Wednesday, August 20, 2008

Tonometer disinfection practice in the United Kingdom: A national survey

Eye (2008) 22, 1029–1033; doi:10.1038/sj.eye.6702831; published online 20 April 2007

Tonometer disinfection practice in the United Kingdom: A national survey
Financial or proprietary interest: nil

Financial Support: nil

R J Hillier1 and N Kumar1

1Ophthalmology Department, Aintree University Hospitals NHS Foundation Trust, Walton Hospital, Liverpool, UK

Correspondence: RJ Hillier, SpR in Ophthalmology, Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WH, UK. Tel: +44 07811 190588; Fax: +44 0161 276 5555; E-mail:

Received 2 October 2006; Revised 16 March 2007; Accepted 16 March 2007; Published online 20 April 2007.

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To assess current tonometer disinfection practice in the UK, and compare with published recommendations.


Every ophthalmology unit with training recognition in the UK was contacted (n=155). A senior nurse at each institution completed a telephone questionnaire regarding local tonometer disinfection practice.


The response rate was 100%. Thirty-five units (23%) reported exclusive use of disposable tonometer heads and were excluded from further analysis. One hundred and twenty units (77%) used either reusable or a combination of reusable and disposable tonometer heads. Where reusable heads were used, 80 units (67%) immersed them in a chlorine-based solution such as sodium hypochlorite or sodium dichloroisocyanurate. Others used isopropyl alcohol (18 units), hydrogen peroxide (12 units), chloramine (5 units), chlorhexidine (4 units) and peracetic acid (1 unit). Where a chlorine-based agent was used, the concentration of available chlorine ranged from 125 to 30 000 p.p.m., with 50 units (63%) using a concentration of less than 5 000 p.p.m. (i.e., inadequate based on published recommendations). Where the tonometer head was immersed in disinfectant between patients (n=101), 29 units (29%) provided just one tonometer head per practitioner, making adequate soak time between patients unlikely. Every unit replenished the disinfectant at least daily, deemed sufficient for most agents. However, hydrogen peroxide solutions should be replenished twice daily, which did not take place in nine units.


This survey reveals disparity between current tonometer disinfection practice and published international recommendations, with some institutions using practices that may render patients susceptible to transmissible infection.

disinfection, tonometry, glaucoma



M. Mangieri1, G. Giaccone1, L. Limido1, G. Di Fede1, S. Suardi1, R. Capobianco1, P. Fociani2, O. Bugiani1, F. Tagliavini1 1 Istituto Nazionale Neurologico Carlo Besta, Division of Neuropathology and Neurology 5, Milano, Italy and 2 Ospedale Luigi Sacco, Division of Pathology, Università di Milano, Milano, Italy


Creutzfeldt-Jakob disease (CJD) is marked by the presence of the protease-resistant prion protein (PrPres) in the brain. Studies of the retina and optic nerve in patients with CJD are scanty and on very small series of patients. We analysed ocular tissues of sporadic CJD patients (retina of 58 and optic nerve of 51), representing all combinations of PRNP codon 129 polymorphisms and PrPres types by Parchi, except VV1. Ocular tissue from 24 patients with other neurological diseases were used as controls. The ocular tissue was collected at autopsy and the samples were fixed in Carnoy solution or frozen. Before immunohistochemistry with 3F4 antibody, the sections were pretreated with proteinase K and guanidine thiocyanate. In all cases of sCJD the retina showed immunoreactivity for PrPres localized in the inner and outer plexiform layers, with a synaptic type of labelling. No difference in the pattern of labeling was detected between CJD patients with different PRNP codon 129 polymorphisms and PrPres types in the brain. In all cases with frozen retinal tissue available (n = 18), the immunoblot was positive for PrPres . Two out of the 51 sCJD showed the deposition of PrPres also in the optic nerve, corresponding to an immunostaining delineating stellate cells and associated with the presence of numerous CD68- and CD45-positive cells. Our results demonstrate the presence of the pathological form of prion protein not only in the retina of all sCJD cases analysed, but also in optic nerve in a small subset of sCJD patients, a finding previously described only in variant CJD and in experimental animal models. Moreover, our data suggest a correlation between the deposition of PrPres and inflammatory changes in the optic nerve in sCJD.


