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Updated on 30/07/2021

Transmissible Spongiform Encephalopathies (TSEs), also known as prion diseases

General information on TSEs

Keywords : Prion (diseases), TSE (Transmissible spongiform encephalopathy), Animal diseases

Transmissible spongiform encephalopathies, or prion diseases, affect the central nervous system (brain and spinal cord) in humans and animals. Some of them can be transmitted through food. They are caused by prions, which are particularly resistant to conventional disinfection procedures. These diseases are always fatal and there is currently no treatment available.

What are TSEs?

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurodegenerative diseases affecting the central nervous system (brain and spinal cord). They affect certain animal species (cattle, sheep, goats, felines, mink, deer and camels) in addition to humans. They are caused by prions, also referred to in the past as "unconventional transmissible agents (UTAs)", as opposed to classical biological agents such as bacteria, viruses, parasites and mould.  

Prions (which is an acronym for PRoteinaceous Infectious ONly particle) are made up of a particular protein, the PrP protein. In the course of a TSE, the normal shape of this protein undergoes major changes and it becomes pathological. Once the process is initiated, it can transmit this anomaly to other PrP molecules, and it then spreads throughout the affected organism, mainly in the central nervous system.

Prions are highly resistant to conventional inactivation procedures such as temperatureTSEs are always fatal and there is currently no therapeutic treatment available.

TSEs are characterised by a long incubation period (usually several years and as much as 40 years in humans). The lesions observed in the brain form cavities within the neurons, hence the spongiform (sponge-like) nature of these diseases.

Some TSEs can be transmitted through food. The classical form of "mad cow disease" (BSE) was due to cattle consuming contaminated meat-and-bone meal, which used to be added to their feed. In humans, the variant of the Creutzfeldt-Jakob disease is caused by the BSE agent, transmitted through the consumption of tissue – especially nerve tissue – from infected animals.

The different types of TSEs

In humans

  • Creutzfeldt-Jakob disease

 First described in 1920, this disease manifests either in sporadic form (the most common, without any apparent cause), genetic form (caused by mutations in the prion protein gene sequence), or iatrogenic form (contamination following a transplant, central nervous system surgery or use of tainted growth hormone, which is now prohibited).

  • Variant Creutzfeldt-Jakob disease (vCJD)

Identified in 1996 among abnormally young patients whose clinical signs differed from the classical forms of Creutzfeldt-Jakob disease, this TSE is the result of human contamination by the agent causing bovine spongiform encephalopathy (BSE).

  • Other human TSEs

Cases of Kuru (Papua New Guinea), Gerstmann-Sträussler-Scheinker disease and fatal familial insomnia (FFI) have also been described.

In animals

Bovine spongiform encephalopathy (BSE)

  • Classical BSE

​​​​​​​Identified for the first time in the United Kingdom in 1986, the number of infected cattle rose drastically in the UK, reaching a peak in 1992 with 37,280 cases identified in cattle in that year alone. The disease also affected the rest of Europe and some other countries (Japan, the United States and Canada) but to a much lesser extent than the UK outbreak. Epidemiological research quickly determined that the pathogen responsible for this disease was being transmitted through contaminated meat-and-bone meal added to cattle feed.

  • Atypical BSE

From 1986 to 2004, it was thought that there was only one BSE agent, with the prion having an invariable biochemical signature in all detected cases. However, in 2004, two new biochemical profiles were discovered and named atypical BSE. There are few scientific data available on the distribution of this prion in the tissues of these animals or on the epidemiology of these forms. The regular occurrence of such cases at very low frequencies suggests that they may be spontaneous.

Scrapie in sheep and goats

Scrapie is a TSE that affects both sheep and goats. It was described back in the 18th century and is found in numerous countries. Historically, this was the first TSE for which transmissibility in animals was proven, in 1936. A distinction is made between:

  • Classical scrapie

Since the discovery of atypical scrapie, what has now been named "classical" scrapie covers multiple different strains. They may be differentiated through biochemical techniques (screening for PrPres then analysing its properties) or through inoculation of a laboratory animal (different incubation times, variations in the distribution of lesions within the central nervous system). Some sheep have been found to be naturally resistant to classical scrapie. This natural resistance is used in a national genetic selection plan to combat classical scrapie.

