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Increased Incidence And Risk Of Septicemia And Urinary Tract Infection After Clostridioides Difficile Infection, Margaret A Olsen, Matthew R Keller, Dustin Stwalley, Holly Yu, Erik R Dubberke

2020-Current year OA Pubs

BACKGROUND: Although increased occurrence of septicemia in persons with

METHODS: The first episode of CDI was identified using 2011-2017 MarketScan and CMS Medicare data and CDI cases categorized by standard surveillance definitions. Uninfected persons were frequency matched 4:1 to cases by the CDI case surveillance definition. Multivariable Cox proportional hazards models were used to identify risk factors for septicemia and UTI within 90 days of CDI onset, accounting for the competing risk of death in the Medicare population.

RESULTS: The incidence of septicemia was highest after hospital-onset CDI in the Medicare, younger commercial, and younger Medicaid populations (25.5%, 15.7%, and …

Pharmacokinetics Of Moxidectin Combined With Albendazole Or Albendazole Plus Diethylcarbamazine For Bancroftian Filariasis, Yashpal S. Chhonker, Catherine Bjerum, Veenu Bala, Allassane F. Ouattara, Benjamin G. Koudou, Toki P. Gabo, Abdullah Alshehri, Abdoulaye Meïté, Peter U. Fischer, Gary J. Weil, Christopher L. King, Philip J. Budge, Daryl J. Murry

2020-Current year OA Pubs

Moxidectin (MOX) is a milbemycin endectocide recently approved by the U.S. FDA for the treatment of onchocerciasis in persons at least 12 years of age. MOX has been shown to have a good safety profile in recent clinical trials. The efficacy of MOX for the treatment of lymphatic filariasis (LF) and its potential use in mass drug administration protocols for the elimination of LF is currently under evaluation. In the context of a clinical trial, we investigated the pharmacokinetics and drug interactions of a combination of MOX plus albendazole (ALB) with or without diethylcarbamazine (DEC) compared to ivermectin (IVM) plus …

Spatial Epidemiologic Analysis And Risk Factors For Nontuberculous Mycobacteria Infections, Missouri, Usa, 2008-2019, Carlos Mejia-Chew, Miguel A Chavez, Min Lian, Angela Mckee, Leighton Garrett, Thomas C Bailey, Andrej Spec, Mansi Agarwal, George Turabelidze

2020-Current year OA Pubs

Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with …

Effect Of Fecal Microbiota, Live-Jslm (Rebyota [Rbl]) On Health-Related Quality Of Life In Patients With Recurrent Clostridioides Difficile Infection: Results From The Punch Cd3 Clinical Trial, Kevin W Garey, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana García-Horton, Mirko Fillbrunn, Hongjue Wang, Glenn S Tillotson, Lindy L Bancke, Paul Feuerstadt

2020-Current year OA Pubs

BACKGROUND: Recurrence of

METHODS: This was a secondary analysis of a randomized, double-blind, placebo-controlled phase 3 study (PUNCH CD3). The disease-specific

RESULTS: Findings were analyzed in a total of 185 patients (RBL, n = 128 [69.2%]; placebo, n = 57 [30.8%]) with available Cdiff32 data. Patients from both arms showed significant improvements in Cdiff32 scores relative to baseline across all outcomes and at all time points (all

CONCLUSIONS: In a phase 3 double-blinded clinical trial, RBL-treated patients reported more substantial and sustained disease-specific HRQL improvements than placebo-treated patients.

CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).

The Stop Covid 2 Study: Fluvoxamine Vs Placebo For Outpatients With Symptomatic Covid-19, A Fully Remote Randomized Controlled Trial, Angela M Reiersen, Caline Mattar, J Philip Miller, William G Powderly, Michael W Rich, Julie Schweiger, Angela Stevens, Lei Yang, Michael Yingling, Torie R Gettinger, Charles F Zorumski, Eric J Lenze, Et Al.

