bluuebunny/crossref_metadata_2025_split huggingface dataset:
2762. A Cohort Analysis of Completion of the Pediatric Measles-Mumps-Rubella-Varicella Series in the United States
Authors: Wolfson Lara J , Nyaku Mawuli K , Surati Shikha , Liu Zhiwen , Pawaskar Manjiri D 
Published: October 2019

Abstract

Background
Since 2006, the recommended US vaccination schedule has included combination Measles-Mumps-Rubella (MMR) vaccine and separate Varicella (V) vaccine administered as first dose between 12–15 months, and second dose between 4–6 years, administered either separately or as a combination MMRV vaccine. Vaccine coverage alone does not provide information on the timeliness of vaccine receipt, a critical step in ensuring optimal protection, thus, we sought to evaluate overall series completion rates and identify factors related to under-vaccination.

Methods
A cohort of children born between 2006 and 2010, with continuous enrollment from birth to age 7 in the MarketScan® Commercial Claims and Encounters Database was studied. The administration of first and second doses of MMR- and V-containing vaccines was evaluated. Administration timeliness was categorized as recommended, acceptably early (prior to age 4 for the second dose), late (after the recommended time period), invalid, or missing at least one vaccine. A logistic regression analysis evaluated factors associated with under-vaccination.

Results
Among the 104,999 children included, 55.9% were vaccinated within the recommended time periods for both first and second doses, with timeliness higher for the second dose (80.1%) than the first dose (63.5%). By age 4, 20.1% of children were missing the first dose of either MMR or V (or both) and by age 7, 26.6% of children were missing at least one dose, with 9.4% missing all required vaccines. Factors associated with missed or delayed vaccination included geographic region, vaccination by a provider other than a pediatrician, and, for the second dose, having missed or delayed the first dose. Having additional children in the family was associated with a higher likelihood of missed or delayed vaccination for the first dose, but with a lower likelihood of missed or delayed vaccination for the second dose.

Conclusion
About one in four children were missing at least one dose of MMR or V by age 7, indicating vaccine coverage is below Healthy People 2020 95% target. Additionally, delays in administration of the first dose indicate a potential for the development of cohorts of susceptible children large enough to sustain outbreaks. Strategies for addressing timeliness of vaccine receipt should incorporate factors associated with under-vaccination.

Disclosures
All authors: No reported disclosures.
169. Multidrug-Resistant Bacteria Are Common Cause of Neutropenic Fever and Increase Mortality Among Patients with Hematologic Malignancies in Uganda
Authors: Lubwama Margaret , Adams Scott , Muwonge Catherine , Bwanga Freddie , Kateete David , Nabiryo Barbara , Kagwa Paul , Namubiru Betty , Orem Jackson , Phipps Warren 
Published: October 2019

Abstract

Background
Cancer patients are at risk of developing severe infections. Empiric management of infections is complicated by emerging antimicrobial resistance and changing local epidemiology of organisms. We sought to determine predominant species causing bacteremia, their antimicrobial resistance profiles, and their contribution to mortality among hematologic cancer patients with febrile neutropenia at the Uganda Cancer Institute.

Methods
Blood drawn from participants during a febrile neutropenic episode (FNE; fever ≥37.5°C and neutrophil count ≤1,000 cells/µL) was cultured in the BACTEC 9120 blood culture system. Bacteria from positive cultures were identified biochemically. Antimicrobial susceptibility testing was performed with the disc diffusion method. Logistic regression and proportional hazards regression were applied to estimate associations between participant characteristics and FNE, bacteremia, and mortality.

Results
Of 246 participants, 74 (30%) had an FNE. During the first FNE, 6/21 (29%) participants with acute lymphocytic leukemia (ALL) developed bacteremia compared with 16/31 (52%) with acute myeloid leukemia (AML) (OR 2.22 (0.65, 7.4)). AML patients were specifically at higher risk of Gram-negative bacteremia (OR 4.59 (1.09, 19.3). Of the 41 aerobic bacteria isolated, 32 (78%) were Gram-negative, the most common being Klebsiella pneumoniae (11; 34%). Seventeen (53%) of the Gram-negative bacteria displayed the extended spectrum β lactamase phenotype and 5 (16%) were resistant to carbapenems. One of the eight Enterococcus species was vancomycin resistant. Overall survival among patients with FNE was 54% at 30 days and 19% at 100 days. Bacteremia was associated with higher mortality within 30 days (HR 2.1 (0.99, 4.45)) and 100 days (31% vs.10%; HR 2.23 (1.09, 4.59)).

