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ASSOCIATION BULLETIN

#07-02

Summary

This Association Bulletin contains recommendations for facilities to implement for the 2007 West Nile virus (WNV) mosquito season. The goals of the recommendations are to 1) ensure that all facilities are prepared and ready to implement appropriate individual donation nucleic acid testing (ID-NAT) triggering criteria for the 2007 WNV mosquito season and 2) link WNV donor screening data from multiple facilities serving overlapping and adjacent geographic areas. Association Bulletins 04-03¹ and 04-04² are updated by this Bulletin.

Background

ID-NAT can identify viremic donations that are not detectable by minipool NAT (MP-NAT). In 2003-2004, seven cases of WNV transmission not detected by MP-NAT were reported to the Centers for Disease Control and Prevention (CDC).³ On the basis of this information, most blood collection and testing facilities developed criteria for triggering conversion from MP-NAT to ID-NAT (and reversion to MP-NAT) during limited periods of the epidemic seasons of 2004-2006. Despite such efforts, two additional cases of WNV transmission from one donor later found to be infected were reported in 2006⁴ (see below). Data are lacking at this time to support a recommendation for a single trigger that will not only have optimal sensitivity but also meet blood center needs to conserve limited resources. However, a set of minimal triggering criteria for US blood collecting and testing facilities can be defined.

Reports in peer-reviewed journals have suggested that statistically meaningful triggering criteria for the conversion from MP-NAT to ID-NAT (and reversion to MP-NAT) should include both the frequency of reactive MPs that contain individually reactive donations and the absolute number of WNV-reactive donations identified from MP-NAT within a predetermined geographic area (eg, facility’s collection area).^5-8 

Recently, CDC reported⁴ WNV transmission to two immunosuppressed transfusion recipients despite nonreactive MP-NAT donor screening results. The recipients had no other apparent source of WNV exposure. Look-back investigations linked the two transfused components (Red Blood Cells and Fresh Frozen Plasma) to a single donor from a rural area of South Dakota where substantial WNV activity in birds, mosquitoes and humans occurred during the 2006 transmission season. The facility testing the samples for the hospital that collected the donated unit adhered to all collection facility policies related to facility-specific triggering criteria. However, there was no established method of linking WNV MP-NAT data from multiple blood collection and testing facilities serving the overlapping and adjacent geographic areas. Such a mechanism might have been used to trigger a change to ID-NAT in this particular instance.

The WNV Task Force, which includes representatives from the national blood organizations and obtains input from liaison representatives from the Food and Drug Administration and CDC, has continued to meet periodically to review issues relating to human WNV infection in the United States (and Canada). The Task Force has reached consensus regarding the information and recommendations contained in this Association Bulletin.

Recommendations

Triggering Criteria

All blood collection and testing facilities should adopt triggering criteria for determining when to convert WNV testing from MP-NAT to the more sensitive ID-NAT and when to cease ID-NAT (revert to MP-NAT). The criteria for conversion from MP-NAT to ID-NAT are based on initial reactive donations (before obtaining confirmatory results). Centralized testing facilities should be responsible for applying these uniform minimal triggering criteria to all centers for which they perform testing, for converting to ID-NAT when the trigger threshold has been met or exceeded and for reverting to MP-NAT when reactive results drop below the established threshold. 

NOTE: The triggering criteria provided are minimal approaches that have been implemented successfully by collection and testing facilities to reduce the risk of WNV transmission through blood transfusions. More stringent approaches may be used.

I.         AABB recommends the use of the following three minimal criteria in determining if and when to convert from MP-NAT to ID-NAT:

a.       An absolute number of reactive donations within a defined period (see I.c.ii./iii. for period)

                                       i.         Conversion to ID-NAT should take place when two individually reactive donations arise from reactive MPs or any ID-NAT that is otherwise performed before obtaining confirmatory results on individually tested donations. 

                                     ii.         At the time the first reactive test result is obtained, facilities should start preparation for possible conversion to ID-NAT.

b.      A rate of greater than one reactive donation per 1000 total tested donations.

                                       i.         Facilities collecting fewer than 1000 donations per week should use the weekly collection volume for the denominator. The trigger formula is then the number of reactive donations divided by the weekly collection volume.

                                     ii.         Small collection facilities must carefully evaluate their data because the length of time that elapses before a second reactive donation is identified may give the inaccurate impression that a trigger has not been reached. These facilities, in particular, should be in close communication with blood collection facilities from overlapping and adjacent geographic areas to determine if, together, they may meet or exceed the triggering criteria (see the Communication Plan section below).

                         c.      A defined geographic area to which the triggering criteria in I.a. and I.b. are applied. It is recognized that there is no simple way for facilities to segment their collection area into defined geographic areas of appropriate size to ensure optimal sensitivity and specificity. Therefore, the following guidance is provided.

i.    For facilities collecting fewer than 1000 donations per week, collection areas should not be segmented for the purpose of establishing a geographic area for application of the triggering criteria.

ii.   For facilities collecting fewer than 5000 donations per week, the defined rolling          period (time from the first MP-NAT-reactive donation to the second MP-NAT-reactive donation) used for the given geographic area is seven days.