2020-Current year OA Pubs

BACKGROUND: Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

METHODS: This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days. The primary modified intent-to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset …

Prospective Role Of Cefiderocol In The Management Of Carbapenem-Resistant Acinetobacter Baumannii Infections: Review Of The Evidence, Marin Kollef, Herve Dupont, David E Greenberg, Pierluigi Viale, Roger Echols, Yoshinori Yamano, David P Nicolau

2020-Current year OA Pubs

Carbapenem-resistant Acinetobacter baumannii (CRAB) has been classified by the World Health Organization as being in the critical category of pathogens requiring urgent new antibiotic treatment options. Cefiderocol, the first approved siderophore cephalosporin, was designed for the treatment of carbapenem-resistant Gram-negative pathogens, particularly the non-fermenting species A. baumannii and Pseudomonas aeruginosa. Cefiderocol is mostly stable against hydrolysis by serine β-lactamases and metallo-β-lactamases, which are leading causes of carbapenem resistance. This review collates the available evidence on the in vitro activity, pharmacokinetics/pharmacodynamics, and efficacy and safety of cefiderocol, and outlines its current role in the management of CRAB infections. In vitro surveillance …

Sars-Cov-2 Uses Cd4 To Infect T Helper Lymphocytes, Natalia S Brunetti, Louis-Marie Bloyet, Spencer Stumpf, Marjorie C Pontelli, Sean Whelan, Alessandro S Farias, Et Al.

2020-Current year OA Pubs

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4

Engineered Reporter Phages For Detection Of Escherichia Coli, Enterococcus, And Klebsiella In Urine, Susanne Meile, Jonas Marschall, Et Al.

2020-Current year OA Pubs

The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, …

Lrp1 Is Essential For Lethal Rift Valley Fever Hepatic Disease In Mice, Madeline M Schwarz, Safder S Ganaie, Annie Feng, Griffin Brown, Tenzin Yangdon, J Michael White, Ryan M Hoehl, Cynthia M Mcmillen, Rachael E Rush, Kaleigh A Connors, Xiaoxia Cui, Daisy W Leung, Takeshi Egawa, Gaya K Amarasinghe, Amy L Hartman

2020-Current year OA Pubs

Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor-related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how …

Proportion Of Physicians Who Treat Patients With Greater Social And Clinical Risk And Physician Inclusion In Medicare Advantage Networks, Jung Ho Gong, Kenton J Johnston, David J Meyers

2020-Current year OA Pubs

IMPORTANCE: Medicare Advantage (MA) plans are expanding rapidly, now serving 50% of all Medicare enrollees. Little is known about how inclusion rates of physicians in MA plan networks vary by the social and clinical risks of their patients.

OBJECTIVE: To examine the association of physicians caring for patients with higher levels of social and clinical risk in traditional Medicare (TM) with the likelihood of inclusion in MA plan networks.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study evaluated the number of patients of physicians participating in TM Part B in 2019. The data analysis was conducted between June 2022 and March …

Early Antiretroviral Therapy Not Associated With Higher Cryptococcal Meningitis Mortality In People With Human Immunodeficiency Virus In High-Income Countries: An International Collaborative Cohort Study, Suzanne M Ingle, Elvin Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings.

METHODS: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 …

Comparison Of Patient Exit Interviews With Unannounced Standardised Patients For Assessing Hiv Service Delivery In Zambia: A Study Nested Within A Cluster Randomised Trial, Kombatende Sikombe, Aaloke Mody, Ingrid Eshun-Wilson, Elvin Geng, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To compare unannounced standardised patient approach (eg, mystery clients) with typical exit interviews for assessing patient experiences in HIV care (eg, unfriendly providers, long waiting times). We hypothesise standardised patients would report more negative experiences than typical exit interviews affected by social desirability bias.

SETTING: Cross-sectional surveys in 16 government-operated HIV primary care clinics in Lusaka, Zambia providing antiretroviral therapy (ART).

