France announced last month a new case of bovine spongiform encephalopathy (BSE), popularly known as “Mad Cow Disease,” in a four year old female cow. This is the first case of this type of BSE in France since 2011, but follows on the heels of two other cases in Europe just last year, one in Ireland and the other in Wales. BSE cases are very rare today, but the French case raises some interesting, and slightly disturbing, questions.

BSE is caused by the abnormal folding of a type of protein, called a prion, which is common in nervous tissues of cattle, humans, and other animals. Much remains to be learned about this process, and some speculate that a virus or bacteria may be involved in catalyzing the transformation of normal prions. But no good candidates have been found so far.

When these abnormal prions interact with normally-folded prions, the latter also become abnormal. The misshapen proteins grow in number, creating cavities that give a characteristic “spongy” appearance to the brain under a microscope. As the abnormal prions are made by the affected animal’s own body, the immune system mounts no response, making it difficult to diagnosis BSE prior to death.

From the time abnormal prions begin to form in cattle, it typically takes anywhere from 2 to 8 years for clinical signs to appear. These include abnormal walking, tremors, aggressive behavior, and/or weight loss, followed by inability to stand, coma, and death usually within six months of the first signs of illness.

Where did BSE Come From?

BSE was first recognized in UK cattle in 1984-86, though cases may have been present as early as the 1970s. The disease spread throughout the UK and, to a limited extent, in a few other countries, peaking in 1993 with around 1000 BSE cases reported each week.

It was hypothesized that BSE occurred when cattle consumed meat and bone meal (MBM), a common feed supplement, contaminated with abnormal prion proteins from slaughtered cattle with BSE. These prions proved highly resistant to heat, ultraviolet and ionizing radiation, and other procedures that were hoped might inactivate the prions in feed. As a result, in 1988 the UK government banned the use of proteins originating from cattle or any other ruminants (particularly sheep and goats) as an ingredient in all ruminant feeds.

This protein feed ban had the intended effect. After more than 37,000 BSE cases in the UK in 1992, the incidence fell steadily over the coming years, to fewer than ten per year by 2011. By the time the situation was under control, over 184,000 BSE cases had occurred in the UK and another 6000 or so elsewhere in the world. These affected Ireland, France, Portugal, Spain, Germany, and Switzerland most, though Canada (18), the US (4), and Japan (37) have each had a few cases, often related to cattle imported from the UK.

BSE cases outside of the UK, however, did not peak until 2002, a full ten years after the UK peak. This may be partly due to the UK’s policy of exporting to other countries its banned MBM and other animal products, with little or no warning that they may have contained prions that cause BSE.

Humans: Cannibals and other Carnivores

BSE was a big deal when it was identified in 1986. But it would not have attained the media attention it did had the disease not begun to cause disease in people too. No human cases were known early on, but when a few cats fed BSE-contaminated food acquired the disease and died, speculation emerged that people may be able to acquire BSE in the same way. As a precaution, in 1989 cattle tissues in which prions may be found (brain, spinal cord, spleen, thymus, tonsils, and intestines) were banned from human foods. But it was too late for some. The first cases of the disease in people began to appear in the mid-1990s.

Humans (along with several other mammal species) have long had their own forms of prion disease very similar to BSE in cattle. One is called Creutzfeldt-Jakob disease (CJD). As with cattle, one way of getting CJD is consuming contaminated tissue, in particular brain, from an affected person. Some societies practicing cannibalism, such as the Kuru people of New Guinea, lost up to 1% of their population to CJD each year. They have now stopped the ritualistic consumption of their dead that spread the disease.

Yet CJD occurs occasionally in non-cannibalistic peoples too. This “sporadic” form of CJD seems to affect about one person in a million around the world each year, and the spark that leads to abnormal folding of the victims’ prions is unknown.

In 1995, when two teenagers and a woman in her 20s were diagnosed with CJD in the UK, alarm bells sounded. “Sporadic” CJD typically occurs in people over 60 years of age, and almost never in those under 40. Other aspects in these and other new patients were also different. While behavioral changes such as depression, anxiety, and hypersensitivity to pain appeared similar to the sporadic CJD, neurological symptoms demonstrated a later-than-expected onset, and included difficulty walking and talking, tremors, and dementia. And patients lived with their symptoms on average for just over a year before death occurred, much longer than the 4-5 months of sporadic CJD patients. It was strongly believed that these recent cases resulted from consumption of foods contaminated with BSE. This new form of CJD was dubbed variant CJD, or vCJD.

I lived in France in the 1990s when these first human cases occurred in the UK, and soon afterwards in France. Rumors ran wild and many people were convinced the disease would end up killing millions of people within a few years. Fortunately this has turned out to be unlikely.

vCJD peaked in the UK in 2000 when 28 cases were reported, then steadily declined to zero in 2012. In total, 229 cases including 27 in France and five or fewer cases in ten other countries have occurred to date. This compares to an average of 63 cases of “sporadic” CJD every year in the UK alone. So BSE-induced CJD, even at its worst, did not affect nearly the number of people that sporadic CJD does.

Sporadic Cases Continue

I mentioned for a reason the age of the cow recently diagnosed with BSE in France. She was born in 2011, more than a decade after France banned the incorporation of meat and bone meal in ruminant feeds.

Similar to humans, cattle also have a form of BSE that is so rare it is considered to be “spontaneous” in nature and does not require consumption of BSE-contaminated feed. However this possibility was dismissed in the recent French cow when her abnormal prions were tested and shown to be incompatible with this form of the disease (one such case, however, was found in France in 2014).

The French are considering 4 explanations in this recent case:

1. BSE-contaminated tissues somehow made it into the animal’s feed (considered highly unlikely given the long-standing ban on animal proteins in ruminant feed)

2. Vertical transmission of BSE, i.e. from mother to daughter in this case (considered very unlikely in that vertical transmission of BSE has been suspected in only a very few cases and never proven, and given that the mother in this case was slaughtered in 2015 with no signs of BSE)

3. The existence of an unidentified form of “spontaneous” BSE that closely resembles the form of BSE thought to be induced by consumption of BSE-contaminated feed (possible, but very difficult to prove)

4. A genetic predisposition of the cow to acquire BSE (only one such case has been identified before)

The mystery behind this recent case of BSE in France may never be answered. And there will be other isolated BSE cases posing similar questions. In the meantime, France will await to see if its international status as a country with “negligible BSE risk,” obtained only 7 months ago, will change, leading to potential trade restrictions.

 

References

Baron, T., Biacabe, A-G., Calavas, D. (2016). Un Cas d’ESB classique chez un bovin né en 2011. Plateforme ESA.

“Bovine Spongiform Encephalopathy.” Technical Fact Sheet. Center for Food Security and Public Health, May 2012.

Collinge, J. (2008). Lessons of kuru research: background to recent studies with some personal reflections. Phil. Trans. R. Soc. B., 363, 2689-3696.