bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-634. Effect of Pre-existing OPV-induced immunity on development of canonical and non-canonical poliovirus virulence mutations
Authors: Carrington Yuan J , Zhou Frank , Altamirano Jonathan , Maldonado Yvonne A 
Published: January 2025

Abstract

Background
Preventing vaccine-derived polio is crucial, yet polio evolution and transmission mechanisms remain unclear. Our previous study in Mayan infants found that preexisting OPV-induced polio antibodies did not affect S3 immunogenicity. We now explore if viral mutations differ in those with and without preexisting antibodies. Using NGS, we identify and characterize vaccine poliovirus’ mutation patterns from stool sample isolates post one and two OPV doses. We hypothesize that OPV-induced intestinal immunity will correlate with increased mutations after the 2nd dose compared to the 1st.
S1 Canonical Mutations vs. Mutation Rates Post 1st and 2nd Dose of 116 OPV Isolates

Methods
179 OPV samples from a previous study were used. Participants received an OPV dose at study weeks 1 and 9 with stool samples collected at weeks 0, 1, 2, 4, 6, 8, 9, 10, 14, 16, and 17. A multiplex qPCR was used to determine serotype positivity. PCR amplicons created from stool viral RNA were purified and sequenced. Sequences were analyzed using the Illumina workflow nf-core/viralrecon (ver 2.5) and R (ver. 4.2.2).
S2 Canonical Mutations vs. Mutation Rates Post 1st and 2nd Dose of 82 OPV Isolates

Results
303 isolates were sequenced: 127 serotype 1 (S1), 91 serotype 2 (S2) and 85 serotype 3 (S3); 35 from week 0, 187 from weeks 1-8 (post dose 1: D1) and 81 from weeks 9-17 (post dose 2: D2). S1 and S2 in D2 showed significantly higher mutation rates (% of samples with mutation(s) at a given genome location) at all positions (S1 p = 0.0014, S2 p &lt; 2.2e-16), while S3 showed no difference (p = 0.9899). For canonical mutations, S1 D2 had higher mutations at G480A (D1 65.3% vs. D2 68.6%) and A2795G (D1 8.5% vs. D2 10.5%), but 0% at A2438T while D1 had 6%; no mutations were seen at T525C and T2879C. For S2, D2 had higher mutations at A481G (D1 11.4% vs. D2 16.7%), with no mutations at T2909C in either set. In S3, D2 showed higher mutations at T472C (D1 36.6% vs. D2 46.4%), but lower mutations at C2493T (D1 26.9% vs. D2 16.7%) and T2034C (D1 3.8% vs. D2 0%).
S3 Canonical Mutations vs. Mutation Rates Post 1st and 2nd Dose of 70 OPV Isolates

Conclusion
Overall, isolates post the 2nd OPV dose showed significantly higher mutation rates for S1 and S2, but not for S3. Preexisting antibodies may be associated with higher mutation rates and long-term likelihood of neurovirulent reversion. Serotype differences may be related to shedding patterns and other serotype specific characteristics. Further studies are planned to understand the impact of pre-existing intestinal immunity on polio viral mutation and evolution.

Disclosures
Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Member, DSMB
P-646. Culture Positive Pneumococcal Pneumonia Requiring Hospital Admission from 2017-2022 at Eight US Children’s Hospitals
Authors: Engstrom Eric , Hulten Kristina G , Barson William J , Lin Philana L , Dahl Steven , Ramirez Kacy A , Bradley John S , Pannaraj Pia , Tan Tina Q , Dien Bard Jennifer , Kaplan Sheldon L 
Published: January 2025

Abstract

Background
The incidence of pneumococcal pneumonia (PP) has decreased significantly since the introduction of pneumococcal conjugate vaccines (PCV7, PCV13), however, pneumococci still remain the most common cause of bacterial pneumonia in children. We evaluated the current clinical presentation, isolate serotypes, and isolate antibiotic susceptibility of PP cases from 2017-2022.

