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
Right kidney recipient	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.

Organ Procurement and Transportation Network. Transplants by donor type. 2014 [cited 2015 Dec 21]. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#
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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, PhD
CME Released: 2/16/2017
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 2/16/2018, 11:59 PM EST

Start Activity

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:

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
Evaluate diagnostic testing and confirmation of E cuniculi infection in 3 solid-organ transplant recipients
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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From Emerging Infectious Diseases

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

processing....

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.

Page 1 of 4

Methods

CME Information

Abstract and Introduction
Methods
Results
Discussion

References

References

Disclaimer

The educational activity presented above may involve simulated case-based scenarios. The patients depicted in these scenarios are fictitious and no association with any actual patient is intended or should be inferred.

The material presented here does not necessarily reflect the views of Medscape, LLC, or companies that support educational programming on medscape.org. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.

Table 1.

Table 2.

References

Faculty and Disclosures

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

Editor

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

CME Author

Laurie Barclay, MD

CME Reviewer

Robert Morris, PharmD

CME

Three Cases of Neurologic Syndrome Caused by Donor-Derived Microsporidiosis

Target Audience and Goal Statement

Disclosures

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

Editor

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

CME Author

Laurie Barclay, MD

CME Reviewer

Robert Morris, PharmD

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Three Cases of Neurologic Syndrome Caused by Donor-Derived Microsporidiosis

Abstract and Introduction

Abstract

Introduction

Table of Contents