bluuebunny/crossref_metadata_2025_split huggingface dataset:
1744. Next generation sequencing (NGS) optimization of Oral Polio Vaccine samples
Authors: Carrington Yuan J , Zhou Frank , Tzou Philip , Xiao Mingze , Leary Sean , Altamirano Jonathan , Maldonado Yvonne A 
Published: November 2023

Abstract

Background
As wild poliovirus is eradicated, preventing circulation of vaccine-derived poliovirus is top priority. Our lab developed real-time multiplex PCR and deep sequencing methods to detect and characterize OPV strains directly from stool samples. This method requires gel purification of PCR product created from viral RNA in stool samples. However, gel purification causes significant genetic material loss and is time consuming. Here, we explore combinations of different purification and NGS methods to optimize sequencing.

Methods
554 OPV positive samples from a previous study were used. 991 isolates were identified: 268 serotype 1 (S1), 405 serotype 2 (S2), and 318 serotype 3 (S3). PCR amplicons created from viral RNA in stool were run through a 0.08% agarose gel to identity presence of the ∼3.5kb amplicon of interest. Amplicons then underwent 1 of 4 purification methods (Table 1) with those yielding DNA &gt;10ng/ul sequenced using 1 of 2 NGS techniques (Miseq vs Nextseq).
Different Purification Methods Used Prior to NGS

Results
Gel purification: 42/126 (33.3%) S1 and 45/121(37.2%) S2 banded amplicons had a DNA concentration of &gt;10ng/ul, as required for NGS. DNA purification: 449/450 (99.8%) S2 (259 banded) and all 318 (100%) S3 (170 banded) amplicons had concentrations &gt;10ng/ul. S1 (n=145) samples had a higher mean coverage (MC) of 2850.02 than S2’s (n=208) MC of 792.56 and S3’s (n=217) MC of 256.78. Also, Nextseq (n=315) had a higher MC of 1486.78 than Miseq’s (n=255) MC of 648.99. Table 2 shows the MC for each purification and NGS method grouping and Graph 1 shows each grouping’s sample Ct value graphed against MC. 5/71 (7%) non-banded amplicons yielded sufficient sequencing coverage. There was a negative correlation between increasing Ct and coverage and a weak positive correlation between DNA concentration and coverage.
Coverage of OPV Positive Samples by Purification and NGS Methods
Ct Value Against Mean Coverage of Samples by Serotype and Purification and NGS Method Groups

Conclusion
DNA-purification methods (DPM) retain more DNA than gel-purification methods (GPM), therefore capturing a wider range of data. GPM may cause data loss and misrepresentation from reduction of sample size and variety, particularly of samples for within host variation analysis. However, the DNA retained via DPM were not OPV-specific, causing a need for a higher amplicon input volume to than GPM for the same coverage. DPM of band-producing samples with a Ct value of &lt; 34 followed by Nextseq may be most optimal for NGS.

Disclosures
Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member
1745. Respiratory Syncytial Virus Surveillance of Child Care Attendees, Family Members, and Child Care Providers
Authors: Chedid Khalil , Shope Timothy , Hashikawa Andrew , Wang-Erickson Anna , Williams John V , Martin Emily T 
Published: November 2023

Abstract

Background
Respiratory syncytial virus (RSV) is a leading cause of severe respiratory illness among young children. In the U.S., a third of these children attend child care centers (CCC), where RSV can spread rapidly and be transmitted to family members. The study objective was to determine the incidence of RSV in CCC attendees and their household contacts.

Methods
The prospective cohort enrolled students (&lt; 6 years old), their household contacts and child care providers (CCP) at six CCC in Ann Arbor, MI from May 2021 to March 2022. Participants completed a symptom diary and weekly nasal swabs. RT-PCR was used to detect RSV. Incidence rates were calculated using Poisson regression.

