Evidence For CJD/TSE
Transmission Via Endoscopes

From Terry S. Singletary, Sr

I have researched human/animal TSEs now for over 5 years due to the death of my Mother from the Heidenhain Variant Creutzfeldt Jakob disease, one of six - known - variants of the infamous 'sporadic' CJD.
I did a little survey several years ago about CJD and ENDOSCOPY in 2001, and then went there again when another article was released recently. However, they seemed to only be concerned with the vCJD strain and risk from endoscopy equipment.
My concerns are if vCJD can be transmitted by blood, and there are now 6 variants of the infamous sporadic CJDs that they are documenting to date, how do they know that none of these 6 variants will not transmit the agent (prion) via blood?...especially since the sporadic CJDs are the only ones documented to date to transmit via the surgical arena and now that the CWD is spreading more and more, who knows about the cattle?
I would always read this study and it would bring me back to reality as to how serious/dangerous this agent is in the surgical/medical arena. You might want to read this short abstract from the late, great Dr. Gibbs twice, and let it really sink in. And please remember while reading some of these transmission studies, that most all, if not ALL these agents transmit freely to primates. Humans, of course, are primates.
Regarding claims that:
'Well, it has never been documented to transmit to humans."
There are two critical factors to think about:
A. CJD/TSEs in the USA are NOT reportable in most states and there is NO CJD/TSE questionnaire for most victims and their families, and the one they are now issuing asks absolutely nothing about route and source of the (prion) agent, only how the disease was diagnosed. Furthermore, the elderly are only very rarely autopsied, ie looking for Alzheimer's or 'FAST Alzheimer's' OR prion disease-related factors and phenomena, such as heart failure caused by disease.
B. It is unethical and against the law to do transmission studies of TSEs to humans, they are 100% FATAL.
I suggest you read these case studies about medical arena CJD transmission very carefully:
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
Tissue Infectivity and TSEs (brain = high / rectum = medium)
[PDF]TSE infectivity distribution in ruminant tissues
... small intestine Distal small intestine Proximal colon Distal colon Rectum ... on the basis of the most recent scientific data, the sheep tissue infectivity ...
... entire bovine intestine from duodenum to rectum ... in any other extra neural tissue ... could promote the spread of infectivity ... Abnormal prion protein could also be ...
Transmission of prion diseases by blood transfusion
Nora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 David Parnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2
1 Journal of General Virology (2002), 83, 2897-2905. Printed in Great Britain Published ahead of print (16 July 2000) in JGV Direct as DOI 10.1099/vir.0.18580-0 Transmission of prion diseases by blood transfusion Nora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 David Parnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2 1 Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK 2 Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK Author for correspondence: Nora Hunter. Fax +44 131 668 3872. e-mail Received 16 May 2002; Accepted 9 July 2002 This article is now available in the November 2002 print issue of JGV (vol. 83, 2897-2905). The complete issue of the journal may be seen in electronic form on JGV Online ( 0001-8580 © 2002 SGM
Attempts to detect infectivity in the blood of humans and animals affected with transmissible spongiform encephalopathies (TSEs or prion diseases) have often been inconclusive because of the limitations of cross-species bioassays and the small volumes of blood that can be injected by the intracerebral route. A model has been developed for the experimental study of TSE transmission by blood transfusion using sheep experimentally infected with bovine spongiform encephalopathy (BSE) or natural scrapie as donors and susceptible scrapie-free sheep as recipients. Donors and recipients of the same species greatly increase the sensitivity of the bioassay and in sheep large volumes of blood can be injected by the intravenous (i.v.) route. Transmission of BSE to a single animal using this approach was reported recently. This study confirms this result with a second transmission of BSE and four new cases of transmission of natural scrapie. Positive transmissions occurred with blood taken2 at pre-clinical and clinical stages of infection. Initial studies indicate that following such infection by the i.v. route, deposition of the abnormal prion protein isoform, PrPSc, in peripheral tissues may be much more limited than is seen following oral infection. These results confirm the risks of TSE infection via blood products and suggest that the measures taken to restrict the use of blood in the UK have been fully justified.
Creutzfeldt-Jakob disease (CJD) is one of a group of related diseases known as prion diseases or transmissible spongiform encephalopathies (TSEs), a group that also includes scrapie in sheep and bovine spongiform encephalopathy (BSE) in cattle. A new variant of CJD (vCJD) in human beings in the UK (Will et al., 1996) is thought to have been the result of infection with the same agent that causes BSE in cattle (Bruce et al., 1997). The numbers of vCJDinfected people remain unknown, although, to date, over 100 clinical cases have been recordedin the UK. Amongst many sources of concern, one major question relates to the safety of blood transfusions and blood products - especially when inadvertently sourced from individuals during the long pre-clinical phase of vCJD, a time at which these individuals may act as asymptomatic carriers of the infectious agent. There is no epidemiological evidence to indicate that iatrogenic CJD has ever occurred via blood or blood products but vCJD is a new disease with a different pathogenesis and may present different risks.
The TSE disease-associated form of the prion protein (PrPSc) of the neuronal glycoprotein PrPC is often used as a marker for infectivity. Using a sensitive Western blotting technique, no PrPSc was detected in the buffy coat from one vCJD patient (Wadsworth et al., 2001). Although a novel method for detection of PrPSc in scrapie sheep blood has been described (Schmerr et al., 1997), the study was limited by a low number of samples and the technique requires further validation. Other investigators using the more conventional method of immunocytochemistry failed to demonstrate PrPSc in peripheral blood leucocytes of scrapie-infected sheep (Herrmann et al., 2002).
An alternative to PrPSc detection is direct bioassay of infectivity by inoculation of material into hosts of the same or different species. In laboratory rodents experimentally infected with TSE, a number of investigators have demonstrated infectivity in blood and blood components during the pre-clinical and clinical phases of infection (Brown et al., 1998; Diringer, 1984; Manuelidis et al., 1978). However, infectivity has not been isolated, so far, from blood components of natural animal hosts of TSEs (Hadlow et al., 1982; Marsh et al., 1973). Isolated reports of transmission of CJD to laboratory rodents by whole blood or buffy coat from human3 patients have been questioned for a variety of reasons (Brown, 1995).
A large-scale study conducted by the National Institutes of Health failed to demonstrate infectivity in blood from 13 patients with CJD, using either highly susceptible primates or rodents as bioassay hosts (Brownet al., 1994). With vCJD, no infectivity was detected in blood from two patients using mouse bioassays (Bruce et al., 2001). Many of these studies could have failed to reveal low levels of infectivity in blood because of the use of rodents as bioassay hosts, thus limiting the sensitivity by crossing a species barrier. Also, in most cases, the intracerebral (i.c.) route of inoculation was used, because it is the most efficient, but this severely limits the volume of blood that can be assayed.