Methods
We collected pneumococcal isolates and limited clinical data prospectively from patients with invasive pneumococcal disease ages ≤18 years at 8 children’s hospitals in the United States. Serotyping was performed at a central research laboratory. Patients with PP were identified and further clinical and laboratory data for each episode of pneumonia was collected retrospectively with a standardized case report form.

Results
We collected 159 pneumococcal isolates and clinical data from patients with PP over the study period; extended clinical data was available for 95 patients (Figure 1). 9/159 (5.8%) isolates were non-susceptible to ceftriaxone (MIC &gt; 1.0 µg/mL; 7/9 were 19A), and 10/159 (6.5%) were non-susceptible to penicillin (MIC &gt; 2.0 µg/mL; 10/10 were 19A). 20/159 (12.6%) patients were completely unimmunized, while 108/159 (67.9%) were fully immunized with PCV7 or PCV13. Serotypes unique to PCV20 caused 34 episodes (21.4% of all isolates) (Figure 2). The risk ratio of a patient having PCV13 vaccine serotypes vs non-vaccine serotypes was not different between fully immunized and unimmunized (p=0.23), fully immunized and under-immunized by age (p=0.59), or any vaccination and unimmunized (p=0.11) patients. Of patients with extended clinical data, 40% had uncomplicated pneumonia, 31% had empyema (14/29-serotype 3, 6/29-19A, 1/29-19F), and 24% had necrotizing pneumonia (15/23-serotype 3, 4/23-19F, 0/23-19A). 78/95 (82.1%) patients had respiratory viral testing, of which 57.1% were positive for at least one virus (Table 1 and 2).

Conclusion
PP continues to be an important cause of morbidity in the United States. Antibiotic resistance is a major concern for serotype 19A, but overall antibiotic resistance in pneumococcal pneumonia is low. The introduction of PCV20 in 2023 for routine administration to infants may modestly reduce incidence of PP.

Disclosures
Kristina G. Hulten, PhD, Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support William J. Barson, MD, Pfizer: Grant/Research Support Pia Pannaraj, MD, MPH, AstraZeneca: Grant/Research Support|Pfizer: Grant/Research Support Tina Q. Tan, MD, Astra Zeneca: Grant/Research Support|GSK: Grant/Research Support|Iliad: Advisor/Consultant|Merck: Advisor/Consultant|Moderna: Advisor/Consultant|Novavax: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi Pasteur: Advisor/Consultant Sheldon L. Kaplan, MD, Pfizer: Grant/Research Support
P-649. Unusual Increase in Bordetella parapertussis Cases Detected in Pediatric Reference Centers in Mexico and Colombia During 2023: Is this Trend Emerging Elsewhere?
Authors: Gutiérrez Tobar Ivan Felipe , Carbajal-César Ana C , Londono-Ruiz Juan Pablo , Antonio-González Viviana , Salinas-Morales Daniel A , Robledo-Vega Carolina , Cuéllar Nicolás , Gutiérrez-Reyes Gloria M , de la Garza Eduardo Arias , Saltigeral Simental Leonor Patricia , Manzano-Arredonda Dámaris , Díaz-Jiménez Virginia 
Published: January 2025

Abstract

Background
Bordetella parapertussis infections clinically present with symptoms similar to Bordetella pertussis, albeit less severe and less frequent. We describe a multinational experience of an increase in cases from three pediatric reference centers in Mexico and Colombia
Graph 1
Distribution of B. parapertussis cases by date and country

Methods
Observational, retrospective study conducted at 3 pediatric reference centers, 2 in Mexico and 1 in Colombia. We included patients positive for Bordetella parapertussis via multiplex PCR respiratory assays from January 2023 to April 2024. Analysis focused on clinical characteristics and outcomes. Descriptive statistics were utilized and statistical comparisons were performed with the Mann-Whitney U test and Fisher's exact or chi-squared tests, significance was set at p &lt; 0.05
Graph 2
Age distribution by PICU admission status

