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Table 1.  

Pathogen All recipients Right kidney recipient Left kidney/heart recipient Liver recipient
Bacterial Bacterial culture (blood, urine) Mycoplasma Borrelia burgdorferi Treponema pallidum
Mycobacterium tuberculosis Anaplasma/Ehrlichia
Borrelia burgdorferi Treponema pallidum
Brucella spp. Tropheryma whipplei
Rickettsia spp.  
Pneumocystis jiroveci
Legionella spp.
Viral Cytomegalovirus Enterovirus Enterovirus None
Herpes simplex virus Lymphocytic choriomeningitis Adenovirus
Epstein-Barr virus Measles virus Lymphocytic choriomeningitis
Parvovirus JC virus Measles virus
HIV Human herpesvirus-6 JC virus
  Viral fecal cultures Human herpesvirus-6
BK virus  
Human T-cell lymphotropic virus
Meningoencephalitis panel*
Fungal/parasitic/other Cryptococcus spp. Coccidioides spp. (1→3)β-D-glucan Toxoplasma gondii
Aspergillus spp. Galactomannan
Strongyloides spp. Coccidioides spp.
  Cryptococcus spp.
Schistosoma spp. Toxoplasma gondii
Babesia spp. Babesia spp.
  14–3-3 testing for prion disease (cerebrospinal fluid)

Table 1. Infectious disease testing performed for 3 transplant recipients with donor-derived microsporidiosis

*Panel contains the following viruses: West Nile, Lacrosse, Eastern equine encephalitis, St. Louis encephalitis, Western equine encephalitis, lymphocytic choriomeningitis, herpex simplex 1 and 2, adenovirus, influenza A and B, measles, mumps, varicella, coxsackie A and B, echovirus, cytomegalovirus.

Table 2.  

Patient Specimen IHC TEM PCR† Culture
Right kidney recipient Renal allograft + + + Not performed
CNS tissue‡ + + Not performed Not performed
Left kidney/heart recipient Renal allograft Not performed + Not performed
Cardiac allograft Indeterminate - Not performed
Bone marrow Not performed Not performed
Urine Not performed Not performed + Not performed
Liver recipient Urine + + + +

Table 2. Transplant recipient testing for microsporidiosis, by specimen and test type*

*CNS, central nervous system; IHC, immunohistochemistry; TEM, transmission electron microscopy; +, positive; –, negative.
†All PCR positive tests confirmed Encephalitozoon cuniculi
‡CNS tissue included cortex and brainstem.

CME

Three Cases of Neurologic Syndrome Caused by Donor-Derived Microsporidiosis

  • Authors: Rachel M. Smith, MD, MPH; Atis Muehlenbachs, MD, PhD; Joanna Schaenman, MD, PhD; Sanjiv M. Baxi, MD, PhD; Sophia Koo, MD; Dianna M. Blau, DVM, PhD; Peter Chin-Hong, MD; Anna R. Thorner, MD; Matthew J. Kuehnert, MD; Kristina Wheeler, RN, BSN, CPTC; Alexis D. Liakos, PA-C; Jonathan W. Jackson, BS; Theresa K. Benedict, BSc; Alexandre J. da Silva, PhD; Jana M. Ritter, DVM; Dominique C. Rollin, MD; Maureen G. Metcalfe, MS Biology; Cynthia S. Goldsmith, MGS; Govinda S. Visvesvara, PhD; Sridhar V. Basavaraju, MD; Sherif Zaki, MD, PhD
  • CME Released: 2/16/2017
  • THIS ACTIVITY HAS EXPIRED FOR CREDIT
  • Valid for credit through: 2/16/2018, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for infectious disease specialists, transplant physicians, hematologists, immunologists, and other clinicians caring for patients undergoing organ transplantation.

The goal of this activity is to describe findings from and implications of a US Centers for Disease Control and Prevention (CDC) investigation of 3 solid-organ transplant recipients infected with Encephalitozoon cuniculi from a single infected donor.

