bluuebunny/crossref_metadata_2025 huggingface dataset:
874. Rapid Prediction of Antibiotic Susceptibility in Blood Stream Infections Using Direct Sequencing from Blood Cultures Coupled with Neighbour-Typing Prediction Algorithms.
Authors: Purssell Andrew , Carroll Amanda C , Puchacz Natalia , Mortimer Leanne , MacFadden Derek
Published: November 2023

Background

Increasing rates of antimicrobial resistance in Gram-negative (GN) bacteria make empiric treatment challenging. Culture-based techniques form the basis of pathogen and antibiotic susceptibility determination yet are limited by long turn-around-times that can prolong the time a patient remains on inappropriate therapy. Direct sequencing of positive blood cultures coupled with neighbour-typing prediction algorithms could help anticipate antibiotic susceptibility and improve selection of empiric therapy. We sought to develop a rapid metagenomic diagnostic workflow and evaluate its performance for blood stream infections.

Methods

We developed a metagenomic workflow for pathogen identification and prediction of antibiotic susceptibilities outlined in Figure 1. We performed Nanopore-based metagenomic sequencing on positive blood cultures from critically ill patients admitted to a quaternary care center. Isolates belonging to six common GN blood stream pathogens were subjected to a rapid lineage-based prediction algorithm (RASE) that predicts antibiotic susceptibility against a reference set of local isolates. We calculated test performance of predictions compared to phenotypic susceptibility testing. Impact of prediction on post-test probability was calculated for each agent and in aggregate benchmarked against minimum susceptibility thresholds for empiric treatment of 80% for mild infections and 90% for moderate-severe infections.

Results

We performed metagenomic sequencing and RASE analysis on twelve unique GN blood culture samples with predictions available in 2.5 hours. Across all organisms and antibiotics tested, sensitivity and specificity were 0.87 (95% CI 0.76-0.94) and 0.56 (95% CI 0.31-0.78) although these values approached one for some agents. Impact of RASE predictions on probability of susceptibility is shown in Figure 2. For all antibiotics combined, baseline susceptibility was 79% but improved to 88% or reduced to 47% when RASE predicted a susceptible or resistant phenotype respectively, an effect echoed by specific agents tested.

Probability of susceptibility to specific agents or in aggregate after prediction of a susceptible or resistant phenotype by RASE. This was benchmarked against minimum susceptibility thresholds for empiric treatment of 80% for mild infections and 90% for moderate-severe infections.

Conclusion

We developed a novel metagenomic diagnostic workflow for rapidly predicting antibiotic susceptibility of common GN blood stream pathogens that could improve early selection of empiric therapy.

Disclosures

All Authors: No reported disclosures
878. Clinical impact of plasma cell-free metagenomic next-generation sequencing: A retrospective cohort study
Authors: Vasishta Shilpa , Vo Christopher , Neogi Sushrita , Alahmdi Bayan , Sullivan Timothy , Gitman Melissa R
Published: November 2023

Background

Plasma cell-free metagenomic next-generation sequencing (cf-mNGS) offers potential for rapid, noninvasive diagnosis of complex infections, though clinical impact remains incompletely characterized. Here, we describe impacts on diagnosis and antimicrobial management among patients evaluated with plasma cf-mNGS.

Methods

Patients evaluated with plasma cf-mNGS (Karius®) in the Mount Sinai Health System from January 1, 2019 to December 23, 2022 were included. Cases were each reviewed independently in the medical record by two investigators using a standardized data collection form with discrepancies adjudicated collectively. Data were analyzed descriptively.

Results

Plasma cf-mNGS was sent for 37 patients of whom 29 (78%) were immunocompromised. 26 (70%) had prior invasive diagnostics. Median time from admission to NGS was 15 days. NGS was positive in 24 cases (65%), with results reflecting 20 bacterial infections, 9 viral, and 4 fungal (14 monomicrobial, 10 polymicrobial). Results were deemed clinically relevant in 18 cases (49%) including 12 positive and 6 negative tests. Testing led to antimicrobial changes in 11 cases (30%), discontinuation in 3 cases (8%), and no change in 23 cases (62%). After plasma cf-mNGS (compared with prior), fewer patients received 3 or 4 antimicrobials, while more received 0, 1, or 2 antimicrobials (Fig. 1A); fewer patients received combined antibiotic/antifungal therapy, while more received no antimicrobials or antifungal therapy alone; there was no change in use of antibiotic therapy alone (Fig. 1B). Final diagnoses included 15 bacterial infections (41%), 9 fungal (24%), 0 viral, and 7 noninfectious conditions (19%). Final diagnoses were attributed to NGS in 6 cases (16%), other diagnostics in 9 cases (24%), and both NGS and other diagnostics in 6 cases (16%); in the latter group, NGS provided a diagnosis prior to another study in 3 cases by intervals of 13, 19, and 72 days, respectively.

A. Changes in number of antimicrobials, B. Changes in classes of antimicrobials

Conclusion

Plasma cf-mNGS, as an adjunct to traditional methods, may provide unique or expedited diagnosis of bacterial or fungal infections, accelerate diagnosis of noninfectious conditions, or inform changes in broad-spectrum antimicrobial regimens. Continued study is warranted to delineate clinical impact and optimal use of plasma cf-mNGS.

