Infectious Disease Commons^™

Standardization Of An Antiviral Pipeline For Human Norovirus In Human Intestinal Enteroids Demonstrates Nitazoxanide Has No To Weak Antiviral Activity, Miranda A Lewis, Nicolás W Cortés-Penfield, Khalil Ettayebi, Ketki Patil, Gurpreet Kaur, Frederick H Neill, Robert L Atmar, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis. In immunocompetent hosts, symptoms usually resolve within 3 days; however, in immunocompromised persons, HuNoV infection can become persistent, debilitating, and sometimes life-threatening. There are no licensed therapeutics for HuNoV due to a near half-century delay in its cultivation. Treatment for chronic HuNoV infection in immunosuppressed patients anecdotally includes nitazoxanide, a broad-spectrum antimicrobial licensed for treatment of parasite-induced gastroenteritis. Despite its off-label use for chronic HuNoV infection, nitazoxanide has not been clearly demonstrated to be an effective treatment. In this study, we standardized a pipeline for antiviral testing using multiple human …

Risk Factors For Health Impairments In Children After Hospitalization For Acute Covid-19 Or Mis-C., Aline B. Maddux, Cameron C. Young, Suden Kucukak, Laura D. Zambrano, Margaret M. Newhams, Caitlin K. Rollins, Natasha B. Halasa, Shira J. Gertz, Elizabeth H. Mack, Stephanie Schwartz, Michele Kong, Laura L. Loftis, Katherine Irby, Courtney M. Rowan, Keiko M. Tarquinio, Matt S. Zinter, Hillary Crandall, Natalie Z. Cvijanovich, Jennifer E. Schuster, Julie C. Fitzgerald, Mary A. Staat, Charlotte V. Hobbs, Ryan A. Nofziger, Steven Shein, Heidi Flori, Melissa L. Cullimore, Brandon M. Chatani, Emily R. Levy, Katri V. Typpo, Janet R. Hume, Angela P. Campbell, Adrienne G. Randolph, Overcoming Covid-19 Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic.

METHODS: Across 25 U.S. Overcoming COVID-19Network hospitals, we conducted a prospective cohort study of patients

RESULTS: Of 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (n = 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms [aRR 1.83 …

A Single Nanobody Neutralizes Multiple Epochally Evolving Human Noroviruses By Modulating Capsid Plasticity, Wilhelm Salmen, Liya Hu, Marina Bok, Natthawan Chaimongkol, Khalil Ettayebi, Stanislav V Sosnovtsev, Kaundal Soni, B Vijayalakshmi Ayyar, Sreejesh Shanker, Frederick H Neill, Banumathi Sankaran, Robert L Atmar, Mary K Estes, Kim Y Green, Viviana Parreño, B V Venkataram Prasad

Faculty, Staff and Students Publications

Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed …

A Single-Dose Intramuscular Immunization Of Pigs With Lipid Nanoparticle Dna Vaccines Based On The Hemagglutinin Antigen Confers Complete Protection Against Challenge Infection With The Homologous Influenza Virus Strain, The N. Nguyen, Sushmita Kumari, Sarah Vitosh-Sillman, Jayeshbhai Chaudhari, Danh C. Lai, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The Influenza A virus of swine (IAV-S) is highly prevalent and causes significant economic losses to swine producers. Due to the highly variable and rapidly evolving nature of the virus, it is critical to develop a safe and versatile vaccine platform that allows for frequent updates of the vaccine immunogens to cope with the emergence of new viral strains. The main objective of this study was to assess the feasibility of using lipid nanoparticles (LNPs) as nanocarriers for delivering DNA plasmid encoding the viral hemagglutinin (HA) gene in pigs. The intramuscular administration of a single dose of the LNP-DNA vaccines …

Tuberculosis Presentation And Outcomes In Older Hispanic Adults From Tamaulipas, Mexico, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Javier E Rodríguez-Herrera, Moncerrato García-Viveros, Blanca I Restrepo

Faculty, Staff and Student Publications

Older people are at high risk of developing and dying from pulmonary infections like tuberculosis (TB), but there are few studies among them, particularly in Hispanics. To address these gaps, we sought to identify host factors associated with TB and adverse treatment outcomes in older Hispanics by conducting a cross-sectional study of TB surveillance data from Tamaulipas, Mexico (2006-2013; n = 8381). Multivariable logistic regressions were assessed for older adults (OA ≥65 years) when compared to young (YA, 18-39 years) and middle-aged adults (40-64 years). We found that the OA had features associated with a less complicated TB (e.g., lower …