Results
The study involved 61 patients, 42 from Mexico and 19 from Colombia, with initial cases originating in Colombia (Graph 1). Median age was 3 years (1 month to 13 years), with no significant age differences between countries. Males accounted for 59% of cases. Approximately 70.49% of children were fully vaccinated, and 26.23% had contact with individuals displaying respiratory symptoms. Common symptoms included cough (90.16%), rhinorrhea(60.66%), respiratory distress (59.02%), fever (59.02%), and paroxysms (22.95%). Coinfections were prevalent in 85.25% of cases, mainly rhinovirus (45.9%) and RSV (18.0%). Laboratory findings showed median leukocyte count of 9,450 (IQR: 7,250-14,922.5).Chest X-rays indicated interstitial patterns in 58.33% and consolidation in 8.33% of cases. The PICU admitted 24.59% of patients, with 6.56% requiring intubation. A significant age difference was observed between PICU admissions (median 0.58 years) and non-admissions (median 4 years), p = 0.037 (Graph 2). No fatalities occurred.

Conclusion
The increase in cases occurred in two countries, initially emerging and then subsiding in Colombia. Most patients had viral co-detection, mainly with Rhinovirus. Despite typically mild descriptions in the literature, around a quarter required ICU admission, particularly among younger patients, suggesting increased vulnerability in this group. Continuous monitoring of evolving circulation patterns is vital locally and regionally, as similar phenomena may be happening elsewhere.

Disclosures
All Authors: No reported disclosures
P-659. Active Surveillance of Mucosal Pneumococcal Infections to Predict the Potential Added Benefits of Extended-Spectrum PCVs in Children &lt; 24 Months in Southern Israel
Authors: Dagan Ron , Benisty Rachel , van der Beek Bart Adriaan 
Published: January 2025

Abstract

Background
Although mucosal infections, such as otitis media (OM) and acute conjunctivitis (AC) are the most common manifestations of pneumococcal disease in young children, surveillances have been based mainly on invasive pneumococcal disease (IPD) due to paucity of serotype-specific data on mucosal infection rates. We present rates and serotype dynamics of OM and AC as a means for assessing potential added benefits of the new PCVs, (PCV15/PCV20) against OM and AC in children &lt; 24m.
Annual incidence rates of P-OM and P-AC episodes, children &lt;24 months of age*,
southern Israel, July 2004 through June 2023

Methods
A retrospective analysis of two prospective, population-based surveillance projects on OM (Ben-Shimol CID 63:611, 2016) and AC (Dagan CID 72:1200, 2021) in southern Israel. All episodes in children &lt; 24m with OM and/or AC with cultures in southern Israel have been included. All middle-ear fluid (MEF) and conjunctival cultures in the region are processed in a single laboratory of the hospital where ∼95% of all children are born and treated, permitting incidence calculations. The current analysis covers all pneumococcal OM and AC (P-OM, P-AC) from July 2004 through June 2023.
Distribution of individual serotypes in P-AC and P-OM episodes, children &lt;24 months of age*,
southern Israel, July 2015 through June 2023 (late PCV13 period)

Results
A total of 2,312 and 1,039 episodes of P-OM and P-AC, respectively, were observed. The P-OM and P-AC annual rates are presented in Figure 1. The respective incidence rate ratios (95% CI) for 2017-2023 (excluding Corona year 2020-2021) vs. 2004-2008 were 0.12 (0.09-0.16) and 0.37 (0.26-0.53). During the stable PCV13 period (2015-2023), 32% and 24% of all P-OM and P-AC, respectively, were PCV20 serotypes (Figure 2). In both diseases, the PCV13 serotypes 19A, 19F, 3, and 14, and the PCV20-non-PCV13 serotypes 10A, 11A, 33F, and 15 B/C, predominated. PCV13 serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 18C, 23F (grouped) constituted only 0.6% and 1.7% of all P-OM and P-AC, respectively.

