bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Primary Amebic Meningoencephalitis Case Associated with Rafting on an Artificial Whitewater River
Authors: Cope Jennifer , Murphy Jennifer , Kahler Amy , Gorbett Daniel , Ali Ibne , Taylor Brandi , Corbitt Lisa , Roy Shantanu , Lee Nicole , Roellig Dawn , Brewer Scott , Hill Vincent 
Published: October 2017

Abstract

Background
Naegleria fowleri is a climate-sensitive thermophilic ameba found in freshwater that causes primary amebic meningoencephalitis (PAM; 0–8 infections per year in the U.S.) when it enters the nose and migrates to the brain. Patient exposure to water containing the ameba typically occurs in warm freshwater lakes and ponds during recreational water activities. In June 2016, an 18-year-old woman died of PAM after traveling to North Carolina, where she participated in whitewater rafting on an artificial whitewater river.

Methods
To determine water exposures, we reviewed medical records and conducted interviews with family and individuals who had traveled with the case-patient. To further investigate the artificial whitewater river as a possible exposure source, we visited the whitewater facility and collected water, biofilm, and sediment samples from the facility and from the nearby natural river. We performed select water quality tests onsite and tested for the presence of N. fowleri by culture and real-time PCR in the laboratory.

Results
Interviews revealed that the case-patient’s most probable water exposure in the 10 days before becoming ill occurred while rafting on an artificial whitewater river during which she was thrown out of the raft and submerged underwater. The ~11.5 million gallons of water in the whitewater facility were filtered, subjected to UV light, and occasionally chlorinated. Heavy algal growth was noted. The free chlorine residual was 0.05 mg/L, turbidity was 6.7 NTU, and water temperature was 30°C in the whitewater facility during the site visit. All 11 water-related samples taken from the facility were positive for N. fowleri. Of 5 samples taken from the natural river, 1 sediment sample was positive for N. fowleri.

Conclusion
This investigation documents a novel exposure to an artificial whitewater river as the likely exposure causing PAM in this case. Conditions in the whitewater facility (warm, turbid water with little chlorine and heavy algal growth) rendered the water treatment ineffective and provided an ideal environment for N. fowleri to thrive. The combination of natural and engineered elements at the whitewater facility create a challenging environment to control the growth of N. fowleri.

Disclosures
All authors: No reported disclosures.
Varicella-zoster virus Neurovasculitis (VZV-NV) in the Setting of Autoantibodies to Interferon alpha (anti-IFNα)
Authors: Ansari Rahila , Zerbe Christa , Lisco Andrea , Rosen Lindsey , Holland Steven , Bonomo Robert A 
Published: October 2017

Abstract

Background
VZV-NV resulting in CNS damage is rare in immunocompetent hosts. Humoral immunity protects against acquiring VZV, and T-cell mediated immunity shields against reactivation of the latent virus. Individuals who are immunocompromised due to T-cell mediated defects can present with systemic VZV.

Methods
Case report of a previously healthy man who developed VZV-NV associated with autoantibodies to IFNα.

Results
A previously healthy 64 year-old man developed an acute T3 Brown-Sequard syndrome. Symptoms progressed to include bilateral lower extremity weakness, ptosis, ophthalmoplegia, and encephalopathy. Magnetic resonance imaging (MRI) showed diffuse T2 hyperintensities with enhancement throughout the spine and brain, including enhancement of his meninges, roots, and cranial nerves. Successive cerebrospinal fluid (CSF) studies revealed increasing B-cell lymphocytosis, (maximum 661 cells/mcl), and CSF protein (maximum 242 mg/dL). CSF PCR was positive for VZV and IgM antibodies. Further testing showed anti-IFNα autoantibodies in the plasma and CSF. Serum anti-IFNα fluorescence intensity was 30 times normal, and his plasma blocked IFNα-induced STAT-1 phosphorylation in normal monocytes. Treatment with acyclovir and methylprednisolone resulted in improvement. Repeat LP following treatment revealed 32 WBC/mcl with normal protein. Follow-up MRI did not show any new lesions. Three years after initial presentation, he continues to be stable without clinical relapses, or subclinical changes on MRI. Serum studies were positive for VZV IgG and negative for IgM. CSF PCR was positive for VZV. Lastly, serum anti-IFNα fluorescence intensity remained 25 times normal, and his plasma continued to block IFNα-induced STAT-1 phosphorylation in normal monocytes.

