions and infection remains less well understood. Long polar fimbriae can mediate bacterial attachment to host cells in vitro, yet the regulation and function of its two fimbrial operons, lpf1 and lpf2 in vivo remain poorly understood. Preliminary RNA-seq data from zebrafish infected with EHEC reveal that expression of …

Defining The Role Of Spxa1 And Spxa2 In Group A Streptococcus (Gas), Gretchen Anne Morrison

Dissertations and Theses (Open Access)

Group A Streptococcus (GAS) is a human-restricted pathogen whose global incidence has surged in the post-COVID era. The ability of GAS to shift from a colonizing to invasive phenotype depends on coordinated virulence gene regulation in response to host-imposed stressors. The paralogous global transcriptional regulators, SpxA1 and SpxA2, have emerged as central mediators of these adaptive responses; however, the mechanisms by which these regulators influence both global gene regulation in direct response to external stresses and the host response as a result of regulatory changes remain incompletely understood. Using an integrated multi-omic approach, we define the distinct yet interconnected regulatory …

Antigen Discovery In Multiple Myeloma Using Integrated Long-Read Transcriptomics And Immunopeptidomics, Aya Albittar

Dissertations and Theses (Open Access)

Multiple myeloma (MM) remains an incurable plasma cell malignancy, with relapse driven by persistent chemotherapy-resistant cells and residual disease following treatment. Although immunotherapies have transformed MM care, their success depends on identifying tumor-specific antigens that can be safely targeted. While aberrant genomic structural variation and transcriptional dysregulation are increasingly recognized as sources of novel antigens in MM, the HLA-presented antigenic landscape of MM remains incompletely characterized, particularly for non-canonical, structurally-derived peptides, and long-read transcriptome-informed immunopeptidomic data specific to MM remain scarce.

We established an integrated antigen discovery platform combining long-read RNA sequencing (Iso-Seq) with mass spectrometry-based HLA immunoprecipitation and immunopeptidomics …

Computable Phenotypes For Research Using Real-World Data: Experiences From The Nih Pragmatic Trials Collaboratory, Marisa L Conte, Judith M Schlaeger, Guilherme Del Fiol, James R Campbell, Andrea L Cheville, Keith Marsolo, Kari A Stephens, Miriam O Ezenwa, Andrew D Boyd, Juanita E Darby, Nadine S Matthie, P Michael Ho, Alice Pressman, Morgan Justice, Carol Reynolds Geary, Keturah R Faurot, Alex Fist, Karen Staman, Hulin Wu, Rachel L Richesson

Faculty, Staff and Student Publications

Objectives: Embedded pragmatic clinical trials (ePCTs) are conducted as part of routine clinical care and therefore use data collected from real-world data sources, such as electronic health record systems and administrative claims. A common approach for using these types of data across all phases of trial conduct is to create a computable phenotype (an explicitly defined data query data, including specified data types, data codes, and logical parameters) to capture patients with a clinical condition, exposure, symptom, characteristic, treatment, or outcome of interest.

Materials and methods: The Electronic Health Record (EHR) Core Working Group of the NIH Pragmatic Trials Collaboratory …

Fuimos Olvidados Y Descuidados [Forgotten And Neglected]: Lessons Learned And Findings From On-Farm Covid-19 Education And Vaccine Clinics For Agricultural Workers And Their Multigenerational Families In Texas, Anabel Rodriguez, David I Douphrate, Ana L Pineda Reyes, Susana Zavala, Lus Chavez, Sofia Nicole Lopez, Andrea V Cabrera Cruz, Annie J Keeney, Nora Hernandez, Brenda Berumen-Flucker, Eva M Shipp, Matthew W Nonnenmann, Shannon P Guillot-Wright, Bethany Boggess Alcauter, G Lopez Ixta, Paula M Cuccaro, Higinio Fernandez-Sanchez, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

Background: Despite being deemed essential non-healthcare workers, agricultural workers were excluded from COVID-19 vaccine prioritization in Texas. This professional practice report describes the multifaceted worker health and safety approaches to protecting agricultural workers and their families during the COVID-19 pandemic.

Methods: Between March 2020 and January 2025, several outreach, education, and training grants from various funding agencies were leveraged to deliver training, personal protective equipment, vaccines, and economic relief to agricultural workers in partnership with community-based organizations, industry, local public health departments, and academic institutions.

