bluuebunny/crossref_metadata_2025_split huggingface dataset:
904. Epidemiology of Rotavirus Group A Mixed Genotypes Isolated from Children with Acute Gastroenteritis over a 15-Year Period
Authors: Dellis Charilaos , Michos Athanasios , Tatsi Elizabeth-Barbara , koukou Dimitra-Maria , Syriopoulou Vasiliki 
Published: November 2023

Abstract

Background
Limited data exist worldwide regarding the genetic epidemiology of mixed G and/or P Rotavirus group A (RVA) strains and their association with demographic and clinical characteristics in children with acute gastroenteritis (AGE).

Methods
Positive fecal samples for mixed RVA previously G (VP7) and P (VP4) genotyped from children aged ≤16 years with AGE between 2007-2021 (15 years) in Greece were further genotyped for I (VP6) and E (NSP4) using RT-PCR and Sanger sequencing. Demographic, clinical and laboratory data of children infected with a mixed RVA strain were also collected.

Results
Over the 15-year period, 129/4427 (2.9%) mixed RVA strains were detected. Higher detection rate was observed in 2016 (7.5%) and in 2021 (5.8%) (Figure 1). Children infected with a mixed RVA strain had a median age of 21.1 months (IQR: 56.2) and were predominantly males (85/129, 65.9%). Mixed G genotype were 73/129 (56.6%), mixed P type 54/129 (41.1%) and both G and P mixed genotypes 3/129 (2.3%). In total, 27 different G/P combinations were detected with most prevalent the: G1G4P[8] (47/129, 36.4%), G1P[4]P[8] (18/129, 14%) and G4P[4]P[8] (18/129, 14%) (Figure 2). Higher seasonal peaks were observed for G mixed types in spring (68.8%) and for P mixed types in summer (66.7%). Infection with a G mixed type had a higher relative frequency in children aged 0-12 months, while infection with P mixed type had a higher relative frequency in children aged 13-48 months (p=0.043). I and E typing was successful in 49.6% (64/129) of mixed samples from 2013-2021. Two different I (I1, I2) and three different E (E1, E2, E3) genotypes were detected, with I1 (42.2%, 27/64) and E1 (39.1%, 25/64) being the most common I and E genotypes, respectively. In 31.3% (20/64) of samples, mixed I (I1I1, I1I2) and/or E (E1E1, E1E2) genotypes were also detected. No association has been detected between mixed genotypes and clinical characteristics of the patients.
Annual distribution of total and mixed RVA cases in a 15-year period
G-P combinations of RVA mixed strains.
Other combinations found in a smaller proportion (&lt;2.3%) were: G3P[4]P[8] (1.6%), G4P[8]P[9] (1.6%), G6P[4]P[9] (1.6%), GUDP[4]P[8] (1.6%), G2G4P[4]P[8] (1.6%), G1G2P[4] (0.8 %), G1G3P[9] (0.8%), G1G8P[4]P[8] (0.8%), G10P[8]P[10] (0.8%), G12P[4]P[8] (0.8%), G2P[8]P[10] (0.8%), G2G4P[8] (0.8%), G2G9P[8] (0.8%), G4G12P[4] (0.8%), G8G9P[8] (0.8%), G9P[4]P[8] (0.8%), G9P[6]P[8] (0.8%), G9G12P[8](0.8%).

Conclusion
These results indicate the great genetic diversity of RVA strains. Significant differences were found in the seasonality of the mixed G and P strains as well as in the age group of children infected with mixed G and P strains.

