bluuebunny/crossref_metadata_2025_split huggingface dataset:
902. A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of a Single Immunization of Ad26.RSV.preF against RSV Infection in a Viral Challenge Model in Healthy Adults
Authors: DeVincenzo John , Gymnopoulou Efi , De Paepe Els , Murray Bryan , Rosemary Bastian Arangassery , Haazen Wouter , Noulin Nicolas , Comeaux Christy , Heijnen Esther , Eze Kinglsey , Gilbert Anthony , Lambkin-Williams Rob , Schuitemaker Hanneke , Callendret Benoit , Sadoff Jerald 
Published: October 2019

Abstract

Background
Despite the high disease burden of RSV in older adults and children, there is currently no approved vaccine. Ad26.RSV.preF, an experimental RSV vaccine, has demonstrated immunogenicity and tolerability in first-in-human clinical studies. The aim of this study was to assess the potential of the Ad26.RSV.preF vaccine to protect against RSV infection and disease in an established RSV human challenge model, used for the first time to evaluate a vaccine.

Methods
We conducted a randomized, double-blind, placebo-controlled, human challenge study (NCT03334695). Healthy adults received 1 × 1011 vp Ad26.RSV.preF vaccine (active) or placebo (pbo) intramuscularly. After 28 days, volunteers were challenged intranasally with a low-passage clinical strain of RSV-A (0.8 mL of Memphis 37b) and then quarantined for 12 days. Nasal washes were collected twice daily throughout quarantine, starting 2 days post-challenge (viral load [VL] by qRT-PCR and quantitative cultures). Disease severity was recorded thrice daily using symptom diary cards.

Results
Fifty-three volunteers (active, n = 27; pbo, n = 26) were challenged with RSV-A. Quantitative viral assessments were consistently lower in active than pbo. The primary endpoint of the study was met: the area under the curve (AUC) for RSV VL over time (via qRT-PCR) was significantly lower in active pbo (P = 0.012). Median peak VL was lower for active (0 log10 copies/mL) than pbo (5.4 log10 copies/mL). Median AUC for RSV VL over time (quantitative culture) was lower for active than pbo (0 vs. 109, P = 0.002). Disease severity was lower for active than pbo, with a median AUC total symptom score of 35 (active) vs. 167 (pbo) (P = 0.002). Overall, RSV infection (defined by qRT-PCR alone or combined with symptoms) and disease severity over time were lower in active vs. pbo.

Conclusion
RSV infections, VL, and RSV disease severity were consistently lower in healthy adults receiving Ad26.RSV.preF vs. placebo, demonstrating promising protection from RSV infection and disease. This was the first time that antiviral prevention was observed against RSV after active immunization. Ad26.RSV.preF warrants further evaluation in field trials for efficacy against natural RSV infections in populations considered at risk of severe RSV disease.

Disclosures
All Authors: No reported Disclosures.
978. Changes in BMI Associated with Antiretroviral Regimens in Treatment-Experienced, Virologically Suppressed Individuals Living with HIV
Authors: Mounzer Karam , Brunet Laurence , Hsu Ricky , Fatukasi Terra , Fusco Jennifer S , Vannappagari Vani , Henegar Cassidy , van Wyk Jean A , Crawford Melissa , Lo Janet , Fusco Gregory 
Published: October 2019

Abstract

Background
A potential association between integrase inhibitor (INSTI) use and weight gain has been reported in people living with HIV (PLWH). We examined body mass index (BMI) increases after a switch to dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV) among virologically suppressed ART-experienced PLWH.

Methods
ART-experienced, suppressed (ART-ES; baseline viral load < 200 copies/mL) PLWH ≥ 18 years of age initiating DTG, EVG/c, RAL, RPV, or bDRV for the first time were identified in the OPERA® cohort. The association between core agents and mean increases in BMI at 6, 12, and 24 months was estimated with multivariable linear regression. Inverse probability-of-censoring weights (IPCW) were used to account for censoring (regimen discontinuation, loss to follow-up, death, pregnancy, or no BMI measured). Analyses were stratified by baseline BMI categories (underweight: <18.5, normal weight: ≥18.5 to <25, overweight: ≥25 to <30, obese: ≥30).

