Digital Commons Network^™

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, And Death: United States, 2022-2023, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain.

METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by …

A Physiological Approach To Renal Clearance: From Premature Neonates To Adults, Nick Holford, Conor J. O'Hanlon, Karel Allegaert, Brian Anderson, Amilcar Falcão, Nicolas Simon, Yoke Lin Lo, Alison H. Thomson, Catherine M.T. Sherwin, Evelyne Jacqz-Aigrain, Carolina Llanos-Paez, Stefanie Hennig, Linas Mockus, Carl Kirkpatrick

Pediatrics Faculty Publications

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results: This study demonstrates that GFR is a predictor of two distinct …

A Multi-Ancestry Genetic Study Of Pain Intensity In 598,339 Veterans., Sylvanus Toikumo, Rachel Vickers-Smith, Zeal Jinwala, Heng Xu, Divya Saini, Emily E Hartwell, Mirko Pavicic, Kyle A Sullivan, Ke Xu, Daniel A Jacobson, Joel Gelernter, Christopher T Rentsch, Million Veteran Program, Eli Stahl, Martin Cheatle, Hang Zhou, Stephen G Waxman, Amy C Justice, Rachel L Kember, Henry R Kranzler

Epidemiology and Environmental Health Faculty Publications

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, …

Monophosphoryl Lipid A-Based Adjuvant To Promote The Immunogenicity Of Multivalent Meningococcal Polysaccharide Conjugate Vaccines, Kishore Alugupalli

Department of Microbiology and Immunology Faculty Papers

Activation of the adaptive immune system requires the engagement of costimulatory pathways in addition to B and T cell Ag receptor signaling, and adjuvants play a central role in this process. Many Gram-negative bacterial polysaccharide vaccines, including the tetravalent meningococcal conjugate vaccines (MCV4) and typhoid Vi polysaccharide vaccines, do not incorporate adjuvants. The immunogenicity of typhoid vaccines is due to the presence of associated TLR4 ligands in these vaccines. Because the immunogenicity of MCV4 is poor and requires boosters, I hypothesized that TLR4 ligands are absent in MCV4 and that incorporation of a TLR4 ligand-based adjuvant would improve their immunogenicity. …

Potential Impact Of Annual Vaccination With Reformulated Covid-19 Vaccines: Lessons From The Us Covid-19 Scenario Modeling Hub, Sung-Mok Jung, Sara L Loo, Emily Howerton, Lucie Contamin, Claire P Smith, Erica C Carcelén, Katie Yan, Samantha J Bents, John Levander, Jessi Espino, Joseph C Lemaitre, Koji Sato, Clifton D Mckee, Alison L Hill, Matteo Chinazzi, Jessica T Davis, Kunpeng Mu, Alessandro Vespignani, Erik T Rosenstrom, Sebastian A Rodriguez-Cartes, Julie S Ivy, Maria E Mayorga, Julie L Swann, Guido España, Sean Cavany, Sean M Moore, T Alex Perkins, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Ajitesh Srivastava, Majd Al Aawar, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Spencer J Fox, Lauren Ancel Meyers, Przemyslaw Porebski, Srini Venkatramanan, Aniruddha Adiga, Benjamin Hurt, Brian Klahn, Joseph Outten, Jiangzhuo Chen, Henning Mortveit, Amanda Wilson, Stefan Hoops, Parantapa Bhattacharya, Dustin Machi, Anil Vullikanti, Bryan Lewis, Madhav Marathe, Harry Hochheiser, Michael C Runge, Katriona Shea, Shaun Truelove, Cécile Viboud, Justin Lessler

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval).

METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub …

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik

Faculty, Staff and Student Publications

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19: A Secondary Analysis Of The Activ-1 Im Randomized Clinical Trial, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik, Activ-1 Im Study Group

2020-Current year OA Pubs

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …

Severity Of Respiratory Syncytial Virus Vs Covid-19 And Influenza Among Hospitalized Us Adults, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making.

