Variant CJD. 18 years of research and surveillance

Abstract

It is now 18 years since the first identification of a case of vCJD in the UK. Since that time, there has been much speculation over how vCJD might impact human health. To date there have been 177 case reports in the UK and a further 51 cases worldwide in 11 different countries. Since establishing that BSE and vCJD are of the same strain of agent, we have also shown that there is broad similarity between UK and non-UK vCJD cases on first passage to mice. Transgenic mouse studies have indicated that all codon 129 genotypes are susceptible to vCJD and that genotype may influence whether disease appears in a clinical or asymptomatic form, supported by the appearance of the first case of potential asymptomatic vCJD infection in a PRNP 129MV patient. Following evidence of blood transfusion as a route of transmission, we have ascertained that all blood components and leucoreduced blood in a sheep model of vCJD have the ability to transmit disease. Importantly, we recently established that a PRNP 129MV patient blood recipient with an asymptomatic infection and limited PrP(Sc) deposition in the spleen could readily transmit disease into mice, demonstrating the potential for peripheral infection in the absence of clinical disease. This, along with the recent appendix survey which identified 16 positive appendices in a study of 32,441 cases, underlines the importance of continued CJD surveillance and maintaining control measures already in place to protect human health.

Keywords: Abbreviations: BSE; Gerstman–Sträussler–Scheinkerdisease; M; abnormal prion protein; QuIC; bovine spongiform encephalopathy; CWD; chronic wasting disease; GSS; methionine; PPS; pentosan polysulphate; PrPres; prion; prion protein; protease-resistant prion protein; PrPSc; quaking-induced conversion; TSE; transmissible spongiform encephalopathy; transmissible spongiform encephalopathy; V; valine; vCJD; variably protease-sensitive prionopathy; variant Creutzfeldt–Jakob disease; variant Creutzfeldt–Jakob disease; VPSPr.

Figure 1.

Vacuolation scoring in the mouse brain. Lesion profile comparison of vCJD and BSE following transmission to RIII mice. Data shows mean lesion profile ± standard error of the mean (n ≥ 6). G1-G9, gray matter scoring regions; (G1) dorsal medulla, (G2) cerebellar cortex, (G3) superior colliculus, (G4) hypothalamus, (G5) thalamus, (G6) hippocampus, (G7) septum, (G8) retrosplenial and adjacent motor cortex, (G9) cingulate and adjacent motor cortex.

Figure 2.

Abnormal PrP deposition in hippocampus of RIII and VM mice following inoculation with BSE or vCJD. (A) BSE in RIII mouse; (B) vCJD in RIII mouse; (C) BSE in VM mouse; (D) vCJD in VM mouse (bar, 100 μm; anti-PrP antibody: 6H4).

Figure 3.

Reported incidence of vCJD deaths in the UK and in non-UK countries.

Figure 4.

MRI brain scan in variant CJD. FLAIR axial section at the level of the basal ganglia showing bilateral symmetrical dorsomedial and pulvinar thalamic hyperintensity. Courtesy of Dr David Summers.