An e-Network Forum colleague's donor center just got the results of their first falsely positive WNV test. They were surprised to learn that they had to bring the donor in for follow-up testing even though the repeat test on the initial specimen was negative (Chiron). She laments that counseling and follow-up testing is a logistical problem for a true positive but at least it's understandable. She complains that "other than helping Gen Probe with their research project and forthcoming papers" she is not clear about the value of follow up testing for false positives. She pleads for advice.

Before sending the inquiring colleague's plea to the full network, her question was forwarded to a colleague who is extremely knowledgeable in donor screening for WNV. This expert says that because the performance characteristics of the test are as of yet undefined, any donor having a reactive test result, even if nonreproducible based on additional testing, must be followed to confirm which test represents truth. The IND specifies that if a pool is reactive followed by an individual test being reactive, or if single unit testing is performed, and the individual test is reactive, the donor is deferred and products are destroyed. At this point, additional testing from the index unit is performed for donor counseling, and even if non-reactive, the donor must provide a follow up sample for donor reinstatement. Certainly one could envision the situation of a low viral load that was detected in the primary screening, but then due to variability around the assay cutoff, or sample handling, that the repeat tests performed later may be non-reactive. All indications to date are that such donors who repeat test non-reactive were false positive in initial testing; in order to be confident during the investigational period, a follow up sample is requested (and required if it is to lead to donor reinstatement).

The following responses were received.

ADDENDA Aug. 23, 2003

1. A transfusion medicine physician affiliated with Chiron, who is very familiar with the circumstances of the WNV testing of blood donors, reports that this assay is only available for investigational use under IND at this time, since the clinical performance characteristics have not been fully established. Given this, follow-up requirements were placed in the IND to better define the true parameters of the assay.

He comments that (verbatim) "Follow-up testing is important to determine if the initial reactive is a false positive or a low viral titer positive. Since little is known about viral load and infectivity, it is important to determine if the assay has clinical specificity, and consequently additional studies must be undertaken to verify the sensitivity and specificity of an assay. Follow-up will help to provide the true value of the new assay. With limited studies available at the start up of the WNV assay development, the true specificity can only be measured by doing donor follow-up studies. The logistical problems of donor follow-up may be significant, but this data is vital both to determining the value of an initial reactive result and also for getting the information needed to support for approval of the intended use of the assay, which will be needed by any user. Since the CDC has reported many cases of low viral titers in WNV infection, the follow-up data will be needed to allow analysis of the value of a single WNV NAT positive result."

ADDENDA Aug. 28, 2003

2. A senior scientist at a Northern California donor center is of the opinion that follow-up on any WNV NAT reactive donor is vital. He comments (verbatim) "We don't completely understand the natural history of WNV infection as it pertains to the blood supply. We do know that very low viral loads have been detected in blood donors and are not rare events. Without a very clear understanding of the natural history of WNV infection in relationship to the blood supply, it will be very difficult to protect blood recipients from infection and at the same time take reasonable protective measures within the industry. At this point in the epidemic this really has nothing to do with publishing papers. Yes, papers will be published, but only because this is an important way of documentation and disseminating information."

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator