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  • 10% of transmissions resulted in Death; ~25% due to bacteria; Mortality rate with bacterial transmission ~20%


  • 1. Infectious Disease Screening of the Organ Donor: Balancing Risks of Transmission with Wait List Mortality
    Karen Doucette, MD, MSc, FRCPC
    Division of Infectious Diseases
    ATLS June 9, 2010
  • 2. Objectives
    To review the goals and current approach to pretransplant screening for infection in the potential organ donor
    To discuss some of the challenges and limitations of current screening methods
    To discuss approaches to safely optimize utilization of the “marginal” donor
  • 3. What are the Goals of Screening?
    To identify conditions which may disqualify the donor (e.g. HIV)
    To identify and initiate treatment for active infection prior to donation (e.g. bacteremia)
    To stratify the risk of infection and optimal prevention strategies (e.g. CMV)
  • 4. Defining what we want to prevent
    Epidemiology in donors
    What incidence would be needed to require testing?
    Is the prevalence sufficiently high for the PPV of test to be useful
    Is the infection transmissible by organ transplant?
    Organ specific risk?
    Does transmission result in significant morbidity/mortality?
    Available monitoring protocols?
    Is there a reliable and logistically applicable test available for screening?
    Serology vs. NAT
    Incidence of false positives vs. false negatives
    Prospective or Retrospective?
    What level of risk is “acceptable”?
  • 5. Unique Screening Issues in Deceased Donors
    Donor history
    Second hand story
    No standardization
    Incomplete Data Collection
    Restricted timeline
    Different Screening Paradigm – individual testing
    Serology-based Screening
    Challenges due to hemodilution
    Variable NAT capacity and practice
    No expectation for “Zero Risk”
    Risk-benefit ratio for organs differs from blood/tissues
  • 6. Serologic Screening: Limitations
    Can have false negative results
    Window Period
    Dilution of antibodies
    IV fluid
    Not all develop & maintain antibody response
    False positives
    Blood products
    Kids up to 18 months – maternal antibody
    Screening of a low risk population
  • 7. Pathogens Transmitted with Organ Transplant
    True incidence of DDDT unknown; estimated to be uncommon (~1%)
    Ison et al AJT 2007
    AST ID Guidelines. AJT. 2009
  • 8. DTAC: Summary of Reported Cases: 2005 - 2009
    Additionally, there were a large number of “expected” transmissions with CMV and toxoplasmosis reported to DTAC but not included in the above numbers.
  • 9. Significant Organ Shortage
    2009 DATA
    *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.
  • 10. Donor Risk Assessment
    Medical & Social History
    Review of charts
    Interview of next of kin
    Physical Examination
    Organ Procurement Coordinator (external)
    Surgeons (internal)
    Laboratory Screening
    Antigen detection
    Nucleic Acid Testing (NAT)
  • 11. Donor Assessment: History
  • 12. Suggested Data to Collect Regarding Eligibility of Organ Donors
    AST ID Guidelines. AJT. 2009
  • 13. Aspects of ID Screening that rely Heavily on History
    • Tuberculosis - No currently approved donor screening methods
    TST: Cannot be implemented with deceased donors
    Interferon-g Release Assays – no studies
    History and risk factor identification
    CXR, gross assessment of lungs +/- pathology
    Endemic fungal or parasite risk – serology/other case-by-case
    Place of birth, travel history
    Unusual neurologic presentations
    Increased Risk Donor
  • 14. Standard Screening Tests and Impact on Organ Utilization
  • 15. Standard Screening Tests
    HIV Antibody
    Hepatitis B – HBsAg, anti-HBc +/- anti-HBs
    Hepatitis C Antibody
    Human T-cell lymphotrophic virus (HTLV-1/2) Antibody
    Syphilis EIA
    Cytomegalovirus IgG