Disclosures

All Authors: No reported disclosures
882. Gender Disparities in Faculty Rank and Mentorship opportunities Within a Sample of US Academic Infectious Disease Divisions
Authors: Hollenberg Benjamin , Cawcutt Kelly , Marcelin Jasmine R , Zimmer Andrea J , Cortes-Penfield Nicolas W
Published: November 2023

Background

Gender inequities in promotion within academic medicine, including academic infectious diseases (ID), are well-documented. Effective mentorship is a key component of career advancement and data show that same-gender mentorship can be valuable for women junior faculty learning to navigate academia. We compared the gender, bibliometrics, and mentorship opportunity distributions of ID faculty at each academic rank (instructor vs assistant, associate, or full professor) across several US medical centers.

Methods

We randomly selected five academic medical centers from the US World News & Reports top 100 medical school rankings that had ID division websites including a faculty listing with ranks and years since graduation. We recorded each physician faculty’s rank and gender based on the written biography, using a validated tool (genderize.io) to determine gender if not given, and collected each faculty’s traditional bibliometric data via Google Scholar.

Results

We included 221 faculty (107 women) from five ID divisions (mean 44 faculty). Women accounted for 5/12 (42%) of instructors, 62/109 (57%) of assistant professors, 19/44 (43%) of associate professors, and 21/56 (38%) of full professors. Junior faculty women (instructor or assistant) had a median 0.6 potential same-gender senior mentors per mentee within their divisions versus 1.1 for men; associate professor women had a median 1.0 potential same-gender senior mentor per mentee versus 1.7 for men. Measures of academic productivity, such as annual publications, citations, and h-index growth since graduation from fellowship were similar between men and women.

Conclusion

Our findings support published studies demonstrating lower proportions of women in successively senior positions within academic ID divisions despite similar scholarly activity and suggest that fewer within-institution opportunities for senior mentorship might be a contributing factor.

Disclosures

Andrea J. Zimmer, MD, Allovir: Grant/Research Support
889. The age of RSV cases changes consistently over the course of annual epidemics: potential insights into RSV transmission dynamics based on surveillance data from seven countries.
Authors: Casalegno Jean-Sebastien , Rodrigues Ana Paula , Lee Vernon , Cohen Cheryl , Sue Huang Q , Caicedo Alfredo Bruno , Guiomar Raquel , Ang Li Wei , Cook Tim , de Mora Domenica , Bangert Mathieu , Kramer Rolf , Staadegaard Lisa , Heemskerk Susanne , van Summeren Jojanneke , Meijer Adam , Paget John , Caini Saverio , Teirlinck Anne
Published: November 2023

Background

RSV infections affects people of all ages but the seasonality of RSV among different age groups have not been thoroughly examined. In this study, we investigated changes in the age distribution of RSV cases during the course of annual epidemics.

Methods

We analyzed surveillance data (2008-2019) from the Netherlands, the city of Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand using the Global Epidemiology of RSV (GERi) study database. We defined annual RSV seasons as the period from July to June in the Northern hemisphere, or the calendar year in the tropics and Southern hemisphere. Within each season, we divided the data into “epidemic quartiles”, corresponding to each quartile of RSV cases in the season. We used multilevel multinomial logistic regression models with season as the higher-level variable to assess whether the likelihood of RSV cases being aged < 1 year or ≥5 years (vs. those aged 1 to < 5 years) changed over time during the season.

Results

A total of 27,391 RSV cases were included. Across all countries, the odds of RSV cases being aged < 1 year (vs. 1 to < 5 years) were significantly higher in the fourth epidemic quartile compared to the first quartile; the relative risk ratio (RRR) ranged between 1.35 in Lyon, France, and 2.56 in the Netherlands. Similarly, the odds of RSV cases being aged ≥5 years (vs. 1 to < 5 years) were significantly higher in the fourth epidemic quartile compared to the first quartile (except in Singapore); the RRR ranged from 1.75 in Ecuador to 6.70 in Lyon, France. The results were consistent when stratifying the data by level of care (primary vs. secondary) or using a lower cut-off of six months of age.

Conclusion

The age distribution of RSV cases changes over the course of a season, with infants (< 1 year) and older children (≥5 years), adults, and elderly people constituting a higher proportion of RSV cases in the later phases of annual epidemics. These findings provide potential insights into the transmission dynamics of RSV and may inform prevention and control measures, e.g. the implementation of targeted age-specific interventions. Funding: This research was funded by a collaborative agreement with Sanofi / AstraZeneca and is part of the RODEO research program for RSV disease.

Disclosures

Mathieu Bangert, PhD, Sanofi: Staff member Rolf Kramer, n/a, Sanofi: Stocks/Bonds John Paget, n/a, Sanofi Pasteur: Grant/Research Support
896. Epidemiology and effect of pandemic on regional coxsackie viral testing
Authors: Kordi Ramesh , Chang Arthur , Hicar Mark D
Published: November 2023

Background

Coxsackie viruses (CV-A, CV-B), are a member of Picornaviridae of the genus Enterovirus and are commonly considered in summer and fall pediatric febrile illnesses. We noted an increase in CV testing post-pandemic and a lack of literature on the interpretation of seroprevalence and interpretation of CV testing.

Methods

We accessed a regional health database (HEATHeLINK), between February 2017 and February 2023, and examined CV serum testing by Complement Fixation (CF). We analyzed data by age (21 years of age cutoff), month of testing, and compared testing pre-Covid-19 (February 2017-Feb 2020) and post-Covid-19 (March 2020-February 2023). We used the chi-square test to compare seropositivity between groups and SPSS version 28 for statistical analysis. CF titers ≥ 1:8 were considered positive.

