bluuebunny/crossref_metadata_2025_split huggingface dataset:
2737. Comparison of Antibody Responses to Vaccination with a Pure Hemagglutinin Influenza Vaccine (rHA) and Licensed Subvirion Influenza Vaccine Made in Eggs or Cell Culture in Adults 60 Years and Older
Authors: Sarker Moumita , Branche Angela , Peasley Michael , Topham David 
Published: October 2019

Abstract

Background
Influenza is associated with increased mortality and morbidity for older adults. High-dose egg grown trivalent inactivated influenza vaccine (Fluzone HD) is safe and provides superior immune responses in older adults compared with standard dose (SD). Recently, two new vaccines have been licensed in the United States: cell cultured inactivated vaccine FluCelVax and baculovirus-expressed pure hemagglutinin (HA) vaccine FluBlok. Data from one study demonstrated higher efficacy with FluBlok than SD Fluzone in older adults. There is no data however comparing HD Fluzone to FluBlok and FluCelVax has not been studied at all. The purpose of this study was to assess hemagglutinin inhibition (HAI) antibody responses to vaccination with three vaccines in adults ≥ 60 years.

Methods
Adults ≥ 60 years were randomly assigned to receive one of the three vaccines: Fluzone HD, FluBlok and FluCelVax (Figure 1). Active influenza-like illness (ILI) surveillance was conducted with bi-weekly telephone calls. Serum samples were collected prior to vaccination and at day 7, 14, 28 and 180 and antibody responses assessed by HAI titer to A/Singapore/INFIMH-16–0019(H3N2), A/Michigan/45/2015(H1N1) and B/Colorado/6/2017 (Victoria) viruses as well as a circulating H3N2 strain. The primary endpoint was a 4-fold rise in antibody titer at day 28.

Results
48 subjects were vaccinated in October 2018. Mean age was 69 and 65% were female. Two subjects reported ILI symptoms and one was positive for infection (H1N1). A majority of subjects demonstrated pre-existing antibody to all three viruses (Figure 2, Blue). Geometric mean titers (GMT) for antibody responses to the influenza A viruses were similar for FluBlok (FB) and HD Fluzone (FZ) but lower for FluCelVax(FCB) subjects (Figure 2, Orange). A higher percent of FlubBlok subjects demonstrated 4-fold rise in antibody responses to the Victoria influenza B virus (FB GMT 140 vs. FZ GMT 116, P = 0.26).

Conclusion
In this small study, antibody responses were similar or higher in older adults after vaccination with FluBlok compared with Fluzone HD with lower responses demonstrated with FluCelvax. Emerging concerns about HA egg adaptation during vaccine development compels further study to determine the appropriate vaccination strategy for this vulnerable population.

Disclosures
All authors: No reported disclosures.
2739. Comparison of Hemagglutination Antibody Inhibition (HAI) Titers Following Influenza Vaccination by Birth Cohort and Repeated Influenza Vaccination History
Authors: Sherman Amy C , Lai Lilin , Bower Mary B , Natrajan Muktha S , Huerta Christopher M , Xu Yongxian , Mulligan Mark , Rouphael Nadine , Rouphael Nadine 
Published: October 2019

Abstract

Background
The host immune response to influenza vaccination can be affected by prior imprinting to a specific influenza strain based on birth cohort and prior influenza vaccination history. Understanding the underlying immune mechanisms is essential to development of an improved seasonal vaccine and an effective universal influenza vaccine.

Methods
This is a prospective pilot study, with a total of 20 subjects in either the H3N2 cohort (N = 10, born 1968–1977) or the H1N1 cohort (N = 10, born 1948–1957). Each cohort was further stratified by subjects who have received the influenza vaccine < 2 or ≥ 3 of the past 5 years. The FDA-approved quadrivalent 2018–19 influenza vaccine (containing A(H1N1), an A/Michigan/45/2015-like virus; A(H3N2), an A/Singapore/INFIMH-16–0019/2016-like virus; B/Colorado/06/2017-like virus; and B/Phuket/3073/2013-like virus) was administered on Day 1. Demographic information included age, gender, ethnicity, and BMI. HAI titers for each component of the vaccine were obtained at baseline, 29 days post-vaccination, and 180 days post-vaccination. HAI fold-change and HAI geometric mean titers (GMT) were analyzed.

