bluuebunny/crossref_metadata_2025 huggingface dataset:
860. Immediate Access to Post-Exposure Prophylaxis (PEP) Through a 24/7 New York City PEP Hotline
Authors: Glaser Allison , Kaplan-Lewis Emma , Ventuneac Ana , Gates Wyley , Cruz Michael , Aracena Joaquin , Tider Diane , Duah Bianca , Aberg Judith , Urbina Antonio
Published: November 2018

Background

Oral post-exposure prophylaxis (PEP) is effective in preventing HIV transmission. To minimize barriers to PEP for New York City (NYC) residents, the Institute for Advanced Medicine (IAM), Mount Sinai Health System, and the NYC Department of Health and Mental Health established a 24-hour 7-days PEP hotline to provide eligible callers with immediate access to PEP and follow-up clinical care.

Methods

Data from hotline callers (January to December 2017) was analyzed utilizing multivariable logistic regression to determine whether a call resulted in PEP access within 72 hours of exposure by sociodemographic variables and exposure characteristics. We describe transitions from PEP to PrEP (pre-exposure prophylaxis).

Results

The PEP hotline cohort (n = 1278) was 83% male, 11% female, 1% transgender; 66% LGBTQ and 20% heterosexual; 35% White, 15% Black, 9% Asian; 41% other/unknown; 25% Hispanic; mean age of 30 years (range 14–72). The majority of callers learned about the hotline by Internet search (59%). Mean exposure time prior to call was 31 hours with 57% within 24 hours. Exposures were 98% sexual; 73% anal sex (43% receptive; 30% insertive), 21% vaginal, and 6% other. 63% reported condomless sex and 29% condom failure. 15% of callers reported a partner with HIV. 35% of callers reported alcohol or recreational substances at the time of the exposure. Prior PEP and PrEP use was 20% and 9%, respectively. 91% of callers were eligible for PEP; 69% called afterhours and received a telephone PEP prescription, and 27% called during business hours and were directed to a clinic. Access to PEP within 72 hours of exposure occurred in 1,081 (93%) of eligible callers and within 36 hours in 68%. 90% of callers had confirmed follow-up clinic appointments. Of the 472 callers linked to care at the IAM, 89 (19%) transitioned to PrEP.

Conclusion

This unique program demonstrates a timely initiative to facilitate PEP access to a diverse cohort with the purpose of mitigating risk from potential exposure to HIV. Further investigation is needed to explore adherence to PEP, follow-up testing results, transitions to PrEP for prevention planning, and coordination of health care and substance use services.

Disclosures

E. Kaplan-Lewis, Viiv: Consultant, Consulting fee. J. Aberg, Gilead: Research Contractor, Research support. GSK: Research Contractor, Research support. ViiV: Research Contractor, Research support. A. Urbina, Theratechnologies: Scientific Advisor, Consulting fee. ViiV: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Gilead: Scientific Advisor, Consulting fee.
866. Increased Diagnosis of Varicella-Zoster Virus Infection of the Central Nervous System With the BioFire FilmArray Meningitis/Encephalitis Panel
Authors: Chen Lynette , Pettengill Matthew , Hess Bryan , DeSimone Joseph
Published: November 2018

Background

Varicella-zoster virus (VZV) infection of the central nervous system (CNS) is relatively uncommon. Diagnostic tests historically utilized culture, serologies, and targeted PCR methods. In April 2016, our institution began using the BioFire FilmArray meningitis/encephalitis (BFME) panel for cerebrospinal fluid (CSF) specimen analysis. We hypothesized that the diagnosis of VZV CNS infection increased at our institution with the implementation of this diagnostic panel.

Methods

We conducted chart reviews of patients from 2 time periods. In the first period, April 2013–March 2016, BFME was not available for CSF analysis (pre-BFME period). We reviewed all positive CSF VZV PCR results during this period. Medical charts of these patients were reviewed for epidemiology, clinical presentation, treatment course, and outcome. In the second period, April 2016–March 2018, BFME was performed on all CSF specimens obtained by lumbar puncture (BFME period). Patients with a positive VZV result on BFME underwent similar chart review.

Results

In the 3-year pre-BFME period, 292 VZV PCR tests were performed. Six patients were diagnosed with VZV CNS infection; median age 61 years. Five of the 6 patients (83%) had cutaneous zoster. All 6 patients received antiviral therapy. Five of the 6 patients clinically improved; 1 patient with VZV encephalitis died. In the 2-year BFME period, 1,113 CSF samples were evaluated, and 18 of these were positive for VZV (1.6%); median age 55 years. Only 7 of the 18 (39%) had cutaneous zoster at the time of hospitalization. All 18 received antiviral therapy with clinical improvement.

Conclusion

Prior to implementation of the BFME panel at our institution, VZV CNS infection was rarely diagnosed. Diagnosis at that time relied on physicians’ requests for a targeted CSF VZV PCR. The majority of the patients during that period had a concurrent zoster rash. In a shorter period utilizing syndromic testing (BFME) on CSF specimens, we diagnosed 3 times as many cases of VZV CNS disease. Only a minority of these patients presented with a concurrent zoster rash. The use of syndromic testing of CSF will likely identify more cases of VZV CNS disease.

