bluuebunny/crossref_metadata_2025_split huggingface dataset:
2571. Norovirus Infection and Gut Microbiota in Transplant Recipients
Authors: Chong Pearlie P , Chong Pearlie P , Hussain Sarah K , Poulides Nicole , Coughlin Laura , Koh Andrew Y 
Published: October 2019

Abstract

Background
In vitro studies have shown that enteric viruses require the gut microbiota (specific members of the Enterobacteriaceae family) for efficient infection of the gastrointestinal tract. Human norovirus (NV) infection in transplant recipients may be chronic and severe. The role of gut microbiota has not been defined in this setting. We hypothesized that gut microbiota diversity and composition are different in norovirus-infected transplant patients.

Methods
We performed a single-center, pilot, prospective cohort study of adult solid-organ transplant and hematopoietic stem cell transplant recipients with diarrhea. Serial fecal samples were collected and processed for gDNA. Norovirus levels were quantified by PCR and gut microbiota profiling determined by 16S rRNA gene sequencing.

Results
Twenty-five transplant recipients were included: 9 with NV infection and 16 without. Age (61 ± SEM 2.3 years vs. 54 ± 3.5 years; P = 0.172), duration of diarrhea prior to diagnosis (105 ± 43 days vs. 20 ± 7 days; P = 0.146), prior cumulative antibiotic use (42 ± 12 days vs. 46 ± 17 days; P = 0.646), anti-anaerobic antibiotic use (7 ± 3 days vs. 11 ± 6 days; P = 0.643) and length of hospitalization (12 ± 6 days vs. 12 ± 3 days; P = 0.624) were not different between transplant recipients with and without NV infection. Interestingly, the relative abundance of Enterobactericeae was significantly higher in NV-infected transplant recipients compared with those without NV infection (26 ± 5.8% vs. 6.2 ± 2.8%; P = 0.017, Mann–Whitney) (Figure 1). In contrast, the abundance of the Phyla Bacteroidetes (11.2 ± 5.2% vs. 26.3 ± 6.5%; P = 0.191), and Firmicutes (26.8 ± 7.6% vs. 24.9 ± 4.7%; P = 0.803), were not significantly different between those who were NV and not NV-infected. Of note, the diversity metrics of Shannon (3.5 ± 0.4 vs. 3.8 ± 0.3; P = 0.637) and inverse Simpson indices (1.3 ± 0.1 vs. 1.1±0.1; P = 0.419) were not significantly different between the two groups.

Conclusion
Norovirus-infected transplant recipients had a significantly higher relative abundance of Enterobactericeae in their gut microbiota compared with transplant recipients without norovirus infection. Future studies are needed to explore if this association is mechanistically important for norovirus infection.

Disclosures
All authors: No reported disclosures.
2596. Invasive Fungal Disease in Patients with GATA2 Variant Hematologic Malignancy
Authors: Bold Tyler D , Vedula Rahul S , Cheng Matthew P , Marty Francisco M , Lindsley R Coleman 
Published: October 2019

Abstract

Background
Patients with hematologic malignancies (HM) are at risk of invasive fungal disease (IFD). Identification of those patients at the highest risk for IFD would help optimize prophylactic or preemptive treatment decisions in this population. We previously found that among patients with myeloid malignancies who develop invasive aspergillosis, 15% had a mutation in the gene GATA2. Here, we report the incidence of IFD in a cohort of patients with HM related to a pathogenic sequence variant of GATA2.

Methods
We identified 6343 patients cared for at Dana-Farber/Brigham and Women’s Cancer Center between January 2014 and August 2018 who underwent a next-generation sequencing assay of 95 genes recurrently mutated in hematologic malignancy. Those found to have a pathogenic GATA2 sequence variant were selected for retrospective chart review with respect to serious infectious complications including IFD.

Results
We identified 54 patients with a pathogenic GATA2 variant. 5 had a germline mutation related to familial GATA2 deficiency. The other 49 had a HM, mostly (41/49) acute myeloid leukemia or myelodysplastic syndrome. The frequency of the variant GATA2 allele in this group ranged from 2.5 to 92.0% of sequencing reads. 14 patients were excluded due to lack of sufficient follow-up, often related to treatment at another institution. Of the remaining 35 patients, 13 (37%) had proven/probable invasive fungal infection (IFI). Fourteen others had syndromes consistent with possible IFD. In total, 16 of these 35 patients (46%) received antifungal therapy for proven, probable or possible IFD. Four of the patients not treated with antifungals were diagnosed with a serious infection including 2 cases of Staphylococcus aureus bacteremia, and one case of disseminated Mycobacterium avium complex.

