bluuebunny/crossref_metadata_2025_split huggingface dataset:
853. Rapid, non-invasive detection of Borrelia miyamotoi infection using a plasma-based microbial cell-free DNA sequencing test
Authors: Ahmad Sharjeel , Kasper Douglas , Rubio Luis , Marinez Javier E 
Published: November 2023

Abstract

Background
Borrelia miyamotoi is a zoonotic infection transmitted by the same genus of ticks that transmits Borreliella burgdorferi which causes Lyme disease. It can cause an acute non-specific febrile illness ("hard tick-borne relapsing fever") with chills, sweats, headache, neck stiffness, fatigue, myalgias, and arthralgias. Serious manifestations such as meningitis or meningoencephalitis or uveitis can occur in immunocompromised hosts. Many features of this infection are indistinguishable from other tick-borne illnesses. Rapid, non-invasive diagnosis of B. miyamotoi by microbial cell-free DNA (mcfDNA) sequencing of plasma offers a means to overcome these limitations.

Methods
The Karius TestTM (KT) detects and quantifies mcfDNA in molecules/µL (MPM) from &gt; 1000 organisms in plasma (performed at the CLIA certified/CAP accredited Karius laboratory). KT detections of B. miyamotoi were compiled from three medical centers in different regions of United States. Clinical review was performed by the health care providers.

Results
KT detected B. miyamotoi in three patients. All were adult males in whom the diagnosis was unexpected. None of the patients recalled tick bites. (See Table 1 for patient characteristics). Two patients were on immunomodulator therapy while the third one had hepatitis C (treated) – mediated cirrhosis. A broad infectious disease work-up was performed and broad-spectrum empiric antibiotic was initiated in one case. KT was the first test to identify B. miyamotoi as the microbiological diagnosis in all cases and was the only test to establish the diagnosis in two cases, with the third having subsequent positive Borrelia PCR testing. All responded well to treatment with doxycycline with resolution of symptoms and lab abnormalities.

Conclusion
KT enabled rapid, non-invasive, plasma-based diagnosis of "hard tick-borne relapsing fever" caused by B.miyamotoi. Given an unclear etiology and a potentially diverse differential diagnosis, especially in immunocompromised patients, an unbiased diagnostic test such as the KT can prove a useful complement to conventional diagnostic work-up to provide real-time results. Additionally, mcfDNA sequencing can prove useful in detecting emerging, diagnostically challenging microbes.

Disclosures
All Authors: No reported disclosures
869. Evaluation of the Impact of Polymicrobial Bloodstream Infections (BSIs) on the Performance of BioFire Blood Culture Identification 2 (BCID2) Multiplex Polymerase Chain Reaction (PCR) Panel
Authors: Lapin Jonathan S , Gogineni Aishwarya , Singh Karan , Gao Nina , Johnson J Kristie , Claeys Kimberly C 
Published: November 2023

Abstract

Background
Rapid diagnostic tests (RDTs) have led to a paradigm shift in the management of BSIs, allowing for earlier species identification and decreased time to appropriate antimicrobials. The University of Maryland Medical Center recently switched from Verigene, a nucleic acid microarray panel, to BioFire BCID2, a multiplex PCR panel. Whereas Verigene is known to perform poorly in polymicrobial BSIs, it is unknown how BioFire BCID2 performs and how this impacts downstream antimicrobial therapy decisions.

Methods
We performed a retrospective cohort study of adult patients with polymicrobial blood cultures tested with BioFire BCID2 between 01/01/2022 and 05/31/2022. Family, genus, species, and resistance identification from BioFire BCID2 were compared to conventional microbiological methods and phenotypic antimicrobial susceptibility testing (AST) to assess the on-panel accuracy of BCID2 in polymicrobial BSI. Antimicrobial prescribing based on BioFire BCID2 results was collected to determine how the BCID2 impacts decision making in polymicrobial BSIs.

Results
Among 504 patients with positive blood cultures, 52 (10.3%) were polymicrobial BSIs. Among these 52 BSIs, 91 distinct organisms were identified using BCID2, and 19 Enterobacterales, 33 Staphylococcus spp., and 14 Streptococcus spp. identified at the family or genus level. Additionally, 105 organisms and 19 Coagulase-negative Staphylococci were recovered with conventional methods. BCID2 correctly identified 89.4% (101/113) of on-panel organisms at the species level. There was 88.5% concordance between BCID2 resistance identification and phenotypic AST. 36 (69.2%) and 20 (38.5%) patients had antimicrobial regimen changes within 24 hours of BCID2 results and AST, respectively – most were de-escalations (66.7% and 85%, respectively). 12 of these patients had further changes in antimicrobials; 2 of which were escalations due to discrepant BCID2 and AST results.