Results
A total of 2,342 swabs were collected during 19,121 person-days from 32 students, 13 household child contacts (7 of whom were also students), 45 household adult contacts, and 10 CCP. The incidence rates per 10,000 person-days (95% CI) for total vs. asymptomatic cases were 10.2 (4.2, 24.5) vs. 2.0 (0.3, 14.5) for students, 8.4 (2.1, 33.7) vs. 4.2 (0.6, 30.0) for child contacts, and 5.4 (2.2, 12.9) vs. 1.1 (0.2, 7.6) for adult contacts, respectively. Twelve people tested positive for RSV: 5 (15.6%) were students, 2 (15.4%) were child contacts, 5 (11.1%) were adult contacts, and none were CCP. Semiquantitative cycle threshold was comparable between samples from asymptomatic and symptomatic cases. Three students, 1 child contact and 3 adult contacts had serial positive swabs for a single illness. Asymptomatic cases were detected in 1 (20%) student, 1 (20%) adult contact, and 1 (50%) child contact. Suspected transmission events were observed in 3/24 (12.5%) households with documented infection. All cases were detected between 9/6/21 and 1/17/22, coinciding with RSV circulation in Michigan during the study period.

Conclusion
This study demonstrates the continued presence of RSV in CCC, including during times of increased disease mitigation, and transmission between children and household contacts may have occurred. Asymptomatic infection was detected, albeit at lower rates than symptomatic infections. Given the incidence of RSV detected, our findings underscore the importance of implementing additional surveillance and infection prevention policies in CCC to mitigate the impact of RSV on vulnerable populations.

Disclosures
Khalil Chedid, MPH, MD, PHD, Merck: Grant/Research Support Timothy Shope, MD MPH, Merck: Grant/Research Support Andrew Hashikawa, MD, Merck: Grant/Research Support Anna Wang-Erickson, PhD, Merck: Grant/Research Support John V. Williams, MD, Merck: Grant/Research Support|Quidel: Board Member Emily T. Martin, PhD, MPH, Merck: Grant/Research Support
1749. Clinical Characteristics and Enteric Viral Detection Among Children with One Vomiting Episode in the Absence of Diarrhea
Authors: Johnson Jacob D , Amarin Justin Z , Stopczynski Tess , Hayek Haya , Qwaider Yasmeen Z , Hamdan Olla , Stewart Laura S , McHenry Rendie , Hall Aron J , Payne Daniel C , Wikswo Mary , Dunn John R , Spieker Andrew J , Chappell James , Halasa Natasha B 
Published: November 2023

Abstract

Background
Clinical presentations and etiologies of acute gastroenteritis (AGE) are variably captured by current definitions. Nonspecific presentations of AGE, such as a single vomiting episode within 24 hours without diarrhea, are common. We described clinical characteristics and viral detection among children presenting with one vomiting episode without diarrhea, comparing them to those presenting with multiple episodes or those who were asymptomatic.

Methods
We conducted population-based surveillance of children presenting to Monroe Carell Jr. Children's Hospital at Vanderbilt as part of the New Vaccine Surveillance Network (12/01/2012–01/30/2016). Eligible children were aged &gt;14 days and &lt; 18 years, had ≥1 vomiting episode or ≥3 episodes of loose stool within 24 hours, and presented within 10 days of symptom onset. Additionally, we recruited asymptomatic children and collected stool samples within 5 days of enrollment. We tested stool samples by enzyme immunoassay for rotavirus and by reverse transcription polymerase chain reaction assays for rotavirus (confirmatory), norovirus, sapovirus, and astrovirus. We restricted our analysis to children without diarrhea. For comparisons, we used Pearson’s χ2 test and the two-sample t-test with unequal variances for categorical and continuous variables, respectively.

Results
Our final study population included 180 children with one vomiting episode, 853 children with multiple episodes, and 1,255 asymptomatic children. Demographic and clinical characteristics of the children are compared in Table 1. At least one virus was detected in 32 children with one vomiting episode (17.8%; reference), 364 children with multiple episodes (42.7%; p &lt; 0.001), and 212 asymptomatic children (16.9%; p = 0.77). Norovirus was the most common virus detected across all three groups, and children with one vomiting episode were more likely to present with fever than those with multiple episodes.
Table 1
Clinical characteristics and viral detection among children presenting with one vomiting episode without diarrhea, those presenting with multiple episodes without diarrhea, and those who were asymptomatic.

