bluuebunny/crossref_metadata_2025_split huggingface dataset:
1731. Immune Dysregulation in Mucormycosis
Authors: Gupta Chhavi , Das Shukla , Rai Gargi , Singh Praveen K , Dar Sajad , Ansari Mohammad A 
Published: October 2019

Abstract

Background
Mucormycosis is a fatal fungal infection with unique predisposition to infect diabetics. Dysregulated adaptive immunity contributes to the pathogenesis in all fungal diseases, but activated Th17 cells have laid a new dimension to chronic inflammatory response which was previously attributed to uncontrolled Th1 response. We attempted to study the Th17 and T regulatory (Treg) immune response in diabetic patients with mucormycosis and compared the data with a healthy control and a T2DM case without fungal infection. In addition we could follow-up one patient post 6-month treatment and performed immunological studies.

Methods
2 mL of blood samples were collected in EDTA vial from two patients who were suffering from diabetes with mucormycosis for immunological investigations. Samples were also taken from age-matched T2DM patient without fungal infection and a healthy volunteer as controls for T-cell parameters. Repeat blood sample was taken to study immune parameters in one patient who was followed up after 6 months. The expression of various T-cell markers was analyzed by immunostaining with the antibodies against CD3, CD4, CD25, CD161, IL-23R [Becton Dickinson (BD) PharMingen]. Fluorescence profiles were analyzed using Flow Jo software (BD Biosciences). The results are expressed as a percentage of positive cells.

Results
The percentages of CD4+ cells were low in both patients when compared with and healthy control but it is much higher in diabetes case when compared with others. CD161+ cell population was higher in both patients when compared with healthy control and diabetic patient without fungal infection. The percentage of IL23R+ cells was significantly high in patient before treatment when compared with, healthy control and diabetics. and decline after treatment. The percentage positivity of CD25+ cells was highest in healthy control when compared with others. The profile of CD25+ cells was comparatively similar in patient before treatment and diabetics but we found a higher percentage, in patients after treatment.

Conclusion
The findings in this study imminently indicate the mechanism of immune dysregulation involving Th17 and Treg pathways in mucormycosis and provide evidence that restoration of Th17/Treg may be considered as a therapeutic option for long-term benefit in diabetics.

Disclosures
All authors: No reported disclosures.
1732. A Canine Target Species Challenge Model to Evaluate Efficacy of a Coccidioidomycosis Vaccine
Authors: Shubitz Lisa F , Bowen Richaard , Robb Edward J , Powell Daniel A , Bosco-Lauth Angela , Hartwig Airn , Trinh Hien , Lewis Maria L , Frelinger Jeffrey A , Galgiani John N 
Published: October 2019

Abstract

Background
The preferred efficacy design for licensing a vaccine for animal use (United States Department of Agriculture (USDA)) is a prospective, placebo-controlled, randomized, and double-blinded vaccination-challenge trial. In such studies, each subject receives the same exposure to the virulent pathogen by active challenge. To test a cps1, live avirulent canine coccidioidomycosis vaccine, an inhalation disease model was developed in beagle dogs.

Methods
6-month old male beagle dogs were housed according to PHS standards. All procedures, approved by the Institutional Animal Care and Use Committee for Colorado State University, were performed at ABSL3. Dogs were infected by nebulization with low, medium or high counts of arthroconidia of Coccidioides posadasii, strain Silveira, delivered via endotracheal tube under injectable anesthesia. Thoracic radiographs, CBC, and serum chemistries and body weights were obtained at 2- or 3-week intervals and dogs were euthanized 8 weeks p.i., or earlier if necessary. Approximately 1 gram lung specimens from each lobe were cultured for fungal burden. Fixed tissues were examined histologically. Serum was tested for antibodies.

Results
Ten of 11 dogs were successfully infected; 5 required early removal at 33 to 48-days p.i. Elevated globulin, decreased albumin, decreased A/G ratio, monocytosis and weight loss were present in all infected dogs. Radiographic and histopathological lesions were very extensive at the high challenge doses. Medium doses had the most consistent scoring and clinical findings, including some early removal, without overwhelming disease, while the low dose produced the least consistent quantifiable features. All dogs developed antibodies.