Results

901 serum CV-A tests were performed in 263 patients (median age 42, range 3-89) among whom 6 (2.3%) were positive for at least one serotype. No statistical difference was found between age groups (0.7% vs. 0.8%, p=0.9). The number of tests performed nearly doubled in the post-pandemic period with a notable lack of positive tests in the summer. 891 CV-B tests were performed in 238 patients (median age 41, range 3-80), among whom 129 (54.2%) were positive for at least one serotype. Positive test results were more notable in adults (26.7% vs. 37.7%, p=0.014). The testing had a higher rate of positive results pre-pandemic (176/381, 46.2% vs 145/510, 28.4%, p-value< 0.001). Tests and positive results were low for the first year of the pandemic (2020) compared to the following years, and the seasonality of testing and positive cases showed variability compared to pre-pandemic tests. In accessing a tertiary care center’s data, with a median age of 7 years old, testing was also notably increased post-pandemic (50 and 59 persons tested in 2021 and 2022 compared to an average of 13.5 cases pre-2021).

Data is from Western New York regional health database HEALTHeLINK. Gray and black dotted line represents two years preceding the pandemic and show normal seasonality pattern. The green dashed line shows that the number of positive cases during social distancing in our area, and blue and purple lines represent following years and display variability in cases clustering.

Conclusion

Testing increased post-pandemic and results show variability in seasonality and utilization compared to pre-pandemic. Effects of social isolation and secondary viral circulation are potential explanations. Further detailed studies that include a higher level of confidence in diagnosis are warranted.

Disclosures

Mark D. Hicar, MD/PhD, Pfizer: site investigator for 2 trial
899. Epidemiology of the 2022 Mpox Outbreak in the US Veterans Health Administration (VHA)
Authors: Lucero-Obusan Cynthia A , Oda Gina , Schirmer Patricia , Edson Connor W , Trevino Christina , Holodniy Mark
Published: November 2023

Background

Mpox, an orthopoxvirus zoonotic disease, is endemic to Africa. In May 2022, cases were reported concurrently in endemic and non-endemic countries, including the US. WHO and DHHS subsequently declared Mpox a public health emergency. Herein, we examine Mpox in the Veterans Health Administration (VHA).

Methods

Mpox diagnostic and whole genome sequencing (WGS) results, demographics, hospitalizations, deaths, diagnosis codes, exposure information, pharmacy and immunization data were obtained from VHA data sources and/or chart review (5/23/22-4/11/23). Association of risk factors with Mpox was determined using multivariable logistic regression.

Results

Of 1,034 Veterans tested, 251 (24%) were orthopox positive in 32 states (peaking in August 2022), with 50.2% HIV+ and 32.7% with other concurrent sexually transmitted infections (STIs). Significant associated Mpox risk factors included: male gender, age < 55 years, non-Hispanic Black race/ethnicity, and HIV positivity. Among 193 with confirmed Mpox, 90% reported intimate contact and/or an epi link to another Mpox case; 83% were men who have sex with men (MSM); 24% received Tecovirimat; and 11% were hospitalized with no deaths attributable to Mpox. 13% had reported or documented smallpox vaccine(s) >2 weeks prior to exposure (primarily as active duty) and an additional 14 (7%) received JYNNEOS < 2 weeks prior to presentation (or precise date not recorded). Review of 80 patients with evaluable WGS results found all were clade IIb, representing 10 different lineages from 18 states and District of Columbia. Serial WGS samples (n=3) evaluated after Tecovirimat regimens revealed no drug resistance. Since July 2022, over 4,300 Veterans have received at least 1 dose of smallpox/Mpox vaccine with over 6,700 doses having been administered at a VA facility.

Conclusion

The Mpox outbreak primarily affected younger, MSM, non-Hispanic Black race and HIV+ males among those in VHA care. Although some were vaccinated, the protective effect may have been diminished, or it was received too close to the exposure to provide adequate protection. Viral diversity was noted across geographic regions. Veterans with risk factors would benefit from vaccination and risk reduction strategies for Mpox and other STIs.

Disclosures

All Authors: No reported disclosures
906. Risk of Shingles among Patients Aged 45–49 versus 50–54 Years in the US, by Immune Status
Authors: Miles Amanda C , McGrath Leah , Malhotra Deepa , Welch Verna
Published: November 2023

Background

Shingles burden has historically focused on older adults, with the currently licensed vaccine in the US approved for adults aged ≥50 years. Our study aimed to estimate the incidence of shingles among adults aged 45–49 years and to ascertain whether the adjusted incidence rate (IR) was similar to adults aged 50-54 years, stratified by immune status.

Methods

We conducted a retrospective analysis of de-identified Optum Clinformatics® Data Mart insurance claims to identify patients in the US diagnosed with shingles each year between 2015–2021. Adults aged 45–54 were included if they were enrolled on January 1 of a given year (index date), had at least 1 year of prior continuous enrollment, and had no shingles diagnosis in the 90 days prior. Adults could contribute to multiple calendar years, and were followed from index until the earliest of 1) shingles diagnosis, 2) disenrollment, 3) December 31 of the calendar year, or 4) death. Yearly IRs were calculated using Poisson regression models and combined time period IRs used generalized estimating equations (GEE). Models were adjusted for demographics, comorbidities, and healthcare utilization and stratified by immunocompromised (IC) status at baseline. IRs were reported as events per 100,000 person-years.

