Wednesday, January 02, 2008

Risk factors for sporadic Creutzfeldt-Jakob disease

Wednesday, January 02, 2008 Risk factors for sporadic Creutzfeldt-Jakob disease


Risk factors for sporadic Creutzfeldt-Jakob disease



We observed and increased risk for sCJD associated with a reported lifetime history of ever having had surgery. However, contrary to what might have been expected if this association was causal, risk did not appear to increase with the total number of operations reported. The increase in risk associated with having had surgery was restricted to the category "other surgery." This category contained a range of procedures from minor, the most common of which was skin stitches, through to more complicated operations, such as urological and cardiovascular procedures. The association between sCJD and any surgery was reduced when those "other" operations likely to be most prone to recall bias and misclassification were excluded, and the association largely disappeared when the whole of the "other surgery" category was excluded.

The association between any surgery and sCJD appeared strongest for operations in the preceding 10 to 20 years. This is compatible with the deduced incubation periods form previous neurosurgical transmissions (12-28 months) and from one of the two transmissions from corneal transplants (18 and 320 months).[7] "Other surgery" further back in the past was also associated with sCJD. Longer incubation periods would be expected from more peripheral routes of surgical transmission. However, differential recall bias for respondents for cases and control subjects is also a possible explanation for these observations. Kondo and Kuroiwa [28] describe an association between any surgery within 5 years of disease onset and risk for sCJD; however, they did not examine any other time period. The mean time between first surgery and death was 29 (standard deviation, 17.4) years in the Australian study, and the median time between first gynecological surgery and onset was 21 (range, 0-60) years in the European study. [16] [17]

Although our results appear broadly consistent with two previous large case-control studies from Australia and Europe, some important differences are apparent when examined in detail.[16][17] All reported an increased risk for sCJD associated with "any surgery" and with "other surgery." Whereas in this study there was some evidence that both eye and orthopedic surgeries within the preceding 20 years were associated with increased risk for sCJD, we found no evidence of an association of risk with other categories of surgery. The Australian study found increased risk associated with a range of surgical procedures (carpal tunnel, eye, heart, hemorrhoid, gall bladder, hernia, hysterectomy, varicose vein), and the European study found a small increased risk associated with gynecological surgery (and reduced risk associated with tonsillectomy and appendectomy). Other smaller studies have reported varying findings relating to medical risk and sCJD, but have lacked power and/or been subject to bias. [27-32]

All these studies are susceptible to a number of potential sources of bias. In the Australian and European studies, interviews were performed with relatives of cases, but directly with control subjects, which may have resulted in systematic differences in the quality of information available for cases and control subjects.[16][17] To minimize this problem, we interviewed relatives of control subjects rather than control subjects themselves to "match" the approach used to obtain data on cases. Nevertheless, we cannot exclude the possibility that recall bias accounts for the differences we observed between cases and control subjects, particularly for "other surgery." Relatives of cases may make more effort to recall all surgical procedures, even the most minor, than relatives of control subjects. On the other hand, the analysis of anatomic categories rather than specific procedures could dilute the association of a particular high-risk procedure with CJD and lead to failure to detect that association.[33] Furthermore, relatives were asked to recall procedures that occurred many years in the past. This is likely to have resulted in some data from cases and control subjects being misclassified. If the tendency to misclassification was similar for cases and control subjects, this could have obscured real causal associations. Response bias is a possibility because no risk factor information was obtained for 72 cases who were, on average, 3 years older than the 431 cases with risk factor data.

The relationship of the respondent to the case or control subject may also contribute to bias if systematically different between cases and control subjects. Respondent types were similar for those born before 1950, but for those born after 1950, 25% of the control respondents were parents compared with none of the case respondents. Restricting the analysis to those born before 1950 did not alter our findings (data not shown). Other potential sources of bias relating to the NatCen controls have been detailed previously.[22]

Examining a large number of sCJD cases, we found no evidence of temporal-geographic links suggestive of onward transmission through use of contaminated instruments during neurosurgery or gynecological surgery. Given the distribution of infectivity in sCJD and the resistance of the infectious agent to decontamination, we might have expected to find evidence of iatrogenic transmission via neurosurgery in this group of cases classified as sCJD. However, in addition to the negative results here, there have been no reported instances of iatrogenic transmission of sCJD through neurosurgery or through stereotactic electrode use since the 1970s.[7] Possible explanations for this are that there have been no further transmissions through neurosurgery, that we have failed to identify them, or that transmission is episodic.[34] Alternatively, perhaps, decontamination has improved sufficiently to prevent transmission occurring. Since the early 1980s in the United Kingdom, it has been recommended that neurosurgical instruments used on people with known CJD should not be reused. However, how strictly this has been adhered to is unknown, and transmission from those incubating the disease certainly remains a possibility. The establishment of further guidance in the late 1980s aimed to reduce this possibility.[35][36]

We may have missed some potential sources of iatrogenic transmission for a variety of reasons, including referral to other centers in the United Kingdom and atypical presentations being unrecognized as CJD. In addition, we only had general practitioner records in a small proportion of cases, having to rely on reported surgical histories from relatives for most cases. Because a proportion of the operations were performed relatively recently, there may not have been a long enough period of follow-up to detect cases of transmission. However, given that the observed neurosurgical transmissions had incubation periods of 15 to 28 months and the 16-year period examined, we would expect to have identified any neurosurgical transmissions that occurred in the first 10 to 12 years of that period. Also, some people incubating the disease may have died of competing causes, for example, from cancer, before symptoms of CJD had developed.

