11 Donor Derived Infections- Prevention, Recognition & Treatment Daniel Kaul MD Division of Infectious Disease University of Michigan

22 Topics  Universal Screening  Directed Screening  Clinical Donor Evaluation  Communication  Time Course  Epidemiology

3 Required Screening for Deceased Donors  Hepatitis B core antibody  Hepatitis C serology, including  Hepatitis C nucleic acid amplification testing (NAT) (all donors)  HIV antibody  HIV NAT or 4th generation EIA (PHS increased risk)  Syphilis  Cytomegalovirus serology (CMV)  Epstein-Barr virus serology (EBV)  Blood culture  Urine culture

44 NAT testing shortens the window period

55 Risk of HIV, hep C window period infection by risk factor

66 Living Donors: Protocol for assessing TB and other endemic diseases required

77  Site specific protocols are used  West Nile virus nucleic acid amplification testing  During periods of increased mosquito activity or known outbreaks  Trypansoma cruzi (serology)  At-risk donors  Coccidiomycosis (serology)  Southwestern states  Strongyloides (serology)  Human T-cell lymphotropic virus (HTLV-1) (serology)  At-risk donors Donor Screening Tests for Selected Situations

8 Considerations when Evaluating Organs from Donors with Possible Infection  Has the infection been identified, and is effective treatment available?  Pneumococcal meningitis  Is the cause of presumed infection unknown?  Encephalitis of unknown cause  Is it a multidrug resistant organism?  Toxicity and poor efficacy of available treatment options  What is the extent of the infection?  Septic shock with multiple organ involvement

99 Case  Potential donor: male with injection drug use  MRSA bacteremia  Septic emboli to brain  Afebrile, on antibiotics for more than 48 hours  Recipient critically ill  End stage pulmonary fibrosis  Mechanical ventilation in ICU  Should organs from this donor be transplanted? MRSA: Methicillin-resistant Staphylococcus aureus ICU: Intensive care unit. Wendt JM, et al. Am J Transplant, 2014

10  Both doing well, without infection more than one year after transplant Outcome of Recipients of MRSA Endocarditis Donor  Lungs, liver, kidneys, and pancreas transplanted  Prophylaxis given to all recipients  Liver and lung recipient with recurrent MRSA MRSA: Methicillin-resistant Staphylococcus aureus

11 Donors with bacteremia or endocarditis  About 5% of donors have bacteremia at procurement  Outcomes good  Recipient and donor treated  Not an MDR organism  Typically treat recipients for 7 days  Donors with endocarditis  One publication with 5 donors with good outcomes  4/5 with coagulase negative staph, one with enterococcus  MRSA and other more virulent organisms; exercise caution American Journal of Transplantation 2005; 5: 781–787

12 Case  Healthy man with nausea/paresthesia/emesis after fishing trip  ED febrile/seizures/dysphagia  LP with 9 wbc, HIV/CMV/VZV/HSV/Crypto all negative  MRI no abnormalities  Deteriorated brain dead 17 days later  Presumed diagnosis was ciguatera toxin poisoning  Should this donor be used?

13 Donors with encephalitis of unknown cause should be avoided JAMA. 2013;310(4):

14 Unusual Transplant-transmitted Infectious Encephalitis Clusters Clusters in the United States, Reported to CDC, Infectious Agent Total donors and clusters Total Recipients Total Deaths West Nile virus LCMV Rabies 2 8 5* Balamuthia mandrillaris 2 7 3** Total * Three recipients received rabies post-exposure prophylaxis and survived. LCMV: Lymphocytic choriomeningitis virus ** Four recipients received prophylatic treatment. Basavaraju SV, et al. Emerg Infect Dis 2014.

15 Transplantation 2014 Sep 27;98(6):666-70

16 Many donors with alternative diagnosis Transplantation 2014 Sep 27;98(6):666-70

17 Donor characteristics that suggest CNS infection Transplantation 2014 Sep 27;98(6):666-70

18 Most Donor-Derived Infections Present within 30 Days of Transplantation Kaul et al. Am J Transplant 2013; 12: suppl 5

19 Deceased Donors Living Donors Deceased and Living Combined Donors recovered N (%) with PDDTE through (1.9%)24 (0.08%)787 (1.1%) N (%) with prov/prob PDDTE through (0.4%)5 (0.02%)146 (0.2%) Total recipient transplants performed N (%) recipients with prov/prob disease177 (0.16%)4 (0.01%)181(0.13%) N (%) recipient deaths due to prov/prob disease 39 (0.04%)1 (0.003%)40 (0.03%) Cumulative Incidence of Disease Transmission: Reported Through 2013 Involving Donors Recovered

20 Transmission of Coccidioidomycosis through Organ Transplantation S Kusne 1, S Taranto 2, S Covington 2, D Kaul 1, W Bell 1, SW Biggins 1, E Blumberg 1, GD DeStefano 1, E Dominguez 1, D Ennis 1, M Klassen-Fischer 1, C Kotton 1, Y Law 1, M Menegus 1, R Miller 1, M Pavlakis 1, TL Pruett 1, D LaPointe Rudow 1, P Ruiz 1, N Siparsky 1, M Souter 1, L Weiss 1, C Wolfe 1, and, M Green 1. 1 OPTN Ad Hoc Diseases Transmission Advisory Committee. 2 United Network or Organ Sharing ATC 2013 Seattle Number of Recipients Recipient Mortality at 4 months 6 proven or probable cases /21 recipients infected Dx median 30 days 6 deaths median 21 days post tx

21 Communication Critical to Reduce Impact of Donor Derived Infection OPTN Transplant Center OPO

22 Summary  Unexpected donor derived disease remains uncommon  NAT + serological testing will prevent transmission of most hepatitis B, C and HIV  Selected testing based on seasonal and other geographic exposures  Donor evaluation caution  Meningoencephalitis of unknown cuse  MDR organisms  Robust communication