Results
There was no significant difference between H1N1 or H3N2 HAI fold-change in the H3N2 birth cohort (P = 0.7496) or in the H1N1 birth cohort (P = 0.8237), Figure A. Comparing HAI fold-change for the repeatedly vs. minimally vaccinated groups, there was a significant higher fold change in the minimally vaccinated group (H1N1 HAI (P = 0.002) and H3N2 HAI (P < 0.0001), Figure B). GMT was higher at baseline for the repeatedly vaccinated group (H1N1, 70; H3N2, 98; vs. H1N1, 30; H3N2, 21 for the minimally vaccinated group); however, the GMT for the minimally vaccinated group was higher at day 29 (H1N1, 172; H3N2, 184; vs. H1N1, 422; H3N2, 299 for the minimally vaccinated group; Figure C). HAI titers and analysis at day 180 post vaccination are in progress.

Conclusion
There was no evidence of an imprinting effect by birth cohort for HAI titer magnitudes, even when stratified by vaccination history. There was a significantly higher HAI fold change for individuals who had received minimal influenza vaccinations in the past 5 years at 29 days post-vaccination. Individuals who had repeated vaccinations in the last 5 years had higher HAI GMT at baseline.

Disclosures
Nadine Rouphael, MD, Merck: I conduct as Emory PI the PNEUMO MERCK study at Emory, Research Grant; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Sanofi-Pasteur: I conducted as Emory PI the CDIFFENSE trial at Emory, Research Grant.
167. Deep Space Infections in Injection Drug Users (IDU)
Authors: Bacon Alfred Emmanuel , Claudine Jurkovitz , Horton Terry , Caplan Richard , Fawcett Mitchell , Dal Nogare Ryan , Saunders Jessica , McGraw Patty 
Published: October 2019

Abstract

Background
The opioid epidemic in the US has increased attention to infectious complications of injection drug use (IDU). The goal of our study was to ascertain the impact of these infections on the health of our community and institutional burden considering that our institution does not discharge patients with IDU for outpatient IV antibiotic treatments due to lack of safe environment and compliance concerns.

Methods
This retrospective study reviewed IDU-associated deep space infections in an 1100 -bed medical center from 2010 through 2014. Pathogens, site of infection, mortality rates and, length of stay (LOS), 3- month readmission (inpatient + observation), leaving against medical advice (AMA) rates for those alive at discharge, were evaluated. ICD-9/10 coding identified admissions related to opioid use and deep infections (endocarditis, diskitis/osteomyelitis, sepsis/bacteremia, empyema). Only the most severe infection was counted for each patient. Charts were reviewed to determine whether IDU was associated with the entree infections.

Results
A total of 505 patients met criteria for deep space infections associated with IDU over 5 years. Of those, 305 (60%) were male, 146 (29%) black, 335 (66%) white, 271 (54%) were on Medicaid, 246 (49%) had sepsis/bacteremia, 67 (13%) had endocarditis,143 (28%) discitis/osteomyelitis, 22 (4%) empyema and 27 (5%) other. Mean age was 46 ± 12 years. LOS varied by disease state. The overall median was 10 days, from 8 days for bacteremia/sepsis up to 27 for endocarditis. There were 43 (9%) hospital deaths; 30 (6%) patients left AMA and 209 (45%) patients were readmitted within 3 months.

Conclusion
Deep space infections in IDU patients result in long LOS, high mortality and high rates of readmissions and departures AMA. Improved algorithms for management that include psychosocial models and incorporate cost-effective and safe antibiotic administration need to be developed.