    Epstein Barr virus antibody (EBNA IgG)
    Toxoplasma IgG (hearts)
    Blood and urine cultures; respiratory cultures (lung)
    Depending on Risk
    West Nile virus NAT
  • 16. Case 1
    Donor MSSA bacteremia, septic pulmonary emboli, meningitis
    On antibiotics ~36 hrs prior to offer
    Repeat BC drawn – negative at offer
  • 17. The Bacteremic Donor or Donor with Meningitis
    Donor bacteremia, particularly with virulent organisms (e.g. S. aureus, Pseudomonas, Candida), may result in early posttransplant sepsis or mycotic aneurysm
    95 bacteremic donors
    No transmission with mean 3.8 days directed antimicrobial therapy posttransplant1
    Organs successfully transplanted from donors with meningitis with appropriate antimicrobial therapy2
    Donor infection should be controlled
    Directed posttransplant antibiotics to recipient(s); 2-4 weeks if virulent organism
    1Freeman et al. Transplantation. 1999
    2Lopez-Navidad et al. Tansplantation. 1997
    3AST ID Guidelines. AJT. 2009
  • 18. Case 1 continued
    60M, OLT Mar/10 for HCV/EtOH; status 3
    Donor MSSA bacteremia (Abx ~36 hrs)
    BC still 1/3 positive at procurement (retrospect)
    Received iv cloxacillin prophylaxis
    Transplant OR end of case 2100h
    Blood cultures 2130h – MSSA in 1/2 (confirmed donor-derived by PFGE)
    Clinically stable, cloxacillin continued 4 weeks, well
    2 renal recipients – post-op BC negative; 2 weeks iv cloxacillin
  • 19. Disease Transmission Associated DeathDTAC: 2005-2009 (33/338)
    Lung Cancer (2) • Lymphoma (2)
    Melanoma (1)
    Pseudomonas (3) • Acinetobacter (1)
    Serratia(1) • Bacteroides (2)
    LCMV (5) • HIV/HCV (2)
    HIV (1)
    Coccidiomycosis (3) • Aspergillus (2)
    Candida (2) • Mucor (1)
    Tuberculosis: 2
    Balmuthia (2) • Strongyloides (2)
    Chagas (2)
  • 20. Case 2
    28F, born in Romania
    MVC, closed head injury
    History unremarkable
    Living in Canada since age 9
    No high risk activity
  • 21. Generally do notTransplant HCV+ Organ into HCV- Recipient
    Essentially universal transmission from HCV-Ab+/RNA+ donors
    HCV RNA often not available prior to procurement
    Risk from HCV RNA negative donors not defined
    No prophylaxis; posttransplant treatment complex, low success rates, common A/Es
    Has been associated with fibrosingcholestatic hepatitis (FCH), rapidly progressive fibrosis, increased mortality
    May be considered in high status patients with informed consent
  • 22. Good outcomes with HCV+ Liver Allografts in HCV+ Recipients
    OPTN/SRTR database. 56 275 OLT Apr 94-Feb 08
    19 496 HCV+ recipients and 934 HCV+ donors
    • Highly selected donors
    • 23. Impact of genotype?
    Northup et al. Transpl Int. 2010
  • 24. Non-Hepatic Transplant of HCV+ Organ to HCV+ Recipient
    Heart Transplant
    Renal Transplant
    AHR 1.43 (1.02 to 2.02)
    Abbott, KC et al. J Am Soc Nephrol. 2003
    Gasink, LB. JAMA. 2006
  • 25. Transplant of Donor HCV+ Kidneys to HCV+ Recipients Improves Survival Compared to Waitlist
    Abbott, KC et al. AJT. 2004
  • 26. Underutilization of HCV+ Organs: UNOS 1995-2009
    • Of 6830 HCV+ candidates, 29% received HCV+ RTx
    • 27. HCV+ Kidneys 2.6 times discard rate
    • 28. HCV D+/R+ waited 395 d less
    Kucirka, LM. AJT. 2010
  • 29. Case 3
    45 y M, NDD donor after SAH
    History unremarkable
    Worked as lab technician
    Serology: Anti-HBc total POSITIVE
    Anti-HBcIgM, HBsAg, Anti-HBs negative
  • 30. You Suggest:
    Accept all organs
    Accept all organs except liver
    Decline all organs
    Additional testing is required
    Call Transplant ID
  • 31. The Anti-HBc Positive Donor
    Transmission 50-80% in HBV naïve in absence of prophylaxis 1,2,3
    Prophylaxis reduces transmission in both anti-HBc/anti-HBs+ (3%) and naïve (12%) 3
    Lamivudine more effective than HBIg (2.6% vs 19%) 3
    No benefit of combination (2.8%) 3