----- Original Message ----- From: "Terry S. Singeltary Sr." <[log in to unmask]> To: <[log in to unmask]> Sent: Thursday, December 28, 2006 10:23 AM Subject: Ophthalmic Surgery in Prion Diseases

Volume 13, Number 1–January 2007 Dispatch Ophthalmic Surgery in Prion Diseases Tsuyoshi Hamaguchi,*1 Moeko Noguchi-Shinohara,* Yosikazu Nakamura,†2 Takeshi Sato,‡2 Tetsuyuki Kitamoto,§2 Hidehiro Mizusawa,¶2 and Masahito Yamada*2 *Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; †Jichi Medical University, Shimotsuke, Japan ‡National Center for Neurology and Psychiatry, Ichikawa, Japan; §Tohoku University Graduate School of Medicine, Sendai, Japan; and ¶Tokyo Medical and Dental University, Tokyo, Japan

Suggested citation for this article

Abstract Eleven (1.8%) of 597 patients underwent ophthalmic surgery within 1 month before the onset of prion disease or after the onset. All ophthalmologists reused surgical instruments that had been incompletely sterilized to eliminate infectious prion protein. Ophthalmologists should be aware of prion diseases as a possible cause of visual symptoms and use disposable instruments whenever possible.

Visual impairment occurs in 10% to 20% of patients with sporadic Creutzfeldt-Jakob disease (sCJD) during an early stage of the disease (Heidenhain variant) (1,2). Some patients with prion diseases may visit ophthalmologists with visual impairment due to prion diseases or with coexisting age-related eye diseases (3,4).

Infectious prion protein (PrPSc) was identified in the retina and optic nerve in patients with variant CJD (vCJD) and sCJD (5,6), and CJD has been transmitted by corneal transplantation (7,8). In the World Health Organization (WHO) guidelines, eyes were classified as highly infectious tissues (9).

Secondary transmission of PrPSc through ophthalmic surgery could possibly be prevented around the onset of prion diseases, although surgery that is performed long before the onset of prion diseases would not have that potential. It is important to understand the current status of ophthalmic surgery for patients with prion diseases and to clarify the clinical features of the patients with prion diseases who undergo ophthalmic surgery. Here, we describe the relevant data from CJD surveillance in Japan.

The Study.....snip full text ;

----- Original Message ----- From: "Terry S. Singeltary Sr." <[log in to unmask]> To: <[log in to unmask]> Sent: Wednesday, December 27, 2006 12:21 PM Subject: ABNORMAL PRION ACCUMULATION ASSOCIATED WITH RETINAL PATHOLOGY IN EXPERIMENTALLY INOCULATED SCRAPIE-AFFECTED SHEEP

Eye procedure raises CJD concerns

November 19, 2004 United Press International by STEVE MITCHELL

A New York man who died from a rare brain disorder similar to mad cow disease in May underwent an eye procedure prior to his death that raises concerns about the possibility of transmitting the fatal disease to others, United Press International has learned. The development comes on the heels of the announcement Thursday by U.S. Department of Agriculture officials of a possible second case of mad cow disease in U.S. herds.

Richard Da Silva, 58, of Orange County, N.Y., died from Creutzfeldt Jakob disease, an incurable brain-wasting illness that strikes about one person per million.

Richard's wife Ann Marie Da Silva told UPI he underwent a check for the eye disease glaucoma in 2003, approximately a year before his death. The procedure involves the use of a tonometer, which contacts the cornea -- an eye tissue that can contain prions, the infectious agent thought to cause CJD.

Ann Marie's concern is that others who had the tonometer used on them could have gotten infected.

A 2003 study by British researchers suggests her concerns may be justified. A team led by J.W. Ironside from the National Creutzfeldt-Jakob Disease Surveillance Unit at the University of Edinburgh examined tonometer heads and found they can retain cornea tissue that could infect other people -- even after cleaning and decontaminating the instrument.

"Retained corneal epithelial cells, following the standard decontamination routine of tonometer prisms, may represent potential prion infectivity," the researchers wrote in the British Journal of Ophthalmology last year. "Once the infectious agent is on the cornea, it could theoretically infect the brain."

Prions, misfolded proteins thought to be the cause of mad cow, CJD and similar diseases, are notoriously difficult to destroy and are capable of withstanding most sterilization procedures.

Laura Manuelidis, an expert on these diseases and section chief of surgery in the neuropathology department at Yale University, agreed with the British researchers that tonometers represent a potential risk of passing CJD to other people.

Manuelidis told UPI she has been voicing her concern about the risks of corneas since 1977 when her own study, published in the New England Journal of Medicine, showed the eye tissue, if infected, could transmit CJD.

At the time the procedure was done on Richard Da Silva, about a year before he died, she said it was "absolutely" possible he was infectious.

