First name
Richard
Middle name
L
Last name
Hodinka

Title

Outcomes of human adenovirus infection and disease in a retrospective cohort of pediatric solid organ transplant recipients.

Year of Publication

2019

Number of Pages

e13510

Date Published

2019 Jun 18

ISSN Number

1399-3046

Abstract

<p>Information about HAdV infection in SOT recipients is limited. We aimed to describe HAdV infection epidemiology and outcomes in a single-center retrospective cohort during the era of PCR availability. SOT recipients transplanted at the CHOP 2004-2013 were followed up for 180&nbsp;days post-transplant. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. HAdV disease was defined by organ-specific radiologic and/or laboratory abnormalities. No HAdV surveillance protocols were employed during the study period; testing was solely per clinician discretion. Progression of HAdV infection was defined as HAdV disease or ≥1-log viral load increase since a corresponding site's first positive specimen. Of the assembled 425 SOT recipients, 227 (52.6%) had ≥1 HAdV PCR. Twenty-four (10.6%) had ≥1 HAdV-positive PCR. HAdV-positive subjects were younger than uninfected subjects (2.0&nbsp;years vs 6.5, P&nbsp;=&nbsp;0.001). Infection incidence rates were highest in liver recipients (15.3%), followed by heart (8.6%), kidney (8.3%), and lung (4.2%). Four subjects (16.7%) met HAdV disease criteria at virus detection. Five subjects (20.8%) had progression of HAdV infection. All-cause mortality rates in positive and negative subjects were 0% and 3.9%, respectively. HAdV infection was infrequently detected in SOT recipients. Over one-third of HAdV-positive patients met disease criteria at detection or had infection progression, but none died. This low all-cause mortality raises questions about benefits of HAdV surveillance. Larger multicenter studies are needed to assess incidence variance by center and comparative effectiveness of therapeutic interventions.</p>

DOI

10.1111/petr.13510

Alternate Title

Pediatr Transplant

PMID

31210395

Title

Outcomes of Human Adenovirus Infection and Disease in a Retrospective Cohort of Pediatric Hematopoietic Cell Transplant Recipients.

Year of Publication

2018

Date Published

2018 Jun 08

ISSN Number

2048-7207

Abstract

<p><strong>Background: </strong>Human adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir.</p>

<p><strong>Methods: </strong>A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for infection.</p>

<p><strong>Results: </strong>Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV infection versus those without infection (25.9% vs 11.3%; P = .01). Factors associated with infection included an age of 6 to 12 years, an absolute lymphocyte count of &lt;200 cells/μL, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of infection progression (odds ratio, 0.96 [95% confidence interval, 0.30-3.05]).</p>

<p><strong>Conclusions: </strong>HAdV infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies.</p>

DOI

10.1093/jpids/piy049

Alternate Title

J Pediatric Infect Dis Soc

PMID

29893957

Title

A Case of Adenovirus Viremia in a Pediatric Liver Transplant Recipient With Neutropenia and Lymphopenia: Who and When Should We Treat?

Year of Publication

2015

Number of Pages

e1-5

Date Published

2015 Mar

ISSN Number

2048-7207

Abstract

<p>Human adenovirus (HAdV) is one of the most feared infections among immunocompromised patients. In particular, in liver transplant patients, HAdV has been implicated in acute liver failure with resultant mortality. The development of current molecular techniques and surveillance testing protocols have provided tools for early detection of HAdV infection, prior to or at the early onset of HAdV disease. Although reduction in immune suppression is the mainstay of therapy, many researchers have also advocated for early administration of antiviral therapy. In multiple reports, cidofovir treatment has been associated with declines in HAdV viral loads or clinical improvement in solid organ and bone marrow transplant recipients. However, there have also been case reports that raise questions about the effectiveness of antiviral therapy in controlling systemic HAdV disease. We report a case of a 26-month-old male recipient of a liver transplantation for hepatoblastoma who developed adenoviremia with an associated hepatitis and gastroenteritis. He recovered with reduced immune suppression but without antiviral therapy, thus avoiding potential toxicities associated with cidofovir therapy. This case a contrast to previous reports, and it highlights the ambiguity regarding which patients should receive HAdV-specific antiviral therapy. Additional knowledge regarding specific pediatric host factors and HAdV factors that predict poor outcomes are needed. Such information would allow clinicians to better stratify patients by risk at the time of adenoviremia detection so that low-risk patients are not unnecessarily exposed to medications with potential toxicities.</p>

DOI

10.1093/jpids/pit081

Alternate Title

J Pediatric Infect Dis Soc

PMID

26407369

Title

Identification of a novel intertypic recombinant species D human adenovirus in a pediatric stem cell transplant recipient.