Disclosures
All Authors: No reported disclosures
921. Clinical characteristics of hospitalized adults with herpes zoster in a Portuguese hospital: 11 years of experience
Authors: Pena Eduarda , Gonçalves Maria João M S , Azeredo Constança , Oliveira Susana , Araújo Sara , Moura Luís , Duarte Frederico , Jordão Sofia , Guimarães Mário , Abreu Ricardo Correia , Neves Isabel , Batista Clara 
Published: November 2023

Abstract

Background
Herpes zoster (HZ) results from the reactivation of latent varicella-zoster virus and commonly affects older or immunocompromised patients. Clinical manifestations include painful vesicular skin eruptions that normally respect a dermatomal distribution. Prognosis is normaly favorable but a minority of patients develop complications such as generalized infection, ocular involvement, meningoencephalitis or visceral dissemination. Post-herpetic neuralgia and secondary bacterial infections are frequent complications. Preventive strategies like vaccination are important to mitigate the burden of HZ.

Methods
This retrospective study reviewed the charts of all patients older than 18 years hospitalized in a Portuguese hospital with the diagnosis of herpes zoster infection diagnosis between January 1, 2012 and December 31, 2022.

Results
The study included 152 patients with a mean age of 70 years old; 58% were female. In terms of clinical manifestations: 47% suffered from localized herpes zoster (thoracic dermatome in 40%) and only 11% had generalized zoster. Other manifestations included meningitis/encephalitis (7%), keratitis (n=4) and Ramsay-Hunt syndrom (n=3). About half of patients (51%) had an identified cause of imunodepression upon hospital admission: 25% had malignancy on chemotherapy and 6% had a reumatic disead on immunossupressive therapy, only 7 patients were HIV positive. Most patients (78%) were treated with aciclovir (mean duration 9 days). Post-herpetic neuralgia and secondary bacterial infections were common (35% and 20%, respectively). All-cause in-hospital mortality was 6%.

Conclusion
Patients hospitalized for herpes zoster are frequently elderly people with comorbidities, especially cancer. Thoracic envolvement was most frequent in localized infection. Post-herpetic neuralgia and bacterial infections were frequent complications. Its important to implement preventive strategies such as vaccination for herpes zoster to prevent shingles and post-herpetic neuralgia in older adults, especially in those who are immunosupressed. This measure would probably help mitigate the burden of this disease in this population.

Disclosures
All Authors: No reported disclosures
923. EDP-938, A Respiratory Syncytial Virus (RSV) antiviral, demonstrates a high barrier to resistance in a human challenge study
Authors: Levene Rachel E , DeVincenzo John , Conery Annie , Ahmad Alaa , Goodwin Bryan , Or Yat Sun , Rhodin Michael 
Published: November 2023

Abstract

Background
RSV can cause substantial morbidity and mortality to populations at high risk and there are no approved direct acting antiviral treatments. EDP-938, an RSV nucleoprotein (N) inhibitor in Phase 2 clinical development, has demonstrated significant reductions in viral load and symptoms after 5 days of dosing in a human challenge study. In contrast to other mechanisms in development, such as fusion inhibitors, EDP-938 has a high barrier to resistance in vitro. Here, we characterize the clinical resistance profile from the EDP-938 challenge study.

Methods
To assess emerging resistance, the N gene was sequenced from nasal washes of RSV infected subjects at multiple timepoints before, during and after dosing. A subset of the 124 RSV infected subjects (37 EDP-938 and 11 placebo subjects, 159 total nasal wash samples) were chosen for sequence analysis based on viral load curves to encompass the range of patterns observed over the course of the study. Sequences were compared to baseline (RSV-A Memphis 37) and low frequency variant detection (&lt; 1%) was performed.

Results
Of the 158 sequences obtained, no mutations identified in preclinical in vitro resistance studies were observed. Single N-protein mutations were detected in 2 subjects, both of whom received EDP-938. One subject had an E112G mutation detected on day 3 of treatment, however only wildtype virus was subsequently detected, and viral load became undetectable shortly thereafter. The other subject had an L139I mutation detected at days 4 and 5 of treatment and viral load was undetectable the next day. E112G and L139I viral variants were created by reverse genetics and tested for resistance and viral fitness in vitro. The E112G mutation did not confer resistance to EDP-938 nor any changes in viral fitness. The L139I mutation conferred very low-level resistance (10-fold decrease in EDP-938 antiviral activity) and a modest reduction in fitness.