Results

A total of 9.4 million unique patient-year combinations were identified in the database. Patient demographics for 2021 are shown in Table 1. The IR of shingles from 2015–2021 was approximately two-times higher for IC versus immunocompetent patients, and rates were similar for adults aged 45–49 and 50–54 (Figure 1). During the same period, IRs in immunocompetent patients aged 45–49 and 50–54 were 489.3 (95% CI: 480.6, 498.2) and 579.1 (95% CI: 569.1, 589.3) respectively. However, the difference between the IRs for the two age groups narrowed over time. The shingles IR among adults aged 45–49 in 2021 was comparable to the IRs for pneumococcal pneumonia observed when a vaccine recommendation was made for pneumonia in high-risk populations (Figure 2).

Conclusion

Shingles incidence among adults aged 45–49 versus 50–54 was similar for IC patients. In recent years, IRs for immunocompetent patients aged 45–49 vs 50-54 were closer. There is an unmet need for shingles prevention in adults aged 45–49.

Disclosures

Amanda C. Miles, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Leah McGrath, PhD, Pfizer: Employment|Pfizer: Stocks/Bonds Verna Welch, PhD, MPH, Pfizer Inc.: Stocks/Bonds
907. Age-stratified seroprevalence of respiratory syncytial virus in Korean population
Authors: Nham Eliel , Jang A Yeung , Hyun Hakjun , Yoon Jin Gu , Noh Ji Yun , Cheong Hee Jin , Kim Woo Joo , Ji Hyun Jung , Seo Ho Seong , Song Joon Young
Published: November 2023

Background

Respiratory syncytial virus the two modified prefusion (preF) protein antigens (DS-Cav1 and SC-TM) and the fusion (G) protein, (RSV), a major childhood respiratory pathogen, is gaining attention as an important pathogen in adults also, especially in older people and the immunocompromised. Studies on RSV seroprevalence in the adult population are limited, even though it is important to know the level of preexisting immunity to RSV now that approval of RSV vaccines seems imminent. Therefore, we aimed to analyze antibody levels against RSV across age groups.

*This study was funded by the grant of the Ministry of Food and Drug Safety of South Korea (21172MFDS179).

Methods

A total of 150 serum samples were collected from 30 subjects of each age group (under 5 years, 5–18 years, 19–49 years, 50–64 years, and ≥65 years). Considering higher RSV disease burden in infants than older children, children under 5 were further divided into two age groups including 0–12 months and 13–59 months. Age-stratified seroprevalence was estimated using ELISA targeting the two modified prefusion (preF) protein antigens (DS-Cav1 and SC-TM) and the fusion (G) protein, the major immunogens and popular vaccine targets. Seropositivity was determined based on the concentration of medium-titer RSV antiserum manufactured by the United States National Institute of Health.

Results

Antibody titers against SC-TM were similar across age groups. Antibody titers against DS-Cav1 were higher than those against SC-TM in all age groups except children aged 0–12 months. There was no significant difference in antibody titers between children aged 0–12 months and 13–59 months. Only about one fifth participants aged under 5 and over 65 were seropositive to RSV preF.

Conclusion

RSV seroprevalence was low overall. This study supports the importance of vaccination against RSV in infants and people over 65.

Disclosures

Hee Jin Cheong, M.D.,Ph.D., Sequiris: Advisor/Consultant
908. Clinical Characteristics and Outcomes of Cytomegalovirus Disease in HIV-Negative Non-Transplant Patients, a Propensity Score Match Analysis
Authors: Salter Ixchel T , Corbisiero Michaele-Francesco , Chastain Daniel B , Montoya Jose G , Razonable Raymund R , Martínez Andrés F Henao
Published: November 2023

Background

Cytomegalovirus (CMV) infects millions in the US and is a source of comorbidity among immunocompromised patients. Despite its prevalence, there is limited data on clinical characteristics or outcomes among HIV-negative, non-transplant (NHNT) patients in population-based cohorts.

We aim to evaluate a multicenter US-based network to obtain clinical characteristics and outcomes of NHNT patients with CMV disease and explore potential prognostic clinical characteristics implicated in increased morbidity and mortality.

Methods

This is a US-based multicenter, population-based, retrospective cohort study. We queried TrinetX, a global research network, to identify patients with a CMV disease by ICD-10-CM codes and serum and PCR > 5000 IU/mL. We captured comorbidities diagnosed within 90 days of CMV infection diagnosis, symptoms noted within 30 days, and outcomes of interest at 30 days and 1 year. Primary outcome was all-cause mortality. Secondary outcomes were hospitalization and CMV disease-related complications. We performed a propensity score-matched analysis comparing clinical characteristics among patients who survived versus non-survivors at 90 days.

Results

We found 1123 patients with evidence of CMV disease. The mean patient age was 53 years, 48% men and 50% white. Aplastic anemia and neoplasms were the most common comorbidities (Table 1). Thromboembolism was a common complication (15%). Half of the patients had dyspnea, fever, abdominal pain, and nausea. CMV disease was associated with 14%, 22%, and 26% mortality at 30 days, 90 days, and one year, respectively. 35% of patients required hospitalization within 30 days. After propensity score matching, we had 278 patients in each cohort. Dyspnea and weakness were linked to increased 90-day mortality (Figure 1). Purpura, encephalopathy, and sepsis were more common in patients who died. High CMV serum viral load and ferritin were associated with increased mortality.

Conclusion

NHNT patients with CMV disease often have underlying comorbidity, commonly aplastic anemia, and neoplasms. CMV disease was associated with thrombosis and a high risk of hospitalization and mortality. Vascular disease, sepsis, high viral load, and cell lysis markers were prognostic factors for mortality in this cohort.

