bluuebunny/crossref_metadata_2025_split huggingface dataset:
2629. Respiratory Syncytial Virus Epidemiology and Factors Associated with Severity among Hospitalized Infants in Four Middle-Income Countries, 2015–2017
Authors: Biggs Holly , Simoes Eric A , Abu-Khader Ilham Bulos , Thompson Mark G , Gordon Aubree , Hunt Danielle R , DeGroote Nicholas , Whitaker Brett L , Wang Lijuan , Marar Basima , Gresh Lionel , de Jesus Joanne , Bino Silva , Porter Rachael M , McMorrow Meredith , Campbell William , Zhang Yange , Lindstrom Stephen , Thornburg Natalie J , Langley Gayle , Langley Gayle , Peret Teresa C T , Simaku Artan , Gerber Susan I 
Published: October 2019

Abstract

Background
Respiratory syncytial virus (RSV) is the most commonly identified viral pathogen among young children with acute lower respiratory tract infection. Understanding global RSV epidemiology and risk factors for severe illness in low- and middle-income settings is critical as new vaccine candidates become available.

Methods
We prospectively enrolled infants aged < 1 year hospitalized with any acute illness from sites in Albania, Jordan, Nicaragua and Philippines during 2015–2017. Standardized parental interviews and medical record review were conducted. Respiratory specimens collected during enrollment were tested for RSV using rRT–PCR. RSV A or B subgroup was determined using a CDC-developed rRT–PCR assay. Very severe RSV illness was defined as requiring ICU admission or supplemental oxygen. Factors potentially associated with severity were assessed using individual logistic regression models to adjust for age and study site.

Results
Overall, 1,129 (31%) of 3634 enrolled infants had RSV infection. The median age of RSV-positive infants was 2.7 (range: < 1 to 11.9) months, 665 (59%) were male, and 63 (6%) had ≥1 underlying medical condition. RSV subgroup was determined for 1,028 (91%); RSV A and B co-circulated at all sites with alternating predominance by study year (figure). 583 (52%) infants had very severe RSV illness, which was significantly associated with younger age (median: 2.0 vs. 4.3 months; P < 0.01), study site (aOR: Jordan 5.0, Albania 2.9, Philippines 1.2, Nicaragua reference; P < 0.01), birth by cesarean section (aOR: 1.4; 95% CI [CI] 1.0–1.8; P = 0.03), having received ICU care after birth (aOR: 1.6; CI 1.0–2.4; P = 0.03), chronic heart or respiratory tract disease (aOR: 1.9; CI 1.0–3.4; P = 0.04), and a low weight-for-age Z score (aOR: 1.8; CI 1.3–2.7; P < 0.01). RSV subgroup was not associated with severity (aOR: 1.0; CI: 0.7–1.3; P = 0.72).

Conclusion
RSV was associated with a substantial proportion of acute illness among hospitalized infants in middle-income countries. Subgroups co-circulated across sites and study years with varying predominance and resulted in similar illness severity. Significant comorbidities were uncommon, but factors including younger age, low weight-for-age and chronic heart or respiratory tract disease were associated with more severe illness.

Disclosures
All authors: No reported disclosures.
2631. Influenza-Associated Intensive Care Unit Hospitalizations and Deaths in Children, During 2010–2019 in Greece
Authors: Magaziotou Ioanna , Tsiodras Sotirios , Andreopoulou Anastasia , Mouratidou Elisavet , Vernardaki Alexandra , Gkolfinopoulou Kassiani , Panagiotopoulos Takis , Kossyvakis Athanasios , Exindari Maria , Mentis Andreas , Papa Anna , Theodoridou Maria , Georgakopoulou Theano 
Published: October 2019

Abstract

Background
The clinico-epidemiological characteristics of children with severe influenza-related intensive care unit (ICU) admissions in Greece during 2010–2019 are described.

Methods
All laboratory-confirmed influenza cases (real-time PCR), in children 0–16 years old, admitted to Pediatric ICUs throughout the country, are reported using a mandatory notification system to the National Public Health Organization of Greece. Case fatality rates (CFR) were analyzed according to age and presence of comorbidities.