Conclusion
In conclusion, no significant clinical resistance to EDP-938 was observed in this Phase 2 challenge study. These data demonstrate that EDP-938 has a high barrier to the development of clinical resistance.

Disclosures
Rachel E. Levene, PhD, Enanta Pharmaceuticals: Salary|Enanta Pharmaceuticals: Stocks/Bonds John DeVincenzo, MD, Enanta Pharmaceuticals: employee of Enanta Pharmaceuticals Annie Conery, Ph.D., Enanta Pharmaceuticals, Inc.: Stocks/Bonds Alaa Ahmad, PhD, Enanta Pharmaceuticals Inc.: Employee|Enanta Pharmaceuticals Inc.: Stocks/Bonds Bryan Goodwin, Ph.D., Enanta Pharmaceuticals: Former Employee|Enanta Pharmaceuticals: Stocks/Bonds Yat Sun Or, Ph. D, Enanta Pharmaceuticals: Co-inventor of EDP-938 patents|Enanta Pharmaceuticals: Stocks/Bonds Michael Rhodin, Ph. D, Enanta Pharmaceuticals Inc.: Employee of Enanta|Enanta Pharmaceuticals Inc.: Stocks/Bonds
1139. Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Compared to a Meningococcal Reference Vaccine (MCV4-TT) in Healthy Adolescents
Authors: Díez-Domingo Javier , Simkó Róbert , Icardi Giancarlo , Chong Chan Poh , Zocchetti Céline , Syrkina Olga , Bchir Siham , Bertrand-Gerentes Isabelle 
Published: November 2023

Abstract

Background
MenACYW-TT (MenQuadfi®) is a quadrivalent meningococcal conjugate vaccine licensed for use in individuals ≥ 12 months age in the EU and certain other countries and ≥ 2 years of age in the US. Safety and immunogenicity of a single dose of MenACYW-TT were evaluated in 10-17 years old healthy adolescents vs a quadrivalent (MCV4-TT [Nimenrix®]) meningococcal vaccine licensed ex-US. Co-administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines was also studied.

Methods
In this modified double-blind, Phase-3 study (NCT04490018) conducted in Hungary, Italy, Spain, and Singapore, meningococcal vaccine-naïve adolescents or MenC-primed (when &lt; 2 years of age) were randomized to receive either MenACYW-TT or MCV4-TT and co-administration with 9vHPV and Tdap-IPV vaccines. Serum bactericidal assays with human complement (hSBA) were used to measure anti-meningococcal antibodies against all 4 serogroups at baseline and 30 days post-vaccination. Antibodies against antigens contained in Tdap-IPV and 9vHPV were also measured. Safety data were collected within 30 days post-vaccination.

Results
A total of 463 subjects were enrolled in this study. Non-inferiority between MenACYW-TT and MCV4-TT, based on seroprotection rate (percentage of subjects achieving hSBA titers ≥ 1:8), was demonstrated for all 4 serogroups one month following meningococcal vaccination. Thirty days post vaccination, hSBA geometric mean titers (GMTs) were higher for MenACYW-TT vs MCV4-TT for serogroups C, Y and W, and comparable for serogroup A. The percentages of subjects with an hSBA vaccine seroresponse were higher for MenACYW-TT vs MCV4-TT for all 4 serogroups (Table). When MenACYW-TT was administered alone or concomitantly with 9vHPV and Tdap-IPV vaccines, the immunogenicity results were comparable or higher in subjects receiving MenACYW-TT alone than in those receiving all vaccines concomitantly. The safety profiles were comparable between MenACYW-TT and MCV4-TT, administered alone or concomitantly with 9vHPV and Tdap-IPV vaccines, with no safety concerns observed during this study.