Conclusion
On-panel agreement between BioFire BCID2 and conventional methods was high in polymicrobial BSI, although less than reported in studies assessing only monomicrobial BSI. In patients with polymicrobial BSIs, the implementation of BCID2 allowed for early changes to antimicrobial therapy.

Disclosures
Kimberly C. Claeys, PharmD, Abbvie: Advisor/Consultant|bioMérieux Inc.: Advisor/Consultant|bioMérieux Inc.: Speaker|La Jolla Pharmaceuticals: Advisor/Consultant|Melinta Therapeutics: Advisor/Consultant
887. Associated factors with Monkeypox in patients with suspected infection in a university hospital in Colombia.
Authors: Arboleda Santiago , Mantilla Fabian , Reyes Elizabeth , Valderrama Sandra , Alvarez Carlos 
Published: November 2023

Abstract

Background
Monkeypox was an infection limited to the African continent, the study of which regains relevance after the breaking of its geographical barrier in May 2022. In Colombia, in agreement to the Colombian National Institute of Health 4090 cases have been confirmed and 97% have occurred in men. We evaluate epidemiological and clinical characteristics of people suspected of being diagnosed with monkeypox and we compare the differences between patients who underwent positive RT-PCR tests with those who had negative results in order to determine clinical variables that increase the possibility of having a positive result.

Methods
This is a cross-sectional case-control study between August and December 2022 in adult patients who consulted due to suspected Monkeypox infection in a university hospital in Bogota-Colombia. We characterized the different epidemiological and clinical characteristics of the disease. We performed an exploratory analysis of the variables related to a positive RT-PCR for Monkeypox. The cases were patients with positive RT-PCR and the controls were patients with a negative result. A multivariate analysis was carried out by unconditional logistic regression and the variables with a p&lt; 0.2 and that did not present collinearity were included in the model. All analyses were conducted in R software version 4.1

Results
A total of 162 medical records of patients with suspected diagnosis of smallpox were analyzed. 102 samples were RT-PCR positive for monkeypox and 60 were negative. Table 1 describes the bivariate analysis. All patients who had positive RT-PCR were MSM. In the multivariate model the associated factors with having a positive RT-PCR test for Monkeypox were: age (OR:0.01, CI95%:0.01-0.17), contact with a suspected or confirmed case (OR:6.08, CI95%:1.96-21.65), fatigue (OR:3.91, CI95%:1.47-11.43), arthralgia (OR:7.45, CI95%:1.48-58.41), lymphadenopathy (OR:10.46, CI95%:3.50-36.44) and perianal lesions (OR:18.64, CI95%:4.64-104.53).

Part1

Part 2

Conclusion
This study reaffirms the increased frequency of monkeypox infection in MSM and HIV-positive patients. In patients who consult for suspected monkeypox, there is an increased odds of infection in patients with contact with Monkeypox, fatigue, arthralgia, lymphadenopathy or perianal lesions.

Disclosures
All Authors: No reported disclosures
898. Influenza Surveillance in the US Veterans Health Administration (VHA): 2022-2023 Season
Authors: Lucero-Obusan Cynthia A , Schirmer Patricia , Edson Connor W , Oda Gina , Holodniy Mark 
Published: November 2023

Abstract

Background
Influenza causes seasonal epidemics with substantial morbidity and mortality. Veterans Health Administration’s (VHA) large elderly population is at higher risk for influenza complications, including hospitalization, and death. Herein we summarize VHA’s national annual surveillance data for influenza activity and vaccinations.

Methods
Influenza-like-illness (ILI) as well as influenza-coded outpatient visits and hospitalizations, laboratory testing, and antivirals were obtained from VHA data sources (10/2/2022-4/22/23) and compared to prior years and CDC data. Vaccinations were captured starting 8/1/2022, with rates calculated based on VHA users in each fiscal year. Influenza RT-PCR positive respiratory samples underwent whole genome sequencing (WGS) to analyze clade and antiviral resistance.

