West Nile Virus Screening for Viremic Blood Donors

1. West Nile Virus Screening forViremic Blood Donors Karen A. Reiner, Ph.D. Student Walden University PUBH8165-10 Dr. Raymond W. Thron Fall Quarter, 2010

2. Intended Audience • Immunohematologists • Blood banks specialists • Transfusion medicine personnel • Physicians

3. Learning Outcomes • After completing this presentation, participants should be able to: • Describe the etiology and epidemiology of West Nile Virus. • Describe the signs and symptoms of West Nile Virus. • Discuss potential interferences with current serological testing of West Nile Virus. • Discuss the importance of West Nile Virus screening of blood.

4. Introduction • West Nile Virus can cause serious illness • Seasonal epidemic in the US • Can be fatal • Humans and animals affected • Cases reported to the CDC (so far in 2010) • 789 cases • 33 deaths CDC. (2010). West Nile Virus: Statistics, surveillance, and control . Available from http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount10_detailed.htm

5. Background • First isolated in 1937 • Recognized as etiologic agent of meningoencephalitis • First identified in the US in 1999

6. Etiology • Caused by a single-stranded RNA virus • Family Flaviviridae • Genus: Flavivirus Red Blood Cells Viron

7. Epidemiology • Transmitted primarily by: • Infected mosquitoes • Other transmission routes are: • Blood transfusions • Organ transplant • Intra utero • Breast feeding Animated graphic available from http://www.co.washington.or.us/HHS/WestNileVirus/

8. West Nile Virus Transmission Cycle The transmission cycle for the West Nile Virus is depicted on this diagram. Humans are considered accidental hosts. Human to human transmission is also possible and of increasing concern. WNV transmission cycle. Available from http://www.publichealth.lacounty.gov/acd/VectorWestNile.htm

9. Distribution of West Nile Virus in the US So far this year Arizona has the highest number of reported West Nile Virus cases. CDC. (2010). West Nile Virus: Statistics, surveillance, and control . Available from http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount10_detailed.htm

10. Arizona: Cases per Week The graph below shows the increase in human disease cases during the summer months; consistent with increased mosquito activity . CDC. (2010). West Nile Virus: Statistics, surveillance, and control . Available from http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount10_detailed.htm

11. Epidemiology 39% 61% CDC. (2010). West Nile Virus: Statistics, surveillance, and control . Available from http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount10_detailed.htm

12. Epidemiology Cases by State as of October 2010 CDC. (2010). West Nile Virus: Statistics, surveillance, and control . Available from http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount10_detailed.htm

13. Disease Manifestation • West Nile Virus infections may be: • Asymptomatic • 80% of infections • Mild • 10-20% of infections • Severe • 1 in 150 infections • Fatal • 3-15%; mostly elderly individuals CDC. (2010a). Cases of West Nile Virus human disease. Available from http://www.cdc.gov/ncidod/dvbid/westnile/qa/cases.htm

14. Signs and Symptoms • Asymptomatic • Mild • Fever • Headache • Body aches • Nausea • Vomiting • Stomach & back pain • Swollen lymph glands • Skin rash

15. Signs and Symptoms • Severe • High fever • Headache • Stiff neck • Disorientation • Coma • Tremors • Convulsions • Muscle weakness • Loss of vision • Numbness • Paralysis

16. Diagnosis • Detection of increased IgM in serum or CFS • Serology • ELISA • Nucleic Acid • Plaque reduction neutralization (PRN) test • Indirect Immunofluorescence (IFA) • Hemagglutination inhibition

17. Treatment • No specific treatment • Supportive care • Interferon • Antisense nucleotides • Experimental • Intravenous immunoglobulins

18. Prevention • Infection prevention • Limit outdoor activities during peak biting times • Use mosquito repellent • Wear appropriate protective clothing • Long pants • Long-sleeved shirts • Vector elimination • Pesticides • Eliminate water holding containers