Conclusion
The trial met the primary objective. MenACYW-TT induced non-inferior immune responses to all serogroups based on seroprotection rates, and higher or comparable GMTs and seroresponse rates compared to MCV4-TT.

Disclosures
Céline Zocchetti, MSc, Sanofi: Stocks/Bonds Olga Syrkina, MD, Sanofi: Stocks/Bonds Siham Bchir, MSc, Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Isabelle Bertrand-Gerentes, MD, Sanofi: Stocks/Bonds
1141. Incidence of adolescent syncope and related injuries following vaccination and routine venipuncture
Authors: Groom Holly C , Brooks Neon , Slaughter Matthew T , Mittendorf Kathleen , Naleway Allison L 
Published: November 2023

Abstract

Background
Vaccination is associated with syncope in adolescents. However, incidence of vaccine-associated syncope and resulting injury, and how it compares to syncope incidence following other medical procedures, is not known. Here, we describe the incidence of syncope and syncope-related injury in adolescents following vaccination and routine venipuncture.

Methods
We identified all Kaiser Permanente Northwest (KPNW) members ages 9 to 18 years with a vaccination or routine venipuncture and a same-day ICD diagnosis of syncope and collapse from 2013 through 2019. All cases were chart reviewed to establish chronology of events (vaccination, venipuncture, syncope, and injury, as applicable) and determine whether the event was attributed to vaccination or venipuncture. Incidence rates for vaccine- and venipuncture-associated syncope were calculated overall and by sex and age group. Incidence rates for vaccine-associated syncope were also calculated by vaccine type (Human Papillomavirus (HPV) vs. non-HPV).

Results
Of 197,642 vaccination and 12,246 venipuncture events identified, 549 vaccination and 67 venipuncture events had same-day codes for syncope. Chart validation confirmed 59/549 (10.7%) and 20/67 (29.9%) as vaccine-associated and venipuncture-associated syncope, respectively. Overall rates of syncope were 2.99 per 10,000 vaccination events (95% CI: 2.27-3.85) and 16.33 per 10,000 venipuncture events (95% CI: 9.98-25.21), yielding an incidence rate ratio of 0.18 (95% CI: 0.11-0.31). The incidence of vaccine-associated syncope increased with each additional simultaneously administered vaccine, from 1.51 (95% CI: 0.93-2.30) following a single vaccine to 9.94 (95% CI: 6.43-14.67) following 3 or more vaccines. When stratified by the number of vaccines received, rates of syncope were similar following vaccination events with and without the HPV vaccine. Among those with syncope events, documented injury occurred in about 15% of both vaccine and venipuncture events.

Conclusion
Syncope occurs more commonly following venipuncture than vaccination. A higher number of simultaneously administered vaccines is a risk factor for post-vaccination syncope in adolescents.

Disclosures
Kathleen Mittendorf, PhD, GE Healthcare: Grant/Research Support
1142. Impact of Informational Vaccine Notices Sent to Parents Prior to their Child’s 11th Birthday on Receipt of Adolescent Vaccines
Authors: Hanson Kayla E , Eggebrecht Meranda , Funk Penny , Christianson Ben , Belongia Edward , VanWormer Jeffrey J , Williams Charnetta L , McLean Huong 
Published: November 2023

Abstract

Background
Several vaccines, including human papillomavirus (HPV), tetanus-diphtheria-acellular pertussis vaccine (Tdap), and meningococcal serogroup ACWY vaccine (MenACWY), are recommended at age 11-12 years. In the United States, uptake of these vaccines, particularly HPV, is suboptimal. Systems to identify and notify patients who are coming due or overdue for vaccinations (reminder/recall) have been shown to be an effective strategy to increase vaccination. We assessed the impact of sending informational vaccine notices to parents of 10-year-old patients on receipt of adolescent vaccines in a predominantly rural, regional healthcare system in northcentral Wisconsin.