Disclosures
All authors: No reported disclosures.
2745. Efficacy and Effectiveness of High-Dose Influenza Vaccine for Older Adults by Circulating Strain and Antigenic Match: A Systematic Review and Meta-Analysis
Authors: Lee Jason K H , Lam Gary K L , Shin Thomas , Samson Sandrine I , Greenberg David P , Chit Ayman 
Published: October 2019

Abstract

Background
Influenza vaccine efficacy/effectiveness can vary from season to season due in part to the dominant circulating strains and antigenic matching. This study reviews the relative vaccine efficacy/effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared with standard-dose influenza vaccines (SD-IIV3) in adults ≥65 years against influenza-associated outcomes across all influenza seasons, during seasons where A/H3N2 or A/H1N1 strains predominantly circulated, and where there was an antigenic match or mismatch of the vaccine and circulating strains.

Methods
A systematic review was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults ≥65 years. Results from individual seasons were extracted from the identified studies, and surveillance data from each season were used to determine the dominant circulating strains and antigenic match. Results were then stratified based on clinical outcomes and seasonal characteristics and meta-analyzed to estimate pooled rVEs of HD-IIV3.

Results
11 studies were meta-analyzed after screening 1,018 studies, providing data on 9 consecutive influenza seasons and over 12 million individuals receiving HD-IIV3. Across all influenza seasons, HD-IIV3 demonstrated improved protection against ILI compared with SD-IIV3 (rVE = 15.9%, 95% CI: 4.1–26.3%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 8.4%, 95% CI: 5.7–11.0%), as well as influenza (rVE = 16.1%, 95% CI: 7.4–24.1%), pneumonia (rVE = 27.3%, 95% CI: 15.3–37.6%), pneumonia/influenza (rVE = 13.4%, 95% CI: 7.3–19.2%) and cardiorespiratory events (rVE = 17.9%, 95% CI: 15.0–20.8%). Some numerical differences were observed in the pooled rVE of outcomes in matched and mismatched seasons and in seasons where A/H3N2 or A/H1N1 strains were predominantly circulating (Table 1).

Conclusion
Evidence over 9 influenza seasons suggest that HD-IIV3 is consistently more effective than SD-IIV3 at reducing the clinical outcomes associated with influenza infection irrespective of circulating strain and antigenic match. This study was funded by sanofi pasteur.

Disclosures
All authors: No reported disclosures.
2749. Disparities in Healthcare Seeking Behaviors in the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) Study
Authors: Schofield Christina , Richard Stephanie , Colombo Rhonda , Collins Limone , Ganesan Anuradha , Geaney Casey , Lalani Tahaniyat , Markelz Ana E , Maves Ryan , Mende Katrin , Seshadri Srihari , Spooner Christina , Utz Gregory , Warkentien Tyler , Coles Christian L , Burgess Timothy 
Published: October 2019

Abstract

Background
Healthcare outcome disparities exist for underrepresented populations, which may be partially due to reduced engagement in clinical research trials. Within the military with free, open access to medical care for members and beneficiaries, some healthcare outcome disparities become less apparent. We sought to assess the impact of the open access to care within the military healthcare system on research engagement among underrepresented populations.

Methods
During the PAIVED study (2018–2019 influenza season) enrollees were randomized to receive an FDA approved influenza vaccine (egg-based, recombinant, or cell-culture derived) followed by weekly surveillance for influenza-like illness (ILI) symptoms throughout the influenza season. At enrollment, participants self-identified gender, race, ethnicity, and level of education.