Conclusion
This is the first identified case of CNS VZV-NV in the setting of binding and blocking autoantibodies to IFNα in the serum and CSF. Elevated serum and CSF levels of anti-INFα may impair natural killer, T-cell and neuronal antiviral activity. Disruption of T-cell mediated immunity due to anti-IFNα could cause an adult-onset immunocompromised state with severe VZV reactivation. The association of high-titer neutralizing autoantibodies to INFα in an adult with CNS VZV is novel and may be clinically relevant.

Disclosures
All authors: No reported disclosures.
PCR Array Profiling of Antiviral Genes in Human Embryonic Kidney Cells Expressing Human Coronavirus OC43 Structural and Accessory Proteins
Authors: Beidas Meshal , Chehadeh Wassim 
Published: October 2017

Abstract

Background
Human coronavirus OC43 (HCoV-OC43) causes common cold, and is associated with severe respiratory symptoms in infants, elderly and immunocompromised patients. HCoV-OC43 is a member of Betacoronavirus genus that includes also the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) coronaviruses. Both SARS-CoV and MERS-CoV were shown to express proteins with the potential to evade early innate immune responses. However, the ability of HCoV-OC43 to antagonise the intracellular antiviral defences has not yet been investigated. The objective of this study was to investigate the role of HCoV-OC43 structural (membrane and nucleocapsid) and accessory (ns5a and ns2a) proteins in the modulation of antiviral gene expression profile in human embryonic kidney 293 (HEK-293) cells using PCR array analysis.

Methods
HCoV-OC43 membrane (M), nucleocapsid (N), ns5a and ns2a mRNA were amplified and cloned into the pAcGFP1-N expression vector (Clontech), followed by transfection in HEK-293 cells. Expression of M, N, ns5a and ns2a proteins were confirmed by indirect immunofluorescence test. Three days post-transfection, the cells were challenged by Sendai virus. The Human Antiviral Response PCR array system (Qiagen) was used to profile the antiviral gene expression in HEK-293 cells, using the fold regulation comparison and the manual normalisation methods.

Results
Around 50–60 genes were downregulated by HCoV-OC43 proteins, the most prominent genes being those critical for the activation of transcription factors involved in the antiviral response like interferon regulatory factors (IRFs) and activator protein 1 (AP-1). Among the most important downregulated genes were those coding for Interferons (IFNs) mitogen-activated protein kinases (MAPKs), pro-apoptotic and pyroptotic proteins (Caspases, cathepsins, tumour necrosis factor), pro-inflammatory cytokines (Interleukins), pattern recognition receptors (PRRs; toll-like receptors and NOD-like receptors) and their signaling transduction proteins (TICAM1, MAVS).

Conclusion
This study shows for the first time that similarly to SARS-CoV and MERS-CoV, HCoV-OC43 has the ability to downregulate the transcription of genes critical for the activation of different antiviral signaling pathways.

Disclosures
All authors: No reported disclosures.
Risk Factors for Herpes Zoster: a Systematic Review and Meta-Analysis
Authors: Kawai Kosuke , Yawn Barbara P 
Published: October 2017

Abstract

Background
Well-recognized risk factors for herpes zoster (HZ), commonly known as shingles, are age and immunosuppression. Numerous studies have investigated other various risk factors for HZ in recent years. The objective of our study is to systematically review studies examining risk factors for HZ and discuss implications based on the updated evidence.

Methods
We performed a literature search using PubMed, Embase, and Web of Science and included studies that examined risk factors for HZ. Random effects model was used to summarize the risk ratio (RR) or odds ratio (OR) and 95% confidence interval (CI).

