Prions are comprised principally of aggregates of a misfolded host protein and cause fatal transmissible neurodegenerative disorders of mammals, such as variant Creutzfeldt–Jakob disease in humans and bovine spongiform encephalopathy in cattle. Prions pose significant public health concerns through contamination of blood products and surgical instruments, and can resist conventional hospital sterilization methods. Prion infectivity binds avidly to surgical steel and can efficiently transfer infectivity to a suitable host, and much research has been performed to achieve effective prion decontamination of metal surfaces. Here, we exploit the highly sensitive Standard Steel-Binding Assay (SSBA) to perform a direct comparison of a variety of commercially available decontamination reagents marketed for the removal of prions, alongside conventional sterilization methods. We demonstrate that the efficacy of marketed prion decontamination reagents is highly variable and that the SSBA is able to rapidly evaluate current and future decontamination reagents.
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.
One hundred pregnant women, not anemic and not receiving iron or vitamin supplements, were chosen at random among the three trimesters of pregnancy to determine the incidence of unexpected iron, plasma folate and/or cobalamin deficiency, and the significance of fluctuating levels of their respective binding proteins. Pregnant females had a nonsignificant fall in serum iron and a fourfold decline in serum ferritin in the 3rd trimester compared with 1st trimester values. There was a steady decrease in plasma cobalamin and cobalophilin levels in every trimester but no difference in transcobalamin II values. Unsaturated cobalamin (UBBC) and unsaturated transcobalamin binding capacity (UTCBC) were lower in the 1st trimester fully recovering afterwards. Plasma folate levels were not lower, although there was a steady reduction in total and unsaturated folate binding capacity throughout pregnancy
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