Results
Surveillance metrics are presented (Table). Vaccinations were decreased compared to 2021-22, but the used of adjuvanted vaccine was increased. Weekly ILI ranged from 0.4%-1.4% in primary/urgent care settings. Activity was highest for 2022 Week 48, matching national influenza trends (Fig.1). Testing found 23,297 influenza positives of 457,020 tests performed (5.1%). Median length of stay (3 days) for hospitalized patients and deaths (127, 3%) were stable. Among 115 deaths where influenza type was available, 110 had Influenza A and 5 Influenza B. Following two low activity seasons, total influenza positives, outpatient visits, and hospitalizations during 2022-23 tracked closer to seasons prior to the COVID-19 pandemic (Table, Fig.2). 411 samples (in 16 states) were sequenced (410 Flu A: 136 H1, 274 H3; 1 B/Victoria), representing 12 subclades, which aligned with CDC reporting. No drug resistance mutations were found (Fig.3).

Conclusion
For 2022-23, influenza vaccinations in VHA dropped but percent vaccinated was stable. For the first time, over half of VHA-administered vaccines were adjuvanted formulation. The influenza season was notable for an earlier than usual peak (late Nov/early Dec), with overall increased activity compared to the prior two seasons. Testing for influenza during 2022-23 season was decreased but remained higher than pre-COVID-19 pandemic testing levels. VHA influenza activity and WGS analysis tracks closely with national CDC reporting.

Disclosures
All Authors: No reported disclosures
909. Clinical features and management of a human monkeypox outbreak: a retrospective observational study in Harlem New York
Authors: Shaw Raphael , Schliep Tjark , Sivaplan Vel , Bratu simona , Mannheimer Sharon , Dowie Donna , Sayegh Mark , Hajihossainlou Behnam , Dickerson Erika , Sinsmyr Guerline 
Published: November 2023

Abstract

Background
In this paper, we report the descriptive, epidemiological, virologic and clinical features of the response to the investigational antiviral Tecovirimat, during the last Human Monkeypox outbreak in New City.

Methods
This is a retrospective observational study, based on data obtained from a convenient sample of patients evaluated for monkeypox infection at Harlem Hospital Infectious Diseases Clinic, from June 30th 2022 to September 1st 2022. Outbreak analysis was completed using grid-like/mapping approach to evaluate the distribution of the lesions. Statistical analysis was conducted using binary logistic and Chi-square analysis.
Mapping of lesions

Results
44 patients were included in the study 16 (36%) patients were immunocompromised with HIV with an absolute CD4 count ranging from 22 to 1048. Of the 44 patients, 30 (68%) were prescribed oral tecovirimat. Follow up showed that 13(43.3%) and 3 (3%) patients who received tecovirimat had complete resolution of symptoms at 7 days and 14 days respectively. 4 (9%) patients were lost to follow up and 2 (4.5%) were hospitalized for worsening symptoms. Overall medication was well tolerated with no reported events that were felt to be related to the medication.
Symptoms grid mapping showed a higher prevalence of lesions at the genital and rectal area, highly significant in the treatment group.
We were not able to establish a significant statistical correlation between HIV status/CD4 count and resolution of symptoms. However statistical analysis showed a significant positive correlation between treatment with Tecovirimat and resolution of symptoms at 14 days (P = 0.047).

Conclusion
The results published in the abstract are mostly descriptive of the sample and the general management including the use of Tecovirimat.
Most patients who received tecovirimat had a complete resolution of symptoms n= (53%) at 14 days. It is not clear whether this difference was attributable to the efficacy of the treatment versus the natural course of disease. Indeed, several patients in the non-treatment group were lost to follow up.
Further studies are needed to define the effect of severe immunosuppression and the efficacy of available antiviral drugs on the course of disease.

Disclosures
All Authors: No reported disclosures
910. Herpes Zoster in Children: A Literature Review
Authors: Simpson Chris , Dilley Anne , Viscidi Emma 
Published: November 2023

Abstract

Background
Herpes zoster (HZ), known as shingles, is caused by reactivation of the varicella zoster virus (VZV) and is characterized by a painful and/or itchy vesicular rash. The incidence of HZ in adults is approximately 4-10 per 1,000 person-years (PY). While the condition occurs mostly in older adults, it can develop in childhood after primary infection or rarely varicella vaccination (VV). The contemporary burden of HZ in children, and the impact of VV policies on incidence rates (IRs), are not well described.

Methods
A systematic literature search was conducted to identify studies reporting the incidence of HZ among pediatric populations (&lt; 20 or &lt; 18 years of age). A search of peer-reviewed literature published from 2010 onward in the PubMed and EMBASE databases was conducted of studies published through January 31st, 2023. While reviewing potentially relevant papers, reference lists were explored to discover additional peer-reviewed articles and reports. Publications were eligible for inclusion if they reported estimates of the IR of medically-attended HZ in nationally-representative samples of pediatric patients, using clearly stated and defensible methods.

