Bovine Spongiform Encephalopathies
Bovine spongiform encephalopathy (BSE) is the most recent addition to the group of SE diseases and is an infectious disease transmitted orally to many other animals including humans. There is a clear evidence of maternal transmission although there is disagreement on the source of the BSE agent. The current theories link the origin of BSE to common scrapie in sheep.
All SEs can be experimentally transmitted from one species to another and therefore the term transmissible spongiform encephalopathies (TSEs) has become a general term.
From scrapie infected sheep, 20 different strains of the agent have been isolated. Cattle have selected out of the various "wild types strain" one, the single most virulent strain.
Like scrapie in sheep, in cattle there appears to be clear evidence of maternal transmission. This type of maternal/paternal transmission is also seen in AIDS.
The Origin of BSE: scrapie?
Since scrapie in sheep has existed for at least 250 years, a number of questions obviously need to be answered. How and why did a disease resembling scrapie suddenly erupt all over Great Britain? We have to answer whether infected animal feed was the only source of infection.
The current working theory links the origin of BSE to common scrapie. I believe this common strain is vaccine against BSE.
A search of literature shows two distinct clinical syndromes in sheep, both being called scrapie. Type 1 is an "itchy" type and Type 2 a "trotting" type.
Type 1 scrapie
Throughout the world, the itchy type is by far the most common. Most of the scientific research has been done on this type. The majority of clinical cases are seen in the 4 to 5-year age group and by that time they will have had four breeding seasons, producing 6 to 8 lambs. The majority of these lambs will develop the clinical disease due to vertical transmission of the agent.
To test whether Type 1 scrapie is the source of BSE, calves were fed with large quantities of Type 1 scrapie sheep brains. It is important to note that none of them developed clinical disease or showed any degenerative changes in the CNS. In comparison, calves inoculated or fed with 1 gram of BSE revealed much greater vacuolar degeneration.
In calves these were injected with brain tissue from infected sheep, a few developed a clinical disease but the clinical signs were not typical of BSE. Furthermore, none of the calves revealed spongy vacuolar changes in brains similar to those seen in BSE.
Type 2 scrapie
In the "trotting" type of scrapie, sheep suffer trembling and ataxia. The clinical disease appears in the 2-year age group and by that time they will have had only one breeding season, producing one or two lambs.
Sheep experimentally inoculated or fed with BSE brain tissue exhibited clinical signs very similar to those seen in Type 2 scrapie, such as locomotor incoordination and trembling.
In contrast to Type 1 scrapie, 100% of calves and mink develop clinical disease after feeding with BSE-contaminated tissue.
In its major clinical signs the "trotting" type resembles BSE, Kuru and nvCJD. This data indicates that BSE has been derived from the recycling of the "trotting" type and not from the common "itchy" type of scrapie.
These findings suggest that it is more than likely that sheep affected with Type 2 scrapie were shipped to New Guinea and consumed by the local population, causing kuru. The cannibalistic practice helped the disease to spread further.
Since more than 85 zoo animals of different species have been diagnosed with TSE, one can conclude that the BSE agent can affect almost all mammalian species and therefore man is at a greater risk of being infected than currently assumed.
Primary transmission from any species infected with TSEs to a different new host species might affect only a minority of animals and only after a prolonged incubation period. This species barrier may disappear with further passages in the new host, shortening the incubation period. The recycling of sub-clinically affected cows would at each passage increase the infective titre.
Indeed, in cattle, BSE incubation periods did reduce in steps from about ten years to five or six, then settled at two to three years and more recently rising again to over five years. This suggests that the agent has been derived from another species and has been passaged several times in cattle.
Prusiner: His views changed
Prusiner who earlier advocated the” protein only” theory, told a scientific meeting in Birmingham, in June 2000 that his colleague Mike Scott now believes that sheep carry two strains of the agent, the scrapie prion and the BSE prion. However, Prusiner says it is hypothetical at present that sheep is the source of the BSE agent. But Prof John Collinge believes his hypothesis is "flawed. There's no evidence, BSE came from sheep, and if the prion that causes BSE is there, we can't find it." It is obvious from the discussion during the Birmingham meeting in June 2000 that neither Prusiner nor any one else has real knowledge of the original source of BSE.
Comparison of scrapie and BSE strains
In 1988-1989, I realised that there were two important differences between BSE and scrapie:
1) Passage of BSE to mice was achieved with 100% efficiency both by inoculation and by feeding; scrapie is passaged with less than 50% efficiency.
2) Sheep in the UK are classified either scrapie-resistant (if they do not develop the disease on exposure) or scrapie-susceptible (if they do). Comparative transmission studies were done with these two different types of sheep infecting them with scrapie and BSE. The results unexpectedly revealed that both types of sheep are susceptible to BSE (both by injection and feeding). MAFF had known this since 1989 and SEAC since 1990, neither realised the importance of this experiment or do not want to admit the importance of this observation.
Comparison of scrapie sheep and BSE strains
Click on picture to enlarge
The point to stress here is that scrapie-resistant sheep are highly susceptible to the BSE agent. In consequence, BSE will be present in both sheep and cattle, placing human health at much greater risk.
In conclusion:
1) BSE and scrapie are different strains;
2) BSE is highly efficient, virulent and more dangerous and readily spreads by eating;
3) Breeding of the resistant lines of sheep might free the UK sheep flocks from scrapie while sheep will get infected with the BSE strain;
4) The BSE agent has the unique property of stability when passaged through different animal species.
The clinical symptoms of BSE
In the laboratory, SEs is diagnosed by finding spongy changes in brain sections. Vacuoles and the associated "spongiform" changes are well-entrenched diagnostic hallmarks of BSE and CJD.
