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Original Research |

Microsporidiosis Acquired Through Solid Organ Transplantation: A Public Health Investigation

Susan N. Hocevar, MD; Christopher D. Paddock, MD; Cedric W. Spak, MD; Randall Rosenblatt, MD; Hector Diaz-Luna, MD; Isabel Castillo, RN, BSN; Sergio Luna, RN; Glen C. Friedman, MD; Suresh Antony, MD; Robyn A. Stoddard, DVM, PhD; Rebekah V. Tiller, MPH; Tammie Peterson, RN, MSN/MPH, CPTC; Dianna M. Blau, DVM, PhD; Rama R. Sriram, BS; Alexandre da Silva, PhD; Marcos de Almeida, PhD; Theresa Benedict, BS; Cynthia S. Goldsmith, MGS; Sherif R. Zaki, MD, PhD; Govinda S. Visvesvara, PhD; Matthew J. Kuehnert, MD, for the Microsporidia Transplant Transmission Investigation Team*
[+] Article and Author Information

* For a list of the members of the Microsporidia Transplant Transmission Investigation Team, see the Appendix.


From the Centers for Disease Control and Prevention, Atlanta, Georgia; Baylor University Medical Center and Southwest Transplant Alliance, Dallas, Texas; and Las Palmas Medical Center, El Paso, Texas.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Acknowledgment: The authors thank all members of the clinical care teams involved in treatment of the patients, the organ procurement organization staff, and the organ donor's family.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2226.

Reproducible Research Statement: Study protocol, statistical code, and data set: Not available.

Requests for Single Reprints: Susan N. Hocevar, MD, Centers for Disease Control and Prevention, 1600 Clifton Road, MS A35, Atlanta, GA 30333; e-mail, Igc7@cdc.gov.

Current Author Addresses: Dr. Hocevar: Centers for Disease Control and Prevention, 1600 Clifton Road, MS A35, Atlanta, GA 30333.

Drs. Paddock, Blau, and Zaki and Ms. Goldsmith: Centers for Disease Control and Prevention, 1600 Clifton Road, MS G32, Atlanta, GA 30333.

Drs. Spak and Rosenblatt and Ms. Peterson: Baylor University Medical Center, 621 North Hall Street, Dallas, TX 75226.

Drs. Diaz-Luna, Friedman, and Antony; Ms. Castillo; and Mr. Luna: Las Palmas Medical Center, 1700 North Oregon Street, Suite 680, El Paso, TX 79902.

Dr. Stoddard and Ms. Tiller: Centers for Disease Control and Prevention, 1600 Clifton Road, MS G34, Atlanta, GA 30333.

Ms. Sriram and Dr. Visvesvara: Centers for Disease Control and Prevention, 1600 Clifton Road, MS D66, Atlanta, GA 30333.

Drs. da Silva and de Almeida and Ms. Benedict: Centers for Disease Control and Prevention, 1600 Clifton Road, MS D64, Atlanta, GA 30333.

Dr. Kuehnert: Centers for Disease Control and Prevention, 1600 Clifton Road, MS A07, Atlanta, GA 30333.

Author Contributions: Conception and design: S.N. Hocevar, C.D. Paddock, A. da Silva, S.R. Zaki, M.J. Kuehnert.

Analysis and interpretation of the data: S.N. Hocevar, C.D. Paddock, R. Rosenblatt, S. Antony, R.A. Stoddard, R.V. Tiller, D.M. Blau, A. da Silva, M. de Almeida, S.R. Zaki, G.S. Visvesvara, M.J. Kuehnert.

Drafting of the article: S.N. Hocevar, C.D. Paddock, R. Rosenblatt, S. Antony, R.V. Tiller, A. da Silva, S.R. Zaki, G.S. Visvesvara, M.J. Kuehnert.

Critical revision of the article for important intellectual content: S.N. Hocevar, C.D. Paddock, C.W. Spak, H. Diaz-Luna, S. Antony, R.A. Stoddard, D.M. Blau, A. da Silva, M. de Almeida, S.R. Zaki, G.S. Visvesvara, M.J. Kuehnert.

Final approval of the article: S.N. Hocevar, C.D. Paddock, C.W. Spak, R. Rosenblatt, H. Diaz-Luna, G.C. Friedman, S. Antony, R.A. Stoddard, A. da Silva, S.R. Zaki, G.S. Visvesvara, M.J. Kuehnert.

