1. An Update on Donor-Derived
Disease Transmission Through
Organ Transplantation in the USA
Michael G. Ison, MD MS
Associate Professor
Divisions of Infectious Diseases & Organ Transplantation
2011 Organ Donation Congress – Buenos Aires, Argentina

2. Disclosures
• Research Support°
ADMA, Adamas, BioCryst, Chimerix, GlaxoSmithKline, Roche,
ViraCor*
• Paid Consultation
Abbott, Abbott Molecular*, Astellas*, Biogen Idec, Crucell, ViraCor*
• Unpaid Consultation
BioCryst, Biota, Cellex, Clarassance, GlaxoSmithKline, MP
Bioscience*, NexBio, Roche, Toyama, T2 Diagnostics*
• Data & Safety Monitoring Board Participation
Chimerix, NexBio
As of 11/22/11; °Paid to Northwestern University; *Related to topic.

3. Acknowledgments
DTAC data was supported wholly or in part
by Health Resources and Services
Administration contract 234-2005- 370011C.
The content is the responsibility of the
authors alone and does not necessarily
reflect the views or policies of the
Department of Health and Human Services,
nor does mention of trade names,
commercial products, or organizations imply
endorsement by the U.S. Government.

4. Case 1: Something Rare?
• 54 yo WM with HBV/HCV/HCC
• Day 5: Fever to 102.4, mild frontal HA since Tx
• IS: ATG, Tacrolimus, Azathioprine
• Abx: Pip-Tazo, HBIg, 3TC, Famciclovir, TMP-SMX
• SH: Suburbs, Iron worker
• PE: Non-focal except for a tender RUE
peripheral IV catheter

5. Case 1: Something Rare?
• Continued with fever, LFTs increased
• Seizure (? Hypoxemic)
• Progressive “sepsis” with elevated
LFTs and renal dysfunction
• Call from another Transplant ID
doctor: “how is your recipient doing?”

6. The Culprit
Fischer et al. N Eng J Med. 2006;354:2235-2249.

7. Case 2: Something Common?
• Patient is a 56 yo WM
• Underwent OHT November 2005
 Toxo D+/R–, CMV D+/R–
 Pyramethamine-Sulfadiazine
 Valganciclovir
• 9 Days Post-Transplant
 Donor has + blood cultures drawn the day prior to donation
 Positive for Pseudomonas aeruginosa
• What Went Right? What Went Wrong?
 Took several days to convey results to recipient centers
 Patient was receiving ciprofloxacin for a probable UTI, which
covered the bacteria with no serious sequellae

8. Case 3: Refocusing on Risk
• One recipient was identified with post-transplant
HCV & HIV infection with no obvious risk factors
and negative pre-transplant testing
• Reported to OPO, UNOS, and CDC
• Donor – Lookback Assessment
 Negative serology for HIV & HCV
 Appropriately labeled as “high risk” by PHS
Guidelines
 Subsequent testing of post-transfusion serum was +
for HIV and HCV by PCR
• All other recipients tested + for HIV & HCV
Ison et al. Am J Transplant. 2011; 11: 1218–1225

9. Case 4: Living Donors Are Not Immune
MMWR. 2011; 60: 297-301.

10. Unique Features of Organ Procurement
• Restricted timeline (typically 24 hours)
• Different Screening Paradigm - Not “Zero Risk”
• Donor History
 Second Hand Story
 Lack of Standardization
 Incomplete Data Collection
• Serology-based Screening
• Variable NAT capacity and practice
Ison et al. Am J Transplant. 2009; 9: 1929-1935. Ison & Nalesnik. Am J Transplant. 2011; 11: 1123–1130.

11. A Significant Organ Shortage Exists
2009 DATA
Organ Transplants 28,465
Waitlist Candidates 105,567
Deaths on Waitlist 9,848
*Waiting list deaths includes removals for death, too sick to transplant, and those non-transplanted removals identified to have died within
seven days of removal from linkage to SSDMF data. Based on OPTN data as of April 16, 2010.

12. A Delicate Balance
Organ Availability Patient Safety

13. Current US Donor-Derived Disease Policy
• Policy 2: Focused on Donor Screening
 Review of donor medical/social history
 Defines donors at increased risk of transmitting infections
 Defines required donor screening (serologic)
• Policy 4: Focused on recognizing and reporting
disease transmission
 Requirement to inform recipients of new data relative to risk
 „When a transplant program is informed that an organ recipient at that
program is confirmed positive for or has died from a transmissible
disease or medical condition for which there is substantial concern that
it could be from donor origin, the transplant program must notify by
phone and provide available documentation, as soon as possible and
not to exceed one complete working day, to the procuring OPO‟
 Patient Safety Contact (required for each OPO and TC)
http://optn.transplant.hrsa.gov/policiesAndBylaws/policies.asp

14. Disease Transmission Advisory Committee
• Workflow
 Report made to Patient Safety Staff
o Prepare summary of event
o Redact identifiers
o Upload key materials to SharePoint Server
 E-mail based discussion
o Initial e-mail sent to all members
o Ongoing electronic discussion
 Day 45 Follow-up Reports submitted
 Special Cases
o Reportable Diseases: Inform CDC
o Event-Specific Conference Calls
 Monthly Conference Calls & Bi-Annual Meetings
Ison et al. Am J Transplant. 2009; 9: 1929-1935.