Results
Overall, the non-recruit study population (n = 852) was 52% male, 18% Hispanic, 15% African American, 70% White, 24% with High School or less, 22% with Associate’s, 24% with Bachelor’s and 30% with Post-Bachelor degree at enrollment. Individuals who reported African American race (OR 2.1, 95% CI (1.4, 3.3)) or Hispanic ethnicity (OR 1.7 (1.1, 2.6)) were more likely to have missed > 15% of the surveys, whereas military retirees (OR 0.5 (0.3, 0.9)) and dependents (OR 0.6 (0.4, 0.95)) were less likely to have missed > 15%. Individuals with African American race (OR 2.2 (1.3, 3.9)) or Hispanic ethnicity (OR 1.9 (1.1, 3.0)) were more likely to have missed the past 3 survey weeks. Retirees (OR 0.4 (0.2, 0.7)), dependents (OR 0.5 (0.3, 0.9)) and those with higher levels of education were less likely to have missed the past 3 weeks. There were no gender differences for these outcomes.

Conclusion
Healthcare outcome disparities may be partially explained by disparities in healthcare research engagement from underrepresented populations. Our cohort provides a unique perspective where access to and affordability of care and reliable income are minimized. Despite this, there remained differences in research engagement by race, ethnicity and education level, but not by gender. Future efforts should inform research design to increase research engagement from underrepresented populations.

Disclosures
All authors: No reported disclosures.
2765. Pediatric Mumps during the 2015–2017 Mumps Resurgence in the United States
Authors: Marlow Mariel , Zhang John , Clemmons Nakia S , Marin Mona , Patel Manisha , Patel Manisha 
Published: October 2019

Abstract

Background
Numerous mumps outbreaks occurred in the United States over the last decade, with outbreaks affecting young adults on college campuses being among the largest and most widely publicized. However, at least half of mumps cases and outbreaks occurred in other age-groups and settings. We describe reported mumps cases among children and adolescents during 2015 through 2017.

Methods
The Centers for Disease Control and Prevention (CDC) analyzed reports of confirmed and probable mumps cases in persons aged ≤18 years (defined here as pediatric mumps) transmitted electronically through the Nationally Notifiable Diseases Surveillance System (NNDSS) by the 52 reporting jurisdictions.

Results
Between January 1, 2015 and December 31, 2017, 49 jurisdictions reported 4,886 pediatric mumps cases (35% of all US reported cases, 13,807); 8 jurisdictions reported >100 cases each, representing 82% of all pediatric cases. Overall, 29 (1%) cases were in infants <1 yr, 406 (8%) were in children aged 1–4 years, 1,408 (29%) in children aged 5–10 years, 1,365 (28%) in adolescents aged 11–14 years, and 1,678 (34%) in adolescents aged 15–18 years. Most (3,548, 73%) cases did not travel outside the state during their exposure period; only 37 (1%) traveled outside the country. Cases in patients aged 1–4 years were more frequently non-outbreak associated (38%) than those in patients <1 years and 5–18 years (24% and 9%, respectively). Among 3,309 (68%) patients with known number of MMR doses received, 81% of those 5–18 years had ≥2 MMR doses, while 67% of those 1–4 years had ≥1 dose. Median time since last MMR dose for patients with 2 doses was 8 years (IQR: 4, 11 years). Four patients had meningitis and 1 had encephalitis; all were ≥10 years old and previously received 2 MMR doses. Of male mumps patients older than 10 years of age (2,113), 46 (2%) reported having orchitis; of these, 33 (72%) had 2 MMR doses. Sixty-four patients were hospitalized and there were no deaths.

Conclusion
About one-third of cases reported during the recent US mumps resurgence were in children and adolescents. The low rate of mumps complications compared with previous studies suggests mumps complications may not be adequately captured in national surveillance or identified by providers. Providers should remain vigilant that mumps can still occur among fully vaccinated pediatric patients, even those recently vaccinated.