Conclusion
We identified a high incidence of IFD among patients with HM related to a pathogenic sequence variant of GATA2. The wide range of variant allele frequency observed raises the possibility that either inherited or acquired GATA2 dysfunction could incur predisposition to infection. These data suggest that personalized genetic diagnostics of patients with HM may be useful for assessment of infectious risk.

Disclosures
All authors: No reported disclosures.
2610. A Deadly Intrusion: Competitive Strain Displacement among Dengue Virus Strains in Sri lanka
Authors: Gallegos Dylan C , Rodriguez Stacy , Hansen Immo , Hanley Kathryn 
Published: October 2019

Abstract

Background
Mosquito-borne dengue virus (DENV), the agent of dengue hemorrhagic fever (DHF), is genetically diverse, and new strains regularly invade distant locations and displace existing strains. Invasive strains often cause higher rates of DHF than displaced strains, so it is critical to identify the mechanisms that enable invasion. We tested the hypothesis that invasive strains are less susceptible to RNA interference (RNAi), the major antiviral defense in mosquitoes, than displaced strains.

Methods
We knocked-down (KD) RNAi in vivo in Aedes aegypti, the DENV vector, by injecting mosquitoes with double-stranded RNA against Argonaute 2 (Ago2), a key enzyme in the RNAi pathway, or a control dsRNA. Ago2 KD and control mosquitoes were fed bloodmeals containing 1 of 3 isolates each of 3 different strains of DENV that had undergone sequential competitive displacement in Sri Lanka, termed, in order of displacement, Pre-DHF, Post-DHF and Ultra-DHF. We predicted that the Pre-DHF strain, which we have previously shown to be less infectious for mosquitoes than the other two strains, would show a greater increase in infectivity than those strains. Engorged mosquitoes were incubated for 10 days, homogenized, and assayed for virus.

Results
Ago2 KD efficiency ranged from 79% to 98%, as determined by semi-quantitative PCR and band densitometry. The percentage of mosquitoes infected following Ago2 vs. control KD was not significantly different (33% vs. 47%; paired t-test, DF = 8, P = 0.08). However, among infected mosquitoes, virus titer was significantly higher in Ago2 KD mosquitoes (3.98 vs. 3.38 log10 plaque forming units/body; t-test, DF = 14, P = 0.02). Contra our prediction, a two-factor ANOVA did not reveal a significant interaction between the effect of virus strain and treatment (DF = 5, P = 0.58), indicating that Pre-DHF viruses did not show a larger response to Ago2 KD than Post and Ultra-DHF viruses.

Conclusion
These data support the role of RNAi as a key mosquito defense against virus replication in mosquitoes but indicate that the differences in competitive success among the 3 DENV strains studied are not due to differences in interactions with Ago2 during initial stages of mosquito infection.

Disclosures
All authors: No reported disclosures.
2619. Clinical Characteristics and Etiology of Community-Acquired Pneumonia in Children: A Contemporary, Prospective, Multicenter Study in Ohio, 2015–2018
Authors: Yun Ki Wook , Wallihan Rebecca , Desai Ankita P , Alter Sherman J , Ambroggio Lilliam , Cohen Daniel M , El-Assal Osama , Marzec Sarah , Florin Todd A , Florin Todd A , Keaton Meghan , Shah Samir S , Mejias Asuncion , Ramilo Octavio , Ramilo Octavio 
Published: October 2019

Abstract

Background
Worldwide, pneumonia is the leading cause of death in children <5 years of age and the second most common reason for hospitalization in children in the United States and Europe. This study was designed to describe the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children.

Methods
We conducted a prospective, multicenter, observational study of CAP among previously healthy children aged 2 months through 18 years in six children’s hospitals in Ohio. Blood, pleural fluid, and nasopharyngeal swabs were collected for pathogen detection by culture and/or molecular diagnostics. Patient clinical management including antibiotic therapy and respiratory support, followed the standard of care at each study site. Follow-up information regarding clinical outcomes was collected via a survey 6–8 weeks after enrollment.