19. Prevention (continued) • Environmental surveillance • Sentinel birds • Death birds • Mosquito populations • Vaccine • No human vaccine is available • Education CLICK on picture to view video on separate window. West Nile Virus Surveillance. Microbe World Video available from http://www.dailymotion.com/video/x6gsx0_west-nile-virus_tech

20. Timeline of West Nile Virus Screening • 2002 - West Nile Virus screening begins after the first transfusion-related infection reported • 2003 – Another case of transfusion-related West Nile Virus infection • 2003 – National blood donation screening for West Nile virus started • 2005 – DFA approves NAT for screening blood donors MMWR. (2004b). Update: West Nile Virus screening of blood donations and transfusion-associated transmission --- United States, 2003. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5313a1.htm

21. Current Criteria for Blood Screening • Mandatory blood screens include: • ABO • Rh • Other antigenic screening • HIV-1 & HIV -2 • Hep B • Hep C • HTLV-I and HTLV-II • Syphillis AABB. (2010). Blood FAQ. Available from http://www.aabb.org/resources/bct/Pages/bloodfaq.aspx#a4

22. Current Criteria for Blood Screening • Optional Screening include: • West Nile Virus • Chaga’s Disease CLICK on picture to view video on separate window. First Donor Screening Test for West Nile Virus. Available from http://www.youtube.com/watch?v=DAqrL8mprm4 AABB. (2010). Blood FAQ. Available from http://www.aabb.org/resources/bct/Pages/bloodfaq.aspx#a4 FDA. (2010). Testing donors for relevant communicable disease agents and diseases. Available from http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/TissueSafety/ucm095440.htm

23. Challenges of Current Protocols • Current blood screening protocols: • Do not reflect current needs • Example: • Human T-Lymphotropic Virus (HTLV) • Last documented transfusion-related exposure was in 1985 • Reportedly, less likely transmission for HTLV than for Hepatitis B • No other transfusion-related HTLV infections have been reported since • West Nile Virus • Steady increase in cases since 1999 MMWR. (1986a). Current trends in human T-Lymphotropic virus type III/Lymphadenopathy-associated virus: Agent summary statement. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/00033677.htm MMWR. (1986b). Epidemiologic notes and reports transfusion-associated Human T-Lymphotropic Virus Type III/ Lymphadenopathy-associated virus infection from a seronegative donor – Colorado. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/00000749.htm

24. Challenges of Current Protocols • West Nile Virus transfusion-related infection reported in 2002 • 23 cases reported • 500 viremic donations • Other transfusion-related West Nile Virus infections reported since MMWR. (2004a). Update: Detection of West Nile Virus in blood donations --- United States, 2003. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm52d918a1.htm MMWR. (2004b). Update: West Nile Virus screening of blood donations and transfusion-associated transmission --- United States, 2003. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5313a1.htm

25. West Nile Virus Viremic Blood DonorActivity in the United States CDC. (2010b). West Nile Virus: Statistics, surveillance, and control archive. Available from http://www.cdc.gov/ncidod/dvbid/westnile/surv&control_archive.htm

26. Proposed West Nile Virus Screening Methods • Approved methods for West Nile Virus testing: • COBAS TaqScreen West Nile Virus Test  Roche Molecular System, Inc. • Procleix West Nile Virus (WNV) Assay  Gen-Probe, Inc. (NAT) CLICK on picture to view video on separate window. How to test for West Nile Virus in blood. Available from http://www.youtube.com/watch?v=dxFsGx6G8l0 FDA. (2009). West Nile Virus nucleic acid testing. Available from http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm173212.htm

27. Summary • West Nile Virus infections can be serious • West Nile Virus can be transmitted via blood transfusion • Many lives have been saved by screening • West Nile Virus screening of blood should be mandatory