Conclusion
Multidrug-resistant bacteria are the main cause of bacteremia and increase mortality in febrile neutropenic hematologic cancer patients at the UCI. Enhanced microbial surveillance, infection control and antimicrobial stewardship programs are needed to guide therapy and address emerging antimicrobial resistance at our institution.

Disclosures
All authors: No reported disclosures.
2764. Generation of a Balanced, Tetravalent Dengue Vaccine Based on Contemporary Strains Using a Computational, Synthetic Biology-Based Platform
Authors: Wang Ying , Stauft Charles B , Raviprakash Kanakatte , Coleman J Robert , Mueller Steffen 
Published: October 2019

Abstract

Background
The WHO estimates that there may be 50 million cases of dengue virus (DENV) infection worldwide every year. There is no safe vaccine against DENV licensed in the United States. The development of a balanced and effective anti-DENV vaccine is vital to preventing morbidity and mortality. Codagenix used its proprietary SAVE (Synthetic Attenuated Virus Engineering) platform to generate and test a live attenuated, tetravalent vaccine against DENV.

Methods
Codagenix used SAVE to substitute under-represented human codons and codon-pairs into the E protein sequences of contemporary strains of DENV1-4, producing either a fully human-cell-deoptimized prM-E (E-Min), or a partially deoptimized prM-E (E-W/Min) to allow for balancing of the vaccine’s immunogenicity. Full genomes containing deoptimized E-Min and E-W/Min in the DENV2 backbone were transfected into cells to recover live-attenuated, human-cell-deoptimized vaccine strains. Mice were vaccinated with 106 FFU of each DENV vaccine (alone or together), boosted on day 21 and assessed for neutralizing antibodies by PRNT50 and survival after lethal challenge with mouse-adapted wild-type (WT) DENV. Cynomolgus macaques were immunized with a mixture of 106 FFU of each DENV vaccine strain. Two doses were administered on study day 1 and 57 and serum neutralizing antibodies were determined on day 57 and 85 by a microneutralization assay.

Results
SAVE deoptimized DENV viruses grew to wild-type (between 107 and 108 FFU/ml) levels at permissive temperatures (<37C). All vaccine strains generated neutralizing antibody levels comparable to WT. A tetravalent formulation containing all four E-Min strains protected mice from lethal challenge with DENV3. A tetravalent formulation of Codagenix DENV-E-W/Min vaccine elicited a robust and balanced neutralizing antibody response in non-human primates (NHPs) against all four DENV serotypes after a single dose. A second vaccine dose did not boost antibody titers significantly.

Conclusion
The ability to rationally balance the attenuation of multiple vaccine strains, thereby avoiding antibody-dependent enhancement, is a unique advantage of the Codagenix SAVE platform. Codagenix DENV vaccine viruses generated balanced, sterilizing immunity in NHPs after one dose.

Disclosures
All authors: No reported disclosures.
2772. HCMV gB Ectodomain Subunit and gB mRNA Vaccines Reduce AD-3 Immunodominance and Elicit More Durable Antibody Responses Than gB/MF59 Immunization
Authors: Nelson Cody S , Jenks Jennifer A , Pardi Norbert , Roark Hunter K , Goodwin Matthew , Weissman Drew , Permar Sallie R 
Published: October 2019

Abstract

Background
A vaccine to prevent maternal acquisition of human cytomegalovirus (HCMV) during pregnancy is one potential strategy to reduce the incidence of congenital disease. The MF59-adjuvanted glycoprotein B (gB/MF59) protein subunit vaccine is the most efficacious tested to-date, though achieved only 50% efficacy in phase 2 trial. We previously identified that gB/MF59 vaccination elicited poor heterologous virus neutralization and an immunodominant response against non-neutralizing/cytosolic antigenic domain 3 (AD-3) (Figure 1). Thus, we sought novel gB vaccination strategies to improve functional antibody responses and reduce AD-3 immunodominance.

Methods
Groups of juvenile New Zealand White rabbits (n = 6) were administered 3 sequential doses of gB protein with an MF59-like squalene adjuvant IM, gB ectodomain protein (lacking AD-3) + squalene adjuvant IM, or lipid nanoparticle (LNP)-packaged nucleoside-modified mRNA encoding gB ID.