Thus, where transmission from blood has been successful, infectivity was usually concentrated in some way, for example, by the use of buffy coat fractions. Transmission by the intravenous (i.v.) route has been shown to be up to seven times less efficient than following i.c. infection (Brown et al., 1999), but there have been very few attempts to transmit TSEs by whole blood transfusion. Units of whole blood from three CJD cases were transfused into chimpanzees with negative results (Brown et al., 1994) and pooled blood from three terminally ill TSEinfected mice produced disease in 1 of 20 transfusion recipients (Brown et al., 1999). Sheep infected orally with BSE show widespread deposition of PrPSc in the lymphoreticular system (LRS) (Foster et al., 1996a, 2001b), similar to that seen in human vCJD patients.
In contrast, in cases of sporadic human CJD and cattle BSE, peripheral pathogenesis does not appear to involve the LRS (Hill et al., 1999; Wells et al., 1998). Sheep were chosen as a model in which to study transmission of TSEs by blood transfusion because of the similarity of the pathogenesis with vCJD and because large volumes of blood can be transferred in the absence of a species barrier. We have transfused whole blood and buffy coat from BSE-infected sheep and natural scrapie-infected sheep into susceptible but scrapie-free recipient animals. In the first report on these experiments (Houston et al., 2000), we described a single case of BSE infection via blood transfusion.
The significance of this finding in a single animal has been questioned. However, the present report gives details of further successful transmissions from BSE and natural scrapie cases, the latter being the first conclusive demonstration of infectivity in blood of naturally infected individuals. Although still incomplete, our study indicates a frequency of transmission of TSEs in at least 10 % of the transfusion recipients. We have decided to provide an update of our results because of the potential importance of the study for human health. In addition, in the two BSE transfusion cases examined so far, deposition of PrPSc in peripheral tissues appears rather limited when compared with sheep infected by the oral route. The potential implications of this observation for pre-clinical diagnosis and screening are discussed.
14 Discussion
With this report we have confirmed and extended our initial observation of a single case of BSE following transfusion of blood from a BSE-infected sheep and have provided the first conclusive evidence of significant levels of infectivity in blood in a naturally occurring TSE (scrapie). The experiment may take up to 5 years to complete; however, so far we have clear evidence of disease transmission by the blood transfusion route in 2 of 24 sheep (8 %) with BSE and 4 of 21 sheep (19 %) with scrapie, with two additional animals showing clinical signs in the BSE group. If the clinically suspect BSE-transfused sheep progress as expected, this would bring the transmission rate for BSE up to 17 %, comparable with the scrapie rate.
Positive transmissions have occurred not only with samples taken from sheep at the clinical phase of disease but also with those from apparently healthy donors as early as halfway through the incubation period (Fig. 1, lane 9; no PrPSc detection in the brain of donor J2746). Each TSE is transmitting to its appropriate susceptible genotype (AXQ/AXQ for BSE and VRQ/VRQ for scrapie) and Western blot/glycoform analyses support the conclusion that donors and recipients are infected with the same strains of BSE and scrapie. Our negative controls remain healthy, although still at relatively early stages post-transfusion and our positive controls are developing clinical signs at around, or greater than, 600 days post-challenge, showing incubation periods very similar to the transfusion cases. Whole blood transfusion (400-450 ml) cases are presenting incubation periods of around 600 days, which is very similar to those resulting from i.v. injection of 0.2 g BSE cattle brain homogenate. The transfusions might be expected to be more efficient because they are a sheepto-sheep transmission with no species barrier, which contrasts with the i.v. brain infections, which is a cattle-to-sheep transmission.
A full titration of the inoculum used in the cattle BSE brain i.v. controls is under way in mice but is incomplete at the time of writing. Accurate estimation of the levels of infectivity in blood will require i.v. titration in sheep; however, the results presented here suggest that they are significantly higher than suspected previously. Another important consideration is the distribution of infectivity among different blood components. Perhaps surprisingly, most positive transmissions so far have followed transfusion of whole blood rather than buffy coat, whereas previous studies have tended to find infectivity concentrated in the buffy coat fraction. As we now have a clinical case of scrapie resulting from transfusion of buffy coat, it is clear that, in our model, infectivity is also carried by the cells in this fraction. However, these preliminary results suggest that infectivity is not confined to the buffy coat fraction and that there may also be significant levels of infectivity in the plasma and/or red cell fractions. 15
The presence of infectivity in blood suggests that it should be possible to detect PrPSc or other surrogates of infectivity by alternative methods, with obvious benefits for development of ante-mortem diagnostic tests. Early reports of the use of capillary electrophoresis to detect PrPSc in the blood of scrapie-infected sheep showed some promise (Schmerr et al., 1997); however, a recent study could not detect PrPSc in peripheral blood leucocytes of scrapie-infected sheep using immunocytochemistry (Herrmann et al., 2002). PrPC is known to be expressed only on peripheral blood mononuclear cells in sheep, in contrast to humans where it is also found on platelets and, at low levels, on erythrocytes (Barclay et al., 2002; Herrmann et al., 2001; Holada et al., 1998). Since tissues that express PrPC do not always equate with areas that accumulate PrPSc and infectivity during disease, the distribution of infectivity in blood fractions of different species clearly merits more detailed analysis.
Immunocytochemical detection of PrPSc in peripheral tissues of two of the BSE transfusion cases has shown a greatly reduced involvement of lymphoid tissues, including tonsil, in the peripheral pathogenesis compared with NPU Cheviot sheep orally infected with BSE or natural scrapie (Foster et al., 2001a). A recent report has shown that a proportion of Romney sheep in the late pre-clinical stages of infection with BSE following oral dosing (22 months post-infection) have PrPSc deposits in the CNS in the absence of any detectable involvement of peripheral lymphoid tissues (Jeffrey et al., 2001). This study also noted the relatively late and variable onset of PrPSc accumulation in the lymphoid tissues of BSE-infected sheep.
A more detailed study of BSE and scrapie transfusion cases, and positive controls, will be undertaken to determine whether lack of involvement of the LRS is a consistent feature in animals infected by the i.v. route; the results will be published at a later date. If our preliminary observations are confirmed, there may be implications for human patients with the misfortune to have received blood products from vCJD cases, because a negative tonsil biopsy as a means of reassurance might very well be unreliable. On the other hand, it also may mean that if a human patient became infected with vCJD by the i.v. route, then the peripheral tissues and blood of this secondary case may not themselves be highly infectious. In conclusion, our results so far indicate that, with more than 10 % of transfusions resulting in disease in the recipients, blood transfusion represents an appreciable risk for transmission of TSEs in sheep and, by extension, of vCJD in human beings. The relatively short and consistent incubation periods seen in positive cases suggests that levels of infectivity in the blood may be higher than suspected previously, even in the pre-clinical stages of infection, and/or that transmission by the i.v. route is highly efficient. From these preliminary results, it would appear that measures taken to safeguard the blood supply in the UK are fully justified. 16
However, further work, in particular a thorough investigation of the distribution of infectivity in different blood fractions, is required before a reliable estimate of the risks associated with contaminated blood products can be made.