Findings: Timely funding efforts led to the distribution of 1,000 PPE kits, with more than …

Dupilumab Versus Placebo In Adults And Adolescents With Eosinophilic Gastritis (Degas): A Double-Blind, Placebo-Controlled, Phase 2, Multicentre, Randomised Controlled Trial, Nirmala P Gonsalves, Evan S Dellon, Kara L Kliewer, Tetsuo Shoda, Regina Yearout, Seema S Aceves, Nicoleta C Arva, John A Besse, Julie M Caldwell, Mirna Chehade, Amaziah Coleman, Margaret H Collins, Sara Anvari, Gary W Falk, Sandeep K Gupta, Girish Hiremath, David A Katzka, Paneez Khoury, John Leung, Calies Menard-Katcher, Paul Menard-Katcher, Kathryn A Peterson, Maria A Pletneva, Amanda K Rudman Spergel, Jonathan M Spergel, Tatyana Vaysman, Joshua B Wechsler, Benjamin L Wright, Guang-Yu Yang, Xue Zhang, Meijian Zhou, Ashish Bansal, Bram P Raphael, Amr Radwan, Jennifer Maloney, Antonio Martin, Yamo Deniz, Glenn T Furuta, Lisa J Martin, Marc E Rothenberg

Faculty, Staff and Students Publications

Background: Eosinophilic gastritis currently has no approved treatments and is postulated to be driven by type 2 inflammation. Dupilumab blocks type 2 cytokines IL-4 and IL-13 and has efficacy in multiple diseases characterised by type 2 inflammation, including eosinophilic oesophagitis. We aimed to assess the efficacy and safety of dupilumab in patients with eosinophilic gastritis.

Methods: DEGAS was a proof-of-concept, phase 2, multicentre, randomised controlled trial consisting of a 12-week, double-blind, placebo-controlled period, followed by a 24-week open-label extension period. Patients aged 12-70 years from 11 hospitals in the USA with histologically active eosinophilic gastritis (≥30 eosinophils per high-power field …

Loss Of Atp-Dependent Citrate Lyase Drives Left Ventricular Dysfunction By Metabolic Remodeling, Shijie Liu, Seth T Gammon, Lin Tan, Yaqi Gao, Kyoungmin Kim, Mahmoud H Elbatreek, Adrian Arrieta, Ian K Williamson, Rebecca L Salazar, Janet Pham, Angela Davidian, Radhika Khanna Neicheril, Benjamin D Gould, Heidi Vitrac, Alia Sadiq, An Q Dinh, Evan C Lien, Francisca N De Luna Vitorino, Joanna M Gongora, Sara A Martinez, Melanie T Odenkirk, Anna K Boatman, Jessie R Chappel, Lawrence S C Czer, Evan P Kransdorf, David J Lefer, Blake M Hanson, Benjamin A Garcia, Erin M Baker, Matthew G Vander Heiden, Philip L Lorenzi, Heinrich Taegtmeyer, David Piwnica-Worms, James F Martin, Anja Karlstaedt

Faculty, Staff and Student Publications

Background: Metabolic adaptation and maladaptation are hallmarks of the failing heart and may be a target for therapeutic interventions. For example, sustained glucose oxidation during cardiac stress is associated with increased activity and abundance of ACL (ATP-dependent citrate lyase, Acly), which produces acetyl-coenzyme A (CoA) from citrate and CoA and supports de novo lipid synthesis. However, our understanding of how ACL supports cardiac metabolic adaptation and its potential to modulate disease pathophysiology has not yet been investigated.

Methods: We used human heart tissue samples from healthy donors and patients with nonischemic cardiomyopathy. Next, we used CRISPR (clustered, regularly interspaced …

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, Robert B Lindell, Samir U Sayed, Jose S Campos Duran, Sydney A Sheetz, Apoorva Babu, Montana S Knight, Andrea A Mauracher, Ceire A Hay, Peyton E Conrey, Julie C Fitzgerald, Nadir Yehya, Stephen T Famularo, Teresa Arroyo, Richard Tustin, Hossein Fazelinia, Edward M Behrens, David T Teachey, Lisa R Forbes Satter, Alexandra F Freeman, Jenna Re Bergerson, Steven M Holland, Jennifer W Leiding, Scott L Weiss, Mark W Hall, Deanne M Taylor, Rui Feng, E John Wherry, Nuala J Meyer, Sarah E Henrickson

Faculty, Staff and Students Publications

BACKGROUND

Sepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear.

METHODS

We integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity.

