Digital Commons Network^™

The Safety Of Combined Triple Drug Therapy With Ivermectin, Diethylcarbamazine And Albendazole In The Neglected Tropical Diseases Co-Endemic Setting Of Fiji: A Cluster Randomised Trial, Myra Hardy, Josaia Samuela, Mike Kama, Meciusela Tuicakau, Lucia Romani, Margot J. Whitfeld, Christopher L. King, Gary J. Weil, Anneke C. Grobler, Leanne J. Robinson, John M. Kaldor, Andrew C. Steer

Open Access Publications

Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days …

Microbiome Restoration By Rbx2660 Does Not Preclude Recurrence Of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report, Eric C. Keen, Preston Tasoff, Tiffany Hink, Kimberly A. Reske, Carey-Ann D. Burnham, Gautam Dantas, Jennie H. Kwon, Erik R. Dubberke

Open Access Publications

A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.

The Struggling Infectious Diseases Fellow: Remediation Challenges And Opportunities, Michael T. Melia, Gerome Escota, Et Al

Open Access Publications

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with …

Impaired Tumor Necrosis Factor-Α Secretion By Cd4 T Cells During Respiratory Syncytial Virus Bronchiolitis Associated With Recurrent Wheeze, Maleewan Kitcharoensakkul, Leonard B Bacharier, Huiqing Yin-Declue, Jonathan S Boomer, Geneline Sajol, Marilyn K Leung, Brad Wilson, Kenneth B Schechtman, John P Atkinson, Jonathan M Green, Mario Castro

Open Access Publications

BACKGROUND: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life.

METHODS: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin-10, interferon-γ, tumor necrosis factor-α (TNF-α), IL-4, and IL-5 production by in vitro anti-CD3/CD28- and anti-CD3/CD46-activated CD4+ T cells, and percentage of peripheral Treg …

Tgfβ1 Orchestrates Renal Fibrosis Following Escherichia Coli Pyelonephritis, Teri N Hreha, Christina A Collins, Allyssa L Daugherty, Joy Twentyman, Nitin Paluri, David A Hunstad

Open Access Publications

Renal scarring after pyelonephritis is linked to long-term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenic Escherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti-androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/6 mice to elucidate the molecular mechanisms of post-infectious renal fibrosis and to determine how these pathways are altered by the presence of androgens. We found that elevated circulating testosterone levels primed the kidney for fibrosis by increasing local production of TGFβ1 before …

The Plasmodium Falciparum Artemisinin Susceptibility-Associated Ap-2 Adaptin Μ Subunit Is Clathrin Independent And Essential For Schizont Maturation, Ryan C Henrici, Rachel L Edwards, Martin Zoltner, Donelly A Van Schalkwyk, Melissa N Hart, Franziska Mohring, Robert W Moon, Stephanie D Nofal, Avnish Patel, Christian Flueck, David A Baker, Audrey R Odom John, Mark C Field, Colin J Sutherland

Open Access Publications

The efficacy of current antimalarial drugs is threatened by reduced susceptibility of

Cryptococcus Neoformans Chitin Synthase 3 Plays A Critical Role In Dampening Host Inflammatory Responses, Camaron R Hole, Woei C Lam, Rajendra Upadhya, Jennifer K Lodge

Open Access Publications

No abstract provided.

Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis At The Blood-Brain Barrier For Central Nervous System Entry, Hamid Salimi, Matthew D Cain, Xiaoping Jiang, Robyn A Roth, Wandy L Beatty, Chengqun Sun, William B Klimstra, Jianghui Hou, Robyn S Klein

Open Access Publications

Venezuelan and western equine encephalitis viruses (VEEV and WEEV, respectively) invade the central nervous system (CNS) early during infection, via neuronal and hematogenous routes. While viral replication mediates host shutoff, including expression of type I interferons (IFN), few studies have addressed how alphaviruses gain access to the CNS during established infection or the mechanisms of viral crossing at the blood-brain barrier (BBB). Here, we show that hematogenous dissemination of VEEV and WEEV into the CNS occurs via caveolin-1 (Cav-1)-mediated transcytosis (Cav-MT) across an intact BBB, which is impeded by IFN and inhibitors of RhoA GTPase. Use of reporter and nonreplicative …

A Qualitative Study Of Physician Perspectives On Adaptation To Electronic Health Records, Cynthia J Sieck, Nicole Pearl, Tiffani J Bright, Po-Yin Yen

Open Access Publications

BACKGROUND: Electronic Health Records (EHRs) have the potential to improve many aspects of care and their use has increased in the last decade. Because of this, acceptance and adoption of EHRs is less of a concern than adaptation to use. To understand this issue more deeply, we conducted a qualitative study of physician perspectives on EHR use to identify factors that facilitate adaptation.

