Background: The contribution of testing errors to the risk of virus transmission by transfusion depends on the rate of false-negative testing errors and the prevalence of infected seropositive donations. Although the false-negative testing error rate has been estimated at 0.1 to 1 percent on the basis of proficiency studies, it has not previously been measured in routine donor screening.
Study design and methods: A 1991 to 1995 database containing 5,153,153 donations from 1.5 x 10(6) donors (including autologous donors) was searched to identify donors who tested seropositive for HIV, HCV, HTLV-I or II and who attempted subsequent donations. The false-negative rate in routinely screened follow-up donations was determined, and false-negative cases were investigated to identify the cause.
Results: Subsequent donations (n = 2015) by 1224 donors with confirmed-positive results were identified. Eleven (0.5%) of these donations did not react in EIA. Ten of the 11 false-negative cases were attributable to borderline-reactive donations. On subsequent donations, there were borderline-nonreactive results on HTLV-I (2 cases), first-generation HCV (5 cases), and second-generation HCV (3 cases) EIAs. The final case was strongly reactive for HCV in a second-generation EIA on two donations (signal-to-cutoff [S:C] ratio >3.5), followed by a baseline nonreactive result on a third donation (S:C = 0.05).
Conclusion: False-negative testing results occur infrequently during routine infectious-disease donor screening. Although most false-negative results occurred with borderline-reactive HTLV-II samples and/or early-generation HCV EIAs, frank technical errors (e.g., sample mixup or failure to add sample to EIA well) also occur at a low rate (0.05%; 95% CI, 0-1.5%). Process enhancements designed to reduce errors (e.g., enhanced automation of data management and testing systems and process controls for EIAs) are warranted to detect and prevent false-negative results.