RESULTS

Unsupervised clustering of plasma cytokines identified 3 immunologic subgroups, including a high-severity group (“Group C”) characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a …

Longitudinal Genomic Surveillance Of Sars-Cov-2 In A University Microcosm Reflects Global Evolutionary Trends, Sankar Prasad Chaki, Melissa M Kahl-Mcdonagh, Benjamin W Neuman, Loni A Taylor, Rebecca S B Fischer, Blake M Hanson, Marlisa S Hardy, Jo Ann Culpepper, Eric Boerwinkle, Kurt A Zuelke

Faculty, Staff and Student Publications

SARS-CoV-2 transmission has declined, yet ongoing viral evolution continues to pose public health challenges. This study conducted long-term (2020-2024) genomic surveillance within a large and globally diverse university community. Viral genomes obtained from clinical (n = 1,786) and surveillance (n = 888) testing samples were classified under clade, lineage, and variant systems, and compared with global genomic data sets. Local patterns broadly paralleled global evolutionary trends, including the phased emergence of major variants, episodic introductions of new lineages, and shifts in dominant clades. Lineage diversity peaked during fall semesters and was highest among undergraduate-aged individuals, with similar distributions …

Pneumococcal Colonization In Pediatric Patients Undergoing Hematopoietic Cell Transplantation, Liset Olarte, Jennifer E Schuster, Ibrahim Ahmed, Kristina G Hulten

Faculty, Staff and Students Publications

Despite the increased risk of invasive pneumococcal disease among pediatric hematopoietic cell transplant (HCT) recipients, pneumococcal colonization has not been evaluated in this population. We prospectively assessed longitudinal pneumococcal colonization in 22 pediatric HCT recipients from conditioning therapy to 100 days post-HCT. A higher likelihood of pneumococcal colonization was observed in the late post-HCT period (weeks 9-14) compared with the early post-HCT period (weeks 1-8), with odds increasing with each additional week after conditioning.IMPORTANCEThis is the first study to longitudinally evaluate pneumococcal colonization in pediatric hematopoietic cell transplant (HCT) recipients from the onset of conditioning therapy to 100 days post-HCT. …

Reducing Communicable-Disease Risk After Earthquakes: Vaccination And Prevention Lessons For Venezuela's Doublet, Alfonso J Rodriguez-Morales, Ivan Arturo Rodríguez-Sabogal, Adriana Sucari, Wendy Moncada, Lili Vanessa Hernández-Serrano, Florencia Escarrá, Pasesa Pascuala Quispe-Torrez, Francisco Javier Membrillo, Tomás Orduna, Susana Lloveras, Tânia S S Chaves, Miguel M Cabada, Cecilia Perret, René Echavarría, Ana F Ribeiro, Melinda Tanabe, Fernando Bazzino, Maximiliano Ramirez, Baruch Diaz, Karen Mirna Loro Morejón, Karen Daly, Reinaldo Rosas, Maria Belen Lopez, Cristina Miranda, Marisa Liliana Fernandez, Yasemin Özsürekçi, Wasin Matsee, Yenddy Carrero, Cristian Biscayart, Sergio Cimerman, Maria L Avila-Aguero, Roberto Debbag, Jose Brea, Alejandro Risquez, Jaime David Acosta-España, Rolando Ulloa-Gutierrez, Carlos Espinal, Carlos N Torres-Martinez, Marta González-Sanz, Aula Abbara, Jill Weatherhead, Bernal Cordero, Virgilio Lezcano, Amanda Guerrero, Herberth Maldonado, Luis Cuellar, Ines Ceron, Yori Roque, Melisa Florentin, Rosa Infante, Ana Carvajal, Lily M Soto-Ávila, Marbelys Hernández, Hector Villaroel, Gianmary Miozzi, Rafael Navas, Moraima Hernández, Carlos Pérez-Vega, Manuela Mérida, David A Forero-Peña, Juan-Carlos Navarro, Claudia Beltrán-Arroyave, Mario Masana

Faculty, Staff and Students Publications

No abstract provided.

