Donors and  Chagas Disease 11 th  Congress of the  International Society for  Organ Donation and Procurement  Buenos Aires...
Disclosures No conflict of interest Roberta Lattes [email_address] Instituto de Nefrología/Nephrology Buenos Aires – Argen...
Chagas disease
Chagas disease <ul><li>Neglected disease:  </li></ul><ul><ul><li>over 100 million at risk (c. 25%  infected) </li></ul></u...
Key questions   <ul><li>Chagas sero-testing for donors  </li></ul><ul><ul><li>from endemic areas  </li></ul></ul><ul><ul><...
-   PCR PCR
C hagas Disease: S ero-testing <ul><li>PAHO 1986 :   </li></ul><ul><li>2 different methodologies for chronic infection  di...
PCR <ul><li>Diez M, et al..  Am J Transplant  2007; 7: 1633  </li></ul><ul><ul><li>PCR preceded positive Strout test or cl...
26 labs in 16 countries  70 samples checked   Inter-lab evaluation Intra-lab evaluation PCR kDNA (330 bp) Highly repetitiv...
Chagas disease:  Transmission from donors <ul><li>Figueiredo JF et al. Transmission of Chagas disease through  renal trans...
Chagas infected donors Effective infected donors in Argentina Source: INCUCAI 2011 Not all Tx teams accept infected donors...
Kidney transplant: outcome Total Kidney Tx R-/D+ (n=56) 2.6% Infection Transmission  (day +35 to 165 ) 12.5% Diagnosis Hos...
Non kidney Tx: outcome <ul><li>Liver Tx </li></ul><ul><ul><li>1 case    Parasitemia, no clinical disease.  </li></ul></ul...
Recommendations <ul><li>Potentially Infected Donors </li></ul><ul><ul><li>Born in endemic areas </li></ul></ul><ul><ul><li...
Guidelines <ul><li>Living or deceased donors with epidemiological risk should be sero-tested for  T. cruzi  infection.   <...
Clinical Case <ul><li>May 2010: </li></ul><ul><li>Deceased donor:   male, 58y. Subarachnoid hemorrhage </li></ul><ul><ul><...
Clinical Case <ul><li>Lung recipient  </li></ul><ul><ul><li>Male, 57, Chagas (-) pre-Tx </li></ul></ul><ul><ul><li>No indu...
Clinical Case <ul><li>Kidney recipient </li></ul><ul><ul><li>Female, 38,  Chagas (-) pre-Tx </li></ul></ul><ul><ul><li>Thy...
Conclusions   <ul><li>Expanding the donor pool with  T.cruzi  infected donors is feasible </li></ul><ul><ul><li>Transmissi...
Collaborators <ul><li>LAURA BARCAN     HOSPITAL ITALIANO  </li></ul><ul><li>CLAUDIA NAGEL  FUNDACION FAVALORO   </li></ul>...
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Roberta Lattes - Argentina - Tuesday 29 - Donor Risk

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Roberta Lattes - Argentina - Tuesday 29 - Donor Risk

  1. 1. Donors and Chagas Disease 11 th Congress of the International Society for Organ Donation and Procurement Buenos Aires – Argentina 27-30 Nov 2011
  2. 2. Disclosures No conflict of interest Roberta Lattes [email_address] Instituto de Nefrología/Nephrology Buenos Aires – Argentina
  3. 3. Chagas disease
  4. 4. Chagas disease <ul><li>Neglected disease: </li></ul><ul><ul><li>over 100 million at risk (c. 25% infected) </li></ul></ul><ul><ul><li>18 million infected in Latin-America </li></ul></ul><ul><ul><li>migration from rural to urban areas </li></ul></ul><ul><li>Classical risk factors: </li></ul><ul><ul><li>vectorial transmission </li></ul></ul><ul><ul><li>unscreened blood transfusion in endemic areas </li></ul></ul><ul><ul><li>vertical transmission </li></ul></ul><ul><li>New risk factors: </li></ul><ul><ul><li>migration to non-endemic countries </li></ul></ul><ul><ul><li>unscreened blood transfusion in non-endemic areas </li></ul></ul><ul><ul><li>transmission through transplanted organ </li></ul></ul><ul><ul><li>more than 300.000 infected in USA </li></ul></ul>
  5. 5. Key questions <ul><li>Chagas sero-testing for donors </li></ul><ul><ul><li>from endemic areas </li></ul></ul><ul><ul><li>from non-endemic areas </li></ul></ul><ul><li>Organ procurement from infected donors </li></ul><ul><li>Treatment of infected living donors before transplantation </li></ul><ul><li>Prophylaxis of recipients </li></ul>
  6. 6. - PCR PCR
