Digital Commons Network^™

Perceptions Of Telemedicine And Costs Incurred By A Visit To A General Infectious Diseases Clinic: A Survey, Emily C. Evers, Stephanie A. Fritz, Graham A. Colditz, Jason P. Burnham

Open Access Publications

Background: The costs of attending in-person general infectious diseases clinics and preferences for visit type (telemedicine vs in-person) are not well known. We aimed to measure the time-related, monetary, social, and societal costs associated with travel to an in-person clinic visit and to assess patients' preferences, questions, and concerns regarding telemedicine.

Methods: Patients (≥18 years, living ≥25 miles from clinic at time of clinic visit) were recruited for this survey study from the general infectious diseases (ID) clinic at Washington University from June 2019 to February 2020. We calculated time and money potentially saved by telemedicine, as well as carbon …

Perceptions Of Risk Of Sars-Cov-2 Transmission In Social And Educational Activities By Infectious Diseases And General Pediatric Healthcare Providers, A Pre-Vaccine Risk Perception Cross-Sectional Survey, Andrew B. Janowski, Philip M. Polgreen, Susan E. Beekmann, Jason G. Newland

Open Access Publications

BACKGROUND: The perception of the transmission risks of SARS-CoV-2 in social and educational settings by US healthcare providers have not been previously quantified.

METHODS: Respondents completed an online survey between September and October 2020 to estimate the risk of SARS-CoV-2 transmission on a scale of 0-10 for different social and educational activities prior to the availability of the SARS-CoV-2 vaccines. Demographic information and experiences during the pandemic were also collected. The risk assessment was emailed to three listservs of healthcare providers, including national listservs of pediatric (PID) and adult infectious diseases (AID) providers, and a listserv of general pediatric practitioners …

Isolation Of Sars-Cov-2 In Viral Cell Culture In Immunocompromised Patients With Persistently Positive Rt-Pcr Results, Abby Sung, Adam L Bailey, Henry B Stewart, David Mcdonald, Meghan A Wallace, Kate Peacock, Candace Miller, Kimberly A Reske, Caroline A O'Neil, Victoria J Fraser, Michael S Diamond, Carey-Ann D Burnham, Hilary M Babcock, Jennie H Kwon

Open Access Publications

Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients' 2

Ethical, Regulatory, And Practical Barriers To Covid-19 Research: A Stakeholder-Informed Inventory Of Concerns, Bryan A. Sisk, Kari Baldwin, Meredith Parsons, James M. Dubois

Open Access Publications

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused death and economic injury around the globe. The urgent need for COVID-19 research created new ethical, regulatory, and practical challenges. The next public health emergency could be worse than COVID-19. We must learn about these challenges from the experiences of researchers and Research Ethics Committee professionals responsible for these COVID-19 studies to prepare for the next emergency.

MATERIALS AND METHODS: We conducted an online survey to identify the ethical, oversight, and regulatory challenges of conducting COVID-19 research during the early pandemic, and proposed solutions for overcoming these barriers. Using criterion-based, convenience sampling, we invited researchers …

Association Of Multidimensional Poverty With Dementia In Adults Aged 50 Years Or Older In South Africa, Jean-Francois Trani, Jacqueline Moodley, May Thu Thu Maw, Ganesh M. Babulal

Open Access Publications

Importance: Limited research exists investigating the association between multidimensional poverty and dementia in low-and middle-income countries (LMICs).

Objective: To investigate the association between multidimensional poverty and dementia among adults aged 50 years or older living in South Africa.

Design, Setting, and Participants: This cross-sectional study was conducted in Soweto, Johannesburg, South Africa, between November 11, 2019, and February 28, 2020. Participants included 227 adults aged 50 years or older. Data analysis was concluded from August 1 to 30, 2021.

Exposures: Multidimensional poverty included 7 dimensions that are central to well-being (education, health, economic activity, living standards, social participation, fair treatment, …

Salaries, Degrees, And Babies: Trends In Fertility By Income And Education Among Japanese Men And Women Born 1943-1975-Analysis Of National Surveys, Cyrus Ghaznavi, Haruka Sakamoto, Lisa Yamasaki, Shuhei Nomura, Daisuke Yoneoka, Kenji Shibuya, Peter Ueda

Open Access Publications

BACKGROUND: While fertility rates have decreased during the second half of the 20th century in Japan, little is known regarding trends in the number of children that men and women have across birth cohorts and whether these differ by education and income.