Conclusion
Nebulized aerosol delivery of spores reproducibly produced significant coccidioidomycosis in 10 of 11 dogs. Overall, the challenge model demonstrated consistent characteristic findings sufficient to assess vaccine efficacy in dogs during an 8-week period post challenge without producing a potentially overwhelming infection. The aerosol nebulization of arthroconidia in beagle dogs should provide a vaccination-challenge experimental design in line with Chapter 9 Code of Federal Regulations, parts 102.5 and 104.5.

Disclosures
All authors: No reported disclosures.
1739. Epidemiology of Invasive Fungal Infections in Allogenic Hematopoietic Stem Cell Transplant Recipients in Utah
Authors: Zurko Jessica , Webb Brandon J 
Published: October 2019

Abstract

Background
Invasive fungal infections are a leading cause of death in allo-HSCT (allogenic hematopoietic stem cell transplant) recipients. We describe the epidemiology of IFIs (invasive fungal infections) in allo-HSCT recipients at a single institution in Salt Lake City, Utah between 2006 and 2015.

Methods
We searched all encounters in the Intermountain Healthcare electronic medical record from 2006 to 2015 for clinical data associated with IFIs in allo-HSCT recipients. EORTC-MSG definitions were applied to categorize IFI as proven, probable, or possible. Linear regression was used to model the variation in incidence over time.

Results
326 unique allo-HSCT were performed; of these 114 episodes of IFI occurred in 105 patients. Mean incidence was 35.9 IFI per 100 transplants, and increased by 2.3 IFI cases/100 transplants per year. 25.4% of cases were classified as proven; 47.4% as probable and 19.3% as possible. Invasive Aspergillus represented the majority of cases (62.3%), followed by non-specified (in most cases positive imaging and a positive β-d-glucan, 18%), Candidiasis (10%), and Mucorales (3.5%). The median age was 50 years, range 22 to 73, with males representing 52.6% of cases. The most common non-hematologic comorbidities were chronic pulmonary disease (42.9%), chronic heart failure (32.4%), and hepatic disease (31.4%). 48.6% of patients received matched unrelated allo-HSCT, 34.3% received matched sibling donor allo-HSCT, 14.3% received haploidentical allo-HSCT, and 3% received cord allo-HSCT. 79% of transplants were myeloablative. Median time from transplant to onset of IFI was 145 days (95% CI 39–259). The median time to onset of Aspergillosis was 120 days (95% CI 34–241 days), Candidiasis was 130 days (95% CI 12–283 days), and Mucorales was 246 days (95% CI 126–338 days). Active GVHD was present in 60% of IFI cases. 63% of cases were on antifungal prophylaxis, most commonly an echinocandin. All-cause mortality was 30.5% at 42 days and 65.7% at 1 year. The median time to death from the onset of IFI was 68.5 days.

Conclusion
IFIs are common in allo-HSCT recipients and appear to be increasing in frequency. Further work is needed to risk-stratify patients, determine optimal prophylaxis and empiric treatment, and define resistance trends.

Disclosures
All authors: No reported disclosures.
1757. Hepatitis C-Infected Donors and Hepatitis C-Infected Recipients: Analysis of Renal Transplant Outcomes
Authors: Crossman Hayley , Tavakol Mehdi , Freise Chris , Chin-Hong Peter 
Published: October 2019

Abstract

Background
Increased utilization of hepatitis C virus (HCV)-infected organs could reduce the supply–demand mismatch in organ transplantation. It is important to determine precise outcomes of HCV-positive organs transplanted into HCV-positive recipients (HCV D+\R+) to quantify risk for patients and other stakeholders. Small studies have identified shorter wait times in HCV D+\R+ compared with HCV-negative donor and HCV-positive recipients (HCV D−\R+), but there is little information about survival and rejection in the era of effective direct-acting antivirals (DAA).

Methods
We performed a retrospective cohort study of all cases of renal transplantation involving HCV-positive recipients at an academic medical center from 2008 to 2019. We extracted data using the institutional electronic transplant database. Demographics, incidence of organ rejection, renal function and patient mortality data were compared between HCV D+\R+ and HCV D−\R+.

Results
Among 3,781 patients who received a kidney transplant between 2008–19, 139 were HCV D-\R+ and 51 were HCV D+\R+. Both groups had similar waiting list time (1,196 ± 889 days vs. 1,301 ± 1240 days, P > 0.20), donor mean age (37 ± 11 y vs. 39 ± 13 years, P > 0.20) and sex (female: 37% vs. 42%, P > 0.20). Follow-up time was similar between both groups (5.2 ± 4 years vs. 5.3 ± 3 years, P > 0.20). The incidence of mortality (16% vs. 17%, P > 0.20) [Figure 1] and rejection (18% vs. 19%, P > 0.20) [Figure 2] was similar between two groups. Using a Cox Hazards model, we found no association between HCV D+/R+ and increasing risk of rejection (HR 0.92, 95% CI 0.43–1.95, P > 0.20) or mortality (HR 0.93, 95% CI 0.42–2.1, P > 0.20). In a multivariate analysis, age was the only independent risk factor for HCV D+/R+ mortality (HR = 1.09, 95% CI 1.03–1.14, P < 0.001).

Conclusion
Patients who are HCV-positive did not have worse mortality or graft rejection if they received HCV-positive kidneys compared with HCV-negative kidneys. Providers can use these data to give specific risk information to HCV-positive patients about accepting an HCV-positive kidney for transplant, even perhaps encouraging it. Increasing the utilization of HCV-positive kidneys for transplantation in the era of effective DAA has the potential to offer life-saving treatment to substantially more patients.

Disclosures
All authors: No reported disclosures.
1770. Access to Kidney Transplantation in Persons Living with HIV and End-stage Renal Disease in Network 6
Authors: Adekunle Ruth O , Zhang Rebecca , Wang Zhensheng , Patzer Rachel , Mehta Aneesh 
Published: October 2019

Abstract

Background
As persons living with HIV (PLWH) live longer, end-stage renal disease (ESRD) is emerging as a significant cause of morbidity and mortality. PLWH had a three-fold increased risk of ESRD, while also experiencing lower survival rates on dialysis compared with the general population. There are limited data on the incidence and prevalence of PLWH on dialysis. Our objective was to determine the incidence of PLWH on dialysis in ESRD Network 6 (GA, NC, SC) and assess their referral to kidney transplantation and waitlisting on the deceased donor waiting list.

Methods
We merged data from the Southeast Transplant Referral Dataset with the United States Renal Data System Medicare Part D Prescription Claims. PLWH were defined as having a prescription for antiretroviral medications or primary cause of ESRD being HIV-associated nephropathy. Descriptive analysis was performed using Student’s t-test for continuous variables and chi-squared test for categorical variables.

Results
The dataset contained 24,587 patients (471 HIV positive) that initiated an ESRD service between 2012 and 2015. Incidence of PLWH on dialysis was 1.92%. Compared with HIV negative persons, PLWH were younger (median age 49 vs. 58, P < 0.001) and more often black (90% vs. 57%, P < 0.001). There were similar rates of referral among PLWH and HIV-negative persons (50% vs. 51%, P = 0.81), though PLWH were statistical significantly less likely to be waitlisted (8% vs. 15%, P < 0.001). PLWH had longer median time to be referred (240 days vs. 147 days, P < 0.001) and waitlisted compared with HIV-negative persons (611 days vs. 420 days, P = 0.04).

Conclusion
This pilot study offers the first ESRD Network-level characterization of PLWH receiving an ESRD service proceeding through the steps of kidney transplantation. PLWH were less likely to traverse the steps of kidney transplant compared with those HIV negative, highlighting the need for targeted interventions to improve access to kidney transplant in PLWH.

Disclosures
All authors: No reported disclosures.
1774. Impact of a Multiplex Polymerase Chain Reaction Assay on the Clinical Management of Adults Undergoing a Lumbar Puncture for Suspected Community-Onset Central Nervous System Infections
Authors: Moffa Matthew , Elrufay Rawiya , Walsh Thomas L , Carr Dustin R , Shively Nathan , Buchanan Carley , Bremmer Derek N 
Published: October 2019

Abstract

Background
Patients admitted from the community with a suspected central nervous system (CNS) infection require prompt antimicrobial treatment and diagnostic evaluation. Our health network recently implemented a multiplex polymerase chain reaction (PCR) assay in-house.

Methods
This was a pre-/post-intervention study evaluating the impact that a multiplex PCR assay had on the clinical management of patients ≥18 years of age admitted from the community with a lumbar puncture (LP) performed for a suspected CNS infection. The primary outcome was Herpes Simplex Virus (HSV) PCR turnaround time (TAT). Secondary outcomes included inpatient length of stay (LOS), total antimicrobial days of therapy (DOT), and antiviral DOT. Patients were excluded if an LP was performed after hospital day 3, if they were on a systemic antimicrobial for a non-CNS indication, if they were a neurosurgical patient, and if they had a fungal CNS infection.