Acknowledgements The authors are indebted to the UK Department of Health, European Union and DEFRA for their financial contribution to this study.
see full text:
also, older data pertaining to CJD/TSEs/BLOOD...TSS
Sir, -- Professor Manuelidis and his colleagues (Oct 19, p896) report transmission to animals of Creutzfeldt-Jakob disease (CJD) from the buffy coat from two patients. We also transmitted the disease from whole blood samples of a patient (and of mice) infected with CJD.1 Brain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.
A 70-year-old man was noted to have a slowing of speech and writing and some disorientation, all of which progressed rapidly. Decorticate rigidity, forced grasping, positive snout reflex, and myoclonus appeared within 2 months. Electroencephalogram revealed typical periodic synchronous discharge, and he died of pneumonia and upper gastrointestinal haemorrhage, about 3 months after onset of the symptoms. The Brain weighed 1290g and showed severe histological changes diagnostic of CJD, including spongiform change, loss of nerve cells, and diffuse proliferation of astrocytes. There were no inflammatory cells, microglia, neurofibrillary tangles, and amyloid plaques, although virus-like particles were detected by electron microscopy.
Results of innoculation in Mice
Inocula NO* Incubation period (days)+ Brain 7/10 (4) 789 (+ or - 112) Cornea 1/6 (0) 1037 Blood 2/13 (0) 1080 (+ or - 69) Urine 5/10 (1) 880 (+ or - 55) CSF 0/10
* Number of mice with CJD change/number examined histologically. Number with amyloid plaques shown in parentheses.
+ means + or - SD
Samples were taken aseptically at necropsy. 10% crude homogenates of brain and cornea in saline, whole blood (after crushing a clot), and untreated CSF and urine were innoculated intracerebrally into CF1 strain mice (20 ul per animal). Some mice showed emaciation, bradykinesia, rigidity of the body and tail, and sometimes tremor after long incubation periods. Tissues obtained after the animal died (or was killed) were studied histologically (table). Animals infected by various inocula showed common pathological changes, consisting of severe spongiform changes, glial proliferation, and a moderate loss of nerve cells. A few mice inoculated with brain tissue or urine had the same amyloid plaques found in patients and animals with CJD.3
In our long-term experiments, inoculating materials taken from twenty patients with CJD or Gerstmann-Straussler-Scheinker's disease (GSS) into rodents, positive results were obtained in seventeen cases, including this patient. Brain tissue transmitted the disease most frequently within the shortes incubation period, except for one case where the lymph node was the most infectious. Transmission through the cornea has been noted in man4 and in guineapigs.5 Whole blood samples taken from three patients were inoculated and a positive transmission occured only in the case recorded here. Mouse-to-mouse transmission through blood inoculation was successful after a mean incubation period of 365 days.1 Transmission through urine was positive in this patient only, and negative in one other patient and in many infected animals. Transmission through the CSF from eight patients was negative, yet transmission via the CSF of infected rats was positive.1
As viraemia has been proved in guineapigs,6 mice,1,7 and lately in patients with CJD, blood for transfusion or blood products for medical use must be tested for unconventional pathogens. For this purpose, we inoculated blood products inot rodents.8 The CJD pathogen was not found in the products examined. However, this approach takes too long to be of practical value. More efficient methods must be developed to detect pathogens and to eliminate them from blood. One proposal9 is to apply membrane filtration to the pruification protocol of human growth hormone suspected of being contaminated with CJD. Similar methods are needed for blood contamination.
Department of Neuropathology, Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka812, Japan
1. Tateishi J, Sato Y, Kaga M. Don H, Ohta M. Experimental transmission of (bum??cannot read) subacute spongiform encephalopathy to small rodents I: Clinical and histological observations. Acta Neuropathol (Berl) 1980; 51: 127.
2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakob disease with demonstration of virus-like particles. Acta pathol Jpn 1982;32: 695.
3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in the brains of mice with Creutzfeldt-Jakob disease. A?? Neurol 1984; 15: 278.
4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D. Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974; 290?: 692.
5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L. Experimental Creutzfeldt-Jakob disease transmitted via the eye with infected cornea. N Engl J Med 1977; 296: 1334.
6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimental Creutzfeldt-Jakob disease. Science 1978: 209?: 1069.
7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC. Creutzfeldt-Jakob disease in mice. Persistent viremiam and preferential replication of virus in low-density lymphocytes. Infect Immun 1983; 41: 154.
8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiform encephalopathis absent in blood products. J Med Virol 1985; 15: 11.
9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob disease pathogen in growth hormone preparations is eliminatable. Lancet (in press).
Something I submitted to GUT previously;
Subject: Re: gutjnl_el;21 Terry S. Singeltary Sr. (3 Jun 2002) "CJDs (all human TSEs) and Endoscopy Equipment" Date: Thu, 20 Jun 2002 16:19:51 -0700 From: "Terry S. Singeltary Sr." <> To: Professor Michael Farthing <> CC: References: <001501c21099$5c8bc620$>
Greetings again Professor Farthing and BMJ,
I was curious why my small rebuttal of the article described below was not listed in this month's journal of GUT? I had thought it was going to be published, but I do not have full text access. Will it be published in the future? Regardless, I thought would pass on a more lengthy rebuttal of mine on this topic, vCJD vs sCJDs and endoscopy equipment. I don't expect it to be published, but thought you might find it interesting, i hope you don't mind and hope to hear back from someone on the questions I posed...
Here is my short submission I speak of, lengthy one to follow below that:
>> Date submitted: 3 Jun 2002 >> eLetter ID: gutjnl_el;21 >> >> Gut eLetter for Bramble and Ironside 50 (6): 888 >> >>Name: Terry S. Singeltary Sr. >>Email: >>Title/position: disabled {neck injury} >>Place of work: CJD WATCH >>IP address: >>Hostname: >>Browser: Mozilla/5.0 (Windows; U; Win98; en-US; rv:0.9.4) >>Gecko/20011019 Netscape6/6.2 >> >>Parent ID: 50/6/888 >>Citation: >> Creutzfeldt-Jakob disease: implications for gastroenterology >> M G Bramble and J W Ironside >> Gut 2002; 50: 888-890 (Occasional viewpoint) >> >> >>----------------------------------------------------------------- >>"CJDs (all human TSEs) and Endoscopy Equipment" >>----------------------------------------------------------------- >> >><!-- article ID: 50/6/888 --> >> >><P> regarding your article; >> >><P> Creutzfeldt-Jakob disease: implications for gastroenterology >> >><P> I belong to several support groups for victims and relatives >>of CJDs. Several years ago, I did a survey regarding >>endoscopy equipment and how many victims of CJDs have >>had any type of this procedure done. To my surprise, many >>victims had some kind of endoscopy work done on them. >>As this may not be a smoking gun, I think it should >>warrant a 'red flag' of sorts, especially since data now >>suggests a substantial TSE infectivity in the gut wall >>of species infected with TSEs. If such transmissions >>occur, the ramifications of spreading TSEs from >>endoscopy equipment to the general public would be >>horrible, and could potential amplify the transmission >>of TSEs through other surgical procedures in that >>persons life, due to long incubation and sub-clinical >>infection. Science to date, has well established >>transmission of sporadic CJDs with medical/surgical >>procedures.
>>Terry S. Singeltary Sr. >>CJD WATCH
Again, many thanks, Kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 CJD WATCH
[scroll down past article for my comments]
Subject: Creutzfeldt-Jakob disease: implications for gastroenterology & CJD 38 years after _diagnostic_ use of hGH (Iatrogenic CJDs & sporadic CJDs) Date: Mon, 17 Jun 2002 16:46:46 -0700 From: "Terry S. Singeltary Sr." <> Reply-To: Bovine Spongiform Encephalopathy <> To:
Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>
Creutzfeldt-Jakob disease' implications for gastroenterology
M G Bramble, J W Ironside
Gut 2002;50:888-890
The current clinical views regarding variant Creutzfeldt-Jakob disease, and in particular transmission via endoscopy, of those representing both gastroenterology and the Spongiform Encephalopathy Advisory Committee are presented in an attempt to guide clinicians as to "best practice" given the current state of our knowledge.
See end of article for authors' affiliations
Correspondence to: Professor MG Bramble, Endoscopy Centre, James Cook University Hospital, Marton Rd, Middlesbrough TS4 3BN, UK;
Most gastroenterologists working in the UK have been aware for some time that endoscopy may be a vector for the transmission of prions from a patient incubating, but not clinically manifesting, variant Creutzfeldt-Jakob disease (vCJD) to the next individuals undergoing the same procedure on the same list. To date there are no recorded cases of iatrogenic transmission of vCJD via endoscopy but it remains a risk which will be present for many years to come. Advice to health authorities on individual cases is through the CJD Incidents Panel. However, we are aware that advice to health professionals performing endoscopy needs to be as comprehensive as current evidence will allow, without making it impossible to perform endoscopic procedures on patients who will clearly derive long term health benefits from an accurate endoscopic diagnosis and/or treatment. This article represents the current clinical views of those representing both gastroenterology and the Spongiform Encephalopathy Advisory Com-mittee (SEAC). Both authors sit on the CJD Inci-dents Panel and have been advising the Depart-ment of Health on individual cases during the last year. It is important to note that the advice given in this article may be superseded if additional information or evidence becomes available.
CJD is a member of a group of neurological disorders known as the transmissible spongilorm encephalopathies or prion diseases, which affect both animals (such as scrapie in sheep or bovine spongiform encephalopathy (BSE) in cows) and humans. The precise nature of the transmissible agents responsible for these disorders is unknown but there is increasing evidence to support the prion hypothesis, which states that the agent is composed of an abnormally folded form of a host encoded protein, prion protein. The normal prion protein (PrPc) is expressed in many tissues but occurs at the highest levels in neurones in the central nervous system (CNS) where it may act as a copper binding protein, although its precise physiological role is unknown. The abnormal form of the protein (PrPSc) accumulates in the CNS in prion diseases; the infectious agent is remarkably resistant to most forms of degradation. The association between PrPSc and the gut has been eloquently described in a previous lead-ing article1 and gastroenterologists need to understand where we are in terms of our present day knowledge of this entity.
In humans, prion diseases occur in three major categories: sporadic, acquired, and familial. All are currently untreatable and universally fatal although recent studies have indicated that a combination of drugs may be effective in experimental prion diseases2: this approach is under consideration as a clinical trial. The sporadic form of CJD affects approximately one person per mil-lion per annum in the population on a worldwide basis. CJD has also occurred as an acquired iatrogenic disorder, transmitted to other humans through direct (inadvertent) inoculation of the brain via contaminated neurosurgical instruments, via corneal and dura mater grafts, or through administration of human pituitary ex-tracts used to treat growth hormone or gonadotrophin deficiency. Variant CJD (vCJD) is a new acquired form of CJD which was first reported in 1996 affecting mainly young adults and with a unique neuropathological phenotype.3 It is now widely accepted that bovine prions passed into the human population through consumption of BSE infected bovine tissues; the transmissible agent responsible for vCJD is identical to the BSE agent (but different from the agent in sporadic CJD). The incubation period for vCJD is likely to be lengthy and may have a mean value of 10-30 years. During this time the affected person has the potential to transmit the disease to others via surgical procedures which might result in the transfer of infected tissue into the next person operated on with the same surgical instruments.
The distribution of PrPSc in the body is different in sporadic and variant CJD, reflecting the differ-ent pathogenesis of the two forms. In the case ot sporadic CJD, prion infectivity is largely limited to the CNS (including the retina) and only opera-tions involving the brain and eye have resulted in iatrogenic transmission of the disease. Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4
"Endoscopy on patients who are incubating vCJD may result in exposure of the instrument (and particularly the biopsy forceps) to PrPsc''
In contrast, in vCJD the lymphoreticular system throughout the body contains PrPSc at the time of death, and experimental evidence suggests that the lymphoreticular system may contain significant levels of infectivity for most of the incuba-tion period.5 To support this, in vCJD abnormal prion protein was found in the germinal centres in the wall of an appendix from a vCJD patient that was removed eight months before the onset of neurological disease.6 As lymphoid follicles and germinal centres are widely distributed in the gastrointestinal tract (and are often biopsied), it is possible that endoscopy on patients who are incubating vCJD may result in exposure of the instrument (and particularly the biopsy forceps) to PrPsc. Consequently, the question now arises, how great is the risk of secondary (person to person) transmission in endoscoping a patient incubating vCJD? There are three scenarios which gastroenterologists are likely to encounter and this editorial will attempt to guide clinicians as to "best practice" given the current state of our knowledge.