PARTICIPANTS: 3526 participants aged ≥18 years receiving ART participated in the exit surveys between August 2019 and November 2021.

INTERVENTION: Systematic sample (every n

OUTCOME MEASURES: We compared patient experience among patients who received brief training prior to …

An Immunostimulatory Glycolipid That Blocks Sars-Cov-2, Rsv, And Influenza Infections In Vivo, Moriya Tsuji, Zhenlu Chong, Tamarand L Darling, Kuljeet Seehra, Adrianus C M Boon, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Prophylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infections in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as …

Assessment Of Gastroesophageal Reflux Symptoms And Sleep Quality Among Women In The Nurses' Health Study Ii, Jane Ha, Raaj S Mehta, Yin Cao, Tianyi Huang, Kyle Staller, Andrew T Chan

2020-Current year OA Pubs

IMPORTANCE: Limited data exist on the association of gastroesophageal reflux (GER) symptoms with sleep quality.

OBJECTIVE: To prospectively investigate the association between GER symptoms and sleep quality.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included data from the Nurses' Health Study II of female nurses in the US. Participants self-reported the frequency and duration of GER symptoms beginning June 2005, with updates every 4 years through June 2015. Follow-up was completed June 2019, and data were analyzed from November 15, 2022, to June 4, 2023.

EXPOSURES: Frequency and duration of GER symptoms.

MAIN OUTCOMES AND MEASURES: Poor sleep quality …

Staphylococcus Aureus Bacteremia In Pediatric Patients: Uncovering A Rural Health Challenge, Kyle J Whittington, Sara M Malone, Patrick G Hogan, Faria Ahmed, Jessieann Flowers, Grace Milburn, John J Morelli, Jason G Newland, Stephanie A Fritz

2020-Current year OA Pubs

BACKGROUND:

METHODS: To investigate factors influencing

RESULTS: Of 251 patients, 69 (27%) were from rural areas; 28 (11%) were initially admitted to an OSH. Treatment failure occurred in 39 (16%) patients. Patients from rural areas were more likely to be infected with methicillin-resistant

CONCLUSIONS: Children from rural areas face barriers to specialized health care. These challenges may contribute to severe illness and worse outcomes among children with

Safety And Efficacy Of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From A Phase 2, Randomized Clinical Trial In Pediatric Participants With Complicated Intra-Abdominal Infection, Carl-Christian A. Jackson, Jason Newland, Nataliia Dementieva, Julia Lonchar, Feng-Hsiu Su, Jennifer A. Huntington, Mekki Bensaci, Myra W. Popejoy, Matthew G. Johnson, Carisa De Anda, Elizabeth G. Rhee, Christopher J. Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.

RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole …

Provider Perspectives On Patient-Centredness: Participatory Formative Research And Rapid Analysis Methods To Inform The Design And Implementation Of A Facility-Based Hiv Care Improvement Intervention In Zambia, Chanda Mwamba, Laura K Beres, Njekwa Mukamba, Lazarus Jere, Marksman Foloko, Kasapo Lumbo, Kombatende Sikombe, Sandra Simbeza, Aaloke Mody, Jake M Pry, Charles B Holmes, Izukanji Sikazwe, Carolyn Bolton Moore, Katerina Christopoulos, Anjali Sharma, Elvin H Geng

2020-Current year OA Pubs

INTRODUCTION: Implementation of patient-centred care (PCC) practices in HIV treatment depends on healthcare workers' (HCWs) perceptions of the acceptability, appropriateness and feasibility of such practices (e.g. use of intentional, metric-driven activities to improve patient experiences).

