Digital Commons Network^™

Measurement Of Severe Acute Respiratory Syndrome Coronavirus 2 Antigens In Plasma Of Pediatric Patients With Acute Coronavirus Disease 2019 Or Multisystem Inflammatory Syndrome In Children Using An Ultrasensitive And Quantitative Immunoassay, George B Sigal, Tanya Novak, Anu Mathew, Janet Chou, Yubo Zhang, Navaratnam Manjula, Pradeepthi Bathala, Jessica Joe, Nikhil Padmanabhan, Daniel Romero, Gabriella Allegri-Machado, Jill Joerger, Laura L Loftis, Stephanie P Schwartz, Tracie C Walker, Julie C Fitzgerald, Keiko M Tarquinio, Matt S Zinter, Jennifer E Schuster, Natasha B Halasa, Melissa L Cullimore, Aline B Maddux, Mary A Staat, Katherine Irby, Heidi R Flori, Bria M Coates, Hillary Crandall, Shira J Gertz, Adrienne G Randolph, Nira R Pollock, Overcoming Covid-19 Investigators

Center for Medical Ethics and Health Policy Staff Publications

Background: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood has high sensitivity in adults with acute coronavirus disease 2019 (COVID-19), but sensitivity in pediatric patients is unclear. Recent data suggest that persistent SARS-CoV-2 spike antigenemia may contribute to multisystem inflammatory syndrome in children (MIS-C). We quantified SARS-CoV-2 nucleocapsid (N) and spike (S) antigens in blood of pediatric patients with either acute COVID-19 or MIS-C using ultrasensitive immunoassays (Meso Scale Discovery).

Methods: Plasma was collected from inpatients (< 21 years) enrolled across 15 hospitals in 15 US states. Acute COVID-19 patients (n = 36) had a range of disease severity and positive nasopharyngeal SARS-CoV-2 RT-PCR within 24 hours of blood collection. Patients with MIS-C (n = 53) met CDC criteria and tested positive for SARS-CoV-2 (RT-PCR or serology). Controls were patients pre-COVID-19 (n = 67) or within 24 hours of negative RT-PCR (n = 43).

Results: Specificities of N and S assays were 95-97% and 100%, respectively. In acute COVID-19 patients, N/S plasma assays …

Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021., Ariana Perez, Joana Y. Lively, Aaron Curns, Geoffrey A. Weinberg, Natasha B. Halasa, Mary Allen Staat, Peter G. Szilagyi, Laura S. Stewart, Monica M. Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L. Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A. Englund, Eileen J. Klein, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Gayle E. Langley, Susan I. Gerber, Angela Campbell, Aron J. Hall, Brian Rha, Meredith Mcmorrow, New Vaccine Surveillance Network Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN …

Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021, Ariana Perez, Joana Y Lively, Aaron Curns, Geoffrey A Weinberg, Natasha B Halasa, Mary Allen Staat, Peter G Szilagyi, Laura S Stewart, Monica M Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A Englund, Eileen J Klein, Rangaraj Selvarangan, Christopher J Harrison, Julie A Boom, Leila C Sahni, Marian G Michaels, John V Williams, Gayle E Langley, Susan I Gerber, Angela Campbell, Aron J Hall, Brian Rha, Meredith Mcmorrow

Faculty, Staff and Student Publications

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN …

Covid-19 And Children, Carl A Pierce, Kevan C Herold, Betsy C Herold, Janet Chou, Adrienne Randolph, Binita Kane, Sammie Mcfarland, Deepti Gurdasani, Christina Pagel, Peter Hotez, Sarah Cobey, Scott E Hensley

Center for Medical Ethics and Health Policy Staff Publications

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in …

Xpert Mtb/Rif Ultra Assay For Tuberculosis Disease And Rifampicin Resistance In Children, Alexander W Kay, Tara Ness, Sabine E Verkuijl, Kerri Viney, Annemieke Brands, Tiziana Masini, Lucia González Fernández, Michael Eisenhut, Anne K Detjen, Anna M Mandalakas, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

BACKGROUND: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of …

Rates Of Laboratory Adverse Events By Course In Paediatric Leukaemia Ascertained With Automated Electronic Health Record Extraction: A Retrospective Cohort Study From The Children’S Oncology Group, Tamara P Miller, Kelly D Getz, Yimei Li, Biniyam G Demissei, Peter C Adamson, Todd A Alonzo, Evanette Burrows, Lusha Cao, Sharon M Castellino, Marla H Daves, Brian T Fisher, Robert Gerbing, Robert W Grundmeier, Edward M Krause, Judy Lee, Philip J Lupo, Karen R Rabin, Mark Ramos, Michael E Scheurer, Jennifer J Wilkes, Lena E Winestone, Douglas S Hawkins, M Monica Gramatges, Richard Aplenc

Center for Medical Ethics and Health Policy Staff Publications

Background: Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia.