28. Questions Please e-mail all questions to: karen.reiner@waldenu.edu

29. References • AABB. (2010). Blood FAQ. Available from http://www.aabb.org/resources/bct/Pages/bloodfaq.aspx#a4 • CDC. (2010). West Nile Virus: Statistics, surveillance, and control . Available from http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount10_detailed.htm • FDA. (2009). West Nile Virus Nucleic Acid Testing. Available from http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm173212.htm • Macedo de Oliveira, A., Beecham, B. D., Montgomery, S. P., Lanciotti, R. S., Linnen, J. M., Giachtti, C., Stramer S.L., Safranek T. J. (2004). West Nile Virus blood transfusion-related infection despite nucleic acid testing. Transfusion, 44(12), 1695-1699. • MMWR. (1986a) Current trends Human T-Lymphotropic Virus Type III/ Lymphadenopathy-associated virus: Agent summary statement. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/00033677.htm • MMWR. (1986b). Epidemiologic notes and reports transfusion-associated Human T-Lymphotropic Virus Type III/ Lymphadenopathy-associated virus infection from a seronegative donor – Colorado. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/00000749.htm • MMWR. (2004a). Update: Detection of West Nile Virus in blood donations --- United States, 2003. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm52d918a1.htm • MMWR. (2004b). Update: West Nile Virus screening of blood donations and transfusion-associated transmission --- United States, 2003. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5313a1.htm

30. Recommended Additional Reading • Biggerstaff, B. J., Petersen, L. R. (2003). Estimated risk of transmission of the West Nile virus through blood transfusion in the US, 2002. Transfusion, 43:8, 1007-1017. doi: 10.1046/j.1537-2995.2003.00480.x. • Complete list of donor screening assays for infectious agents and HIV diagnostic assays. Available from http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm080466.htm • Diamond, M.S., Klein, R.S. (2004). West Nile virus: crossing the blood-brain barrier. National Medicine, 10(12), 1294-1295. • Harrington, T., Kuehnert, M. J., Kamel, H., Lanciotti, R. S., Hand, S., Currier, M., Chamberland, M. E., Petersen, L. R., Marfin, A. A. (2003). West Nile virus infection transmitted by blood transfusion. Transfusion, 43(8), 1018-1022. doi: 10.1046/j.1537-2995.2003.00481.x • Lanciotti, R. S., Roehrig, J. T., Deubel, V., Smith, J., Parker, M., Steele, K., et al. (1999). Origin of the West Nile Virus responsible for an outbreak of encephalitis in the Northeastern United States. Science, 286, 2333 – 2337. doi: 10.1126/science.286.5448.2333. • Macedo de Oliveira, A., Beecham, B. D., Montgomery, S. P., Lanciotti, R. S., Linnen, J. M., et al. (2004). West Nile Virus blood transfusion-related infection despite nucleic acid testing. Transfusion, 44(12), 1695-1699. • MMWR. (2005). West Nile Virus infections in organ transplant recipients --- New York and Pennsylvania, August--September, 2005. Available from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm54d1005a1.htm • Montgomery, S. P., Brown, J. A., Kuehnert, M., Smith, T. L., Crall, N., Lanciotti, R. S., et al. (2006). Transfusion-associated transmission of West Nile virus, United States 2003 through 2005. Transfusion, 46(12), 2038-2046. doi: 10.1111/j.1537-2995.2006.01030.x

31. Recommended Additional Reading • Pealer, L. N., Marfin, A. A., Petersen, L. R., Lanciotti, R. S., Page, P.L., Stramer, S.L., et al. (2003). Transmission of West Nile Virus through blood transfusion in the United States in 2002. New England Journal of Medicine, 349, 1236-1245. • Weiss, D., Carr, J., Kellachan, C., Tan, M., Phillips, E., Bresnitz, M., et al. (2001). Clinical findings of West Nile virus infection in hospitalized patients, New York and New Jersey, 2000. Emerging Infectious Diseases, 7(4): 654–658.