Results
At baseline, endocrine disorders were reported in >40% of PLWH receiving DTG and RAL; >60% were overweight/obese in all groups (Figure 1). Mean BMI (unadjusted) increased for all ARVs over time, with changes at 24 months ranging from 0.30 (DRV) to 0.83 (RPV, Figure 2). At 6 months, the adjusted mean BMI increase was statistically smaller with EVG/c, RAL, and bDRV (range –0.15 to –0.30) than with DTG (Figure 3); these differences only remained significantly different for bDRV at 12 (–0.29) and 24 months (–0.29, Figure 3). Among those with a normal baseline BMI, the adjusted mean change in BMI at 12 months was smaller with EVG/c, bDRV, and RAL than DTG (range –0.26 to –0.27). Among overweight PLWH, the adjusted mean BMI increase was statistically smaller with bDRV than DTG (–0.32, Figure 4). Results were consistent in IPCW estimates.

Conclusion
The majority of PLWH on stable ART in this US-based cohort were overweight/obese at the time of switch to the regimens of interest. Small mean increases in BMI for all regimens were noted over time, for which the clinical significance is not yet known. Apparent differences in BMI changes favoring EVG/c, RAL, and bDRV vs. DTG over the short term were largely attenuated with longer follow-up, with significant differences mainly observed in those with a normal BMI at baseline.

Disclosures
All Authors: No reported Disclosures.
1832. Development of an Ultrasensitive Field-Applicable Plasmodium falciparum Assay for Malaria Diagnosis and Eradication
Authors: Lee Rose , De Puig Guixe Helena , Dvorin Jeffrey , Collins James 
Published: October 2019

Abstract

Background
Malaria control and eradication have been hampered by asymptomatic carriage which serves as a parasite reservoir. Low-density infections (< 100 parasites/microliter) frequently fall below the limit of detection (LOD) of microscopy and rapid diagnostic tests (RDT) which are antigen-based tests. Molecular methods such as polymerase chain reaction are capable of higher sensitivity yet remain impractical for resource-limited settings. We describe development of an isothermal assay using the nucleic acid detection platform SHERLOCK (Specific High-Sensitivity Enzymatic Reporter UnLOCKing), which may also be increasingly important as there has been rising detection of histidine-rich protein 2 (HRP2) gene deletions in Plasmodium spp. HRP2 is the most commonly used antigen in RDTs and deletion of this gene would render many RDTs obsolete.

Methods
SHERLOCK leverages the endonucleases of CRISPR-associated microbial adaptive immunity. Cas12a is an RNA-guided, DNA-cleaving enzyme, which can be programmed with guide RNAs to cleave nontarget reporter ssDNA. We exploit the nonspecific degradation of labeled ssDNA to detect the presence of the dsDNA target that activated Cas12a (Figure 1). Recombinase polymerase amplification (RPA) coupled with Cas12a detection enables a lower LOD. Plasmodium falciparum whole genomic DNA was compared with parasites cultured in red blood cells (RBCs) with known parasitemia and boiled at 95°C for 5 minutes for lysis of RBCs/parasites then diluted 1:2.5 to prevent solidification.

Results
This SHERLOCK assay detected simulated Plasmodium falciparum infection at attomolar LODs when applied to whole genomic DNA and simulated samples of infected RBCs spiked into whole blood. The genomic assay detected down to 0.2 parasites/microliter and the simulated sample detected to 10 parasites/microliter in the final reaction volume. In comparison, LODs from the initial input volume was 5aM and 250aM, respectively (Figure 2).

Conclusion
We demonstrate an isothermal nucleic acid detection platform capable of diagnosis in 60 minutes in a one-pot assay requiring minimal sample preparation and reaching an LOD recommended by the WHO for malaria eradication. In summary, we illustrate the utility of the SHERLOCK platform in application to malaria and global health.

Disclosures
All Authors: No reported Disclosures.
1873. Pregnancy and Birth Outcomes Among Colombian Women with Zika Virus Disease in 3 Surveillance Sites, Proyecto Vigilancia de Embarazadas con Zika
Authors: Honein Margaret (Peggy) , Mercado Marcela , Gilboa Suzanne , Valencia Diana , Daza Marcela , Galang Romeo , Winfield Christina , Godfred-Cato Shana , Benavides Mónica , Villanueva Julie , Daniels Jonathan , Bhatnagar Julu , Schiffer Jarad , Corchuelo Sheryll , Tinker Sarah , Anderson Kayla , Osorio Johana , Burkel Veronica , Hojnacki Jacob , Tong Van , Gonzalez Maritza , Moore Cynthia , Lucia Ospina Martha 
Published: October 2019

Abstract

Background
Proyecto Vigilancia de Embarazadas con Zika (VEZ) was an intensified surveillance system built upon existing national surveillance of pregnant women with symptoms of Zika virus (ZIKV) disease and conducted in three Colombian cities with a high prevalence of Zika. This analysis of data from VEZ estimates the risk of Zika-associated birth defects among pregnant women with symptoms of ZIKV disease, and among a subset with laboratory evidence of possible ZIKV infection during pregnancy.

Methods
During April–November 2016, pregnant women were enrolled if they were reported to the surveillance system (Sivigila) or visited participating clinics with symptoms of ZIKV disease. Maternal and pediatric data were abstracted from prenatal care, ultrasound, and delivery records, as well as from pediatric or specialist visit records. Available maternal and infant specimens were tested for the presence of ZIKV RNA and/or anti-ZIKV immunoglobulin (IgM) antibodies.

Results
Of 1,223 women enrolled, 47.8% and 34.3% reported first or second trimester symptom onset, respectively. Of 381 pregnancies with maternal and/or infant specimens tested, 108 (29%) had laboratory evidence of possible ZIKV infection during pregnancy; half of these (53.3%) were positive for ZIKV RNA only, 37.4% for IgM antibodies only, and 9.3% for both. Of 1,190 of pregnancies with known outcome, 63 (5%) had Zika-associated brain or eye defects; among the subset with any laboratory evidence, 12 (11%) had Zika-associated brain or eye defects. The prevalence of Zika-associated brain or eye defects was 5.9% (35/593) and 4.5% (19/423) among pregnancies with symptom onset in the first and second trimester, respectively.

Conclusion
Among pregnant women with symptoms of ZIKV disease enrolled during the height of the ZIKV epidemic in Colombia, prevalence of any Zika-associated brain or eye defect was 5%, with a higher prevalence among those with laboratory evidence of possible ZIKV infection. Rapid enhancements to Colombia’s national surveillance enabled the estimation of the risk of birth defects associated with ZIKV disease in pregnancy.

Disclosures
All Authors: No reported Disclosures.
1875. La Crosse Virus Neuroinvasive Disease in Children: A Contemporary Review and Evaluation for Predictors of Disease Severity
Authors: Boutzoukas Angelique Eleni , Freedman Daniel , Garrett Hunt W , Mack Kathleen A , Yildiz Vedat , Chung Melissa , Twanow Jamie , de los Reyes Emily , Ouellette Christopher 
Published: October 2019

Abstract

Background
La Crosse Virus (LACV) is the most common neuroinvasive arboviral disease in children. Contemporary data on clinical presentation, management, outcomes, and predictors of disease severity are lacking.

Methods
A retrospective analysis was performed of children (0–18 years) admitted to Nationwide Children’s Hospital from January 2009 to December 2018 diagnosed with LACV neuroinvasive disease (LACV-ND). LACV-ND diagnosis was defined as a compatible clinical illness and serum serologic detection of LACV in the absence of other infectious etiologies. Demographic, clinical, laboratory, electroencephalography (EEG), radiologic, and outcome data were recorded. Severe disease was defined as the presence of clinical or electroencephalographic status epilepticus, SIADH, PICU admission, mechanical ventilation (MV), parenteral/tube feeding, inpatient rehab, or intracranial pressure monitoring. Single variable and multivariate analyses were performed to determine factors predictive of disease severity.

Results
Of the 140 patients, 76 (54%) males with a median age of 8 years [10 months-16 years], were identified with LACV-ND. Symptoms at presentation, laboratory abnormalities, EEG, radiography, and outcomes are shown in Table 1. Fifty-seven (41%) patients met criteria for severe disease, notably for PICU admission (n = 41), status epilepticus (n = 35), MV (n = 13), and inpatient rehab (11). No in-patient deaths were observed. Exploratory analysis revealed that patients with severe disease were often younger at presentation, had higher rates of altered mental status (AMS), and seizures. Elevated serum white blood cell counts (WBC) and polymorphonuclear cell (PMN) predominance in serum and cerebrospinal fluid (CSF) were observed more frequently in severe disease. Multivariate analysis revealed presentation with seizures (OR 4.7 [95% CI 1.7–12.6], P = 0.001), elevated serum WBC (OR 1.7 [95% CI 1.2–2.5], P = 0.004), and a higher CSF PMN% (OR 1.03 [95% CI 1.01–1.06, P = 0.003) to be independent predictors of severe disease.

