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 Iatrogenic
infection of Transmissible Spongiform
Encephalopathies through
Surgical Instruments
Dr I.P. Lipscomb
and Prof C.W. Keevil
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Background
Transmissible Spongiform Encephalopathies (TSE’s) or prion diseases
are a group of rare, transmissible, and fatal, brain diseases, of which probably
the most well-known are Bovine Spongiform
Encephalopathy (BSE) in
cattle and Creutzfeldt-Jakob
Disease (CJD) in humans.
This group of disorders have been coined prion diseases due to the widely held
belief that the main protagonist of the disease is a naturally occurring, but
mis-folded, protein; and it is this proteinaceous
infectious
particle that has provided the basis for the term prion.
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Figure
1: Graphical description of: a) Naturally occurring, α- helical based
protein b) Aberrant mis-folded,
primarily β-pleated sheet, ‘prion’ version.
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CJD itself can be split into three distinct sub-types:
- Familial
CJD. An inherited form of CJD in which offspring inherited a mutation within
their genome causing the onset of CJD in later life.
- Sporadic
CJD. Currently the most prolific of the human TSE’s with recorded
incidences of around 0.5 – 1 person per million. Sporadic CJD is
considered to occur when there is either a random mutation in the prion
protein or its gene.
- Acquired
CJD. A form of CJD that is by definition, obtained through a third party
source. An example being variant CJD which is linked to the consumption of
infected beef products, or iatrogenic CJD, where infection is induced
inadvertently by the medical
treatment
or procedures
or activity of a physician.
At the
University
of
Southampton
work on the elimination of iatrogenic CJD has been initiated.
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Iatrogenic
Creutzfeldt Jakob Disease (iCJD) |
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As
the pre-symptomatic incubation time for human TSE’s is relatively unknown the
risk of iatrogenic transmission is of great concern indeed if one considers that
over 6 million operative procedures are carried out, annually. Then even if
there is a relatively small number of the population harbouring the infection,
the possibility of human-to-human transmission is very real.
Indeed 40 people have died in
Britain
since 1990 as a result of surgical procedures. Most had accidentally used
contaminated growth hormone, and some received infected tissue to repair the
protective membrane around the brain.
An official guideline for the safe handling, and use of suspected
contaminated instruments was issued in 1998. These guidelines indicate that any
instruments used on suspect CJD patients should be removed from circulation and
quarantined immediately. To date there is no method of assessing these
instruments for possible prion protein contamination. Surgical stainless steel
instruments can be very expensive (e.g. £50,000) and some devices such as
endoscopes, require specialised decontamination procedures.
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Detecting the Undetectable?
At the
University of
Southampton
, the U.K. Department of Health have funded work to unlock the mysteries of
whether surgical instruments that have been in contact with CJD victims are
indeed contaminated. This work will assess both the requirement for instrument
destruction and the efficacy of new cleaning methods.
To enable these tasks to be performed the University have collaborated with
Best Scientific
to produce a novel and unique microscopy technique which possesses the
ability to rapidly and clearly display contamination on surgical instruments.
This, in conjunction with a bank of advanced detection procedure’s, has
provided the research group with the ability to ‘label’ and display the prion
protein on surgical stainless steel.
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Although at a relatively early stage, the work has shown
itself to be highly sensitive, able to detect less than 1x10-12 g of protein.
This work is ongoing and with the input of industrial partner Microgen
Bioproducts Ltd, a leading diagnostic company. It is intended that a
standard, easily applicable detection method can be developed, and the problem
of whether surgical tools are contaminated or not, eliminated.
The work has been highly successful so far, and has enabled
the research group to lodge several patents in relation to it.
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Further
Information on TSE’s
UK
CJD Surveillance Unit
Advisory
Committee on Dangerous Pathogens
World
Health Organisation
Department of Health Policy
Unit
PubMed
British
Medical Journal
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