Disclosures

All authors: No reported disclosures.
868. Prospective Pathogen Detection in Patients With Central Nervous System Inflammation Using Metagenomic Sequencing
Authors: Piantadosi Anne , Mukerji Shibani , Ye Simon , Leone Michael , Freimark Lisa , Lemieux Jacob , Solomon Isaac , Ahmed Asim , Kanjilal Sanjat , Goldstein Robert , Ganesh Vijay , Ostrem Bridget , Thon Jesse , Kinsella Cormac , Adams Gordon , Rosenberg Eric , Goldberg Marcia , Sabeti Pardis , Cho Tracey
Published: November 2018

Background

Metagenomic sequencing can identify pathogens in patients with central nervous system (CNS) inflammation, who often have no diagnosis achieved despite extensive clinical testing.

Methods

This prospective study enrolled patients with CNS inflammation at a tertiary hospital from 2016 to 2017. Total nucleic acid was extracted from cerebrospinal fluid (CSF). Libraries were constructed by random primer cDNA synthesis from RNA, and Nextera XT preparation from both cDNA and DNA. Sequencing was performed on an Illumina platform. Reads from human and environmental contaminants were removed. Metagenomic analysis was performed with Kraken and confirmed with viral-ngs. The Institutional Review Board approved the study, and informed consent was obtained.

Results

Of 68 subjects enrolled, 63% were men and 84% were white. The median age was 58 years. The median CSF pleocytosis was 80 cells/mm3 [IQR 17–132]. A median of 2.4 million RNA and 6.8 million DNA sequencing reads were generated per sample. Twenty-five subjects had no diagnosis achieved by routine clinical testing; metagenomic sequencing identified enterovirus in 2 of these subjects, and no pathogen in 23. Thirty-six subjects were clinically diagnosed with an infection. In 12 of these, pathogen nucleic acid was detected in CSF by clinical polymerase chain reaction (PCR); metagenomic sequencing detected the expected pathogen in 10 subjects (83%). The other 24 subjects were clinically diagnosed with infection by serology or PCR from blood. Among these, metagenomic sequencing detected the CSF presence of HIV and locally important tick-borne pathogens Powassan virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. Four subjects with West Nile Virus (WNV) infection did not have WNV RNA detected in CSF by sequencing or clinical PCR testing. Among 7 subjects diagnosed with malignancy or autoimmune disease, no pathogens were detected by metagenomic sequencing.

Conclusion

When applied broadly to patients with CNS inflammation, metagenomic sequencing identified known and unexpected pathogens in CSF, including emerging tick-borne pathogens, highlighting its potential as a diagnostic tool. Patients in whom no pathogen nucleic acid was detected could have had an infection with low pathogen burden or short duration in CSF, or a noninfectious syndrome.

Disclosures

All authors: No reported disclosures.
931. Telemedicine for the Treatment of Hepatitis C: A Systematic Review and Meta-Analysis
Authors: De Gijsel David , Kruger Blake , Hakim Dema , Moore Sarah
Published: November 2018

Background

Hepatitis C (HCV) is a curable cause of liver disease, typically treated by specialists. Access to specialists is limited in rural areas. Telemedicine between generalists and specialists could yield outcomes comparable with care provided by specialists in face-to-face (FTF) encounters. To assess the effectiveness of HCV treatment through telemedicine compared with usual care, as measured by sustained virologic response (SVR).

Methods

We searched MEDLINE, the Cochrane Library, ClinicalTrials.gov, the Database of Abstracts of Reviews of Effects, and Excerpta Medica DataBASE from inception to March 2018. We included Randomized Controlled Trials (RCTs) and cohort studies comparing telemedicine in rural settings to FTF encounters with specialists in treating HCV. Studies reported cure as measured by SVR. We did not apply any exclusion criteria. At least 2 independent researchers used PRISMA guidelines to extract data. We used a modified Newcastle-Ottawa Scale and the Cochrane Collaboration Tool for Assessing Risk of Bias to assess observational studies and RCTs. We used a random-effects model to calculate pooled odds ratios (OR). The primary outcome was clinical cure. Cure was defined as SVR at 12 weeks after completion of treatment.

Results

Of 1,211 potentially eligible studies, 10 studies, representing 43,117 subjects, met inclusion criteria. Pooled analysis showed no difference in the odds of achieving SVR when comparing telemedicine to FTF specialist care (OR 1.01 [95% CI 0.78–1.30]). This result was robust across sensitivity analyses, including restriction to patients who completed treatment (OR 0.78 [95% CI 0.43–1.43]), exclusion of outliers, and exclusion of abstracts. There was significant heterogeneity [P = 0.003, I2 = 64].

Conclusion

In rural areas with limited access to specialists, care provided by telemedicine-supported generalists is as effective as FTF specialist care in achieving cure of HCV. Telemedicine is a viable option to expand access to HCV care in rural settings.

Disclosures

All authors: No reported disclosures.
932. Universal Hepatitis C Virus Screening in a Tennessee Tertiary Care Emergency Department
Authors: Chastain Cody A , Johnson Jakea , Miller Karen , Moore Katie , Lako Amanda , Zuckerman Autumn , Han Jin H , Self Wesley H
Published: November 2018

Background

Despite hepatitis C virus (HCV) age cohort and risk factor screening recommendations, many at-risk individuals remain undiagnosed. Current screening practices may not adequately capture those at high risk for infection, especially in regions with increasing injection drug use (IDU). Universal HCV screening in a Tennessee tertiary care emergency department (ED) was introduced to help define regional epidemiology and to improve diagnosis and linkage to care.

Methods

This screening program was implemented in the Vanderbilt University Medical Center ED. Adult patients who underwent phlebotomy for clinical purposes were offered HCV screening. Samples were initially tested for HCV antibodies; if positive, samples were reflexed for HCV RNA testing. Patients with positive HCV RNA tests (i.e., active HCV infection) were notified, counseled, and offered linkage to care.