OBJECTIVE: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively …

Association Of Nightly Fasting, Meal Frequency, And Skipping Meals With Metabolic Syndrome Among Kuwaiti Adults, Fatema Alkhulaifi, Suad Al-Hooti, Sameer Al-Zenki, Husam Alomirah, Qian Xiao, Wenyaw Chan, Fuqing Wu, Charles Darkoh

Faculty, Staff and Student Publications

Mounting evidence suggests that meal timing and frequency are associated with cardiometabolic health by influencing circadian rhythms. However, the evidence is inconsistent and limited, especially in non-Western cultures. This cross-sectional study aims to investigate the association between temporal habits of dietary intake, such as nightly fasting duration and meal frequency, and metabolic syndrome among Kuwaiti adults. A 24-hour recall was used to assess temporal habits of dietary intake. Meal frequency was defined as the number of daily eating episodes. The study included a total of 757 adults aged 20 years and older. The participants' mean age was 37.8 ± 12.3 …

Efficacy And Feasibility Of Short-Stretch Compression Therapy For Filarial Lymphedema In Sri Lanka, Jaimee M Hall, Nirmitha Lalindi De Silva, Janaka Ruben, Sandani S Thilakarathne, Thishan Channa Yahathugoda, Philip J Budge

2020-Current year OA Pubs

The WHO-recommended essential package of care (EPC) for filarial limb lymphedema consists of daily limb washing, entry lesion management, limb protection, exercises, and elevation. Decongestive therapy (DT) with compression bandaging by trained lymphedema therapists adds additional benefit but is unavailable for most in low- and middle-income countries (LMICs). To determine whether DT using self-adjustable, short-stretch compression garments (SSCG), prefitted using portable, three-dimensional infrared imaging (3DII), would be effective and feasible in LMIC settings, we conducted a pilot 6-week, interventional, single-group, open-label pilot study in Galle, Sri Lanka. Ten participants with Dreyer stage 3 lymphedema used SSCG for 2 weeks after …

What Do Cervical Cancer Patients Know, How Do They Learn, And Who Do They Tell? A Pilot Study, Sharon Larson, Brian Mcanany, Ilene Ladd, Radhika Gogoi

College of Population Health Faculty Papers

BACKGROUND: This study explored what patients identified with cervical cancer know about the link between human papillomavirus (HPV) and cervical cancer and where they learned this information. Patients share a great deal of information with family, friends and colleagues and we were interested in the accuracy and sources of information they are sharing.

METHODS: Patients identified through the EHR of a health system who had a history of cervical cancer were invited to participate in a brief survey of their experience. The sample represents an opportunity sample of patients who responded.

RESULTS: Generally, these patients, drawn from the Geisinger Health …

Outpatient Covid-19 Convalescent Plasma Recipient Antibody Thresholds Correlated To Reduced Hospitalizations Within A Randomized Trial, Han-Sol Park, Anna Yin, Caelan Barranta, John S Lee, Christopher A Caputo, Jaiprasath Sachithanandham, Maggie Li, Steve Yoon, Ioannis Sitaras, Anne Jedlicka, Yolanda Eby, Malathi Ram, Reinaldo E Fernandez, Owen R Baker, Aarthi G Shenoy, Giselle S Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L Heath, Adam C Levine, Barry R Meisenberg, Emily S Spivak, Shweta Anjan, Moises A Huaman, Janis E Blair, Judith S Currier, James H Paxton, Jonathan M Gerber, Joann R Petrini, Patrick B Broderick, William Rausch, Marie Elena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L Hammitt, Catherine G Sutcliffe, Donald N Forthal, Martin S Zand, Edward R Cachay, Jay S Raval, Seble G Kassaye, Christi E Marshall, Anusha Yarava, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Atika Singh, Daniel E Ford, Douglas A Jabs, Lawrence J Appel, David M Shade, Bryan Lau, Stephan Ehrhardt, Sheriza N Baksh, Janna R Shapiro, Jiangda Ou, Yu Bin Na, Maria D Knoll, Elysse Ornelas-Gatdula, Netzahualcoyotl Arroyo-Curras, Thomas J Gniadek, Patrizio Caturegli, Jinke Wu, Nelson Ndahiro, Michael J Betenbaugh, Alyssa Ziman, Daniel F Hanley, Arturo Casadevall, Shmuel Shoham, Evan M Bloch, Kelly A Gebo, Aaron Ar Tobian, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, David J Sullivan

Faculty, Staff and Students Publications

BACKGROUND

COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.

METHODS

This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors …

Neuroinvasive West Nile Virus Infection In Immunosuppressed And Immunocompetent Adults., Amir A Mbonde, David Gritsch, Ehab Y Harahsheh, Sabirah N Kasule, Shemonti Hasan, Angela M Parsons, Nan Zhang, Richard Butterfield, Harn Shiue, Kathryn A Norville, Jenna L Reynolds, Holenarasipur R Vikram, Brian Chong, Marie F Grill

Neuroscience Articles

IMPORTANCE: West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored.

OBJECTIVE: To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS.