    Transmission 0-5.2% in HBV naïve in absence of prophylaxis 4,5
    Immune recipients (anti-HBs+) risk eliminated
    HBV DNA in donor serum may be used to stratify risk 6
    Non-immune recipients of anti-HBc/HBV DNA+ organ managed with Lamivudine X 12 mo or HBIg X 3-6 mo 6
    1Wachs, ME et al. Transplantation. 1995; 2Dickson, RC et al. Gastroenterology. 1997; 3Cholongitas, E et al. J Hepatol. 2010; 4Madayag, RM et al. Transplantation. 1997; 5Fabrizio, F et al. J Nephrol. 2002; 6Chung RT et al. AJT. 2001
  • 32. Variable Utilization and Prevention Strategies in OLT Recipients of Anti-HBc+ Donor
    Variation in strategies for prevention persist2
    In a survey of US transplant centers in 2001, 57% indicated they would utilize these organs in HBV naïve recipients1
    1Burton, JR et al. Liver Transpl. 2003
    2Perrillo, R. Liver Transpl. 2009
  • 33. Case 4
    62 yo farmer from rural Saskatchewan
    Previously healthy
    No travel or other risk history
    No prior transfusions
    Massive intracerebral hemorrhage
  • 34. HTLV in Organ Transplantation
    Human T-cell lymphotrophic virus 1 (HTLV-1)
    Endemic in Caribbean, parts of SA, W Africa, Asia and Oceana
    Transmission: breast feeding, sexual, IDU, blood (up to 0.05% US blood donors HTLV 1/2+)
    Acute T-cell leukemia/lymphoma (2-5%); HTLV-associated myelopathy (<1%); no effective therapy
    HTLV-2: no clear disease association
    Organ Transplant and HTLV-1
    Several case reports DDDT (ATL/HAM)
    Several small series of HTLV D+/R- with no transmission; absolute risk uncertain
  • 35. High Rate of False Positive HTLV Serology in US Organ Donors
  • 36. OPTN policy requiring HTLV screening for potential organ donors eliminated in Nov, 2009
    100 potential donors may be ruled out, of whom only 1-10 likely actually have HTLV-1. 90-99 of the donors ruled out would carry no risk of HTLV-1 transmission.
  • 37. Potential Downside to Donor Screening: WNV
    WNV has been transmitted by organ transplant rarely but high rate of morbidity/mortality
    1 donor transmission was blood WNV NAT negative, but tissues in recipients positive
    Rate of WNV infection has dropped in NA
    Is WNV testing of organ donors worth performing?
    Shift testing paradigm based on epidemiology?
    Kiberd BA, Forward K. Am J Transplant. 2004.
  • 38. Case 5
    38 M NDD donor
    Known history of IDU
    Found down in public washroom with a syringe still in arm
    HIV, HCV and HBV serology all negative
  • 39. The “Increased Risk Donor” (IRD): Exclusionary Criteria for Donation of Cells, Tissues, or Organs
    men who have had sex with another man in the preceding five years;
    persons who report nonmedical intravenous, intramuscular, or subcutaneous injection of drugs in the preceding five years;
    persons with hemophilia or related clotting disorders who have received human-derived clotting factor concentrates;
    persons who have engaged in sex in exchange for money or drugs in the preceding five years;
    persons who have had sex in the preceding 12 months with any persons described in Items a) to d) or with a person known or suspected to have HIV, clinically active HBV, or HCV;
    persons who have been exposed in the preceding 12 months to known or suspected HIV-, HBV-,and/or HCV-infected blood through percutaneous inoculation or through contact with an open wound, nonintact skin, or mucous membrane;
    current inmates of correctional systems (including jails and prisons) and individuals who have been incarcerated for more than 72 consecutive hours during the previous 12 months;
    persons who within 12 months of donation have undergone tattooing, ear piercing, or body piercing in which shared instruments were used; and
    persons who have had close contact within 12 months preceding donation with another person having clinically active viral hepatitis (e.g., living in the same household, where sharing of kitchen and bathroom facilities occurs regularly).
