First name
William
Middle name
R
Last name
Otto

Title

Prospective Evaluation of the Fungitell® (1→3) Beta-D-Glucan Assay as a Diagnostic Tool for Invasive Fungal Disease in Pediatric Allogeneic Hematopoietic Cell Transplantation: A Report from the Children's Oncology Group.

Year of Publication

2023

Number of Pages

e14399

Date Published

02/2023

ISSN Number

1399-3046

Abstract

BACKGROUND: Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non-invasive biomarkers, such as the beta-D-glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta-D-glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post-HCT period.

METHODS: Weekly surveillance blood testing with the Fungitell® BDG assay was performed during the early post-HCT period in the context of a randomized trial of children, adolescents, and young adults undergoing allogeneic HCT allocated to triazole or caspofungin prophylaxis. Positivity was defined at the manufacturer cutoff of 80 pg/ml. IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the Fungitell® BDG assay for the outcome of proven or probable IFD.

RESULTS: A total of 51 patients (out of 290 patients in the parent trial) contributed blood specimens. In total, 278 specimens were evaluated. Specificity was 80.8% (95% confidence interval [CI]: 75.6%-85.3%), and NPV was over 99% (95% CI: 86.8%-99.9%). However, there were no true positive results, resulting in sensitivity of 0% (95% CI: 0.0%-84.2%) and PPV of 0% (95% CI: 0.0%-6.7%).

CONCLUSIONS: Fungitell® BDG screening is of limited utility in diagnosing IFD in the post-HCT period, mainly due to high false-positive rates. Fungitell® BDG surveillance testing should not be performed in children during the early post-HCT period while receiving antifungal prophylaxis as the pretest probability for IFD is low.

DOI

10.1111/petr.14399

Alternate Title

Pediatr Transplant

PMID

36299233

Title

Absolute lymphocyte count recovery following initial acute myelogenous leukemia therapy: Implications for adoptive cell therapy.

Year of Publication

2022

Number of Pages

e30062

Date Published

11/2022

ISSN Number

1545-5017

Abstract

BACKGROUND: An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML.

PROCEDURE: ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 and 2018 at one of three hospitals in the Leukemia Electronic Abstraction of Records Network (LEARN) consortium.

RESULTS: Among 193 patients with sufficient ALC data for analysis, the median ALC following induction 1 was 1715 cells/μl (interquartile range: 1166-2388), with successive decreases in ALC with each subsequent course. Similarly, the proportion of patients achieving an ALC >400 cells/μl decreased following each course, ranging from 98.4% (190/193) after course 1 to 66.7% (22/33) for patients who received a fifth course of therapy.

CONCLUSIONS: There is a successive decline of ALC recovery with subsequent courses of chemotherapy. Despite this decline, ALC values are likely sufficient to consider apheresis prior to the initiation of each course of upfront therapy for the majority of newly diagnosed pediatric AML patients, thereby providing a window of opportunity for T-cell collection for those patients identified at high risk of relapse or with refractory disease.

DOI

10.1002/pbc.30062

Alternate Title

Pediatr Blood Cancer

PMID

36370087

Title

Ribavirin Use in Hospitalized Children.

Year of Publication

2022

Number of Pages

386-387

Date Published

06/2022

ISSN Number

2048-7207

DOI

10.1093/jpids/piac039

Alternate Title

J Pediatric Infect Dis Soc

PMID

35699489

Title

Risk of bacterial bloodstream infection does not vary by central-line type during neutropenic periods in pediatric acute myeloid leukemia.

Year of Publication

2022

Number of Pages

1-8

Date Published

2022 Apr 25

ISSN Number

1559-6834

Abstract

<p><strong>BACKGROUND: </strong>Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.</p>

<p><strong>OBJECTIVE: </strong>To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.</p>

<p><strong>METHODS: </strong>We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.</p>

<p><strong>RESULTS: </strong>The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75-1.32) and TIC IRR = 0.83 (95% CI, 0.49-1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.</p>

<p><strong>CONCLUSIONS: </strong>In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.</p>

DOI

10.1017/ice.2022.82

Alternate Title

Infect Control Hosp Epidemiol

PMID

35465865

Title

Association between Preferred Language and Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children in the United States.

Year of Publication

2021

Date Published

2021 Sep 01

ISSN Number

1476-1645

Abstract

<p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a disproportionate impact on Black, Hispanic, and other individuals of color, although data on the effect of a person's language on SARS-CoV-2 infection are limited. Considering the barriers suffered by immigrants and non-English-speaking families, we tested whether children with a preferred language other than English was associated with SARS-CoV-2 infection. Children from families with a preferred language other than English had a higher predicted probability of SARS-CoV-2 test positivity (adjusted odds ratio, 3.76; 95% CI, 2.07-6.67) during the first wave of the pandemic. This discrepancy continued into the second wave (adjusted odds ratio, 1.64; 95% CI, 1.10-2.41), although the difference compared with families who prefer to speak English decreased over time. These findings suggest that children from non-English-speaking families are at increased risk of SARS-CoV-2 infection, and efforts to reverse systemic inequities causing this increased risk are needed.</p>

DOI

10.4269/ajtmh.21-0779

Alternate Title

Am J Trop Med Hyg

PMID

34469330

Title

Case Report: Immune Dysregulation Due to Reactivation After Allogeneic Hematopoietic Cell Transplant.