Conclusion
Viral detection in children presenting with one vomiting episode was comparable to that in asymptomatic children and considerably less frequent than in children with multiple vomiting episodes. Our findings suggest that one vomiting episode without diarrhea is not a comparatively strong indicator of viral acute gastroenteritis.

Disclosures
Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support
1766. An Integrated Infectious Disease and Critical Care Staffing Model for Clinical Care of Special Pathogens
Authors: Busch Lindsay M , Harris Gavin , Ockers Sandy , Kraft Colleen S 
Published: November 2023

Abstract

Background
The Serious Communicable Diseases Unit (SCDU) at Emory University Hospital (EUH) is a special pathogen treatment biocontainment unit. Medical care is led by Infectious Disease (ID) specialists with an interdisciplinary group of nurses, infection preventionists, laboratorians, and consultants. In the 2014 Ebola Virus Disease (EVD) outbreak, the SCDU treated four EVD patients, one critically-ill requiring mechanical ventilation and dialysis. Critical care (CC) services were provided through consultation by CC staff, requiring just-in-time (JIT) training in high-level personal protective equipment (PPE) and real-time adaptation of standard operating procedures (SOPs) to meet biocontainment needs. The care provided was successful: all patients survived and no serious PPE breaches or provider exposures occurred. However, these events revealed the need for a comprehensive plan for SCDU CC services.

Methods
SCDU-CC physician liaison and lead advance practice provider (APP) positions were created to implement SCDU CC in conjunction with the Emory Critical Care Center (ECCC). Previous CC services were reviewed and revised.

Results
An integrated staffing model of ID-CC co-management was proposed. CC provider roles were codified: participate in regular high-level PPE training/verification and procedural simulation; attend quarterly interdisciplinary trainings and monthly provider meetings; maintain high quality patient care per ECCC standards. Following unit activation, the SCDU-CC liaisons and lead APP construct a JIT CC schedule. APPs provide 24hour in-house coverage in 12hour day/night shifts. Depending on patient number/acuity, physician coverage consists of in-house day coverage with night home call or 12hour day/night shifts. CC co-manages with the ID physician.

Conclusion
CC delivery in the SCDU has been improved after 2014. CC services were previously deployed ad hoc, with simultaneous need for JIT high-level PPE training of new personnel, urgent patient assessment, and modification of SOPs for biocontainment. We developed an integrated staffing model to provide ID-CC co-management within the SCDU.

Disclosures
All Authors: No reported disclosures
2883. Comparative outcomes following Candida bloodstream infections in patients with left ventricular assist devices (LVAD)
Authors: Mansoor Armaghan-e-Rehman , Krishnan Gayathri , Zuniga-Moya Julio C , Sinclair Dorothy , Spec Andrej , George Ige 
Published: November 2023

Abstract

Background
Left ventricular assist devices (LVAD) are an important management strategy for end-stage heart failure, however they carry a risk of infection. This study examines attributable outcomes of LVAD presence in patients presenting with Candida bloodstream infection (Candidemia).

Methods
1233 patients with candidemia admitted to Barnes Jewish Hospital between January 2010-December 2021 were retrospectively included, of whom 39 had an LVAD at the time of infection. Demographics, comorbidities, microbiologic data, and risk factors for infection were analyzed. Outcome measures included 30 and 90-day mortality, need for mechanical ventilation, and dialysis. Risk factors for candidemia, and outcomes following infection were compared between patients with and without LVAD presence.

Results
Candidemic patients in the LVAD cohort were more likely to be male (77%) compared to the non-LVAD group (54%) (Table 1). Patients with an LVAD were more likely to have central venous access (p-value 0.04), and to have received extracorporeal membrane oxygenation (ECMO) prior to infection (67% vs 46%, p-value=0.01). There were no statistically significant differences in rates of parenteral nutrition, abdominal surgeries, liver disease or malignancies between the two cohorts. C. parapsilosis was the most common causative species in patients with LVAD (38% in LVAD group vs 16%) followed by C. albicans compared to the non-LVAD cohort (24% in LVAD group vs 39%). Patients in both groups had similar rates of mechanical ventilation, and hemodialysis need. HeartMate2 was the most common LVAD strategy in 21 patients (54%). Two patients required LVAD exchange as part of treatment.
Presence of an LVAD did not significantly impact 30-day (31% in LVAD group vs 35%, p-value=0.62) or 90-day mortality (38% in LVAD group vs 41%, p-value 0.77). Within the LVAD cohort, 90-day mortality was associated with a shorter time duration from LVAD placement to candidemia.

