The Case for Continued Surveillance of Human Prion Diseases

Rare Mad Cow Disease Group Triggers Neurological & Neuromuscular Degeneration

Human prion diseases are very rare, yet there exists the potential risk of spontaneous infection, as well as disease acquired due to certain human behavior patterns. Prion disease exposure may be associated with travel to regions where such diseases have occurred in the past, medical treatment/surgery with the risk of blood contamination, eating infected meat or even the handling of infected animals. The mad cow disease (bovine spongiform encephalopathy or BSE) is reported to be the cause of the human disease (variant Creutzfeldt-Jakob disease or vCJD); moreover, there are other animal prion diseases (such as chronic wasting disease among deer and elk) that may not have been eradicated totally. Such factors need to be considered when debating the importance of continued prion disease surveillance, and this article discusses these in detail.

Clinical Features

Currently known human prion diseases include sporadic, familial (inherited) and iatrogenic Creutzfeldt-Jacob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and variant CJD. Better known as transmissible spongiform encephalopathies (TSEs), brain pathology involves the conformational switch of the harmless cellular prion protein (PrP-c) to its harmful isoform PrP-sc that is partially protease-resistant and infectious (see Figure 1). Abnormal changes in the prion protein cause deterioration in certain brain areas, forming sponge-like holes and gaps (thus, the term spongiform encephalopathy). In CJD, this degeneration results in the progressive neurological and neuromuscular symptoms – rapid loss of intellectual abilities, impaired memory and judgment and distinct personality changes (dementia). Later stages of the disorder may be characterized by loss of physical and intellectual functions, coma, and increased susceptibility to repeated infections of the respiratory tract (such as pneumonia). In many cases, life-threatening complications tend to develop less than a year after the disorder becomes apparent.

FIGURE 1: Disease-causing form of the prion protein in the brain.

Origin of CJD

While data is available on the epidemic of variant CJD, it is unclear what caused the first case(s), be it sporadic or variant. Several studies of this rare disease were unable to show an exact association between disease risk and beef/sheep meat consumption. About 90% of CJD cases occur randomly for no apparent reason (sporadic CJD). The remaining 10% present with a hereditary predisposition (familial CJD), suggesting an autosomal dominant mode of inheritance. All forms of CJD are transmissible, even those which are genetically determined. However, if CJD occurs through a spontaneous mutation, it could occur in both vegetarians and non-vegetarians and avoiding meat consumption may not protect against the sporadic form. Even today, sporadic CJD has an unknown etiology and an incidence of around 1/1 million population per annum throughout the world (Incidence and Prevalence Database,

Is it Mad to Eat Meat?

The variant form of CJD, first reported in the United Kingdom, affected younger people (median age at onset: 28 years) more so than did classic CJD. In 1996, the possibility that variant CJD might be associated with beef consumption from cows with a related infectious brain disorder (bovine spongiform encephalopathy, BSE, or mad cow disease) came under scrutiny. BSE, first identified in the U.K. in 1986, showed a peak in reported cases in the winter of 1992-93, with up to 1,000 new cases reported each week. It is speculated that the time period (late 1980s to 1990s) exposed the human population to the BSE agent, consistent with variant CJD cases diagnosed after an incubation period of about 10 years, similar to other prion diseases. Besides the U.K. several other European countries also reported cases of variant CJD, triggering scientific research and debate concerning the potential link between BSE and variant CJD.

Cows with BSE experience rapidly progressive neurological and neuromuscular symptoms similar to those associated with CJD in humans, and abnormal changes in prion proteins are also thought to play a role in the brain degeneration associated with BSE. Concerns that another TSE, scrapie, might be the causative agent of BSE were negated due to the relatively late emergence of BSE; moreover, unlike BSE, there was no evidence that scrapie transmitted to humans despite ongoing exposure to infectivity. The observed progressive rise or rise and fall of BSE cases in affected countries suggested an acquired cause for this disease rather than an intrinsic origin via spontaneous gene mutations within one or more individual animals. One hypothesis presumed that imported animal feed way back in the 1960s was contaminated with human TSE.


In the U.K., the feeding of mammalian meat and bone meal to farm animals has been banned since 1996, and across much of the European Union since 2001. The variant CJD outbreak that peaked in year 2000 is now in decline and there have been no new cases in the U.K. or elsewhere since 2013.


Whereas the epidemic of classical BSE has ended, the chances of new sporadic BSE cases still exist and may lead to future human prion disease incidence. By the summer of 2002, up to 97 people in Great Britain had died or were dying from the new variant of CJD since it was first identified in 1996. All of the cases identified in England had a particular genetic trait (not a mutation) that may have predisposed them to the condition. The genetic abnormality involved a variation of the prion protein and about 40% of the British population have this genetic trait. Moreover, iatrogenic cases open up the possibility of new infections from procedures such as blood transfusions and surgeries, especially in a population with a significant number of genetic carriers.

Ongoing research experiments confirm the transmission of classical sheep scrapie strains to humanized mice and primates, and while these are atypical/unnatural hosts, results indicate the zoonotic potential of small mammals. In certain regions of the U.S., larger animals such as deer and elk have been infected in the past and hunters need to handle with care any animal that appears to be sick, and take precautions such as wearing gloves.

In this scenario, continuation of detailed surveillance of human prion disorders would be prudent when considering all these questions that still need scientific research to better understand the transmission of neurodegenerative prion diseases.