DESIGN, SETTING, …

Efficacy And Safety Of Rezafungin And Caspofungin In Candidaemia And Invasive Candidiasis: Pooled Data From Two Prospective Randomised Controlled Trials, George R Thompson 3rd, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials.

METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) …

Interim Estimates Of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States, Aaron M Frutos, Ashley M Price, Elizabeth Harker, Emily L Reeves, Haris M Ahmad, Vel Murugan, Emily T Martin, Stacey House, Elie A Saade, Richard K Zimmerman, Manjusha Gaglani, Karen J Wernli, Emmanuel B Walter, Marian G Michaels, Mary A Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Julie A Boom, Eileen J Klein, Natasha B Halasa, Adit A Ginde, Kevin W Gibbs, Yuwei Zhu, Wesley H Self, Sara Y Tartof, Nicola P Klein, Kristin Dascomb, Malini B Desilva, Zachary A Weber, Duck-Hye Yang, Sarah W Ball, Diya Surie, Jennifer Decuir, Fatimah S Dawood, Heidi L Moline, Ariana P Toepfer, Benjamin R Clopper, Ruth Link-Gelles, Amanda B Payne, Jessie R Chung, Brendan Flannery, Nathaniel M Lewis, Samantha M Olson, Katherine Adams, Mark W Tenforde, Shikha Garg, Lisa A Grohskopf, Carrie Reed, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Faculty, Staff and Students Publications

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE …

Current And Emerging Antiviral Agents In The Prevention And Treatment Of Cytomegalovirus In Pediatric Transplant Recipients, Kristen G Valencia Deray, Lara A Danziger-Isakov, Kevin J Downes

Faculty, Staff and Students Publications

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients …

A Stool Based Qpcr For The Diagnosis Of Tb In Children And People Living With Hiv In Uganda, Eswatini And Mozambique (Stool4tb): A Protocol For A Multicenter Diagnostic Evaluation, Lucia Carratala-Castro, Willy Ssengooba, Alex Kay, Sozinho Acácio, Joanna Ehrlich, Andrew R Dinardo, Nosisa Shiba, Joachim K Nsubuga, Shilzia Munguambe, Belén Saavedra-Cervera, Patricia Manjate, Durbbin Mulengwa, Busizwe Sibandze, Mangaliso Ziyane, George Kasule, Edson Mambuque, Moorine Penninah Sekadde, Eric Wobudeya, Moses L Joloba, Jan Heyckendorf, Christoph Lange, Sabine Hermans, Anna Mandalakas, Alberto L García-Basteiro, Elisa Lopez-Varela, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed …

How Does Covid-19 Vaccination Affect Long-Covid Symptoms?, Ali Akbar Asadi-Pooya, Meshkat Nemati, Mina Shahisavandi, Hamid Nemati, Afrooz Karimi, Anahita Jafari, Sara Nasiri, Seyyed Saeed Mohammadi, Zahra Rahimian, Hossein Bayat, Ali Akbari, Amir Emami, Owrang Eilami

Department of Neurology Faculty Papers

OBJECTIVE: The current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition.

METHODS: This was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate.

RESULTS: In total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 …

Long-Term Non-Progression And Risk Factors For Disease Progression Among Children Living With Hiv In Botswana And Uganda: A Retrospective Cohort Study, Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A Hanchard, Jacqueline Kyosiimire-Lugemwa, Mogomotsi Matshaba, Dithan Kiragga

Faculty, Staff and Students Publications

OBJECTIVES: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda.

METHODS: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era.

RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve …

Risk Factors For Childhood Brain Tumours: A Systematic Review And Meta-Analysis Of Observational Studies From 1976 To 2022, Felix M Onyije, Roya Dolatkhah, Ann Olsson, Liacine Bouaoun, Isabelle Deltour, Friederike Erdmann, Audrey Bonaventure, Michael E Scheurer, Jacqueline Clavel, Joachim Schüz

Center for Medical Ethics and Health Policy Staff Publications

BACKGROUND: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention.

METHODS: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, …

Fecal Pharmacokinetics And Gut Microbiome Effects Of Oral Omadacycline Versus Vancomycin In Healthy Volunteers, Jinhee Jo, Chenlin Hu, Khurshida Begum, Weiqun Wang, Thanh M Le, Samantha Agyapong, Blake M Hanson, Hossaena Ayele, Chris Lancaster, M Jahangir Alam, Anne J Gonzales-Luna, Kevin W Garey

Faculty, Staff and Student Publications

BACKGROUND: Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults.