Disease transmission in livestock farming conditions can occur between animals (horizontal mode), or from one generation to another (vertical mode).

  • Atypical scrapie

Identified some ten years ago among sheep and goats, atypical scrapie has now been reported in numerous countries since the establishment of active surveillance programmes.

The biochemical properties of the abnormal protein associated with this disease appear to be identical in all the animals identified in the field, and are quite distinct from those found with classical scrapie strains. The pathogen causing the disease does not appear to be contagious or is only slightly contagious in livestock farming conditions.

BSE in small ruminants

Like cattle, small ruminants were exposed to contaminated meat-and-bone meal through their feed. The BSE agent has also been shown experimentally to be orally transmissible to small ruminants. In France, a single case was described in a goat in 2005 (another single case was later described in Scotland). Despite strengthened screening in 2005 (for goats) and 2006 (for sheep), no other cases were detected in France. The prevalence of this disease in the small ruminant population appears to be extremely low.

Other animal TSEs

Other animal TSEs have been described in the past, such as mink spongiform encephalopathy and feline spongiform encephalopathy (resulting from transmission of the BSE agent via food). Chronic wasting disease (CWD) in certain species of deer has been known in North America since the 1960s. New cases of the disease have been reported in reindeer, elk and a red deer in northern Europe (Norway, Sweden and Finland) since 2016. Lastly, a new TSE was identified in 2018 in dromedaries in Algeria and Tunisia.

Main risk management measures for animal TSEs

In France, the ban on meat-and-bone meal for cattle feed was introduced in July 1990. It was then extended to all ruminants in June 1994. In July 1996, the most hazardous tissues (specified risk materials or SRMs, cadavers) were excluded from the manufacture of this meat-and-bone meal for other species (pigs and poultry). Pressurised heat treatment was introduced in 1998 to reduce the potential infectivity of these products.

Despite this, other cattle, born after the introduction of these measures, have developed BSE. These cases were due to a lack of rigour in the application of regulatory measures and/or cross-contamination between the cattle feed industry and other industries (pork, poultry) that were still able to legally use meat-and-bone meal. To remedy this, the ban on meat-and-bone meal was extended to all livestock species at the end of 2000 in France, preceding the European ban by several months.

Since the early 2000s, the main European Union management measures have focused on several areas: 

  • Ban on the use of processed animal protein in feed

Processed animal protein (PAP) is derived from animal carcasses fit for human consumption. It was banned for use in livestock feed in Europe in 2001. Since 2013, pig and poultry PAP has been re-authorised for aquaculture. The European Commission is also planning to re-authorise pig PAP for poultry feed, and vice versa.

  • Removal of specified risk material

This is the tissue with the highest levels of prions in an infected animal (e.g. the central nervous system). It is systematically removed from each slaughtered carcass and destroyed.

  • TSE surveillance

The use of rapid BSE diagnostic tests was introduced in late 2000 on cattle slaughtered in abattoirs and rendering plants. This "active" surveillance enabled development of the BSE outbreak to be monitored, because most cases were not detected merely through surveillance of clinical cases (passive surveillance);

In 2002, an active surveillance plan was set up for small ruminants. Covering a sample of the sheep and goat populations, the scheme monitored trends in the prevalence of the different sheep and goat TSEs such as scrapie.

  • Animal health measures

When a case of BSE or scrapie is detected, specific surveillance or management measures apply in the herd from which the animal originated:

For cattle herds, animals of a similar age to the detected case have potentially been fed the same contaminated feed. These animals are therefore slaughtered and disposed of as unfit for consumption.

For flocks of small ruminants, different measures are applied depending on the background of the case animal (whether it was born in the flock or imported), its genetic sensitivity to the infection, and the type of TSE strain identified.

What is ANSES's role?

Expert appraisals

ANSES, supported by its expert groups, provides the competent authorities with the scientific and technical expertise required to make decisions on TSEs. It has conducted several expert appraisals on TSE risk assessments, for example: 

 

National reference mandate

ANSES’s Lyon Laboratory is France’s National Reference Laboratory for animal TSEs. It is therefore responsible for the techniques used to diagnose TSEs in animals and conducts research on this subject. It also conducts research on TSEs themselves (emergence of strains, chronic wasting disease in deer, etc.)