Results
The AD-3 immunodominant IgG response seen in human vaccinees was closely mimicked in rabbits, with 78% of binding antibodies directed against this region in the gB protein group compared with 1% and 46% in the ectodomain and mRNA-LNP-vaccinated groups respectively (Figure 2). All vaccines were highly immunogenic with similar kinetics and comparable peak gB-binding/functional antibody responses. However, both ectodomain and mRNA-LNP-immunized rabbits exhibited enhanced durability of IgG binding to gB protein (P = 0.04 and 0.02, respectively), and the mRNA-LNP group had more durable binding of cell membrane-associated gB (P < 0.001) (Figure 3). Additionally, ectodomain and mRNA-LNP-vaccinated rabbits had increased durability of antibodies targeting neutralizing epitopes AD-4 and AD-5 (P < 0.01). Finally, low-magnitude gB-specific T-cell activity was observed in the gB protein and mRNA-LNP groups, though not in ectodomain-vaccinated rabbits.

Conclusion
Altogether these data suggest that gB ectodomain subunit and gB mRNA-LNP vaccine formulations reduced targeting of non-neutralizing epitope AD-3 and elicited more durable IgG responses than gB protein vaccination. These next-generation HCMV vaccine candidates aiming to improve upon the partial efficacy of gB/MF59 vaccination should be further evaluated in preclinical models.

Disclosures
All authors: No reported disclosures.
2774. Impact of Yellow Fever Vaccine and Recombinant Zoster Vaccine Shortages on Patients Presenting to a Travel Clinic
Authors: Baca Alec , Gundacker Nathan , Sanchez Joyce L 
Published: October 2019

Abstract

Background
In 2017, the United States experienced a national shortage of the yellow fever vaccine (YF-Vax). In response to this, the US Food and Drug Administration (FDA) approved the use of Stamaril in a limited number of clinics across the country. This was soon followed by a shortage of the recently approved recombinant zoster vaccine (RZV) in 2018. This project describes the impact of both vaccine shortages on patients presenting to the Travel Health Clinic at Froedtert and the Medical College of Wisconsin.

Methods
A retrospective review of Travel Health Clinic medical records between January and December of 2018 was performed. Information regarding patient demographics, travel destination, vaccination rates, reasons for not vaccinating, and referral information was obtained.

Results
Of the 306 patients seen in 2018, 98 were traveling to countries with active yellow fever transmission. Due to the YF-Vax shortage, 59.2% of these patients were referred to another clinic for Stamaril and 7.1% were unable to get the vaccine before departure. The remaining patients qualified for a medical exemption, had an itinerary that was lower risk for yellow fever, or their subsequent vaccine history was unknown. Additional cost for Stamaril at referral locations ranged from $169.50-$315.00 per person with a travel distance of 15–272 miles to the referred clinic. Regarding RZV, 134 clinic patients were qualified to receive the vaccine. 57.5% did not receive RZV due to vaccine shortage, 15.7% were referred to another clinic for RZV, while 15.7% were able to receive the vaccine during their appointment. Of these patients, 31.3% were covered under Medicare, thus necessitating referral to a pharmacy for vaccine coverage.

Conclusion
We encountered high rates of unvaccinated travelers who would have qualified for and benefitted from YF-Vax and RZV in 2018. Even among those who could receive the recommended vaccines, there was substantial additional cost and inconvenience. This illustrates the considerable negative impact of the YF-Vax and RZV vaccine shortages. Further efforts are necessary to make these vaccines more accessible to the community.

Disclosures
All authors: No reported disclosures.
2777. Live-Attenuated Vaccine Against RSV Generates Robust Cellular and Humoral Immune Responses
Authors: Mueller Steffen , Nouen Cyril Le , Buchholz Ursula J , Kalkeri Raj , Koide Fusataka , Collins Peter , Coleman J Robert 
Published: October 2019

Abstract

Background
In people over 65, there are on average 177,000 hospitalizations and 14,000 deaths because of respiratory syncytial virus (RSV) each year. Elderly patients infected with RSV can suffer serious infections leading to pneumonia and congestive heart failure. RSV vaccines have failed in the elderly in part because they have been unable to mount a robust cellular immune response.