METHODS: This was a phase 1, nonblinded, randomized clinical trial conducted in healthy volunteers aged 18-40 years. Subjects received a 10-day course of omadacycline or vancomycin. Stool samples were collected at baseline, daily during therapy, and at follow-up visits. Omadacycline and vancomycin stool concentrations …

Pharmacokinetic-Pharmacodynamic Evidence From A Phase 3 Trial To Support Flat-Dosing Of Rifampicin For Tuberculosis, Huy X. Ngo, Ava Y. Xu, Gustavo E. Velásquez, Nan Zhang, Vincent K. Chang, Ekaterina V. Kurbatova, William C. Whitworth, Erin Sizemore, Kia Bryant, Wendy Carr, Marc Weiner, Kelly E. Dooley, Melissa Engle, Susan E. Dorman, Payam Nahid, Susan Swindells, Richard E. Chaisson, Pheona Nsubuga, Madeleine Lourens, Rodney Dawson, Radojka M. Savic

Journal Articles: Infectious Diseases

BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes.

METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months; TB-related unfavorable outcomes at 9, 12, and 18 months using …

Hpv Vaccination In Africa In The Covid-19 Era: A Cross-Sectional Survey Of Healthcare Providers' Knowledge, Training, And Recommendation Practices, Joel Fokom Domgue, Issimouha Dille, Sharon Kapambwe, Robert Yu, Freddy Gnangnon, Lameck Chinula, Gad Murenzi, Nomonde Mbatani, Mala Pande, Fatoumata Sidibe, Joseph Kamgno, Bangaly Traore, Hicham El Fazazi, Mamadou Diop, Pierre-Marie Tebeu, Mohenou Isidore Diomande, Fabrice Lecuru, Isaac Adewole, Marie Plante, Partha Basu, Jean-Marie Dangou, Sanjay Shete

Faculty, Staff and Student Publications

INTRODUCTION: Although the burden of cervical cancer in Africa is highest, HPV vaccination coverage remains alarmingly low in this region. Providers' knowledge and recommendation are key drivers of HPV vaccination uptake. Yet, evidence about providers' knowledge and recommendation practices about the HPV vaccine against a backdrop of emerging vaccine hesitancy fueled by the COVID-19 pandemic is lacking in Africa.

METHODS: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior training, the availability of the HPV vaccine in their practice, whether they recommended the HPV vaccine, …

Risk-Stratified Treatment For Drug-Susceptible Pulmonary Tuberculosis., Vincent K. Chang, Marjorie Z. Imperial, Patrick P. J. Phillips, Gustavo E. Velásquez, Payam Nahid, Andrew Vernon, Ekaterina V. Kurbatova, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, John L. Johnson, Marc Weiner, Amina Jindani, Thomas Harrison, Erin E. Sizemore, William Whitworth, Wendy Carr, Kia E. Bryant, Deron Burton, Kelly E. Dooley, Melissa Engle, Pheona Nsubuga, Andreas H. Diacon, Nguyen Viet Nhung, Rodney Dawson, Radojka M. Savic, Aids Clinical Trial Group, Tuberculosis Trials Consortium

Journal Articles: Infectious Diseases

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, …

Pyrazinamide Safety, Efficacy, And Dosing For Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized Controlled Clinical Trial, Ava Y. Xu, Gustavo E. Velásquez, Nan Zhang, Vincent K. Chang, Patrick P. J. Phillips, Payam Nahid, Susan E. Dorman, Ekaterina V. Kurbatova, William C. Whitworth, Erin Sizemore, Kia Bryant, Wendy Carr, Nicole E. Brown, Melissa L. Engle, Nguyen Viet Nhung, Pheona Nsubuga, Andreas Diacon, Kelly E. Dooley, Richard E. Chaisson, Susan Swindells, Radojka M. Savic

Journal Articles: Infectious Diseases

Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/AIDS Clinical Trials Group A5349 represents the largest phase 3 randomized controlled therapeutic trial to date for such an investigation. Objectives: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure and efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. Methods: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety …

Assessing The Value And Knowledge Gains From An Online Tick Identification And Tick-Borne Disease Management Course For The Southeastern United States, Catherine A. Lippi, Holly D. Gaff, Alexis L. White, Sadie J. Ryan

Biological Sciences Faculty Publications

Background

Tick-borne diseases are a growing public health threat in the United States. Despite the prevalence and rising burden of tick-borne diseases, there are major gaps in baseline knowledge and surveillance efforts for tick vectors, even among vector control districts and public health agencies. To address this issue, an online tick training course (OTTC) was developed through the Southeastern Center of Excellence in Vector-Borne Diseases (SECOEVBD) to provide a comprehensive knowledge base on ticks, tick-borne diseases, and their management.

