Risky Business Preventing Disease Transmission From Donor Organs. Peter Chin-Hong, MD UCSF September 2012

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1 Risky Business Preventing Disease Transmission From Donor Organs Peter Chin-Hong, MD UCSF September 2012

2 Case 1: Something rare? 54 yo WM with HBV/HCV/HCC Day 5: Fever to 102.4, mild frontal HA since time of transplant 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

3 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?

4 Case 1: Something Rare? Donor Previously healthy woman who was brain dead secondary to a hemorrhagic stroke Donated liver, lungs, kidneys, corneas, skin Purchased a hamster for her son a few weeks prior to death

5 The Culprit Fischer et al. N Eng J Med. 2006;354:

6 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

7 Case 2: Something Common? Positive result on cultures Day of transplant Took several days to convey results to recipient centers Patient was receiving ciprofloxacin for a probable UTI, which covered the bacteria with no serious sequelae

8 Case 3: The Chicago transmission event One recipient was identified with post-transplant HCV & HIV infection with no obvious risk factors and negative pretransplant 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:

9 Case 4: The Live Donor Transmission Event MMWR. 2011; 60:

10 Limitations of Organ Donor Screening Restricted timeline Different screening paradigms Donor history Incomplete data collection Serology-based screening Variable NAT capacity and practice No expectation for Zero Risk Ison et al. Am J Transplant. 2009; 9: Ison & Nalesnik. Am J Transplant. 2011; 11:

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 Exists Organ Availability Patient Safety

13 Background: Donor Screening Policy OPTN Policy 2.2: Donor Evaluation o Requires OPO to: Obtain a medical & social history of the donor Review the donor s chart Perform a physical examination of the donor Perform FDA licensed, approved, or cleared screening tests Serology for: HIV, HCV, HBsAg, HBcAb, CMV, EBV, and syphilis Additional testing may be done at the discretion of the OPO or accepting transplant center OPTN Policy 4.1: Screening Donors for HIV o Prohibits the use of donors with + HIV test result o Defines a donor at increased risk of HIV, HBV or HCV transmission OPO must inform transplant center if the donor is increased risk Transplant Center must obtain special consent from the recipient to use organs from an increased risk donor Rogers et al. MMWR. 1994; 43(RR-8):1-17.

14 Potential Donor Derived Transmission Events Reviewed by DTAC, Through

15 Summary of Reported Cases: Disease Types # of Donor Reports # of Recipients w/ Confirmed Tx # of DDD-Attributable Recipients Deaths Malignancies Viruses Bacteria Fungi Mycobacteria Parasites Other Diseases Total Data includes cases classified as possible, probable or proven from as published in AJT, and all reviewed cases from

16 Malignancy Reports: Malignancy # of Donor Reports # of Recipients with Confirmed Transmission # of DDD-Attributable Recipient Deaths Renal Cell Carcinoma Lung Cancer Thyroid Carcinoma Liver Cancer Hematologic Malignancy Brain Cancer Melanoma Lymphoma Prostate Cancer Pancreas Cancer Neuroendocrine Ovarian Carcinoma Breast Cancer Colon Kaposi s Sarcoma Other ** Malignancy Total Data includes cases classified as possible, probable or proven from as published in AJT, and all reviewed cases from

17 Infection Reports: Disease # of Donor Reports # of Recipients with Confirmed Transmission # of DDD-Attributable Recipient Deaths Virus Bacteria* Fungus Mycobacteria Parasitic Total Infections 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, miasis, strongyloides Data includes cases classified as possible, probable or proven from as published in AJT, and all reviewed cases from

18 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

19 Lessons learned: DTAC data Communications Inefficient system currently in place in the US Poor systems for recognizing DDD transmissions 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 across US Variable understanding of risk by clinicians and patients Variable follow-up of recipients Human Errors Live Donors are not immune

20 Mitigating against the risk Donor Screening Medical & Social History Physical Examination Screening of Blood Samples Serology Nucleic Acid Testing (NAT) Defining the Increased Risk Donor OPTN-Defined Increased Risk Donor Proposed New Definitions Screening of Recipients

21 Nucleic Acid Testing (NAT) Availability NAT increasingly used for donor screening 1,2 Year HIV NAT HBV NAT HCV NAT % of OPOs 34% of OPOs 78% of OPOs % of OPOs 75% of OPOs 96% of OPOs 1 Orlowski et al. Am J Transplant. 2009; 9: Thedoropoulos N et al. Abstract LB17. ATC 2012.