Conclusion
At presentation, patients with severe disease tended to be younger, have greater rates of neurologic symptoms, and leukocytosis with PMN predominance in blood and CSF. These clinical and laboratory findings may serve as useful biomarkers to predict disease severity.

Disclosures
All Authors: No reported Disclosures.
1890. Missed Clinical Opportunities to Prevent Infections and Treat Substance Use Disorder (SUD) in People Who Inject Drugs (PWID)
Authors: Bardossy Ana C , Gokhale Runa H , Hartnett Kathleen , Hatfield Kelly M , Jackson Kelly A , Felsen Christina B , McDonald Robert , Kracalik Ian , Lucas Todd , McGovern Olivia L , Van Beneden Chris , Vallabhaneni Snigdha , Williams Sabrina R , Mendoza Michael , Bohm Michele K , Brooks John , Asher Alice K , Magill Shelley S , Fiore Anthony , Blog Debra , Dufort Elizabeth , See Isaac , Dumyati Ghinwa 
Published: October 2019

Abstract

Background
The age-adjusted rate of drug overdose deaths in the United States tripled from 1999 to 2016. Public health surveillance data indicate that an increasing proportion of infections due to bacterial and fungal pathogens is associated with injection drug use (IDU). We describe healthcare encounters (HCEs) of PWID as potential opportunities to prevent infections related to IDU by identifying risks and treating SUD, including with medication-assisted treatment (MAT) for opioid use disorder.

Methods
At six hospitals in western New York, we abstracted medical records from hospital admissions and emergency department (ED) visits for PWID (i.e., IDU in the preceding year) who had positive cultures for Staphylococcus aureus (any clinical specimen, April–July 2017), group A Streptococcus (invasive specimens, all of 2017) or Candida spp. (blood specimens, all of 2017). We reviewed hospital admission and ED records for 1 year preceding the positive culture to identify visits during which opportunities to prevent infection and treat SUD by addressing SUD and IDU were missed.

Results
We identified 99 PWID with positive cultures. The median age was 33 years (range 19–68) and 61 were female. Sixty-nine had a skin and soft-tissue infection, 44 had a bloodstream infection, and 20 had both. Thirty-one PWID left against medical advice during a hospital admission or an ED visit. Seventy-nine PWID were hospitalized, of whom 4 died. Ninety-five used opioids and 71 used cocaine in the preceding year. Seventy-five PWID had an HCE in the 12 months prior to the index visit, with a median of two HCE per person (interquartile range 1–4); 53 of PWID had a previous HCE for infection and 28 for opioid overdose. SUD was documented during a prior HCE at the same hospital for 61 PWID, but only 10 (16%) were offered MAT during any prior HCE and for 24 (39%) there was no documentation that any form of treatment for SUD was offered.

Conclusion
In this cohort, PWID frequently had one or more healthcare encounters documented at the same hospital in the year prior to a serious bacterial or fungal infection. These prior HCEs were often for infections or overdose that signaled the need for MAT, demonstrating that there are critical missed opportunities to identify risks, prevent infection, and treat SUD.

Disclosures
All Authors: No reported Disclosures.
1960. Lost in Translation: Comparing Rates of Outpatient Antibiotic Use in Three Metrics
Authors: Prestel Christopher , King Laura M , Bartoces Monina , Neuhauser Melinda M , Hicks Lauri , Fleming-Dutra Katherine E 
Published: October 2019

Abstract

Background
The Centers for Disease Control and Prevention (CDC) tracks US outpatient antibiotic use in prescriptions per 1000 persons (Rx/1000), while the World Health Organization uses defined daily doses per 1000 persons (DDD/1000), which are based on average adult dose, for global surveillance. A third metric, days of therapy (DOT)/1,000 persons, has not been previously evaluated at the national level. We aim to compare time trends in outpatient oral antibiotic use as Rx/1000, DDD/1000, and DOT/1,000 in the same data to inform ongoing CDC surveillance and facilitate international comparison.

