Population screening for variant Creutzfeldt-Jakob disease using a novel blood test: diagnostic accuracy and
Graham S Jackson1, Jesse Burk-Rafel2, Julie Ann Edgeworth1
1MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, England.
Insights
A new blood test for variant Creutzfeldt-Jakob disease (vCJD) shows high specificity and sensitivity. This diagnostic assay is suitable for screening prion-exposed populations and clinical diagnosis of vCJD.
Area of Science:
- Neurology
- Biotechnology
- Infectious Diseases
Background:
- Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative prion disease.
- Accurate and sensitive diagnostic tools are crucial for vCJD detection and management.
- Current diagnostic methods for vCJD have limitations, necessitating improved assays.
Purpose of the Study:
- To evaluate the diagnostic accuracy of a prototype blood test for vCJD.
- To determine the assay's suitability for screening prion-exposed populations.
- To assess the assay's utility in clinical diagnosis of vCJD.
Main Methods:
- Retrospective, cross-sectional diagnostic study utilizing blood samples from the US and UK.
- Samples included healthy donors, patients with nonprion neurodegenerative diseases, and confirmed vCJD cases.
- The prototype assay detects disease-associated prion protein in whole blood.
Main Results:
- The assay demonstrated 100% specificity in healthy donor populations and patients with nonprion neurodegenerative diseases.
- Specificity was 98.1% in patients with suspected prion diseases, with 2 sporadic CJD cases testing positive.
- Sensitivity was reconfirmed at 70% (95% CI, 34.8%-93.3%) in a small panel.
Conclusions:
- The prototype blood assay exhibits high specificity and acceptable sensitivity for vCJD detection.
- The assay is suitable for screening prion-exposed populations and for clinical diagnosis.
- Its performance supports its use in differentiating vCJD from other neurodegenerative diseases.
Importance:
Our study indicates a prototype blood-based variant Creutzfeldt-Jakob disease (vCJD) assay has sufficient sensitivity and specificity to justify a large study comparing vCJD prevalence in the United Kingdom with a bovine spongiform encephalopathy-unexposed population. In a clinical diagnostic capacity, the assay's likelihood ratios dramatically change an individual's pretest disease odds to posttest probabilities and can confirm vCJD infection.
Objectives:
To determine the diagnostic accuracy of a prototype blood test for vCJD and hence its suitability for clinical use and for screening prion-exposed populations.
Design, Setting, And Participants:
Retrospective, cross-sectional diagnostic study of blood samples from national blood collection and prion disease centers in the United States and United Kingdom. Anonymized samples were representative of the US blood donor population (n = 5000), healthy UK donors (n = 200), patients with nonprion neurodegenerative diseases (n = 352), patients in whom a prion disease diagnosis was likely (n = 105), and patients with confirmed vCJD (n = 10).
Main Outcome And Measure:
Presence of vCJD infection determined by a prototype test (now in clinical diagnostic use) that captures, enriches, and detects disease-associated prion protein from whole blood using stainless steel powder.
Results:
The assay's specificity among the presumed negative American donor samples was 100% (95% CI, 99.93%-100%) and was confirmed in a healthy UK cohort (100% specificity; 95% CI, 98.2%-100%). Of potentially cross-reactive blood samples from patients with nonprion neurodegenerative diseases, no samples tested positive (100% specificity; 95% CI, 98.9%-100%). Among National Prion Clinic referrals in whom a prion disease diagnosis was likely, 2 patients with sporadic CJD tested positive (98.1% specificity; 95% CI, 93.3%-99.8%). Finally, we reconfirmed but could not refine our previous sensitivity estimate in a small blind panel of samples from unaffected individuals and patients with vCJD (70% sensitivity; 95% CI, 34.8%-93.3%).
Conclusions And Relevance:
In conjunction with the assay's established high sensitivity (71.4%; 95% CI, 47.8%-88.7%), the extremely high specificity supports using the assay to screen for vCJD infection in prion-exposed populations. Additionally, the lack of cross-reactivity and false positives in a range of nonprion neurodegenerative diseases supports the use of the assay in patient diagnosis.
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