Results

A total of 11,637 screening tests were performed between April 1, 2017 and March 31, 2018, with 1,008 (8.7%) HCV antibody positive and 488 (4.2%) RNA positive. Of note, 81 (0.7%) were HCV antibody positive but RNA testing could not be performed due to insufficient sample volume. Several notable populations had high rates of HCV (Table 1). Importantly, 3.9% of people not born between 1945 and 1965 were HCV RNA positive, and they were the majority (63.5%) of patients with active HCV (Table 2). A minority (31.6%) of those with active HCV had a known history of IDU (Table 2).

Conclusion

HCV is common among patients presenting for emergency care at a Tennessee tertiary care ED. Universal screening identified many infections that would have been missed using age cohort and risk factors alone. ED HCV screening may be a useful method to augment guideline-based testing and intervene among populations not consistently screened.

Disclosures

C. A. Chastain, Gilead Sciences, Inc.: Grant Investigator and Research Contractor, Grant recipient and Research support. J. Johnson, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. K. Miller, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. J. H. Han, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. W. H. Self, Gilead Sciences, Inc.: Grant Investigator, Grant recipient.
935. Repeat Pregnancies Among Women Living With HIV: Evaluating Temporal Changes in HIV Disease Status and Exploring the Association Between Preterm Birth and Protease Inhibitor Use in Pregnancy
Authors: O’Brien Brigid , Williams Paige , Kacanek Deborah , Chadwick Ellen , Powis Kathleen , Correia Katharine , Haddad Lisa B , Yee Lynn , Chakhtoura Nahida , Dola Chi , Van Dyke Russell B ,   The Pediatric HIV/AIDS Cohort Study
Published: November 2018

Background

With improved treatment, women living with HIV (WLHIV) are increasingly becoming pregnant. Studies have shown suboptimal viral suppression following pregnancy. In addition, protease inhibitors (PI) have been associated with preterm birth (PTB).

Methods

We studied WLHIV with at least 2 live births while on the PHACS SMARTT study. We first compared CD4 counts and viral loads (VL) between the first and second pregnancies using Wilcoxon rank-sum tests. We then examined trends in these measures over all reported pregnancies using mixed-effect linear regression models adjusting for maternal age and birth year, with a random effect to account for repeated measures in the same woman over time. Finally, we evaluated the association of PI or non-PI use during pregnancy with PTB, using GEE logistic regression models to adjust for pregnancy number, maternal age, and birth year.

Results

Between 2007 and 2018, 699 women had >1 pregnancy while on study, with a total of 1642 children. Their mean CD4 counts remained stable over repeat pregnancies. Their mean log10 VL decreased between the first and second pregnancies, both early and late in pregnancy (–0.42 cp/mL and –0.16 cp/mL respectively, P < 0.001 for each), but increased by 0.61 cp/mL (P < 0.001) between the end of the first pregnancy and early in the next pregnancy. Most women had VL suppression during pregnancy with VL rebound by the next pregnancy (figure). A majority of women (55%) received a PI in both their first and second pregnancies, with an increase in PTB rate of 4.3%, whereas those who changed from a PI to a non-PI had a decrease of 4.7% (table). Changing to a PI resulted in a stable rate, whereas remaining on a non-PI resulted in a drop of 2%. In adjusted models including all pregnancies, first trimester PI use was associated with an increased rate of PTB (adjusted OR 1.35; 95% CI 1.02, 1.97).

Conclusion

Most WLHIV achieved VL suppression during pregnancy, but many had a VL rebound after pregnancy. First trimester PI use was associated with higher risk of PTB.

Disclosures

E. Chadwick, Abbott Labs: Shareholder, stock dividends. AbbVie: Shareholder, stock dividends. R. B. Van Dyke, Giliad Sciences: Grant Investigator, Research grant.
967. Inhibition of Host Neuraminidase Increases Susceptibility to Invasive Pulmonary Aspergillosis
Authors: Van De Veerdonk Frank , Dewi Intan , Cunha Christina , vanderBeeke Lore , Jaeger Martin , Gresnigt Mark , Resendiz Agustin , Lagrou Katrien , Van De Velde Greetje , Wauters Joost , Carvalho Agostinho
Published: November 2018

Background

Influenza-associated aspergillosis (IAA) is an emerging fungal infection with high mortality and morbidity and the pathogenesis of this disease is not well understood. Interestingly, the number of IAA case reports has increased since the widespread use of neuraminidase inhibitors, such as oseltamivir in 2009. We set out to determine whether oseltamivir could contribute to the pathogenesis of IAA by modulating host responses.

Methods

First, peripheral blood mononuclear cells (PBMCs) and neutrophils from healthy donors were stimulated with neuraminidase (NA)-treated A. fumigatus or were pre-exposed to NA prior to stimulation with Aspergillus conidia. In addition, PBMCs and neutrophils were pretreated with oseltamivir carboxylate prior to stimulation. Cytokines were measured from supernatants after 24 hours of incubation at 37°C. C57BL/6 and BALB/c mice were treated with oseltamivir prior to intranasal challenge with A. fumigatus. Immunosuppression was induced by corticosteroid or cyclophosphamide.

Results

We demonstrate that Aspergillus treated with NA induced an enhanced immune response. Moreover, PBMCs and neutrophils treated with NA produced increased cytokine responses. Blocking NA in vitro with oseltamivir reduced Aspergillus-induced cytokine responses. Next we investigated the effects of blocking neuraminidase activity with oseltamivir in vivo. Immunocompetent mice and mice treated with corticosteroids showed increased mortality, lung fungal burden, and decreased cytokine production when treated with oseltamivir. These effects were not observed in cyclophosphamide-treated mice, suggesting that the effects of NA activity in anti-Aspergillus host defense acts mainly via myeloid cells.