22 Survey of OPO Screening Practices: HIV, HBV, HCV Results For what indications do you perform NAT? Never Other Transplant Center request OPO-defined IR donors HCV HBV HIV OPTN IR donors All donors Thedoropoulos et al. ATC 2012

23 Survey of OPO Screening Practices: HIV, HBV, HCV Results How often are NAT results available before transplant decision is made? <10% of the time 50-75% of the time 75-99% of the time HCV HBV HIV Always Thedoropoulos et al. ATC 2012.

24 Survey of OPO Screening Practices: HIV, HBV, HCV Results Do you confirm positive NAT results? Always Some of the time HCV HBV HIV No Thedoropoulos et al. ATC 2012.

25 Survey of OPO Screening Practices: HIV, HBV, HCV Conclusions More OPOs are using NAT to screen potential deceased organ donors (PDODs) for HIV, HBV and HCV in 2010 More OPOs are using NAT for ALL PDODs NAT results are usually available before the transplant decision is made Only a minority of NAT results are confirmed As a result, rates of false positive NAT results will be difficult to assess with existing data There remains significant variability in turn-around-time for NAT results and cost associated with transportation and assay among OPOs Thedoropoulos et al. ATC 2012

26 1994 CDC Exclusionary Criteria Behavior/History Exclusionary Criteria 1. Men who have had sex with another man in the preceding 5 years. 2. Persons who report nonmedical intravenous, intramuscular, or subcutaneous injection of drugs in the preceding 5 years. 3. Persons with hemophilia or related clotting disorders who have received human-derived clotting factor concentrates. 4. Men and women who have engaged in sex in exchange for money or drugs in the preceding 5 years. 5. Persons who have had sex in the preceding 12 months with any person described above or with suspected HIV. 6. Persons who have been exposed in the preceding 12 months to known or suspected HIV-infected blood. 7. Inmates of correctional systems. MMWR. 1994; 44 (RR-8): 1-17.

27 1994 CDC Exclusionary Criteria Laboratory and Other Medical Exclusionary Criteria 1. Persons who cannot be tested for HIV infection because of refusal, inadequate blood samples (e.g., hemodilution that could result in false-negative tests), or any other reasons. 2. Persons with a repeatedly reactive screening assay for HIV-1 or HIV-2 antibody regardless of the results of supplemental assays. 3. Persons whose history, physical examination, medical records, or autopsy reports reveal other evidence of HIV infection or high-risk behavior, such as a diagnosis of AIDS, unexplained weight loss, night sweats, blue or purple spots on the skin or mucous membranes typical of Kaposi s sarcoma, unexplained lymphadenopathy lasting >1 month, unexplained temperature >100.5 F (38.6 C) for >10 days, unexplained persistent cough and shortness of breath, opportunistic infections,unexplained persistent diarrhea, male-to-male sexual contact, sexually transmitted diseases, or needle tracks or other signs of parenteral drug abuse. MMWR. 1994; 44 (RR-8): 1-17.

28 OPTN-Defined High Risk Donor Risk per 10,000 donors HIV ELISA HIV NAT HCV ELISA HCV NAT Window Period 22 days 9 days 66 days 7 days Men who have sex with men IV Drug Users Hemophiliacs Prostitutes Partner with the above Blood product exposure Incarceration Kucirka et al. Am J Transplant. 2011: 11; Kucirka et al. Am J Transplant. 2011: 11;

29 Revised CDC Guidelines

30 Revised CDC Guidelines High Risk Sexual Contacts: Persons who have had sex with a person known or suspected to have HIV, HBV or HCV infection in the preceeding 12 months Men who have had sex with another man (MSM) in the preceeding 12 months Women who have had sex with a man with a history of MSM behavior in the preceeding 12 months Persons who have had sex in exchange for money or drugs in the preceeding 12 months Persons who have had sex with a person who injected drugs by intravenous, intramuscular or subcutaneous route for non-medical reasons in the preceeding 12 months. Birth to a mother infected with HIV, HBV or HCV (for infant donors 2 years of age) Persons who have injected drugs by intravenous, intramuscular, or subcutaneous routes for non-medical reasons in the preceeding 12 months Inmates of a correctional facility (e.g. jail, prison, or juvenile detention) for > 3 days in the preceeding 12 months Persons who have or have been treated for syphilis, gonorrhea, chlamydia, or genital ulcers in the preceeding 12 months Persons who have been on hemodialyalsis in the preceeding 12 months

31 Thank you