Acute Aseptic Meningoencephalitis Due To Covid-19 In An Otherwise Healthy Patient: A Case Report, Shyama Appareddy, Norma Moncayo, Ronkino T. Mccoy, Jared Sperling, George Huddleston, Raza L. Kahn

Research Colloquium

Several studies have shown the extrapulmonary manifestations of COVID-19 disease caused by the SARS-CoV2 virus. Although extrapulmonary manifestation to the heart, kidney, blood, and skin are common, neurological and cerebrovascular manifestations are rare with most of these cases being described in patients who also have the pulmonary manifestation of the disease. Here we present the case of an 18 year-old male with no prior history of respiratory symptoms who presented to the emergency department with altered mental status. Neurology was consulted and the patient was started empirical on ceftriaxone, vancomycin, dexamethasone, and acyclovir for meningoencephalitis. Urine drug screen, head CT, …

Antibiotic Stewardship In Skin And Soft Tissue Infections, Shah Z. Ali, Stephen Gore, Jose E. Campo Maldonado

Research Colloquium

Introduction: Skin and soft tissue infections (SSTIs) are characterized by microbial invasion of the skin layers and are common in various healthcare settings. A study conducted between 2005-2010 in the United States, found a combined total of 2.3 million cases of SSTIs in ambulatory and inpatient settings. This was higher than the rates of pneumonia and urinary tract infections during the same time period. Another study found that between 2000 and 2012, there was a 40% increase (2.4 million to 3.3 million) in cases of SSTIs. Our aim is to study the primary uses of vancomycin and piperacillin/tazobactam and their …

Rare Case Of Prosthetic Joint Infection Caused By Salmonella Enterica - A Case Report, Carlos Ramos, Shyama Appareddy, Peter J. Gonzalez

Research Colloquium

Introduction: Collectively, over 1 million total knee arthroplasties (TKA) and total hip arthroplasties (THA) are performed in the United States each year. In 2010 it was estimated that 1.58% of the United States general population has received a TKA. Prosthetic joint infections (PJI) are the most common indication for a TKA revision1 . In total, S. aureus is responsible for about 50% of all prosthetic joint infections, and about 15% are caused by gram negative pathogens2 .

Objective: This is a case report which describes the presentation and clinical course of a 59-yearold female with Salmonella enterica septic arthritis of …

Multisystem Inflammatory Syndrome In Children (Mis-C): Is There A Relationship To Typhus?, Sravani Mannuru, Juliana Hager, Jacob Smith

Research Colloquium

The United Kingdom first reported in April 2020 a group of eight previously healthy children with a link to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that presented with systemic inflammation and multi-organ involvement, now named multisystem inflammatory syndrome in children (MIS-C). The Centers of Disease Control and Prevention (CDC) have reported over 1000 cases since the primary discovery as of October 2020 with 20 total deaths. [1] The clinical features of MIS-C have been previously compared to inflammatory syndromes including Kawasaki disease (KD) and toxic shock syndrome (TSS). We describe the clinical presentation and management for 3 pediatric cases with …

Cmv? An Uncommon Etiology For Significant Disease In The Immunocompetent Individual, Ashley Sareen, Cade Call, Sonya Saenz

Research Colloquium

A 51-year-old Hispanic male with Type 2 diabetes mellitus and dyslipidemia was admitted from the ED for evaluation of recurrent fevers, multiple joint pains, and tachycardia. Physical exam findings included cachectic appearance and right inguinal lymphadenopathy. Initial laboratory testing was significant for a WBC of 23,300 (80.2% neutrophils, 13.3% lymphocytes), Hb of 11.1, HCT of 33.1, and ESR of 120. Chest x-ray reported no acute findings and x-ray imaging of affected joints were unremarkable. Blood and urine cultures would eventually return negative. Despite acetaminophen and broad-spectrum antibiotic use, the patient continued with fevers and tachycardia, prompting further infectious and rheumatological …

Pneumocystis Jirovecii Pneumonia In A Newly Diagnosed Aids Geriatric Patient, Ashley Sareen, Nathan Tanner, James Fahey

Research Colloquium

Background: Approximately 40% of new HIV infections originate from people who are unaware of their diagnosis. Median time from infection to diagnosis was 3 years in 2015. Cases of newly diagnosed HIV in the geriatric population are rare.