Results
The pre- and post-intervention groups each had 57 patients. The average age was 51 and 52 years in the pre- and post-intervention groups, respectively. Four patients (7%) in the pre-intervention group were immunocompromised, compared with 9 (16%) in the post-intervention group. Four patients in the pre-intervention group had a positive PCR assay for either HSV or Varicella Zoster Virus (VZV), compared with 5 patients in the post-intervention group. Neither group had a positive cerebrospinal fluid culture, bacterial antigen assay, or bacterial PCR assay. The median (IQR) HSV PCR TAT was significantly longer in the pre-intervention group, 85 (78, 96) vs. 3.9 hours (2.9, 4.7), P < 0.001. The mean LOS was numerically greater in the pre-intervention arm (7 vs. 4.7 days, P = 0.069), as were the total antimicrobial DOT (9 vs. 7.4 days, P = 0.279) and antiviral DOT (3.9 vs. 2.7 days, P = 0.136). Pre-intervention antiviral DOT was significantly greater (3.1 vs. 1.6 days, P = 0.011) in patients without a positive HSV or VZV PCR.

Conclusion
Implementing a multiplex PCR assay for adults undergoing an LP for a suspected CNS infection significantly reduced the HSV PCR turnaround time. Antiviral DOT was significantly shorter in patients with a negative PCR result post-intervention. We also found a non-significant reduction in LOS, total antimicrobial DOT, and antiviral DOT.

Disclosures
All authors: No reported disclosures.
1776. Step-Wise Algorithm for the Detection of Respiratory Viruses: Integrating a Rapid Influenza A/B and RSV PCR with a Multiplex Respiratory Virus Panel to Target High-Risk Patient Populations
Authors: Matic Nancy , Lawson Tanya , Karakas Loretta , Jang Willson , Ritchie Gordon , Hinch Michelle , Leung Victor , Romney Marc G , Lowe Christopher F 
Published: October 2019

Abstract

Background
In clinical settings, multiplex molecular panels are becoming increasingly common for the detection of respiratory pathogens. Little evidence is available to guide appropriate use of respiratory multiplex panels, particularly with respect to the patient populations most likely to benefit from such testing.

Methods
During the 2018–2019 influenza season, all patients with a nasopharyngeal swab submitted for respiratory virus detection were initially tested on a commercial rapid PCR platform for influenza A/B and respiratory syncytial virus (RSV) (Cepheid GeneXpert, Sunnyvale, CA). Patients with negative swabs were reviewed by a laboratory physician based on pre-defined criteria (Table 1) for additional testing by a laboratory-developed multiplex assay for parainfluenza 1/2/3, adenovirus, and human metapneumovirus (hMPV).

Results
In total, 1144 nasopharyngeal swabs were tested. 287 (25.1%) were positive on the GeneXpert: influenza A (234, 81.5%), influenza B (13, 4.5%), and RSV (40, 13.9%). Of the patients who tested negative, 234 (27.3%) met criteria for further respiratory virus testing. The most commonly detected viral pathogens on the multiplex assay were hMPV (20/30, 66.7%), parainfluenza 3 (7/30, 23.3%) and adenovirus (3/30, 10%). The yield of the multiplex assay was highest for patients selected for antimicrobial stewardship (AS) criteria (13/56, 23.2%), followed by transplant (2/16, 12.5%), HIV (7/64, 10.9%), cystic fibrosis (2/19, 10.5%), critical care (6/68, 8.8%), and other/upon physician request (0/11, 0%). Of the patients who received multiplex testing for AS criteria and tested positive for a viral pathogen, only 3/13 (23.1%) had antibiotics discontinued by the medical team within 48 hours of the report.

Conclusion
Additional testing for respiratory viral pathogens had low overall diagnostic yield, and further refinement of the algorithm is needed to better target utilization of respiratory virus testing. The patient population with the highest yield (those who met AS criteria) failed to demonstrate consistent timely discontinuation of unnecessary antibiotics by the medical team. Implementation of respiratory multiplex panels would be strengthened by collaboration with AS teams.