Conclusion
1) PCV13 implementation resulted in a rapid and steep decline in both P-OM and P-AC rates, stabilizing within 3-4 years; 2) during the late PCV13 period, only 4 PCV13 serotypes persisted: PCV7 serotypes 19F and 14, and PCV13 non-PCV7 serotypes 3 and 19A; and 3) the non-PCV13 PCV20 serotypes constitute approximately one quarter and one third of P-AC and P-OM, respectively, in children &lt; 24m in southern Israel. Implementation of PCV20 has the potential to add benefit against pneumococcal mucosal disease.

Disclosures
Ron Dagan, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MedIMmune/AstraZeneca: Grant/Research Support|MedIMmune/AstraZeneca: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi Pasteur: Honoraria
P-677. Title: Estimation of Respiratory Syncytial Virus-attributable Hospitalizations among Older Adults in Japan between 2015 and 2018: an Administrative Health Claims Database Analysis
Authors: Seki Masafumi , Kobayashi Yasuhiro , Meroc Estelle , Kitano Takahiro , Polkowska-Kramek Aleksandra , Yoshida Asuka , Liang Caihua , Bruyndonckx Robin , Molalign Moges Solomon , Conde-Sousa Eduardo , Nuttens Charles , Gessner Bradford D , Begier Elizabeth 
Published: January 2025

Abstract

Background
Respiratory Syncytial Virus (RSV) incidence in adults is often underestimated, mainly because of infrequent testing, nonspecific symptoms and lower diagnostic test sensitivity compared to infants. We estimated population-based incidence rates (IRs) of RSV-attributable hospitalizations in adults ≥60 years in Japan using a retrospective time-series model-based approach.

Methods
We obtained hospitalization data from the Medical Data Vision (MDV) database, which is restricted to Diagnosis Procedure Combination (DPC) hospitals; data were included for 01/01/2015-31/12/2018, with 2018 the last complete year available before COVID-19. We estimated the yearly and age-specific RSV-attributable IR of hospitalizations for five cardiorespiratory outcomes defined based on selected ICD-10 codes. We used a quasi-Poisson regression model accounting for periodic and aperiodic time trends, as well as viral activity proxies. An offset was included in the model to account for the increase of the source database size. We extrapolated our results to all DPC hospitals in Japan.

Results
In adults aged ≥60 years, the IRs of RSV-attributable cardiorespiratory hospitalizations were 100-124 per 100,000 person-years (up to 7% of selected cardiorespiratory hospitalizations) and 69-85 per 100,000 person-years for respiratory-specific hospitalizations (up to 8% of all respiratory hospitalizations). IRs for all outcomes were higher in adults aged ≥80 years compared to those aged 60-79 years (Table 1).

Conclusion
Modeled RSV-attributable IRs in Japan were lower than in most other developed countries, likely due to the MDV database only including advanced treatment hospitals. Taking this into account, our results indicate a high burden of RSV-attributable hospitalizations in older adults in Japan, highlighting the need to implement effective RSV prevention strategies. Future work will include a sensitivity analysis extrapolating IRs to all hospitals in Japan.

Disclosures
Yasuhiro Kobayashi, MS, Pfizer Japan Inc: employee of Pfizer Japan Inc.|Pfizer Japan Inc: Stocks/Bonds (Private Company) Aleksandra Polkowska-Kramek, n/a, Pfizer: employee of P95 which received funding from Pfizer to conduct this study Caihua Liang, MD, PhD, Pfizer: Stocks/Bonds (Private Company) Charles Nuttens, n/a, Pfizer: Stocks/Bonds (Private Company) Bradford D. Gessner, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Elizabeth Begier, MD, M.P.H., Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds (Private Company)
P-685. Investigation of Influenza antibody transfer following maternal vaccination using the PREVAIL Birth Cohort
Authors: Cline Allison R , Conrey Shannon C , Morrow Ardythe L , Staat Mary A , Fayad Danielle , Olson Samantha M , Payne Daniel C , Campbell Angela P 
Published: January 2025