Results
Of the 3450 studies screened, we included 84 studies in the systematic review and conducted meta-analysis in 62 studies. Women are at increased risk of HZ compared with men (pooled adjusted RR = 1.31; 95% CI: 1.27, 1.34). Black individuals have almost half the risk of HZ than White individuals (pooled RR = 0.54; 95% CI: 0.47, 0.63). Family history was found to be a risk factor for HZ (pooled OR = 3.59; 95% CI: 2.39, 5.40). Autoimmune diseases, including rheumatoid arthritis (pooled RR = 1.67; 95% CI: 1.41, 1.98) and systemic lupus erythematous (RR = 2.10; 95% CI: 1.40, 3.15), were associated with an elevated risk of HZ. Other comorbidities were associated with an increased risk of HZ, with the pooled RRs ranging from 1.25 (95% CI: 1.13, 1.39) for asthma to 1.30 (1.17, 1.45) for diabetes mellitus, and 1.31 (95% CI: 1.22, 1.41) for chronic obstructive pulmonary disease. Statin use was also associated with a modest increased risk of HZ (pooled RR = 1.14; 95% CI: 1.11, 1.17). Recent physical trauma increased risk of HZ by almost two-fold (pooled RR = 2.56; 95% CI: 1.97, 3.33).

Conclusion
In addition to age and immunocompromised conditions, our review shows that female sex, race/ethnicity, family history, and comorbidities are risk factors for HZ. Efforts are needed to better understand risk factors and to increase the uptake of zoster vaccination.

Disclosures
B. P. Yawn, GSK: Consultant and Scientific Advisor, Consulting fee
Co-circulation of Influenza A and B During the 2016–2017 Influenza Season at Rush University Medical Center
Authors: Simms Andrew , Gonzalez Hemil , Moore Nicholas M , Chapman Leslie A , Lolans Karen , Trenholme Gordon M 
Published: October 2017

Abstract

Background
Two strains of influenza B virus, B/Yamagata and B/Victoria, co-circulate in the USA, typically appearing in late March. This year, influenza B virus (FluB) co-circulated consistently with influenza A virus (FluA). We hypothesized that this could be explained by an increased use of influenza trivalent vaccine, which lacks the B/Yamagata strain, over the quadrivalent vaccine.

Methods
We performed a retrospective, observational cohort study of patients with laboratory-diagnosed influenza from October 2016 through April 2017. Age, comorbidity categories, pregnancy status, symptoms, The presence of opacity on chest film, ICU admission, death, and receipt of oseltamivir were reviewed for 256 patients. A subset of FluB specimens were subtyped for lineage using RT–PCR.

Results
Influenza was detected in 495 (10.4%) of 4,754 samples collected, including 305 FluA and 190 FluB. The H3 strain represented 97% of FluA cases. FluB subtypes were: 70, B/Victoria; 21, B/Yamagata; and 41, not subtyped. Chart review was conducted for 124 randomly selected FluA and 132 sequential FluB patients. Median age of patients with FluA was 44 compared with 27 with FluB (P &lt; 0.001). Forty-three (34.7%) FluA patients had heart disease compared with 21 (15.9%) FluB patients (P &lt; 0.001). Otherwise, there were no differences in comorbidities, pregnancy status, clinical symptoms, or infectious complications between FluA vs. FluB patients. Ninety-three (75%) FluA patients and 78 (59.1%) FluB patients received oseltamivir. ICU admission occurred in 15 (12.1%) FluA and 9 (6.8%) FluB patients (OR 1.414; 95% CI 0.83-2.4). Seventy-seven (30%) patients received flu vaccine, 39 with FluA, and 38 with FluB; 97 (37.9%) were not vaccinated and 82 (32%) were missing data. Of those vaccinated, 6 patients received trivalent vaccine, and 71 received quadrivalent. Only 24 patients with B/Victoria and 7 patients with B/Yamagata were vaccinated.

Conclusion
The proportion of infected patients who had received vaccination was low, limiting our ability to detect the effect of the trivalent vaccine on the incidence of infection with B/Yamagata. In contrast to conventional thought, when compared with influenza B, influenza A (predominantly H3N2) did not appear to disproportionally affect those with most medical comorbidities, and was not disproportionately associated with our identified clinical complications.

Disclosures
All authors: No reported disclosures.
Influenza Vaccination and Treatment with Antiviral Agents Among Hospitalized Adults in the 2014–2015 and 2015–2016 Influenza Seasons
Authors: E Segaloff Hannah , Petrie Joshua G , Malosh Ryan E , Cheng Caroline K , Ferdinands Jill M , Lamerato Lois , Lauring Adam S , Monto Arnold S , Martin Emily T 
Published: October 2017

Abstract

Background
Vaccination and treatment with neuraminidase inhibitors can reduce incidence and severity of influenza. Observational studies suggest antiviral treatment reduces influenza symptom duration and severe outcomes among hospitalized patients. The interaction of the effects of vaccination and antiviral treatment against severe influenza has not been established.