Disclosures

Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support
912. Influence of a Global Pandemic on Bronchiolitis at a Bronx Hospital
Authors: Rosenberg Michael , Schaeffer Karen , Boni Alexandra J , Strydom Christiaan
Published: November 2023

Background

Bronchiolitis is a common respiratory illness among young children, particularly during the winter season. The illness is usually caused by a viral infection, with the most common pathogens being respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (hMPV). The COVID-19 pandemic has led to changes in healthcare-seeking behavior and infection control practices that may have affected the incidence of other viral diseases.

Methods

This study aimed to compare the rates of bronchiolitis at a community hospital in The Bronx, New York before, during, and after the COVID-19 pandemic and identify the viruses that caused it. We identified all patients admitted to the hospital with a diagnosis of bronchiolitis from July 2019 to January 2023. We conducted a retrospective analysis on these patients including length of hospital stay and viral test results.

Results

We included a total of 220 bronchiolitis cases in the analysis. Prior to the COVID-19 pandemic the number of bronchiolitis admissions peaked from November 2019 through January 2020. During the first year of the pandemic, 2020, there was no significant bronchiolitis peak. In 2021, there was a longer season with bronchiolitis cases from July through January, although it did not have as sharp of a peak as 2019. In 2022, there was a large peak in September-December with almost double the cases at the peak compared to 2019. In almost half of the cases, RSV was identified. In one-fourth of cases, there was no organism identified. HRV and hMPV were the next most common viruses. Covid-19 identified as a cause of bronchiolitis in October and November 2022 only.

Bronchiolitis Admissions by Month July 2019 to January 2023

Conclusion

Our findings show a significant decrease in the rate of bronchiolitis during the COVID-19 pandemic compared to the pre-pandemic period, with an increased rate of bronchiolitis after the COVID-19 pandemic. These findings suggest that the implementation of public health measures to mitigate the spread of COVID-19 may have inadvertently reduced the transmission of other respiratory viruses, with a shift in epidemiology after these measures were lifted. However, ongoing surveillance is needed to determine whether this shift in viral epidemiology is temporary or represents a long-term trend.

Disclosures

All Authors: No reported disclosures
913. Incidentally Positive Measles Results with a Commercially Available Multiplex Polymerase Chain Reaction Panel for Exanthems — Tennessee, 2022–2023
Authors: Thomas Christine , Hartley Amanda , Newhouse Caitlin N , Jones Timothy F , Schaffner William , Fill Mary-Margaret A , Dunn John R
Published: November 2023

Background

In January 2023, the Tennessee Department of Health (TDH) received report of a positive measles result from a multiplex polymerase chain reaction (PCR) panel ordered to evaluate a fever and rash in a child. Immediate public health investigation concluded that the positive test was because of recent measles vaccination. Because multiplex PCR tests have not typically included measles, we assessed patient characteristics, provider responses, and measles virus strain when multiplex PCR identified measles to guide public health response in Tennessee.

Methods

We retrospectively identified Tennessee residents who tested positive for measles by 2 multiplex PCR panels, commercially available since 2022, that include 7–9 viruses and Streptococcus pyogenes. We queried the state immunization registry for measles vaccine records for those persons and asked ordering providers about their clinical assessment, test use, and response to the positive result. CDC performed the Measles Vaccine (MeVA) assay (real-time RT-PCR) on available clinical specimens.

Results

Of 296 multiplex PCR tests on Tennessee residents, 7 (2.4%) were positive for measles. Median age was 1 year (range: 1–6 years). All 7 received a measles vaccine within 8–15 days before the test. Among 7 providers, 6 did not suspect measles prior to testing. All ordered testing to evaluate a rash, with or without fever, and none were aware of patient exposure to persons with measles. After the positive result, 2 providers contacted TDH for guidance, 4 attributed the result to recent vaccination, and 1 reported not having received the test result. Three patients tested positive for additional viruses in the panel including enteroviruses (n = 2), human herpesvirus type 6 (n = 2), human herpesvirus type 7 (n = 1), and Epstein-Barr virus (n = 1). MeVA testing of 2 specimens identified measles vaccine strain in 1 specimen and an inconclusive result in the other.

Conclusion

Inclusion of measles in multiplex PCR panels can incidentally identify measles virus in recently vaccinated persons, requiring MeVA testing to confirm vaccine strain. In recently vaccinated persons, medical and public health professionals must carefully consider use and interpretation of measles results in multiplex PCR panels.

Disclosures

All Authors: No reported disclosures
914. Incidence of Herpes Zoster and Postherpetic Neuralgia and Herpes Zoster Vaccination in a United States Administrative Claims Database
Authors: Jain Purva , Embry Alan , Arakaki Brent , Estevez Irisdaly , Marcum Zachary , Viscidi Emma
Published: November 2023

Background

An estimated one in three adults in the United States (US) will develop Herpes zoster (HZ) during their lifetime, with substantially increased risk after age 50. Approximately 15% of individuals with HZ develop postherpetic neuralgia (PHN). HZ is vaccine-preventable, and vaccination is currently recommended for those 50 years of age and older, as well as individuals 19 years of age and older with weakened immune systems. Contemporary data on HZ vaccination, and the burden of HZ and PHN in US adults, is needed.

Methods

This observational cohort study was conducted using administrative medical and pharmacy claims data from HealthVerity and included insured individuals (commercial, Medicare Advantage, or Medicaid plans) across the US. Among patients with continuous enrollment from 01/01/2019 to 05/31/2022, the distribution of patients with 1 and 2 doses of Shingrix (Recombinant zoster vaccine) was estimated. Crude and US age-sex standardized incidence rates of HZ and PHN were calculated from 01/01/2019 to 12/31/2021, by calendar year, in persons >19 years. HZ was defined as >1 ICD-10 diagnosis code for HZ. PHN was defined as >1 ICD-10 diagnosis code for PHN. Analyses were stratified by age, sex, and immunocompromised status.