Upon completion of this activity, participants will be able to:

  1. Distinguish the clinical presentation and course of 3 solid-organ transplant recipients infected with Encephalitozoon cuniculi from a single infected donor, based on an investigation from the US Centers for Disease Control and Prevention
  2. Evaluate diagnostic testing and confirmation of E cuniculi infection in 3 solid-organ transplant recipients
  3. Determine management and clinical implications of E cuniculi infection in 3 solid-organ transplant recipients


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Authors

  • Rachel M. Smith, MD, MPH

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Rachel M. Smith, MD, MPH, has disclosed no relevant financial relationships.

  • Atis Muehlenbachs, MD, PhD

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Atis Muehlenbachs, MD, PhD, has disclosed no relevant financial relationships.

  • Joanna Schaenman, MD, PhD

    University of California, Los Angeles, California, USA

    Disclosures

    Disclosure: Joanna Schaenman, MD, PhD, has disclosed no relevant financial relationships.

  • Sanjiv M. Baxi, MD, PhD

    University of California, San Francisco, California, USA

    Disclosures

    Disclosure: Sanjiv M. Baxi, MD, PhD, has disclosed no relevant financial relationships.

  • Sophia Koo, MD

    Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA

    Disclosures

    Disclosure: Sophia Koo, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: GI Windows, Infinity Pharmaceuticals, Pfizer China
    Received grants for clinical research from: Wako Diagnostics

  • Dianna M. Blau, DVM, PhD

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Dianna M. Blau, DVM, PhD, has disclosed no relevant financial relationships.

  • Peter Chin-Hong, MD

    University of California, San Francisco, California, USA

    Disclosures

    Disclosure: Peter Chin-Hong, MD, has disclosed no relevant financial relationships.

  • Anna R. Thorner, MD

    Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA

    Disclosures

    Disclosure: Anna R. Thorner, MD, has disclosed the following relevant financial relationships:
    Employed by a commercial interest: UpToDate, Inc./Wolters Kluwer Health

  • Matthew J. Kuehnert, MD

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Matthew J. Kuehnert, MD, has disclosed no relevant financial relationships.

  • Kristina Wheeler, RN, BSN, CPTC

    OneLegacy, Los Angeles, California, USA

    Disclosures

    Disclosure: Kristina Wheeler, RN, BSN, CPTC, has disclosed no relevant financial relationships.

  • Alexis D. Liakos, PA-C

    Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA

    Disclosures

    Disclosure: Alexis D. Liakos, PA-C, has disclosed no relevant financial relationships.

  • Jonathan W. Jackson, BS

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Jonathan W. Jackson, BS, has disclosed no relevant financial relationships.

  • Theresa K. Benedict, BSc

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Theresa K. Benedict, BSc, has disclosed no relevant financial relationships.

  • Alexandre J. da Silva, PhD

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Alexandre J. da Silva, PhD, has disclosed no relevant financial relationships.

  • Jana M. Ritter, DVM

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Jana M. Ritter, DVM, has disclosed no relevant financial relationships.

  • Dominique C. Rollin, MD

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Dominique C. Rollin, MD, has disclosed no relevant financial relationships.

  • Maureen G. Metcalfe, MS Biology

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Maureen G. Metcalfe, MS Biology, has disclosed no relevant financial relationships.

  • Cynthia S. Goldsmith, MGS

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Cynthia S. Goldsmith, MGS, has disclosed no relevant financial relationships.

  • Govinda S. Visvesvara, PhD

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Govinda S. Visvesvara, PhD, has disclosed no relevant financial relationships.

  • Sridhar V. Basavaraju, MD

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Sridhar V. Basavaraju, MD, has disclosed no relevant financial relationships.

  • Sherif Zaki, MD, PhD

    Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Disclosures

    Disclosure: Sherif Zaki, MD, PhD, has disclosed no relevant financial relationships.

Editor

  • P. Lynne Stockton Taylor, VMD, MS, ELS(D)

    Technical Writer-Editor, Emerging Infectious Diseases

    Disclosures

    Disclosure: P. Lynne Stockton Taylor, VMD, MS, ELS(D), has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed the following relevant financial relationships:
    Owns stock, stock options, or bonds from: Pfizer

CME Reviewer

  • Robert Morris, PharmD

    Associate CME Clinical Director, Medscape, LLC

    Disclosures

    Disclosure: Robert Morris, PharmD, has disclosed no relevant financial relationships.