Antibody-Oligonucleotide Conjugates: An Emerging Modality For Precision Rna Therapeutics, Chen-Hsu Yu, Summer Y Y Ha, Zhiqiang An, Kyoji Tsuchikama, Wenbo Li

The Brown Foundation: Institute of Molecular Medicine

RNA-targeting therapeutics have enormous potential to precisely target disease-causing RNAs, extending beyond the traditional limits of "druggability" for small molecules, antibodies, and protein-targeting cell therapies. However, one crucial limitation is that RNA-targeting drug modalities (such as oligonucleotides) cannot effectively reach diseased tissue or cell types. Antibody-oligonucleotide conjugates (AOCs) emerge as a promising frontier in aiding RNA therapeutics by harnessing antibodies to deliver drug modalities to target specific RNAs in desired tissues or cells. In this Review, we summarize the critical components of AOCs, key considerations for their design and manufacturing, ongoing AOCs in preclinical/clinical development, and disease indications. We discuss …

Reducing Over-Isolation: Baseline Evaluation Of Isolation Precaution Reassessment In Hospitalized Children, Laura Brambilla, Wan-Hsuan Chen

Summer Research Program Abstracts

No abstract provided.

Antibody-Oligonucleotide Conjugates: An Emerging Modality For Precision Rna Therapeutics, Chen-Hsu Yu, Summer Y Y Ha, Zhiqiang An, Kyoji Tsuchikama, Wenbo Li

The Brown Foundation: Institute of Molecular Medicine

RNA-targeting therapeutics have enormous potential to precisely target disease-causing RNAs, extending beyond the traditional limits of "druggability" for small molecules, antibodies, and protein-targeting cell therapies. However, one crucial limitation is that RNA-targeting drug modalities (such as oligonucleotides) cannot effectively reach diseased tissue or cell types. Antibody-oligonucleotide conjugates (AOCs) emerge as a promising frontier in aiding RNA therapeutics by harnessing antibodies to deliver drug modalities to target specific RNAs in desired tissues or cells. In this Review, we summarize the critical components of AOCs, key considerations for their design and manufacturing, ongoing AOCs in preclinical/clinical development, and disease indications. We discuss …

Does Antibiotic Therapy Affect Multiplex Pcr Results In Community-Acquired Bacterial Meningitis?, Caroline Reckart, Elizabeth Aguilera, Audrey Wanger, Rafael Bravo-Santos, Rodrigo Hasbun

Faculty, Staff and Student Publications

No abstract provided.

Clinical Features And Dental Pathologies In Maxillary Sinus Fungal Balls And Odontogenic Sinusitis, Eunice Im, Lane Donaldson, Avraham Adelman, Nithin D Adappa, Yi-Wei Chen, Nikita Chapurin, Jennifer E Douglas, Glen E D'Souza, Jacob Eide, Maria Espinosa, Chia-Hsiang Fu, Meha G Fox, Rohit Garg, Edward C Kuan, Michael A Kohanski, Marta Kwiatkowska, Kevin Li, Derek H Liu, Tran Bao Locke, Chih-Feng Lin, Chadi Makary, Alice Ottavi, Peter Papagiannopoulos, James N Palmer, Charles C L Tong, Bobby A Tajudeen, Sanjena Venkatesh, Kimberly Wei, Frederick Yoo, Alison J Yu, Jun Jin, Alberto M Saibene, John R Craig

Faculty, Staff and Students Publications

Objectives: While maxillary sinus fungal balls (MSFB) can be associated with odontogenic conditions (MSFBO), MSFBO clinical and dental features have not been compared to odontogenic sinusitis (ODS). This multicenter study aimed to compare characteristics of MSFB, MSFBO, and ODS.

Methods: A multicenter international retrospective cohort study was conducted on adults with MSFBs and ODS who underwent sinus surgery. First in MSFBs, it was determined whether different dental conditions were more likely in FB versus non-FB sides. Second, clinical features and dental pathologies were compared between MSFBO and ODS. For analyses, dental conditions were considered individually and as two groups: infectious …

Longitudinal And Cross-Sectional Evidence That Daily Resting And Activity Energy Expenditures Are Independent In Humans, Andrew K Yegian, Elizabeth Pachus, Leanne M Redman, Steven B Heymsfield, K Falkenhain, Alexandra R Harris, Shaji K Chacko, William W Wong, Daniel E Lieberman

Faculty, Staff and Students Publications

Total energy expenditure (TEE) is commonly modelled as the sum of resting energy expenditure (REE), activity energy expenditure (AEE), and diet-induced thermogenesis (DIT). This additive model has recently been challenged by the constrained energy balance model, which proposes that reductions in mass-adjusted REE compensate to some extent for increases in AEE, rendering mass-adjusted TEE effectively invariant. We tested these competing models using two complementary approaches. First, we conducted a short-term longitudinal, repeated-measures experiment in 12 adults who completed 10-day periods of high and low physical activity separated by a washout period. TEE was measured with doubly labelled water, AEE with …