Conclusion

Our results provide evidence that host neuraminidase activity is important for protective anti-Aspergillus immune responses. Treatment with oseltamivir, thus blocking host NA activity, in a setting of corticosteroid use might therefore increase susceptibility to Aspergillus infection. These results warrant further study on the role of neuraminidase and the effects of oseltamivir on susceptibility to invasive pulmonary aspergillosis during active influenza infection.

Disclosures

All authors: No reported disclosures.
970. Emerging Pathogen Candida auris Evades Neutrophil Attack
Authors: Johnson Chad , Davis J Muse , Huttenlocher Anna , Kernien John , Nett Jeniel
Published: November 2018

Background

Candida auris, an emerging fungal pathogen, causes hospital-associated outbreaks of invasive candidiasis with mortality near 60%. Little is known about the pathogenesis of this species that has newly arisen in the last 10 years, and it is unclear why this species is rapidly spreading worldwide. Neutrophils, critical for control of invasive candidiasis, kill fungi through phagocytosis or the release of neutrophil extracellular traps (NETs), which are structures of DNA, histones, and proteins with antimicrobial activity. The objective of this study was to delineate the neutrophil response to C. auris.

Methods

We examined interactions of human neutrophils with C. auris and included C. albicans for comparison. Neutrophil–Candida interactions were visualized by time-lapse fluorescent microscopy and scanning electron microscopy (SEM). We utilized oxidative stress indicator CM-H2DCFDA to measure the generation of reactive oxygen species (ROS) in neutrophils. NET formation was quantified by Sytox Green staining and assessed by SEM and immunofluorescent labeling of NET-associated proteins. Fungal viability was evaluated using microbiological counts and viability stains. We utilized a zebrafish larvae infection model to evaluate neutrophil–Candida interactions in vivo.

Results

Imaging revealed the phagocytosis of C. albicans by human neutrophils followed by the formation of NETs. In contrast, neutrophils encountering C. auris rarely engaged in phagocytosis or produced NETs. By Sytox Green staining, C. auris triggered negligible NET release by human neutrophils, with levels 7-fold lower when compared with C. albicans (Figure A). C. auris did not induce neutrophils to generate ROS, a key signaling mechanism for NET formation. The ineffective neutrophil response to C. auris correlated with diminished fungal killing (Figure B). Imaging of neutrophils in a zebrafish model of invasive candidiasis revealed the recruitment of approximately 50% fewer neutrophils in response to C. auris when compared with C. albicans (Figure C).

Conclusion

C. auris evades neutrophils by altering multiple aspects of their usual anti-candidal responses. We propose that this diminished innate immune response may contribute to the unexpected virulence of C. auris.

Disclosures

All authors: No reported disclosures.
975. Clostridium difficile Infection and Antibiotic Prescription Rates in the Community: Explaining the Gender Gap
Authors: Younas Mariam , Royer Julie , Rac Hana , Justo Julie Ann , Bookstaver P Brandon , Weissman Sharon , Maki Anton , Bell Linda , Waites Katie Stilwell , Dash Sangita , Al-Hasan Majdi N
Published: November 2018

Background

Previous studies have reported higher incidence rates of community-associated Clostridium difficile infection (CA-CDI) in women than in men. This cross-sectional population-based study examines whether this difference in CA-CDI rates across genders is driven by or independent of antibiotic use.

Methods

Medicaid and State Employee Health Plan pharmacy claims for outpatient oral antibiotics and associated medical claims were utilized for estimation of community antibiotic prescription rates in South Carolina population 18 to 64 years of age from January 1, 2015 to December 31, 2015. CA-CDI cases were identified from National Healthcare Safety Network (NHSN) and South Carolina Infectious Disease and Outbreak Network (SCION) through complete enumeration of South Carolina population of the same age and study period as above. Incidence rates of CA-CDI were reported in both men and women 18–39 and 40–64 years of age before and after adjustments for antibiotic prescription rates in the same gender and age group. The 95% confidence intervals (CI) were calculated to examine statistical difference in incidence rates across genders within the same age group.

Results

During the calendar year 2015, a total of 1,564 CA-CDI cases were identified in South Carolina residents 18–64 years of age. The incidence rate of CA-CDI per 100,000 person-years was higher in women than in men in age groups 18–39 years (37.3 [95% CI: 32.8–41.8] vs. 21.0 [95% CI: 17.6–24.4]) and 40–64 years (86.4 [95% CI: 80.1–92.8] vs. 56.6 [95% CI: 51.2–61.9]. Similarly, antibiotic prescription rates per 100 person-years were higher in women than men in the 2 respective age groups (118.8 [95% CI: 118.3–119.3] vs. 54.3 [95% CI: 53.9–54.8] and 130.4 [95% CI: 129.8–130.9] vs. 83.8 [95% CI: 83.3–84.4]. After adjustments for antibiotic prescriptions, there was no significant difference in the incidence rates of CA-CDI per 100,000 prescriptions between women and men 18–39 years of age (31.4 [95% CI: 27.6–35.2] vs. 38.6 [95% CI: 32.4–44.8] and 40–64 years old (66.3 [95% CI 61.5–71.2] vs. 67.5 [95% CI: 61.1–73.8]).