  7. 7. C hagas Disease: S ero-testing <ul><li>PAHO 1986 : </li></ul><ul><li>2 different methodologies for chronic infection diagnosis </li></ul><ul><li>WHO 2009 (TRANSFUSION 49:1076) </li></ul><ul><ul><li>437 plasma units tested in 10 different blood bank facilities </li></ul></ul><ul><ul><li>18 screening assays (11 EIA + 5 IHA + 2 PA + 1 rapid test) </li></ul></ul><ul><ul><li>4 confirmatory tests (IF – Wb – RIPA – RIB) </li></ul></ul><ul><ul><li>EIA  7/11 sensitivity and specificity > 98% </li></ul></ul><ul><ul><li>IHA  2/5 sensitivity and specificity > 95% </li></ul></ul><ul><ul><li>PA and rapid test  low sensitivity and specificity </li></ul></ul><ul><ul><li>RIPA  gold standard for confirmation </li></ul></ul><ul><ul><li>IFA  confirmation if limited financial resources </li></ul></ul><ul><li>A single EIA could be used for blood screening </li></ul>
  8. 8. PCR <ul><li>Diez M, et al.. Am J Transplant 2007; 7: 1633 </li></ul><ul><ul><li>PCR preceded positive Strout test or clinical reactivation by 30-60 days in infected heart recipients </li></ul></ul><ul><li>Duffy T, et al. PLoS Negl Trop Dis 2009;3(4):e419 </li></ul><ul><ul><li>Accurate real-time PCR strategy for monitoring bloodstream parasitic loads in Chagas disease patients </li></ul></ul><ul><li>Burgos JM,et al. Clin Infect Dis 2010; 51(5): 485 </li></ul><ul><ul><li>Multiple discrete typing units coexist in patients with Chagas disease. </li></ul></ul><ul><li>Schijman A et al PLoS Negl Trop Dis. 2011; 5(1): e931 </li></ul><ul><ul><li>First crucial step towards international validation of PCR procedures for the detection of T.cruzi in human blood samples </li></ul></ul>
  9. 9. 26 labs in 16 countries 70 samples checked Inter-lab evaluation Intra-lab evaluation PCR kDNA (330 bp) Highly repetitive sequences: Detection of low parasitic loads Useful for chronic infection diagnosis Early detection of reactivation and transmission PCR satellite (180 bp ) Nuclear DNA 50.000-100.000 p/parasite Kinetoplast DNA 40.000-80.000 p/parasite 2011;5(1):e931
  10. 10. Chagas disease: Transmission from donors <ul><li>Figueiredo JF et al. Transmission of Chagas disease through renal transplantation: report of a case </li></ul><ul><li>Trans R Soc Trop Med Hyg. 1990;84(1):61-2. </li></ul><ul><li>Cantarovich F et al. Special infections in organ transplantation in South America. </li></ul><ul><li>Transplant Proc. 1992 24(5):1902-8. </li></ul><ul><li>de Faria JB, et al. Transmission of Chagas’ disease through cadaveric renal transplantation . </li></ul><ul><li>Transplantation 1993;56:1583–1584 . </li></ul><ul><li>Vazquez MC,et al. Chagas’ disease can be transmitted through kidney transplantation. </li></ul><ul><li>Transplant Proc 1993;25:3259–3260 . </li></ul><ul><li>Riarte A, Luna R, Sabatiello R, et al. Chagas’ disease in patients with kidney transplants: 7 years experience, 1989–1996. </li></ul><ul><ul><li>Clin Infect Dis 1999;29:561–567. </li></ul></ul><ul><li>Zayas et al. MMWR, 2002; 51 </li></ul><ul><li>Mascola et al. MMWR, 2006; 55 </li></ul><ul><li>Kun et al. Transmission of Trypanosoma cruzi infection by heart transplantation Clin Infect Dis 2009;48(11):1534-40 </li></ul>
  11. 11. Chagas infected donors Effective infected donors in Argentina Source: INCUCAI 2011 Not all Tx teams accept infected donors 3.7 5.1 4.6 4.6 2.5 5.7
  12. 12. Kidney transplant: outcome Total Kidney Tx R-/D+ (n=56) 2.6% Infection Transmission (day +35 to 165 ) 12.5% Diagnosis Hospital Argerich 650 27 4 Strout 1 Strout + fever 2 Strout+ Paniculitis 1 INBA 1019 27 2 Strout 1 PCR+Strout 1 Fundación Favaloro 478 2 1 PCR
  13. 13. Non kidney Tx: outcome <ul><li>Liver Tx </li></ul><ul><ul><li>1 case  Parasitemia, no clinical disease. </li></ul></ul><ul><ul><li>Barcán L et al. Liver Transpl 2005 11(9):1112 </li></ul></ul><ul><ul><li>6 cases  5 with post-Tx benznidazole. No de novo infection. </li></ul></ul><ul><ul><li>D’Albuquerque LA et al Am J Transplant. 2007; 7(3):680 </li></ul></ul><ul><ul><li>3 cases  1 Parasitemia by PCR </li></ul></ul><ul><ul><li>(Nagel C Fundación Favaloro personal communication ) </li></ul></ul><ul><li>Kidney – Pancreas Tx </li></ul><ul><ul><li>1 case  No transmission </li></ul></ul><ul><ul><li>(Lattes- INBA) </li></ul></ul>