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  • Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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CME

Three Cases of Neurologic Syndrome Caused by Donor-Derived Microsporidiosis

Authors: Rachel M. Smith, MD, MPH; Atis Muehlenbachs, MD, PhD; Joanna Schaenman, MD, PhD; Sanjiv M. Baxi, MD, PhD; Sophia Koo, MD; Dianna M. Blau, DVM, PhD; Peter Chin-Hong, MD; Anna R. Thorner, MD; Matthew J. Kuehnert, MD; Kristina Wheeler, RN, BSN, CPTC; Alexis D. Liakos, PA-C; Jonathan W. Jackson, BS; Theresa K. Benedict, BSc; Alexandre J. da Silva, PhD; Jana M. Ritter, DVM; Dominique C. Rollin, MD; Maureen G. Metcalfe, MS Biology; Cynthia S. Goldsmith, MGS; Govinda S. Visvesvara, PhD; Sridhar V. Basavaraju, MD; Sherif Zaki, MD, PhDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED FOR CREDIT

CME Released: 2/16/2017

Valid for credit through: 2/16/2018, 11:59 PM EST

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Abstract and Introduction

Abstract

In April 2014, a kidney transplant recipient in the United States experienced headache, diplopia, and confusion, followed by neurologic decline and death. An investigation to evaluate the possibility of donor-derived infection determined that 3 patients had received 4 organs (kidney, liver, heart/kidney) from the same donor. The liver recipient experienced tremor and gait instability; the heart/kidney and contralateral kidney recipients were hospitalized with encephalitis. None experienced gastrointestinal symptoms. Encephalitozoon cuniculi was detected by tissue PCR in the central nervous system of the deceased kidney recipient and in renal allograft tissue from both kidney recipients. Urine PCR was positive for E. cuniculi in the 2 surviving recipients. Donor serum was positive for E. cuniculi antibodies. E. cuniculi was transmitted to 3 recipients from 1 donor. This rare presentation of disseminated disease resulted in diagnostic delays. Clinicians should consider donor-derived microsporidial infection in organ recipients with unexplained encephalitis, even when gastrointestinal manifestations are absent.

Introduction

Each year in the United States, ≈30,000 solid organ transplants are performed.[1] It is estimated that 0.3%–2.0% of transplants may be complicated by donor-derived infection, most commonly of bacterial or viral origin.[2–4] Parasitic and fungal infections, including microsporidiosis, make up a minority of donor-derived infections.[2–4] Maintaining a high index of suspicion for donor-derived infection in solid organ transplant recipients and prompt investigation of illness suspected to be donor derived are critical because multiple recipients often receive solid organs from a common donor. Thus, identification of donor-derived infection in 1 recipient has consequences for the clinical care of the other recipients.

Enlarge

Figure 1. Timeline of events for transplant donor and 3 solid organ recipients with microsporidiosis (Encephalitozoon cuniculi). AVM, arteriovenous malformation; CDC, Centers for Disease Control and Prevention; CNS, central nervous system; CSF, cerebrospinal fluid; DVT, deep vein thrombosis.

Potential donor-derived disease transmission events are reported to the Organ Procurement and Transplantation Network (https://optn.transplant.hrsa.gov/) per policy and reviewed by the Network’s ad hoc Disease Transmission Advisory Committee, which categorizes each by the likelihood of disease transmission. Through representation on this advisory committee, the Centers for Disease Control and Prevention (CDC), with support from state and local health departments, leads investigations of select cases of public health importance. In April 2014, CDC was notified of a renal transplant recipient hospitalized with signs and symptoms of encephalitis (Figure 1). Postmortem testing revealed infection with microsporidia, and concern was raised for donor-derived central nervous system (CNS) infection. We conducted an investigation to 1) identify other ill recipients from the common donor, 2) determine whether the illness was donor derived, and 3) make treatment recommendations for the surviving recipients.

Table of Contents

  1. Abstract and Introduction
  2. Methods
  3. Results
  4. Discussion