1. International Blood Safety Forum Washington, DC Confronting Emerging Pathogens with Limited Resources José Eduardo Levi MARCH 20 th, 2015

2. MANDATORY TESTING IN BRAZIL Hepatitis B – anti-HBc + HBsAg + HBV-DNA Hepatitis C – anti-HCV + HCV-RNA HIV– anti-HIV (1, 2 and O) + HIV-RNA Chagas Disease – anti-T. cruzi Syphilis – Treponemic or non-treponemic assay HTLV-1 and HTLV-2 – anti-HTLV 1 and 2 Malaria – In endemic areas (Amazon) CMV – Selected recipients Abnormal hemoglobin – Sickle cell trait

3. DENGUE

5. Affected municipalities and Incidence

7. Sao Paulo 15,000,000 inhabitants < 1,000 dengue cases in 2010 Santos 800,000 inhabitants > 20,000 dengue cases in 2010 60 km

8. Tabela 1 – Número de casos de dengue comprovados e incidência por 100.000 habitantes em municípios da baixada santista. Fonte: Secretaria do estado da Saúde (Grupo de Vigilância Epidemiológica) e IBGE. DENGUE LABORATORY MARKERS AMONG BLOOD DONORS FROM SANTOS, BRAZIL. LEVI, UNPUBLISHED IgGIgMIgG + IgMTMA MONTH/YEARN= JAN/201050074,0%7,2%5,8%0,0% FEB/201049364,5%8,5%6,9%1,4% MARCH/201049568,7%15,2%13,7%1,2% APRIL/201050070,2%24,4%23,8%0,8% JULY/201050071,6%17,8% 0,0% JULY/201150074,4%8,6%7,8%0,0% MEAN 70,6%13,6%12,6%0,6%

9. Rate symptomatic/ asymptomatic = 1:3

10. VIREMIC DONOR (RNA+) RECIPIENT PRE-TX NEGATIVE AND POST-TX NEGATIVE SIGNS, SYMPTOMS AND LABORATORY MARKERS COMPATIBLE WIH DENGUE OCCURRING 1-14 DAYS POST-TRANSFUSION EVIDENCE OF TRANSFUSION-TRANSMITTED DENGUE

12. STRAMER SL, TRANSFUSION 2012, IN PRESS

13. Transfusion.Transfusion. 2015 Jan 21. doi: 10.1111/trf.12944. [Epub ahead of print

15. HYPOTHESIS FOR THE LOW NUMBER OF TT CASES REPORTED: 1)Hemovigilance may be deficient 2) Presence of protective immunity in recipients in endemic areas 3) Frequent cotransfusion of antibody-positive units which neutralize infectivity of viremic donations 4) Clinical outcomes may not be as severe in immunosuppressed patients infected with dengue 5) Need for mosquito saliva to enhance dengue replication and virulence;

16. ?

18. HYPOTHESIS FOR THE LOW NUMBER OF TT CASES REPORTED: 1)Hemovigilance may be deficient 2) Presence of protective immunity in recipients in endemic areas 3) Frequent cotransfusion of antibody-positive units which neutralize infectivity of viremic donations 4) Clinical outcomes may not be as severe in immunosuppressed patients infected with dengue 5) Need for mosquito saliva to enhance dengue replication and virulence;

19. Tabela 1 – Número de casos de dengue comprovados e incidência por 100.000 habitantes em municípios da baixada santista. Fonte: Secretaria do estado da Saúde (Grupo de Vigilância Epidemiológica) e IBGE. DENGUE LABORATORY MARKERS AMONG BLOOD DONORS FROM SANTOS, BRAZIL. LEVI, UNPUBLISHED IgGIgMIgG + IgMTMA MONTH/YEARN= JAN/201050074,0%7,2%5,8%0,0% FEB/201049364,5%8,5%6,9%1,4% MARCH/201049568,7%15,2%13,7%1,2% APRIL/201050070,2%24,4%23,8%0,8% JULY/201050071,6%17,8% 0,0% JULY/201150074,4%8,6%7,8%0,0% MEAN 70,6%13,6%12,6%0,6%

20. DENGUE SEROTYPES CIRCULATING IN BRAZIL, 2012

22. HYPOTHESIS FOR THE LOW NUMBER OF TT CASES REPORTED: 1)Hemovigilance may be deficient 2) Presence of protective immunity in recipients in endemic areas 3) Frequent cotransfusion of antibody-positive units which neutralize infectivity of viremic donations 4) Clinical outcomes may not be as severe in immunosuppressed patients infected with dengue 5) Need for mosquito saliva to enhance dengue replication and virulence;

23. 2 casos de dengue, 1 DF e 1 DSS, ambos transplante de fígado cerca de 8 meses pós-transplante.

24. HYPOTHESIS FOR THE LOW NUMBER OF TT CASES REPORTED: 1)Hemovigilance may be deficient 2) Presence of protective immunity in recipients in endemic areas 3) Frequent cotransfusion of antibody-positive units which neutralize infectivity of viremic donations 4) Clinical outcomes may not be as severe in immunosuppressed patients infected with dengue 5) Need for mosquito saliva to enhance dengue replication and virulence;

27. DONOR`S SCREENING: IF AND HOW -EPIDEMIOLOGY Important negative impact on donor availability -CLINICAL SIGNS Low efficiency -LABORATORIAL ?

30. PROOF OF TT WNV - USA

31. WNV INTRODUCTION IN SOUTH AMERICA

34. No cases Imported(38) Autoctonous (850) CHIKUNGUNYA CASES – BRAZIL NOVEMBER 2014

35. NEW/EMERGING AGENTS

37. A. albopictusA. aegypti

38. MEASURES TAKEN AT SÃO PAULO BLOOD BANK: -DEVELOPMENT OF A DENGUE/CHKV REAL-TIME PCR ASSAY FOR APHERESIS PLATELET UNITS -EMERGENCY PLAN TO STOP BLOOD COLLECTION AT AREAS OF HIGH INCIDENCE -MOBILIZATION OF FIDELIZED BLOOD DONORS FROM NON-AFFECTED AREAS - ESTABLISHMENT OF EPIDEMIOLOGICAL CRITERIA FOR RESTARTING BLOOD COLLECTION (TRIGGERS)

39. ACKNOWLEDGMENTS Dr Ésper G. Kallas and team - Immunology Dept., São Paulo University Medical School Eliana Perroud – Santos Blood Center Dr Cláudio Pannuti and team – Virology Lab, tropical medicine Institute, University of São Paulo Dr Ester Sabino – Infectious Diseases Dept., São Paulo University Medical School Dr Alfredo Mendrone and team – Fundação Pró-Sangue Dr Michael P. Busch - Blood Systems Research Institute, EUA Novartis (Grifols) – Sponsor, Santos Dengue Blood Donors Study