At 08:03 10/08/04 +0100, John Logsdon wrote:

>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?

That is, of course, the point/question I was raising - give or take my
reservations about the words 'live' and 'die' (see below).

>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

I thought there were documented cases of vCJD resulting from 'infected'
blood transfusion.  If that is the case, (1) and (3) would clearly not be
true.  (5) is contrary to the concept of individual 'susceptibility'
(however defined).  The question I raised, and John L has repeated above,
relates to whether (2) or (4) is the case (i.e. whether the susceptibility
is to 'becoming infected' or to 'developing clinical vCJD').

Actually, (4) as worded above is ambiguous, since it is not clear as to
whether 'in susceptible hosts only' relates to 'lives' as well as to 'leads
to vCJD'.  To be clear, the (4) I have in mind (to be contrasted with (2)
would more precisely be worded ... "Prion lives in all hosts, but leads to
vCJD in susceptible hosts only".

In fact, I think that my thought processes may just have answered my own
question, at least in relation to ouyr present knowledge.  It would seem
most unlikely that we could yet have the knowledge to identify  2), unless
it goes on to result in vCJD [in which case it becomes (4)] .... since not
enough 'screening' is/can be done to know about transmission of prions in
people who have not developed vCJD (hence the interest in the one recently
reported case).  It therefore seems very likely, on reflection, that all
present knowledge about 'susceptibility' must relate to development of
vCJD, not to 'asymptomatic' persistence ('living') of the prion.

'Live' and 'die' are probably not the most appropriate words for a prion;
something like 'persist' and 'disappear' would probably be more appropriate.

>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 .....

That is obviously true - but, as John L says, it is not impossible that
there is a mechanistic reason why 'true unsusceptibility' could/can
exist.  We must remember that we are dealing with a very odd type of
'infective agent' and disease, about which our knowledge is relatively limited.

>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.

As I implied in what I wrote yesterday, the existence of any true
'asymptomatic carrier' state would give rise to such concerns.  Having said
that, it appears that the incubation period can be so long that the
distinction is almost moot; the potentially long incubation period before
an individual develops vCJD is, as far as the world is concerned,
effectively a 'carrier state'.

>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.

Yes, that is very possible - and not necessarily only because of
'cross-infection' from people who are already infected.  I'm far from
convinced that we understand enough about this disease (and the prion) to
be sure that there is not a (very low level) persisting source of potential
environmental exposure which could lead to 'new cases'.

Kind Regards,


John

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