Conclusion

Higher crude incidence rates of CA-CDI in women are likely due to higher outpatient antibiotic prescription rates in women when compared with men.

Disclosures

P. B. Bookstaver, CutisPharma: Scientific Advisor, <$1,000. Melinta Therapeutics: Speaker’s Bureau, <$1,000.
977. An Innovative 3-Year Medical Student Spiral Curriculum in Antimicrobial Stewardship and Infectious Diseases
Authors: Chin-Hong Peter , Teherani Arianne , Irby David , Schwartz Brian
Published: November 2018

Background

By 2050, infections due antimicrobial-resistant organisms are predicted to account for 10 million deaths/year worldwide. Physician antibiotic prescribing patterns are a significant factor in the development of antibiotic resistance organisms. Early, continual, and integrated medical student education may help students develop a framework for responsible antimicrobial use as they develop prescribing patterns.

Methods

We designed a spiral antimicrobial stewardship curriculum (defined as revisiting the same concept but with increasing complexity) for medical students in years 2–4. Data provided by the Graduation Questionnaire (GQ) administered by the US Association of American Colleges were used. We compared student responses during the curriculum rollout in 2013–2015 between students at our institution and other schools. We also surveyed graduating seniors in 2015 about antimicrobial stewardship training.

Results

Using GQ data for the class of 2013 (preintervention), a similar proportion of UCSF medical students compared with other US medical students rated microbiology clinical preparation as excellent (43.6% vs. 45.1%, P > 0.20). For the 2014 class, we developed interactive case-based sessions at the beginning of years 3 and 4. After this first intervention, a higher proportion of UCSF students rated the microbiology clinical preparation as excellent (51.3%) compared with responses at all schools (39.8%, odds ratio [OR] 1.59, 95% confidence interval [CI] 1.1–2.3, P = 0.013). For the class of 2015, we added content during the medicine clerkship and 1 week before graduation. For the 2015 class, an even higher proportion of UCSF students rated microbiology preparation as excellent (57.6%), compared with all schools (41.2%, OR 2.23, 95% CI 1.54–3.22, P < 0.0001). From our survey, 88% were very or extremely satisfied with antimicrobial stewardship training.

Conclusion

A spiral curriculum focusing on antimicrobial stewardship and infectious diseases increases student perception of clinical preparation prior to graduation. As the curriculum was incrementally introduced, students’ knowledge increased indicating a dose–response pattern. Based on these positive results, we plan to introduce more content throughout UME, and link to curriculum for GME and practicing clinicians.

Disclosures

All authors: No reported disclosures.
1717. The Impact of Routine Molecular Point-of-care Testing for Gastrointestinal Pathogens in Adults Hospitalized With Suspected Gastroenteritis: Results of a Pragmatic Randomized Controlled Trial (GastroPOC)
Authors: Malachira Ahalya , Beard Kate , Brendish Nathan , Clark Tristan
Published: November 2018

Background

Adults hospitalised with diarrhoea are routinely isolated as an infection control measure, but many have non-infectious etiology. Side room facilities are a limited resource in hospitals. Routine laboratory testing takes several days to generate results but rapid molecular platforms can test comprehensively for GI pathogens and generate a result in 1 hour, making them deployable as point-of-care tests (POCT). POCT could reduce unnecessary isolation facility use in addition to other benefits.

Methods

In this pragmatic, pilot randomised controlled trial, adults hospitalised with suspected gastroenteritis were recruited and randomised 1:1 to receive either POCT (using the FilmArray GI panel) or routine clinical care. Results of POCT were communicated directly to clinical and infection control teams. The primary outcome was duration of time in a side room and secondary outcomes included turnaround time, proportion of patients with a pathogen detected, proportion of patients correctly de-isolated, time to de-isolation, antibiotic use and length of hospital stay.

Results

140 patients were recruited. Groups (n = 70) were well matched in terms of baseline characteristics. The median [IQR] turnaround time for results was 1.7 [1.6–2.3] hours in the POCT group and 61 [49–84] hours in the control group, P < 0.0001. Pathogens were detected in 44% of patients in the POCT group and 23% in the control group; P = 0.012. Overall the duration of side room isolation was 1.9 [1.0–2.9] days in the POCT group compared with 2.7 [1.8–5.1] days in the control group; P = 0.001. For those testing negative for pathogens this was 1.3 [0.8–2.5] days in the POCT group versus 2.7 [1.8–5.0] days in the control group, P < 0.0001. 63% of pathogen-negative patients were correctly de-isolated in the POCT group versus 28% in the control group, P = 0.0012. Antibiotic use and length of stay data will be available subsequently.

Conclusion

POCT using the FilmArray GI panel resulted in a substantially reduced turnaround time for results and an increase in the proportion of patients with pathogens correctly detected. POCT was associated with a reduction in the duration of unnecessary side room use. If these benefits are confirmed in further studies and cost effectiveness is demonstrated, molecular POCT for GI pathogens should replace current diagnostic pathways.

Disclosures

T. Clark, BioFire LLC: Collaborator, Research support and Speaker honorarium. NIHR: Grant Investigator, Grant recipient.
1721. An Outbreak of Botulism Associated With Nacho Cheese Sauce From a Gas Station in California
Authors: Rosen Hilary , Kimura Akiko , Mukhopadhyay Rituparna , Nash June , Boetzer Jason , Poe Alyssa , Tecle Selam , McAuley Katherine , Kasirye Olivia , Garza Alvaro , Crandall John , Shahkarami Mahtab , Chaturvedi Vishnu , Kiang David , Vidanes Jeff , McCoy Kelly , Derby Tammy , Barcellos Mark , Jain Seema , Vugia D
Published: November 2018

Background

Foodborne botulism is rare with 0–6 cases reported annually in California. During April 24–28, 2017, 4 hospitalized patients with suspect foodborne botulism were reported to the California Department of Public Health (CDPH) from 2 adjacent California counties. In collaboration with local public and environmental health, CDPH conducted an investigation to determine the magnitude of the outbreak, identify potential sources, and implement control measures.

