Only one take home point for the talk 9/26/2018. Infectious Diseases and Donor Derived Infections. Don t forget about donor-derived infections

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Shane Colombo 1993 2018 Infectious Diseases and Donor Derived Infections Peter Chin-Hong, MD

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1 Shane Colombo Infectious Diseases and Donor Derived Infections Peter Chin-Hong, MD Division of Infectious Diseases UCSF Only one take home point for the talk Don t forget about donor-derived infections Potential transmission events reported to UNOS/DTAC ( ) Courtesy Mike Ison 1

Courtesy Mike Ison How to think about donor derived infections How to think about

2 Don t forget about donor-derived infections How to think about donor derived infections Potential transmission events reported to UNOS/DTAC ( ) Courtesy Mike Ison How to think about donor derived infections How to think about donor derived infections Good: Bacterial infections Bad Ugly: HIV, HepB, HepC Rabies, LCMV 2

3 How to think about donor derived infections Which of these organisms is safe to transplant? Good: Bacterial infections Bad Ugly: HIV, HepB, HepC Rabies, LCMV 34 year-old male with diabetes s/p kidney pancreas transplant 6 weeks prior Gram negative rod sepsis and abdominal rash U.S. born, no foreign travel. From Fresno, CA What is your zebra differential diagnosis? 34 year-old male with diabetes s/p kidney pancreas transplant 6 weeks prior Gram negative rod sepsis and abdominal rash U.S. born, no foreign travel. From Fresno, CA What is your next best management step? 3

34 year-old male with diabetes s/p kidney pancreas transplant 6 weeks prior Gram negative rod sepsis and abdominal rash U.S.

(hyperinfx BAL, urine for O&P) Rhabitiform larvae CLINICAL -Serology ( sens) - Mild GI symptoms - Hyperinfection TREATMENT -Ivermectin Larva

4 34 year-old male with diabetes s/p kidney pancreas transplant 6 weeks prior Gram negative rod sepsis and abdominal rash U.S. born, no foreign travel. From Fresno, CA Donor information: Immigrant from Mexico. Immigrated 6 years prior. Farm worker Skin biopsy: What is this? 34 year-old male with diabetes s/p kidney pancreas transplant 6 weeks prior Gram negative rod sepsis and abdominal rash U.S. born, no foreign travel. From Fresno, CA Donor information: Immigrant from Mexico. Immigrated 6 years prior. Farm worker Skin biopsy: What is this? A worm! STRONGYLOIDES LIFE CYCLE/EPI - Skin->lung->gut - Can complete lifecycle w/in host (peri-anal skin) - Severe disease in IS host DIAGNOSIS -Stool O&P (hyperinfx BAL, urine for O&P) Rhabitiform larvae CLINICAL -Serology ( sens) - Mild GI symptoms - Hyperinfection TREATMENT -Ivermectin Larva currens Racing larva Autoinfection cycle 4

Worldwide seroprevalence of strongyloides 55 year-old renal transplant recipient presents with fever, cough, abdominal pain Blood cultures: E.

transmissions and screening Three donors from Strongyloides endemic areas Transmission 1: 5 organs transplanted; 1 recipient affected (CA)

Results known but not reported to TC Transmission 3: 4 organs; donor tested prior to transplantation; all recipients treated.

program)-2013, 18 organs transplanted 233 screened Abanyie F et al, 2015, AJT, 15:1369 Abanyie F et al, 2017, Trans ID Screening

5 Worldwide seroprevalence of strongyloides 55 year-old renal transplant recipient presents with fever, cough, abdominal pain Blood cultures: E. coli and Enterococcus U.S. transmissions and screening Three donors from Strongyloides endemic areas Transmission 1: 5 organs transplanted; 1 recipient affected (CA) Transmission 2: 5 organs; 2 recipients dead. Results known but not reported to TC Transmission 3: 4 organs; donor tested prior to transplantation; all recipients treated. No disease (NY) CDC Since 2009, 7 clusters; 20 recipients; 2 deaths 86% Latin America born NYODN 10 positive donors 2010 (started program)-2013, 18 organs transplanted 233 screened Abanyie F et al, 2015, AJT, 15:1369 Abanyie F et al, 2017, Trans ID Screening recommendations Strongyloides Risk stratified screening Lived in the following areas for any period of time: Southeastern United States, Mexico, Puerto Rico, the Caribbean, Latin America, South America, SubSaharan Africa, Asia, India, and Oceania Don t have to wait for results before doing transplant Consider doing screening pretransplant on recipients too Ivermectin for positive cases 5

Centers for Disease Control contacted Nifurtimox x 4 months Donor investigation: Immigrant female from Central America Two other organ rercipients from same

6 37 year old woman s/p cadaveric kidney pancreas transplant 6 weeks prior Presents with fever What is this? 37 year old woman s/p cadaveric kidney pancreas transplant 6 weeks prior Presents with fever Peripheral blood smear: Trypanosoma cruzi trypomastigotes U.S. Centers for Disease Control contacted Nifurtimox x 4 months Donor investigation: Immigrant female from Central America Two other organ rercipients from same donor (kidney, liver) found to be infected with T. cruzi Outcome: recurrent reactivation several weeks after completing therapy; died of Chagas myocarditis Trypanosoma cruzi and vector Courtesy Patricia Doyle, PhD, UCSF 6

S. Chagas reactivation: Brazil 11 U.S. organ transplant recipients identified since 2001 from 3 known or highly

(36%) died; 1 (9%) definitely attributable to Chagas disease Chin Hong PV et al, 2011, AJT, 11:672 792 patients s/p