METHODS: We conducted semi-structured interviews with 9 physicians across a range of inpatient disciplines at a large Academic Medical Center. Interviews were conducted by phone, lasting approximately 30 min, and were transcribed verbatim for analysis. We utilized …

Mechanism Of Differential Zika And Dengue Virus Neutralization By A Public Antibody Lineage Targeting The Diii Lateral Ridge, Haiyan Zhao, Lily Xu, Robin Bombardi, Rachel Nargi, Zengqin Deng, John M. Errico, Christopher A. Nelson, Kimberly A. Dowd, Theodore C. Pierson, James E. Crowe, Michael S. Diamond, Daved H. Fremont

Open Access Publications

We previously generated a panel of human monoclonal antibodies (mAbs) against Zika virus (ZIKV) and identified one, ZIKV-116, that shares germline usage with mAbs identified in multiple donors. Here we show that ZIKV-116 interferes with ZIKV infection at a post-cellular attachment step by blocking viral fusion with host membranes. ZIKV-116 recognizes the lateral ridge of envelope protein domain III, with one critical residue varying between the Asian and African strains responsible for differential binding affinity and neutralization potency (E393D). ZIKV-116 also binds to and cross-neutralizes some dengue virus serotype 1 (DENV1) strains, with genotype-dependent inhibition explained by variation in a …

Emerging Priorities For Hiv Service Delivery, Nathan Ford, Elvin Geng, Et Al.

Open Access Publications

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.

Glopid-R Report On Chikungunya, O'Nyong-Nyong And Mayaro Virus, Part 5: Entomological Aspects, L. Pezzi, M. S. Diamond, Et Al.

2020-Current year OA Pubs

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through …

Redefining And Revisiting Cost Estimates Of Routine Art Care In Zambia: An Analysis Of Ten Clinics, Austin Tucker, Tannia Tembo, Radhika P Tampi, Jacob Mutale, Mpande Mukumba-Mwenechanya, Anjali Sharma, David W Dowdy, Carolyn B Moore, Elvin Geng, Charles B Holmes, Izukanji Sikazwe, Hojoon Sohn

2020-Current year OA Pubs

INTRODUCTION: Accurate costing is key for programme planning and policy implementation. Since 2011, there have been major changes in eligibility criteria and treatment regimens with price reductions in ART drugs, programmatic changes resulting in clinical task-shifting and decentralization of ART delivery to peripheral health centres making existing evidence on ART care costs in Zambia out-of-date. As decision makers consider further changes in ART service delivery, it is important to understand the current drivers of costs for ART care. This study provides updates on costs of ART services for HIV-positive patients in Zambia.

METHODS: We evaluated costs, assessed from the health …

Hope On The Horizon: Novel Fungal Treatments In Development, Adriana M. Rauseo, Ariella Coler-Reilly, Lindsey Larson, Andrej Spec

Open Access Publications

The treatment of invasive fungal infections remains challenging due to limitations in currently available antifungal therapies including toxicity, interactions, restricted routes of administration, and drug resistance. This review focuses on novel therapies in clinical development, including drugs and a device. These drugs have novel mechanisms of action to overcome resistance, and some offer new formulations providing distinct advantages over current therapies to improve safety profiles and reduce interactions. Among agents that target the cell wall, 2 glucan synthesis inhibitors are discussed (rezafungin and ibrexafungerp), as well as fosmanogepix and nikkomycin Z. Agents that target the cell membrane include 3 fourth-generation …

Multicenter Evaluation Of The New Etest Gradient Diffusion Method For Piperacillin-Tazobactam Susceptibility Testing Of Enterobacterales, Pseudomonas Aeruginosa, And Acinetobacter Baumannii Complex, Sergio García-Fernández, Yohann Bala, Tom Armstrong, María García-Castillo, Carey-Ann D. Burnham, Meghan A Wallace, Dwight Hardy, Gilles Zambardi, Rafael Cantón

Open Access Publications

Piperacillin-tazobactam (P/T) is a β-lactam-β-lactamase inhibitor combination frequently used in the hospital setting. Etest is a gradient diffusion method that represents an alternative to broth microdilution (BMD) for performing antimicrobial susceptibility testing. We conducted a multicenter evaluation of the performance of the new P/T Etest compared to that of BMD following U.S. Food and Drug Administration (FDA) and International Standards Organization (ISO) standard ISO 20776-2 criteria using Clinical and Laboratory Standards Institute (CLSI)-FDA and European Committee on Antimicrobial Susceptibility Testing (EUCAST) interpretive breakpoints, respectively. A total of 977 isolates (775