Na-Gst-1 Adsorbed On Alhydrogel Co-Administered With Different Toll-Like Receptor Agonists In Hookworm-Naive Adults Using A Controlled Human Infection Model In The Usa: A Phase 2, Double-Blind, Randomised Controlled Trial, Caroline K Dirosato, Elissa M Malkin, Sean M Lee, Guacyara Erwin, Lara Hoeweler, Larissa Scholte, Maria Elena Bottazzi, David I Pritchard, Peter J Hotez, Jeffrey M Bethony, David J Diemert

Faculty, Staff and Students Publications

Background: Necator americanus glutathione S-transferase-1 (Na-GST-1) performs a crucial enzymatic step in hookworm blood feeding and is a leading target for vaccine development. Phase 1 trials in Brazil, Gabon, and the USA of recombinant Na-GST-1 adsorbed on Alhydrogel (Na-GST-1/Al), co-administered with or without AP 10-701 (Toll-like receptor [TLR] 4 agonist) or CpG 10104 (TLR9 agonist), showed the vaccine was well tolerated, safe, and immunogenic. A controlled human hookworm infection (CHHI) model was previously developed to evaluate the effect of candidate hookworm vaccines on infection. We aimed to assess the effect of vaccination with three different Na-GST-1 vaccine formulations on subsequent …

Ebneo Commentary: The Lakana Trial: Mass Administration Of Azithromycin To Infants In Mali Did Not Reduce Mortality, Maya I Brasher, Monika S Patil

Faculty, Staff and Students Publications

The LAKANA trial: a randomized control trial evaluating the impact of mass administration of azithromycin to infants 1 to 11 months of age in Mali showed no reduction in mortality.

Human Exposure To Spirochete-Infected Ornithodoros Turicata In A Residential Setting In The Austin, Texas Metropolitan Area, Serhii Filatov, Bonny Mayes, Sarah M Gunter, Alexander R Kneubehl, Job E Lopez

Faculty, Staff and Students Publications

A central Texas resident found an engorged Ornithodoros turicata tick attached to their ankle while at home. The tick tested positive for Borrelia turicatae, an agent for soft tick-borne relapsing fever. Three weeks earlier, the patient started experiencing febrile episodes, rash, and nausea, yet the etiological agent went undiagnosed.

Plasma And Extracellular Vesicle–Enriched Protein Profiles In Chronic Rhinosinusitis, Aryana Amin, Rutviben P. Shah Bds, Dhvani Parikh Mph, Niki Mirhosseini Bs, Baharan Fekry Phd, Donyea L. Moore, Mahboobeh Mahdavinia Md, Phd

Summer Research Program Abstracts

No abstract provided.

Detection, Persistence, And Rising Prevalence Of Oncogenic Viruses Revealed By Wastewater Metagenomics, Harihara Prakash, Ryan K Perez, Matt Ross, Michael Tisza, Sara J Javornik Cregeen, Jennifer Deegan, Joseph F Petrosino, Eric Boerwinkle, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Oncogenic viruses cause high-risk cancers in humans and are responsible for nearly 20% of all cancer cases worldwide. Currently, very limited data exist in the realm of wastewater-based viral epidemiology (WBE) for cancer-causing viruses, with existing studies using targeted approaches (i.e., PCR-based approaches) that lack genomic resolution. In this study, we used a hybrid-capture approach to detect, filter, and sequence all known oncogenic virus signals from wastewater samples collected over 3 years (May 2022-May 2025) in 16 Texas cities, covering nearly 25% of the state's population. Once sequenced, we used custom computational tools designed for wastewater metagenomics to assign reads …

Targeted Next-Generation Sequencing Implementation In Eswatini Identifies Rifampicin And Bedaquiline Resistance Undetected By Routine Diagnostic Testing, Debrah Vambe, Alexander Kay, Mangaliso Ziyane, Mdigo Thunzini, Sein Sein Thi, Leonardo De Araujo, Viola Dreyer, Tanja Niemann, Busizwe Sibandze, Sijabu Masina, Andrea Maurizio Cabibbe, Jennifer Furin, Tafadzwa Mazuruse, Lindokuhle Dlamini, Thulani Jele, Bheki Mamba, Gugu Maphalala, Makhosazana Dlamini, Mbongeni Dube, Nomthandazo Lukhele, Daniela Maria Cirillo, Anna Mandalakas, Christoph Lange, Sphiwe Ngwenya, Christian Utpatel, Sindisiwe Dlamini, Stefan Niemann