Results
We enrolled 441 children (n = 380, 86% hospitalized) with CAP from 2015 to 2018. Median age was 5 years (IQR: 2.1–8.9y). Intensive care and respiratory support were required for 15% and 49% of children, respectively. Consolidation and pleural effusion were identified in 26% and 21%, respectively. Among hospitalized children, 99% received antibiotics during hospitalization, and 91% continued antibiotic treatment at discharge. There were no children with any kind of sequelae or deaths from CAP, but 4.4% were readmitted within 30 days after discharge. Pathogens were identified in 64% patients; including pyogenic bacteria in 4%, atypical bacteria in 9%, and viruses in 56%. A total of 18 (4%) children had both bacterial (9 pyogenic and 9 mycoplasma) and viral pathogens. Among children with a virus detected (n = 245), 17% had more than one virus. The most commonly detected bacteria were M. pneumoniae (n = 39) and S. pneumoniae (n = 10). Rhinovirus was the most common virus detected (RV; n = 81, 28%), followed by respiratory syncytial virus (RSV; n = 75, 26%).

Conclusion
In this multicenter cohort, the most commonly detected viruses in children with CAP were RV and RSV, and M. pneumoniae and S. pneumoniae among bacteria. Clinical outcomes in children with CAP were overall good, but there was a high burden of hospitalization and antibiotic use.

Disclosures
Octavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.
2632. Cord Blood Vitamin D and Maternal Vaccination Status Associated with Decreased Laboratory Confirmed Influenza Infections in Infants
Authors: Betz Kristina , Fenchel Matthew , Steinhoff Mark C , Schlaudecker Elizabeth P 
Published: October 2019

Abstract

Background
Maternal influenza vaccination has been demonstrated to reduce influenza infections in infants. Influenza infections generally peak during the winter season, and several studies support the association between low levels of vitamin D during winter months and an increase in respiratory infections, including influenza. We examined the effects of vitamin D and maternal influenza vaccination status on laboratory confirmed influenza infections in infants less than 6 months of age.

Methods
Pregnant Bangladeshi mothers were randomized to receive influenza vaccine or pneumococcal vaccine as part of the Mother’s Gift study. Mothers reported breastfeeding frequency, along with episodes of infant respiratory illness with fever, every week for the first 6 months of life. If a respiratory illness with fever was reported, nasal swabs were obtained from the infant and tested with a commercial rapid influenza test. Infants with confirmed influenza disease were matched with four controls by birth month and sex, for a total of 84 controls. We measured 25-hydroxyvitamin D levels from cord blood in all cases and controls. A conditional logistic regression was performed to test the effect of vitamin D on the odds of laboratory confirmed influenza while controlling for birth weight, gestational age, crowding, number of siblings, and socioeconomic status score.

Results
A total of 21 infants had laboratory confirmed influenza disease. There were no significant differences in birth weight, crowding, family size, gestational age, socioeconomic status score, infant gender, and smokers in the home between cases and controls (Table 1). Frequency of maternal influenza vaccine was lower in cases when compared with controls (23.81% vs. 58.33%). Serum vitamin D was lower in cases than in controls (8.73 ± 3.34 vs. 10.67 ± 4.08, Table 2).

Conclusion
Both vitamin D levels and maternal vaccination status have medically relevant, and statistically significant, independent effects on the odds of infants contracting influenza. Although the vitamin D levels in the infants at birth were low, there was a significant association of lower levels at birth with an increased risk of influenza virus infection. Further study with a larger sample-size is needed to explore these effects.

Disclosures
All authors: No reported disclosures.
2637. Third Trimester Immunization with an Respiratory Syncytial Virus F Protein Vaccine for the Prevention of RSV Lower Respiratory Tract Infection in Infants
Authors: Fries Louis F , Cho Iksung , Thomas D Nigel , Wen Judy L , Spindler Michelle S , Fix Amy B , Plested Joyce S , Chen Chang-Min , Glenn Gregory M 
Published: October 2019

Abstract

Background
Respiratory syncytial virus (RSV) is the leading viral cause of severe lower respiratory tract infection (LRTI) in infants worldwide, with severe disease occurring in the first months of life. We assessed the efficacy of maternal immunization with an RSV F protein vaccine against RSV LRTI over the first 180 days of life.

Methods
We enrolled 4,636 women with low-risk third trimester singleton pregnancies in 11 countries to receive RSV F vaccine or placebo in a randomized, observer-blind trial. Women were followed for 6 months post-delivery, and infants for ~1 year. Surveillance for RSV LRTI in infants, identified by RT–PCR detection of RSV, physical examination, and pulse oximetry, was carried out for 180 days from delivery.

