Transmission and biosafety

Which blood fractions carry infectivity?

Two kinds of result need to be kept apart. Amplification assays report seeding activity, meaning the capacity of a sample to template further misfolding in vitro. A bioassay reports infectivity, meaning that inoculated animals went on to develop disease.

The bioassay evidence in human blood is small. Douet and colleagues reported infectivity in erythrocytes, leukocytes and plasma from one patient with variant CJD, and in the plasma of 2 of 4 patients whose tests were positive for sporadic CJD, describing the levels as comparable to those reported in animals with transmissible spongiform encephalopathies.

The amplification evidence is larger. Concha-Marambio and colleagues applied protein misfolding cyclic amplification to blood from 14 variant CJD cases and 153 controls, which included sporadic CJD and other neurological patients, and reported 100 percent sensitivity and specificity, detection in every blood fraction tested, a requirement of only a few microlitres, and an estimated PrPSc concentration near 0.5 pg per ml, while stating that further work is needed for full validation. In the same issue, Bougard and colleagues combined plasminogen bead capture with amplification and identified 18 clinical variant CJD patients among 256 plasma samples, with 100 percent sensitivity, 99.2 percent analytical specificity and 100 percent diagnostic specificity. Their assay also detected silent carriage in two blood donors who later developed variant CJD, 1.3 and 2.6 years before clinical onset.

Both studies used variant CJD. Neither establishes equivalent performance in sporadic or genetic disease. For the donor policy built on this evidence, see blood and plasma.

How effective are decontamination methods?

Belondrade and colleagues ran the comparison that anchors much of this field. Stainless steel wires were contaminated with variant CJD brain homogenate, air dried, treated, then implanted intracerebrally in tgBov tg110 mice, which overexpress bovine prion protein about six times the physiological level. The same treatments were assessed by Surf-PMCA, which counts the amplification rounds needed before residual seeding activity is detected.

Three treatments gave no transmission and survival beyond 700 days: 2 percent sodium hypochlorite, 1 N sodium hydroxide and steam at 134 degrees. The water control gave 75 percent transmission, with all 8 wires positive after a single amplification round. Of six commercial products, one gave no transmission and one gave 10 percent; the other four gave 90 to 100 percent transmission, with survival times of roughly 376 to 490 days.

The two methods broadly agreed in rank order without matching exactly. One wire treated with 1 N sodium hydroxide and one treated with the effective commercial product were positive by Surf-PMCA although no mouse developed disease. The authors present the method as a rapid and sensitive screen that provides complementary data to help manufacturers improve products, and they do not propose replacing bioassays. Their stated caveats are that the wires were air dried while clinical devices are usually moist, and that the commercial products had been approved using hamster assays with a different prion strain, so that approval is a poor predictor of efficacy against variant CJD prions. See decontamination for the method detail.

A 2026 review in Viruses describes current prevention as resting on donor selection, traceability of tissues and instruments, and validated decontamination. It raises direct screening of donor tissue by RT-QuIC or amplification, particularly for corneal grafts, and notes that the Czech Republic has required Western blot testing of brain tissue from corneal donors since 2007, with all samples reported negative to date. See tissue and organs.

Can animal prion strains infect primates?

Comoy and colleagues inoculated one cynomolgus macaque intracerebrally with 25 mg of brain from a naturally infected sheep classical scrapie isolate. Neurological signs appeared about 110 months after inoculation and the animal was euthanised at 118 months, an incubation two to four times longer than the authors observed with bovine prion strains. They state that the case gives experimental evidence of zoonotic potential for that isolate, that the human risk should not be dismissed, and that confirmation would require duplicate intracerebral exposures and oral transmission studies. They present the work as a case report and call for long-term studies of chronic wasting disease and atypical or Nor98 scrapie. The author affiliations include the CEA prion unit SEPIA, INRA-ENVT Toulouse, the Istituto Zooprofilattico Sperimentale del Piemonte in Turin, the USDA laboratory at Ames, ANSES Lyon and the Norwegian Veterinary Institute.

A single animal with an incubation period near the limit of a primate study constrains what can be concluded. The questions this leaves open are set out in food chain and chronic wasting disease and zoonotic risk.

What containment do the assays require?

Amplification of human prions is itself a containment problem. When the Montpellier group moved their method to cerebrospinal fluid, they reported 40 of 41 clinical variant CJD samples positive and 0 of 57 non-variant samples positive, using untreated CSF with brain from humanised transgenic mice as substrate and 160 cycles of incubation and sonication. The report states that the work needs a biosafety level 3 laboratory and highly experienced personnel, and it presents the evaluation as a research result on a panel of 98 samples rather than a validated clinical test. The practical consequences for laboratories are covered in laboratory safety, and the diagnostic performance of these assays in diagnostics research.

Which bodies set the rules?

In England, the Department of Health and Social Care publishes Minimise transmission risk of CJD and vCJD in healthcare settings, produced by the Advisory Committee on Dangerous Pathogens TSE risk management subgroup, formerly the TSE Working Group. It was first published on 27 November 2012 and last updated on 18 November 2021. Its three parts cover introduction, health and safety management, and laboratory containment and control measures, followed by annexes A1 to M on the distribution of infectivity in human and animal tissues, diagnostic criteria, decontamination and waste disposal, transport of infected material, quarantining of surgical instruments, endoscopy, handling of bodies after death, presurgical assessment, pathology laboratory handling and ophthalmology.

In Germany, the Arbeitskreis Blut lists three current prion statements: S 27 of 6 December 2024 on exclusion criteria for blood and plasma donation in relation to variant CJD, an undated statement on the risk of variant CJD transmission by plasma derivatives, and a 2005 statement published in Bundesgesundheitsblatt 9/2005 and posted on 13 September 2005.

Where is the cross-border work?

NEURO-COOP is an Interreg POCTEFA 2021-2027 project co-financed up to 65 percent by the European Regional Development Fund, which began in March 2024. Its partners are the Universidad de Zaragoza, INRAE, CIC bioGUNE, IRTA-CReSA, the Universite de Toulouse and ATLAS Molecular Pharma. Among its stated aims are assessing how resistant misfolded proteins are to decontamination and the risk of transmission through medical care. Its grant reference EFA031/01 appears in the funding acknowledgements of recent prion papers from the Basque and Toulouse groups. For the wider programme map, see research.