Methods: For this retrospective cohort study from the Children's Oncology Group (COG), we included patients aged 0-22 years treated for acute myeloid leukaemia or acute lymphoblastic leukaemia at Children's Healthcare of Atlanta (Atlanta, GA, USA) from Jan 1, 2010, to Nov 1, 2018, at the Children's Hospital of Philadelphia …

Factors Associated With Severe Illness In Patients Aged <21 Years Hospitalized For Covid-19, Rewa Choudhary, Bryant J Webber, Lindsay S Womack, Hannah K Dupont, Sophia K Chiu, Valentine Wanga, Megan E Gerdes, Sophia Hsu, Dallas S Shi, Theresa M Dulski, Osatohamwen I Idubor, Arthur M Wendel, Nickolas T Agathis, Kristi Anderson, Tricia Boyles, Eleanor S Click, Juliana Da Silva, Mary E Evans, Jeremy A W Gold, Julia C Haston, Pamela Logan, Susan A Maloney, Marisol Martinez, Pavithra Natarajan, Kevin B Spicer, Mark Swancutt, Valerie A Stevens, Jessica Rogers-Brown, Gyan Chandra, Megan Light, Frederick E Barr, Jessica Snowden, Larry K Kociolek, Matthew Mchugh, David L Wessel, Joelle N Simpson, Kathleen C Gorman, Kristen A Breslin, Roberta L Debiasi, Aaron Thompson, Mark W Kline, Julie A Boom, Ila R Singh, Michael Dowlin, Mark Wietecha, Beth Schweitzer, Sapna Bamrah Morris, Emilia H Koumans, Jean Y Ko, David A Siegel, Anne A Kimball

Faculty, Staff and Students Publications

OBJECTIVES: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness.

METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients agedchildren's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation.

RESULTS: Of 947 hospitalized patients, 759 …

A Case Series Of Children With Acute Hepatitis And Human Adenovirus Infection, L Helena Gutierrez Sanchez, Henry Shiau, Julia M Baker, Stephanie Saaybi, Markus Buchfellner, William Britt, Veronica Sanchez, Jennifer L Potter, L Amanda Ingram, David Kelly, Xiaoyan Lu, Stephanie Ayers-Millsap, Wesley G Willeford, Negar Rassaei, Julu Bhatnagar, Hannah Bullock, Sarah Reagan-Steiner, Ali Martin, Michael E Rogers, Anna M Banc-Husu, Sanjiv Harpavat, Daniel H Leung, Elizabeth A Moulton, Daryl M Lamson, Kirsten St George, Aron J Hall, Umesh Parashar, Adam Macneil, Jacqueline E Tate, Hannah L Kirking

Faculty, Staff and Students Publications

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia.

METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children’s of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing.

RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 …

Acylcarnitines And Genetic Variation In Fat Oxidation Genes In Hiv-Infected, Antiretroviral-Treated Children With And Without Myopathy, Brian Kirmse, Charlotte Hobbs, Lisa Aaron, Grace Montepiedra, Marshall Summar, Paige L Williams, Caitlin J Smith, Russell Van Dyke, Chunli Yu, Kelli K Ryckman, William Borkowsky

Faculty, Staff and Student Publications

BACKGROUND: Mitochondrial toxicity resulting in myopathy and lactic acidosis has been described in antiretroviral (ARV)-exposed patients. We hypothesized that myopathy in HIV-infected, ARV-treated children would be associated with metabolic (acylcarnitines) and genetic (variants in metabolic genes) markers of dysfunctional fatty acid oxidation (FAO).

METHODS: Acylcarnitine profiles (ACP) were analyzed for 74 HIV-infected children on nucleoside reverse transcriptase inhibitor (NRTI)-containing ARV. Thirty-seven participants with ≥2 creatine kinase measurements >500 IU (n = 18) or evidence of echocardiographic cardiomyopathy (n = 19) were matched with 37 participants without myopathy. Single nucleotide polymorphisms (SNPs) in FAO genes were also evaluated.