Scenario No 1
Occasionally gastroenterologists may be requested to endo-scope a patient with known or probable sporadic CJD (usually to site a PEG feeding tube). This can be carried out in the rou-tine way provided vCJD is not suspected. If inadvertently a patient with suspected vCJD is endoscoped, the instrument used should be quarantined until the postmortem diagnosis is known. If sporadic CJD is diagnosed, the endoscope can be returned to use following thorough cleaning and decontami-nation, as is normal practice. If vCJD is diagnosed the endoscope cannot be used again and should be quarantined or sent to the National CJD Surveillance Unit in Edinburgh for research purposes. The previous advice to destroy such instru-ments represents a lost opportunity to study the risks involved in more detail. It would also be good practice to inform colleagues locally that a quarantined instrument was available for use in other endoscopy units if they too had a patient with suspected vCJD requiring endoscopy.
Scenario No 2
For patients with known or probable vCJD,7 endoscopy should only be a last resort. Ultrasound guided insertion of a gastrostomy feeding tube would be preferable to a PEG feeding tube if local expertise is available. If not, endoscopy should be per-formed using an instrument already set aside for such patients. If no such instrument is available locally, one can be loaned to any hospital by the National CJD Surveillance Unit in Edinburgh (contact telephone number 0131 537 1980). If scenario No 2 becomes more common, endoscopes may need to be held regionally for this purpose.
Scenario No 3
This scenario covers patients who have been endoscoped by an instrument previously used on a patient who was not known to be incubating vCJD at the time of endoscopy but who sub-sequently went on to develop the disease. This could become the commonest scenario and it must be assumed that the patient who went on to develop vCJD was incubating the dis-ease at the time of the original endoscopy. This also means that infectious material may not have been removed completely by current methods of decontaminating endoscopes, and that subsequent patients have been exposed to the prion agent. The instrument used should therefore be quaran-tined until advice has been sought from the CJD Incidents Panel (Department of Health, Skipton House, London; contact telephone 0207 972 1761) as to the management of the situa-tion. Local infection control teams will need to be involved with contact tracing and information handling.
It is unlikely that colonoscopy would be clinically justifiable in a patient known or strongly suspected as suffering from vCJD. However, it is quite possible that an asymptomatic patient incubating vCJD may undergo colonoscopy prior to diagnosis and this situation is essentially the same as in scenario 3. The risks of transmitting prion protein to the next patient are much greater however, due to a number of factors which relate to the amount of lymphatic tissue encountered during endos-copy and the number, site, and size of mucosal biopsies obtained by this method.
In general the risks of transmitting vCJD from one patient to another are dependent on the infectivity of the tissues involved, the amount of tissue contaminating the instrument, the effectiveness of the decontamination processes, and the susceptibility of subsequently exposed patients. Experimental studies suggest that levels of infectivity in prion diseases are highest in the CNS and retina, which are approximately two logs higher than in the tonsils and other lymphoreticular tis-sue. A recent study has also detected the abnormal form of the prion protein in rectal tissue from a patient with vCJD by western blot examination of autopsy tissues.8 The risk of transmitting vCJD through the endoscopy procedure itself is likely to be small, but contamination of the endoscope and forceps as a result of biopsy of lymphoid tissues may represent a larger (but currently unquantifiable) risk, even though only small amounts of tissue are involved.
"The risks of transmitting vCJD from one patient to another are dependent on the infectivity of the tissues involved, the amount of tissue contaminating the instrument, the effectiveness of the decontamination processes, and the susceptibility of subsequently exposed patients"
The greatest risk is undoubtedly that which ensues from biopsy of the terminal ileum where Peyer's patches may con-tain significant levels of prion protein for a patient incubating vCJD. The biopsy forceps and the colonoscope become poten-tial vectors for disease transmission under these circum-stances. Meticulous manual cleaning of the colonoscope is probably the best defence against person to person transmis-sion. The same is true of the biopsy forceps, but as disposable forceps are now available there is a strong argument for mov-ing towards the universal use of disposable biopsy forceps for mucosal samples taken at colonoscopy. Endoscopy units should now work towards a policy of using disposable biopsy forceps as the only practical way of minimising the risk which results from ileal biopsy. In addition, "random" biopsies should be kept to a minimum as lymphoid tissue is distributed widely throughout the gastrointestinal tract. Although thor-ough cleaning of flexible endoscopes ensures patient safety for "normal" pathogens, the same process may not be adequate for the PrPsc. The main benefit of the decontamination process under these circumstances is undoubtedly effective manual cleaning, as glutaraldehyde may stabilise PrPSc on the metal surface of the endoscope, with potentially adverse conse-quences. It follows that brushes used to clean the channels of the endoscope are used only once to ensure maximum efficiency and biopsy forceps should also be functioning opti-mally and discarded as soon as they appear to be under performing (tearing tissue rather than cutting it). The rubber valve protecting the biopsy channel is another item which is potentially disposable and serious consideration should be given to single use valves. Again, more research is required to determine "best practice". For rigid endoscopes, autoclaving at the recommended conditions for CJD9 is the best way of attempting decontamination.
What should endoscopists do in the short term? The answer to this question must be to ensure as far as possible that manual cleaning of endoscopes and reuseable accessories is of the highest standard. Endoscopy has a major role in patient care, and this should not be compromised unless it is absolutely unavoidable in the public interest. It is also essen-tial that endoscopes should be individually identifiable and their use traceable in any given patient population. Random biopsies should be kept to an absolute minimum (particularly of the ileum in colonoscopy) and endoscopy itself should be as atraumatic as possible, especially gastroscopy where the instrument is in contact with the mucosa covering the tonsils. Biopsy forceps should be treated as "high risk" and undergo thorough ultrasonic cleaning followed by autoclaving. As research in the UK progresses, it is likely that other procedures will be developed to inactivate prion infectivity and to remove proteins from instrument surfaces. The development of such techniques (along with more sensitive tests for prion detection) may well have an impact on future advice concern-ing endoscopy and CJD.
Depending on the final numbers of people infected with vCJD, we must assume that a significant number may undergo endoscopy before neurological symptoms appear10. It is there-fore up to every endoscopist to be aware of the dangers and follow the advice set out here. Further advice on specific cases and possible exposure incidents can be obtained from the CJD Incidents Panel (Department of Health, Skipton House, London; contact telephone 0207 972 1761).
Authors' affiliations M G Bramble, Endoscopy Centre, James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK J W Ironside, CJD Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
Accepted for publication 19 November 2001
1 Shmakov AN, Ghosh S. Prion proteins and the gut: une liaison dangereuse? Gut 2001;48:443-7.
2 Korth C, May BCH, Cohen FE, et al. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Nail Acad Sci USA 2001;98:9836-41.
3 Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347:921-5.
4 Report of a Working Party of the British Society of Gastroenterology Endoscopy Committee. Cleaning and disinfection of equipment for gastrointestinal endoscopy. Gut 1998;42:585-93.
5 Hill AF, Butterworth R J, Joiner S, et al. Investigation of variant Creutzfeldt-Jacob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999;353:183-9.