Year of Publication

2021

Number of Pages

719679

Date Published

2021

ISSN Number

2296-2360

Abstract

<p>Disseminated toxoplasmosis is an uncommon but highly lethal cause of hyperferritinemic sepsis after hematopoietic cell transplantation (HCT). We report two cases of disseminated toxoplasmosis from two centers in critically ill adolescents after HCT: a 19-year-old who developed fever and altered mental status on day +19 after HCT and a 20-year-old who developed fever and diarrhea on day +52 after HCT. Both patients developed hyperferritinemia with multiple organ dysfunction syndrome and profound immune dysregulation, which progressed to death despite maximal medical therapies. Because disseminated toxoplasmosis is both treatable and challenging to diagnose, it is imperative that intensivists maintain a high index of suspicion for infection when managing immunocompromised children, particularly in those with known positive serologies.</p>

DOI

10.3389/fped.2021.719679

Alternate Title

Front Pediatr

PMID

34447731

Title

Fatal Neonatal Sepsis Associated with Human Adenovirus Type 56 Infection: Genomic Analysis of Three Recent Cases Detected in the United States.

Year of Publication

2021

Date Published

2021 Jun 09

ISSN Number

1999-4915

Abstract

<p><strong>BACKGROUND: </strong>Human adenovirus (HAdV)-D56 was first described in 2011 by genomics analysis of a strain isolated in France in 2008 from a fatal case of neonatal infection. Since then, it has been reported in cases of keratoconjunctivitis and male urethritis. Three epidemiologically unrelated fatal cases of neonatal sepsis associated with infection by HAdV-D strains with a similar genetic makeup were documented in the United States between 2014 and 2020.</p>

<p><strong>METHODS: </strong>Whole genome sequences were obtained for the isolated strains, and genomics analyses were conducted to compare them to phylogenetically related HAdV-D genomic sequences available in GenBank.</p>

<p><strong>RESULTS: </strong>The three new US strains were indistinguishable by in silico restriction enzyme analysis. Their genome sequences were 99.9% identical to one another and to the prototype strain isolated in 2008 from a similar context of disease. The phylogenetic reconstruction revealed a highly supported clustering of all HAdV-D56 strains isolated in various countries since 1982. Our comparison to serologically intermediate strains 15/H9 described in the literature indicated that HAdV-D56-like viruses have circulated worldwide since the late 1950s.</p>

<p><strong>CONCLUSION: </strong>As with other HAdV-D genotypes with the ability to infect ocular and genital mucosae, the risk of severe prenatal or perinatal HAdV-D56 infection must be considered.</p>

DOI

10.3390/v13061105

Alternate Title

Viruses

PMID

34207791

Title

Human Adenovirus 7-Associated Hemophagocytic Lymphohistiocytosis-Like Illness: Clinical and Virological Characteristics in a Cluster of Five Pediatric Cases.

Year of Publication

2020

Date Published

2020 Aug 31

ISSN Number

1537-6591

Abstract

<p><strong>BACKGROUND: </strong>Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking.</p>

<p><strong>METHODS: </strong>We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018-2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed.</p>

<p><strong>RESULTS: </strong>All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identified as genomic variant 7d. Adenovirus type 7 DNA was detected in the fifth case. Phylogenetic analysis of genome sequences identified two clusters - one related to strains implicated in 2016-2017 outbreaks in Pennsylvania and New Jersey, the other related to a 2009 Chinese strain.</p>

<p><strong>CONCLUSIONS: </strong>It can be challenging to determine whether HLH is the result of an infectious pathogen alone or genetic predisposition triggered by an infection. We describe 5 children from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infection. None of the patients were found to have a genetic predisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH.</p>

DOI

10.1093/cid/ciaa1277

Alternate Title

Clin. Infect. Dis.

PMID

32866230

Title

The Epidemiology of SARS-CoV-2 in a Pediatric Healthcare Network in the United States.

Year of Publication

2020

Date Published

2020 Jun 19

ISSN Number

2048-7207

Abstract

<p><strong>BACKGROUND: </strong>Understanding the prevalence and clinical presentation of COVID-19 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic.</p>

<p><strong>METHODS: </strong>Retrospective case series of patients tested for SARS-CoV-2 across a pediatric healthcare network, including the clinical features and outcomes of those with positive test results.</p>

<p><strong>RESULTS: </strong>Of 7,256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients 18-21 years of age had the highest test positive rate (11.2%) while those 1-5 years of age had the lowest (3.9%). By race, 10.6% (226/2132) of Black children tested positive vs. 3.3% (117/3592) of White children. Of those with an indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs. 3.8% (53/1410) of those undergoing pre-procedural or pre-admission testing. Of the 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbid medical conditions, 87 (20.5%) had asthma, 55 (13.0% had obesity, and 38 (9.0%) had mental health disorders. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2 positive patients were hospitalized, of which 24 (31.2%) required any respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2 positive patients developed critical illness requiring mechanical ventilation and 2 patients required extracorporeal membrane oxygenation. Two patients died.</p>

<p><strong>CONCLUSIONS: </strong>In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low, but varied by testing indication. The majority of cases were mild, few children had critical illness, and two patients died.</p>

DOI

10.1093/jpids/piaa074

Alternate Title

J Pediatric Infect Dis Soc

PMID

32559282

WATCH THIS PAGE

Subscription is not available for this page.