Clinical Controversies In Anticoagulation Monitoring And Antithrombin Supplementation For Ecmo, Meghan M Chlebowski, Sirine Baltagi, Mel Carlson, Jerrold H Levy, Philip C Spinella

Open Access Publications

During extracorporeal membrane oxygenation (ECMO), a delicate balance is required to titrate systemic anticoagulation to prevent thrombotic complications within the circuit and prevent bleeding in the patient. Despite focused efforts to achieve this balance, the frequency of both thrombotic and bleeding events remains high. Anticoagulation is complicated to manage in this population due to the complexities of the hemostatic system that are compounded by age-related developmental hemostatic changes, variable effects of the etiology of critical illness on hemostasis, and blood-circuit interaction. Lack of high-quality data to guide anticoagulation management in ECMO patients results in marked practice variability among centers. One …

Perfect Timing: Circadian Rhythms, Sleep, And Immunity - An Nih Workshop Summary, Jeffrey A Haspel, Andrew E Gelman, Brian S Kim, Et Al

Open Access Publications

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses - ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation -are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, …

L-Plastin Deficiency Produces Increased Trabecular Bone Due To Attenuation Of Sealing Ring Formation And Osteoclast Dysfunction, Meenakshi A. Chellaiah, Megan C. Moorer, Sunipa Majumdar, Hanan Aljohani, Sharon C. Morley, Vanessa Yingling, Joseph P. Stains

Open Access Publications

No abstract provided.

Protective Role Of Brain Derived Neurotrophic Factor (Bdnf) In Obstructive Sleep Apnea Syndrome (Osas) Patients, Krisstopher Richard Flores, Fausta Viccaro, Mauro Aquilini, Stefania Scarpino, Francesco Ronchetti, Rita Mancini, Arianna Di Napoli, Davide Scozzi, Alberto Ricci

Open Access Publications

Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by repeated episodes of upper airways collapse during the sleep. The following intermittent hypoxia triggers a state of chronic inflammation, which also interests the nervous system leading to neuronal damage and increased risk of cognitive impairment. Brain derived neurotrophic factor (BDNF) is a growth factor often associated with neuroplasticity and neuroprotection whose levels increase in several condition associated with neuronal damage. However, whether patients affected by OSAS have altered BDNF levels and whether such alteration may be reflective of their cognitive impairment is still controversial. Here we show that, when …

Effects Of Tdp2/Vpg Unlinkase Activity On Picornavirus Infections Downstream Of Virus Translation, Autumn C Holmes, Guido Zagnoli-Vieira, Keith W Caldecott, Bert L Semler

Open Access Publications

In this study, we characterized the role of host cell protein tyrosyl-DNA phosphodiesterase 2 (TDP2) activity, also known as VPg unlinkase, in picornavirus infections in a human cell model of infection. TDP2/VPg unlinkase is used by picornaviruses to remove the small polypeptide, VPg (Virus Protein genome-linked, the primer for viral RNA synthesis), from virus genomic RNA. We utilized a CRISPR/Cas-9-generated TDP2 knock out (KO) human retinal pigment epithelial-1 (hRPE-1) cell line, in addition to the wild type (WT) counterpart for our studies. We determined that in the absence of TDP2, virus growth kinetics for two enteroviruses (poliovirus and coxsackievirus B3) …

The Long-Term Effects Of A Family Based Economic Empowerment Intervention (Suubi+Adherence) On Suppression Of Hiv Viral Loads Among Adolescents Living With Hiv In Southern Uganda: Findings From 5-Year Cluster Randomized Trial, Fred M. Ssewamala, Darejan Dvalishvili, Claude A. Mellins, Elvin H. Geng, Fredderick Makumbi, Torsten B. Neilands, Mary Mckay, Christopher Damulira, Proscovia Nabunya, Ozge Sensoy Bahar, Gertrude Nakigozi, Godfrey Kigozi, William Byansi, Miriam Mukasa, Flavia Namuwonge

Open Access Publications

BACKGROUND: The rapid scale-up of HIV therapy across Africa has failed to adequately engage adolescents living with HIV (ALWHIV). Retention and viral suppression for this group (ALWHIV) is 50% lower than for adults. Indeed, on the African continent, HIV remains the single leading cause of mortality among adolescents. Strategies tailored to the unqiue developmental and social vulnerabilities of this group are urgently needed to enhance successful treatment.