6 Hilton DA, Fathers E, Edwards P, et al. Prion immunoreactivity in the appendix before the clinical onset of new variant Creutzfeldt-Jacob disease. Lancet 1998;352:703-4.
7 Will RG, Zeidler M, Stewart GE, et al. Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neuro12000;47:575-82.
8 Wadsworth JD, Joiner S, Hill AF, et al. Tissue distribution of protease resistant prion protein in variant Creutxfleldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 2001 ;358:171-80.
9 Dangerous Pathogens Spongiform Encephalopathy Advisory Committee. Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. London: The Stationary Office, 1998.
10 Ironside JW, Hilton DA, Ghani A, et al. Retrospective study of prion protein accumulation in tonsil and appendix tissue. Lancet 2000;355:1693-94. ========================================================
Greetings List Members,
This is _very_ disturbing to me:
The distribution of PrPSc in the body is different in sporadic and variant CJD, reflecting the different pathogenesis of the two forms. In the case ot sporadic CJD, prion infectivity is largely limited to the CNS (including the retina) and only operations involving the brain and eye have resulted in iatrogenic transmission of the disease. Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4
i personally believe it is irresponsible for anyone to state in this day and time, that sporadic CJDs (now at 6 variants) will not transmit the disease by this route. considering infective dose cannot be quantified, only speculated, such a statement is thus, irresponsible. to hypothosize that sporadic CJD just happens spontaneously (with no scientific proof), that the PrPSc distribution in tissues of all sporadic CJDs is entirely different than that of vCJD, without being able to quantify the titre of infection, or even confirm all the different variants yet, again is _not_ based on all scientific data, then it's only a hypothosis. who is to say that some of these variants of sporadic CJD were not obtained _orally_?
also stated:
Although thorough cleaning of flexible endoscopes ensures patient safety for ''normal'' pathogens, the same process may not be adequate for the PrPSc.
The sporadic form of CJD affects approximately one person per mil-lion per annum in the population on a worldwide basis.
who is to say how much infectivity are in some of these variants of sporadic CJDs, without confirming this? if we look at the 6 different variants of sporadic CJDs, has the infective dose for all 6 _documented_ variants been quantified, and documented as being 'measurable'?
will there be more variants of sporadic CJDs, and what of the ramifications from them?
what of other strains/variants of TSE in cattle, BSE in sheep, CWD in cattle, or any of the 20+ strains of Scrapies in deer/elk? i get dizzy thinking of the different scenerio's. what would the human TSEs from these species look like and how can anyone quantify any tissue infectivity from these potential TSE transmissions to humans, and the risk scenerio described here from this potential route? could not some of these sporadic CJDs have derived directly or indirectly from one of these species, and if so, pose a risk by the route described here?
something else to consider, in the recent finding of the incubation period of 38 years from a _small_ dose of human growth hormone;
> We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogentic CJD. Furthermore, our patient was _not_ treated with hGH, but only received a _low_ dose as part of a diagnostic procedure. (see full text below).
so my quesion is, how low is 'low' in quantifing the infectious dose in vCJD, comparing to _all_ sporadic CJDs, from the different potential routes, sources, and infectivity dose?
will the titre of infectivity in every tissue and organ of all sporadic CJDs stay exact or constant, no matter what the infective dose, route and species may be? this is considering you don't buy the fact that sporadic CJDs 85%+ of _all_ CJDs, are a happen stance of bad luck, happen spontaneously without cause, and are one-in-a-million world wide, with no substantial surveillance to confirm this.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease T. S. Singeltary, Sr; D. E. Kraemer; R. V. Gibbons, R. C. Holman, E. D. Belay, L. B. Schonberger
and what of Dr. Prusiner et al recent work about tissue infectivity;
Prions in skeletal muscle
Our data demonstrate that factors in addition to the amount of PrP expressed determine the tropism of prions for certain tissues. That some muscles are intrinsically capable of accumulating substantial titers of prions is of particular concern. Because significant dietary exposure to prions might occur through the consumption of meat, even if it is largely free of neural and lymphatic tissue, a comprehensive effort to map the distribution of prions in the muscle of infected livestock is needed. Furthermore, muscle may provide a readily biopsied tissue from which to diagnose prion disease in asymptomatic animals and even humans.
can the science/diagnostic measures used to date, measure this, and at the same time guarantee that no titre of infectivity exists from sporadic CJDs (all of the variants), from this potential mode and route of transmission?
i don't think so, this is just my opinion. this is why i get paid nothing, and these scientists get the big bucks. i just hope i am wrong and the big bucks are correct in their _hypothisis_ of this potential mode/route of transmission with endoscopy equipment, from _all_ human TSEs.
i understand we have to weigh the risks of what we know to what we don't know, to the disease we _may_ catch to what we are having the procedure for, but to categorically state at this present time of scientific knowledge;
"Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4"
but, to categorically state this, in my opinion, is not only wrong, but potentially very dangerous to the future of human health...TSS
Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone
E A Croes, G Roks, G H Jansen, P C G Nijssen, C M van Duijn ...............................................................
J Neurol Neurosurg Psychiatry 2002;72:792-793
A 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic CJD. This is the longest incubation period described so far for iatrogenic CJD. Furthermore, this is the first report of CJD after diagnostic use of hGH. Since the patient was one of the first in the world to receive hGH, other cases of iatrogenic CJD can be expected in the coming years.
Prion diseases are potentially transmissible. Human to human transmission was first reported in 1974, when a 55 year old woman was described who developed symptoms of Creutzfeldt-Jakob disease (CJD) 18 months after a corneal transplant.1 Since then, transmission has been reported after stereotactic electroencephalographic (EEG) depth recording, human growth hormone (hGH) and gonadotrophin treatment, and dura mater transplantation.2-5 More than 267 patients with iatrogenic CJD are known today and their number is growing.6 The most important iatrogenic cause of CJD is still contaminated cadaveric hGH. Exposure to contaminated hGH occurred before 1985, when recombinant growth hormone became available. In a recent study, incubation periods in 139 patients with hGH associated CJD were found to range from 5-30 years, with a median of 12 years.6 One of the factors influencing incubation time is genotype on polymorphic codon 129 of the prion protein gene.7 The incubation time is significantly shorter in people who are homozygous for either methionine or valine on this polymorphism.7
We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogenic CJD. Further-more, our patient was not treated with hGH but only received a low dose as part of a diagnostic procedure.
This patient presented at the age of 47 years with paraesthesia in both arms for six months, difficulty with walking for four weeks, and involuntary movements of mainly the upper extremities of two weeks' duration. He did not notice any change in cognitive function, although his twin sister had noticed minor memory disturbances. There was no family history of neurological disease. During childhood the patient had experienced a growth delay compared with his twin sister and with the average in the Netherlands. When he was 9 years old, a nitrogen retention test with 6 IU hGH over five days was performed to exclude growth hormone deficiency. Since the result was not decisive, a quantitative amino acid test was performed, which measures 30 amino acids during fasting and one, two, and three hours after growth hormone injection. No abnormal amino acid concentrations were found making the diagnosis of primordial dwarfism most likely. Therefore, no treatment with hGH was given.