On the farm, however, affected cows may demonstrate little more than bad temper and disorientation. The earliest symptom a farmer may observe is a "loss of seniority", where the affected cows gradually recede from their "pecking-order" position during the feeding and milking routines. It is clearly of paramount importance to be able to identify preclinical cases.
In 1987, I developed a so-called "touch technique" which could reveal whether asymptomatic cattle were incubating the disease. This has not been used even in random trials. In a random study, cow brains from apparently healthy cattle over four years old, being processed for the human food chain, were collected from a local abattoir for examination by the "touch technique" and about 29% were found positive. Granada’s “World in Action” reported this result in 1995. Testing would have prevented asymptomatic animals from becoming part of the human food chain.
The BSE epidemic
By June 1999, there were nearly 175,000 confirmed cases of BSE in Great Britain. It was originally estimated that the BSE epidemic would peter out in 1992 with 20,000 cattle developing the clinical disease. It is not possible to determine how many subclinical cases of BSE are being slaughtered or were slaughtered and went into the human food chain.
Feeding of sheep with meat and bone meal (MBM): On some farms in the UK before BSE was recognised, sheep were also being fed with small quantities of MBM. However, following the July 1988 ban on the use of MBM for cattle, MBM became very cheap. Some farmers fed their sheep extensively with BSE-contaminated MBM. This practice produced sheep infected with the "trotting" type of scrapie, including those sheep breeds which were resistant to the "itchy" type scrapie. The "trotting" type has therefore changed from being a minor strain to a major strain.
So far in the literature there has been no reported cases of Type II scrapie from the USA. This may explain why the USA does not have a recognised BSE problem despite having used similar rendering processes. It is probable that the USA may not have scrapie Type II. However, it appears carcasses from Type 2 sheep may have been used in mink feed, which have produced a few small outbreaks of TME.
The ban on contaminated food began in July 1988. This should have stopped that mode of infection. However, up to June 1999, 39,384 BSE cases had been confirmed in cattle born after the feed ban. MAFF attribute these cases to leftover contaminated feed being used illegally, the "bin end" theory.
In late 1996, after a delay of 8 years, MAFF also introduced ban on the use of MBM for pigs, poultry and fish.
Effect of heat on the agent
Why this disease appeared only in the 1980's? One big significant of the TSEs agent, which had intrigued us, has been the survival of the agent after boiling. The question has to be asked: can we really destroy this agent by heating?
The effect of heating inoculums at various temperatures has been checked using infective scrapie material. These experiments have shown that heating does destroy the agent. However, it is not completely killed. Even heating scrapie-infective brain at 121ºC for 15 hours revealed that one animal out of eight injected developed the disease in 285 days. Unheated material took 90 days to infect one animal out of eight. This demonstrates an increase in incubation period as infectivity is being destroyed.
In another study, a difference was observed between the drowsy strains where the titre was reduced 99% by levels of germicidal UV irradiation, whilst the same amounts of UV irradiation had no effect on hyper strains of the TME agent. The different heat resistant feature to heat during rendering process into MBM would also help a minor "trotting" type of the scrapie strain to become a major strain to produce BSE in epidemic form.
BSE in other countries
BSE has occurred in the Republic of Ireland where movement restrictions were placed and then a scheme of voluntary depopulation of the herds was introduced. Depopulation of affected herds formed a major difference between the UK and the Republic of Ireland.
Clinical cases of BSE were recorded in cattle exported to the Sultanate of Oman in two Jersey cows. BSE has also been confirmed in France, Denmark, Switzerland and the Falkland Islands.
Risk assessment on the possible occurrence of BSE in the United States has been carried out and despite intensive surveillance efforts for the past three years, no variant of this disease has been detected in the US cattle population. It is important to take into account the existence of two types of scrapie and it is also important to know whether any cattle remains were included with sheep carcasses in the preparation of MBM in the USA or other countries as appears to be the case in the British foodstuff. The details of this study can be found in my book "The Link".
Congenital/vertical transmission in BSE and scrapie
The evidence implicating a hereditary or congenital mechanism in the spread of scrapie among sheep has been suggested throughout the literature.
Since natural scrapie has never been recorded in some breeds of NPU Cheviot sheep, they were used as surrogate ewes for embryo transfer to investigate maternal transmission of scrapie in sheep and BSE in goats. In these experiments, donor ewes were infected with the scrapie agent and artificially inseminated six months later with semen from an uninfected but scrapie-susceptible ram. Embryos were transferred by laparoscope's into recipient ewes. The offspring were grazed on pasture never previously exposed to scrapie-infected sheep. Ten of the 26 lambs born of these surrogate ewes and all donor infected sheep eventually developed the clinical disease, while the surrogate ewes remained healthy. These studies conclusively reveal that eggs in the affected donor ewes carried the infective agent.
Since calves have been fed with contaminated MBM starting from 4 to 6 weeks old and throughout their life, it is more than likely that embryos in BSE affected cattle will be maternally infected. Based on these results it is very hard to predict what proportion of calves born of affected cattle would develop clinical BSE.
The continued epidemiological studies have revealed a fall in BSE cases in recent years, however, BSE is still being reported in BAB (born after the ban) cattle. The majority of these cases are most likely to be due to vertical transmission. Currently, in 1999, 94% of BSE cases being confirmed are in cattle born after July 1988 when the ruminant feed ban was imposed in the UK.
It is important to stress that beef cattle are normally slaughtered before 18 months of age while the minimum incubation period of BSE is now over 50 months. At this age not many cattle are alive to develop the clinical disease.