West Nile virus (WNV) has rapidly spread across North America to the BC border since first being recognized in 1999 in New York City.[1-3] Although no indigenously acquired WNV was detected in animals, birds, mosquitoes, or humans in BC up to early 2004,[4] public health officials are anticipating and actively planning for its emergence in BC this year. If the intensity of WNV activity in BC approaches that observed last year in Saskatchewan, where 858 human cases (over 90% WNV fever syndrome) were reported,[5] then a plausible scenario could range as high as several thousand symptomatic human WNV cases in BC during 2004.

Primary WNV infection is associated with a transient viremia, detectable within 1 to 2 days after being inoculated by an infected mosquito and lasting for approximately 7 days (range 1 to 11 days).[6-8] Most WNV infections are not clinically recognized[9] and infectious blood donors may therefore inadvertently pose a risk of introducing the virus into the blood supply. The following information updates BC physicians about the risk of WNV transmission through blood transfusion, methods of reducing risk of transfusion-transmitted WNV (TT-WNV), and the important role physicians have in WNV surveillance and appropriately informing patients who may receive blood or blood products about these risks.

Can WNV be transmitted through blood transfusion?
Yes.[8,10-12] During 2002 there were 23 cases in the US and 4 cases in Canada of probable or confirmed TT-WNV.[11] The risk of TT-WNV has significantly decreased since implementing universal donor WNV testing in the US and Canada in July 2003. A small residual risk remains; in 2003, six confirmed cases of TT-WNV infection were reported in the US in recipients of blood which had undergone WNV testing.[13] In Canada during 2003 there were no cases of TT-WNV identified.

What donor WNV testing is done by CBS?
The Canadian Blood Service (CBS) tests every donation for WNV with an investigational nucleic acid test using minipools of blood from six donors. The test detects WNV and other genetically similar Flaviviruses, none of which (except St. Louis encephalitis virus) is endemic to North and Central America. In Canada, a positive test result most likely reflects WNV infection.

The minimum viral dose that causes TT-WNV infection is unknown. The six confirmed cases of TT-WNV that were reported in the US in 2003 occurred following transfusion of blood that was negative for WNV by minipool testing and subsequently found to also be IgM-negative. Limited data suggest that minipool testing detects 75% to 90% of positive WNV specimens that are detected by single-unit testing. Therefore, single-unit testing may improve overall sensitivity in detecting asymptomatic donors with low levels of virus early in the infectious period (i.e., IgM-negative). US data from 2003 indicated that up to 6% of viremic donors detected by single-unit testing but missed by minipool testing were IgM-negative.

To better detect these high-risk units, CBS is increasing WNV laboratory testing capacity by 50% during the 2004 WNV season. This will permit single-unit WNV testing for up to 10% of national collections. Single-donor testing will be implemented in mid-July and continue for 6 to 10 weeks, initially targeting regions expected to be hardest hit by WNV, but redirected as necessary to regions of highest risk over the course of WNV season. Regions to be targeted for single-unit donor testing will be determined according to the incidence of asymptomatic WNV viremia among donors, and in consultation with public health officials. At this time, there is no predetermined incidence threshold of viremic donors that will trigger CBS to switch between minipool and single-unit WNV testing in a particular region.

What is the risk of transfusion-transmitted WNV from blood?
At an equivalent peak level of WNV incidence as in Saskatchewan during 2003 (approximately 1 in 500 WNV-positive donors), an estimated theoretical risk of TT-WNV from an infectious whole blood unit (collected from an asymptomatic donor) is between 1 in 6250 and 1 in 7500 donor units collected. Since each donor whole blood unit is manufactured into three components (red cells, plasma and platelets), each infectious donor unit could transmit WNV to several recipients.

What other measures does CBS have in place to prevent WNV from entering the blood supply?

a) Stockpiling plasma collected in winter and spring

During winter and early spring, prior to mosquito season, CBS has stockpiled tested, fresh-frozen plasma that will be issued for transfusion in regions experiencing high WNV activity.

b) Routine, ongoing donor screening and post-donation information

Donors must be feeling healthy and well on collection day. Donors with fever or a history of fever and headache in the previous week are temporarily deferred from donating. Donors who develop fever or other symptoms of possible WNV are instructed to contact CBS and are also temporarily deferred and any in-date components from that donation are retrieved. Donors with a positive WNV test are deferred for 56 days.

c) Discontinuing collections from areas of high WNV activity

In areas with high WNV activity, blood collections may also be temporarily discontinued if capacity for single-unit testing is exceeded, provided patient needs can be met from the national blood inventory.

What procedures are followed after a positive donor WNV screening test?
Turnaround time for results from donor screening tests is 48 hours to 72 hours after blood collection. CBS will attempt to contact a test-positive donor as soon as possible by phone, and with the donor’s consent, also contact the family physician by phone and by follow-up fax/letter. Since WNV is also reportable in British Columbia, the medical health officer in the donor’s region will also be notified as soon as possible. Physicians may be contacted by public health to coordinate follow-up, which may include further testing if clinically appropriate or collecting added epidemiologic information. This added information will enable public health to better characterize the ongoing risk of WNV in a particular region, to determine if additional WNV prevention or control measures may be warranted.

What is my role as a physician?
WNV risk from blood transfusion should be discussed with patients prior to surgical procedures where use of blood is reasonably anticipated. Physicians should also ask patients who are being tested for suspected WNV infection if they recently (i.e., within 4 weeks) donated or received blood or a blood product. If so, please report this to the CBS BC/Yukon Blood Centre at 1 888 332-5663 local 2207 or by fax at (604) 879-6352. This will enable CBS to remove in-date inventory or assist in investigating a possible transfusion-transmitted infection. A positive WNV test in a person who has recently donated or received blood is also a reportable infection to public health in BC and physicians should notify their local medical health officer.

Where can I get more information?
Physicians with questions about WNV-related transfusion practice may contact the Provincial Blood Coordinating Office at (604) 806-8840 (within Lower Mainland) or 1 866 508-5501 (outside Lower Mainland). Current information will be available from hospital blood banks, and an excellent Internet resource for current information on WNV-blood safety issues is the Provincial Blood Coordinating Office web site at www.traqprogram.ca/wnv-contingencies.asp [8].

See the related article [9].
—ED.

—Mark Bigham, MD, FRCPC
Canadian Blood Services, BC & Yukon Centre