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Abstract
The route of transmission of most naturally acquired transmissible spongiform encephalopathy (TSE) infections remains speculative. To investigate urine as a potential source of TSE exposure, we used a sensitive method for detection and quantitation of TSE infectivity. Pooled urine collected from 22 hamsters showing clinical signs of 263K scrapie contained 3.8 +/- 0.9 infectious doses/mL of infectivity. Titration of homogenates of kidneys and urinary bladders from the same animals gave concentrations 20,000-fold greater. Histologic and immunohistochemical examination of these same tissues showed no indications of inflammatory or other pathologic changes except for occasional deposits of disease-associated prion protein in kidneys. Although the source of TSE infectivity in urine remains unresolved, these results establish that TSE infectivity is excreted in urine and may thereby play a role in the horizontal transmission of natural TSEs. The results also indicate potential risk for TSE transmission from human urine-derived hormones and other medicines.
Highlights
Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases
We used a highly sensitive and precise method of measuring low concentrations of TSE infectivity, which we have successfully used for quantitation of TSE infectivity in blood [1,2], to measure the concentration of TSE infectivity in urine of scrapie-infected hamsters
In a limiting dilution titration, all animals in the bioassay are inoculated with the highest concentration of inoculum that is tolerated by the intracranial route
Summary
Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases. In humans, a long asymptomatic incubation period is followed by a progressive clinical course that typically lasts a few months to a year. Two other studies have reported infectivity in urine [11] and infectivity with disease-specific prion protein (PrPd) in kidneys of mice with simultaneous scrapie and nephritis but not in those with scrapie alone [12]. To resolve these discrepancies, we used a highly sensitive and precise method of measuring low concentrations of TSE infectivity, which we have successfully used for quantitation of TSE infectivity in blood [1,2], to measure the concentration of TSE infectivity in urine of scrapie-infected hamsters
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