METHODS: We carried out a five-year longitudinal cluster randomized trial (ClinicalTrials.gov ID: NCT01790373) with adolescents living with HIV (ALWHIV) ages 10 to 16 years clustered at health care clinics to test the effect …

A Ten-Year Retrospective Evaluation Of Acute Flaccid Myelitis At 5 Pediatric Centers In The United States, 2005-2014, Margaret M. Cortese, Anita K. Kambhampati, Jennifer E. Schuster, Zaid Alhinai, Gary R. Nelson, Gloria J. Guzman Perez-Carrillo, Arastoo Vossough, Michael A. Smit, Robert C. Mckinstry, Timothy Zinkus, Kevin R. Moore, Jeffrey M. Rogg, Meghan S. Candee, James J. Sejvar, Sarah E. Hopkins

Open Access Publications

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics.

METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 …

Malaria Parasite Plasmepsins: More Than Just Plain Old Degradative Pepsins, Armiyaw S. Nasamu, Alexander J. Polino, Eva S. Istvan, Daniel E. Goldberg

Open Access Publications

No abstract provided.

Understanding Antibiotic Prophylaxis Prescribing In Pediatric Surgical Specialties, Sara M Malone, Natalie S Seigel, Jason G Newland, Jacqueline M Saito, Virginia R Mckay

Open Access Publications

BACKGROUND: Overuse of antibiotics has caused secondary poor outcomes and has led to a current rate of antibiotic resistant infections that constitutes a public health crisis. In pediatric surgical specialties, children continue to receive unnecessary antibiotics.

OBJECTIVE: To understand the factors that contribute to pediatric surgeons' decisions regarding the use of perioperative antibiotic prophylaxis.

METHODS: Focus groups included pediatric proceduralists/surgeons from the following specialties: interventional cardiology, otolaryngology, orthopedic surgery, cardiothoracic surgery, and general surgery.

RESULTS: A total of 23 surgeons with a median of 9 years of experience (range, 0.5-29 years) participated in the focus groups that lasted 30-90 minutes …

Temporary Abdominal Closure Is Associated With Increased Risk For Fungal Intra-Abdominal Infections In Trauma Patients, Christina X. Zhang, Rohit R. Rasane, Qiao Zhang, Ricardo A. Fonseca, Jose A. Aldana, Javier E. Rincon, Maya J. Sorini, Kelly M. Bochicchio, Jennifer M. Leonard, Obeid N. Ilahi, Grant V. Bochicchio

Open Access Publications

No abstract provided.

From Stigma To Validation: A Qualitative Assessment Of A Novel National Program To Improve Retention Of Physician-Scientists With Caregiving Responsibilities, Rochelle D. Jones, Victoria J. Fraser, Et Al.

Open Access Publications

No abstract provided.

Roles Of The Vagina And The Vaginal Microbiota In Urinary Tract Infection: Evidence From Clinical Correlations And Experimental Models, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Mounting evidence indicates that the vagina can harbor uropathogenic bacteria. Here, we consider three roles played by the vagina and its bacterial inhabitants in urinary tract infection (UTI) and urinary health. First, the vagina can serve as a reservoir for

Understanding Patient Transfers Across Multiple Clinics In Zambia Among Hiv Infected Adults, Kombatende Sikombe, Aaloke Mody, Jillian Kadota, Jesse Jake Pry, Sandra Simbeza, Ingrid Eshun-Wilson, Sitali Richard Situmbeko, Chama Bukankala, Laura Beres, Njekwa Mukamba, Mwanza Wa Mwanza, Carolyn Bolton-Moore, Charles B. Holmes, Elvin H. Geng, Izukanji Sikazwe

Open Access Publications

Many patients in HIV care in Africa considered lost to follow up (LTFU) at one facility are reportedly accessing care in another. The success of these unofficial transfers as measured by time to re-entry at the new-facility, prevalence of treatment interruptions, speed of ART-initiation, and overall continuity of care is not well characterized but may reveal opportunities for improvement. We traced a random sample of LTFU HIV-infected patients in Zambia. Among those found alive and reported in care at a new-facility, we reviewed records at the receiving facility to verify transfer; and when verified, documented the transfer experience. We used …

Structural Basis Of Chikungunya Virus Inhibition By Monoclonal Antibodies, Qun Fei Zhou, Julie M. Fox, James T. Earnest, Thiam-Seng Ng, Arthur S. Kim, Guntur Fibriansah, Victor A. Kostyuchenko, Jian Shi, Bo Shu, Michael S. Diamond, Shee-Mei Lok

Open Access Publications

No abstract provided.

Characteristics And Outcomes Among A Hospitalized Patient Cohort With Streptococcus Pneumoniae Infection, Scott T. Micek, James Simmons, Nicholas Hampton, Marin H. Kollef

Open Access Publications

No abstract provided.