    Canadian Standards Guidelines
  • 40. Risk Stratification of Donors
    Simplistic US (and Canadian) System
    Based on 1994 exclusionary criteria for HIV*
    Adult Behavioral Factors
    Pediatric Risk Factors
    Laboratory Risk Factors
    OPTN-defined high risk vs. standard risk
    Based on HIV risk but applied to HIV, HBV, & HCV
    Linked with consent requirement
    But without guidelines about what information to provide
    Multiple transmissions (including HCV) from standard risk donors
    *MMWR. 1994; 43 (RR-8); 1-17.
  • 41. Screening for Infectious Diseases
    Serologic conversion
    Serologic testing
    Nucleic acid testing
  • 42. Nucleic Acid Testing
    Directly detects the pathogen
    Can reduce the “window” period
    VERY sensitive
    Contamination is a potential problem
    Highly technical
    Proficiency is linked with volume
    May be associated with false positive testing
    With resultant loss of donors
  • 43. Residual Risk of BBP After Serology:Average Risk Donor
    1Zou NEJM 2004; 2Zahariadis et al. AJT. 2007
  • 44. Estimated Risk of HIV/HCV After Serology in IRDs
    IDU – HIV
    0.48-2.11 per 1000
    IDU - HCV
    14-65.2 per 1000
    Humar et al. AJT. 2010
  • 45. Residual Risk:Are All “High Risk Donors” the Same?
    Schweitzer et al. Am J Transplant. 2007;7:1515-1525.
  • 46. “Transplant” vs. “Discard” Policy Results in Improved Outcomes
    More kidney transplants (990 vs. 740)
    Greater number of QALYs (5.6 vs. 5.1)
    Lower cost of care
    Schweitzer et al. Am J Transplant. 2007;7:1515-1525.
  • 47. HIV/HCV NAT Consensus Recommendations
    Deceased Donors
    Follow up of Recipients
    Insufficient evidence to recommend routine NAT for all donors (III)
    NAT testing of average-risk donors not likely to identify true-positives frequently enough to offset false-positives; benefits may not outweigh potential disadvantages (II-2)
    For IRDs NAT should be considered to reduce risk of transmission and potentially increase organ utilization (II-2)
    For IRDs, the highest yield of NAT is for HCV due to substantial reduction in window (II-1) and significant differences in HCV prevalence (II-2)
    All recipients receiving organs from IRDs should have periodic testing for HIV, HCV, HBV post-Tx (III), regardless of whether prospective NAT done. Testing for HIV/HCV should include NAT as seroconversion may be delayed or absent
    For average risk donor recipients, further study needed to determine if additional post-Tx testing warranted
    Humar et al. AJT. 2010
  • 48. Variation in Utilization and Practices With Organs from High Risk Donors
    Verbal 33%
    Verbal and written 52%
    14% no special consent
    Post-Tx F/U in recipients
    Serology 60% of centers
    NAT 50%
    Ison, MG et al. Clin Transplant. 2009
  • 49. Use of IRD Donors at U of A 2008-May 2010
    19 Increased Risk Donors Utilized
    12 local, 7 distant
    14 drug use indication
    All HIV/HCV NAT negative
    Recipients (48):
    14 kidney 3 kidney-pancreas
    11 lung 1 small bowel
    11 liver 1 islet
    7 heart
    Follow-up HIV/HCV antibody and NAT, HBsAg, anti-HBs, anti-HBc @ 3, 6 months
    No transmissions
  • 50. Conclusions
    Donor transmission of disease uncommon, but potentially devastating consequences
    Marginal Donor Utilization Optimized:
    Thorough understanding of risks and risk stratification
    Use of NAT
    Appropriate prophylaxis and follow up of recipient
    Need rapid assays of high sensitivity for organs (NO TEST WILL PREVENT ALL TRANSMISSION)
    Cost-effectiveness analysis and formal technology assessment needed to inform evidence based recommendations regarding implementation of new screening tests
  • 52. Cases Reported to the OPTN
  • 53. Potential Disease Transmission Reports for Deceased Donors 3/2006-12/2009 by DSA
    2 DSAs with ZERO reports
    NOTE: Includes reported potential disease transmission cases March, 2006 through April 23, 2010, on deceased donors recovered March, 2006 through December, 2009.