Estimation of variant Creutzfeldt-Jakob disease infectivity titers in human blood

Blood of individuals with variant Creutzfeldt-Jakob disease (vCJD) is infectious but the titer is unknown. Current estimates of possible vCJD infectivity titers in blood have largely relied on an assumption that the titers of vCJD agent in human blood are likely to be similar to those in blood of rodents infected with model transmissible spongiform encephalopathy agents, assayed by intracerebral inoculations of rodents of the same species.

We analyzed published descriptions of experimental transfusion-transmitted (TT) bovine spongiform encephalopathy and scrapie in sheep and reports of TTvCJD in humans, applying statistical approaches to estimate the probable number of intravenous infectious doses (ID(iv) ) per unit of transfused blood (ID(iv) /unit). For humans, ID(iv) /unit of nonleukoreduced red blood cells (NLR-RBCs) were estimated by two statistical models.

Sheep blood collected at or near onset of clinical illness contained a mean of 0.80 ID(iv) /unit. Estimates of infectivity in NLR-RBCs from donors incubating vCJD indicated a probable mean infectivity of 0.29 ID(iv) /unit (Model 1) and 0.75 ID(iv) /unit (Model 2). The analysis predicted a mean of 21 vCJD-infected recipients expected in a cohort transfused with vCJD-implicated NLR-RBCs in the United Kingdom.

Our analysis suggested that, while less than one ID(iv ) is likely to be present in a given unit of NLR-RBCs collected from a donor incubating vCJD, there is a high probability of TT infection among recipients of vCJD-implicated blood components. The analysis supports continuing measures currently recommended to reduce the risk of TTvCJD.