Methods
We used data from a test-negative influenza vaccine effectiveness study. The parent study enrolled adults admitted to two hospitals in Michigan with an acute respiratory illness of ≤10 days duration during the 2014–2015 and 2015–2016 influenza seasons. Respiratory swabs from enrolled patients were tested for influenza by RT-PCR; influenza-positive individuals were included in this analysis. We evaluated predictors of vaccination and antiviral treatment using logistic regression. We also assessed the association between antiviral treatment and hospital length of stay (LOS) using linear regression models stratified by vaccination status.

Results
We included 200 individuals in the analysis; 103 (51.5%) were vaccinated and 135 (67.5%) were treated with antivirals. Significant predictors of vaccination included age ≥65, white race, a Charlson comorbidity index (CCI) score ≥3, study site, and increased past-year health care visits. Antiviral treatment varied by study site and was more common in the 2015–2016 season and among those aged 18–49. Vaccination was not associated with antiviral treatment or with time from illness onset to treatment. Antiviral treatment was associated with reduced LOS (percent change in LOS: −23.6% (−39.2%, −4.1%), P = 0.02) among vaccinated participants but not among unvaccinated participants (21.1% (−10.9%, 64.8%), P = 0.22) after adjustment for sex, age, influenza subtype, site, CCI, frailty, and past-year health care contacts. When an interaction term was used in lieu of stratification the interaction was significant (P = 0.01). This difference in antiviral effectiveness by vaccination status held across age groups, but was most dramatic for those aged 18–49.

Conclusion
Vaccinated individuals were more likely than unvaccinated individuals to benefit from antiviral treatment. This finding warrants confirmation in other populations.

Disclosures
A. S. Monto, sanofi pasteur: Grant Investigator, Research grant. Novartis: Consultant, Consulting fee. Protein Sciences: Consultant, Consulting fee. E. T. Martin, Pfizer: Scientific Advisor, Research grant. Merck: Scientific Advisor, Research grant. Multiparty Group For Advice on Science: Scientific Advisor, Research grant.
Norovirus, Astrovirus, and Sapovirus in a Tertiary Care Research Hospital
Authors: Daniel-Wayman Shelby , Fahle Gary , Palmore Tara , Green Kim , Prevots D Rebecca 
Published: October 2017

Abstract

Background
Norovirus, astrovirus, and sapovirus are known to cause acute gastroenteritis and are associated with chronic viral excretion in stool among immunocompromised patients. Because molecular tools for their detection only recently became widely available, the prevalence and chronic excretion of these viruses has not been well defined. We describe features of these viral infections among patients receiving care at the Clinical Center of the National Institutes of Health.

Methods
We identified patients with a positive BioFire FilmArray® gastrointestinal panel result for norovirus, astrovirus, or sapovirus from September 15, 2015 through November 30, 2016. We reviewed patient medical records to abstract clinical and microbiologic information. Chronic excretion was defined as more than one positive test for a given virus with more than 30 days between tests.

Results
Of 932 samples tested, 102 (11%) samples from 48 patients tested positive for norovirus, 15 (2%) samples from 11 patients tested positive for sapovirus, and 16 (2%) samples from 7 patients tested positive for astrovirus. One of these patients had a sample that tested positive for both sapovirus and norovirus, and one tested positive for astrovirus and sapovirus at separate points during the study period. Of the 48 patients with norovirus, 16 (33%) had evidence of chronic excretion, with a median duration of 189 days (range 72–372). Of these 16, 14 were known or suspected to be immunodeficient, and 4 had hematologic malignancies. Of 7 patients with astrovirus, 1 (14%) had evidence of chronic excretion (132 days). This patient had a hematologic malignancy and was taking immunosuppressive medication. No patients with sapovirus had evidence of chronic excretion. Overall, 20 (31%) patients additionally tested positive for another gastrointestinal pathogen, most commonly enteropathogenic E. coli and C. difficile.

Conclusion
Norovirus remains common in this immunocompromised patient population, and both sapovirus and astrovirus are present. Additional follow-up in this and other cohorts with new molecular tools will enable more complete description of the prevalence, excretion duration, and clinical features of infection with these enteric viruses.
This research was supported by the Intramural Research Program of the NIH, NIAID, and the NIH CC.

