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

Authors

  • Luisa Gregori,

    Corresponding author
    1. From the Division of Emerging and Transfusion-Transmitted Diseases, Office of Blood Research and Review, Rockville, Maryland; and the Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland.
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  • Hong Yang,

    1. From the Division of Emerging and Transfusion-Transmitted Diseases, Office of Blood Research and Review, Rockville, Maryland; and the Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland.
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  • Steven Anderson

    1. From the Division of Emerging and Transfusion-Transmitted Diseases, Office of Blood Research and Review, Rockville, Maryland; and the Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland.
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  • This work was funded by the US Food and Drug Administration.

  • The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.

Luisa Gregori, DETTD/OBRR/CBER/FDA, 1401 Rockville Pike, FDA HFM-313, Rockville, MD 20852; e-mail: luisa.gregori@fda.hhs.gov.

Abstract

BACKGROUND: 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.

STUDY DESIGN AND METHODS: 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 (IDiv) per unit of transfused blood (IDiv/unit). For humans, IDiv/unit of nonleukoreduced red blood cells (NLR-RBCs) were estimated by two statistical models.

RESULTS: Sheep blood collected at or near onset of clinical illness contained a mean of 0.80 IDiv/unit. Estimates of infectivity in NLR-RBCs from donors incubating vCJD indicated a probable mean infectivity of 0.29 IDiv/unit (Model 1) and 0.75 IDiv/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.

CONCLUSION: Our analysis suggested that, while less than one IDiv 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.

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