RESULTS: Abnormal ACP …

Conventional And Advanced Mr Imaging Findings In A Cohort Of Pathology-Proven Dermoid Cysts Of The Pediatric Scalp And Skull, Bettina L Serrallach, Gunes Orman, M John Hicks, Nilesh Desai, Stephen Kralik, Thierry Agm Huisman

Faculty, Staff and Students Publications

BACKGROUND: In the pediatric population, dermoid cysts are among the most frequent lesions of the scalp and skull. Imaging plays a key role in characterizing scalp and skull lesions in order to narrow the differential diagnoses. In general, dermoids are described as heterogeneous T1-/T2-hypo- to hyperintense lesions on magnetic resonance imaging.

METHODS: The goal of this retrospective study is to evaluate the diffusion weighted imaging findings while reviewing the conventional T1-/T2-/T1+C-weighted MR characteristics in a pathology-proven series of 14 dermoids of the pediatric scalp and skull.

RESULTS: In our pediatric cohort (eight boys, six girls, age range 3-95 months), half …

Genome-Wide Association Study In Minority Children With Asthma Implicates Dnah5 In Bronchodilator Responsiveness, Jaehyun Joo, Angel C. Y Mak, Shujie Xiao, Patrick M. Sleiman, Donglei Hu, Scott Huntsman, Celeste Eng, Mengyuan Kan, Avantika R. Diwakar, Jessica A. Lasky-Su, Scott T. Weiss, Joanne E. Sordillo, Ann C. Wu, Michelle Cloutier, Glorisa Canino, Erick Forno, Juan C. Celedón, Max A. Seibold, Hakon Hakonarson, Keoki L. Williams, Esteban G. Burchard, Blanca E. Himes

Center for Individualized and Genomic Medicine Research Articles

Variability in response to short-acting β(2)-agonists (e.g., albuterol) among patients with asthma from diverse racial/ethnic groups may contribute to asthma disparities. We sought to identify genetic variants associated with bronchodilator response (BDR) to identify potential mechanisms of drug response and risk factors for worse asthma outcomes. Genome-wide association studies of bronchodilator response (BDR) were performed using TOPMed Whole Genome Sequencing data of the Asthma Translational Genomic Collaboration (ATGC), which corresponded to 1136 Puerto Rican, 656 Mexican and 4337 African American patients with asthma. With the population-specific GWAS results, a trans-ethnic meta-analysis was performed to identify BDR-associated variants shared across the …

Antibody Responses To Sars-Cov-2 After Infection Or Vaccination In Children And Young Adults With Inflammatory Bowel Disease., Joelynn Dailey, Lina Kozhaya, Mikail Dogan, Dena Hopkins, Blaine Lapin, Katherine Herbst, Michael Brimacombe, Kristen Grandonico, Fatih Karabacak, John Schreiber, Bruce Tsan-Liang Liang, Juan C Salazar, Derya Unutmaz, Jeffrey S Hyams

Faculty Research 2022

BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

METHODS: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and …

Impact Of Risk-Based Sexually Transmitted Infection Screening In The Emergency Department, Fahd A Ahmad, Kayleigh Fischer, Hongjie Gu, Thomas C Bailey, Donna B Jeffe, Christopher R Carpenter, Philip R O Payne

Faculty, Staff and Student Publications

OBJECTIVES: Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV) pose a significant health burden in adolescents. Many adolescents receiving care in the emergency department (ED) are in need of testing, regardless of their chief complaint. Our objective was to determine whether an electronic, risk-based STI screening program in our ED was associated with an increase in STI testing among at-risk adolescents.

METHODS: We conducted a retrospective cohort analysis of patient outcomes in our pediatric ED after integrating an Audio-enhanced Computer-Assisted Self-Interview (ACASI) as standard of care. It obtained a focused sexual history and generated STI testing …

Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

METHODS: In this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. …

Human Metapneumovirus Phosphoprotein Independently Drives Phase Separation And Recruits Nucleoprotein To Liquid-Like Bodies, Kerri Beth Boggs, Kearstin Edmonds, Nicolas Cifuentes-Munoz, Farah El Najjar, Conny Ossandón, Mckenna Roe, Chao Wu, Carole L Moncman, Trevor P Creamer, Gaya K Amarasinghe, Daisy W Leung, Rebecca Ellis Dutch

Open Access Publications

Human metapneumovirus (HMPV) inclusion bodies (IBs) are dynamic structures required for efficient viral replication and transcription. The minimum components needed to form IB-like structures in cells are the nucleoprotein (N) and the tetrameric phosphoprotein (P). HMPV P binds to the following two versions of the N protein in infected cells: N-terminal P residues interact with monomeric N (N