Provision of study materials or patients: C.W. Spak, R. Rosenblatt, H. Diaz-Luna, G.C. Friedman, T. Peterson, S.R. Zaki, G.S. Visvesvara.

Administrative, technical, or logistic support: S.N. Hocevar, C.D. Paddock, R.R. Sriram, A. da Silva, T. Benedict, S.R. Zaki, G.S. Visvesvara.

Collection and assembly of data: S.N. Hocevar, C.D. Paddock, C.W. Spak, R. Rosenblatt, H. Diaz-Luna, I. Castillo, S. Luna, G.C. Friedman, R.A. Stoddard, R.V. Tiller, T. Peterson, D.M. Blau, A. da Silva, M. de Almeida, C.S. Goldsmith, S.R. Zaki, M.J. Kuehnert.


Ann Intern Med. 2014;160(4):213-220. doi:10.7326/M13-2226
Text Size: A A A

Background: Encephalitozoon cuniculi, a microsporidial species most commonly recognized as a cause of renal, respiratory, and central nervous system infections in immunosuppressed patients, was identified as the cause of a temporally associated cluster of febrile illness among 3 solid organ transplant recipients from a common donor.

Objective: To confirm the source of the illness, assess donor and recipient risk factors, and provide therapy recommendations for ill recipients.

Design: Public health investigation.

Setting: Two transplant hospitals and community interview with the deceased donor's family.

Patients: Three transplant recipients and the organ donor.

Measurements: Specimens were tested for microsporidia by using culture, immunofluorescent antibody, polymerase chain reaction, immunohistochemistry, and electron microscopy. Donor medical records were reviewed and a questionnaire was developed to assess for microsporidial infection.

Results: Kidneys and lungs were procured from the deceased donor and transplanted to 3 recipients who became ill with fever 7 to 10 weeks after the transplant. Results of urine culture, serologic, and polymerase chain reaction testing were positive for E. cuniculi of genotype III in each recipient; the organism was also identified in biopsy or autopsy specimens in all recipients. The donor had positive serologic test results for E. cuniculi. Surviving recipients received albendazole. Donor assessment did not identify factors for suspected E. cuniculi infection.

Limitation: Inability to detect organism by culture or polymerase chain reaction in donor due to lack of autopsy specimens.

Conclusion: Microsporidiosis is now recognized as an emerging transplant-associated disease and should be considered in febrile transplant recipients when tests for routinely encountered agents are unrevealing. Donor-derived disease is critical to assess when multiple recipients from a common donor are ill.

Primary Funding Source: None.

Figures

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Figure 1.

Timeline of events for recipients.

Initial posttransplant recovery was unremarkable for all recipients until fever onset 7 to 10 weeks after transplant. BK = BK polyomavirus viremia; BSI = bloodstream infection; CMV = cytomegalovirus infection; UTI = urinary tract infection.

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Figure 2.

Gross and microscopic pathology of tissues from the left kidney recipient.

A. Explanted kidney showing multiple microabscesses and hemorrhages of the renal capsule. B. Intracellular masses of Encephalitozoon cuniculi within renal tubular epithelium in the explanted kidney (original magnification × 100). C. Immunohistochemical staining of Encephalitozoon cuniculi (red) in the explanted kidney (original magnification × 25). D. Electron micrograph of a spore of Encephalitozoon cuniculi, surrounded by a dense exospore and electron-lucent endospore and containing 5 cross-sections through the coils of the polar filament, as is typical for this microsporidian (bar, 100 nm). E and F. Evidence of disseminated microsporidiosis involving thyroid gland (E) and liver (F) (original magnification × 100). Encephalitozoon cuniculi organisms were detected in several other tissues, including the central nervous system, heart, trachea, lung, pancreas, adrenal gland, gallbladder, prostate gland, stomach, colon, and vascular smooth muscle.

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Figure 3.

Encephalitozoon cuniculi immunofluorescent antibody in kidney section.

The spores were birefringent and variably Gram-positive. Stained smears of all initial urine specimens from all recipients revealed oval spores characteristic of microsporidia. The spores fluoresced brightly when reacted with a 1:400 dilution of the rabbit antiserum made against Encephalitozoon cuniculi.

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