METHODS: We applied rapid, rigorous formative research methods to refine a PCC intervention for future trial. In 2018, we conducted focus group discussions (FGDs) with 46 HCWs purposefully selected from two pilot sites. We elicited HCW perceptions of HIV service delivery, HCW motivation and perceived value of patient experience measures intended to improve PCC. FGDs utilized participatory methods to understand HCW responses to patient-reported care …

Healthcare Costs Of Clostridioides Difficile Infection In Commercially Insured Younger Adults, John M Sahrmann, Margaret A Olsen, Matthew R Keller, Holly Yu, Erik R Dubberke

2020-Current year OA Pubs

In a US adult population aged <65 years, attributable costs due to

Histidine-Rich Protein Ii Nanoparticle Delivery Of Heme Iron Load Drives Endothelial Inflammation In Cerebral Malaria, Suong T Nguyen, Daniel Du, Daniel Wychrij, Matthew D Cain, Qingping Wu, Robyn S Klein, Ilaria Russo, Daniel E Goldberg

2020-Current year OA Pubs

Histidine-rich protein II (HRPII) is secreted by

Social Determinants Of Health And Us Cancer Screening Interventions: A Systematic Review, Ariella R Korn, Callie Walsh-Bailey, Margarita Correa-Mendez, Peter Delnero, Meagan Pilar, Brittney Sandler, Ross C Brownson, Karen M Emmons, April Y Oh

2020-Current year OA Pubs

There remains a need to synthesize linkages between social determinants of health (SDOH) and cancer screening to reduce persistent inequities contributing to the US cancer burden. The authors conducted a systematic review of US-based breast, cervical, colorectal, and lung cancer screening intervention studies to summarize how SDOH have been considered in interventions and relationships between SDOH and screening. Five databases were searched for peer-reviewed research articles published in English between 2010 and 2021. The Covidence software platform was used to screen articles and extract data using a standardized template. Data items included study and intervention characteristics, SDOH intervention components and …

Evaluation Of The Ng-Test Carba 5 Lateral Flow Assay With An Imp-2-Producing Morganella Morganii And Other Morganellaceae, Nicole J. Tarlton, Meghan A. Wallace, Robert F. Potter, Kailun Zhang, Gautam Dantas, Erik R. Dubberke, Carey-Ann D. Burnham, Melanie L. Yarbrough

2020-Current year OA Pubs

An isolate of Morganella morganii (MMOR1) that tested susceptible to 3

Poly(Adp-Ribose) Polymerase 9 Mediates Early Protection Against Mycobacterium Tuberculosis Infection By Regulating Type I Ifn Production, Shyamala Thirunavukkarasu, Mushtaq Ahmed, Bruce A. Rosa, Mark Boothby, Sung Hoon Cho, Javier Rangel-Moreno, Stanley K. Mbandi, Valérie Schreiber, Ananya Gupta, Joaquin Zuniga, Makedonka Mitreva, Deepak Kaushal, Thomas J. Scriba, Shabaana A. Khader

2020-Current year OA Pubs

The ADP ribosyltransferases (PARPs 1-17) regulate diverse cellular processes, including DNA damage repair. PARPs are classified on the basis of their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). Although PARP9 mRNA expression is significantly increased in progressive tuberculosis (TB) in humans, its participation in host immunity to TB is unknown. Here, we show that PARP9 mRNA encoding the MARylating PARP9 enzyme was upregulated during TB in humans and mice and provide evidence of a critical modulatory role for PARP9 in DNA damage, cyclic GMP-AMP synthase (cGAS) expression, and type I IFN production during TB. Thus, Parp9-deficient mice were susceptible …

Safety Of Fecal Microbiota, Live-Jslm (Rebyota™) In Individuals With Recurrent Clostridioides Difficile Infection: Data From Five Prospective Clinical Trials, Christine Lee, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Paul Feuerstadt, Sahil Khanna, Robert Orenstein, Erik R Dubberke

2020-Current year OA Pubs

BACKGROUND: Microbiota-based treatments reduce the incidence of recurrent

OBJECTIVES: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults.

DESIGN: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL.

METHODS: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or …

Guidance On The Use Of Convalescent Plasma To Treat Immunocompromised Patients With Coronavirus Disease 2019, Evan M Bloch, Jeffrey P Henderson, Brenda J Grossman, Et Al.