Disclosures
All authors: No reported disclosures.
2778. Impact of Reactogenicity on Quality of Life and Physical Functioning in Adults ≥50 Years Receiving Both Doses of the Adjuvanted Recombinant Zoster Vaccine
Authors: Schmader Kenneth E , Levin Myron J , Chen Michael , Matthews Sean , Riley Megan , Woo Wayne , Hervé Caroline , Grupping Katrijn , Schuind Anne , Oostvogels Lidia , Curran Desmond 
Published: October 2019

Abstract

Background
The adjuvanted recombinant zoster vaccine (RZV) is efficacious in preventing herpes zoster in adults ≥ 50 years. The current study investigates whether the vaccinees’ quality of life (QoL) and physical functioning (PF) are impacted by local and systemic reactions due to RZV. In a previous report of this phase III, open-label, multicenter study (NCT02979639), overall PF and QoL were not significantly affected by a first RZV dose. [1] Here we report the results from the same study after a second RZV dose and safety results from dose 1 up to study end.

Methods
Adults aged ≥ 50 years were to receive 2 doses of RZV 2 months apart. Changes in mean Short Form health survey (SF-36) PF score between pre- and post-each RZV dose for 7 days, QoL, reactogenicity and safety were assessed.

Results
401 adults received dose 1 and 391 received dose 2 of RZV. Post-second RZV dose, the reported solicited local symptoms were pain (75.1%), erythema (22.4%) and swelling (13.9%), and the most frequent solicited systemic symptoms were fatigue (46.3%), headache (37.5%) and myalgia (32.9%). Grade 3 solicited symptoms were reported by 7.2% (local) and 11.1% (general) of participants, and 5 (1.2%) participants reported reactogenicity triggering medical attention post-second RZV dose. From first dose up to study end, 14 (3.5%) participants reported 21 serious adverse events, none related to RZV. In days 1–2, post-second RZV dose, a transient, clinically-important decrease in SF-36 PF score (table) was seen in those reporting grade 3 solicited symptoms, which impacted activities such as walking and climbing stairs. Overall, during the 7 days post-second RZV dose, a mean change of −0.4 points was observed from the mean baseline score, indicating the PF was not clinically meaningfully impacted. No overall quality-adjusted-life-year loss was recorded.

Conclusion
Overall, the QoL and PF of adults ≥ 50 years were not affected post-second RZV dose; a transient impact was observed in adults with grade 3 reactogenicity. These results and the observed reactogenicity and safety profile are consistent with first RZV dose results, as well as that of previous studies with the RZV vaccine in adults of similar age.
Funding: GlaxoSmithKline Biologicals SA.
1. Schmader et al., Abstract 2488, IDWeek 2018

Disclosures
All authors: No reported disclosures.
2784. Increased Frontal Lobe Volume and Density in Macaques Exposed to Zika Virus In Utero
Authors: Mohr Emma L , Koenig Michelle , Razo Elaina , Mitzey Ann , Semler Matt , Stewart Laurel , Breitbach Meghan , Newman Christina , Dudley Dawn , Weiler Andrea , Rybarczyk Sierra , Bach Kathryn , Mohns Mariel , Simmons Heather , Mejia Andres , Teixeira Leandro , Schotzko Michele , Nork T Michael , Rasmussen Carol , Katz Alex , Hou Jiancheng , Hartman Amy , Hoeve James Ver , Kim Charlene , Schneider Mary , Ausderau Karla , Kohn Sarah , Aliota Matthew , Salamat M Shahriar , Hayes Jennifer , Schultz-Darken Nancy , Antony Kathleen , Noguchi Kevin , Zeng Xiankun , Ikonomidou Chrysanthy , Prabhakaran Vivek , Capuano III Saverio , Friedrich Thomas , Golos Thaddeus , O’Connor David 
Published: October 2019

Abstract

Background
In utero Zika virus (ZIKV) infection causes birth defects and neurodevelopmental deficits in neonates. We reasoned that a translational macaque model of congenital ZIKV infection could define disease pathophysiology not possible in human clinical studies.

