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West Nile Virus

West Nile Virus. Transfusion Medicine Residents Nov.30, 2007 Margaret Fearon. First Case of West Nile infection in Canada. 75 yr old man visits relatives in Queen’s, New York, Sept. 1 - 5, 1999 Returns to Toronto and is seen by GP for myalgia and ‘heartburn

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West Nile Virus

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  1. West Nile Virus Transfusion Medicine Residents Nov.30, 2007 Margaret Fearon

  2. First Case of West Nile infection in Canada • 75 yr old man visits relatives in Queen’s, New York, Sept. 1 - 5, 1999 • Returns to Toronto and is seen by GP for myalgia and ‘heartburn • Seen in Emerg on Sept. 10 with fever, myalgia, diarrhea, headache and confusion • Lapsed into coma on Sept. 11

  3. West Nile Encephalitis: Toronto Case (cont.) • CSF exam typical for viral meningo-encephalitis (^protein, ^WBC, n. gluc.,neg. gram) • Serology at Toronto PHL (haemagglutination inhibition) • Sept. 13 SLE <1:10 • Sept. 18 SLE 1:40 • Sept. 25 SLE 1:350 • Confirmed as WNV specific Ab. by CDC

  4. West Nile Encephalitis: Toronto Case (cont.) • Required mechanical ventilation Sept. 15 • Developed nosocomial pneumonia • Treated with Clinda/Ceftriax., Acyclovir, IVIG • Died Sept. 25, 1999

  5. Organ Donation Transmission of WNV – 1st caseIwamoto M et al. NEJM 2003;348:2196-2203 1st reported case of WNV transmission by organ donation August 2002 • Organ donor from Georgia (epizootic WNV) • Trauma July 30, 2002 • Received 63 blood components • Declared brain dead July 31  organs recovered August 1 • No WNV pre/post transfusion, but PCR + at time of organ recovery

  6. Organ Donation Transmission of WNV – 1st caseIwamoto M et al. NEJM 2003;348:2196-2203 2 recipients of cadaveric kidneys from same donor in Georgia develop headache and fever  WNV encephalitis  1 died 2 recipients of heart and liver from same donor in Florida develop febrile illness  1 with encephalitis

  7. Transfusion Transmission Cases of WNV in U.S, 2002Pealer L.,et al. NEJM 2003;349;13 1236-1245 • 23patients confirmed to have acquired WNV infection via RBCs, platelets, FFP • 15 identified by development of WNV illness (13 - meningoencephalitis, 2 – fever) • 7 received co-components • 1 post-donation notification by donor • Incubation 2 - 21 days • 7 deaths

  8. Transfusion Transmission Cases of WNV in U.S, 2002 • 16 donors • Found to have evidence of viremia at time of donation (PCR) retrospectively (low viral load <80 pfu/mL) • All IgM negative at time of donation • 9 symptomatic before or after donation

  9. Transfusion Transmission of WNV in Canada 2002 414 cases of reported probable or confirmed WNV (majority in Ontario) 5 cases of reported WNV had received blood transfusion within 28 days: Total 4 probable cases of TT-WNV • 2 cases - 1 platelet, and companion (RBC) component from an antibody positive donor • 2 cases with multiple transfusions (60 – 100), 1 with organ transplant with no other risk factor (antibody positive donors not located) • 5th case – all donors tested and no antibody positive donor located

  10. Public Health Agency of Canada WNV Human Cases – Surveillance Maps* 2002 414 cases 2003 1481 cases *Pink – endemic cases Yellow – travel related cases

  11. 2004 25 cases 2005 225 cases

  12. 2006 151 cases 2007 2335 cases

  13. CBS preparations for 2003 • Inventory management • Withdrew frozen plasma collected in Ontario prior to October 31, 2002 • Stockpiled red cells and frozen plasma prior to 2003 WNV season • Donor questionnaire • Added question about fever and headache in week prior to donation (U.S. and Canada) • Fast-tracked development of NAT assays (U.S., Canada) • Roche TaqScreen WNV Assay (mini-pools of 6) • Chiron Procleix WNV Assay (mini-pools of 16) • CBS tested all collected units as of July 2, 2003 • (used an in house assay June 17-July 2, 2003)

  14. CBS WNV NAT • Roche TaqScreen WNV Assay • Qualitative Real Time PCR • Automated specimen prep. (COBAS AmpliPrep) • Automated amplification & detection (COBAS TaqMan Analyzer) • Minipools of 6 • Reactive with all flaviviruses in Japanese encephalitis group • Reported sensitivity* • 95% LOD 77.7 – 36.8 c/mL *After 2004 modification of elution buffer and positive control

  15. Supplemental WNV Testing WNV NAT repeat reactives sent to National Testing Lab (NTL) in Ottawa for: 1) Alternate NAT - Chiron (Gen Probe) Procleix WNV Assay • Qualitative Transcription Mediated Amplification format • Minipool of 16 (we run in single unit for this purpose) • Specific for West Nile Virus 2) Serology • PanBio- ELISA – IgM and IgG

  16. Transfusion Transmission Cases of WNV in North America, 2003 • 914 presumptive viremic donors identified in U.S., • 14 presumptive viremic donors in Canada • 5 cases of transfusion transmission reported in U.S. (0 in Canada) • Cases occurred in donors with viral load too low to be detected in MP.