Results
From October 2010 to April 2019, 131 influenza cases [7.2/100,000 children, 65 (49.6%) girls] with PICUs admissions were recorded. The majority of cases (n = 78; 60%) occurred in the age group 0–4 years-old [31 (24%) children were < 12 months-old]. Sixty-five (49.6%) children had underlying comorbidities (22 neurological disease, 12 congenital syndromes, 7 cancer, 5 chronic respiratory, 19 other). The most common diagnosis was febrile ARDS and 67 (51.14%) had severe pneumonia (40% viral, 7% bacterial). Seventy-five (57.2%) children required invasive ventilation. Influenza A accounted for 102 (77.86%) of cases; out of 86 (84.31%) subtyped, 68 (79%) were AH1N1pdm09, and 18 (21%) were AH3N2. Influenza B accounted for 29 (22.13%) of cases. All children received oseltamivir. Median length of stay was 10 days (range 1–90). A total of 32 deaths was recorded (CFR 24.4%, total rate: 1.76/100,000 children); 13 (40.1%) deaths occurred in children with no known co-morbidity. Mortality rates were higher in children aged > 4 years (18/53, 33.9% vs. 14/78, 17.9%, P = 0.04) while there was a trend for children with comorbidities (19/65, 29.2% vs. 13/66, 19.69%, P = 0.1). Only 4% of children were previously immunized against influenza.

Conclusion
AH1N1pdm09 accounted for the vast majority of severe cases and influenza associated deaths in children in Greece over the last 10 years. Severe disease occurred also in children with no comorbitidies. Longitudinal clinico-epidemiological data should be considered in shaping the national immunization program.

Disclosures
All authors: No reported disclosures.
2641. The Characteristics of Influenza-Like Illness (ILI) Management in Japan
Authors: Tsuzuki Shinya , Yoshihara Keisuke 
Published: October 2019

Abstract

Background
Influenza-like illness (ILI) is a common disease that imposes a severe disease burden at the population level. ILI management is important in view of population health, and Japan’s management is distinct from that in other countries, especially regarding diagnosis and treatment of seasonal influenza. This study’s main objective was to quantitatively assess ILI management in Japanese healthcare settings.

Methods
In February 2019, we conducted an online survey of 600 participants in 200 households concerning ILI and its management in Japan. Respondents reported ILI episodes they and/or their family members experienced during January 2019. The 12-Item Short-Form Health Survey, Version 2 (SF-12v2) was included in the questionnaire to estimate quality of life (QOL) lost through ILI, and quality-adjusted life years (QALYs) lost in that way. We analyzed participants’ healthcare-seeking behavior to clarify the characteristics of Japanese ambulatory care for ILI.

Results
Of the participants, 261 of 600 (43.5%) reported at least one episode of ILI during January 2019. Of these, 194 (75.5%) visited healthcare facilities and 167 (86.1%) visited facilities within 2 days of symptom onset. A rapid influenza diagnostic test (RIDT) was given to 169 of 191 (88.5%) and 101 patients received a diagnosis of influenza, rather than ILI. Antivirals were used to treat 92.2% of the influenza cases. The median values of QOL and QALYs lost during a symptomatic period of ILI were 0.67 (interquartile range: 0.60–0.79) and 0.0055 (interquartile range: 0.0040–0.0072), respectively.

Conclusion
In Japan, most ILI patients visit healthcare facilities in the early phase of symptoms, and most physicians examine them using the RIDT. Most laboratory-diagnosed influenza cases are treated using antivirals. Future work should examine the relation between this early diagnosis and treatment practice, and the duration and severity of ILI symptoms.

Disclosures
All authors: No reported disclosures.
2648. Terminating the Troll of Transplantation: Letermovir for Cytomegalovirus Prophylaxis
Authors: Hedvat Jason , Lake Patrick , Swamy Siddharth , Zecchini Julia , Pereiras Maribel , Sebti Rani 
Published: October 2019

Abstract

Background
Letermovir is a novel antiviral that was approved for cytomegalovirus (CMV) prophylaxis after allogeneic hematopoietic stem cell transplant (allo-HSCT). The objective was to assess the real-world outcomes of CMV prophylaxis with letermovir compared with preemptive therapy (PT) alone.

Methods
This retrospective pre- and post-study evaluated the clinical impact of using letermovir prophylaxis in CMV-seropositive allo-HSCT recipients at our institution. The electronic medical record was used to identify patients that received PT alone from July 2016 to November 2017 and letermovir prophylaxis from November 2017 to March 2019. The primary endpoint was the proportion of patients with CMV infection requiring PT through week 24 after transplant. Secondary endpoints included the proportion of patients with CMV infection requiring PT through week 14 after transplant, time to CMV infection requiring PT, incidence of CMV disease, CMV-related hospitalization and all-cause mortality through week 14 and 24 after transplant. Safety data included incidence and time to engraftment and adverse effects due to letermovir. Chi-squared and t-test were utilized for categorical and continuous data respectively.