Results

Among those >50 years (N=25,286,865), 4.3% (N=1,087,066) received 1 dose and 9.0% (N=2,273,827) received 2 doses of Shingrix anytime from 01/01/2019 to 05/31/2022.

The standardized annual incidence rates of HZ from 2019-2021 ranged from 542 to 685 per 100,000 person-years (py) and from 35 to 38 per 100,000 py for PHN. The incidence rates of HZ and PHN were higher among females, older adults, and immunocompromised individuals.

Conclusion

In this analysis in a US claims database, 9% of persons aged 50+ years received 2 doses of the Shingrix vaccine. Herpes zoster and PHN were more frequent among older adults, females, and immunocompromised individuals. This study provides contemporary, representative estimates of the incidence of herpes zoster and PHN, as well as the frequency of herpes zoster vaccination, which is important information on disease burden in the US.

Disclosures

Alan Embry, PhD, Moderna Therapeutics: Stocks/Bonds Brent Arakaki, BS, Aetion, Inc.: Employee Emma Viscidi, PhD, MHS, Moderna: Employee|Moderna: Stocks/Bonds
924. D-Mannose Metabolome Regulates Influenza A Disease via Immunometabolic Reprogramming
Authors: Liang Ronghui , Yuan Shuofeng , Ye Ziwei , Chan Jasper F W
Published: November 2023

Background

Host survival depends on the elimination of viruses and mitigation of tissue damage. Host tolerance to viruses depends on the severity of collateral damage by exuberant innate immune response which also diverts energy away from essential physiological functions.

Methods

Using influenza A H1N1 virus as the study object, we performed targeted quantitation of metabolites on the human lung A549 cells to demonstrate the metabolic profile before and after virus infection. Meanwhile, the real-time glycolysis rate with and without D-mannose supplement, in the context of H1N1 infection, was monitored by the Seahorse XF Analyzers. For in vivo study, BALB/c mice (n=5 per group) were orally administrated with 2g/kg/day of mannose or PBS control after lethal challenge with H1N1 until 6 days post-infection (dpi), followed by health surveillance until 14dpi. For the delayed antiviral treatment, we recorded the survival rate of H1N1-infected balb/c mice with the combinational treatment of zanamivir (50mg/kg/day, I.P.) and mannose (2g/kg/day, P.O.) from 2dpi to 6dpi. The mice receiving PBS treatment or zanamivir alone were taken as controls (n=5).

Results

The modulation of D-mannose flux rewired the H1N1-triggered immunometabolic response cascade and reduced tissue damage. Mechanistically, D-mannose competed with glucose with the same transporter(s) and hexokinase but accumulates as mannose-6-phosphate, which slowed down the glycolysis rate, reduced mitochondrial reactive-oxygen-species and succinate-mediated hypoxia-inducible factor-1α, and thus reduced virus-induced proinflammatory cytokine production. Administration of D-mannose alone or in combination with Zanamivir protects against mortality after a lethal dose of influenza A virus challenge in vivo.

Conclusion

These results highlight a potential therapeutic strategy in which reprogramming of host-metabolism by D-mannose for the therapeutic cure of influenza diseases.

Disclosures

All Authors: No reported disclosures
926. Risk factors for post-letermovir cytomegalovirus (CMV) reactivation in allogeneic hematopoietic stem cell transplant (HSCT) recipients
Authors: Mendoza Maria Alejandra , Thoendel Matthew J , Razonable Raymund R , Alkhateeb Hassan
Published: November 2023

Background

Letermovir (LTMV) is approved for CMV prophylaxis during the first 100 days after HSCT. Thereafter, CMV reactivation (CMVr) may still occur. This study aims to evaluate the incidence and risk factors for any CMVr and clinically significant CMV infection (csCMVi) in patients who received LTMV prophylaxis.

Methods

Retrospective multicenter cohort study of HSCT patients who received 100 days of LTMV prophylaxis from 08/2018 to 09/2022. Categorical and continuous variables were compared with Fisher’s exact and Kruskal-Wallis test respectively. Logistic regression was used to identify risk factors.

Results

Of 115 HSCT patients, 28 had CMVr after LTMV prophylaxis (Table 1), including 21 with csCMVi (Table 2). Of note, 29 (25.2%) patients had breakthrough CMV during LTMV prophylaxis. Among 28 cases of post-LTMV CMVr, DNAemia occurred with a median of 38.5 (31.3 – 47) days after stopping LTMV. The median absolute lymphocyte count (ALC) at diagnosis was 1.29 (0.41 – 2.04) x109cells/L. Median peak CMV DNAemia at was 482 (100.5 – 2600) IU/mL, with a duration of 29 (20- 35) days; none had end organ disease. All were receiving immunosuppression for graft-versus-host disease treatment (n=18) or prophylaxis (n=10).

Risk factors for CMVr and csCMVi are listed in Table 3. For CMVr, univariate analysis showed that CMV D-/R+ status is associated with increased risk, while having CMV D+ donors or acute myeloid leukemia (AML) had lower risk. Multivariable analysis showed D-/R+ status and breakthrough viremia while on LTMV were associated with increased risk.

csCMVi in 21 patients were treated with valganciclovir (n=15) or IV ganciclovir (n=6) for a median duration of 37 (25.5 – 50) days. Univariate analysis showed that acute lymphoblastic leukemia (ALL) and reduced intensity conditioning were associated with increased risk, while AML had lower risk of csCMVi. On multivariable analysis, ALL, and D-/R+ had higher risk while AML had lower risk.