On neurological examination we found a slight dysarthria without aphasia. Cranial nerve function was normal. Walking was unstable and wide based. During movements of the upper extremities myoclonic jerks were present. Sensation, muscle tone, and strength were normal. Co-ordination was impaired in all four limbs with a disturbed balance. Tendon reflexes were brisk at the arms and increased at the legs with a clonus in the ankle reflex. Plantar responses were both normal. On the mini mental state examination, the patient scored 30/30. Routine laboratory investigation, thyroid function, vitamin concentrations (B-1, B-6, B-12, and E), and copper metabolism were normal. Admission EEG examination showed generalised arrhythmic slow activity with diffuse spikes and spike waves. EEG examination two months later showed a further slowing of the rhythm with bilateral diphasic sharp waves but was not typical for CJD. Cerebral magnetic resonance imaging was normal. Cerebrospinal fluid examination showed 1 cell/3 µl, normal glucose and protein concentrations, and a strongly positive 14-3-3 protein test. The patient was homozygous for methionine on the PRNP codon 129 polymorphism. On clinical grounds, CJD was diagnosed. Within one month the patient's condition deteriorated rapidly and because of severe disturbances in coordination and progressive myoclonus he became bedridden. An eye movement disorder developed with slow saccadic and dysmetric eye movements. Temperature became unstable with peaks of 39°C without an infectious focus, for which a disorder of autoregulation was presumed. Until a very advanced stage, cognitive function was intact. The patient died five months after admission. The diagnosis of CJD was confirmed at necropsy. The brain weighed 990 g and showed clear cortical and cerebellar atrophy. Spongiosis, neuronal loss, and gliosis were found predominantly in the putamen, caudate nucleus, and basotemporal and cerebellar cortex; the cerebellum was the most severely affected of these. Vacuoles ranged from 2-12 µm. No amyloid or Kuru plaques were found. Immunohistochemical staining (3F4 antibody 1:1000, Senetek, USA) was clearly positive for prion protein accumulation in a "synaptic" distribution. Most deposition was found in the stratum moleculare of the cerebellum.
We describe a 47 year old patient who developed pathology proven CJD 38 years after hGH injections. The patient was never treated with hGH but received a small dose as part of a diagnostic procedure. The onset of CJD was signalled by prodromal symptoms of paraesthesia followed by a rapidly progressive ataxia. The disease presentation and course with predominantly cerebellar and eye movement disorders are compatible with iatrogenic CJD caused by hGH treatment.6 8
Growth hormone treatment was first described in 1958 but hGH was not produced on a larger scale from human pituitary glands until the beginning of the 1960s. In the Netherlands growth hormone extraction started in 1963 and was soon centrally coordinated. Until 1979 growth hormone was extracted non-commercially from pituitaries by a pharmaceutical company. In 1971 commercial products also became available. Our patient was one of the first to receive hGH in the Netherlands but the origin of this product was not recorded. A causal relation can therefore not be established with full certainty, but coincidentally receiving growth hormone and developing this very rare disease is unlikely. Since the clinical course in this relatively young patient is in accordance with an iatrogenic cause, we think the probability is high that the hGH injections explain the development of CJD in this patient.
The first Dutch patient with hGH related CJD died in 1990. 9 During several periods from 1963 to 1969 she received intramuscular injections of hGH. During an unknown period the hGH was derived from South America. At age 39, 27 years after starting the treatment, she developed an ataxic gait, slurred speech, sensory disorders, and myoclonus, but her cognitive function remained normal. Postmortem examination of the brain confirmed the diagnosis of CJD.9 Following the identification of this patient, a retrospective study was started to trace all 564 registered hGH recipients who were treated before May 1985. Until January 1995, none of these was suspected of having CJD.10 Since 1993 prospective surveillance for all forms of human prion disease has been carried out in the Netherlands and, apart from the patient described above, a further two patients with iatrogenic CJD have been identified, who developed the disease after dura mater transplantation.11
An incubation period as long as 38 years had never been reported for iatrogenic CJD. Huillard d'Aignaux et al7 studied the incubation period in 55 patients with hGH related CJD in a cohort of 1361 French hGH recipients. The median incubation period was between 9 and 10 years. Under the most pessimistic model, the upper limit of the 95% confidence interval varied between 17 and 20 years. Although the infecting dose cannot be quantified, it can be speculated that the long incubation period in our patient is partly explained by the administration of a limited amount of hGH. This hypothesis is supported by experimental models, in which higher infecting doses usually produce shorter incubation periods.6 Since our patient was one of the first in the world to receive hGH, this case indicates that still more patients with iatrogenic CJD can be expected in the coming years. Another implication of our study is that CJD can develop even after a low dose of hGH. This case once more testifies that worldwide close monitoring of any form of iatrogenic CJD is mandatory.
We are grateful to M Jansen PhD MD for his search for the origin of the growth hormone and P P Taminiau MD. CJD surveillance in the Netherlands is carried out as part of the EU Concerted Action on the Epidemiology of CJD and the the EU Concerted Action on Neuropathology of CJD, both funded through the BIOMED II programme, and is supported by the Dutch Ministry of Health. This surveillance would not have been possible without the cooperation of all Dutch neurologists and geriatricians. ........................................
Authors' affiliations
E A Croes, G Roks*, C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands
P C G Nijssen, Department of Neurology, St Elisabeth Hospital, PO Box 90151, 5000 LC Tilburg, Netherlands
G H Jansen, Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands
*Also the Department of Neurology, St Elisabeth Hospital
Correspondence to: Professor C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands;
Received 27 December 2001 In revised form 1 March 2002 Accepted 12 March 2002
Competing interests: none declared
1 Duffy P, Wolf J, Collins G, et al. Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974;290:692-3.
2 Bernoulli C, Siegfried J, Baumgartner G, et al. Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1977;i:478-9.
3 Koch TK, Berg BO, De Armond SJ, et al. Creutzfeldt-Jakob disease in a young adult with idiopathic hypopituitarism: possible relation to the administration of cadaveric human growth hormone. N Engl J Med 1985;313:731-3.
4 Cochius JI, Burns RJ, Blumbergs PC, et al. Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin. Aust NZ J Med 1990;20:592-3.
5 Thadani V, Penar PL, Partington J, et al. Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft: case report. J Neurosurg 1988;69:766-9.
6 Brown P, Preece M, Brandel JP, et al. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000;55:1075-81.
7 Huillard d'Aignaux J, Costagliola D, Maccario J, et al. Incubation period of Creutzfeldt-Jakob disease in human growth hormone recipients in France. Neurology 1999;53:1197-201.