Methods

A case was defined as clinical botulism in a visitor to or resident of Sacramento County with illness onset during April 20 to May 5, 2017. Case-patients or their proxies were interviewed. Patient specimens and suspect food items were tested for the presence of botulinum toxin and toxin-producing Clostridium botulinum; C. botulinum isolates underwent whole genome sequencing (WGS) at the CDPH laboratory.

Results

In April–May 2017, a total of 10 patients were hospitalized with laboratory-confirmed botulism. Median age was 34 years (range 16–57); 7 were male, and 8 were Latino. All patients required intensive care, 7 required ventilator support, and 1 died. Nine patients confirmed visiting Gas Station A in the week before illness onset; 8 reported consuming nacho cheese sauce served from a dispenser there. Inspection of Gas Station A on May 5 indicated that the cheese in the dispenser had a best by date of April 11; the dispenser was removed that day, before all patients were identified. The remaining pouch of nacho cheese sauce was laboratory confirmed to have botulinum toxin type A and toxin-producing C. botulinum. C. botulinum isolates from 3 patients clustered with the cheese isolate by WGS.

Conclusion

Contaminated nacho cheese sauce served at a local gas station was the source of the largest outbreak of foodborne botulism reported to date in California. No other botulism cases associated with this commercial cheese sauce were identified elsewhere in the United States; although the mechanism of contamination is unclear, the cheese was likely contaminated locally. Intensive public health investigation and intervention, before all cases were identified and C. botulinum toxin was detected in the product, likely prevented additional cases and possible deaths

Disclosures

All authors: No reported disclosures.
1724. Characteristics of the Ongoing Measles Outbreak in Greece in the Context of the Recent European-wide Epidemic and Public Health Measures
Authors: Georgakopoulou Theano , Horefti Elina , Maltezou Helena , Gkolfinopoulou Kassiani , Vernardaki Alexandra , Triantafyllou Eleni , Mavraganis Pantelis , Pogka Vasiliki , Theodoridou Maria , Panagiotopoulos Takis , Mentis Andreas , Tsiodras Sotirios
Published: November 2018

Background

Measles is a highly contagious disease which still remains a cause of severe complications, including deaths worldwide, despite the existence of safe and effective vaccines. In the last 3 decades, the incidence of measles in Greece has constantly declined with only sporadic clusters or outbreaks (last outbreak in 2010–2011). We describe the characteristics of the ongoing measles outbreak and the Public Health response.

Methods

All measles cases are reported through the mandatory notification system (EU case definition 2012) to the Department of Surveillance and Intervention of the Hellenic Centre for Disease Control and Prevention. For laboratory confirmation patient sera were tested for IgM antibodies and pharyngeal swabs for the presence of measles virus RNA with RT-PCR. Sequencing of the measles nucleoprotein gene was applied in positively tested serological samples.

Results

From 9 May 2017 to 26 April 2018, 2,659 cases were reported in all 13 regions in Greece; 1,605 (60.4%) were laboratory confirmed. Most cases (n = 1,595; 60%) were Roma (73% children <10 years) followed by nonminority Greek nationals (n = 781; 29.4%, of whom 57% young adults 25–44 years), highlighting the immunity gap in Roma population. The vast majority of cases (80.5%) were unvaccinated. Ninety-four (3.5%) cases were healthcare workers (HCW); all were partially or not vaccinated. Genotype B3 was identified by molecular testing in all 88 cases tested. Severe complications were reported in 429 (16.1%) patients, most frequently pneumonia (43.8%) and hepatitis (21.2%). Three deaths were recorded in an 11-month-old immunocompromised Roma infant, a 17-year-old unvaccinated Roma, and a 35 year olds partially vaccinated individual from the general population. Extensive vaccination in refugee/migrant hosting sites prevented the emergence of a large number of cases. Mitigation efforts focused on closing the immunization gap in Roma population through emergency vaccination and raising awareness among HCWs to prevent further spread.

Conclusion

The current outbreak highlights the need to achieve high vaccination coverage with 2 doses of MMR vaccine in the general population (children, adolescents, and young adults) and in hard-to-reach vulnerable populations like Roma and refugees.

Disclosures

All authors: No reported disclosures.
1759. High Proportion of Discordant Results in Culture-Independent Diagnostic Tests (CIDT) for Shiga Toxin, Foodborne Disease Active Surveillance Network (FoodNet), 2012−2017
Authors: Barrett Kelly A , Tack Danielle , Medus Carlota , Garman Katie N , Dunn John , Hurd Sharon , Hatch Julie , Parada Karleys , Wilson Siri , Wilson Elisha , Wymore Kathryn , Griffin Patricia M , Geissler Aimee L
Published: November 2018

Background

FoodNet conducts active laboratory-based surveillance for 9 pathogens transmitted commonly through food, including Shiga toxin-producing E. coli (STEC). Adoption of CIDTs has allowed for rapid identification of Shiga toxin or Shiga toxin genes, but incorporating multiple test results with differing sensitivity and specificity complicates treatment decisions and public health surveillance. Between 2007 and 2017, FoodNet reported increases in the use of CIDTs and decreases in rates of confirmation by culture.