Case Presentation: 71 year old Hispanic man with history of diabetes and anemia presenting to the hospital with generalized weakness, presyncopal episodes, shortness of breath, loose stools, and falls for past two weeks. He is a poor historian so wife contacted to provide detailed history. Patient with 100 pound weight loss in 6 months. Intravenous drug use 30 years ago, and blood …

Catheter-Associated Urinary Tract Infections: Patient Characteristics, Treatment, And Clinical Outcomes In One South Texas Acute Care Hospital, Kimberly A. Ambrosini, Jose Campo Maldonado

Research Colloquium

Background: Catheter-associated urinary tract infections (CA-UTIs) account for 40 percent of nosocomial infections worldwide. Their elimination is at the forefront of quality improvement in one South Texas acute care hospital.

Methods: Over a period of 6 months, five CA-UTIs occurred in one South Texas acute care hospital. These cases were identified via regular surveillance by Infection Prevention staff and the Laboratory Department of the hospital. This research reviews patient age, sex, length of stay, bacteria contracted, appropriate antibiotic use, patient characteristics, and overall outcomes.

Results: Between the months of July and December 2021, 5 CAUTIs were contracted. Patients ranged in …

A Simple Case Of Viral Myopericarditis Or A Complication Of Monoclonal Antibody Infusion?, Jose A. Rivera, Michael Menowsky

Research Colloquium

Background: Myocarditis has been a rare, but well-documented side effect of the mRNA-based vaccines against SARS-CoV-2 as well as a complication of viral infections including SARS-CoV-2. However, myopericarditis as a complication of monoclonal antibody infusion or as complication of allergic reaction to antibody infusions might be and underreported.

Case presentation: In this case, we report a 30-year-old man with a previous diagnosis of COVID infection 1 week prior to presentation, unvaccinated for SARS-CoV-2 who was referred from a monoclonal infusion center where he received casirivimab and imdevimab and 15 minutes after infusion began to complain of chills, chest pain, shortness …

Covid-19 As A Second Hit For Anti-Phospholipid Syndrome, Himabindu Kolli, Pooja Maknoor, Celin Rajan, Nevin Varghese

Research Colloquium

Background: Anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis, usually in setting of underlying autoimmune disorders. Here, we present a case of anti-phospholipid syndrome post covid infection.

Case Presentation: 41-year-old lady presented to the ER with complaints of left sided facial droop for 3-day duration. On further evaluation, she was found to have subacute ischemic stroke and was managed with anticoagulation and supportive treatment. Past medical history is significant for a recent diagnosis of Covid infection and for subsequent development of lower extremity deep vein thrombosis (DVT). She was started on anticoagulation with rivaroxaban for …

Bacillus Calmette-Guérin Vaccination As Defense Against Sars-Cov-2 (Badas): A Randomized Controlled Trial To Protect Healthcare Workers In The Usa By Enhanced Trained Immune Responses, Andrew R Dinardo, Moshe Arditi, Ashish M Kamat, Kent J Koster, Santiago Carrero, Tomoki Nishiguchi, Maxim Lebedev, Aaron B Benjamin, Pablo Avalos, Marisa Lozano, Madeleine G Moule, Brittany Mccune, Baysia Herron, Malik Ladki, Daanish Sheikh, Matthew Spears, Ivan A Herrejon, Courtney Dodge, Sathish Kumar, Robert W Hutchison, Theresa U Ofili, Lynne A Opperman, Jessica A Bernard, Seth P Lerner, George Udeani, Gabriel Neal, Mihai G Netea, Jeffrey D Cirillo

Faculty, Staff and Students Publications

BACKGROUND: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.

METHODS: This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at …

Comparison Of Bacterial Culture With Biofire® Filmarray® Multiplex Pcr Screening Of Archived Cerebrospinal Fluid Specimens From Children With Suspected Bacterial Meningitis In Nigeria, S Obaro, F Hassan-Hanga, N Medugu, Rasaq Olaosebikan, G Olanipekun, B Jibir, S Gambo, Theresa Ajose, Carissa Duru, B Ebruke, H D Davies

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis.

METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens …

Should We Use Rifampicin In Periprosthetic Joint Infections Caused By Staphylococci When The Implant Has Been Exchanged? A Multicenter Observational Cohort Study, Tobias Siegfried Kramer, Alex Soriano, Sarah Tedeschi, Antonia F. Chen, Pierre Tattevin, Eric Senneville, Joan Gomez-Junyent, Victoria Birlutiu, Sabine Petersdorf, Vicens Diaz De Brito, Ignacio Sancho Gonzalez, Katherine A. Belden, Marjan Wouthuyzen-Bakker

Division of Infectious Diseases and Environmental Medicine Faculty Papers

BACKGROUND: Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision.