METHODS: We used data from four rounds of the National Fertility Survey (1992, 2005, 2010 and 2015) and included men and women aged 40-49 years (16728 men and 17628 women). By 5-year birth cohorts, we assessed the distribution of number of children (0, 1, 2 and 3 or more) and total fertility (the mean number of children) at …

Dysregulation Of The Leukocyte Signaling Landscape During Acute Covid-19, Isaiah R. Turnbull, Anja Fuchs, Kenneth E. Remy, Michael P. Kelly, Elfaridah P. Frazier, Sarbani Ghosh, Shin-Wen Chang, Monty B. Mazer, Annie Hess, Jennifer M. Leonard, Mark H. Hoofnagle, Marco Colonna, Richard S. Hotchkiss

Open Access Publications

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation …

Medication For Opioid Use Disorder At Hospital Discharge Is Not Associated With Intravenous Antibiotic Completion In Post-Acute Care Facilities, Edward C Traver, Patrick R Ching, Shivakumar Narayanan

Open Access Publications

Background: People with opioid use disorder and severe infections may complete their prolonged courses of outpatient parenteral antimicrobial therapy at a post-acute care facility due to adherence and safety concerns. We hypothesized that treatment with medications for opioid use disorder, such as methadone and buprenorphine, would increase antibiotic completion in these facilities.

Methods: We performed a retrospective cohort study of people with opioid use disorder and severe infections who were discharged from the University of Maryland Medical Center to a post-acute care facility to complete intravenous antibiotic therapy. The primary outcome was completion of outpatient parenteral antimicrobial therapy. We compared …

Rotavirus Nsp1 Contributes To Intestinal Viral Replication, Pathogenesis, And Transmission, Gaopeng Hou, Qiru Zeng, Jelle Matthijnssens, Harry B Greenberg, Siyuan Ding

Open Access Publications

Rotavirus (RV)-encoded nonstructural protein 1 (NSP1), the product of gene segment 5, effectively antagonizes host interferon (IFN) signaling via multiple mechanisms. Recent studies with the newly established RV reverse genetics system indicate that NSP1 is not essential for the replication of the simian RV SA11 strain in cell culture. However, the role of NSP1 in RV infection

Myeloid-Derived Suppressor Cells Mediate T Cell Dysfunction In Nonhuman Primate Tb Granulomas, Bindu Singh, Dhiraj K Singh, Shashank R Ganatra, Ruby A Escobedo, Shabaana Khader, Larry S Schlesinger, Deepak Kaushal, Smriti Mehra

Open Access Publications

Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell population comprised of immature myeloid cells and myeloid progenitors with very potent immunosuppressive potential. MDSCs are reported to be abundant in the lungs of active tuberculosis (TB) patients. We sought to perform an in-depth study of MDSCs during latent TB infection (LTBI) and active TB (ATB) using the nonhuman primate (NHP) model of pulmonary TB. We found a higher proportion of granulocytic, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the lungs of ATB animals compared to those with LTBI or naive control animals. Active disease in the lung, but not LTBI, was …

Ccr2 Signaling Restricts Sars-Cov-2 Infection, Abigail Vanderheiden, Jeronay Thomas, Allison L Soung, Meredith E Davis-Gardner, Katharine Floyd, Fengzhi Jin, David A Cowan, Kathryn Pellegrini, Pei-Yong Shi, Arash Grakoui, Robyn S Klein, Steven E Bosinger, Jacob E Kohlmeier, Vineet D Menachery, Mehul S Suthar

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a historic pandemic of respiratory disease (coronavirus disease 2019 [COVID-19]), and current evidence suggests that severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2 signaling restricts the viral burden in the lung. We find that a recently developed mouse-adapted SARS-CoV-2 (MA-SARS-CoV-2) strain as well as the emerging B.1.351 variant trigger an inflammatory response in the lung characterized by the expression of …

Impact Of Semi-Annual Albendazole On Lymphatic Filariasis And Soil-Transmitted Helminth Infection: Parasitological Assessment After 14 Rounds Of Community Treatment, Sébastien D S Pion, Cédric B Chesnais, Gary J Weil, Frédéric Louya, Michel Boussinesq, François Missamou

