Distribution and Quantitative Estimates of Variant Creutzfeldt-Jakob Disease Prions in Tissues of Clinical and Asymptomatic Patients

Emerg Infect Dis. 2017 Jun;23(6):946-956. doi: 10.3201/eid2306.161734.

Abstract

In the United-Kingdom, ≈1 of 2,000 persons could be infected with variant Creutzfeldt-Jakob disease (vCJD). Therefore, risk of transmission of vCJD by medical procedures remains a major concern for public health authorities. In this study, we used in vitro amplification of prions by protein misfolding cyclic amplification (PMCA) to estimate distribution and level of the vCJD agent in 21 tissues from 4 patients who died of clinical vCJD and from 1 asymptomatic person with vCJD. PMCA identified major levels of vCJD prions in a range of tissues, including liver, salivary gland, kidney, lung, and bone marrow. Bioassays confirmed that the quantitative estimate of levels of vCJD prion accumulation provided by PMCA are indicative of vCJD infectivity levels in tissues. Findings provide critical data for the design of measures to minimize risk for iatrogenic transmission of vCJD.

Keywords: Creutzfeldt-Jakob disease; Scotland; United Kingdom; asymptomatic patients; clinical patients; intracerebral inoculation; meningitis/encephalitis; prions and related diseases; protein misfolding cyclic amplification; public health; tissues; vCJD; variant Creutzfeldt-Jakob disease; variant Creutzfeldt-Jakob disease prions; variant infectivity.

MeSH terms

  • Animals
  • Asymptomatic Diseases
  • Biological Assay*
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Creutzfeldt-Jakob Syndrome / diagnosis*
  • Creutzfeldt-Jakob Syndrome / metabolism
  • Creutzfeldt-Jakob Syndrome / pathology
  • Female
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / metabolism
  • Liver / pathology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • PrPC Proteins / chemistry*
  • PrPC Proteins / metabolism
  • PrPC Proteins / pathogenicity
  • Protein Folding
  • Salivary Glands / metabolism
  • Salivary Glands / pathology
  • United Kingdom

Substances

  • PrPC Proteins