Methods
10-year-old patients with an upcoming 11th birthday (i.e., aged 10 years, 10 months or 10 years, 11 months) were identified at Marshfield Clinic Health System on a monthly basis and were randomized 1:1 to intervention (informational vaccine notice sent to the patient’s parent) vs. usual care (no notice). Randomization was stratified by rurality (rural, nonrural; defined by Rural-Urban Commuting Area Codes) and the parent’s preferred communication method (letter, text message, email). Receipt of adolescent vaccines (HPV, Tdap, MenACWY), as well as receipt of seasonal influenza vaccine and COVID-19 vaccine primary series, was assessed during the 90 days after randomization.

Results
From August 2021 through May 2022, 2,266 10-year-old patients were randomized (1,122 to the intervention and 1,144 to usual care) and 1,122 notices were sent to parents (576 letters, 544 text messages, and 2 emails). The majority of patients were non-Hispanic white (82%), lived in a rural area (63%), and approximately half were female (51%). Demographics did not vary by study arm. Receipt of HPV, Tdap, and MenACWY was 3.7 to 4.4 percentage points higher among patients randomized to the intervention vs. usual care (Table 1). No difference in uptake was observed for COVID-19 or influenza vaccines.

Conclusion
Informational notices sent to parents prior to their child’s 11th birthday resulted in modestly higher uptake of adolescent vaccines. Healthcare systems should consider sending vaccination notices, mailed or electronic, to parents whose children are coming due for recommended vaccines.

Disclosures
Kayla E. Hanson, MPH, Seqirus: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support
1154. Impact of Vaccination Protocol Implementation and Splenectomized Patient Management in a Specialized Clinic on Incidence of Encapsulated Bacterial Infections: a Retrospective Cohort Study in Quebec, Canada
Authors: Croft Émilie , Gingras-Lessard Florence , Musonera Jean Berchmans , Carignan Alex 
Published: November 2023

Abstract

Background
Splenectomy weakens immunity against encapsulated bacteria and is associated with increased overwhelming post-splenectomy infection rates. The impact of recommended vaccines for these bacterial infections has not been studied in Quebec. This study aims to i) assess changes in the incidence of encapsulated bacterial infections in patients who underwent splenectomy at Centre Hospitalier Universitaire de Sherbrooke (CHUS) from 1990 to 2019; ii) Investigate any changes in vaccine coverage following the implementation of: 1) a peri-splenectomy vaccination protocol in 2005 and 2) the creation of a clinic dedicated to splenectomized patients in 2015.

Methods
This retrospective cohort study selected splenectomy cases performed between 1990 and 2019 at CHUS. Bacterial infections (S. pneumoniae, H. influenzae, and N. meningitidis) were identified from electronic files of microbiology laboratories. Temporal trends were assessed over three periods according to the years in which pneumococcal polysaccharide and conjugate vaccines were recommended (1990–1998; 1999–2012; 2013–2019). The primary outcome was occurrence of vaccine-preventable infection within 5 years of splenectomy.

Results
The study included 544 splenectomized patients. The proportion of patients aged ≥65 years significantly increased over time [1990–1998: 30%; 1999–2012: 39%; 2013–2019: 44%; p=0.03]. S. pneumoniae [1990–1998: 6%; 1999–2012: 3%; 2013–2019: 0%; p=0.007] and H. influenzae infections significantly decreased [1990–1998: 11%; 1999–2012: 6%; 2013–2019: 0%; p=0.007]. Vaccination protocol implementation was associated with increase in the number of adequately vaccinated patients (Hib and PPV) in the 6 months after splenectomy [pre-protocol: 21%; post-protocol: 66%; p&lt; 0.0001]. A significant difference between vaccination coverage (Hib, VPP, and VPC) in the 6 months after the splenectomy of patients seen in the immunization clinic (49%) and those not referred (8%) was observed (p&lt; 0.0001).