Open Access Publications

Between October 2012 and October 2015, we conducted a community trial to assess the impact of semi-annual (twice yearly) community treatment with albendazole on lymphatic filariasis in Seke Pembe, a village in the Republic of the Congo. Semi-annual community treatment with albendazole has been continued in the community since October 2015. We conducted an additional parasitological assessment survey in October 2019, 6 months after the 14th round of semi-annual treatment. Between October 2012 and October 2015, Wuchereria bancrofti antigenemia and microfilaremia rates in the community had decreased from 17.3% to 4.7% and from 5.3% to 0.3%, respectively. In October 2019, …

Utility Of Facebook's Social Connectedness Index In Modeling Covid-19 Spread: Exponential Random Graph Modeling Study, Beth Prusaczyk, Kathryn Pietka, Joshua M Landman, Douglas A Luke

Open Access Publications

BACKGROUND: The COVID-19 (the disease caused by the SARS-CoV-2 virus) pandemic has underscored the need for additional data, tools, and methods that can be used to combat emerging and existing public health concerns. Since March 2020, there has been substantial interest in using social media data to both understand and intervene in the pandemic. Researchers from many disciplines have recently found a relationship between COVID-19 and a new data set from Facebook called the Social Connectedness Index (SCI).

OBJECTIVE: Building off this work, we seek to use the SCI to examine how social similarity of Missouri counties could explain similarities …

Bleeding Assessment Tools In The Diagnosis Of Vwd In Adults And Children: A Systematic Review And Meta-Analysis Of Test Accuracy, Mohamad A. Kalot, Jorge Di Paola, Et Al

Open Access Publications

No abstract provided.

Advancing Pediatric Antimicrobial Stewardship: Has Pharmacodynamic Dosing For Gram-Negative Infections Taken Effect?, Laura M. Puckett, Jason G. Newland, Jennifer E. Girotto

Open Access Publications

No abstract provided.

Using Nasal Povidone-Iodine To Prevent Bloodstream Infections And Transmission Of Staphylococcus Aureus Among Haemodialysis Patients: A Stepped-Wedge Cluster Randomised Control Trial Protocol, Ana-Monica Racila, Amy O'Shea, Rajeshwari Nair, Kimberly Dukes, Loreen Herwaldt, Linda Boyken, Daniel Diekema, Melissa Ward, Jason Cobb, Jesse Jacob, David Pegues, Susan Bleasdale, Anitha Vijayan, Anubha Mutneja, Mony Fraer, Debra O'Connell-Moore, Pam Tolomeo, Minerva Mendez, Erin Jaworski, Marin Schweizer

Open Access Publications

INTRODUCTION: Approximately 38% of haemodialysis patients carry

METHODS AND ANALYSIS: We will perform an open-label, stepped-wedge cluster randomised trial to assess the effectiveness of nasal PVI compared with standard care. Sixteen outpatient haemodialysis units will participate in the study. The 3-year trial period will be divided into a 4-month baseline period and eight additional 4-month time blocks. The primary outcome of the study will be

ETHICS AND DISSEMINATION: This study has received IRB approval from all study sites. A Data Safety and Monitoring Board will monitor this multicentre clinical trial. We will present our results at international meetings. The study …

Access To And Safety Of Covid-19 Convalescent Plasma In The United States Expanded Access Program: A National Registry Study, Jonathon W. Senefeld, Brenda J. Grossman, Et Al

Open Access Publications

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma.

METHODS AND FINDINGS: Mayo Clinic served as the central …

Minimizing The Impact Of The Triple Burden Of Covid-19, Tuberculosis And Hiv On Health Services In Sub-Saharan Africa, Jean B Nachega, Nathan Kapata, Nadia A Sam-Agudu, Eric H Decloedt, Patrick D M C Katoto, Tumaini Nagu, Peter Mwaba, Dorothy Yeboah-Manu, Pascalina Chanda-Kapata, Francine Ntoumi, Elvin H Geng, Alimuddin Zumla

Open Access Publications

In this perspective, we discuss the impact of COVID-19 on tuberculosis (TB)/HIV health services and approaches to mitigating the growing burden of these three colliding epidemics in sub-Saharan Africa (SSA). SSA countries bear significantly high proportions of TB and HIV cases reported worldwide, compared to countries in the West. Whilst COVID-19 epidemiology appears to vary across Africa, most countries in this region have reported relatively lower-case counts compared to the West. Nevertheless, the COVID-19 pandemic has added an additional burden to already overstretched health systems in SSA, which, among other things, have been focused on the longstanding dual epidemics of …

From Canines To Humans: Clinical Importance Of Staphylococcus Pseudintermedius, Karen C. Carroll, Carey-Ann D. Burnham, Lars F. Westblade

Open Access Publications

No abstract provided.