8 Billette de Villemeur T, Deslys JP, Pradel A, et al. Creutzfeldt-Jakob disease from contaminated growth hormone extracts in France. Neurology 1996;47:690-5.
9 Roos RA, Wintzen AR, Will RG, et al. Een patiënt met de ziekte van Creutzfeldt-Jakob na behandeling met humaan groeihormoon. Ned Tijdschr Geneeskd 1996;140:1190-3.
10 Wientjens DP, Rikken B, Wit JM, et al. A nationwide cohort study on Creutzfeldt-Jakob disease among human growth hormone recipients. Neuroepidemiology 2000;19:201-5.
11 Croes EA, Jansen GH, Lemstra AF, et al. The first two patients with dura mater associated Creutzfeldt-Jakob disease in the Netherlands. J Neurol 2001;248:877-81.
re-CJD after diagnostic use of human growth hormone
from a donor sourcing aspect, seems the record keeping here has a lot to be desired for, let us hope it has improved for recipients sake.
also, they speak of 'low dose fitting long incubation'. what about KURU still existing after some 40 years exposure had ceased. i don't believe in most instances the dose with kuru is low. just something else to ponder?
1: Ann Neurol 1999 Aug;46(2):224-33
Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.
Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.
were not all CJDs, even nvCJD, just sporadic, until proven otherwise?
Terry S. Singeltary Sr., P.O. BOX 42, Bacliff, Texas 77518 USA
Professor Michael Farthing wrote:
Louise Send this to Bramble (author) for a comment before we post. Michael
Subj: Reprocessing of Flexible Endoscopes and Endoscopic Accessories - an International Comparison of Guidelines Date: 9/17/02 3:28:43 AM Eastern Daylight Time From: flounder@WT.NET (Terry S. Singeltary Sr.) Sender: BSE-L@UNI-KARLSRUHE.DE (Bovine Spongiform Encephalopathy) Reply-to: BSE-L@UNI-KARLSRUHE.DE (Bovine Spongiform Encephalopathy) To: BSE-L@UNI-KARLSRUHE.DE
Bovine Spongiform Encephalopathy <BSE-L@UNI-KARLSRUHE.DE>
Reprocessing of Flexible Endoscopes and Endoscopic Accessories - an International Comparison of Guidelines
Zeitschrift für Gastroenterologie
© Georg Thieme Verlag Stuttgart New York More about this journal
Endoscopic examinations and procedures are essential for diagnosis and treatment of gastrointestinal diseases. As a result of poor reprocessing practice microorganisms can be transmitted via endoscope. The majority of infection transmissions is due to insufficient performance of cleaning and disinfection disregarding guidelines of societies of gastrointestinal endoscopy.
A review of the literature and a comparison of European and American guidelines for reprocessing flexible endoscopes are given. Differences in the classification of endoscopic devices, on the possibility of prion transmission, recommendations on staff training and protection, quality assurance of reprocessing and evidence-based graduation of guidelines are stressed and discussed. With respect to the procedure of endoscope reprocessing, differences concerning the cleaning solution to choose, necessity of thoroughly manual cleaning and brushing of the accessible endoscope channels (even in the case of subsequent automatic reprocessing endoscopes in washers-disinfectors), disinfection solution, microbiological quality of water for final rinsing and rationale for alcohol flush of endoscope channels for better drying are mentioned.
The need for experimental investigations of the cleaning and disinfection process is stressed. In contrast to recent guidelines of European and American societies of gastrointestinal endoscopy, the now updated recommendations of the Robert Koch-Institute for reprocessing flexible endoscopes and endoscopic accessories are evidence-based and graduated.
Original Article Z Gastroenterol 2002; 40: 531-542 DOI: 10.1055/s-2002-32807 Table of Contents Leitlinien zur Aufbereitung flexibler Endoskope und endoskopischen Zusatzinstrumentariums im internationalen Vergleich Reprocessing of Flexible Endoscopes and Endoscopic Accessories - an International Comparison of Guidelines O. Leiß1, U. Beilenhoff2, L. Bader3, M. Jung2, M. Exner4 1Fachbereich Gastroenterologie, Deutsche Klinik für Diagnostik, Wiesbaden 2St. Hildegardis-Krankenhaus, Mainz 3Max von Pettenkofer-Institut der LMU München, München 4Hygiene-Institut der Universität Bonn, Bonn
Endoskopische Untersuchungen und Eingriffe sind für Diagnostik und Therapie gastrointestinaler Erkrankungen unverzichtbar. Durch mangelhaft aufbereitete Endoskope können Mikroorganismen übertragen werden. Die Mehrzahl der Infektionsübertragungen bei Endoskopie ist auf unzureichende Reinigungs- und Desinfektionsmaßnahmen unter Missachtung aktueller Aufbereitungsrichtlinien der Fachgesellschaften zurückzuführen.
In einer Literaturübersicht werden die Leitlinien europäischer und amerikanischer Fachgesellschaften zur Aufbereitung flexibler Endoskope verglichen. Es werden Unterschiede in der Klassifikation des endoskopischen Instrumentariums, in der Bewertung der Prionenproblematik, in den Anforderungen an Personalschulung und Personalschutz, in der Betonung qualitätssichernder Maßnahmen und in der wissenschaftlichen Untermauerung und Graduierung der ausgesprochenen Empfehlungen dargestellt und diskutiert. Zu Einzelschritten der Aufbereitung werden Unterschiede hinsichtlich der einzusetzenden Reinigungslösung, der Notwendigkeit einer manuellen Bürstenreinigung der Endoskopkanäle (auch bei nachfolgender maschineller Aufbereitung), der Wahl des Desinfektionsmittels, der mikrobiologischen Qualität des zur Schlussspülung verwendeten Wassers und der Empfehlung einer Spülung der Endoskopkanäle mit Alkohol für eine verbesserte Trocknung herausgestellt und kritisch bewertet.
Es wird offensichtlich, dass experimentelle Untersuchungen zu Einzelaspekten der Endoskop-Aufbereitung weitgehend fehlen bzw. erst in jüngster Zeit bearbeitet wurden. Im Gegensatz zu bisherigen Leitlinien europäischer und amerikanischer Fachgesellschaften zur Endoskop-Aufbereitung sind die aktualisierten Empfehlungen des Robert Koch-Instituts zur Aufbereitung flexibler Endoskope und endoskopischen Zusatzinstrumentariums mit der verfügbaren Evidenz verknüpft und graduiert. Schlüsselwörter
Flexible Endoskope - Aufbereitung - Reinigung - Desinfektion - Personalschulung - Qualitätssicherung - Mikrobiologische Prüfungen - Hygiene Abstract



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