Active Prions Detected in Donated Cadaver

Investigators detected prions in one of 75 cadavers received by an institution in Japan for anatomical practice, according to a letter published in the New England Journal of Medicine.

“The potential for exposure to prions through accidental contact with prion-infected tissues…is of concern, since prions are not inactivated by formalin fixation,” the authors wrote, adding, “Abnormal prion protein (PrPSc) accumulates in the central nervous system long before the onset of disease,” putting others at risk for transmission.

Asked for independent comment, Ilia V. Baskakov, PhD, a professor in the Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, told Medscape Medical News, “The most important finding of the study is the message that it is important to screen cadavers for prions. Cadavers need to be tested for prions before they are used in medical practice to prevent iatrogenic transmission of prions to pathologists, other medical personnel, and students.

“Pathologists, dieners, and others need to be cautious and follow safety practices when dealing with cadavers,” advised Baskakov, who was not involved in the study. “They need to wear personal protective equipment and follow safety protocols. They need to avoid direct body contact with cadavers and body fluids, and injuries such as cuts when examining tissues and taking samples.”

Takehiro Nakagaki, MD, PhD, from Nagasaki University, and colleagues used real-time quaking-induced conversion to screen for prion disease in 75 cadavers received by one institution for anatomical practice. Of these, prions were detected in one cadaver, with the mean 50% seeding dose of 10 per gram of tissue taken from five specimens from the frontal lobe.

The donor died 8 years earlier at 92 years of age, with aspiration pneumonia listed as the cause of death, and had no surviving relatives to provide a medical or family history.

Specimens viewed under the microscope that were stained with hematoxylin and eosin showed extensive spongiform changes in the neocortex, vacuoles of varying sizes that did not tend to coalesce, neurons that were mostly preserved, and mild gliosis. Without frozen tissue or blood specimens, the researchers could not confirm the presence of a mutation in the gene encoding prion protein.

Specimens treated with immunohistochemical staining suggested that the donor likely carried the V180I mutation. Abnormal prion protein (PrPSc) showed only weak signals in the temporal cortex, and the forms of the vacuoles were characteristic of this genotype commonly found in older Japanese people.

The researchers acknowledged that weaknesses of the study included its small sample size and inability to determine whether the prions in this case were transmissible.

Conventional Disinfection Methods Don’t Work Against Prions

“Like viruses, prions exist in many different shapes, many different strains,” Baskakov said. “Prion proteins mis-folded into abnormal forms cause disease.”

Because prions are biochemically different from viruses and bacteria, surgical instruments and body tissues can’t be disinfected using methods that work against those conventional pathogens, he explained.

“And prion stability toward disinfectant agents varies by strain, so no disinfectant agent works against all strains,” he noted. “We can reduce the titer of the prions, but it is very difficult to eliminate them completely.

“Autoclaving of surgical instruments is approved by [the Centers for Disease Control and Prevention]. But autoclaving is not 100% effective and cannot be done to tissues being examined.”

The global incidence of known prion diseases is estimated at one to two cases per million people per year, the authors write. The incidence of undiagnosed prion disease, though unknown, is estimated to be as high as one case per 30,000.

Baskakov advised that establishing whether the etiology of a case is iatrogenic, familial, or sporadic is important because that knowledge can help researchers determine their incidence rates.

“Our understanding of the etiology of sporadic prion diseases is poor,” he said. “We don’t know whether environmental factors or lifestyle affect incidence, so when new cases in cadavers are identified, it’s very important to establish, if possible, whether they are familial or sporadic.

“The case in this study seems to be subclinical, with the death not due to prion disease,” Baskakov said. “We don’t know how many cases of prion disease are subclinical.”

NEJM. Published online June 9, 2022. Letter

The authors of the NEJM letter and Baskakov all report having no conflict of interest with the study.

The study was supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Ministry of Health, Labor and Welfare of Japan; and the Takeda Science Foundation.

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