Australian Study Suggests Millions of People
May Be Incubating Mad Cow-Like Diseases

Morning Herald (Sydney)Date: 09/09/2000

Dormant but deadly

Animal experiments have revealed a silent carrier role for a deadly prion
disease in mice which may point to dire consequences for humans. Jennifer
Cooke reports.

Dr Andrew Hill realised the implications immediately. A flurry of calls
from the animal house to the lab where he worked in London early last year
warned of eight mice with signs of prion disease. It had been assumed for
years that this could not happen.

But not only did these results show new evidence for a "sub-clinical" or
undetectable form of disease in mice; they lent credence to theories that
mad cow disease could be carried silently by apparently healthy cows and
that humans incubating the mad cow-related new variant Creutzfeldt-Jakob
disease (vCJD) may infect surgical and dental patients through contaminated
instruments.

All prion disease experiments are lengthy and these important findings,
published last week in the Proceedings of the National Academy of Sciences,
capped years of lab work.

More than four years ago, Hill and colleagues at the Medical Research
Council Prion Unit in London, headed by Professor John Collinge, began an
experiment in which 20 normal mice were injected with the mulched-up brains
of hamsters who had died from one strain of the prion disease called scrapie.

There are more than 20 known strains of scrapie, which is endemic in
British sheep flocks. Scrapie is believed to have given rise to the
epidemic of mad cow disease or bovine spongiform encephalopathy (BSE) that
began around 1985 and has since spread to Europe.

More than 20 years ago researchers had noted that mice lived a full life
with no apparent disease despite being injected with hamster scrapie. The
assumption had been that this strain could not be passed on to mice.

But Hill and his colleagues took that old experiment a step further and
injected the liquefied brain matter of these apparently healthy mice, into
another bunch of healthy mice and hamsters - just to confirm that there was
no disease present.

It was supposed to be a simple control experiment but, to the shock of
everyone involved, the mice and hamsters started staggering around their
cages five months afterwards, indicating that prion disease had taken hold
and spongy holes had begun destroying their brains. What's more, the mice
had produced their own lethal prions, which were different from the hamster
prions injected into the original 20 mice.

The control experiment had evolved into a major finding itself. It proved
that those original 20 mice had been silent carriers of the disease and
were able to pass it on.

A new-generation test in which proteins are examined to identify the
molecular signature of different prion diseases also confirmed the presence
of high levels of prions in the brains of those mice.

If the same were found to be true of cattle, then many cows in Britain, and
other European countries where it has surfaced may be silent carriers of
the related BSE.

Diseased cattle may then freely enter the human food chain and escalate
what is fast becoming a mini-epidemic of the human equivalent, vCJD.

Test findings published in 1998 showed that vCJD had an identical molecular
signature to BSE - as close to absolute proof as is likely, experts say,
that BSE caused the disease in humans.

Species including poultry, pigs and sheep were also exposed to BSE in
Britain from the cannibalistic feeding practices of the 1980s when dead
sheep and cows were ground down into cakes of meat and bonemeal protein
supplements. Speculation now surrounds whether those species might also be
capable of harbouring symptom-free prion disease.

The most worrying implication of all is that transmission could occur from
silent animal carriers to humans and then to other humans.

No test is sensitive enough yet to detect rogue prions in a person who has
no symptoms of vCJD (or any other type of CJD).

If the mice experiments prove in future to be applicable to cows, and thus
humans, as BSE has already shown, then anyone who has been exposed to
prions from mad cows has the potential to be a silent carrier. Include in
this group British migrants (fed on baby food or at British schools, in
particular), returned expatriates, and possibly even tourists who indulged
in the English passion for pies, hamburgers, sausages or beef products that
included brain and spinal cord material - the most infectious parts.

And if that were the case, the potential would in turn loom large for
transmission between humans via CJD-contaminated surgical instruments and
tissue donations - routes via which another type of CJD has already killed
neurosurgical patients and recipients of corneas and pituitary-derived
human growth hormone.

The infectious agent that causes CJD cannot be removed by hospital-standard
sterilisation or cleaning techniques, although infectiousness can be reduced.

So far, no transmission has occurred through organ donations. And blood and
plasma derivatives are not believed to be implicated in the transmission of
any type of CJD. However, the fear with vCJD, which can be detected in
tonsil and appendix tissue, is that it might behave differently (having
sprung from animals) and pose more of a threat.

Tighter restrictions on blood transfusions and wider use of disposable
surgical instruments are among the anti-vCJD measures introduced over the
past two years in Britain alone, to reduce the risk of spread between humans.

Earlier this year the United States, Canada, Austria and New Zealand also
banned blood donations from anyone who lived in Britain for longer than six
months between 1980 and 1996. Canada last week applied the same ban to
those who had lived in France.

Australia has followed suit on the grounds of the small, theoretical risk
of CJD transmission via blood and fears of diminishing an already small
pool of vital donors.

Only this year, nine neurosurgery patients at the Royal Melbourne Hospital
were potentially exposed to CJD when instruments used on a patient later
found to be suffering from CJD were reused. CJD was not initially suspected
in the patient so the normal procedure of quarantining the instruments for
later destruction, if CJD was confirmed, was not followed.

Just last month, to head off a similar occurrence with vCJD in Britain, the
Department of Health announced that surgical instruments used in tonsil,
appendix and brain operations are to be destroyed after one use in a move
likely to cost millions of pounds.

At the pathology department of the University of Melbourne researcher Andy
Hill, has been dogged by calls from the British media over the past week
concerned at what his work might mean.

"The bottom line," he says of the implications of the mice experiment that
sparked it all, "is that healthy cattle may harbour infectivity and never
show any signs of BSE. It is entirely possible that, in the same way,
humans might be harbouring the disease at this sub-clinical level. As we
don't know how many people may be incubating the disease - which may be
longer than the normal lifespan - then there are possible implications for
medical and surgical procedures."

In the five years since its discovery in two British teenagers, vCJD has
been reported in 79 people in Britain, two in France and one in Ireland.
Alarmingly, 36 of those were reported in only the past year.

Despite the introduction of a series of controls dating from 1989,
including a ban on the most infective cattle offals entering food, a bar on
cattle over 30 months old being used for food, and an end to feeding cow
and sheep remains to other meat-producing livestock, they were not policed
effectively and the BSE epidemic was not contained quickly.

A devastating report on the British Government's inadequate role in
guarding public health is expected from The BSE Inquiry, a two-year-old
probe into the handling of the BSE epidemic up to 1996. It is due within
weeks - about the time of the next meeting of the Spongiform
Encephalopathy Advisory Committee (SEAC) at which scientists may yet decide
to re-examine controls against vCJD.

The British Government, which denied for a decade until 1996 that British
beef was anything but perfectly safe to eat, has spent the past week
confidently asserting that existing measures are more than adequate to
guard against the possibility of silent BSE cases.

Hill's old boss, Professor John Collinge, also an SEAC member, is not in
total agreement.

"My own view is that probably the 30-month rule and the offal ban would
still protect us from [BSE] but I am not sure," he said.

"This data shakes me up a bit."

Jennifer Cooke is the author of Cannibals, Cows & the CJD Catastrophe,
which won last year's Eureka Science Book Prize.

http://www.smh.com.au/news/0009/09/text/review5.html