Demographics and clinical characteristics of allogeneic hematopoietic stem cell recipients with or without late clinically significant CMV infection

Conclusion

One in four allogeneic HSCT patients who received LTMV developed post-prophylaxis CMVr within 100 to 200 days post-transplant. CMV D-/R+ status had a higher risk for CMVr and csCMVi after LTMV discontinuation. Patients with AML had a lower risk for CMVr and csCMVi.

Disclosures

Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support
1140. Impact of an Implementation Science Initiative to Improve Vaccine Confidence for Invasive Meningococcal Disease (IMD) Prevention within American Indian (AI) Communities
Authors: Ignace Lyle , Hursman Ruth , Jimenez Jenniffer A Meza , Carter Jeffrey D , Corona Abigail K , Douglas Bonnie , Simone Laura , Molloy Leah
Published: November 2023

Background

Meningococcal vaccine uptake among adolescents remains suboptimal. This project aimed to identify barriers and motivators for vaccination in AI communities.

Methods

Between 12/2022 and 2/2023, 3 live family education sessions were held within AI communities in WI and ND. Healthcare provider (HCP) participants also attended a workshop to review current vaccine recommendations. Surveys were administered before/after the workshop and family education sessions.

Results

Surveys were completed by 56 family members. Baseline confidence in vaccine safety, efficacy and benefit was low, which increased after the sessions (Fig. 1). Parent understanding that the vaccine cannot cause disease improved from 51% to 82% (p =.001). Top reported barriers to vaccination were concern for immediate side effects and long-term side effects, and low perceived risk for IMD (34%, 26%, 25%, respectively). Parents identified learning more about IMD (40%), friends/family getting vaccinated (19%), and a local outbreak (12%) as top motivators to seek vaccination. When asked what they thought would motivate families to seek vaccination, HCPs leading the sessions (n=11) identified learning more about IMD (82%) and friends/family getting vaccinated (27%) only. HCP confidence in counseling families was low and improved after the sessions (Fig. 2). HCPs attending the workshop (n=28) reported discomfort contradicting patients/families as the top challenge in addressing vaccine hesitancy, and more HCPs felt confident having conversations to reduce vaccine hesitancy after the workshop (80%) than before (28%). HCP knowledge improved after the workshop, and more HCPs understood that MenACWY booster doses are not needed when initial vaccination occurs at age ≥16 (50%), and correctly identified “provider recommendation” as the top literature-reported factor influencing parental vaccine decisions (50%) compared to baseline (32% and 14%, respectively). HCP action plans for after the sessions prioritized routinely discussing vaccines at well visits (80%), providing written materials (50%) and staying current on new vaccines (50%).

Conclusion

Parent and provider knowledge and confidence improved after the program and offered insights into community-level motivators and barriers to vaccination.

Disclosures

All Authors: No reported disclosures
1151. Assessing Vaccine Hesitancy and Logistical Barriers to Undergraduate Students Receiving a Flu Vaccine
Authors: Benzaken Casey , Tan Tina Q , Jhaveri Ravi , Mithal Leena B
Published: November 2023

Background

Rates of annual flu vaccine receipt among college students remains significantly lower than the 2030 Healthy People target of > 70%. College students are at increased risk of contracting influenza due to close living and dining conditions, and illness due to influenza can have a negative impact on school attendance and academic achievement. This study assessed the extent to which vaccine hesitancy and logistical factors impacted college students’ ability to receive a flu vaccine.

Methods

This study consisted of three surveys administered through REDCap. During the 2021-22 and 2022-23 flu seasons, we administered a baseline survey to assess intention to receive a flu vaccine and logistical barriers that students face in receiving a flu vaccine. We also assessed vaccine hesitancy using a modified Parental Attitudes about Childhood Vaccines (PACV) questionnaire. One month later, we administered a follow-up survey to assess whether students had received a flu vaccine and to rank the importance of several factors in their decision-making.

Sociodemographic information of respondents to the baseline survey.

Results

We had a total of 156 participants in the baseline survey and 97 participants in the follow-up survey. Sociodemographic information can be seen in Table 1. There was a self-reported flu vaccination rate of 63.9%. Only 4.5% of participants scored ≥50 for their adapted PACV survey, indicating that a small proportion of students are flu vaccine hesitant. Individuals who self-reported that they typically receive a flu vaccine yearly had statistically significantly (p < 0.0001) lower adapted PACV scores (11.0[9.5]) compared to individuals who self-reported that they do not typically receive a flu vaccine annually or have only received the vaccines needed to enter school (31.3[21.3]). Among individuals who did not receive a flu vaccine, the top three concerns were easiness of forgetting (78.6%), inconvenience (57.2%), and lack of time (49.9%).

Conclusion

Understanding undergraduate barriers to receiving flu vaccines is critical in designing interventions that increase flu vaccine uptake in this population. Our study found that logistical barriers, rather than vaccine hesitancy, was the limiting factor in preventing college students from receiving flu vaccines.

