Transmissible Spongiform Encephalopathies

The term

• scrapie in sheep and goats
• chronic wasting disease in deer
• bovine spongiform encephalopathies (BSE) in cattle, and
• Creutzfeldt-Jakob disease (CJD) in humans

These diseases affect the nervous system of mammals and, although the exact mechanism for transmission is as yet unknown, it is thought to be due to a putative infectious protein or protein-like substance called a prion, a ubiquitously expressed protein termed PrP or PrPc which undergoes conversion to an abnormal prion protein termed PrPsc.

Variant CJD (vCJD) is a rare and fatal human neurodegenerative condition first described in March 1996. As with CJD, vCJD is classified as a TSE because of characteristic spongy degeneration of the brain and its ability to be transmitted. The development of vCJD is strongly linked with exposure, probably through the consumption of meat and meat products, to the agent causing BSE which was first reported in the UK in 1986. In contrast to the traditional forms of CJD (sporadic, familial, and iatrogenic), vCJD has affected younger patients, average age 29 years, compared to >65 years for the other forms. vCJD has a relatively longer duration of illness, median of 14 months, compared to 4.5 months for CJD.

There is also concern about the possibility that bovine-derived materials involved in the production of vaccines and other pharmaceutical products could represent a way of potential transmission of the disease. Fetal calf serum is a widespread component of growth media, and other media components such as enzymes, and hormones are extracted from cattle. Additionally, bovine materials have been used in a variety of materials such as gelatin, a component of capsules.

An intense regulatory effort has therefore been made to eliminate materials potentially contaminated with BSE from all stages of production. Where bovine materials are still required, they must be sourced from geographical areas that are not endemic for BSE. In addition, difficult regulatory decisions have been necessary where the relative risks inherent in replacing fully characterized materials (such as vaccine seed strains) are compared with the mathematically small risk of vCJD transmission. The field is also complicated by the difficulty in assaying materials for TSEs, and in conducting studies to detect major routes of transmission and infection of this highly novel class of pathogen.

Biological Product Standardization

Written standards

WHO guidelines to minimize the risks associated with the use of vaccines, blood products and other pharmaceutical products containing bovine-derived and human-derived materials, were updated in 2003 following a review of the latest available data on the epidemiology, ante-mortem and post-mortem diagnosis, detection of the infectious agents, and distribution of infectivity in tissues or body fluids of relevant species with TSEs.

WHO Guidelines on Transmissible Spongiform Encephalopathies in relation to Biological and Pharmaceutical Products, ECBS 2003

Reference materials

WHO Reference Reagents for In Vitro Assays of CJD Specimens. ECBS 2003. WHO/BS/03.1965 Rev.1

International Reference Preparations Catalogue

Global Advisory Committee on Vaccine Safety - Committee report on Transmissible spongiform encephalopathies

Zoonoses and veterinary public health