Abstract

Background
Seasonal influenza vaccine is recommended during pregnancy; however, data are limited on transplacental antibody transfer. We used the PREVAIL Cohort of healthy, term infants and their mothers in Cincinnati, Ohio, to describe hemagglutination-inhibition (HAI) titers in pregnancy and measure the association between maternal and cord HAI relative to maternal vaccination during pregnancy.Table 1.Maternal GMT by Vaccination Status and by Influenza A Subtypes and Influenza B Lineages

Methods
Maternal immunization status was abstracted from medical charts/state registries. HAI titers were measured in maternal blood collected in the third trimester, and in cord blood. HAI &gt; 1:40 were considered seroprotective. Paired T tests (log normal distribution) and Fisher’s exact tests were used to compare geometric mean titers (GMT) and proportion of participants with seroprotective HAI, respectively, for each influenza subtype/lineage by vaccination status. Association between maternal and cord HAI was assessed using Spearman correlation and Maternal HAI/Cord HAI ratios.Table 2.Maternal Seroprotection by Vaccination Status and by Influenza A Subtypes and Influenza B Lineages

Results
155 mothers were included and delivered in the 2017-2018 influenza season (July 1st 2017-June 30st 2018); H3N2, H1N1 and B viruses circulated this season. 105 mothers received influenza vaccine during or 4 months prior to pregnancy. Vaccinated mothers had significantly higher GMTs for all influenza subtype/lineage compared to unvaccinated mothers (p&lt; 0.005) (Table 1). A significantly higher proportion of vaccinated mothers exhibited seroprotective titers against influenza subtype/lineage H3N2 and B-Victoria compared to unvaccinated mothers (p&lt; 0.05) (Table 2). There was a significant correlation between maternal and cord blood HAI for all subtype/lineage (r &gt; 0.85, p&lt; 0.05) (Figure 1). Cord GMTs tended to exceed maternal GMTs, with statistically significant differences in Influenza B lineage (p&lt; 0.05) (Table 3). More than 75% of the mother-infant pairs exhibited transplacental antibody transfer ratios ≤ 1.Table 3.Maternal GMT and Cord GMT by Influenza A Subtypes and Influenza B Lineages

Conclusion
Vaccinated mothers displayed protective influenza antibodies levels which were significantly higher than those found in unvaccinated mothers. Maternal HAI was strongly correlated with cord HAI, suggesting efficient transplacental transfer. Moving forward, investigation of factors influencing this transfer will be undertaken.Figure 1.Scatter plots of maternal vs cord log-transformed HAI titers

Disclosures
Mary A. Staat, MD, MPH, Cepheid: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria
P-688. Pediatric Pneumonia trapped in ‘NET’ (Neutrophil Extracellular Traps)
Authors: Mitra Barnali , Mitra Debdeep 
Published: January 2025

Abstract

Background
Neutrophil extracellular traps (NETs) were initially recognized for their role in the immune system, primarily immobilizing and sometimes killing microorganisms. However, further research has revealed their involvement in various diseases due to the harmful effects of their components on surrounding tissues. The innate immune system's role in pneumonia pathogenesis has been emphasized in several studies. Investigating the involvement of NETs in pulmonary infections and their potential as biomarkers for community-acquired pneumonia (CAP) outcomes has been explored in adult patients. Current data suggests that controlled NET release and clearance are beneficial in pneumonia, but any imbalance in this process could lead to harmful inflammation or increased risk of infection dissemination and sepsis.
However, there is a gap in understanding NET activity in pediatric lung infections. Therefore, this study aimed to assess NET activity in pediatric pneumonia patients and correlate it with blood culture results and viral panels for respiratory infections.