7 Worldwide prevalence of Chagas U.S. seroprevalence of Chagas Source: AABB Chagas Biovigilance program, as of June 4, 2018 Transmissions and screening: U.S. Chagas reactivation: Brazil 11 U.S. organ transplant recipients identified since 2001 from 3 known or highly suspected infected donors Heart (2), liver (3), kidneypancreas (1), kidney (5) 5 (45%) developed Chagas disease 4 (36%) died; 1 (9%) definitely attributable to Chagas disease Chin Hong PV et al, 2011, AJT, 11: patients s/p heart transplantation in Brazil idiopathic; 196 ischemic; 117 Chagas disease Long-term survival of Chagas heart transplant patients greatest (p<0.027) Bocchi EA et al, 2001, Ann Thorac Surg,71:1833 7

Screening recommendations Chagas Risk-stratified screening in donors and heart recipients with a history of Chagas Post-transplant PCR monitoring immediately following

cruzi PCR and microscopy weekly for months 1 and 2, every 2 weeks for month 3, then monthly for at least 6 months If positive, benznidazole or nifurtimox (CDC) Chin Hong

platelets and LFTs CXR diffuse infiltrates Despite broad spectrum antibiotics and ganciclovir the patient expired one month after admission A post mortem examination was

parasitic specific antigens positive Donor: Toxo IgG positive, IgM indeterminate Recipient (pre-transplant): Toxo IgG negative, IgM negative Other kidney recipient: also

8 Screening recommendations Chagas Risk-stratified screening in donors and heart recipients with a history of Chagas Post-transplant PCR monitoring immediately following transplantation Monitoring strategy: T. cruzi PCR and microscopy weekly for months 1 and 2, every 2 weeks for month 3, then monthly for at least 6 months If positive, benznidazole or nifurtimox (CDC) Chin Hong PV et al, 2011, AJT, 11:672 Schwartz B et al, 2011, AJT, 11: year old woman with ESRD with polycystic kidney disease s/p CRT 1 month prior Admitted with T, BP, platelets and LFTs CXR diffuse infiltrates Despite broad spectrum antibiotics and ganciclovir the patient expired one month after admission A post mortem examination was performed Heart Lung H&E: staining of myocardium, lung and liver showed intracytoplasmic inclusions suggestive of Toxoplasma gondii Immunohistochemistry: staining for parasitic specific antigens positive Donor: Toxo IgG positive, IgM indeterminate Recipient (pre-transplant): Toxo IgG negative, IgM negative Other kidney recipient: also died. Found to have disseminated toxoplasmosis on autopsy. Toxo IgG, IgM negative pre transplant Liver H&E Liver IHC Toxoplasmosis Ingestion of infected or contaminated food/water Oocysts in soil from cat feces Raw/undercooked meat Transplacentally Tissue cysts remain latent reactivation during immunosuppression 8

Worldwide seroprevalence of toxoplasmosis Transmissions and screening: U.S.

these were in nonheart recipients (liver, kidney, lung) 45% died Wolfe C et al, 2016, AJT, 16 Screening

If D+/R-, treat recipients with TMP/SMX If intolerant to TMP/SMX: pyrimethamine or atovaquone 22 year old Mexican

9 Worldwide seroprevalence of toxoplasmosis Transmissions and screening: U.S. 14 cases reviewed by UNOS/DTAC Probable or proven transmissions in 11 recipients from 10 donors 5 of these were in nonheart recipients (liver, kidney, lung) 45% died Wolfe C et al, 2016, AJT, 16 Screening recommendations Toxoplasmosis All donors now required to have toxoplasmosis screening (4/2017) with Toxoplasma IgG If D+/R-, treat recipients with TMP/SMX If intolerant to TMP/SMX: pyrimethamine or atovaquone 22 year old Mexican IVDU migrant farm worker admitted with fevers, wasted, basal ganglia infarcts, CVA Exam with lime sized cervical LN Accept? Any further work-up? R basal ganglia infarct 9

CT chest CT chest Cryptococcus gattii Fungus among us Coccidioides Histoplasma

10 22 year old Mexican IVDU migrant farm worker admitted with fevers, wasted, basal ganglia infarcts, CVA Exam with lime sized cervical LN Accept? Scary Any further work-up? CT chest CT chest Cryptococcus gattii Fungus among us Coccidioides Histoplasma Blastomyces Cryptococcus gattii Fungus among us *Histoplasma Blastomyces *Coccidioides *super important 10

cruzi Toxoplasma Coccidioides Strongyloides T. cruzi Toxoplasma Coccidioides Chin Hong et al, Am J Transplant.

11 Next-generation sequencing for infections Next-generation sequencing for malignancies UCSF 500 gene panel Fung M et al, IDSA 2017 Courtesy Chloe Atreya Which of these organisms is safe to transplant? Which of these organisms is safe to transplant? Strongyloides T. cruzi Toxoplasma Coccidioides Strongyloides T. cruzi Toxoplasma Coccidioides Chin Hong et al, Am J Transplant. 2011; (11)4 Roy et al, Am J Transplant. 2014; (14)1 Kumar et al, Am J Transplant. 2010; (10)1 Chin Hong et al, ATC

12 How to think about donor derived infections Good: Bacterial infections Thank you Bad: Strongyloides, Chagas Toxoplasma, Coccidioides, West Nile, TB Ugly: HIV, HepB, HepC Rabies, LCMV 12

Risk of Other Donor-Derived Infections (nonhiv, nonhcv) Daniel Kaul MD Associate Professor University of Michigan

Risk of Other Donor-Derived Infections (nonhiv, nonhcv) Daniel Kaul MD Associate Professor University of Michigan Conflict of Interest Disclosure I have no relevant financial relationships to disclose