Disclosures
All authors: No reported disclosures.
Incidence of Norovirus-Associated Acute Gastroenteritis in Four Veteran’s Affairs Medical Center Populations in the United States, 2011–2015
Authors: Grytdal Scott , Browne Hannah , Collins Nikail , Vargas Blanca , Rodriguez-Barradas Maria , Beenhouwer David , Brown Sheldon , Lucero-Obusan Cynthia , Holodniy Mark , Kambhampati Anita , Parashar Umesh D , Vinje Jan , Lopman Benjamin , Hall Aron , Cardemil Cristina 
Published: October 2017

Abstract

Background
In the USA, norovirus is an important cause of epidemic acute gastroenteritis (AGE) as well as a leading cause of pediatric AGE. However, the burden of sporadic norovirus disease in US adults has not been well-documented. Our objective was to estimate the incidence of outpatient visits and hospitalizations for community-acquired norovirus AGE at four Veterans Affairs Medical Centers (VAMCs) and their associated outpatient clinics in Atlanta, GA; Bronx, New York; Houston, TX; and Los Angeles, CA.

Methods
From November 2011 to September 2015, stool specimens collected for clinician-requested diagnostic testing within 7 days of AGE symptom onset and with reported vomiting or diarrhea were tested for norovirus by real-time RT-PCR and positive samples were genotyped by Sanger sequencing. Incidence of norovirus-associated outpatient visits and hospitalizations were calculated by multiplying the prevalence of norovirus among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the unique patients served at each VAMC.

Results
1,620 stool specimens were tested from all 4 sites. Seven percent of outpatient (n = 795) samples (annual range: 3%–10%; range by site: 3%–10%) and 6% of&#x2028;(n = 825) samples from hospitalized patients tested positive for norovirus (annual range: 3%–8%; range by site: 3%–10%). Forty-four percent of norovirus-positive specimens were typed as GII.4 Sydney. Seventy-four percent of norovirus-positive specimens were collected between November and April. From 2011 to 2015, outpatient norovirus incidence was 250/100,000 population (annual range: 129 to 426/100,000; range by site: 87 to 428/100,000), and the incidence of norovirus hospitalizations was 28/100,000 population (annual range: 19 to 39/100,000; range by site: 14 to 57/100,000). By age group and setting, the highest incidence was observed among 45- to 64-year-old outpatients (370/100,000 population), and 85+-year-old inpatients (63/100,000 population).

Conclusion
This study provides estimates of the incidence of norovirus AGE outpatient visits and hospitalizations across multiple years among a geographically distributed VA population, highlighting the substantial burden of norovirus in US adults.

Disclosures
All authors: No reported disclosures.
Severe Fever with Thrombocytopenia Syndrome Virus Infection Associated with Hemophagocytic Lymphohistiocytosis as Poor Prognostic Factor
Authors: Park Sunmin , Kim Juwon , Kim Hyo Youl , Uh Young , Kim Young Keun 
Published: October 2017

Abstract

Background
Severe fever with thrombocytopenia (SFTS) is an emerging infectious disease caused by a novel bunyavirus designated SFTS virus (SFTSV) with a high fatality rate. Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated life-threatening disease triggered by infections, neoplasms and noninfectious inflammatory diseases. A few HLH associated with SFTSV were reported. According to the diagnostic criteria of HLH, 11 patients with SFTS were reviewed.

Methods
During last 2 years (2015–2016), 11 SFTS patients were diagnosed at the Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea. Clinical features were analyzed using diagnostic criteria of 2004-HLH trial. We described if the prognosis of SFTSV-infected patients was associated with clinical features of HLH.

Results
Of 11 patients, four patients were fulfillled the diagnostic criteria of 2004-HLH trial (five of eight criteria). Two patients were fulfilled the four criteria. Five patients were fulfilled three or less criteria. Three of six patients who fulfilled four or more criteria were died. There was no mortality in five patients who fulfilled three or less criteria. Hemophagocytosis in bone marrow (BM) was observed in all six patients who were taken BM study.

Conclusion
In SFTS, HLH was severe clinical feature and it might be associated with poor prognosis.

Disclosures
All authors: No reported disclosures.