15. DTAC Members as of July 2011
Dr. Emily Blumberg, Chair (TID) Dr. Michael Green, Vice Chair (Peds TID)
Ms. Carrie Comellas (TX Coordinator) Dr. Edward Dominguez (TID)
Dr. Afshin Ehsan (Thoracic TX Surgeon) Mr. Barry Friedman (TX Administrator)
Dr. Thomas Gross (Oncology) Dr. Daniel Kaul (TID)
Dr. Simone Kushne (TID) Dr. G. Marshall Lyon (TID)
Dr. Rachel Miller (TID) Ms. Samantha Mitchell (OPO)
Dr. Michael Nalesnik (Pathology) Dr. Volker Nickeleit (Pathology)
Dr. Timothy Pruett (Abd TX Surgeon) Dr. Phillip Ruiz (Pathology)
Dr. Michael Souter (Tx Anesthesiology) Ms. Linda Weiss (Dir of OPO Lab Services)
Dr. Betsy Tuttle Newhall (Abd TX Surgeon) Dr. Russell Wiesner (Hepatology)
Dr. Jim Bowman (Ex Officio, HRSA) Dr. Bernard Kozlovsky (Ex Officio, HRSA)
Ms Raelene Skerda (Ex Officio, HRSA)
OPTN Staff: Shandie Covington, Robert Metzger, MD, Kimberly Parker,
Sarah Taranto, Kimberly Taylor, RN
OPTN

16. Potential Disease Transmission Cases
Reported to DTAC
200
176*
180
152 152
160
140
102
120
97
100
80
60
60
40
7
20
0
2005 2006 2007 2008 2009 2010 2011
OPTN *Estimated based on 161 reports through November 21, 2011.

17. Potential Disease Transmission Reports for
Deceased Donors 3/2006-12/2010 by
Donor Service Area (DSA)
Number of Donor Reports
1 DSA with
ZERO
reports
Individual DSAs
OPTN

18. Percent of Deceased Donors Recovered
2008-2009 Reported to DTAC by Region
OPTN

19. Potential Disease Transmission Reports for
Deceased Donors During 2010 by DSA
Number of Donor Reports
12 DSAs
with ZERO
reports
Individual DSAs
OPTN

20. Malignancy Reports: 2005-2010
Malignancy # of Donor Reports # of Recipients with # of DDD-Attributable
Confirmed Transmission Recipient Deaths
Renal Cell Carcinoma 78 9 1
Lung Cancer 15 10 7
Lymphoma 11 6 2
Thyroid Carcinoma 11 0 0
Melanoma 7 4 3
Glioblastoma multiforme 7 1 1
Liver Cancer 6 3 2
Prostate 6 1 0
Neuroendocrine 5 2 2
Pancreas 2 3 0
Ovarian Carcinoma 2 2 0
Other ** 35 0 0
Total 185 34 17
Malignancies
**Other reported malignancies without confirmed transmission: angiomyolipoma, astrocytoma,
breast, colon carcinoma, dermatofibrosarcoma protuberans, Kaposi‟s sarcoma, leukemia,
medulloblastoma, mesothelioma, myeloid sarcoma, pinealoblastoma,, liposarcoma,
gastrointestinal stromal tumor (GIST) spindle cell CNS carcinoma, carcinoma not otherwise
specified (4), urothelial carcinoma.
OPTN

21. Infection Reports: 2005-2010
Disease # of Donor # of Recipients with # of DDD-Attributable
Reports Confirmed Transmission Recipient Deaths
Virus∞ 122 34 9
Bacteria* 75 31 9
Fungus° 56 37 10
Mycobacteria§ 37 11 2
Parasitic† 30 18 6
Total Infections 320 131 36
∞Viruses: Adenovirus, HBV, HCV, HEV, HIV, HTLV, herpes simplex, influenza, LCMV,
Parainfluenza (PIV)-3, Parvovirus B19, rabies, West Nile Virus
°Bacteria: Acinetobacter, Brucella Enterococcus (including VRE), Ehrlichia spp, E. coli, Gram
Positive Bacteria, Klebsiella, Legionella, Listeria, Lyme Disease, Nocardia, Pseudomonas, Rocky
Mountain Spotted Fever, Serratia , S. aureus (MRSA), Streptococcus spp, Syphilis, Veillonella;
bacterial meningitis & bacterial emboli
° Fungi: Aspergillus spp, Candida spp, Coccidioides imitis, Cryptococcus neoformans,
Histoplasma capsulatum, zygomyces
§ Mycobacteria: Tuberculosis, Non-TB Mycobacteria
†Parasites:Babesia , Balmuthia mandrillaris, Chagas (Trypanosoma cruzi), Naegleria fowleri,
schistosomiasis, strongyloides
OPTN

22. Lessons Learned: DTAC Data
• Bacterial Transmissions
 Likely under-recognized & under-reported
 Often involves resistant bacteria
 Follow-up of outstanding culture data
• Fungi
 Endemic mycoses & Cryptococcus increasing
 High morbidity and mortality
• Mycobacteria
• Parasites
 Increase in Strongyloides, Chagas, & Amoeba
• Viral Transmissions
 Increased recognition of PB19, LCMV
 Need to use NAT to diagnose transmission, esp for HCV
Ison et al. Am J Transplant. 2009; 9: 1929-1935. Ison & Nalesnik. Am J Transplant. 2011; 11: 1123–1130.

23. Lessons Learned: DTAC Data
• Communications
 Inefficient systems in place
 Delays are common
• Poor systems for recognizing DDD
 No cluster analysis
 Severe outcomes not recognized by all recipient teams
 Variable recognition and report
 Management of positive cultures/result information locally
• Increased risk donors
 Variable definitions used
 Variable understanding of risk
 Variable follow-up of recipients
• Living donors
Ison et al. Am J Transplant. 2009; 9: 1929-1935. Ison & Nalesnik. Am J Transplant. 2011; 11: 1123–1130.

24. Michael G. Ison, MD MS
Questions? 312-695-4186
mgison@northwestern.edu
I am a registered organ donor!
Are you?