                                       iii.      For facilities collecting greater than or equal to 5000 donations per week, the defined rolling period (time from the first MP-NAT-reactive donation to the second MP-NAT-reactive donation) used for the given geographic area is three days.

                                      iv.      As an alternative approach to I.c.ii. and I.c.iii. above, sites could monitor the number of donations tested between the first and second MP-NAT-reactive donations for the defined geographic area. If the number of tested donation samples that occurred between the two reactive donations is 2000 or fewer, the trigger has been reached.

II.       The donor’s residential zip code should be used to determine geographic area. Although exposure may occur at any location, it is most likely that exposure occurred while the donor was at his or her residence (dawn or dusk, when mosquito activity is highest). The use of residential zip codes provides a standardized method for numerator data collection.  

III.      Monitoring of reactive donations should occur in real time. When a defined geographic area has reached its trigger, conversion to ID-NAT should occur within 24 hours of the collection time of the most recent reactive donation responsible for the trigger being reached. If the conversion to ID-NAT cannot take place within 24 hours, facilities should consider retrospective testing of retained samples from donations dating back to the collection date when the triggering criteria were met.

IV.    In addition to the use of established triggering criteria, other epidemiologic data may guide the decision to convert from MP-NAT to ID-NAT, if such data are available in a timely fashion. Examples include the number of clinical cases that have been reported, number of positive birds or mosquito pools reported, prior trigger history, etc.

V.      A facility may cease ID-NAT and revert to MP-NAT when a minimum of seven days has passed without a presumptively confirmed reactive donation (ie, an initially NAT-reactive donation that is repeatedly reactive by the same or alternate NAT technique or is positive for antibodies to WNV).

VI.    Centralized testing facilities are encouraged to perform a retrospective validation of the sensitivity of their triggering criteria by performing retrospective ID-NAT of retained frozen samples from the one to two weeks immediately before initiation of ID-NAT.

Communication Plan

All blood collection and testing facilities serving overlapping and adjacent geographic areas should work together to create a communication plan for linking data to develop a “multi-site” trigger. Responsibility for tracking both the number of reactive donations and the total number of tested donations, as well as the monitoring of overlapping and adjacent collection areas, should be clearly defined among collection and testing facilities.

The communication plan should address the following:

I.                     The AABB Web site (www.aabb.org) has an established WNV Biovigilance Network reporting “tool” for monitoring WNV activity in blood donors. Facilities should enter data for reactive donations (initial reactive donations by reactive sample identification) into the reporting tool within 24 hours following the facility’s verification of the test results. Facilities should enter and track data on the Web site; however, this is not a substitute for direct communication with other organizations serving overlapping and adjacent geographic areas.  

II.                   Facilities should review the entries of adjacent collection and testing facilities on a regular basis—frequently enough to ascertain complete information about WNV infection rates among donors in their geographic area. It is essential for facilities within a geographic area to communicate when combined data indicate that a multi-site trigger may have been reached.

III.                  AABB has provided a listing of facilities that have provided contact information for reporting their WNV data on the AABB Web site as a link within this Association Bulletin. This listing is intended to assist facilities in making necessary arrangements for real-time communications during the WNV season.

Effective communication among facilities—regardless of the number of blood collectors in a given area—will permit efficient application of triggering criteria that is based on complete information about WNV infection rates among donors in a geographic area. 

References

1. Sazama K, Lipton KS. Update on WNV-related activities and considerations, 2004; a summary of the WNV Task Force meeting. Association Bulletin No. 04-03. Bethesda, MD: AABB, 2004:1-3.

2. Sazama K, Lipton KS. Joint statement of AABB, America’s Blood Centers and American Red Cross on implementation of individual donation nucleic acid amplification testing for West Nile virus. Association Bulletin No. 04-04. Bethesda, MD: AABB, 2004:1-3.

3. Montgomery SP, Brown JA, Kuehnert M, et al. Transfusion-associated transmission of West Nile virus, United States 2003-2005. Transfusion 2006;46:2038-46. 

4. Centers for Disease Control and Prevention. West Nile virus transmission—South Dakota, 2006. MMWR Morb Mortal Wkly Rep 2007;56:76-9.

5. Stramer SL, Fang CT, Foster GA, et al. West Nile virus among blood donors in the United States, 2003 and 2004. N Engl J Med 2005;353:451-9.

6. Busch MP, Caglioti S, Robertson EF, et al. Screening the blood supply for West Nile virus RNA by nucleic acid amplification testing. N Engl J Med 2005;353:460-7.

7. Custer B, Tomasulo PA, Murphy EL, et al. Triggers for switching from minipool testing by nucleic acid technology to individual-donation nucleic acid testing for West Nile virus: Analysis of 2003 data to inform 2004 decision making. Transfusion 2004;44:1547-54.

8. Custer B, Busch MP, Marfin AA, Petersen LR. The cost-effectiveness of screening the US blood supply for West Nile virus. Ann Intern Med 2005;143:486-92.

Resources
West Nile Virus Association Bulletin FAQ
West Nile Virus Biovigilance Network
West Nile Virus Web Reporting Lab Contacts