It is perhaps not surprising that we did not find evidence of transmission of sCJD through gynecological surgical procedures. Although to our knowledge, infectivity has not been tested for in gynecological tissues (ovary and nongravid uterus) other than placenta in humans, cattle, sheep, or goats,[37] these tissues would not be expected to contain high infectivity titers. Also, if this were an important route of transmission, an excess of female sCJD cases might be expected. The female/male ratio over the study period in the United Kingdom was 1.08: 1.

Our data suggest that it is unlikely that a high proportion of UK sCJD cases are the result of transmission during surgery. However, we cannot exclude the possibility that such transmission occurs occasionally. We observed an increased risk for sCJD associated with reported surgical history, but this could be because of recall bias. We did not find any convincing individual links of sCJD cases related to surgery. However, it is important to determine whether the increased risk

associated with reported surgical history reflects a causal association or recall bias. A study based on accurate surgical histories obtained from medical records is underway. In the meantime, decontamination and public health guidance should be followed, [34-36] and efforts to imporve decontamination of surgical instruments are paramount.

Acknowledgements. ...snip...end...TSS,ftx_abs

ALSO, some additional information on the UK export history of mad cow tainted pharmaceutical products as follows ;

10 January 1990





2.1 At the first meeting of the Working Party on Bovine Spongiform Encephalopathy on 6 September 1989, detailed consideration was given to XXXXX Surgical Catgut. This arose from the Company's response to the Letter to Licence Holders, indicating that the bovine small intestine source material was derived from UK cattle, unlike 8 other licenced catgut sutures. In contrast XXXXX Surgical Catgut was stated to hold over 90% share of the market for catgut sutures, and to constitute approximately 83% of all sutures used in U.K.



U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)

<--- Dec 1998 ---> <--- 1998 YTD --->

Country Quantity Value Quantity Value


WORLD TOTAL . . . . . . . 10,801 3,116 143,058 40,068

Belgium . . . . . . . . . --- --- 107 14 France . . . . . . . . . 81 49 2,727 1,132 Switzerland . . . . . . . --- --- 1,357 1,693 United Kingdom . . . . . 1,188 242 35,001 5,564

U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date Subheading 300210: ANTISERA AND OTHER BLOOD FRACTIONS, AND MODIFIED IMMUNOLOGICAL PRODUCTS

3002.10.0010: HUMAN BLOOD PLASMA

snip... see full text ;


(Adopted by the International Committee of the OIE on 23 May 2006)

11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau, ......

THE only difference between the UK poisoning the globe, and the USA, it is now legal with GWs and OIEs BSE MRR policy ;

IT's O.K. to poison 3rd world countries ;

On 20 February 1990, Dr Pickles wrote to Ms Verity (APS/CMO). Dr Picklesí minute included the following:

1. Mr Meldrum is arguing that MAFF have already taken all the necessary and responsible steps to warn importing countries of the BSE dangers in UK meat and bone meal. Yet the action taken so far overseas suggest the message has not got through, or where it has this has been late. The first nation that woke up to the danger did so a year after our own feed ban. It seems even now several EC countries neither ban our imports or the general feeding of ruminant protein. It also seems the OIE and CVO have yet to inform the rest of the world.

2. I do not see how this can be claimed to be responsible. We do not need an expert group of the Scientific Veterinary Committee to tell us British meat and bone meal is unsafe for ruminants. I fail to understand why this cannot be tackled from the British end which seems to be the only sure way of doing it, preferably by banning exports. As CMO says in his letter of 3 January surely it is short sighted for us to risk being seen in future as having been responsible for the introduction of BSE to the food chain in other countries.[79]




I am concerned at the possible ban on the export of glands and organs for pharmaceutical purposes. No doubt you will be liaising with Brian Taylor to determine what products are being exported for these purposes and whether responsibility falls to DoH or ourselves.

Like you, I would prefer to avoid a further Commission Decision covering exports of bovine offals since it removes some of the flexibility that we now enjoy.

K C Medlrum 19 February 1990

We decided NOT to recommend that exports for pharmaceutical products etc be similarly stopped because it is less likely that these would find their way onto the human consumption market, and in these circumstances it seemed unjustifiable to propose a ban on the trade, particularly without consultation. ...

IT looks as if the SVC will want to discuss this again on 7/8th March. DOES it need someone from CPMP to tell the SVC to mind their own business. IF they persist in discussing it, we may need to have a DH representative at the meeting. IF the SVC convince themselves there is a problem with pharmaceuticals sourced from bovine ingredients in the UK, there is no telling what a mess they might be able to cause for our pharmaceutical manufacturers, as they have done for our beef industry. ...