Results
The baseline characteristics were similar (Table 1) and 78.7% of patients were high risk for CMV. Fewer patients in the letermovir group (n = 50) than in the historic control group (n = 100) had CMV infection requiring PT through week 24 after transplant (9 [18%] vs. 63 [63%], P < 0.001). The mean time to CMV infection requiring PT through week 24 after transplant was 93.4 days (28–161) in the letermovir group vs. 37.4 days (11–126) in the historic control group (P < 0.001). The all-cause mortality and incidence of CMV-related hospitalization were not statistically different between the two groups through week 24 after transplant (Table 2). The incidence and time to engraftment were not statistically different between the two groups (Table 3).

Conclusion
Letermovir prophylaxis in the real-world setting resulted in less CMV infection requiring PT when compared with a historic control of patients receiving PT alone. The majority of patients in the letermovir group experienced delayed-onset CMV reactivation. Letermovir was well-tolerated with no apparent myelosuppressive toxicities.

Disclosures
All authors: No reported disclosures.
2650. Evaluating Antiviral Agents for Human Noroviruses Using a Human Intestinal Enteroid Model
Authors: Cortes-Penfield Nicolas W , Ramani Sasirekha , Neill Frederick , Ettayebi Khalil , Atmar Robert , Estes Mary 
Published: October 2019

Abstract

Background
Norovirus can cause chronic infections with serious morbidity and mortality in immunocompromised patients. While there are no FDA-approved medications for these infections, nitazoxanide, ribavirin, and enterally administered pooled immunoglobulin (IVIG) are used off-label on the basis of expert opinion. Nitazoxanide and ribavirin show antiviral activity in a murine norovirus infection model and an in vitro replicon model of genotype GI.I human norovirus RNA expression, respectively. However, these drugs have not been evaluated in in vitro infections with GII.4 human noroviruses, responsible for most human norovirus disease. We used the stem cell-derived nontransformed human intestinal enteroid (HIE) system, which supports GII.4 human norovirus replication, to evaluate the antiviral activities of nitazoxanide, ribavirin, and IVIG.

Methods
We inoculated HIEs with GII.4 human norovirus in the presence of half-log dilutions of nitazoxanide (3 µM to 100 µM), ribavirin (10 µM to 10 mM), or IVIG (1:100 to 1:3,000) and a media control. One and 48 hours after inoculation, we extracted and quantified GII.4 norovirus RNA from the HIEs. To demonstrate that replication inhibition was not due to cytotoxicity, we performed quantitative lactate dehydrogenase release assays on the HIEs across the therapeutic range of each compound.

Results
Nitazoxanide reduced GII.4 replication at 48 hours in a dose-dependent manner, achieving a >90% reduction in viral replication at 10 µM without cytotoxicity. These findings were confirmed in multiple HIE lines representing different intestinal segments and established from different donors. IVIG completely inhibited GII.4 replication at up to a 1:1,000 dilution and was not cytotoxic at therapeutic concentrations. Ribavirin did not reduce GII.4 replication at concentrations up to 10 mMµM, well in excess of levels achieved in human sera with standard doses.

Conclusion
Nitazoxanide and IVIG, but not ribavirin, potently inhibit GII.4 human norovirus replication in a biologically relevant in vitro model of human norovirus infection. These data highlight the use of HIEs as a new pre-clinical model for developing therapeutics for human norovirus disease.

Disclosures
All authors: No reported disclosures.
2653. Epidemiology and Risk Factors for Healthcare-Associated Viral Infections in Children
Authors: Hanley Samantha E , Odeniyi Folasade , Feemster Kristen , Coffin Susan E , Sammons Julia S 
Published: October 2019

Abstract

Background
Healthcare-associated viral infections (HA-VI) are common in hospitalized children and are increasingly recognized as a cause of preventable harm. Yet, epidemiology and modifiable risk factors related to pediatric HA-VI are currently poorly understood.

Methods
We performed a prospective case–control study to identify the risk factors and outcomes associated with pediatric HA-VI at a quaternary care children’s hospital between November 2016 and August 2018. Prospective surveillance for HA-VI was performed hospital-wide by certified infection preventionists using NHSN definitions. Cases were matched 1:1 to controls by age, duration of hospitalization, and hospital unit. We abstracted data from the electronic medical record and conducted semi-structured interviews with patient caregivers to identify potential exposures beginning 4 days prior to HA-VI identification date. We also measured length of antibacterial therapy (LOT) in the 7 days following enrollment.