Results
Sixteen publications meeting criteria were identified. IRs increased with age, from a median of 0.15 per 1,000 PYs in &lt; 1 year old to 1.88 per 1,000 PYs in 15-19 years of age. In 3 countries with long-standing VV programs, IRs were 0.38 per 1,000 PY in the US, 0.82 per 1,000 PY in Canada, and 1.2 per 1,000 PY in Germany. In countries without widespread VV, incidence was higher, ranging from 0.8 per 1,000 PY in Norway to 2.5 per 1,000 PY in the Netherlands. The median hospitalization rate in children across 5 studies was 2.0 per 100,000 per year (range: 0.4 to 3.7). Immunocompromised (IC) children are at higher risk for HZ; in two studies that compared HZ in IC and non-IC children, the incidence rate ratios were 5.7 and 8.6. Post-herpetic neuralgia, the largest contributor to the HZ health burden, is much less likely to develop in children.

Conclusion
Based on a contemporary literature review, the incidence of HZ was lower in the children than in adults and HZ IRs were lower in countries with routine childhood VV. The incidence in children increased with age and is higher in the immunocompromised.

Disclosures
Chris Simpson, MSPH, Epidemiologic Research & Methods: Advisor/Consultant Anne Dilley, PhD, Epidemiologic Research & Methods: Advisor/Consultant Emma Viscidi, PhD, MHS, Moderna: Employee|Moderna: Stocks/Bonds
918. Identification of novel druggable host targets for Middle East respiratory syndrome coronavirus using a quantitative phosphoproteomics approach
Authors: Chan Jasper F W , Hu Bingjie , Chik Kenn K H , Yuan Shuofeng , Chu Hin 
Published: November 2023

Abstract

Background
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease and extrapulmonary complications with a high mortality rate. The molecular mechanisms of MERS remain incompletely understood. Phosphoproteomics identifies proteins containing a phosphate group as posttranslational modification and allows rapid analysis of entire phosphorylation-based signaling networks. It has been increasingly used to study virus-host interactions and identify potential host-targeting treatments.

Methods
Label-free quantitative phosphoproteomics on MERS-CoV-infected lung epithelial Calu-3 cells was performed. A comprehensive siRNA library knockdown screen was then performed for all upregulated phosphoproteins followed by in-silico prediction with Group-based Prediction System 3.0 to identify the top-ranked kinases for further investigations. siRNA knockdown and kinase inhibitor treatment were then performed to validate the biological relevance of the identified host targets in MERS-CoV infection. Human dipeptidyl peptidase 4-knock in (hDPP4-KI) mice were used to evaluate the treatment effects of selected inhibitors.

Results
We identified more than 300 phosphopeptides that showed a change in phosphorylation status. This markedly perturbed host protein phosphorylation profile included many proteins that were involved in various cellular processes. siRNA library knockdown screen of all upregulated phosphoproteins followed by in silico prediction identified the 5 top-ranked kinases for further investigations. Both siRNA knockdown and kinase inhibitor treatment of these kinases resulted in the significant MERS-CoV load reduction in vitro. Treatment of hDPP4-KI mice with selected kinase inhibitors led to improved clinical outcome with significantly higher survival rate, less body weight loss, and lower lung viral burden.

Conclusion
Quantitative phosphoproteomics is a useful platform for identifying host factors involved in MERS-CoV infection. Inhibition of these host factors may be a potential treatment strategy for this highly pathogenic coronavirus infection.

Disclosures
All Authors: No reported disclosures
1136. A Systematic Literature Review of Disparities That May Influence Health Equity in Invasive Meningococcal Disease Prevention in the US
Authors: Begum Shahina , Herrera-Restrepo Oscar , Rolland Catherine , Purushotham Sneha , Hortobagyi Linda , Kocaata Zeki 
Published: November 2023

Abstract

Background
Meningococcal serogroup A, C, W, Y (MenACWY) and B (MenB) vaccines are recommended in the US to prevent invasive meningococcal disease (IMD), a rare but life-threatening disease. Yet the suboptimal uptake of and adherence to these vaccines may relate to inequities for healthcare access. This systematic literature review (SLR) synthesized the US evidence on disparities associated with IMD prevention.

Methods
Embase, MEDLINE and six conferences were searched and handpicked studies included from 01/01/2012 to 23/08/2022. Studies were screened twice against inclusion criteria (Table 1) via a standardised form. Newcastle Ottawa Scale was used for quality assessment. Synthesis findings reported here were from a broader SLR on IMD risk, prevention and control.