Conclusion
In patients presenting with Candidemia, presence of an LVAD did not impact 30 or 90-day mortality. A shorter time from LVAD placement to infection was associated with poorer outcomes.

Disclosures
All Authors: No reported disclosures
1787. Association of Lifestyle Factors with Sepsis Incidence: A Population-Based Cohort Study in South Korea
Authors: Lee Eun Hwa , Lee Kyoung Hwa , Han Kyung-Do , Song Young Goo , Hoon Sang 
Published: November 2023

Abstract

Background
Sepsis, a critically-ill syndrome that can cause damage to multiple organs, is a leading cause of death worldwide with significant healthcare costs. However, there was no large-scale study to evaluate the association of daily modifiable lifestyles with the risk of sepsis, which will be very important that the occurrence of sepsis can be sufficiently prevented by individual volition and effort.

Methods
A retrospective population-based cohort study was performed to assess the association between the incidence rate (IR) of sepsis and alcohol consumption, tobacco smoking, and physical activity. Clinical data from health checkup arranged by the Korean National Health Insurance System (NHIS) were obtained from individuals 20 years or older in 2009 (n=4,234,415). The final 3,837,953 patients were analyzed, excluding personnel with sepsis during the 1 year before and after the checkup and patients with missing data. The NHIS claim data of all patients in the cohort were followed up until December 31, 2019. The primary outcome was the occurrence of sepsis as defined by the ICD-10 codes (A02, A32, A40, A41, A42, B37, R57, and R65). Lifestyle factors were collected through health-related behavior questionnaires in the health checkup.

Results
During a median 9.32 years of follow-up, 78,188 sepsis cases were identified. The multivariate model, which adjusted for age, socioeconomic status, body mass index, diabetes mellitus, hypertension, and dyslipidemia, revealed that smoking was independently associated with a higher risk of developing sepsis in both male (adjusted hazard ratio: 1.29, 95% confidence interval: 1.26-1.32, P&lt; 0.0001) and female (1.48, 1.40-1.56, P&lt; 0.0001). Heavy drinking was associated with a higher IR in female (1.33, 1.18-1.51. P&lt; 0.0001), but a lower IR in male (0.95, 0.92-0.97, P&lt; 0.0001). The individuals who engage in regular exercise have a lower risk of developing sepsis in both male (0.94, 0.92-0.96, P&lt; 0.0001), and female (0.89, 0.86-0.91, P&lt; 0.0001) compared to those who reported physical inactivity.

Conclusion
This study suggests that lifestyle factors such as smoking, drinking, and regular exercise may play a role in the incidence of sepsis, and that modifying these factors may have potential benefits for preventing or reducing the incidence of sepsis.

Disclosures
All Authors: No reported disclosures
1789. Comparison of influenza vaccine effectiveness estimates from the US Influenza Vaccine Effectiveness Network and Electronic Health Record Source Population Data, 2021-2022
Authors: McLean Callie , Chung Jessie R , Gaglani Manjusha , Nowalk MaryPatricia , Martin Emily T , Tartoff Sara , Wernli Karen , Belongia Edward , Grijalva Carlos G , Flannery Brendan 
Published: November 2023

Abstract

Background
The COVID-19 pandemic led to increased respiratory viral testing for patients presenting with acute respiratory infection (ARI). Electronic health record (EHR) data from these visits can be used to assess influenza and COVID-19 vaccine effectiveness (VE). We compared VE data from participating healthcare institutions with VE against medically attended influenza among systematically tested patients actively enrolled in the US Flu VE Network.

