bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt; 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 &lt; 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

Abstract

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

Abstract

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 &lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.
1178. A Multicenter Prospective Study of Clinical and Molecular Epidemiological Analysis of Carbapenem-Resistant Enterobacteriaceae (CRE) and Carbapenemase-Producing Enterobacteriaceae (CPE) in Japan
Authors: Hayakawa Kayoko , Kato Hideaki , Hase Ryota , Hasumi Jumpei , Nei Takahito , Nakano Ryuichi , Yano Hisakazu , Nagashima Maki , Ohmagari Norio 
Published: November 2018

Abstract

Background
Data of a multicenter study on CRE from Japan are limited. Comparative analyses of carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing CRE (NCP-CRE) have not yet been conducted.

Methods
Cases with CPE or CRE (defined as (1) meropenem [MPM] MIC, ≥2 mg/L or (2) imipenem [IPM] MIC, ≥2 mg/L and cefmetazole MIC, ≥64 mg/L [CLSI criteria]) were included from August 2016 to May 2017. PCR was used to detect carbapenemase.

Results
From five tertiary hospitals, 24 isolates (14 CPE and 10 NCP-CRE) were collected from 22 patients. Of the 10 NCP-CRE, seven were Enterobacter aerogenes and three were Enterobacter cloacae; of the 14 CPE, five were Klebsiella pneumoniae; 3, E. cloacae; 3, E. coli; 2, Citrobacter freundii; and 1, E. aerogenes. CPE were frequently isolated from the urine (5 [42%]) and sputum (3 [25%]) and NCP-CRE from sputum (4 [40%]), bile (3 [30%]), and urine (2 [20%]). Cases with CPE were older with more frequent use of urinary catheter and/or NG tube than NCP-CRE (table). The 30-day mortality or length of hospital stay (LOS) did not differ between the two groups. Majority (n = 12) of CPE were identified to carry blaIMP (MPM MIC, ≥2 mg/L), and two CPE were positive for blaOXA-181 and blaOXA-232 (MPM MIC, ≤1 mg/L). All NCP-CRE had IPM MIC of ≥2 mg/L; 7 (70%) had MPM of ≤1 mg/L. Resistance to amikacin (AMK) and levofloxacin (LFX) was noted in one and five CPE, respectively, whereas all NCP-CRE were sensitive, and nine blaIMP and 1 blaoxa-232 were transferable by conjugation.

Conclusion
CPE and NCP-CRE had different clinical characteristics. Non-β-lactam treatment options were more available for NCP-CRE than CPE. CPE and NCP-CRE might require different control strategies.

Disclosures
All authors: No reported disclosures.