Methods
We identified dispensed outpatient oral antibiotics using pharmacy claims in 2011–2016 IBM® MarketScan® Commercial Databases for individuals <65 years old. Using enrollment data, we calculated mean annual membership with drug coverage. Annual rates of outpatient oral antibiotic use were calculated for Rx/1000, DDD/1000, and DOT/1000 persons. Prescriptions written with a ratio of DDD to days supplied >10 were considered biologically implausible and excluded from DDD calculations. We examined trends for each metric from 2011 to 2016 using negative binomial regression.

Results
Annual numbers of outpatient oral antibiotic prescriptions ranged from 18.6 million to 30.0 million (mean 24.3 million). Overall, Rx/1000 decreased by 7% from 892 in 2011 to 829 in 2016 (Figure 1). From 2011 to 2016, DDD/1000 increased 2% from 23.8 to 24.2 while DOT/1000 decreased 9% from 25.4 to 23.1. Significant per-year decreases were found from 2011 to 2016 for Rx/1000 (−1.1%) and for DOT/1000 (−1.6%), while no significant per-year change was seen with DDD/1000 (table). DDD/1000 underestimate use in pediatrics under the age of 10 (Figure 2). Prolonged duration is seen in adolescents and reflected by DOT/1000.

Conclusion
Trends in DDD/1000 for population aged <65 years do not mirror trends in Rx/1000 and DOT/1000. These differences may reflect that Rx/1000 and DOT/1000 more accurately capture antibiotic prescriptions in children than DDD/1000. As DDD/1000 underestimate antibiotic use in children, DDD/1000 underestimates reduction in antibiotic use over time and may not accurately reflect changes in use over time.

Disclosures
All Authors: No reported Disclosures.
1961. Grindr™ on Screen Activity on iPhones Correlates with HIV Risk and Substance Use in Men Who Have Sex with Men, San Diego
Authors: Hoenigl Martin , Little Susan J , Stockman Jamila K , Skaathun Britt , Grelotti David , Weibel Nadir , Smith Davey M 
Published: October 2019

Abstract

Background
Technology has changed the way men-who-have-sex-with-men (MSM) seek sex; ≥60% of MSM in the United States use the internet to find sex partners, primarily via Grindr™ which is the most used dating app among MSM. Studies to date have mostly evaluated Grindr™ use as a dichotomous variable and found inconsistent results regarding associations with increased HIV risk behavior. Importantly, Grindr™ “on-screen” activity is monitored by phones and can provide an objective measure of app usage. Here we aimed to assess Grindr™ “on-screen” activity in MSM undergoing community-based HIV and sexually transmitted infection (STI) screening in San Diego, and to correlate activity with sexual risk behavior and substance use.

Methods
This nested cohort study was conducted between December 2018 and April 2019 and leveraged our “Good to Go” (AI106039) screening program for participant recruitment. During their testing encounter participants not on HIV PrEP were provided with surveys on demographics, substance use and risk behavior during previous 3 months, and Grindr™ usage. Participants with iPhones were instructed on how to assess Grindr™ on-screen activity (i.e., time on-screen during last 7 days) on their phones (Figure 1). Risk behavior was classified using the validated San Diego Early Test (SDET) Score (Figure 2).

Results
Overall 378/784 (48%) MSM participants indicated that they had opened Grindr™ during the previous 7 days. Grindr™ users had higher SDET scores than those not using Grindr™ (median SDET 2, IQR 0–5; mean 2.29) while there was no difference in proportion of substance users (alcohol and marijuana excluded, 21% vs. 17%; P = 0.14). Of 231 MSM who indicated recent Grindr™ use (61%) had iPhones; median on-screen activity during the previous 7 days was 144 minutes (range 1–2,640 minutes). Participants with high Grindr™ utilization (>80th percentile of time on screen corresponding to >480 minutes), had significantly higher SDET scores (median 5 vs. 2; mean 4.02 vs. 3.26; P < 0.001) and a tendency toward a higher proportion of substance users (29% vs. 20%) than those with lower Grindr™ utilization.

Conclusion
This study introduces Grindr™ on-screen activity as an objective measure that can help identify MSM at high risk for HIV.

Disclosures
All Authors: No reported Disclosures.