The By-Products Problem





Comment- It is known that British Bone Meal has been exported to the Netherlands and the USA. It is possible that it may have been used to compound animal feed stuffs, which may have been used for cattle. The use of ruminant protein has NOT been banned in the USA. The Company have not addressed the issue of ensuring that source cattle have not been fed ruminant protein, and that feeding practices are recorded and certified.

Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001 Date: Tue, 9 Jan 2001 16:49:00 -0800 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To:

Bovine Spongiform Encephalopathy

Greetings List Members,

I was lucky enough to sit in on this BSE conference call today and even managed to ask a question. that is when the trouble started.

I submitted a version of my notes to Sandra Blakeslee of the New York Times, whom seemed very upset, and rightly so.

"They tell me it is a closed meeting and they will release whatever information they deem fit. Rather infuriating."

And I would have been doing just fine, until I asked my question. I was surprised my time to ask a question came so quickly.

(understand, these are taken from my notes for now. the spelling of names and such could be off.)

[host Richard Barns] And now a question from Terry S. Singeltary of CJD Watch.

[TSS] Yes, Thank You. U.S. cattle - what kind of guarantee can you give for serum or tissue donor herds?

[no answer, you could hear in the background, mumbling and "We can't. Have him ask the question again."]

[host Richard] Could you repeat the question?

[TSS] U.S. cattle..what kind of guarantee can you give for serum or tissue donor herds?

[not sure whom ask this] What group are you with?

[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.

[not sure who is speaking] Could you please disconnect Mr. Singeltary

[TSS] You are not going to answer my question?

[not sure whom speaking] NO

From this point, I was still connected, got to listen and tape the whole conference. at one point someone came on, a woman, and ask again;

[unknown woman] What group are you with?

[TSS] CJD Watch and my Mom died from hvCJD We are trying to tract down CJD and other human TSE's world wide. I was invited to sit in on this from someone inside the USDA/APHIS and that is why I am here. Do you intend on banning me from this conference now?

At this point the conference was turned back up, and I got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, I will try and give you a run-down for now, of the conference.

IF I were another Country, I would take heed to my notes, BUT PLEASE do not depend on them. ask for transcript from:

RBARNS@ORA.FDA.GOV 301-827-6906

He would be glad to give you one ;-)


----- Original Message ----- From: "Terry S. Singeltary Sr." To: Sent: Sunday, December 16, 2007 3:52 PM Subject: [CJD-L] Risk factors for sporadic Creutzfeldt-Jakob disease

Published Online: 11 Dec 2007 Copyright © 2007 American Neurological Association Original Article

Risk factors for sporadic Creutzfeldt-Jakob disease

Hester J. T. Ward, FFPH 1 *, Dawn Everington, MSc 1, Simon N. Cousens, MA 2,Blaire Smith-Bathgate, RGN 1, Michelle Gillies, MRCP 1, Katy Murray, MRCP 1,Richard S. G. Knight, FRCPE 1, Peter G. Smith, DSc 2, Robert G. Will, FRCP 11National Creutzfeldt-Jakob Disease Surveillance Unit, University ofEdinburgh, Western General Hospital, Edinburgh, United Kingdom2Department of Epidemiology and Population Health, London School of Hygieneand Tropical Medicine, London, United Kingdomemail: Hester J. T. Ward (*Correspondence to Hester J. T. Ward, National CJD Surveillance Unit,Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, United KingdomFunded by:Department of Health; Grant Number: 121/7400Scottish Executive Health Department; Grant Number: R39924



Although surgical transmission of Creutzfeldt-Jakob disease (CJD) has been demonstrated, these iatrogenic cases account for only a small proportion of all CJD cases. The majority are sporadic CJD (sCJD) cases of unknown cause. This study investigated whether some cases classified as sCJD might have an unrecognized iatrogenic basis through surgical or other medical procedures


This study compared medical risk factors from 431 sCJD cases referred 1998 to 2006 with 454 population control subjects. Possible geographic and temporal links between neurological and gynecological operations in 857 sCJD cases referred from 1990 to 2006 were investigated


A reported history of ever having undergone surgery was associated with increased risk for sCJD (odds ratio, 2.0; 95% confidence interval, 1.3-2.1;p = 0.003). Increased risk was not associated with surgical categories chosen a priori but was confined to the residual category other surgery, in which the increase in risk appeared most marked for three subcategories: skin stitches, nose/throat operations, and removal of growths/cysts/moles. No convincing evidence was found of links (same hospital, within 2 years) between cases undergoing neurosurgery or gynecological surgery


It is unlikely that a high proportion of UK sCJD cases are the result of transmission during surgery, but we cannot exclude the possibility that such transmission occurs occasionally. A study based on accurate surgical histories obtained from medical records is required to determine whether the increased risk associated with reported surgical history reflects a causal association or recall bias.

Ann Neurol 2007--------------------------------------------------------------------------------

Received: 24 May 2007; Revised: 5 September 2007; Accepted: 1 October 2007

Digital Object Identifier (DOI)10.1002/ana.21294 About DOIAdditional Material


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