A Reevaluation Of The Tolerability And Effects Of Single-Dose Ivermectin Treatment On Onchocerca Volvulus Microfilariae In The Skin And Eyes In Eastern Ghana, Nicholas O Opoku, Michael E Gyasi, Felix Doe, Daphne Lew, Augustine R Hong, Sithembele Chithenga, Peter U Fischer, Christopher L King, Gary J Weil

Open Access Publications

Mass administration of ivermectin (IVM) has significantly reduced onchocerciasis prevalence, intensity, and morbidity in most endemic areas. Most IVM clinical trials were performed long ago in persons with high-intensity infections that are uncommon in West Africa today. This cohort treatment study recruited participants from a hypoendemic area in eastern Ghana to reevaluate the efficacy and tolerability of IVM with a special focus on the kinetics of microfilaria (Mf) clearance. Mf in the skin and anterior chambers (AC) were assessed by skin snip and slit lamp examinations at baseline and at 3 and 6 months after treatment with IVM 150 μg/kg. …

Impact Of Annual Versus Semiannual Mass Drug Administration With Ivermectin And Albendazole On Helminth Infections In Southeastern Liberia, Obiora A Eneanya, Lincoln Gankpala, Charles W Goss, Fatorma K Bolay, Gary J Weil, Peter U Fischer

Open Access Publications

We compared the impact of three rounds of annual and five rounds of semiannual mass drug administration (MDA) with albendazole plus ivermectin on helminthic infections in Liberia. Repeated annual cross-sectional community surveys were conducted between 2013 and 2019 in individuals of 5 years and older. Primary outcome was the change of infection prevalence estimates from baseline to month 36 (12 months after the last treatment). After three rounds of annual MDA, Wuchereria bancrofti circulating filarial antigen (CFA) and microfilaria (Mf) prevalence estimates decreased from 19.7% to 4.3% and from 8.6% to 0%, respectively; after semiannual MDA, CFA and Mf prevalences …

Staphylococcus Aureus Injection Drug Use-Associated Bloodstream Infections Are Propagated By Community Outbreaks Of Diverse Lineages, Laura R Marks, Juan J Calix, John A Wildenthal, Meghan A Wallace, Sanjam S Sawhney, Eric M Ransom, Michael J Durkin, Jeffrey P Henderson, Carey-Ann D Burnham, Gautam Dantas

Open Access Publications

Background: The ongoing injection drug use (IDU) crisis in the United States has been complicated by an emerging epidemic of

Methods: We performed a case-control study comparing

Results: Here we show that patients with IDU-BSI experience longer durations of bacteremia and have lower medical therapy completion rates. In phylogenetic analyses, 45/154 and 1/91 contemporaneous IDU-BSI and non-IDU BSI staphylococcal isolates, respectively, group into multiple, unique clonal clusters, revealing that pathogen community transmission distinctively spurs IDU-BSI. Lastly, multiple

Conclusions: We identify clonal expansion of multiple

A Class Ii Mhc-Targeted Vaccine Elicits Immunity Against Sars-Cov-2 And Its Variants, Novalia Pishesha, Paul W Rothlauf, Mariel J Liebeskind, Maria A Vakaki, Louis-Marie Bloyet, Marjorie Cornejo Pontelli, Ma Xenia G Ilagan, William J Buchser, Sean P J Whelan, Et Al

Open Access Publications

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (Spike

Novel Radiographic Presentation Of Primary Syphilis Of The Tonsil, Garrett Camps, Cole Pavelchek, Rami Eldaya, Matthew Parsons