Methods
We inoculated 5 pregnant rhesus macaques with a Puerto Rican isolate of ZIKV (ZIKV-PRVABC59) during the first trimester, monitored infection with plasma viral RNA (vRNA) loads, and evaluated infants for birth defects and neurodevelopmental deficits during their first week of life. Assessments included neurobehavioral assessments, ophthalmic examinations, optical coherence tomography, electroretinography with visual evoked potentials, hearing examinations, brain magnetic resonance imaging (MRI), and tissue histopathological analyses.

Results
All five pregnant dams demonstrated plasma viremia and seroconversion following ZIKV inoculation. One of the five pregnancies resulted in a stillbirth. All liveborn infants had decreased feeding volumes and weight gain compared with control infants. A comprehensive voxel-based morphometric comparison of ZIKV-exposed and control infant brain MRIs identified increased gray matter volume and density in the frontal lobe in the ZIKV-exposed infant group, which corresponds to the pharyngeal motor cortex responsible for coordinating swallowing. Ocular studies identified differences between ZIKV-exposed and control infants in retinal layer thicknesses (inner plexiform, outer nuclear layers, photoreceptor outer segment) and visual evoked potentials (increased amplitude of waveforms). While ZIKV vRNA was detected in the decidua of 2/5 pregnancies, no ZIKV vRNA was identified in infant tissues and none of the infants developed an anti-ZIKV IgM response.

Conclusion
In utero ZIKV exposure resulted in decreased feeding volumes and weight gain, which may be related to the gray matter changes identified in the pharyngeal motor cortex. Changes in retinal layer thicknesses and increased cortical visual pathway waveform amplitude suggest vision may be impaired. These changes occurred despite the lack of evidence of vertical transmission, suggesting that ZIKV exposure without measurable vertical transmission affects fetal brain development.

Disclosures
All authors: No reported disclosures.
2799. Inability to Locally Differentiate Rhinovirus/Enterovirus Results Impacts Infection Control Practices
Authors: Donelan Susan V , Spitzer Silvia , Spitzer Eric 
Published: October 2019

Abstract

Background
Rhinoviruses and Enteroviruses are closely related members of the family picornavirideae; however, they have distinct clinical manifestations. Rhinoviruses cause respiratory infections while Enteroviruses often present as nonspecific febrile illnesses. Enterovirus D68 (EV-D68) is unusual in that although it is classified as an enterovirus it causes respiratory illness. Most of the currently used nucleic acid amplification assays for respiratory viruses do not distinguish between Rhino and Enteroviruses because of their shared homology. Rhino/Enterovirus infections are common in the Summer and Fall. In October of 2018 the NYS DOH issued a health advisory describing increased numbers of EV-D68 infection. Although there is no specific treatment for EV-D68, the advisory recommended contact precautions in addition to the droplet precautions recommended for other respiratory viruses. This recommendation creates logistical difficulties since there are no commercial test-kits that can identify EV-D68. The aim of this study was to determine the incidence of EV-D68 among patients admitted to Stony Brook Hospital that tested positive for Rhino/Enterovirus.

Methods
Nasopharyngeal swabs were tested with the BioFire® FilmArray® Respiratory Panel (RP 2) test. 44 Rhino/Enterovirus positive specimens were sent for further identification to the NYS DOH Virology Lab. Enterovirus was differentiated from Rhinovirus by qRT–PCR. EV-D68 was identified by sequencing.

Results
During one week in October, 10 patients were admitted with positive EV-D68 (5 adults and 5 children). In contrast, all 21 admitted patients who had specimens sent for typing had Rhinovirus.

Conclusion
This study confirmed that there was significant EV-D68 activity among patients who required hospitalization consistent with the NYS DOH advisory in the Fall of 2018. In contrast, in the Winter a drop in the prevalence of Rhino/enterovirus was observed. EV-D68 was not found in any of the samples sent for typing. These data informed our internal decision to cohort all patients this past Winter with positive Rhino/enterovirus results, positively impacting patient cohorting capabilities during a time with increased local influenza activity.

Disclosures
All authors: No reported disclosures.