  17. WNV Donor Testing after 2003 • After 2003 it was recognized that low viral load viremic donors could only be identified by single unit testing (SUT) rather than mini-pool. • Testing all donors (CBS tests approximately 1 million donors/yr.) would not be feasible or cost-effective. • A strategy for selected SUT had to be devised.

  18. SUT in 2004 • The Plan • Use the detection of a positive donor (by mini-pool testing) to trigger SUT for clinics in that health region. • Use a population trigger to initiate SUT in those areas where regular donor clinics are not held. • The Reality • CBS given an arbitrary start date in the absence of positive donors or reported human cases - used positive birds as a trigger for SUT in health regions.

  19. Strategy for Single Unit Testing2005 - 2007 SUT initiated in a health region when one WNV positive donor is identified, or The number of new confirmed community cases reported in a health region reaches the level of 1/1,000 (rural areas) or 1/2,500 (urban) for the past 2 consecutive weeks. SUT discontinued if no more positive donors or # of community cases fall below population trigger 2005 - SUT discontinued after 14 days 2006 – 2007 SUT discontinued after 7 days *Stockpiling of frozen plasma and RBCs discontinued in 2005

  20. Clinics for Single Unit Testing • The clinics selected for single unit testing are decided on a weekly basis and/or within 24 hours when a new WNV positive donor is identified. • Selected clinics are located: • Within the public health district where the donor lives, donated, + any clinics in close proximity in neighbouring health regions

  21. Identification of Samples • High tech solution • Manufacturing will put red stripe on lower label of NAT EDTA tubes with industrial “Sharpie” pen

  22. CBS Blood Donor Clinics Map Key Green – No WNV activity Blue – Non-human cases Yellow – Prob.or Conf. Human Cases Orange - >1 MP pos.donor Red – Prob.or Conf. Human Cases >1/1,000 (rural) >1/2,500 (urban)

  23. CBS Blood Donor Clinics

  24. Donor Follow-up • Donors contacted by Centre M.D. • Advised to visit family practitioner • Further testing through local PHL • Permission for further (NAT and antibody) testing by CBS • Questioned re any symptoms • Defer for 56 days from date of reactive test • If donor develops WNV after donation, recall donations made in past 56 days

  25. WNV testing at CBS* *No cases of transfusion transmission reported in Canada since implementation of WNV testing

  26. West Nile Virus Transmission Through Blood Transfusion --- South Dakota, 2006 MMWR WeeklyFebruary 2, 2007 / 56(04);76-79 This report describes two cases of probable transfusion-transmitted WNV from a common blood donor despite a negative MP-NAT result at the time of donation. The source of infection cannot be proven because blood samples or co-components from the implicated donation were unavailable for testing; however, evidence of WNND in two recipients of blood products from a common donor with serologic evidence of recent infection makes WNV transfusion-transmission probable. Because these two transfusion recipients were hospitalized for at least 2 weeks each before onset of WNND, neither patient was likely to have acquired infection from a mosquito bite. Furthermore, for the patient who underwent transplant surgery on August 25, transmission through the transplanted kidney is unlikely, given that neither the organ donor nor the other organ recipient had evidence of WNV infection

  27. Public Health Agency of Canada WNV Report

  28. Public Health Agency of Canada WNV Report

  29. AABB WNV Biovigilence MapIncludes ARC, ABC, CBS and HQUpdate Nov 13Usually significant delay in updatesCBS provides data only if Presumptive Positive

  30. Donations Screen for WNV by SUT and MP per Week

  31. WNV NAT Screen Reactive Donors by Province *2 donors with travel history 1 1 false positive donor (alt. NAT and antibody negative)

  32. Alternate NAT and Antibody Results

  33. Donor Characteristics • Age Range 19 – 69 • First time vs Repeat donor 3 vs 67 • Sex Male 50 Female 20 • Symptomatic * • 40/70 donors reported symptoms • 28 pre-donation • 5 post donation • 7 timing of symptoms unknown • 3 Presence of symptoms unknown • 27 Asymptomatic *Donors reported symptoms ranging from mild headache to rash and muscle pains , chills and fever

  34. Donor Studies 6 donors identified as WNV positive by SUT Results of Replicate Testing 2005

  35. Proposed Studies on 2007 Donors "What I need is an exact list of specific unknown problems we might encounter." (Lykes Lines Shipping)

  36. Proposed Follow-up Studies • Donor Survey • Survey of 70 WNV NAT positive donors • Impact of positive WNV test on behaviour - self, family • Knowledge of West Nile – presence in community, preventative measures • Symptoms

  37. Laboratory Studies and Strategy Evaluation • All SUT positives to be tested by MP in replicates of (TBD). • Effectiveness of SUT strategy evaluated. • Viral load testing – Roche Diagnostics and National Microbiology Lab (NML) Winnipeg • Viral sequencing and comparison to Idaho strain (stable mutation at 3’NCR) - NML

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