Methods

We examined STEC cases reported to FoodNet during 2012−2017 with a positive immunoassay (IA) or polymerase chain reaction (PCR) test performed at a clinical laboratory, followed by positive or negative test at a state public health laboratory. Three test type combinations were assessed (IA/IA, PCR/PCR, and IA/PCR) by state, symptoms, test discordance, and culture (cx) result.

Results

During 2012−2017, 8,298 (76% of all STEC reported) specimens were tested by IA or PCR at both a clinical and a public health laboratory, 58% by IA/PCR, 27% by IA/IA, and 25% by PCR/PCR; some specimens had more than one test at each laboratory. Among these, 8,132 (98%) were also tested by cx. Among the IA/PCR test results, 20% were discordant and 75% of these were cx-negative. Even more of IA/IA (27%) and PCR/PCR (24%) results were discordant, and 75% of these were cx-negative. A median of 24% of test results were discordant (range by state, 13%–44%). Persons with discordant test results were less likely to have diarrhea (91% vs. 97%) and bloody diarrhea (33% vs. 57%). During 2012–2017, discordant results increased for IA/PCR (14% to 22%), IA/IA (17% to 34%), and PCR/PCR (6% to 25%). Most (85%) specimens with discordant results were cx-negative and 8% did not have a cx.

Conclusion

Almost a quarter of results were discordant, with marked variation by state, and most of these infections could not be confirmed by culture at the public health laboratory. Discordant results can pose problems for patient management. Including or excluding patients with discordant results also affects our ability to measure trends. Sensitivity and specificity of test types, test targets, and specimen transport must be considered when interpreting test results.

Disclosures

All authors: No reported disclosures.
2554. Safety and Immunogenicity of NasoVAX, a Novel Intranasal Influenza Vaccine
Authors: Tasker Sybil , Krishnan Vyjayanthi , Bart Stephan , Suyundikov Anvar , Booth Peta-Gay , Wight O’Rourke Anna , Zhang Jianfeng , Georges Bertrand , Roberts Scot
Published: November 2018

Background

NasoVAX is a replication-deficient adenovirus-based vaccine designed to express influenza hemagglutinin in nasal epithelial cells when given as a nasal spray. In preclinical studies, NasoVAX was associated with divergent strain protection. Prior preclinical and clinical studies with the vector demonstrated lack of impact from baseline adenovirus immunity.

Methods

Sixty healthy adults were randomized to an A/California 2009-based monovalent NasoVAX formulation at doses of 109, 1010, or 1011 viral particles or saline placebo, all given as a 0.25 mL nasal spray in each nostril. Subjects were followed for safety, including solicited local and systemic side effects. Immune measures included hemagglutination inhibition (HAI) and neutralizing antibody (MN) at days 1, 15, 29, 90, and 180, and γ-interferon ELISpot at day 1 and 8. A parallel cohort of 20 similar subjects were dosed with Fluzone® injectable influenza vaccine containing an A/California 2009 component and had assessments at the same timepoints. The laboratory was blind to treatment assignment for these comparator samples.

Results

NasoVAX was well tolerated with no serious adverse events and no fever. Solicited symptoms such as nasal congestion, sore throat, and headache did not increase with dose and were not statistically different than placebo. Available immune response data are shown below.

Conclusion

NasoVAX intranasal influenza vaccine was well tolerated and elicited comparable antibody responses and nearly 6-fold higher cellular immune responses than a licensed injectable vaccine.

Disclosures

S. Tasker, Altimmune, Inc: Employee and Shareholder, Salary. V. Krishnan, Altimmune, Inc.: Employee and Shareholder, Salary. S. Bart, Altimmune, Inc.: Research Contractor, fee for research services. A. Suyundikov, Altimmune, Inc.: Employee, Salary. P. G. Booth, Altimmune, Inc.: Research Contractor, fee for research services. A. Wight O’Rourke, Altimmune, Inc.: Employee and Shareholder, Salary. J. Zhang, Altimmune, Inc.: Employee and Shareholder, Salary. B. Georges, Altimmune, Inc.: Employee and Shareholder, Salary. S. Roberts, Altimmune, Inc.: Employee and Shareholder, Salary.
2556. Retrospective Evaluation of Mismatch From Egg-Based Isolation of Influenza Strains Compared With Cell-Based Isolation and the Possible Implications for Vaccine Effectiveness
Authors: Rajaram S , Van Boxmeer Josephine , Leav Brett , Suphaphiphat Pirada , Iheanacho Ike , Kistler Kristin
Published: November 2018

Background

Lower influenza vaccine effectiveness (VE) against circulating H3N2 strains compared with other influenza viruses is partly explained by antigenic mismatch between circulating strains and the vaccine strain (Belongia 2016). This mismatch has recently been linked to a new glycosylation site introduced in the egg-adaptation step (Zost 2017) and HA L194P substitution (Wu 2017) for H3N2. Vaccine manufactured using seed virus wholly grown in mammalian (e.g., Madin–Darby Canine Kidney—MDCK) cells, as with the NH17-18 version of Flucelvax®, avoids these mutations. Preliminary reports suggest that this cell-based vaccine showed greater VE than did similar egg-based vaccines [FDA Statement]. This study aimed to compile existing data on antigenic similarity to measure the degree of match with circulating wild-type isolates of egg- and MDCK-propagated versions of the vaccine H3N2 virus over multiple seasons.

