KAREN A. REINER, PH.D. STUDENT

WALDEN UNIVERSITYPUBH8165-10

DR. RAYMOND W. THRONFALL QUARTER, 2010

West Nile Virus Screening for

Viremic Blood Donors

Intended Audience

ImmunohematologistsBlood banks specialistsTransfusion medicine personnelPhysicians

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.

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

Background

First isolated in 1937Recognized as etiologic agent of

meningoencephalitisFirst identified in the US in 1999

Etiology

Caused by a single-stranded RNA virusFamily FlaviviridaeGenus: Flavivirus

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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/

West Nile Virus Transmission Cycle

WNV transmission cycle. Available from http://www.publichealth.lacounty.gov/acd/VectorWestNile.htm

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.

Distribution of West Nile Virus in the US

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

So far this year Arizona has the highest number of reported West Nile Virus cases.

Arizona: Cases per Week

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

The graph below shows the increase in human disease cases during the summer months; consistent with increased

mosquito activity .

Epidemiology

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

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

Cases by State as of October 2010

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

Signs and Symptoms

Asymptomatic Mild

Fever Headache Body aches Nausea Vomiting Stomach & back pain Swollen lymph glands Skin rash

Signs and Symptoms

Severe High fever Headache Stiff neck Disorientation Coma Tremors Convulsions Muscle weakness Loss of vision Numbness Paralysis

Diagnosis

Detection of increased IgM in serum or CFS

Serology ELISA Nucleic Acid Plaque reduction neutralization (PRN) test Indirect Immunofluorescence (IFA) Hemagglutination inhibition

Treatment

No specific treatmentSupportive care

Interferon Antisense nucleotides

Experimental Intravenous immunoglobulins

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

Prevention (continued)

Environmental surveillance Sentinel birds Death birds Mosquito populations

Vaccine No human vaccine is

availableEducation

West Nile Virus Surveillance. Microbe World Video available from http://www.dailymotion.com/video/x6gsx0_west-nile-virus_tech

CLICK on picture to view video on separate window.

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

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

Current Criteria for Blood Screening

Optional Screening include: West Nile Virus Chaga’s Disease

AABB. (2010). Blood FAQ. Available from http://www.aabb.org/resources/bct/Pages/bloodfaq.aspx#a4FDA. (2010). Testing donors for relevant communicable disease agents and diseases. Available from http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/TissueSafety/ucm095440.htm

First Donor Screening Test for West Nile Virus. Available from http://www.youtube.com/watch?v=DAqrL8mprm4

CLICK on picture to view video on separate window.

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.htmMMWR. (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

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.htmMMWR. (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

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

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)

FDA. (2009). West Nile Virus nucleic acid testing. Available from http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm173212.htm

How to test for West Nile Virus in blood. Available from http://www.youtube.com/watch?v=dxFsGx6G8l0

CLICK on picture to view video on separate window.

Summary

West Nile Virus infections can be seriousWest Nile Virus can be transmitted via blood

transfusionMany lives have been saved by screeningWest Nile Virus screening of blood should be

mandatory

Please e-mail all questions to:

karen.reiner@waldenu.edu

Questions

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

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

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.