Methods

The OTTC consisted of training modules covering topics including tick biology, tick identification, tick-borne diseases, and public health, personal tick …

Exploring The Relationship Between Vaccine Hesitancy And Mothers’ Perspectives On Covid-19 Vaccines For Children Ages 5–11 Years During The Omicron Predominant Period 2021–2022: A Qualitative Study, Tiffany A Suragh, David Adzrago, Marlyn A Allicock, Paul G Yeh, Paula Cuccaro

Faculty, Staff and Student Publications

Background: The United States Food and Drug Administration authorized COVID-19 vaccines for children ages 5-11 years in October 2021 during the Omicron predominant period. Parental vaccine hesitancy was prevalent during this time, resulting in low childhood COVID-19 vaccine uptake. Most studies exploring factors influencing parental vaccine hesitancy have focused on racial and ethnic minorities and lower socioeconomic populations; however, there is little knowledge of the drive drivers of vaccine hesitancy among White parents with higher education and socioeconomic statuses.

Methods: We conducted semi-structured interviews with a sample of 15 White mothers of children ages 5-11 years in Atlanta, GA, between …

Social Determinants Of Health Predict Readmission Following Covid-19 Hospitalization: A Health Information Exchange-Based Retrospective Cohort Study, Micaela N Sandoval, Jennifer L Mikhail, Melyssa K Fink, Guillermo A Tortolero, Tru Cao, Ryan Ramphul, Junaid Husain, Eric Boerwinkle

Faculty, Staff and Student Publications

INTRODUCTION: Since February 2020, over 104 million people in the United States have been diagnosed with SARS-CoV-2 infection, or COVID-19, with over 8.5 million reported in the state of Texas. This study analyzed social determinants of health as predictors for readmission among COVID-19 patients in Southeast Texas, United States.

METHODS: A retrospective cohort study was conducted investigating demographic and clinical risk factors for 30, 60, and 90-day readmission outcomes among adult patients with a COVID-19-associated inpatient hospitalization encounter within a regional health information exchange between February 1, 2020, to December 1, 2022.

RESULTS AND DISCUSSION: In this cohort of 91,007 …

Absolute Concentration Estimation Of Covid-19 Convalescent And Post-Vaccination Igg Antibodies, Melvin E Klegerman, Tao Peng, Ira Seferovich, Mohammad H Rahbar, Manouchehr Hessabi, Amirali Tahanan, Audrey Wanger, Carolyn Z Grimes, Luis Z Ostrosky-Zeichner, Kent Koster, Jeffrey D Cirillo, Dinuka Abeydeera, Steve De Lira, David D Mcpherson

Faculty, Staff and Student Publications

Soon after commencement of the SARS-CoV-2 disease outbreak of 2019 (COVID-19), it became evident that the receptor-binding domain of the viral spike protein is the target of neutralizing antibodies that comprise a critical element of protective immunity to the virus. This study addresses the relative lack of information regarding actual antibody concentrations and binding affinities in convalescent plasma (CP) samples from COVID-19 patients and extends these analyses to post-vaccination (PV) samples to estimate protective IgG antibody (Ab) levels. A direct enzyme-linked immunosorbent assay (ELISA) was used to measure IgG anti-spike protein (SP) antibodies (Abs) relative to human chimeric spike S1 …

A Search For Bacteria Identified From Cerebrospinal Fluid Shunt Infections In Previous Surgical Events, Paul Hodor, Christopher E. Pope, Kathryn B. Whitlock, Patrick J. Mcdonald, Jason Hauptman, Lucas R. Hoffman, David D. Limbrick Jr., Tamara D. Simon, Cerebrospinal Fluid Microbiota In Shunts (Climb) Study Group

2020-Current year OA Pubs

Shunt infections are a common complication when treating hydrocephalus by cerebrospinal fluid (CSF) shunt placement. The source of infecting pathogens is not well understood. One hypothesis, which we explored here, is that microorganisms persist chronically in the host long before a symptomatic infection occurs and may be detectable in surgical events preceding infection. A cohort of 13 patients was selected, for which CSF samples were available from an infection episode and from a previous surgery event, which was either an initial shunt placement or a revision. Microbiota were analyzed both directly from CSF and from isolates cultured from CSF on …