Results
During the study period, we identified 143 eligible patients with HA-VI and enrolled 64 matched case–control pairs. In total, 79 viruses were identified among 64 case patients, of which 53 (67.1%) were respiratory viruses and 26 (32.9%) were GI. Case patients were more frequently exposed to a sick visitor, specifically either caregiver or sibling, compared with controls (18.8% vs. 9.4%; P = 0.20, Fisher exact test). During the exposure period, case patients also had a significantly higher number of hospital procedures performed when compared with controls (n = 320 vs. 232; X2 = 58.43, P < 0.001). Case, when compared with control, patients had a greater average LOT (2.89 vs. 1.08).

Conclusion
Results of study show that exposure to a sick visitor is a potentially modifiable risk factor for pediatric HA-VI. In addition, hospitalized children with HA-VI have increased exposure to antibacterial antibiotics when compared with matched controls. Prevention of pediatric HA-VI may have implications for antibiotic stewardship. Our findings suggest that hospital policies may need to be revised, with emphasis on visitor screening and partnership with families, to reduce the incidence of pediatric HA-VI during hospitalization.

Disclosures
All authors: No reported disclosures.
2655. A Prospective Study of Cytomegalovirus Infection in Active Systemic Lupus Erythematosus Patients with Intense Immunosuppressive Therapy: Epidemiology, Associated Risk Factors, Pathogenesis, and Clinical Outcomes
Authors: Bushyakanist Asalaysa , Rotjanapan Porpon , Ngamjanyaporn Pintip , Suangtamai Tanitta , Bruminhent Jackrapong , Pisitkun Prapaporn 
Published: October 2019

Abstract

Background
Systemic lupus erythematosus (SLE) patients with intense immunosuppressive therapy (IT) are at higher risk for cytomegalovirus (CMV) reactivation and may develop the end-organ disease. However, the real epidemiology, associated risk factors, pathogenesis, and clinical outcomes have not been fully elucidated.

Objectives
To investigate the associated risk factors, possible predictors in the aspect of immunology of CMV infection and to study epidemiology, and clinical outcomes prospectively in active SLE patients within 3 months after intense IT.

Methods
A prospective cohort study of active SLE patients required intense IT from November 2017 to March 2019 was conducted. We collected patients’ demographics, potential risk factors, onset and presentations of CMV infection after intense IT, data on IT, cytokine panels, and flow cytometry at weeks 0, 2, 4, 8, and 12 after enrollment. Intense IT was defined as an induction therapy of active SLE disease with either the National Institute of Health or Euro-Lupus Nephritis Trial protocol regimens.

Results
A total of 24 patients have enrolled with a median age of 32 years old and 22/24 patients were female. Renal involvement was the most common and found in 79.2% of the patients. Median SLE disease activity index at enrollment was 14 (25%-75% interquartile range (IQR) = 8–19). At week 0, no CMV infection was documented, 91.7% of the patients had positive CMV IgG, and the median absolute lymphocyte count was 938 cells/mm3. At week 12, the median cumulative corticosteroid dose was 0.74 mg/kg/day (25%-75%IQR = 0.34–1.20) and the prevalence of CMV infection was 12.5%. Elevated interleukin-23 and tumor necrotic factor-α levels were associated with protective effect (hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02–0.58, p = 0.009 and HR 0.55, 95% CI 0.31–0.99, p = 0.049, respectively). Neurologic involvement was the independent factor that increased the risk of CMV infection (HR 0.26; 95% CI 0.08–0.79, p = 0.018). No mortality was detected.

Conclusion
CMV infection is common when IT is used, but only some SLE patients with intense IT develop CMV infection. Certain characteristics of the patients may assist predict future CMV infection following IT. However, further study on a larger scale is encouraged.

Disclosures
All authors: No reported disclosures.
2658. Meningitis in Kidney Transplant Recipients: TransMéninges, a French Multicentric Retrospective Cohort Study
Authors: Tamzali Yanis , Scemla Anne , Taupin Pierre , Randhawa Sunny , Moal Valérie , Garandeau Claire , Levi Charlène , Matignon Marie , Fihman Vincent , Le Quintrec Moglie , Luque Yosu , Retbi Aurelia , Bertrand Dominique , Thervet Eric , Cherrak Ilham , Chemouny Jonathan M , Barrou Benoît , Tourret-Arnaud Jerôme 
Published: October 2019

Abstract

Background
The management of meningitis requires the prompt introduction of high-dose probabilistic anti-infectious therapy. The literature reporting on meningitis in kidney transplant recipients (KTR) is scarce and no recommendation exists for this specific population.