Methods
RSV-MinL4.0 is a live-attenuated intranasal vaccine candidate that was generated by codon pair deoptimization of the L gene followed by the addition of four stabilizing mutations found via stress passaging. Four African Green Monkeys (AGMs) per group were vaccinated with RSV-MinL4.0 or wild-type (WT) RSV at 2 × 106 PFU, boosted on day 28 and challenged with wild-type (WT) RSV on day 104. Oropharyngeal swabs and tracheal lavage were collected daily and every other day, respectively, to evaluate virus shedding (qPCR) and blood was drawn on days 1, 14, 21, 28, and 49 for antibody titers (PRNT50), and PBMC activation (IFNγ ELISPOT with whole inactivated virus).

Results
MinL4.0 was 2 to 3 log10 attenuated when compared with WT RSV in AGMs. Despite the presence of antibodies on day 28, there was a “take” of the boost indicating the potential for this vaccine to be immunogenic in the elderly with pre-existing circulating antibodies (Figure 1A). MinL4.0 led to robust activation of PBMCs comparable to WT RSV (> 2,000 spots per 106 total cells, Figure 1B). Shedding of the vaccine and challenge viruses was minimal (data not shown).

Conclusion
MinL4.0 led to robust activation of cellular and humoral immune responses, which are critical for induction of protective immunity in the elderly. Animals were protected from WT challenge. Preliminary data in AGMs with pre-existing antibodies to RSV indicate that circulating antibodies do not prevent vaccine “take,” critical for a vaccine targeting sero-positive elderly individuals.

Disclosures
All authors: No reported disclosures.
2782. Host Immune Response to Enterovirus and Parechovirus Systemic Infections in Children
Authors: Sasidharan Anjana , Hassan Ferdaus , Selvarangan Rangaraj 
Published: October 2019

Abstract

Background
Enterovirus (EV) and human Parechovirus (PeV) cause a range of illness including asymptomatic to systemic infections. The host immune response in children, especially the one induced by PeV, is largely unknown. The aim of this study was to determine the immune response induced by EV and PeV in cerebrospinal fluid (CSF) and plasma obtained from children with systemic infection.

Methods
Left-over CSF and paired blood samples collected from children with laboratory confirmed EV and PeV central nervous system-infection were enrolled in this study. EV/PeV-negative CSF and paired plasma from children was used as controls. Level of cytokines and chemokines were measured using a customized 21-plex ELISA panel that included 16 cytokines and 5 chemokines (Millipore, CA). Additionally, clinical characteristics of all the patients were collected to determine the potential association between the immune response and pathogenicity.

Results
Total of 74 samples were enrolled and divided into 3 groups, EV (n = 27), PeV (n = 23) and control group (n = 24). Median age of all the three groups was 2 weeks (IQR 2–4 weeks).The key analytes which had a significant difference between each groups are show in the Table. In general, EV induced more robust cytokine secretion than PeV and control group. Anti-viral response such as IFN-g was remarkably absent in both CSF and plasma in PeV group compared with EV group (P < 0.05). Only IL-8 was significantly higher (P < 0.05) in EV CSF group compared with any other groups or sample types. Level of all the chemokines measured were much higher in all the three groups but significant difference was found between PeV CSF and plasma for IP-10 and MCP-1 chemokines (P < 0.05).

Conclusion
In this study, we demonstrate that EV and PeV induces distinct immune response in children with systemic infections. While EV induces more robust inflammation, PeV-induced inflammation appears to be either weak or absent in CSF, but robust in plasma. The suppressed pro-inflammatory response might facilitate PeV growth and proliferation in CSF and might play a role in disease severity. Further studies are needed to fully understand the differential immune response induced by these two viruses.

Disclosures
All authors: No reported disclosures.
2786. The Role of Respiratory Panel PCR in Decreasing Antibiotic Exposure in Patients Diagnosed With a Respiratory Viral Infection
Authors: Vostal Alexander , Gonzalez Michael Antonio , Darling Nellie , Papastamelos Christine , Natarajan Madhuri , Kumar Princy , Timpone Joseph 
Published: October 2019

Abstract

Background
Respiratory viral infections (RVI) are becoming increasingly recognized as an important cause of pneumonia. There is limited data regarding the role of rapid PCR testing for RVI and its effect on antibiotic duration and length of stay (LOS).