2020-Current year OA Pubs

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP …

Brain Abscess And Stroke In Children And Adults With Hereditary Hemorrhagic Telangiectasia: Analysis Of A Large National Claims Database, Andrew J. White, Itay Marmor, Kate M. Peacock, Katelin B. Nickel, Jessica Zavadil, Margaret A. Olsen

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in transforming growth factor-β signaling pathway-related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adults and children with HHT.

METHODS: We conducted a case-control study among participants aged 1-64 years in the MarketScan Commercial (2006-2019) and Multistate Medicaid Databases (2011-2019). We identified cases with HHT using

RESULTS: …

Acinetobacter Baumannii Atcc 17978 Encodes A Microcin System With Antimicrobial Properties For Contact-Independent Competition, Fabiana Bisaro, Howard A Shuman, Mario F Feldman, Michael J Gebhardt, Stefan Pukatzki

2020-Current year OA Pubs

No abstract provided.

Autophagy Prevents Early Proinflammatory Responses And Neutrophil Recruitment During Mycobacterium Tuberculosis Infection Without Affecting Pathogen Burden In Macrophages, Rachel L. Kinsella, Jacqueline M. Kimmey, Asya Smirnov, Reilly Woodson, Margaret R. Gaggioli, Sthefany M. Chavez, Darren Kreamalmeyer, Christina L. Stallings

2020-Current year OA Pubs

The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment …

Igg4 Antibodies To The Recombinant Filarial Antigen Wb-Bhp-1 Decrease Dramatically Following Treatment Of Lymphatic Filariasis, Sarah E. Greene, Yuefang Huang, Kurt C. Curtis, Christopher L. King, Peter U. Fischer, Gary J. Weil

2020-Current year OA Pubs

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease and a major cause of chronic disability. Improved diagnostic tests are needed because of long-term persistence of anti-filarial antibodies or circulating filarial antigenemia after treatments that clear microfilaremia. Here, we assess changes in levels of antibodies to the recombinant filarial antigens Wb-Bhp-1, Wb123, and Bm14 after anti-filarial treatment.

METHODOLOGY/PRINCIPAL FINDINGS: IgG4 antibodies to recombinant filarial antigens were assessed by ELISA. We tested serial plasma samples from a clinical trial in Papua New Guinea. Before treatment, 90%, 71% and 99% of participants had antibodies to Wb-Bhp-1, Wb123, and Bm14, respectively. Antibodies to …

Biological Rhythms In Covid-19 Vaccine Effectiveness In An Observational Cohort Study Of 1.5 Million Patients, Guy Hazan, Or A. Duek, Hillel Alapi, Huram Mok, Alex Ganninger, Elaine Ostendorf, Carrie Gierasch, Gabriel Chodick, David Greenberg, Jeffrey A. Haspel

2020-Current year OA Pubs

BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19-associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800-1159 hours), afternoon (1200-1559 hours), or evening hours (1600-1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities.RESULTSBreakthrough infections differed based on …

Replicative Acinetobacter Baumannii Strains Interfere With Phagosomal Maturation By Modulating The Vacuolar Ph, Jesus S. Distel, Gisela Di Venanzio, Joseph J. Mackel, David A. Rosen, Mario F. Feldman

2020-Current year OA Pubs

Bacterial pneumonia is a common infection of the lower respiratory tract that can afflict patients of all ages. Multidrug-resistant strains of Acinetobacter baumannii are increasingly responsible for causing nosocomial pneumonias, thus posing an urgent threat. Alveolar macrophages play a critical role in overcoming respiratory infections caused by this pathogen. Recently, we and others have shown that new clinical isolates of A. baumannii, but not the common lab strain ATCC 19606 (19606), can persist and replicate in macrophages within spacious vacuoles that we called Acinetobacter Containing Vacuoles (ACV). In this work, we demonstrate that the modern A. baumannii clinical isolate 398, …