Methods
During the 2021-2022 influenza season, seven sites in the US Flu VE Network identified medically attended episodes of ARI in ambulatory settings based on ICD-10 diagnostic codes and clinical influenza and SARS-CoV-2 testing. Influenza status was determined from the clinical test results. Vaccination status was extracted from the EHR. During the same period, patients with ARI presenting at ambulatory clinics were actively enrolled and tested for influenza. VE and 95% confidence intervals (CI) were estimated comparing the odds of vaccination among influenza-positive versus influenza-negative patients using logistic regression models controlling for age, site, and calendar time.

Results
During the 2021-2022 season, 220,162 medical visits for ARI with clinical testing were identified; 2% of tests were influenza positive, 26% were SARS-CoV-2 positive and 73% were negative for both. Overall, 34% of influenza positive and 42% of influenza negative patients had received influenza vaccines; VE using EHR data was 34% [95% CI 29-38]. Among 6,260 enrolled patients, 7% tested positive for influenza, 34% were SARS-CoV-2 positive and 62% were negative for both. Overall, 42% of influenza positive and 59% of influenza negative patients had received influenza vaccines. VE using enrolled patient data was 36% [95% CI 20-49]. VE using EHR data was 35%, 34%, and 6% for patients aged 6 months-17 years, 18-49, and 50+ years versus 40%, 32%, and 10% for enrolled patients.

Conclusion
EHR based influenza VE estimates were similar to estimates from the US Flu VE study. Through continued widespread clinical testing, EHR-based platforms may present opportunities to assess VE in sub-groups with insufficient sample size in active surveillance.

Disclosures
MaryPatricia Nowalk, PhD, RDN, Merck & Co.: Grant/Research Support|Merck & Co.: Honoraria|Sanofi: Grant/Research Support Emily T. Martin, PhD, MPH, Merck: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support
2886. The Clinical Implications of High Echinocandin Persistence of a Major Fungal Pathogen and Development of a Rapid and Convenient Approach to Determine Echinocandin Persistence
Authors: Arastehfar Amir , Daneshnia Farnaz , Floyd Daniel , Mansour Michael 
Published: November 2023

Abstract

Background
Candida glabrata is a major human fungal pathogen known for its rapid acquisition of antifungal resistance and its ability to replicate inside the macrophages. Echinocandins are the first-line antifungal drugs and the number of echinocandin resistant (ECR) C. glabrata isolates are on the rise. Echinocandin persistent (ECP) C. glabrata cells are one of the major drivers of ECR. Although bacterial isolates with high antibiotic persistence are associated with a higher rate of resistance and burden, it is not clear if ECP level in C. glabrata bears a clinical significance. Additionally, ECP level determination traditionally relies on labor-intensive and time-consuming approaches.

Methods
Six C. glabrata isolates with similar minimum inhibitory concentrations of micafungin were included and their ECP was determined using traditional colony forming counting. An ex vivo primary macrophage model was used to assess the intracellular replication, the dynamic of killing, and the ECR colony rates of all isolates in the absence and presence of micafungin treatment. Two isolates, including a high and a low ECP C. glabrata isolates, were used to induce systemic infection and to evaluate the fungal burden and the rate of ECR colonies in spleen, liver, and kidney in the absence and presence of humanized dosage of micafungin (5mg/kg). A SYTOX-based assay was used as a proxy to determine the ECP levels of various C. glabrata.

Results
We show that high ECP-Cg isolates better replicate inside the macrophages and establish systemic infection than low ECP isolate. Additionally, under echinocandin treatment high ECP-Cg isolates have a higher burden and exclusively develop ECR colonies in our ex vivo and systemic infection models. Finally, we report a convenient SYTOX-based assay that reliably and rapidly measures the ECP level.

Conclusion
C. glabrata isolates with a higher ECP level are less effectively cleared by echinocandins and more likely to develop ECR and as such are clinically relevant. Our rapid and convenient SYTOX-based protocol reliably determines the ECP level and therefore has the potential to be used in clinical settings, high throughput screening studies, and has the potential to be extended to measure persistence level of various fungal pathogens.

Disclosures
Michael Mansour, MD, PhD, Thermofisher: Grant/Research Support