Following John's comments, there are a number of issues:

Upon infection by blood contamination (eg from transfusion), does the
prion live or die according to genetic predisposition?  Or is it that the
predisposition is to getting vCJD from infected blood?

There are therefore 5 states on getting infected blood:

1 Prion dies in all hosts
2 Prion lives 'benignly' in susceptible hosts only, dying otherwise
3 Prion lives 'benignly' in all hosts
4 Prion lives and leads to vCJD in susceptible hosts only.
5 Prion lives and leads to vCJD in all hosts

The concept of susceptibility is of course a matter of probability rather
than certainty - unless there is a clear mechanistic reason it is unlikely
that anyone is truly unsusceptible but the less susceptible an individual
is, the more likely s/he is of dying from other causes.  So 2 and 3 may be
considered the same thing with large variations between individuals,
likewise 4 and 5.

Scenarios 2 and 3 are more worrying in that if prions can carry on living
undetected as postmortems are not routinely carried out, this disease may
carry on presenting itself - and reproducing by chance cross-infection -
for many years or even generations to come and medical staff in particular
will be continually at risk.  At least in the third scenario, the symptoms
eventually reveal themselves so we will have a better estimate.

It is possible therefore that the tail of the distribution will be
stretched out to the right and that there will remain a very low incidence
of vCJD for a long time but, as John says, quantitatively at the level of
death by lightning strike.

Today's reports from French scientists that the young may be more
susceptible to vCJD is actually good news in a rather bizarre way if the
susceptibility is to prions living in a host.  Young people are much less
likely to have become blood donors.

Just some more thoughts.  Anyone for a 5 in 1 jab today?

(There is a paper at RSS 2004 here in Manchester 6-10 September on the
effect of individual heterogeneity on the future vCJD epidemic for those
interested - places still available at www.mbs.ac.uk/rss2004).

John

John Logsdon                               "Try to make things as simple
Quantex Research Ltd, Manchester UK         as possible but not simpler"
[log in to unmask]              [log in to unmask]
+44(0)161 445 4951/G:+44(0)7717758675       www.quantex-research.com


On Mon, 9 Aug 2004, John Whittington wrote:

> At 15:27 08/08/04 +0100, John Logsdon wrote (in part):
>
> >As I understand it, someone died not of vCJD but something completely
> >different yet vCJD prions were found in his lymph nodes and spleen.  He
> >had had a transfusion - presumably quite a long time ago - from someone
> >who subsequently died of vCJD in 1999.  The complication is that the
> >patient that recently died is of a different genotype to that for which
> >susceptibility to vCJD is thought and which comprises about 37% of the
> >population.
>
> I'm not fully up-to-speed on this, but are you sure that the
> genetically-determined predisposition is to having vCJD prions in one's
> body, rather than to having a susceptibility to developing  clinical
> vCJD?  If the later, what you describe would obviously be fully consistent
> - in that situation, it could be that this genotypically 'non-suscepitible'
> individual may never have developed clinical vCJD, even if he hadn't died
> of something else first.
>
> If that were the case, it would obviously mean that a 'carrier state' could
> exist in genetically non-susceptible individuals.
>
> >My underlying question is - what is the underlying epidemiological reason
> >for the explosion of interest?  Or is it just trying to keep the issue
> >alive and possibly increasing research funding?  I am not averse at all to
> >maintaining and increasing the research funding - the more money put into
> >science the better - but I don't think it warrants headline scare stories.
> >The Today program - that authority to which we all wake up - ran it as a
> >top story.
>
> I suspect that it's primarily a combination of academic interest in the few
> and the usual (often irresponsible) interest of the media in dramatic
> 'scare stories'.  In the early days of BSE/vCJD there were obviously
> serious concerns that a very high proportion of the population may have
> been infected (or, at least, exposed to BSE), leading to the possibility of
> a catastrophic disaster some years/decades down the road.  At that time,
> one could understand both scientists and the media taking the topic very
> seriously.  Now, however, that it seems that such a situation is extremely
> unlikely, and that we are talking about something that rivals the risk of
> 'death by lightning strike', it is much more difficult to see an objective
> justification for large investments in research or significant media interest.
>
> ... just my few initial thoughts!
>
> Kindest Regards,
>
>
> John
>
> ----------------------------------------------------------------
> Dr John Whittington,       Voice:    +44 (0) 1296 730225
> Mediscience Services       Fax:      +44 (0) 1296 738893
> Twyford Manor, Twyford,    E-mail:   [log in to unmask]
> Buckingham  MK18 4EL, UK             [log in to unmask]
> ----------------------------------------------------------------
>

******************************************************
Please note that if you press the 'Reply' button your
message will go only to the sender of this message.
If you want to reply to the whole list, use your mailer's
'Reply-to-All' button to send your message automatically
to [log in to unmask]
*******************************************************