Methods
We performed a single-center, retrospective chart review in adult patients who were admitted and underwent evaluation with the FilmArray Multiplex Respiratory Panel (RP) (Biomerieux™) using a random sample from July 1, 2016 through April 1, 2018. Patient clinical and virologic characteristics, LOS, antibiotic use, and duration of treatment were collected. A Student’s t-test was performed for all comparisons.

Results
We identified 540 patients who were admitted and underwent RP testing. The mean age was 57.1 years (range 19–99), 50.2% were immunocompromised, 23.8% were transplant recipients, 70.4% had respiratory symptoms, and 35.7% had an admitting diagnosis of pneumonia. 55.6% required supplemental O2 and 24.6% had an ICU admission that required either noninvasive or mechanical ventilation. 22.6% (N = 122) of these patients were diagnosed with an RVI, of which 15 were co-infected with two or more respiratory viruses. There were 41 (34%) rhinovirus/enterovirus, 41 (34%) influenza (Types A/H1, A/H3, A/H1-2209, and B), 16 (13%) RSV, 15 (12%) coronavirus (Types NL63, OC43, 229E, and HKU1), 13 (11%) metapneumovirus, and 7 (5%) parainfluenza (Types 2, 3, and 4). 85.2% (104/122) of patients with an RVI received antibiotics. The mean LOS and antibiotic duration were 9.07 days and 7.31 days for patients with an RVI when compared with 11.5 days and 10.4 days for patients without an RVI (P = 0.098; P = 0.032), respectively. In patients with an RVI and negative bacterial cultures, the mean LOS was 8.4 days and mean antibiotic duration was 5.9 days when compared with 16.4 days and 15.5 days for all patients with positive bacterial cultures (P = 0.003; P < 0.0001), respectively. The mean time from available results of + RP to antibiotic discontinuation was 5.1 days in the setting of negative bacterial cultures.

Conclusion
Although antibiotic exposure and time to discontinuation still remained significant in patients diagnosed with an RVI, there was a marked reduction in LOS and antibiotic duration in the subset of patients with an RVI and negative bacterial cultures.

Disclosures
All authors: No reported disclosures.
172. Risk Factors for 30-Day Mortality in Patients with Staphylococcus aureus Bacteremia at a Community Hospital: A Prospective Case–Control Study
Authors: Hoffmann Charles , Watkins Gordon , DeSimone Patrick , Hallisey Peter , Hutchinson David , Colodny Stephen , Burket Jeffrey , Michael Amanda , Klein Jo-anne , Welc Christina 
Published: October 2019

Abstract

Background
Staphylococcus aureus bacteremia (SAB) is associated with 30-day all-cause mortality rates approaching 20–30%. The purpose of this case–control study was to evaluate risk factors for 30-day mortality in patients with SAB at a community hospital.

Methods
As part of an antimicrobial stewardship program (ASP) initiative mandating Infectious Diseases consultation for episodes of SAB, our ASP prospectively monitored all cases of SAB at a 341-bed community hospital in Jefferson Hills, PA from April 2017–February 2019. Cases included patients with 30-day mortality from the initial positive blood culture. Only the first episode of SAB was included; patients were excluded if a treatment plan was not established (e.g., left against medical advice). Patient demographics, comorbidities, laboratory results, and clinical management of SAB were evaluated. Inferential statistics were used to analyze risk factors associated with 30-day mortality.

Results
100 patients with SAB were included; 18 (18%) experienced 30-day mortality. Cases were older (median age 76.5 vs. 64 years, P < 0.001), more likely to be located in the intensive care unit (ICU) at time of ASP review (55.6% vs. 30.5%, P = 0.043), and less likely to have initial blood cultures obtained in the emergency department (ED) (38.9% vs. 80.5%, P < 0.001). Variables associated with significantly higher odds for 30-day mortality in univariate analysis: older age, location in ICU at time of ASP review, initial blood cultures obtained at a location other than the ED, and total Charlson Comorbidity Index (CCI). Variables with P < 0.2 on univariate analysis were analyzed via multivariate logistic regression (Table 1).

Conclusion
Results show that bacteremia due to MRSA and total CCI were not significantly associated with 30-day mortality in SAB, whereas older age was identified as a risk factor. Patients with initial blood cultures obtained at a location other than the ED were at increased odds for 30-day mortality on univariate analysis, which may raise concern for delayed diagnosis.

Disclosures
All authors: No reported disclosures.