Efficacy And Outcomes Of Faecal Microbiota Transplantation For Recurrent Clostridioides Difficile Infection In Children With Inflammatory Bowel Disease, Maribeth R Nicholson, Erin Alexander, Sonia Ballal, Zev Davidovics, Michael Docktor, Michael Dole, Jonathan M Gisser, Alka Goyal, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Richard Kellermayer, Judith R Kelsen, Melissa A Kennedy, Sahil Khanna, Elizabeth D Knackstedt, Jennifer Lentine, Jeffery D Lewis, Sonia Michail, Paul D Mitchell, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, Sarah Sidhu, Aliza B Solomon, David L Suskind, Madison Weatherly, Steven Werlin, Edwin F De Zoeten, Stacy A Kahn, North American Society Of Pediatric Gastroenterology And Nutrition Faecal Microbiota Transplantation Special Interest Group

Faculty, Staff and Students Publications

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD.

METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data …

Temporal Changes In Gastrointestinal Fungi And The Risk Of Autoimmunity During Early Childhood: The Teddy Study, Thomas A Auchtung, Christopher J Stewart, Daniel P Smith, Eric W Triplett, Daniel Agardh, William A Hagopian, Anette G Ziegler, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Åke Lernmark, Beena Akolkar, Jeffrey P Krischer, Kendra Vehik, Jennifer M Auchtung, Nadim J Ajami, Joseph F Petrosino

Faculty, Staff and Students Publications

Fungal infections are a major health problem that often begin in the gastrointestinal tract. Gut microbe interactions in early childhood are critical for proper immune responses, yet there is little known about the development of the fungal population from infancy into childhood. Here, as part of the TEDDY (The Environmental Determinants of Diabetes in the Young) study, we examine stool samples of 888 children from 3 to 48 months and find considerable differences between fungi and bacteria. The metagenomic relative abundance of fungi was extremely low but increased while weaning from milk and formula. Overall fungal diversity remained constant over …

Social And Demographic Disparities In The Severity Of Multisystem Inflammatory Syndrome In Children, Fabio Savorgnan, Sebastian Acosta, Alexander Alali, Axel Moreira, Ananth Annapragada, Craig G Rusin, Saul Flores, Rohit S Loomba, Alvaro Moreira

Faculty, Staff and Students Publications

Social constructs are known risk factors for multisystem inflammatory syndrome in children. A review of 206 patients demonstrated that children who were non-Hispanic Black, over the age of 12 years or living in a disadvantaged neighborhood associated with severe multisystem inflammatory syndrome in children (intensive care unit admission, intubation and/or vasopressor use).

Cross-Reactive Immunity Against The Sars-Cov-2 Omicron Variant Is Low In Pediatric Patients With Prior Covid-19 Or Mis-C., Juanjie Tang, Tanya Novak, Julian Hecker, Gabrielle Grubbs, Fatema Tuz Zahra, Lorenza Bellusci, Sara Pourhashemi, Janet Chou, Kristin Moffitt, Natasha B. Halasa, Stephanie P. Schwartz, Tracie C. Walker, Keiko M. Tarquinio, Matt S. Zinter, Mary A. Staat, Shira J. Gertz, Natalie Z. Cvijanovich, Jennifer E. Schuster, Laura L. Loftis, Bria M. Coates, Elizabeth H. Mack, Katherine Irby, Julie C. Fitzgerald, Courtney M. Rowan, Michele Kong, Heidi R. Flori, Aline B. Maddux, Steven L. Shein, Hillary Crandall, Janet R. Hume, Charlotte V. Hobbs, Adriana H. Tremoulet, Chisato Shimizu, Jane C. Burns, Sabrina R. Chen, Hye Kyung Moon, Christoph Lange, Adrienne G. Randolph, Surender Khurana

Manuscripts, Articles, Book Chapters and Other Papers

Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection …

Evaluation Of Mrna-1273 Covid-19 Vaccine In Children 6 To 11 Years Of Age, C Buddy Creech, Evan Anderson, Vladimir Berthaud, Inci Yildirim, Andrew M. Atz, Ivan Melendez Baez, Daniel Finkelstein, Paul Pickrell, Judith Kirstein, Clifford Yut, Ronald Blair, Robert A. Clifford, Michael Dunn, James D. Campbell, David C. Montefiori, Joanne E. Tomassini, Xiaoping Zhao, Weiping Deng, Honghong Zhou, Daniela Ramirez Schrempp, Kelly Hautzinger, Bethany Girard, Karen Slobod, Roderick Mcphee, Rolando Pajon, Rituparna Das, Jacqueline M. Miller, Sabine Schnyder Ghamloush, Walter N. Dehority, Kidcove Study Group

Pediatrics Research and Scholarship

BACKGROUND: Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown.

METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 μg each) or placebo, administered 28 days apart. The primary objectives were evaluation of …

Covid-“14-17”: A Case For Florida Teens To Choose The Covid Vaccine Without Requiring Parental Consent, Kait Ramsay

Child and Family Law Journal

The novel COVID-19 pandemic has created a huge disruption to almost everyone, forcing many individuals to adapt to entirely new ways of life. In the United States, COVID safety protocols and restrictions, such as mask and vaccine mandates, have been met with huge political polarization and resistance.[1] Even as COVID variants have kept infections in a perpetual cycle of rising and falling, Florida has lifted mask mandates for businesses and schools, and its governor has been one of the largest vocal opponents to requiring vaccines for school attendance.[2] Furthermore, with the passing of Florida’s Parental Consent for Health …

Floridians' Right To Choose Or Refuse Vaccinations, Patrick E. Tolan Jr.

Child and Family Law Journal

Every state must strike the right balance between an individual's freedom to make medical choices and the state's role in protecting the public health and the welfare of its people. Florida, by and through its Constitution, has afforded heightened protections for individual self-determination over medical treatment decisions and evaluates infringement of these private medical rights with strict scrutiny. This article is about legal rights for adults to obtain or refuse vaccines and for parents to decide the timing or administration of any vaccine or group of vaccines proposed for their school-aged, preschool, newborn, or unborn children.

I argue that States …

Differentially Methylated Cpgs In Response To Growth Hormone Administration In Children With Idiopathic Short Stature., Xiaojian Shao, Catherine Le Stunff, Warren A. Cheung, Tony Kwan, Mark Lathrop, Tomi Pastinen, Pierre Bougnères

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic heterogeneity. Since epigenetic marks on the methylome can be dynamically influenced by GH, we performed a comprehensive pharmacoepigenomics analysis of DNA methylation changes associated with long-term rhGH administration in children with ISS.

RESULTS: We measured DNA methylation profiles before and after GH treatment (with a duration of ~ 18 months in average) on 47 healthy children using customized methylC-seq capture sequencing. Their changes were compared and associated …

Nutrients Associated With Stunting Among Children In Sub-Saharan Africa: A Systematic Review, Abby Mae Reynolds

Theses and Dissertations

The purpose of this study was to identify specific nutrients or nutritional biomarkers of dietary intake that are associated with stunting among children ages 2 and older in sub-Saharan Africa. This is a systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twelve studies from sub-Saharan Africa met the eligibility criteria, including 11 observational studies and one randomized control trial. Nine of the 12 studies assessed dietary intake of macronutrients. Four studies found a significant association between proteins and stunting. Four found that children with stunting had lower dietary fat intakes or lower …

Benefits Of Newborn Screening And Hematopoietic Cell Transplant In Infantile Krabbe Disease, Kristin M Page, Margie A Ream, Hemalatha G Rangarajan, Rafael Galindo, Ali Y Mian, Mai-Lan Ho, James Provenzale, Kathryn E Gustafson, Jennifer Rubin, Shalini Shenoy, Joanne Kurtzberg

Open Access Publications

Infantile Krabbe disease (IKD) can be treated with hematopoietic cell transplantation (HCT) if done during the first weeks of life before symptoms develop. To facilitate this, newborn screening (NBS) has been instituted in 8 US states. An application to add IKD to the recommended NBS panel is currently under review. In this report, the outcomes of newborns with IKD diagnosed through NBS and treated with HCT are presented. The unique challenges associated with NBS for this disease are discussed, including opportunities for earlier diagnosis and streamlining treatment referrals. This is a retrospective review of six infants with IKD detected by …

Vikela Ekhaya: A Novel, Community-Based, Tuberculosis Contact Management Program In A High Burden Setting, Alexander W Kay, Micaela Sandoval, Godwin Mtetwa, Musa Mkhabela, Banele Ndlovu, Tara Devezin, Welile Sikhondze, Debrah Vambe, Joyce Sibanda, Gloria S Dube, Robert H Stevens, Bhekumusa Lukhele, Anna M Mandalakas

Faculty, Staff and Student Publications

BACKGROUND: The prevention of tuberculosis (TB) in child contacts of TB cases and people living with human immunodeficiency virus (HIV) is a public health priority, but global access to TB preventive therapy (TPT) remains low. In 2019, we implemented Vikela Ekhaya, a novel community-based TB contact management program in Eswatini designed to reduce barriers to accessing TPT.

