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Optimal Donor & Recipient Screening
Michael G. Ison, MD MS
Divisions of Infectious Diseases & Organ TransplantationTransplant Infectious Diseases Service
Northwestern UniversityFeinberg School of Medicine
Prince of Wales Hospital, Sydney – March 8, 2010
Transplantation Workshop
Disclosures
• Research Support°– Roche (oseltamivir)* – ViraCor*– Biocryst (peramivir)* – Cellex*– ADMAS (TCAD)* – Chimerix– ADMA (RSV Ig)
• Consultation– Abbott Molecular* – ViraCor*– NexBio (Fludase)* – Cellex*– Biota
• DSMB– Chimerix
As of 2/10/10; °Paid to Northwestern University; *Related to topic.
Acknowledgment
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.
Optimal Donor & Recipient Screening
• Goals of Screening– What are we trying to prevent?– How do we assess for risk?– How will the results be used?
• Methods of Screen– Unique features of donor screening– Testing logistics & methods– Potential gaps
• Optimal Screening Advice– Living Donors – Deceased Donors– Recipients
Current DDD Transmission Data
152 cases reported in 2009
Ison et al. Am J Transplant. 2009; 9: 1929-1935.
Reports to DTAC: 2006-2009*
*Other (Each are single cases with no transmission): Basaloid, Brain – Spindle Cell, Cholangiocarcinoma, Dermatofibrosarcoma Protuberans, GIST, Kaposi’s Scarcoma, Lung –
Bronchoalverolar, Lung – Small Cell, Lymphoma, Myeloid Sarcoma, Urothelial Cell
*1/1/06 – 10/31/09
Reports to DTAC: 2006-2009*
∞ All but 3 cases non-reproducible NAT results: •Donor not high risk, Sero -/NAT+ with 3 transmissions•Donor high risk, Sero -/NAT + with 4 transmissions (HIV/HCV) and 1 death•Donor HCV + vessel with 1 transmission
†All but 2 cases non-reproducible NAT results: •1 Case with 4 transmissions of HCV/HIV and 1 death•1 patient with HIV infection post-transplantation
*1/1/06 – 10/31/09
Reports to DTAC: 2006-2009
*1/1/06 – 10/31/09
Reports to DTAC: 2006-2009
§Expected Transmissions: 10 Toxoplasmosis, 7, EBV, 4 CMV. Data 1/1/06 – 10/31/09.
What are the Goals of Screening?
• Defining what we want to prevent– Epidemiology in Donors
• What incidence would be needed to require testing?• Must be data in ORGAN donors
– Is the Infection Transmissible?• Organ specific risk?
– Treatable/untreatable?– Available monitoring protocols?– Available testing platforms?
• Serology vs. NAT• Incidence of false positives vs. false negatives• Prospective or Retrospective?
• What level of risk is “acceptable?”
How will screening results be used?
• Two Types of Screening Assays– Rule in/out donors (HIV)
• False Positive = lose a donor
– Risk stratify donor (CMV, EBV, HBV, HCV)– Transplant community needs to be
educated on how to use these results• Examples:
– HBV utilization is highly variable even for HBV seroprotected donors
– If Chagas serology used to r/o instead of risk stratify, graft loss in too high to use currently
– HTLV utilization in the US
Kaul et al. Am J Transplant. 2010. 10: 207-213.
Unique Donor Issues in Organs
• Restricted timeline• Different Screening Paradigm• Donor history
– Second hand story– No standardization
• Serology-based Screening• Variable NAT capacity and practice• No standard policy with regard to
hemodilution• Incomplete Data Collection• No expectation for “Zero Risk”
Significant Organ Shortage
*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 July 31, 2009.
Organ Transplants 27,963
Waitlist Candidates 100,775
Deaths on Waitlist 9,474
2008 DATA
Screening Methods
• Medical & Social History– Manual review of patient’s chart– Interview of next of kin
• Physical Examination– Surface examination– Internal surgical examination
• Laboratory testing– Serology– Nucleic acid testing
ELISA: Indirect & Sandwich
http://newenglandbiolabs.de/en/images/stories/cst_elisa_gross.jpghttp://microvet.arizona.edu/Courses/MIC419/ToolBox/elisa3.jpg
Serology: Limitations
• Can have false negative results– Window Period
– Dilution of antibodies• Blood products
• IV fluid
• Not everyone develops and maintains antibody response of same magnitude
Screening for Infectious Diseases
• Screening limitations
Exposure
Viremia Serologic conversion
WINDOW
Serologic testingNucleic acid testing
Virus Sero Window NAT WindowHBV 60 days 20 daysHCV 70 days 7 daysHIV 23 days 7 days
AST IDCOP Guidelines. Am J Transplant. 2004; Suppl 4: 10-20.