Results
The SLR found 26 studies, 14 relevant for prevention (Table 2-3). MenACWY series completion had higher odds for adolescents with a family annual income &gt;$75,000 vs. ≤$30,000. Individuals from families below poverty status (annual income ≤$75,000 in 2021) had lower MenB vaccination coverage rates. MenACWY booster compliance was lower in uninsured vs. insured adolescents. Higher odds for ≥1 dose of MenB vaccine were observed if individuals had Medicaid vs. private insurance. For parents/guardians of ≥1 dependent of 16-19 years old, with some insurance was significantly associated with MenB vaccine initiation vs. no insurance. Adolescents living outside a metropolitan statistical area had lower vaccination coverage with ≥1 MenACWY than adolescents in MSA principal cities. MenB series completion rates were lower in rural vs. urban areas in commercial insured populations. Non-Hispanic Black and Hispanic population were more likely to be vaccinated for MenB compared to non-Hispanic Whites, however one study found the opposite. MenB series completion were lower in the Black versus White Medicaid populations.

Conclusion
Disparities in IMD prevention were reported for race/ethnicity, geographical factors, income/poverty level and health insurance status. Simplification of current recommendation (e.g., combination vaccine with increased convenience and reduced injections in the IMD vaccination schedule) could improve low uptake and adherence in disadvantaged groups.

Disclosures
Shahina Begum, GSK: Employee Oscar Herrera-Restrepo, PhD, GSK: Stocks/Bonds Catherine Rolland, PhD, Evidera: Advisor/Consultant Sneha Purushotham, MSc, Evidera: Advisor/Consultant Linda Hortobagyi, MSc, GSK: Contractor Zeki Kocaata, PhD, GSK: Stocks/Bonds
1137. The Value of Invasive Meningococcal Disease Combination Vaccine – a Qualitative Study of Adolescents and Parents/Caregivers’ Preferences in the US
Authors: Begum Shahina , Cabrera Eliazar Sabater , Hortobagyi Linda , Khera Twinkle , Correa Selene Camargo , Batchelder Laurie , Kocaata Zeki 
Published: November 2023

Abstract

Background
MenACWY and MenB are commonly used vaccines to prevent invasive meningococcal disease (IMD), targeting serogroups A, B, C, W, Y. MenABCWY combination vaccines are under development and could provide increased vaccine coverage of serogroups. This qualitative study aimed to identify concepts affecting preferences in adolescents (Ado) and parents/caregivers (P/C) decision making towards combination vaccine in the US.

Methods
Two focus group discussions (FGD), 90-minutes with Ado (16-23 years) and P/C of adolescents (16-18 years) were conducted (Table 1). Guides were developed based on a targeted literature review to investigate preferences for potential features of a combination vaccine. Participants were presented with IMD and vaccines information. Important/least important factors for decision-making were transcribed in response to open-ended/probes questions. FGDs were coded to apply thematic assessment. Results were synthesized separately by moderator-probed and spontaneously mentioned themes. Percentages were calculated on participant numbers contributing to a theme.

Results
Thirteen participants were included in FGDs (6 Ado, 7 P/C, 57% P/C with college or lower degree, Table 2). Ado preferred a combination vaccine which provided time saving (100%) and convenience (83%) by reducing the number of injections in the immunization series (100%) and number of visits (100%). P/C considered injection site discomfort (71%) as an important decision factor for a combination vaccine, however Ado considered this as least important (100%). Both groups considered impact on healthcare system and environment as least important for a combination vaccine (55%) (Table 3). Cross-protection against other infectious disease (55%, probed) and spontaneous themes (e.g. duration of protection, effectiveness, side effects and dosing interval) emerged (Table 4). These concepts were considered relevant for combination vaccine decision-making, although could be applicable to IMD vaccination more generally.

Conclusion
The findings suggest vaccine-receivers preferred a combination vaccine covering serogroups A, B, C, W, Y, with simplified schedules (e.g. fewer visits and injections) and potential cross-protection against other infectious diseases.

Disclosures
Shahina Begum, GSK: Employee Eliazar Sabater Cabrera, PhD, GSK: Employee|GSK: Stocks/Bonds Linda Hortobagyi, MSc, GSK: Contractor Twinkle Khera, Mtech, IQVIA: Advisor/Consultant Selene Camargo Correa, PhD, IQVIA: Advisor/Consultant Laurie Batchelder, PhD, IQVIA: Advisor/Consultant Zeki Kocaata, PhD, GSK: Stocks/Bonds