What are ESTs?
Transmissible spongiform encephalopathies (TSE), 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, camelids), as well as humans. They are caused by prions, also called in the past “unconventional transmissible agents (UCTA)”, as opposed to conventional biological agents (bacteria, viruses, parasites, moulds).
Prions (acronym for Proteinaceous Infectious Only Particle) are made up of a particular protein, the PrP protein. During TSE, the normal shape of this protein undergoes major shape changes and becomes pathological. Once the process has been initiated, it is able to transmit this anomaly to other PrP molecules, this anomaly propagating in the affected organism, mainly in the central nervous system.
Prions are particularly resistant to conventional inactivation processes, such as temperature. TSEs are always fatal and no therapeutic treatment yet exists.
ESTs are characterized by a long incubation period (generally several years, up to 40 years in humans). The lesions observed are located in the brain and form cavities within the neurons, hence the spongiform nature of these diseases.
Some of the TSEs can be transmitted through food. Thus, mad cow disease (BSE), in its classic form, was linked to the ingestion by cattle of contaminated animal meal which was used in their diet. In humans, variant Creutzfeldt-Jakob disease is caused by the BSE agent transmitted through the consumption of tissue, particularly nerve tissue, from infected animals.
The different types of EST
In man
Creutzfeldt-Jakob disease
This disease, described since 1920, exists in the form of isolated cases (the most frequent, without apparent cause), genetic (mutations in the sequence of the prion protein gene), or iatrogenic (contamination via a transplant, a surgical intervention affecting the central nervous system, or the use of contaminated human growth hormone, now prohibited).
Variant Creutzfeldt-Jakob disease (vCJD)
Identified in 1996 in abnormally young patients and showing clinical signs distinct from the classic forms of Creutzfeldt-Jakob diseasethis TSE is the result of human contamination by the bovine spongiform encephalopathy (BSE) agent.
Other human ESTs
Kuru (Papua New Guinea), Gerstmann-Sträussler-Scheinker syndrome, or fatal familial insomnia have been described.
In animals
Bovine spongiform encephalopathy (BSE)
- Classic BSE
First identified in 1986 in the UK, the number of affected cattle then increased dramatically in the UK to a maximum in 1992, with 37,280 affected cattle identified in that year alone. This disease affected the rest of Europe, then certain other countries (Japan, United States, Canada) without however reaching the size of the British epizootic. Epidemiological studies quickly identified that the agent of this disease was transmitted through contaminated meat and bone meal (MBM)introduced into cattle feed.
- Atypical BSE
From 1986 to 2004, the BSE agent was believed to be unique with an invariant prion biochemical signature in all detected cases. In 2004, two new biochemical profiles were however highlighted, corresponding to what was subsequently called atypical BSE. Few scientific data concerning the distribution of this prion in the tissues of these animals or the epidemiology of these forms are available. The regular appearance of such cases at very low frequency suggests that they might be spontaneous.
Sheep and goat scrapie
Scrapie is a common TSE in sheep and goats, described since the XVIIIth century and present in many countries. Historically, it is the first TSE for which the transmissible character in animals might be established in 1936. We distinguish:
- classic scrapie
Scrapie, described as “classic” since the discovery of atypical scrapie, includes multiple distinct strains. These can be differentiated by biochemical techniques (search for PrPres and analysis of its properties) or by inoculation into the laboratory animal (different incubation time, variations in the distribution of lesions within the central nervous system itself ). Some sheep have been found to have a natural resistance to classical scrapie. This natural resistance is used as part of a national genetic improvement plan to control classical scrapie.
The transmission of the disease in farming conditions can be done between animals (horizontal mode), or from one generation to another (vertical mode).
- atypical scrapie
Identified for regarding ten years in sheep and goats, it is now described in many countries since the implementation of active surveillance programs.
THE biochemical properties of the abnormal protein associated with this disease appear identical in all the animals detected in the field and clearly distinct from those demonstrated with the strains of classical scrapie.
The agent of this disease seems little or not contagious in breeding conditions.
BSE in small ruminants.
Small ruminants, such as cattle, have been exposed to contaminated animal meal through their diet. Furthermore, the BSE agent is experimentally transmissible by the oral route to small ruminants. In France, a single case was described in goats in 2005 (a single case was described in Scotland subsequently). Despite increased screening during 2005 (for goats) and 2006 (for sheep), no other case might be detected in the territory. The prevalence of this disease in the small ruminant population appears to be extremely low.
Other animal ESTs
Other animal TSEs have been described in the past, such as mink spongiform encephalopathy, or feline spongiform encephalopathy (resulting from transmission of the BSE agent via food). Chronic wasting disease affecting certain species of deer has been known since the 1960s in North America. New cases of this disease have been reported in reindeer, elk and red deer in northern Europe (Norway, Sweden and Finland) since 2016. Finally, a new TSE was identified in 2018 in camels, in Algeria and in Tunisia.
Main risk management measures related to animal TSEs
In France, a 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 at risk (specified risk materials or SRM, corpses) were excluded from the manufacture of these meals intended for other species (pigs and poultry). Heat treatment under pressure was introduced in 1998 to reduce the potential infectivity of these flours.
Despite this, other cattle, born following these measures were put in place, developed BSE. These cases are the result of a lack of rigor in the application of regulatory measures and/or cross-contamination between the cattle feed sectors and the other sectors which might still legally use animal meal (pork, poultry). To remedy this, measures banning animal meal were extended to all cash crops at the end of 2000 in France, a few months before the ban at European level.
Since the beginning of the 2000s, the main community management measures have revolved around several axes:
- Bans on the use of processed animal protein in animal feed
Processed animal proteins come from animal carcasses suitable for human consumption. They were banned for farm animal feed in Europe in 2001. Since 2013, PAPs from pigs and poultry have been re-authorized for aquaculture. The European Commission also plans to re-authorize PAP from pigs for poultry feed and vice versa. - Removal of Specified Risk Materials
These are the tissues in which the presence of prion is most important in an infected animal (for example the central nervous system). They are systematically removed from each slaughtered carcass and destroyed. - Monitoring of TSEs
The use of rapid BSE diagnostic tests was introduced at the end of 2000 on cattle slaughtered in slaughterhouses and for rendering. This so-called “active” surveillance system makes it possible to follow the evolution of the BSE epizootic, since most cases were not detected by simple surveillance of clinical cases (passive surveillance). In 2002, active surveillance was put in place for small ruminants. Carried out on a sample of the sheep and goat populations, it makes it possible to monitor changes in the prevalence of the different sheep and goat TSEs, such as scrapie. - The health policy
When a case of BSE or scrapie is detected, specific surveillance or management measures apply in the herds from which the animal comes:- for cattle herds, animals close to the age of the detected case potentially received the same contaminated feed. These animals are therefore slaughtered and removed from consumption;
- for herds of small ruminants, different measures are applied depending on the history of the case (born in the herd or nomadic), the genetic susceptibility of the animals to infection, and the nature of the TSE strain identified.
What is ANSES’s role?
La production d’expertise
ANSES, supported by its groups of experts, provides the competent authorities with the scientific and technical expertise necessary for decision-making on TSEs. It has thus provided several expert assessments of the risk associated with TSEs, for example:
A national reference mandate
In addition, the ANSES laboratory in Lyon holds the mandate of national reference laboratory for animal TSEs. It is thus responsible for the techniques used to diagnose TSEs in animals and conducts research on this theme (emergence of strains, chronic wasting diseases of deer, etc.).
