1. Susan N. Hocevar, MD Medical Officer Office of Blood, Organ, and Other Tissue Safety Division of Healthcare Quality and Promotion Investigation Framework for Transplant and Transfusion Related Disease Transmissions National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion

2. Background  28,662 organ transplants in 2010 1  Transmission reported in only 0.96% of deceased donor donations overall 2  Substantial morbidity and mortality  2,000,000 tissues distributed  Risk of transmission depends on tissue type and organism  Recent Investigations: HCV, Clostridium sordellii, WNV  30 million blood components transfused each year 3  Estimates of disease transmission vary based on component and disease  HIV and HCV about 1 in 1.5 million donations 4 1 OPTN / SRTR 2010 Annual Data Report. HHS/HRSA/HSB/DOT 2 Ison, M. G., et. al. (2009), Donor-Derived Disease Transmission Events in the United States 3 http://www.redcrossblood.org/learn-about-blood/blood-facts-and-statisticshttp://www.redcrossblood.org/learn-about-blood/blood-facts-and-statistics 4 Dodd, R. Y. (2004). "Current safety of the blood supply in the United States."

3. Background  Oversight / regulation of blood, organs, and tissues vary  Multiple agencies and organizations involved in each investigation  Organ  Health Resources and Services Administration (HRSA)  Blood  US Federal Drug Administration (US FDA)  Tissue  US FDA

4. Organ Oversight in the US: Who are the Players?  HRSA contracts with the United Network for Organ Sharing (UNOS) to administer the Organ Procurement and Transplantation Network (OPTN)  OPTN oversees organ transplant in the US  In order to do transplants or procure organs, must be a member of OPTN in good standing  Follow policies including reporting of potential donor derived diseases to UNOS patient safety

5. Organ Oversight in the US: Who are the Players?  Organ Procurement Organizations (OPO) evaluate and test potential organ donors  Transplant centers review donor testing and history prior to acceptance of organs via the OPO’s report  Both the OPO and the transplant center can report potential disease transmissions to UNOS patient safety http://optn.transplant.hrsa.gov/members/directory.asp

6. Investigation Overview  CDC is notified of potential transmissions in several ways  Notification directly from United Network for Organ Sharing via an agreement with HRSA (organ)  Health Department calls (blood, organ, tissue)  US FDA fatality reports (Blood)  Specimens sent to CDC for testing or consultation on treatment recognized as belonging to an organ recipient (blood, organ, tissue)

7. CDC and HRSA Agreement  Transplant centers and OPOs are required to report potential donor derived disease transmissions to UNOS patient safety  UNOS sends CDC these notifications and pertinent contact information for:  Nationally notifiable diseases  Disease reports involving >1 recipient (cluster)  Per the agreement, health departments should be notified as well

8. Example of Health Department Notifications  Report of Brucella in a Kidney recipient noted by state health department with notation that other recipients were ill….  Microspordia identified on kidney biopsy sent to CDC  3 recipients all with confirmed disease  One death with disseminated microsporidiosis  Two treated with improvement

9. Health Department High Index of Suspicion  Often such reports turn into clusters of donor-derived illness  Many recipients have been successfully provided care or prophylaxis through coordinated efforts of local and state health departments, CDC, OPOs, and transplant physicians  They may have never been recognized or reported if not for the health department  Consider the potential for donor derived disease in transplant recipients and transfusion recipients

10. Transplant Investigation Steps  Obtain UNOS Donor ID from transplant center / OPO  Recommend that the center / OPO report to UNOS Patient Safety  Contact the OPO to obtain:  Transplant center for all other organ recipients  Tissue / eye procurement status and tissue/ eye bank contact  Donor chart  Status of remaining donor specimens Serum (stored for 10 years) Cultures Tissue biopsy HLA typing tissue (lymph node, spleen) Autopsy specimens if applicable

11. Transplant Investigation Steps  Contact the transplant centers and other health departments  Ensure that the center is aware and has followed up with their recipients  Arrange specialized testing if needed  Provide consultation for treatment  Contact the tissue banks  Notify of potential disease  Request that the bank begin compiling a list of all tissues released with contact information for follow up  Begin contacting hospitals that received tissue

12. Transplant Investigation Steps  Donor investigation  Will depend on suspected disease  The OPO can coordinate contact with the donor’s surviving relatives  Risk factor evaluation in the donor (consider transfusion)  Disease activity in donor’s county of residency

13. Tissue and Blood Oversight in the US  US FDA regulates tissue:  Rules for testing  Tracking tissue to the ‘hospital door’  Mandatory reporting of adverse reactions involving communicable diseases  US FDA regulates blood:  Rules for testing  Tracking throughout healthcare system (donor to each recipient)  Only serious reactions or errors in manufacturing/handling require mandatory reporting (fatalities, biologic product deviations) Infection transmission not required to be reported

14. Issues with Tissues  Delays in notifications to the tissue bank and hospitals with stored tissue can lead to preventable transmissions  Hospital systems are variable for tracking to individual recipients  There have been incidences where a hospital can not determine where a particular tissue went (or delays of weeks in determining this)  Public health often calls each hospital and physician to locate tissues and recipients for follow up

15. Transfusion Confusion  Transfusion associated diseases can involve:  Blood product recipients alone  Organ donors  Organ recipients  During transplant investigations consider the possibility of transmission via transfusion  Time consuming process and can be incomplete

16. Transfusion Investigation Steps  Contact the hospital blood bank to notify of the need for a trace back investigation  The hospital blood bank will contact the blood collection agency (ex. Red Cross) and provide the blood product unit numbers for all products given  This number is unique and links the product to the donor  The blood collection agency will begin quarantine (of remaining products), trace back of donors, testing of retained segments  Your role may vary as the blood collection agency may handle the investigation completely

17. Conclusion  CDC can assist in any step in the Investigation process  These investigations can be complex and involve many partners  Health departments play an integral role in identifying potential transmission and leading or participating in investigations  Toolkits in development : general transfusion and general transplant

18. For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333 Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: cdcinfo@cdc.gov Web: www.cdc.gov 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. Thank You National Center for Emerging and Zoonotic Infectious Diseases Place Descriptor Here

20. There’s a Report involving a transplant case I’m Considering it…Now what?  Obtain the UNOS Donor ID from the transplant center or OPO reporting the case to public health  Recommend that the center / OPO report to UNOS patient safety  This will trigger notification of other transplant centers  UNOS will generate a report and upload donor information  Request information from the OPO on other recipient status and location  OPO can follow up on other recipients and report back  Inquire about tissue status and tissue bank notification  CDC can aid in these steps as one transplant may involve several states

21. Report Information  Organ Procurement Organization contact information  If applicable, reporting transplant center contact  Brief donor history and history of reported illness in the recipient or finding in the donor  Organs transplanted  Occasionally information on if tissues / eyes were procured

22. Organ,Tissue, and Blood Oversight and Testing OrgansTissuesBlood Regulation / Oversight Organ Procurement and Transplantation Network (OPTN) US Food and Drug Administration (US FDA) US Food and Drug Administration Screening Assessment Organ Procurement Organization Tissue BankBlood Bank TimeframeImmediate usageProlonged storage potential Link between Donor and recipient UNOS Donor identification number Tissue linked to facility only Barcode links product to donor and all recipients Testing RequiredAntibody Screening Nucleic Acid Testing