Results
The RSV F vaccine induced modest reactogenicity and no excess fever. Live births resulted from 98.7% of pregnancies, with no difference between treatment groups in prematurity (< 37 weeks) or mean interval from treatment to delivery. There were no apparent negative impacts on pregnancy, delivery, or infant well-being. Vaccine immunogenicity resembled that in non-pregnant women. Transplacental transfer of vaccine-induced antibodies was markedly more efficient when the interval from immunization to delivery was ≥30 days. 85 to 95% of primary and secondary endpoint RSV LRTI events in the placebo group occurred in the first 90 days of life (see Figure 1). Overall, through 180 days of infant life, RSV was associated with 11.3% of all acute respiratory illnesses and 16.7% of all LRTI, but 49.1% of LRTI with SpO2 < 95% or tachypnea, and 60.3% of all LRTI with SpO2 < 92% in the placebo group. Vaccine efficacy was greatest in the first 75 days of life but clearly persisted to the primary, per-protocol analysis at 90 days, and was supported by the ITT analysis, per Table 1. Efficacy against all-cause LRTI with severe hypoxemia (46.0%) or hospitalization (27.8%) was observed in the per-protocol population, as well as an apparent impact on the clinical diagnosis of pneumonia through both 180 and 364 days.

Conclusion
RSV F vaccine in the third trimester was safe and had clinically-meaningful impacts on RSV and all-cause LRTI over the first 6 months of life.

Disclosures
All authors: No reported disclosures.
2663. Impact of Pre-Transplant Microbiology on Acute Outcomes in Cystic Fibrosis Patients Receiving Bilateral Lung Transplants
Authors: (Michael) Ji Xincheng , Jain Raksha , Greenberg David E 
Published: October 2019

Abstract

Background
Lung transplantation is a life-prolonging intervention for cystic fibrosis (CF) patients; however, their tendency to be colonized with multiple respiratory pathogens poses a unique risk for post-transplant complications. While infections with certain CF-related pathogens have been identified as contraindications for transplant, much remains uncertain about the influence of pre-transplant microbiological factors on post-transplant outcomes.

Methods
A retrospective cohort study was performed for all CF patients receiving bilateral lung transplants at a single center during the 2016–2018 period. Patient and microbiological data were collected and analyzed from 1 year pre-transplant to 3 months post-transplant. Patients were categorized according to pre-transplant microbiology, with consideration to multidrug-resistant organisms (MDROs) and chronic organisms (positive culture in ≥ 50% of encounters).

Results
Twenty-seven CF patients received a transplant during this time period. Twenty-five patients (92.6%) had re-isolation with ≥ 1 pre-transplant organism in the 3 month period post-transplant, with 16 (59.3%) developing infectious complications, and 11 (40.7%) developing rejection. Isolates associated with chronic infections were the principal factor in determining re-isolation post-transplant (OR = 4.353, 95% CI = 1.455–13.027, P = 0.009). Multidrug-resistance (P = 0.095) and species (P > 0.3) were not significant predictors of re-isolation. There was no difference in early post-transplant outcomes (infectious complications, rejection, FEV1% predicted, ICU and hospital LOS) for patients chronically infected with MDROs vs. those who were not (P > 0.3). Chronic infections with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus were not predictors of poor outcomes (P > 0.3). However, chronic fungal infections (n = 7) produced more infectious complications (median 2 vs. 0, P = 0.0453) and longer ICU stays (median 22 days vs. 5 days, P = 0.0191).

Conclusion
Chronic infections are associated with a greater risk of post-transplant re-isolation of pathogens in CF patients, more so than drug resistance or species. Chronic infections with fungi were associated with worse transplant outcomes.

Disclosures
All authors: No reported disclosures.
2665. Intestinal Microbiome of Patients Submitted to Hematopoietic Stem Cell Transplantation Using Lactobacillus plantarum to Decolonized Multidrug-Resistant Bacteria
Authors: Moraes Bruna G C , Martins Roberta C R , Franco Lucas A M , Lima Victor A C C , Pereira Gaspar C O , Santos Juliana T , Fernandes Tamiris H , Guimaraes Thais , Rocha Vanderson G , Sabino Ester C , Costa Silvia F 
Published: October 2019

Abstract

Background
Patients colonized by multidrug-resistant bacteria (MDR) have high risk for infection after hematopoietic stem cell transplantation (HSCT). Probiotic is a strategy that can be used to decolonize patients. Our aim was to describe the impact of use of Lactobacillus plantarum (LP) on decolonization, MDR infections and intestinal microbiome (IM) of autologous HSCT patients colonized by vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Gram-negative (CRGN).