Disclosures

Tina Q. Tan, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Iliad: Advisor/Consultant|Merck: Advisor/Consultant|Moderna: Advisor/Consultant|Novavax: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support Ravi Jhaveri, MD, AbbVie: Grant/Research Support|AliOS: Grant/Research Support|AstraZeneca: Advisor/Consultant|Gilead: Grant/Research Support|MedImmune: Advisor/Consultant|Merck: Grant/Research Support|Saol Therapeutics: Advisor/Consultant|Seqirus: Advisor/Consultant
Associations of sleep duration and daytime sleepiness with plasma amyloid beta and cognitive performance in cognitively unimpaired, middle-aged and older African Americans
Authors: Cook Jesse D , Malik Ammara , Plante David T , Norton Derek , Langhough Koscik Rebecca , Du Lianlian , Bendlin Barbara B , Kirmess Kris M , Holubasch Mary S , Meyer Matthew R , Venkatesh Venky , West Tim , Verghese Philip B , Yarasheski Kevin E , Thomas Kevin V , Carlsson Cynthia M , Asthana Sanjay , Johnson Sterling C , Gleason Carey E , Zuelsdorff Megan
Published: November 2023

Study Objectives

Given the established racial disparities in both sleep health and dementia risk for African American populations, we assess cross-sectional and longitudinal associations of self-report sleep duration (SRSD) and daytime sleepiness with plasma amyloid beta (Aβ) and cognition in an African American (AA) cohort.

Methods

In a cognitively unimpaired sample drawn from the African Americans Fighting Alzheimer’s in Midlife (AA-FAiM) study, data on SRSD, Epworth Sleepiness Scale, demographics, and cognitive performance were analyzed. Aβ40, Aβ42, and the Aβ42/40 ratio were quantified from plasma samples. Cross-sectional analyses explored associations between baseline predictors and outcome measures. Linear mixed-effect regression models estimated associations of SRSD and daytime sleepiness with plasma Aβ and cognitive performance levels and change over time.

Results

One hundred and forty-seven participants comprised the cross-sectional sample. Baseline age was 63.2 ± 8.51 years. 69.6% self-identified as female. SRSD was 6.4 ± 1.1 hours and 22.4% reported excessive daytime sleepiness. The longitudinal dataset included 57 participants. In fully adjusted models, neither SRSD nor daytime sleepiness is associated with cross-sectional or longitudinal Aβ. Associations with level and trajectory of cognitive test performance varied by measure of sleep health.

Conclusions

SRSD was below National Sleep Foundation recommendations and daytime sleepiness was prevalent in this cohort. In the absence of observed associations with plasma Aβ, poorer self-reported sleep health broadly predicted poorer cognitive function but not accelerated decline. Future research is necessary to understand and address modifiable sleep mechanisms as they relate to cognitive aging in AA at disproportionate risk for dementia.

Clinical Trial Information

Not applicable.
Multiple Eruptive Keratoacanthomas Secondary to Nivolumab Immunotherapy
Authors: Olsen Eric , Svoboda Steven A. , Montanez-Wiscovich Marjorie , Saikaly Sami K.
Published: November 2023

Immune checkpoint inhibitors are increasingly being utilized for the treatment of advanced neoplastic disease and have been associated with wide-ranging cutaneous adverse effects. Though exceedingly rare, eruptive keratoacanthomas have been associated with the use of immune checkpoint inhibitors such as pembrolizumab and nivolumab, whose molecular target is the programmed cell death protein 1. Herein, we detail a case of numerous eruptive keratoacanthomas arising in a patient one month after initiation of nivolumab for recurrent metastatic oropharyngeal squamous cell carcinoma. Treatment with multiple rounds of intralesional corticosteroids and a several-month course of oral acitretin resulted in partial improvement. Subsequent treatment with intralesional 5-fluorouracil demonstrated near-complete resolution of the keratoacanthomas without discontinuation of nivolumab. Although eruptive keratoacanthomas secondary to immune checkpoint inhibitors are exceptionally rare, physicians should be aware of this cutaneous adverse effect as their use becomes more widespread.
Porta Hepatis Tuberculous Lymphadenopathy: Clinical and Imaging Features of 10 Cases
Authors: Hu Wenjuan , Hu Ming , Xia Jiafeng , Chen Shengyue , Li Xiaomeng , Sheng Chengmin , Guo Wanru , Feng Xuewen , Shangguan Yanwan , Lu Bin , Shi Yunzhen , Qiu Junke , Xu Kaijin
Published: November 2023

Porta hepatis tuberculous lymphadenopathy (TL) is rare, and the clinical and imaging manifestations often mimic tumors. To offer a better understanding of porta hepatis TL and thus improve its diagnosis and treatment, here, we retrospectively reviewed and analyzed 10 porta hepatis TL cases between May 2017 and November 2022. In this study, porta hepatis TL occurred predominantly in women (70%), with a mean age of 43.1 years (range, 16–70 years). Among the patients, 60% were initially suspected of malignancy (metastatic lymphadenopathy and lymphoma). The clinical manifestations were nonspecific, such as fever and weight loss, without overt abdominal malaise. Many patients showed high concentrations of serum C-reactive protein, erythrocyte sedimentation rate, alkaline phosphatase, γ-glutamyl transpeptidase and carbohydrate antigen 125. Peripheral rim-like enhancement was a characteristic finding on contrast-enhanced CT for all the patients. Pathological examination confirmed the diagnosis in 90% of patients with caseous granulomatous inflammation and positive results of Xpert MTB/RIF, quantitative real-time PCR and/or metagenomic next-generation sequencing assays. All patients underwent antituberculosis therapy with a median treatment duration of 13.5 months (range, 1–43 months). They all showed satisfactory therapeutic responses with improved symptoms and resolution on imaging after treatment. Pathological examination by biopsy remains the primary diagnostic method. A combination of the characteristic epidemiologic, clinical, imaging features and lesion biopsy for histopathology are essential for the diagnosis and treatment of TL.