Human Risks and Preventative Measures

What is the risk that BSE will infect humans?

It appears the risk of infection is dependent on:.

1. Susceptibility to infective agent. Susceptibility depends on both species differences and within species protein sequence variations.
2. Dose of infective agent

The possibility of human transmission of BSE no longer an open question. It is widely accepted that BSE can be transmitted to humans and indeed has occurred.

However, there is a statistical species barrier that depresses cross-species transmission of BSE to man?

The concept of a "Species barrier" is based on the observation that interspecies transmission is less efficient than within species transmission:

• For example, titres for transmission of BSE to mice are 10⁷, but for mouse TSE transmission to mice of different strains is 10⁴.
• This would suggest a intra-species genetic barrier as high as 1:1,000 .

Based on this information, minimal barriers between species would be at least as high as the 1:1000 barrier within a species, but probably higher.

Within humans, we know that prion codon 129 polymorphism (either Methionine (M) or Valine (V)) predisposes individuals to CJD.

• The distribution of the polymorphism in the Caucasian population is:
  • 12% V/V, 37% M/M, 51% M/V
• The distribution of these polymorphisms in individuals who have Sporadic CJD risk is:
  • 69% V/V, 25% M/M, 6% M/V
  • thus homozygousity for either V predisposes individuals to sporadic CJD
  • homozygousity possibly favors interactions between homologous proteins favoring the conversion of PrP to PrP^Sc
• The distribution of these polymorphisms in individuals who have iatrogenic CJD from human cadaver growth hormone is:
  • 50% V/V, 31% M/M, 19% M/V
  • thus homozygousity for either V again predisposes individuals to iatrogenic CJD
  • homozygousity possibly favors interactions between homologous proteins favoring the conversion of PrP to PrP^Sc
• The distribution of vCJD patients examined is:
  • 100% M/M
  • Thus heterozygosity at codon 129 (M/V) or homozygosity for V (V/V) may protect individuals from CJD
  • The M129 in bovine PrP^Sc probably favors interaction between the bovine protein and human PrP M129 thus allowing the interaction of the two proteins from different species and the conversion of human PrP M129 to human PrP^Sc M129
  • Since sheep scrapie PrP^Sc M129 does not appear to be transmitted to humans, additonal species barriers exist other than those associated with PrP sequences

Human PrP V129 protects mice from BSE but not CJD

• Transgenic mice (mPrP M129) with a human transgene (hPrP V129) develop prion disease when challenged with an isolate of human prions from a CJD case
• Mice expressing only hPrP V129 (no mPrP; produced by breeding PrP null mice with human PrP V129 mice) developed disease with a much shorter incubation time
  • thus the heterozygosity of mouse M129 with human V129 in the first test delayed the onset of CJD in mice
  • the homozygosity for hPrP V129 in mice elevated the risk for CJD infection (as it does for sporadic and iatrogenic CJD in humans)
• Transgenic mice (mPrP M129) challenged with BSE appeared to produce mouse PrP^sc, ie. contracted BSE.
• Mice expressing only hPrP V129 then challenged with BSE remained symptom free at the conclusion of the study, 60 days longer than the time required for the appearance of CJD in mice of this genotype .
  • thus the hPrP V129 was probably unable to interact with bovine PrP^Sc M129 and thus transmit the disease
  • but the mPrP M129 was able to interact with BSE PrP^Sc's

Biochemical properties of the prion protein make it possible to trace the likely cause and similarities of non-familial vCJDs .

When prion protein chemical signature tests were applied to brain tissue samples from 26 human patients who had died from all four forms of CJD and compared with samples of tissue from laboratory animals who were experimentally infected with BSE

• the patterns for familial, acquired and sporadic CJD were similar
• the patterns were different from the BSE pattern
• However, the vCJD pattern was similar to the BSE pattern.

Scrapie is very common in sheep while TSE type diseases are very rare in humans. If BSE were transmitted to man, the clinical disorder would probably resemble CJD or Kuru. Theoretically, the greatest risk to man would be by direct infection through injection of products derived from bovine brain or lymphoid tissue.

Because prion diseases lack immunological involvement in host animals, for human infection with the BSE agent

• infants and children are not likely to be more susceptible than adults
• similarly, hospital patients, pregnant women and people taking immunosuppressive drugs would not be expected to have a greater risk.

How much exposure to BSE infective material has there been?

With the exception of brain and spinal cord, and more recently, the retina, all other tissues and secretions from confirmed BSE cattle have failed to transmit the disease when either injected into or fed to mice. In particular, milk and beef meat have not caused the disease in experimentally infected animals.

Prior to the 1989 SBO ban in Great Britain, some 446,000 BSE-infected animals likely entered the food chain and were consumed. Between 1989 and 1995 when there was about a 50% compliance with the SBO ban, another 283,000 BSE-infected animals entered the food chain. It has been estimated that 3-5% of the animals that entered the food chain were BSE infected.

Scrapie infectivity is about 10⁷ LD₅₀ / g wet tissue when administered by the intracerebral route. Infectivity seems about the same for BSE when administered to mice. The oral or gastric LD₅₀ = 100,000 intracerebral LD₅₀ doses (i.e. 10¹²).

Actual exposure remains an open, and perhaps unanswerable, question.

click on image for information concerning the dissemination of possible MBM containing BSE

World Health Organization (WHO) officials may be contacted to provide further information about health risks.