Methods
A prospective study was conducted at Hospital das Clinicas of University of Sao Paulo Brazil from 2017 to 2018. Candidates for auto-HSCT colonized by MDR received LP in capsules, 5 × 109 CFU twice daily until neutropenia (NP). Rectal swabs were performed and cultured using selective media as well as PCR for carbapenemases, vanA and vanB. Stool samples for IM analysis were collected weekly as baseline (before LB use) until the NP. The V4 region of 16S rDNA gene were sequenced by Ion Torrent PGM and analyzed using alpha and β diversities by Qiime. Demographic and clinical data including previous antibiotics use were evaluated; CDC criteria was applied for colonization and infection.

Results
All of seven patients were colonized by VRE and CRGN (Table 1). Only one patient remained colonized by CRGN after 61 days of LP. Four patients developed seven bloodstream infections (BSI) during the NP, two of them by CRGN. There was no infection caused by VRE neither by LP. One patient, with low adherence to LP use (66%), died due to MDR K. pneumoniae BSI. We observed a decrease of Clostridia, Verrucomicrobiae, Blautia and an increase of Enterobacteriaceae. Baseline samples from patients who used TMP/SMX had higher concentrations of Bacteroidetes when compared with those who had not use it. The Shannon index in controls ranged 1.98–5.55 and during NP 1.15–5.99. The β diversity analysis showed no clear patterns between patients.

Conclusion
We observed a heterogeneity among IM of auto-HSCT patients prior and after LP. It was not possible to establish an IM pattern, probably, because of small number of patients. Although, clinical infections by CRGN occurred despite of LP use, no cases of colonization and infection by VRE were identified. Thus, it seems that LP is a good and safe strategy to decolonized HSCT.

Disclosures
All authors: No reported disclosures.
2670. Clostridioides difficile Infection (CDI) in Solid-Organ (SOT) and Hematopoietic Stem Cell Transplant (HCT) Recipients: A Prospective Multinational Study
Authors: Blumberg Emily , Gary Collins , Young Jo-Anne H , Nguyen Minh-Hong , Michonneau David , Temesgem Zelalem , Origuen Julia , Barcan Laura , Obeid Karam , Belloso Waldo , Gras Julien , Corbelli Giulio Maria , Neaton James , Lundgren Jens , Snydman David R , Molina Jean-michel 
Published: October 2019

Abstract

Background
CDI is an important cause of morbidity and mortality in SOT and HCT patients (pts). In retrospective single-center analyses, severe disease and relapse were common. We undertook a multicenter prospective observational study to evaluate outcomes of CDI among both SOT and HCT patients.

Methods
Adults with a first episode of CDI, defined as 3 liquid stools/24 h with the detection of C. difficile toxin in stool, within the first 2 years of SOT or HCT were recruited from 12 centers internationally in the INSIGHT network. At enrollment, demographics, comorbidities, medication histories and outcomes were collected prospectively over 90 days to assess clinical cure, recurrences and complications and to define baseline risk factors for clinical cure and recurrent CDI.

Results
132 patients (81 SOT, 51 HCT (32 allogeneic)) were enrolled: median age 56 years, 62.1% were males, 97% were hospitalized. 80.3% were diagnosed by DNA assay. CDI occurred a median of 20 days post transplant (IQR: 6–133). 108 patients were on PPIs. 98.5% were on antibiotics before CDI. 1st line treatment regimen was oral vancomycin in 66 patients (40 SOT, 26 HCT), metronidazole in 48 patients (27 SOT, 21 HCT), both drugs in 14 (10 SOT, 4 HCT), fidaxomicin (3) and linezolid (1). Rejection within 60 days before CDI was uncommon (6.2% SOT) as was GVHD (27.5%). 110 patients (83%, 95% CI: 46–89)) (65 SOT, 45 HCT) had clinical cure; 18% (95% CI: 11–27) had recurrent CDI, 2 were admitted to the ICU due to CDI, 11 (8.3%) died (2 HCT related to CDI). Among baselines variables, only first-line regimen was associated with a higher rate of clinical cure (P = 0.003), most notably for SOT. Factors that did not have a statistically significant negative impact on clinical cure included sex, age > 60, race, country, transplant type, steroids, diabetes, CMV viremia/disease, WBC > 15,000, creatinine > 1.5 mg/dL, or specific antibiotic given prior to CDI. Higher recurrence rates were associated with metronidazole-only regimen (OR: 4.6, 95% CI: 1.6–12.8; P = 0.004) and a history of CMV after transplant (OR: 5.2, 95% CI: 1.7–15.7; P = 0.003).

Conclusion
Despite their immunosuppressed state, recurrence, ICU admission and mortality occurred in a minority of SOT and HCT with CDI. Initial use of metronidazole and CMV viremia/disease were associated with higher recurrence rates.

Disclosures
All authors: No reported disclosures.