Methods
It was a Cross sectional Observational study at a tertiary care hospital and all children diagnosed to be suffering from pnuemonia. 30 Pediatric pneumonia patients were assessed at the time of presentation and evaluated clinically, radiologically and severity was scored based on Modified respiratory distress assessment instrument score (mRDAI). NET values were checked at the time of presentation and at the time of recovery. These values of NET were correlated with blood culture results, Respiratory viral panel and mRDAI score.

Results
Higher levels of Neutrophil extracellular traps (NETs) correlated with increased disease severity (mRDAI score) and with a poor prognosis and higher hospital stay and increased mortality. There was no statistical significance in the NET score of bacterial and viral pneumonia.

Conclusion
An increase in Neutrophil extracellular traps (NETs) levels is a common occurrence during severe respiratory infections. It is plausible to hypothesize that their migration to the lungs and subsequent activation could worsen tissue damage and contribute to the progression of the disease. NET has been identified as one of the markers linked with poor prognosis and severe pediatric respiratory symptoms.

Disclosures
All Authors: No reported disclosures
P-691. Characteristics Associated with the Presence of One or More Risk Factors for Severe Respiratory Syncytial Virus Disease among Adults in the United States
Authors: Horn Emily K , Singer David , Booth Alison , Saiontz-Martinez Cynthia , Berger Ariel 
Published: January 2025

Abstract

Background
Respiratory syncytial virus (RSV) can cause severe disease in older adults and adults with certain medical conditions. In June 2023, RSV vaccination was recommended for United States (US) adults ≥60 years of age (YoA) using shared clinical decision-making. This study explored factors associated with having diagnosed and undiagnosed risk factors (RFs) for severe RSV disease among US adults.

Methods
A retrospective analysis of pooled National Health and Nutrition Examination Survey data from 4 survey waves (January 2011 - March 2020) was conducted, comprising adult respondents (≥20 YoA), and weighted to allow extrapolation to all non-institutionalized US adults (Table 1). Diagnosed RFs were identified via self-report; undiagnosed RFs were assessed via lab test/exam results (limited to diabetes and renal disease). Multivariable logistic regression models were developed to assess associations between respondents’ sociodemographic characteristics and presence of ≥1 RF for severe RSV disease (cardiopulmonary, endocrine, and metabolic conditions).

Results
After extrapolation to the US population, 35.5% of adults ≥20 YoA (n=82,715,916/233,102,301) had ≥1 RF (diagnosed or undiagnosed) for severe RSV disease. For both diagnosed and undiagnosed RFs, older age, lower income, being a smoker, and obesity were associated with significantly higher odds of having ≥1 RF (Table 2). Adults with government insurance had a higher likelihood of having ≥1 diagnosed RF compared with those with private insurance (p &lt; 0.05). Adults from racial and ethnic minority groups were more likely than non-Hispanic White adults to have ≥1 undiagnosed RF (p &lt; 0.01). Compared to adults whose routine place for healthcare was doctors’ offices, adults with no routine place were less likely to have ≥1 diagnosed RF (p &lt; 0.001), while those whose routine place was the emergency room were less likely to have ≥1 undiagnosed RF (p &lt; 0.05).

Conclusion
Among US adults, several social determinants of health are associated with the presence of ≥1 diagnosed and undiagnosed RF for severe RSV disease. Understanding characteristics associated with RFs for severe RSV disease can help to ensure RSV vaccination among these higher risk groups.
Funding: GSK (GSK study identifier: VEO-000686)

Disclosures
Emily K. Horn, MSc, GSK: employee|GSK: Stocks/Bonds (Private Company) David Singer, PharmD, MS, GSK: employee|GSK: Stocks/Bonds (Public Company) Alison Booth, MSc, GSK: Grant/Research Support|Other pharmaceutical, biotech, and medical device companies: Grant/Research Support Cynthia Saiontz-Martinez, MSc, GSK: Grant/Research Support|Other pharmaceutical, biotech, and medical device companies: Grant/Research Support Ariel Berger, MPH, GSK: Grant/Research Support|Other pharmaceutical, biotech, and medical device companies: Grant/Research Support