Rapid Testing for Creutzfeldt-Jakob Disease in Donors of Cornea

Abstract

Background: Creutzfeldt-Jakob disease (CJD) has been accidentally transmitted by contaminated corneal transplants. Eye donors are not ordinarily tested for CJD, in part because an easy test is not available. We propose a relatively simple postmortem procedure to collect brain samples without performing full autopsy and show that a test currently marketed for veterinary diagnosis would offer an effective screening test.

Methods: We selected 6 brains from confirmed cases of human sporadic CJD and sampled each in triplicate (18 specimens), 28 control brains of individuals with non-CJD neurodegenerative diseases and 10 normal brains. We also applied a procedure involving retro-orbital puncture after enucleation and biopsied the frontal lobes and optic nerves of a macaque experimentally infected with variant CJD. All samples were tested with the IDEXX HerdChek BSE-Scrapie Ag Kit to detect the abnormal prion protein, PrP.

Results: The test discriminated between control and CJD-infected brains. All 18 infected brain samples diluted to 0.1%, except one, showed signals above cutoff, and a number of samples were reactive at even higher dilutions. These results suggest the test could detect the low concentrations of PrP probably present in brains of donors at early stages of CJD. Our collection procedure obtained sufficient macaque brain and optic nerve tissues to detect PrP.

Conclusions: We showed that a commercial test combined with rapid sample collection might offer a practical solution to screen brains of cornea donors for evidence of CJD. Such a test might enhance safety of corneal transplants and some other tissue-derived products.

FIGURE 1.

HC test signal distributions for normal control human samples (gray bars) and for CJD-infected samples (black bars). Normal samples included 10 healthy brains and 28 brains from patients with a variety of non-TSE degenerative neurological diseases: 8 with Lewy Body dementia, 7 with Alzheimer disease, 5 with Parkinson disease, 4 with Pick disease and 4 with Huntington disease. All normal brains were tested as 10% w/v homogenates. All CJD-infected brains were tested as 1% brain homogenates.

FIGURE 2.

HC results with macaque DER9 optic nerve (ON) right (R) and left (L) and brain tissues from behind the right and left eyes. Optic nerve tissue had lower levels of PrP^TSE so double volumes were tested. Positive and negative run controls were provided as part of the HC test kit.