METHODS: Vikela Ekhaya offered differentiated TB and HIV testing for household contacts of TB cases by using mobile contact management teams to screen contacts, assess their TPT eligibility, and initiate and monitor TPT adherence in participants' homes.

RESULTS: In total, 945 contacts from …

Association Of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events And Health Care Expenditures, Anne M Butler, Derek S Brown, Michael J Durkin, John M Sahrmann, Katelin B Nickel, Caroline A O'Neil, Margaret A Olsen, David Y Hyun, Rachel M Zetts, Jason G Newland

2020-Current year OA Pubs

Importance: Nonguideline antibiotic prescribing for the treatment of pediatric infections is common, but the consequences of inappropriate antibiotics are not well described.

Objective: To evaluate the comparative safety and health care expenditures of inappropriate vs appropriate oral antibiotic prescriptions for common outpatient pediatric infections.

Design, Setting, and Participants: This cohort study included children aged 6 months to 17 years diagnosed with a bacterial infection (suppurative otitis media [OM], pharyngitis, sinusitis) or viral infection (influenza, viral upper respiratory infection [URI], bronchiolitis, bronchitis, nonsuppurative OM) as an outpatient from April 1, 2016, to September 30, 2018, in the IBM MarketScan Commercial Database. …

Epigenetic And Transcriptional Dysregulation In Cd4+ T Cells In Patients With Atopic Dermatitis, Amy A. Eapen, Sreeja Parameswaran, Carmy Forney, Lee E. Edsall, Daniel Miller, Omer Donmez, Katelyn Dunn, Xiaoming Lu, Marissa Granitto, Hope Rowden, Adam Z. Magier, Mario Pujato, Xiaoting Chen, Kenneth Kaufman, David I. Bernstein, Ashley L. Devonshire, Marc E. Rothenberg, Matthew T. Weirauch, Leah C. Kottyan

Allergy & Immunology Articles

Atopic dermatitis (AD) is one of the most common skin disorders among children. Disease etiology involves genetic and environmental factors, with 29 independent AD risk loci enriched for risk allele-dependent gene expression in the skin and CD4+ T cell compartments. We investigated the potential epigenetic mechanisms responsible for the genetic susceptibility of CD4+ T cells. To understand the differences in gene regulatory activity in peripheral blood T cells in AD, we measured chromatin accessibility (an assay based on transposase-accessible chromatin sequencing, ATAC-seq), nuclear factor kappa B subunit 1 (NFKB1) binding (chromatin immunoprecipitation with sequencing, ChIP-seq), and gene expression levels (RNA-seq) …

Novel And Extendable Genotyping System For Human Respiratory Syncytial Virus Based On Whole-Genome Sequence Analysis, Jiani Chen, Xueting Qiu, Vasanthi Avadhanula, Samuel S Shepard, Do-Kyun Kim, James Hixson, Pedro A Piedra, Justin Bahl

Faculty, Staff and Student Publications

BACKGROUND: Human respiratory syncytial virus (RSV) is one of the leading causes of respiratory infections, especially in infants and young children. Previous RSV sequencing studies have primarily focused on partial sequencing of G gene (200-300 nucleotides) for genotype characterization or diagnostics. However, the genotype assignment with G gene has not recapitulated the phylogenetic signal of other genes, and there is no consensus on RSV genotype definition.

METHODS: We conducted maximum likelihood phylogenetic analysis with 10 RSV individual genes and whole-genome sequence (WGS) that are published in GenBank. RSV genotypes were determined by using phylogenetic analysis and pair-wise node distances.

RESULTS: …

American Society For Transplantation And Cellular Therapy Series: #5-Management Of Clostridioides Difficile Infection In Hematopoietic Cell Transplant Recipients, Carolyn D Alonso, Gabriela Maron, Mini Kamboj, Paul A Carpenter, Arun Gurunathan, Kathleen M Mullane, Erik R Dubberke

2020-Current year OA Pubs

The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables, and figures. Adult and pediatric infectious disease and HCT content experts developed and then answered FAQs and finalized topics with harmonized recommendations that were made by assigning an A through E …