West Nile Recent Developments

Information provided January 9th, 2003

West Nile Virus - Background

WNV is a mosquito-borne flavivirus with a natural reservoir in different species of birds.

Most people infected with WNV develop no symptoms or only minor disease with fever, headaches, skin rash and body aches and sometimes swollen lymph nodes (less than 1% develop serious health effects associated with neurological disease (encephalitis or meningitis). There is no specific treatment or vaccination and most of infected individuals recover. WNV infection exhibits a brief period of viremia prior to the onset of symptoms

West Nile Virus: Transmission Through Transfusion & Transplantation - What do we know?

• In September 2002 U.S. Centers for Disease Control and Prevention (CDC) confirmed that 4 individuals who received organs during transplantation from a single organ donor were infected with WNV
• WNV infection was confirmed by NA testing of serum from the organ donor: 3 organ recipients developed encephalitis with 1 death
• Organ donor infected with WNV by mosquito exposure or through transfusion (63 units of blood transfused)
• Other subsequent confirmed reports of transmission of WNV through blood transfusion

West Nile Virus: Transmission through Blood

• Clear evidence of transmission through blood
• Higher risk of infection through mosquito bites than by Blood Transfusion
• WNV can survive in RBC units for at least 26 days, some data that other blood components may also harbour the virus. 44 days in FFP; platelets - 5 days More studies are needed
• In U.S., 14 cases of transmission of WNV through transfusion
• In Canada, 2 possible cases of transmission of WNV through transmission

West Nile Virus: Paths to Human Infection

• Blood Transfusion
• Organ transplantation
• Mosquito bites
• Intrauterine infection
• Occupational exposure-percutaneous transmission
• Possibly breast milk

West Nile Virus: Managing Risks

• General Measures for WNV infection
• Co-operative action by all stakeholders, multi-jurisdictional co-operation
• Active Surveillance System to detect WNV activity
• Education & Prevention: Reduce Exposure
• Communication re: exposure risks
• Vector abatement and control measures

West Nile Virus: Managing Risks - Blood

• Blood donor screening tests or pathogen inactivation for WNV would provide effective risk management strategies
• Contingency planning for options in the even that tests or pathogen inactivation for WNV may not be available
• For test development
  • Industry to move early WNV tests in an expedited fashion through development pipeline to a validated test to screen blood donors
  • Blood operators to have in place processes to adapt new technology in a timely manner
  • Health Canada to have in place flexible regulatory regime toreview data for approval of tests

West Nile Virus: Risk Management Options - Blood

• Pre-donation screening-rigorous assessment
• Post Donation action on probable cases
• Post Donation action on confirmed cases

West Nile Virus: Risk Management Options - Blood

• Retrieve blood components collected during mosquito season-replace with "out of season" components; stockpiling of latter
• Obtain blood from low risk areas for "high risk" patients
• Consideration of introduction of pathogen inactivation technologies
• Testing of donated blood for WNV

West Nile Virus: Test Development - Challenges

• WNV serological based screening tests for donor screening are not ideal
• Even when using NA based tests, titres of virus may be low and this complicates testing of more dilute minipools
• Several unknowns e.g. period of veremia, infectious dose, prevalence in donors, transfusion transmission incidence rate etc.
• Need to develop reference standards, reagents and test panels

West Nile Virus: Test Development - Challenges

• While recognizing that a Nucleic Acid based test for WNV donor screening is a preferred option:
  • Moving a research or clinical diagnostic test to a full fledged donor screening test, including regulatory approval and implementation in a manufacturing environment, is generally a very lengthy process (several years)
  • Reducing this timeframe will represent a considerable challenge for all stakeholders

West Nile Virus: Testing in Canada - Status

• Health Canada has been in contact with Industry to discuss the status of their WNV testing programs and to discuss regulatory options for bringing these tests to market in Canada
• Health Canada has met with CBS and HQ to discuss interest and feasibility of moving existing research and diagnostics WNV tests to within blood operators manufacturing environment
  • This is one of several options to be considered as part of contingency planning in case no test is available

West Nile Virus: Health Canada Actions to Date

• Managing WNR Risk is a high priority for Health Canada
• Formed internal working group on WNV
• WNV Issues raised, options discussed with EAC-BR
• Reviewed options and issued requirements to operators indicating:
  • no additional tests or donor screening questions are required at this time
  • for confirmed cases, products are to be withdrawn and donor deferred
  • for probable cases, products are to be quarantined and donors deferred
  • no requirement for retrieval of plasma once pooled for fractionation

West Nile Virus: Health Canada Actions to Date

• Active surveillance system for WNV has been established across Canada
• Working with Provincial and Territorial Health Authorities, procedures have been established for recording and transmitting case data from physicians/hospitals to provincial labs to CBS and HQ
• Health Canada is working with all jurisdictions in testing of WNV in Canada

Summary

• Health Canada is moving forward with various options to address WNV risk
• Development of tests for WNV are being closely followed and Health Canada will analyze data and prepare recommendations for test implementation once a test is available
• Health Canada will continue to evaluate the potential impact of WNV risks in the area of transfusion and transplantation and will take steps to ensure that adequate measures are in place to protect the public

Information From The U.S. Presentation Included

Evidence for West Nile Virus Transmission By Blood Transfusion

• 10 of 10 implicated donors had PCR positive initial donation sample
• WNV isolated from unit of FFP
• 10 of 10 donors seroconverted after donation
• 8 of 10 donors had viral symptoms before or after donation
• Three of fourteen recipients were unlikely to have mosquito exposure
• Four instances of multiple recipients associated with a single implicated donor
• Compatible timing between transfusion, viremia, and symptom onset in recipients

Transfusion-associated West Nile Virus Infection Unanswered Questions

• Better definition of clinical course of WNV infection and viremia
• Define scope and magnitude of transfusion transmission
  • Prevalence of viremia in donors
  • Rate of transmission from viremic donors and associate risk factors
  • Seroprevalence in frequently transfused persons
• Transmission of other flaviviruses (SLE dengue)?

Other West Nile Virus Links:

West Nile Virus Update - October 27, 2003

West Nile Virus Developments - January 2003