Conclusion
Marked decrease in post-splenectomy infection rates was observed in our population over 30 years, despite aging. Vaccination protocol implementation and splenectomized patient management in a specialized clinic can improve vaccination coverage.

Disclosures
Alex Carignan, MD, MSc, GSK: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Moderna: Advisor/Consultant|Moderna: Honoraria|Orimed Pharma: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria
1159. A Phase 2 Drug-Vaccine Interaction Study of AV7909 and Ciprofloxacin or Doxycycline on Antibiotic Pharmacokinetics
Authors: Akintunde Gideon , Drobic Bojan , Bedell Lisa , Gan Lu , Kim Julia , Beah Marinda , Ghinai Isaac , Collado Santiago Barona 
Published: November 2023

Abstract

Background
AV7909 (Anthrax Vaccine Adsorbed, Adjuvanted) vaccine was developed for post-exposure prophylaxis (PEP) of disease following suspected or confirmed exposure to Bacillus anthracis administered in conjunction with recommended antibacterial regimen. A drug-vaccine interaction study (NCT04067011) was conducted to examine whether co-administration of AV7909 with ciprofloxacin (CIP) or doxycycline (DOX) affects antibiotic pharmacokinetics (PK) or AV7909 immunogenicity in healthy adults.

Methods
A Phase 2, randomized, open-label study was conducted to assess the effects of AV7909 (intramuscularly (IM) at 0, 2 weeks) on PK profiles of orally administered CIP and DOX in healthy adults between 18 and 45 years of age. Participants (n=210) were randomized to receive AV7909+CIP, AV7909+DOX or AV7909 alone. Serum concentrations of CIP and DOX were determined using liquid chromatography with tandem mass spectrometry, while AV7909 immunogenicity was evaluated using 50% neutralizing factor (NF50) values generated by a toxin neutralizing antibody (TNA) assay. Steady-state maximum concentration, Cmax and area under the curve from 0 to 12 hours, AUC0-12hrs for CIP and DOX were calculated. Safety was evaluated by collection of solicited reactogenicity and reports of adverse events (AEs).

Results
Primary PK endpoint for CIP was met, wherein 90% confidence intervals (CIs) of mean ratios for steady-state AUC0-12h [90% CI: 0.89, 1.07] and Cmax [90% CI: 0.87, 1.08] were contained within the equivalence criteria [0.80, 1.25]. The endpoint was marginally missed for DOX, wherein lower bound (LB) of 90% CI for AUC0-12h [90% CI: 0.82, 1.03] was within the equivalence criteria, but LB of 90% CI for Cmax (0.79) was below the equivalence criteria [0.80, 1.25]. This result for steady-state DOX Cmax is likely limited given that its efficacy is mainly AUC-driven. The immunogenicity endpoint was met, wherein LB of two-sided 95% CI of the geometric mean ratio of TNA NF50 was &gt;0.5 (0.78 for CIP, 0.81 for DOX). The majority of solicited reactogenicities and AEs were Grade 1 or 2 in severity.

Conclusion
Co-administration of CIP or DOX with AV7909 did not alter the relevant PK parameters of antibacterials or immunogenicity of AV7909 and was well tolerated in healthy adults.

Disclosures
Gideon Akintunde, Director Clinical Development, Emergent Biosolutions: Employee Bojan Drobic, Director Clinical Development, Emergent Biosolutions: Employee Lisa Bedell, Director Biostatistic, Emergent Biosolutions: Employee Lu Gan, Director Biostatistic, Emergent Biosolutions: Employee Julia Kim, Scientist Clinical Development, Emergent Biosolutions: Employee Marinda Beah, Manager Clinical Trials Development, Emergent Biosolutions: Employee Isaac Ghinai, Medical Director, Emergent Biosolutions: Employee Santiago Barona Collado, Medical Director, Emergent Biosolutions: Employee