Faculty, Staff and Students Publications

In Eswatini, multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains harbouring the rifampicin-resistance (RR) rpoB I491F mutation are missed by routine diagnostics, including GeneXpert MTB/RIF Ultra (Xpert Ultra), line probe assays (LPA), and mycobacterium growth indicator tube (MGIT) phenotypic drug susceptibility testing (pDST). To address this diagnostic gap, Eswatini introduced targeted next-generation sequencing (tNGS) in 2019. We analysed 234 patient samples enrolled from June 2021 to December 2024 with isoniazid and/or rifampicin resistance detected by routine diagnostics, or suspected treatment failure, and obtained detailed clinical and outcome data from 59 patients. tNGS detected RR in 159 strains, of which 101 (64%) carried …

Statewide Multi-Year Wastewater Sequencing Reveals Dual Origins Of Hiv-1 Signal, Justin R Clark, Dylan Chirman, Harihara Prakash, Austen Terwilliger, Marlene Mcneese, Matt Ross, Mike Tisza, Sara J Javornik Cregeen, Loren Hopkins, Jennifer Deegan, Catherine L Troisi, Eric Boerwinkle, Kristina Mena, Fuqing Wu, Jason T Kimata, Marc Johnson, Devon Gregory, Faith E Fletcher, Thomas P Giordano, Anthony W Maresso

Faculty, Staff and Students Publications

Human immunodeficiency virus 1 (HIV-1) is a retrovirus which has infected 90 million people and resulted in over 40 million deaths. Despite advances in diagnostics, treatment, and prophylaxis, HIV-1 continues to spread due to undiagnosed and untreated infections. Traditional monitoring methods are ineffective when access to testing is limited or people do not seek care, particularly given the long period between infection and symptom onset, allowing undetected transmission to continue. Here, we use a hybrid-capture sequencing approach to track HIV-1 signal in municipal wastewater in 15 different cities over nearly 3 years. We obtain near-complete genomic coverage of HIV-1, enabling …

Global Burden Of Drug-Resistant Tuberculosis In Children: A Systematic Analysis For The Global Burden Of Disease Study, Xuhui Liu, Peierdun Mijiti, Lu Xia, Sylvia M Lacourse, Wulan Talafuhan, Alexander W Kay, Yang Yang, Huarui Liu, Dan Ye, Leonardo Martinez, Shuihua Lu, Adong Shen, Anna M Mandalakas, Feng Li, Christoph Lange, Zhen Huang

Faculty, Staff and Students Publications

Background: Paediatric tuberculosis (TB), particularly drug-resistant TB (DR-TB), is associated with significant mortality. However, the global burden of childhood TB remains poorly understood.

Methods: We analysed incident cases, deaths, and age-standardised incidence and mortality rates among children (0-14 years) with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) and extensively drug-resistant tuberculosis (XDR-TB) using the Global Burden of Disease (GBD) 2021 database. Data were stratified by age, sex, region, country, and HIV/AIDS status. Annual and average annual percentage changes were assessed using joinpoint regression analysis. Secondary analyses compared adult and paediatric TB trends in the End TB era and evaluated the potential impact of the …

The Relationship Between Psychological Stress And Sars-Cov-2 Nucleocapsid-Antibody Response Following Natural Infection: Longitudinal Findings From The Aegis Study, Erika T Beidelman, Ashley Judge, David B Allison, Stephanie Dickinson, Lilian Golzarri Arroyo, Anna L M Macagno, Michael J Ricciardi, Jon Macy, Stanley Perlman, Christina Ludema, Kevin C Maki, Molly Rosenberg

Faculty, Staff and Students Publications

Psychological stress can cause diminished immune response to infectious challenges. The extent this holds true during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the modifying effect of vaccination status is untested. We explored these relationships in a non-random sample standardized to the US adult population. Across 2178 participants in the Aegis study (2021-2022), we identified 507 eligible laboratory-confirmed SARS-CoV-2 infections. We estimated the natural log of nucleocapsid-binding antibody absorbance (N-antibody) at study visits up to 225 days following a positive SARS-CoV-2 test. Linear mixed effects models were fit to estimate the association of baseline perceived stress and, separately, …