  14. 14. Recommendations <ul><li>Potentially Infected Donors </li></ul><ul><ul><li>Born in endemic areas </li></ul></ul><ul><ul><li>Born to mothers from endemic areas (0.5-10%) </li></ul></ul><ul><ul><li>Lived for prolonged time in endemic areas </li></ul></ul><ul><ul><li>Recipients of unscreened blood (5-20%) </li></ul></ul>Kotton C, Lattes R. Parsitic infections in solid organ transplant recipients AST Infectious diseases guidelines AJT 2009;9(54) S4:S234-S251 The Chagas’ Disease Argentine Collaborative Transplant Consortium et al Transpl Proc 2010; 42:3354-3359 Chin-Hong et al “The Chagas in transplant working group” AJT 2011;11:672-680
  15. 15. Guidelines <ul><li>Living or deceased donors with epidemiological risk should be sero-tested for T. cruzi infection. </li></ul><ul><ul><li>Infected living donors should receive trypanocidal treatment for 30 days prior to donation to allow for clearance of parasitemia </li></ul></ul><ul><li>Infected deceased donors: </li></ul><ul><ul><li>hearts should be discarded. </li></ul></ul><ul><ul><li>could be accepted for: </li></ul></ul><ul><ul><ul><li>infected recipients (except heart) </li></ul></ul></ul><ul><ul><ul><li>uninfected kidney recipients </li></ul></ul></ul><ul><ul><ul><li>eventually for uninfected lung and liver recipients </li></ul></ul></ul><ul><li>All recipients should: </li></ul><ul><ul><li>sign an informed consent </li></ul></ul><ul><ul><li>be sequentially monitored for infection transmission and promptly treated if this occurs . </li></ul></ul>
  16. 16. Clinical Case <ul><li>May 2010: </li></ul><ul><li>Deceased donor: male, 58y. Subarachnoid hemorrhage </li></ul><ul><ul><li>Lived in non endemic area. CMV (+), Toxo (+), Chagas HAI (-) PA (-). Left ventricular hypertrophy </li></ul></ul><ul><ul><li>Lung, liver and 1 kidney were distributed to three different transplant centers </li></ul></ul><ul><li>Retesting was performed: </li></ul><ul><ul><li>EIA (+) – PA (+) – HAI (+) </li></ul></ul><ul><li>The results became available after transplantation </li></ul><ul><li>Procurement organization and transplant centers were notified </li></ul>
  17. 17. Clinical Case <ul><li>Lung recipient </li></ul><ul><ul><li>Male, 57, Chagas (-) pre-Tx </li></ul></ul><ul><ul><li>No induction. Tacro +MMF+C-S. </li></ul></ul><ul><ul><li>+106 d  Admitted with febrile syndrome </li></ul></ul><ul><ul><ul><li>Positive PCR and Strout test . </li></ul></ul></ul><ul><ul><ul><li>Trypanocidal treatment  60 days </li></ul></ul></ul><ul><li>Liver recipient </li></ul><ul><ul><li>Male, 41, Chagas (-) pre-Tx </li></ul></ul><ul><ul><li>No induction. Tacro+MMF+C-S </li></ul></ul><ul><ul><li>+96 d  </li></ul></ul><ul><ul><li>Positive Strout test and PCR </li></ul></ul><ul><ul><li>Trypanocidal treatment  60 days </li></ul></ul>
  18. 18. Clinical Case <ul><li>Kidney recipient </li></ul><ul><ul><li>Female, 38, Chagas (-) pre-Tx </li></ul></ul><ul><ul><li>Thymoglobulin induction, Tacro, MMF, C-S </li></ul></ul><ul><ul><li>PCR and Strout test negative to date </li></ul></ul><ul><ul><li>No sero-conversion to date </li></ul></ul><ul><li>Comments </li></ul><ul><ul><li>Not all available tests have the same sensitivity and specificity </li></ul></ul><ul><ul><li>Transmission needs to be monitored </li></ul></ul><ul><ul><li>It generally occurs early after Tx </li></ul></ul><ul><li>Speculation: </li></ul><ul><ul><li>Parasitic load probably differs in different organs </li></ul></ul>
  19. 19. Conclusions <ul><li>Expanding the donor pool with T.cruzi infected donors is feasible </li></ul><ul><ul><li>Transmission may occur </li></ul></ul><ul><ul><li>Use of PCR as a monitoring tool allows for early treatment of transmitted infection </li></ul></ul><ul><ul><li>Trypanocidal treatment yields good results and should be promptly started if transmission occurs </li></ul></ul><ul><ul><li>Prophylactic treatment cannot be recommended at this time and deserves further study </li></ul></ul><ul><ul><li>Immunosuppression management </li></ul></ul>
  20. 20. Collaborators <ul><li>LAURA BARCAN HOSPITAL ITALIANO </li></ul><ul><li>CLAUDIA NAGEL FUNDACION FAVALORO </li></ul><ul><li>RUBEN SCHIAVELLI HOSPITAL ARGERICH </li></ul><ul><li>LILIANA BISIGNANO INCUCAI </li></ul><ul><li>ALEJANDRO SCHIJMAN INGEBI </li></ul><ul><li>MARCELO RADISIC INSTITUTO DE NEFROLOGIA </li></ul>

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