Year of Publication

2014

Number of Pages

496-502

Date Published

2014 Dec

ISSN Number

1873-5967

Abstract

<p><strong>BACKGROUND: </strong>Human adenoviruses (HAdV) are known opportunistic pathogens in hematopoietic stem cell transplant (SCT) recipients. The detection of HAdV infection in children after SCT has been implicated as a determinant of poor outcome but specific associations between HAdV species or individual HAdV types and disease are poorly understood.</p>

<p><strong>OBJECTIVES: </strong>Characterization of a HAdV-D strain isolated from multiple clinical specimens of an 11-year-old female recipient of a matched unrelated donor peripheral SCT for T-cell lymphoma and case report.</p>

<p><strong>STUDY DESIGN: </strong>Archived HAdV PCR-positive plasma, urine, and stool specimens were processed for virus isolation and detailed molecular typing. Complete genomic sequencing was carried out on 2 isolates.</p>

<p><strong>RESULTS: </strong>The patient tested positive for HAdV DNA by real-time PCR of a stool specimen at 44 days after initiation of a SCT conditioning regimen. In the subsequent 3 months, HAdV was detected in plasma, urine and stool specimens in association with symptoms of gastroenteritis and hemorrhagic cystitis. A novel HAdV-D with a HAdV20-like hexon gene was isolated from both urine and stool specimens. All isolates yielded identical restriction profiles with endonucleases BamHI, BglII, BstEII, HindIII, PstI and SmaI. Analysis of 2 complete genomic sequences further identified the virus as a novel intertypic recombinant HAdV-D (P20/H20/F42) closely related to HAdV42.</p>

<p><strong>CONCLUSIONS: </strong>This case highlights the identification of a previously unknown HAdV-D from an immunocompromised host. In this patient, the course of adenovirus infection is compatible with reactivation of a latent virus or a primary opportunistic infection. Adenoviremia in this patient resolved without definitive adenovirus-directed antiviral therapy.</p>

DOI

10.1016/j.jcv.2014.09.009

Alternate Title

J. Clin. Virol.

PMID

25449172

Title

Use of antibiotics in children hospitalized with community-acquired, laboratory-confirmed influenza.

Year of Publication

2009

Number of Pages

447-9

Date Published

2009 Mar

ISSN Number

1097-6833

Abstract

<p>Many children with influenza are treated with antibiotics. In this report, we describe the rate and indications for antibacterial use in children hospitalized with influenza. A total of 333 of 729 (46%) patients received &gt;2 days of treatment with antibacterial medications, of whom 36% did not have an apparent indication for therapy.</p>

DOI

10.1016/j.jpeds.2008.09.026

Alternate Title

J. Pediatr.

PMID

19874761

Title

Treatment with oseltamivir in children hospitalized with community-acquired, laboratory-confirmed influenza: review of five seasons and evaluation of an electronic reminder.

Year of Publication

2009

Number of Pages

171-8

Date Published

2009 Mar

ISSN Number

1553-5606

Abstract

<p><strong>BACKGROUND: </strong>When initiated within 48 hours of the onset of symptoms, oseltamivir has been shown to reduce severity and length of influenza illness. Few studies have evaluated the use of oseltamivir in patients hospitalized with influenza.</p>

<p><strong>OBJECTIVE: </strong>To describe the prescribing practices for oseltamivir in children hospitalized with influenza and to evaluate a mechanism to improve the rate of appropriate prescription.</p>

<p><strong>DESIGN, SETTING, PATIENTS: </strong>Retrospective cohort study of 929 patients aged 21 years or younger hospitalized with community-acquired laboratory-confirmed influenza (CA-LCI) during 5 consecutive seasons (2000-2005). We examined oseltamivir eligibility, which included patients 1 year of age or older with an influenza test result available within 48 hours of symptom onset. During the 2005-2006 season, an observational trial of an electronic reminder was conducted to improve the frequency of oseltamivir prescription.</p>

<p><strong>MEASUREMENTS: </strong>Oseltamivir prescription.</p>

<p><strong>RESULTS: </strong>Of 305 patients (32.8%) eligible for treatment with oseltamivir, 49 (16.1% of those eligible) were prescribed oseltamivir during hospitalization. Prescription rates for indications consistent with the US Food and Drug Administration (FDA) approval ("on label") increased from 0% to 37.2% over 5 seasons (P &lt; 0.0001). Prescriptions outside this recommendation ("off label") also increased over 5 seasons (P &lt; 0.0001). Twenty-nine (5%) of 624 patients were treated with oseltamivir off label; 11 were less than 1 year of age. Initiation of a reminder had no impact on prescription (P &gt; 0.05).</p>

<p><strong>CONCLUSIONS: </strong>Oseltamivir was used infrequently for children hospitalized with influenza. In addition, use inconsistent with the FDA label of oseltamivir occurs. Mechanisms are needed to improve appropriate prescription of oseltamivir.</p>

DOI

10.1002/jhm.431

Alternate Title

J Hosp Med

PMID

19301375

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