Methods

Using publicly available reports from the Worldwide Influenza Centre, London (Crick), we compiled data on antigenic similarity, defined as H3N2 circulating wild-type virus isolates showing no more than a 4-fold reduction in titer to antisera raised against wholly MDCK- or egg-propagated versions of the vaccine H3N2 viruses. Titers were compared using hemagglutination inhibition (HI) assays and/or plaque reduction neutralization assays (PRNA).

Results

Data from Northern Hemisphere influenza seasons of 2011–2012 to 2017–2018 show a substantially higher proportion of tested circulating influenza H3N2 viruses matched the MDCK-propagated reference viruses than did corresponding egg-propagated reference vaccine viruses (Figures 1 and 2). In half of the seasons evaluated, there was little to no antigenic similarity between circulating viruses and the egg-based vaccine viral seed.

Conclusion

These data suggest higher levels of mismatch have occurred consistently with egg-propagated H3N2 reference viruses compared with MDCK-propagated reference viruses when measured against circulating wild-type isolates and may further explain the potential for lower VE observed against H3N2 historically. Furthermore, these data point to the importance of continuing to utilize cell-derived seeds in creating seasonal influenza vaccines for this strain.

Disclosures

S. Rajaram, Seqirus: Employee, Salary. J. Van Boxmeer, Seqirus: Employee, Salary. B. Leav, Seqirus: Employee and Shareholder, Salary. P. Suphaphiphat, Seqirus: Employee, Salary. I. Iheanacho, Seqirus: Consultant, Research support. K. Kistler, Seqirus: Consultant, Research support.
2567. Diagnosis of Invasive Aspergillosis in Hematological Malignancy Patients Receiving Mold-Active Antifungals: Performance of Interleukin-6 and -8, Asp LFD, and Aspergillus PCR in Same-day Blood and Bronchoalveolar Lavage Fluid Samples
Authors: Hoenigl Martin , Heldt Sven , Prattes Juergen , Eigl Susanne , Spiess Birgit , Johnson Gemma , Krause Robert , Buchheidt Dieter
Published: November 2018

Background

Aspergillus spp. induce elevated levels of several cytokines, including Interleukin (IL)-6 and IL-8. It remains unknown whether these cytokines hold value for clinical routine and enhance diagnostic performances of established and novel biomarkers/molecular tests for invasive aspergillosis (IA) in patients receiving mold-active antifungals.

Methods

This cohort study included 106 prospectively enrolled (2014–2017) adult cases with underlying hematological malignancies and suspected pulmonary infection undergoing bronchoscopy. Serum samples were collected within 24 hours of bronchoalveolar lavage fluid (BALF) sampling. Both serum and BALF samples were used to evaluate diagnostic performances of the Aspergillus-specific lateral-flow device test (LFD), Aspergillus PCR, galactomannan, β-d-glucan, and cytokines that have shown significant associations with IA in our previous matched case–control analysis (including IL-6 and IL-8), for IA classified according to the revised EORTC/MSG criteria.

Results

Among the 106 cases, 11 had probable IA, 32 possible IA, and 63 no evidence for IA; 80% received mold-active antifungals at the time of sampling. Diagnostic tests and biomarkers showed significantly better performance in BALF compared with blood, with the exception of serum IL-8 which was highly specific for IA and proved to be the most reliable blood biomarkers. Combinations of serum IL-8 with either BALF LFD (sensitivity 100%, specificity 94%) or BALF PCR (sensitivity 91%, specificity 97%) were highly sensitive and specific for differentiating probable IA from no IA.

Conclusion

High serum IL-8 levels were highly specific, and when combined with either the BALF Aspergillus-specific LFD, or BALF Aspergillus PCR also highly sensitive for diagnosis of IA.

Disclosures

G. Johnson, OLM Diagnostics: Employee, Salary.
2571. Higher Rates of Hospitalization and Infection-Related Hospitalization Among HIV-Exposed Uninfected Infants Compared with HIV Unexposed Uninfected Infants in the United States
Authors: Labuda Sarah M , Huo Yanling , Kacanek Deborah , Patel Kunjal , Jao Jennifer , Huybrecthts Krista , Hernandez-Diaz Sonia , Chadwick Ellen G , Scott Gwendolyn , Burchett Sandra , Smith Christiana , Kakkar Fatima , Van Dyke Russell ,   Pediatric HIV/AIDS Cohort Study
Published: November 2018

Background

Studies from multiple countries have suggested impaired immunity in perinatally HIV-exposed uninfected (HEU) children, with elevated rates of all-cause hospitalization and infections. We estimated the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU children and compared this with HIV-unexposed uninfected (HUU) children in the US Among HEU children, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of infant hospitalization.

Methods

We evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) Study dynamic cohort of the Pediatric HIV/AIDS Cohort Study (PHACS) network who were born 2006–2017 and followed from birth. Data on HUU children were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU children using Poisson regression. Among HEU children, multivariable Poisson regression models were fit to evaluate associations of maternal HIV factors with risk of hospitalization.

Results

Our analysis included 2,404 HEU and 3,605,864 HUU children. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUU children (figure). There was no significant difference in mortality. Among HEU children, maternal HIV disease factors, including viral load, CD4 count, antiretroviral regimen, and mode of HIV acquisition, were not associated with hospitalization rates.

Conclusion

Compared with HUU, HEU children in the United States have nearly twice the rate of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.

Disclosures

E. G. Chadwick, Abbott Labs: Shareholder, stock dividends. AbbVie: Shareholder, stock dividends. R. Van Dyke, Giliad Sciences: Grant Investigator, Research grant.