METHODS: We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant …

Factors Associated With Respiratory Pathogen Panel Utilization In Children Hospitalized With Acute Respiratory Illness — New Vaccine Surveillance Network, Kansas City, 2017–2021, Edward Lyon, Brian R. Lee, Benjamin Clopper, Heidi L. Moline, Rangaraj Selvarangan, Jennifer Schuster

Posters

Background: Respiratory pathogen panels (RPP) are multiplex PCR platforms that detect several respiratory viruses from one specimen. For most children hospitalized with acute respiratory illness (ARI), management is supportive, and detection of a specific virus from RPP does not impact clinical care. Therefore, clinical RPP use is not standardized, and ordering is at the discretion of the clinician. We sought to understand factors associated with RPP utilization among pediatric patients hospitalized with ARI. Methods: From October 2017 to September 2021, participants < 18 years hospitalized with ARI were enrolled at a single site in the New Vaccine Surveillance Network (NVSN). Eligible patients were residents of Jackson County, MO, had one or more ARI symptoms (e.g., cough, fever, nasal congestion) lasting < 14 days, and were enrolled within 48 hours of admission. Parent interviews and medical chart reviews were conducted. All participants had a research RPP, but results were not available to the clinical providers. Clinical providers were able to order a clinical RPP (cRPP), for which they received test results. Characteristics of NVSN enrollees hospitalized with ARI with and without a cRPP are described. Lastly, medical complexity was assessed via the pediatric complex chronic conditions classification system (CCC) then analyzed via chi- square test between groups. Findings: During the study period, 1,038 participants were enrolled, and 555 (53.4%) received a cRPP. Most, 299 (53%), cRPPs were ordered in the emergency department or urgent care before admission. Age was a significant factor associated with cRPP use (Table 1). cRPP participants were more likely to have complex chronic conditions, and/or technology dependence. No difference in cRPP use was observed by race/ethnicity, payer status, or sex. More participants were enrolled in 2020-2021, but the overall usage of cRPP is similar between years (Table 2). Conclusions: In this large cohort of children hospitalized with ARI, medical complexity, technological dependence, and age < 2 months were associated with increased utilization of cRPPs. Understanding the impact of cRPP on clinical care requires further investigation to better understand the utility of these tests.

Reducing The Rate Of Central Line-Associated Bloodstream Infections; A Quality Improvement Project, David Odada, Hellen Munyi, Japhet Gatuiku, Ruth Thuku, Jared Nyandigisi, Anne Wangui, Emilie Ashihundu, Beatrice Nyakiringa, Jemimah Kimeu, Martin Musumbi, Rodney Adam

Internal Medicine, East Africa

Background The burden of central line-associated bloodstream infections is significant and has negative implications for healthcare, increasing morbidity and mortality risks, increasing inpatient hospital stays, and increasing the cost of hospitalization. Efforts to reduce the incidence of central line-associated bloodstream infections have utilized quality improvement projects that implement, measure, and monitor outcomes. However, variations in location, healthcare organization, patient risks, and practice gaps are key to the success of interventions and approaches. This study aims to evaluate interventions of a quality improvement project on the reduction of central line-associated bloodstream infection rates at a university teaching hospital.

Methods This was …

Increasing Vaccination Rates Of 23-Valent Pneumococcal Polysaccharide Vaccine Among Patients At High-Risk For Invasive Pneumococcal Disease., Edward Lyon, Tracey Wetzel, Ann L. Wirtz, Douglas Swanson, Rachel Moran, Jessica Peters, Christine Symes, Liset Olarte, Rana El Feghaly

Posters

Introduction: Pneumococcal disease causes significant morbidity and mortality in children. Routine childhood immunizations protect for 13 or 15 pneumococcal serotypes via two pneumococcal conjugated vaccines. Patients with immunocompromising and chronic medical conditions are at high risk of invasive pneumococcal disease. A 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended in these patients to protect against more pneumococcal serotypes, but many patients have not received it. Our AIM is to increase PPSV23 vaccination rates among eligible patients in both the inpatient and outpatient infectious diseases (ID) settings from a baseline of 44% to 55% by October 2024. Methods: In collaboration with Children’s …