Disclosures
All authors: No reported disclosures.
1777. Metagenomic Approach for the Detection of Viruses in Stool Samples from Infants and Children with Acute Gastroenteritis in Kuwait
Authors: Adel Hawraa , Madi Nada , Al-Nakib Widad 
Published: October 2019

Abstract

Background
Metagenomics techniques are target-independent tools that enable the identification of uncommon disease etiologies and genomic characterization of all microorganisms present in a sample in less time and at a lower cost than previous sequencing techniques. In this study, we developed a metagenomic approach using next-generation sequencing technology to identify known and unknown viruses in stool samples from infants and children with acute gastroenteritis in Kuwait.

Methods
We have investigated 84 stool samples from infants and children aged one month to 10 years old with signs and symptoms of gastroenteritis who attended Mubarak Al-Kabeer and Al-Amiri hospitals in Kuwait from January to December 2017 using both multiplex real-time PCR and metagenomics sequencing (Illumina Miseq instrument) methods.

Results
The metagenomics analysis of viral sequences verified that human adenovirus was the leading cause of gastroenteritis among infants and children in Kuwait, and was detected in 23% of the samples, rotavirus A was detected in 16% of the samples, and the combined infection of human adenovirus and rotavirus was detected in 7% of the samples. Also, newly discovered viruses known to cause gastroenteritis were identified; astrovirus MLB2 and primate bocaparvovirus-1 were detected in 5% of the samples. Also, each of the following new viruses was detected in 2% of the samples; aichivirus A, cardiovirus, parechovirus A, astrovirus VA4, cosavirus F, and bufavirus-3. On the other hand, multiplex real-time PCR showed that the combined infection of human adenovirus and rotavirus was the leading cause of gastroenteritis among infants and children in Kuwait, which was detected in 27% of the samples. However, the rotavirus was the second most common cause of diarrhea, which was detected in 20% of the samples. And the human adenovirus alone was detected in 18% of the samples. Our results showed a 69% agreement between both methods. By applying the Cohen’s Kappa statistics for a measure of agreement, the result gave fair agreement between the two methods (k = 0.388, P = 0.0).

Conclusion
Our findings revealed the capability of a metagenomic approach to detect many viruses causing gastroenteritis in stool samples from infants and children in Kuwait.

Disclosures
All authors: No reported disclosures.
1782. Real-World HIV Diagnostic Testing Patterns in the United States
Authors: Karichu James , Cheng Mindy , Rodriguez Pedro , Robinson Nicole , Burudpakdee Chakkarin , Near Aimee , Tse Jenny , Faccone Jillian 
Published: October 2019

Abstract

Background
Current HIV diagnostic laboratory testing guidelines from the US Centers for Disease Control and Prevention (CDC) recommend a sequence of tests for detection, differentiation, and confirmation of HIV-1 and HIV-2 diagnosis. There is a gap in knowledge about real-world implementation of the testing algorithm. The aim of this study was to characterize the population that underwent HIV antibody differentiation and confirmatory testing and to describe subsequent testing patterns from a large US clinical laboratory database.

Methods
Patients who received one or more HIV-1/2 antibody differentiation test (BioRad Geenius™ HIV 1/2 Supplemental Assay [Geenius]) in the Quest Diagnostics laboratory database between January 1, 2017 and December 31, 2017 were selected into the study; earliest test date was index date. Geenius tests, HIV-1 qualitative RNA (Aptima HIV-1 RNA Qualitative Assay [Aptima]), and HIV-2 DNA/RNA confirmatory tests subsequent to index date were captured. Study measures included pt demographic characteristics, testing frequency and sequencing, and test results. For patients with >1 Geenius test in 2017, concordance between index and subsequent test results was assessed.

Results
There were 26,319 unique patients identified who received ≥1 HIV antibody differentiation result from the Geenius assay. Mean age was 40.7 ± 14.3 years, 66.4% were male, and 42.5% were from southern states. Among the study population, there were 28,954 Geenius, 7,234 Aptima, and 298 HIV-2 DNA/RNA confirmatory tests. 26.4% of Geenius test results were discordant with the initial positive fourth-generation HIV screening results and required subsequent confirmatory testing. In terms of sequencing, the CDC-recommended HIV diagnostic algorithm was followed 74% of the time after screening. 8.5% of patients had >1 Geenius test in 2017; 11.2% of the retests returned different results compared with the first test.

Conclusion
The CDC recommended algorithm for HIV diagnosis is complex for laboratories to implement and currently available assays do not support testing efficiency. To mitigate observed inefficiencies and reduce the laboratory burden of HIV testing, a more accurate and reliable approach for HIV differentiation and confirmatory testing is needed.

Disclosures
All authors: No reported disclosures.