Nucleic Acid Testing
• Directly detects the pathogen• VERY sensitive
– Contamination is an major problem– Highly technical– Proficiency is linked with volume
• Can reduce the “window” period• May be associated with false
positive testing– With resultant loss of donors
Risk Stratification of Donors
• Simplistic US System– Based on 1994 exclusionary criteria for HIV– OPTN-defined high risk vs. standard risk– Multiple transmissions (including HCV) from
standard risk donors
• Comprehensive European System– Based on the Italian Classification Scheme
• Unacceptable Risk (Absolute Contraindications)• Increased but Acceptable Risk• Calculated Risk (i.e. HCV+, meningitis)• Not Assessable Risk• Standard Risk
– Risk system for malignancy available
Guide to Safety and Quality Assurance for the Transplantation of Organs, Tissues, and Cells 3rd Ed. Council of Europe Publishing, Strasbourg, France. 2009.
Potential Gaps in Screening
• Medical & Social History– Must be standardized with internal validators– Assurance of access to all medical records
• Established standard for hemodilution• Funding for donor screening
– Support development of new assays and platforms
– Assessment of new agents and their associated assays in the donor pool
– Mechanism to disseminate data
• Effective biovigilence for organ recipients
Optimal Screening: Living Donor
• Essential Minimum– HIV serology and NAT– HBV sAg, sAb, cAb (?NAT)– HCV serology and NAT– TB (only for lungs?)
• Informs recipient management– CMV serology – RPR– EBV serology
• Depending on history & endemicity– Strongyloides, endemic mycoses, pathogens
present in surrounding areas
Fischer SA & Avery RK. Am J Transplant. 2009; 9 (s4); S7-18.
Optimal Screening: Deceased Donor
• Essential Minimum– HIV serology (NAT – all vs. high risk)– HBV sAg, sAb, cAb– HCV serology and NAT (for all)
• Informs recipient management– CMV serology – RPR– EBV serology– Toxoplasmosis for all heart and muscle
transplants
• Depending on history & endemicity– Strongyloides, Chagas, endemic mycoses,
pathogens present in surrounding areas
Fischer SA & Avery RK. Am J Transplant. 2009; 9 (s4); S7-18.
Optimal Screening: Recipient
• Essential Minimum– HIV serology– HBV sAg, sAb, cAb– HCV serology and NAT– TB screening
• Informs recipient management– CMV serology – VZV & HSV serology – EBV serology – RPR– Toxoplasmosis for all heart and muscle transplants
• Depending on history & endemicity– Strongyloides, Chagas, endemic mycoses, pathogens
present in surrounding areas
Fischer SA & Avery RK. Am J Transplant. 2009; 9 (s4); S7-18.
Screening of Recipients Post-Tx
• Assessment of donor risk requires careful post-transplant follow-up– Biovigilence system to detect transmissions– Reporting systems to accept and investigate
potential transmission reports• Coordinate information sharing• Share findings to inform best practices and policy• Similar to OPTN Policy 4.6 and OPTN PSS/DTAC
– Diligent clinicians to suspect and report cases– Routine assessment of key donors
• HIV, HBV, and HCV (potentially others)• All vs. “at risk”• Requires robust pre-transplant data
Post-Transplant Testing: US Experience
°6/30/04 – 8/31/06 or 2/28/06
Organ High Risk°
Pre-Tx HIV
Pre-Tx HCV
Post-Tx HIV
Post-Tx HCV
H-L 5 (7.9%) 4 (80%) 4 (80%) 0 (0%) 1 (20%)
Heart 333 (9.6%) 232 (69.7%) 278 (83.5%) 26 (8.7%) 26 (8.8%)
Intestine 9 (2.4%) 5 (55.6%) 5 (55.5%) 0 (0%) 0 (0%)
Kidney 1,865 (8.5%) 1,107 (59.4%) 1,523 (81.7%) 40 (2.2%) 44 (2.7%)
K-P 203 (10.3%) 109 (53.7%) 5 (2.5%) 7 (3.6%) 9 (4.7%)
Liver 1,210 (9%) 762 (63%) 501 (41.4%) 50 (4.5%) 77 (11.8%)
Lung 214 (9.7%) 175 (81.8%) 2 (0.9%) 9 (5.1%) 15 (8.5%)
Pancreas 82 (7%) 48 (58.5%) 1 (1.2%) 2 (2.5%) 3 (3.8%)
Total 3,921 (8.8%) 2,422 (62.3%) 3,191 (81.4%) 134 (3.7%) 178 (5.9%)
What is Australia’s Plan?
• How are donor derived infections recognized?• How are DDI’s reported?
– Is this data collected?– How are the reports investigated?– How are findings handled?
• How is pertinent data shared?– When a new issue arises during implantation?– Post-transplant cultures or testing?
• Are donors recognized as donors?– Pertinent to how “late” results (TB, fungal) are
reported to TC/OPO
What is Australia’s Plan?
• How do you manage a potential transmission?– Who will be the key contact
• For the hospital/transplant center?• For the OPO as information is shared?• For the media when questions arise?
– How do you manage the media• As a unified group of all affected centers and
OPOs?
• Do you have a patient safety communication policy?