Methods
We retrospectively included all adult KTRs diagnosed with meningitis (cerebro-spinal fluid (CSF) cell count >10/mm3 or positive fungal antigen or direct examination) between 2007 and 2018 in 16 French hospitals. Clinical, biological, and therapeutic data, and 1-year kidney and patient survival were collected.

Results
Meningitis occurred in 134 KTRs (mean age 57+/11.8 years, 56% male), after a median time of 27 months (IQR 8–65); 25% of patients received an immunosuppressive treatment before kidney transplantation, induction treatment included lymphocyte-depleting antibodies in 63%, and 53% presented diabetes (34% before and 19% after the transplantation). The etiologies included Cryptococcus neoformans (30%), Herpesviridae (22%, including Varicella-Zoster Virus 15%), idiopathic forms (11%), Gram-negative bacilli (8% of which 20% produced an extended spectrum β-lactamase), %), infusion of intravenous immunoglobulins (6%), post-transplant lymphoproliferative disorders (5%), Aspergillus fumigatus (4%), Listeria monocytogenes (4%), Enterovirus (4%), and Mycobacterium tuberculosis (3%).
The most common symptoms were fever (82.5%), headaches (75%), encephalitis (55%), and convulsion (22.5%). CSF hypercellularity (found in 92% of the cases) was lymphocytic in 65% of the cases and neutrophilic in 35%. Initial anti-infectious therapy was inappropriate in 27% of the cases. One-year patient, graft, and death-censored graft survival rates were 84%, 76%, and 89%, respectively.

Conclusion
Meningitis after kidney transplantation encompasses a wide range of causes, with C. neoformans and VZV explaining more than 50% of the cases. Gram-negative bacilli are the most represented bacteria with a high rate of antimicrobial resistance. Treatment guidelines should be reconsidered in the specific population of KTRs as the etiology greatly differs from what is observed in the general population.

Disclosures
All authors: No reported disclosures.
2661. Sarcopenia Increases Risk of Post-Surgical Infections in Kidney Transplant Recipients
Authors: Villacorta Evelyn , Acosta Luis , Myint Thein , Leedy Nicole , Lia Castellanos Ana , Gedaly Roberto 
Published: October 2019

Abstract

Background
Sarcopenia (reduced skeletal muscle mass) has been associated with serious infection in liver transplant recipients. We analyzed the association of sarcopenia and early post-surgical infections in kidney transplant recipients.

Methods
Retrospective cohort study of 125 patients underwent kidney transplantation from 2010 to 2014 at University of Kentucky Medical Center. Sarcopenia was diagnosed by measuring the skeletal muscle mass on computed tomography imaging obtained during the pre-transplant evaluation using SliceOmatic 5.0 software at L3 level (≤ 52.4 cm2/m2 in males and ≤ 38.5 cm2/m2 in females). Early post-transplant infections were confirmed by positive culture from blood, urine, and/or peritoneal fluid within 30 days after kidney transplantation. A generalized linear model (GLM) was used to identify variables predictive of post- surgical infection and Risk Ratio (RR) was obtained, with a P-value of < 0.05. The statistical analysis was performed with STATA version 12.0 (College Station, Texas).

Results
Among 125 patients, 52 (41.6%) were identified with sarcopenia, 110 (88.0%) patients were white, 76 (60.8%) male, with a median age of 56 (range 20–72) at the time of transplant. Diabetes was reported in 50 (40.0%) patients, obesity in 64 (51.6%) patients and smoking in 43 (34.6%) patients. Six (4.8%) patients had graft failure. Infections were identified in 22 (17.6%) patients, more than one source of infection was reported in 4 (3.2%) cases. The most common infections were urinary tract infection in 13 (10.4%) patients and bacteremia in 5 (4.0%) patients. The median time to development of infection was 9 days (range 1–27). In the bivariate analysis, sarcopenia was associated with high risk of post-surgical infections (RR 2.45; 95% CI 1.10–5.44). In multivariable analysis, sarcopenia was a significant independent predictor of infection (RR 2.58; 95% CI 1.20–5.52). None associations were found with other variables; age over 40 years, male sex, smoking, obesity and diabetes.

Conclusion
Our study suggested that sarcopenia was associated with an increased risk of early post-surgical infection in kidney transplant recipients.

Disclosures
All authors: No reported disclosures.