1. Black Bugs Blood: West Nile Virus & the Blood Supply Infectious Transfusion Risks, Screening Blood donations for WNV and other icky things Jed Gorlin, Memorial Blood Centers Duluth TAM 11/04

2. Risks of Transmission Infectious Risks –Viral –Bacterial –Protozoa –Ricketsia –Other ?Prion Non-infectious risks –Transfusion Reaction –Metabolic –Cardiac Overload –Dilutional Coagulopathy –TAGVHD –Alloimmunization

3. Transfusion Safety Product Safety –Donor Recruitment –Donor history screening –Donor Testing –Manufacturing cGMP Transfusion Safety –Patient blood sample –Med indication for Tx. –Special Tx needs –Select right unit –Issue to floor –administration –monitoring & evaluation of reaction

4. 10 1 10 2 10 3 10 4 10 0 10 5 10 6 10 7 10 8 HIV HCV HBV Mis-Transfusion TRALI TA-GVHD Under transfusion Cardiac Paling Risk Scale for Major Transfusion Hazards Metabolic risk in neonates Bacteria General anesthesia Sunny Dzik, MD

5. Window period risk Why is there any residual risk? There is potential for transfusion transmission, if donors is drawn after acquiring the disease but before they make an antibody response. Time from infectivity to test reactivity Chance of transmission is a function of both incidence and length of window period.

6. NAT screening (HCV/HIV/HBV) Two major testing platforms for HIV/HCV Roche-Pools of 24, separate tests for HCV, HIV. Advantage: automated detection, disadvantage, very manual sample prep Chiron-Gen Probe (TMA) Multiplex test –Pools of 16, automated sample prep, manual detection. Requires extra round to resolve positive samples. More false positives

7. MBC Experience After testing almost 2,000,000 samples, MBC has detected 1 HIV NAT window period case and 5 HCV NAT+/EIA negative samples. Almost 1,000,000 samples were tested for both HCV and HIV before a single NAT+/EIA - sample was found.

8. U.S. NAT Program Yields

9. What Has NAT Testing Cost the US?? Assume 13 million blood donations annually Assume an average cost/donation of $16 Cost of HCV/HIV- NAT = $208,000,000/yr or $104M each

10. Cost/HCV-NAT positive donation: Average HCV-NAT pos. rate in US = 1:276,000 donations 13 million donations/yr collected 47 window case donations expected @ $104,000,000 total Cost/HCV-NAT positive donation detected = $>2,200,000/donation

11. Cost/HIV-NAT positive donation: Average HIV-NAT pos. rate in US = 1:3,760,000 donations 13 million donations/yr collected 3.5 window case donations expected @ $104,000,000 total Cost/HIV-NAT positive donation detected = > $28,000,000/donation

12. 200,000 Cost-effectiveness ($/YLE) 600,000 400,000 2,000,000 4,000,000 6,000,000 8,000,000 ALT Testing p24 Ag Testing Anti-HBc Testing for HIV MP NAT HIV+HCV SD FP HCV Look- back RhIg/HDN Prophy- laxis CABG (one vessel) HTN Therapy Annual Mammo- gram Cardiac Trans- plantation Transfusion Safety Interventions Commonly Accepted Medical Practices PAD- CABG MP=>SD NAT Cost-Effectiveness Comparisons

13. Other Transfusable Parasitic Chagas –Trypanosoma cruzi Endemic: Central & So. America –Infected reduviid (kissing) bug falls from thatched roof, defecates and inoculates skin –May be under-recognized cause of heart failure –Only 7 cases Tx transmission in US/Canada –Screened for in Brazil and other LA countries –ARC proposes to implement screening –MBC to participate in Chagas trial ~1/05

14. West Nile Virus: Background and Ecology First isolated in West Nile district, Uganda, 1937 Commonly found in humans and birds and other vertebrates in Africa, Eastern Europe, West Asia, and the Middle East, but has not previously been documented in the Western Hemisphere Basic transmission cycle involves mosquitoes feeding on birds infected with the West Nile virus Infected mosquitoes then transmit West Nile virus to humans and animals when taking a blood meal West Nile Virus: Background and Ecology

15. The Japanese Encephalitis Serocomplex of the Family Flaviviridae

16. 1999 - 2002 Verified WNV Surveillance Results Reported to ArboNet 731919733266/927 + DC2001 44 + DC 11 + DC 4 States 11,450 63 25 Horses 593814,7903949/262 2002 515430521/22000 16?62/61999 Mosquito Pools Birds Humans/ Fatalities Year

17. Date of Symptom Onset, West Nile Virus United States, 1999-2001 0 5 10 15 20 25 30 7/78/49/1 9/29 10/2711/2412/23 Week ending Number of cases 2001 2000 1999

18. Clinical Epidemiology Incubation period 3 - 14 days ~80% of infections are asymptomatic 20% develop “West Nile fever” 1 in 150 develop meningoencephalitis –Advanced age primary risk factor for severe neurological disease and death

19. Outcome of West Nile Virus Infection among Hospitalized Patients At discharge (NY and NJ, 2000) –More than half did not return to functional level –Only one-third fully ambulatory At one year (NYC 1999 patients) –Fatigue 67%, memory loss 50%, difficulty walking 49%, muscle weakness 44%, depression 38%

20. Summer 2003 Implemented WNV NAT screening 7/1/03 Automated DNA extraction Pool size 6-dedicated pooling machines TaqMan platform requires lots of room. Total NAT laboratory space doubled MBC detected ~36 WNV+ blood donors, mostly in Nebraska, South Dakota and Iowa

21. More Automated System COBAS AmpliPrep COBAS TaqMan (96/48) Hamilton Pipettor

23. WNV Human cases and deaths

24. + WNV rate weekly (6/30-9/30)

25. 2004 map as of 10/26/04

26. 2004 counties 10/26/04

27. WNV+ blood donors - 10/26/04

28. 2004 WNV Transfusion transmission in Arizona MMWR Sept 17, 2004 p 842 In 2003 blood centers interdicted ~800 blood components via pooled testing. Because of 6 cases of transfusion transmission, a policy for single donor (SD) testing was implemented for 2004. 3 days before switch to SD in Arizona (from TMA pool of 16), a 43 yo with severe diabetes was transfused following a knee amputation. He subsequently developed WNV and died. The units were traced and one donor was shown to be WNV+ by SD but not pooled testing.

29. Implications Despite reduced pool size and plans to implement single donor testing, window period cases of WNV continue to occur. There have been two HIV transmissions despite pooled NAT testing Both manufacturers are working to create more automated systems that facilitate single donor testing. These will be more expensive, but will allow greater throughput than current manual tests