Open Access Publications

A 61-year-old HIV+ male presented to an infectious disease clinic with a complaint of sore throat. A painless ulcerated mass was discovered on the right tonsil resulting in further evaluation with a CT scan of the neck. Imaging confirmed the presence of a mass centered on the palatine tonsil and associated lymphadenopathy. A presumptive diagnosis of HPV-related squamous cell carcinoma was made due to patient risk factors. However, multiple biopsies found no evidence of carcinoma, but instead revealed the presence of spirochetes that stained positive for

Diagnostics To Support Elimination Of Lymphatic Filariasis-Development Of Two Target Product Profiles, Kimberly Y. Won, Gary J. Weil, Et Al

Open Access Publications

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs …

Mast Cell Activation Symptoms Are Prevalent In Long-Covid, Leonard B Weinstock, Jill B Brook, Arthur S Walters, Ashleigh Goris, Lawrence B Afrin, Gerhard J Molderings

Open Access Publications

OBJECTIVES: Hyper-inflammation caused by COVID-19 may be mediated by mast cell activation (MCA) which has also been hypothesized to cause Long-COVID (LC) symptoms. We determined prevalence/severity of MCA symptoms in LC.

METHODS: Adults in LC-focused Facebook support groups were recruited for online assessment of symptoms before and after COVID-19. Questions included presence and severity of known MCA and LC symptoms and validated assessments of fatigue and quality of life. General population controls and mast cell activation syndrome (MCAS) patients were recruited for comparison if they were ≥18 years of age and never had overt COVID-19 symptoms.

RESULTS: There were 136 …

High Seropositivity Rate Of Neutralizing Antibodies To Astrovirus Va1 In Human Populations, Andrew B Janowski, Macee C Owen, Holly Dudley, Tomás López, Rafaela Espinosa, Memory Elvin-Lewis, Alejandro Colichon, Carlos F Arias, Peter D Burbelo, David Wang

Open Access Publications

Astroviruses are common pathogens of the human gastrointestinal tract, but they have been recently identified from cases of fatal meningoencephalitis. Astrovirus VA1 is the most frequently detected astrovirus genotype from cases of human encephalitis, but the prevalence of neutralizing antibodies to VA1 in human sera is unknown. We developed a focus reduction neutralization assay (FRNT) for VA1 and measured the seroprevalence of neutralizing antibodies from two cohorts of adult and pediatric serum samples: (i) an age-stratified cohort from St. Louis, MO, collected from 2007 to 2008 and (ii) a cohort from the Peruvian Amazonian River Basin collected in the late …

A Novel Class Of Tmprss2 Inhibitors Potently Block Sars-Cov-2 And Mers-Cov Viral Entry And Protect Human Epithelial Lung Cells, Matthew Mahoney, Vishnu C Damalanka, Michael A Tartell, Anne E Mayer Bridwell, Jorine Voss, Partha Karmakar, Paul W Rothlauf, Cassandra E Thompson, Christina L Stallings, Sean P J Whelan, James W Janetka, Et Al

Open Access Publications

The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we have discovered covalent small-molecule ketobenzothiazole (kbt) TMPRSS2 inhibitors which are structurally distinct from and have significantly improved activity over the existing known inhibitors Camostat and Nafamostat. Lead compound MM3122 (4) has an IC

Discovering Disease-Disease Associations Using Electronic Health Records In The Guideline Advantage (Tga) Dataset, Aixia Guo, Yosef M Khan, James R Langabeer 2nd, Randi E Foraker

Open Access Publications

Certain diseases have strong comorbidity and co-occurrence with others. Understanding disease-disease associations can potentially increase awareness among healthcare providers of co-occurring conditions and facilitate earlier diagnosis, prevention and treatment of patients. In this study, we utilized the valuable and large The Guideline Advantage (TGA) longitudinal electronic health record dataset from 70 outpatient clinics across the United States to investigate potential disease-disease associations. Specifically, the most prevalent 50 disease diagnoses were manually identified from 165,732 unique patients. To investigate the co-occurrence or dependency associations among the 50 diseases, the categorical disease terms were first mapped into numerical vectors based on disease …

Elevated Mics Of Susceptible Antipseudomonal Cephalosporins In Non-Carbapenemase-Producing, Carbapenem-Resistant Pseudomonas Aeruginosa: Implications For Dose Optimization, Christian M Gill, Carey-Ann D Burnham, Et Al

Open Access Publications

The present study evaluated the