The CJD Incidents Panel, a body of experts set up by the U.K. Department of Health, noted in a 2001 report that procedures involving the cornea are considered medium risk for transmitting CJD. The first two patients who have a contaminated eye instrument used on them have the highest risk of contracting the disease, the panel said.

In 1999, the U.K. Department of Health banned opticians from reusing equipment that came in contact with patients' eyes out of concern it could result in the transmission of variant CJD, the form of the disease humans can contract from consuming infected beef products.

Richard Da Silva was associated with a cluster of five other cases of CJD in southern New York that raised concerns about vCJD.

None of the cases have been determined to stem from mad cow disease, but concerns about the cattle illness in the United States could increase in light of the USDA announcement Thursday that a cow tested positive on initial tests for the disease. If confirmed, this would be the second U.S. case of the illness; the first was detected in a Washington cow last December. The USDA said the suspect animal disclosed Thursday did not enter the food chain. The USDA did not release further details about the cow, but said results from further lab tests to confirm the initial tests were expected within seven days.

Ann Marie Da Silva said she informed the New York Health Department and later the eye doctor who performed the procedure about her husband's illness and her concerns about the risk of transmitting CJD via the tonometer.

The optometrist -- whom she declined to name because she did not want to jeopardize his career -- "didn't even know what this disease was," she said.

"He said the health department never called him and I called them (the health department) back and they didn't seem concerned about it," she added. "I just kept getting angrier and angrier when I felt I was being dismissed."

She said the state health department "seems to have an attitude of don't ask, don't tell" about CJD.

"There's a stigma attached to it," she said. "Is it because they're so afraid the public will panic? I don't know, but I don't think that the answer is to push things under the rug."

New York State Department of Health spokeswoman Claire Pospisil told UPI she would look into whether the agency was concerned about the possibility of transmitting CJD via tonometers, but she had not called back prior to story publication.

Disposable tonometers are readily available and could avoid the risk of transmitting the disease, Ironside and colleagues noted in their study. Ann Marie Da Silva said she asked the optometrist whether he used disposable tonometers and "he said 'No, it's a reusable one.'"

Ironside's team also noted other ophthalmic instruments come into contact with the cornea and could represent a source of infection as they are either difficult to decontaminate or cannot withstand the harsh procedures necessary to inactivate prions. These include corneal burrs, diagnostic and therapeutic contact lenses and other coated lenses.

Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment.

"They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families.

U.S. Centers for Disease Control and Prevention spokeswoman Christine Pearson did not return a phone call from UPI seeking comment. The agency's Web site states the eye is one of three tissues, along with the brain and spinal cord, that are considered to have "high infectivity."

The Web site said more than 250 people worldwide have contracted CJD through contaminated surgical instruments and tissue transplants. This includes as many as four who were infected by corneal grafts. The agency noted no such cases have been reported since 1976, when sterilization procedures were instituted in healthcare facilities.

Ironside and colleagues noted in their study, however, many disinfection procedures used on optical instruments, such as tonometers, fail. They wrote their finding of cornea tissue on tonometers indicates that "no current cleaning and disinfection strategy is fully effective."

Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading.

"They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all casesof CJD.

"There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said.

Ann Marie Da Silva said she has contacted several members of her state's congressional delegation about her concerns, including Rep. Sue Kelly, R-N.Y., and Sen. Charles Schumer, D-N.Y.

"Basically, what I want is to be a positive force in this, but I also want more of a dialogue going on with the public and the health department," she said.

Cadaver corneal transplants -- without family permission Houston, Texas channel 11 news 28 Nov 99 Reported by Terry S. Singeltary Sr.son of CJD victim

Subject: RE-The Eyes Have It (cjd) and they could be stealing them from your loved one... "pay back time" Date: Sat, 16 Sep 2000 10:04:26 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To:

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

I hate to keep kicking a madcow, but this still is very disturbing to me. Not only for the recipient of the cornea's, but as well, for the people whom would be operated on, using the same tools that were used to put those stolen cornea's in the recipient with. No history of this donor or his family (re-ffi), or anything would be known, using stolen organs and or tissue's. I just think this is not only wrong, but very dangerous to a great many other people, as this is one of the most infectious tissues of TSE's. It seems that this practice of stealing organ/tissue happens more than we think. Anyway, the family of the victim which had their cornea's stolen, are now suing. In the example I used with my Mother, if 3 months before, she would have been in a catastrophic accident (car wreck, whatever), no autopsy (for whatever reason), no family (for whatever reason), she lay in the morgue, and after 4 hours, they come steal the cornea's, lot of people could have been infected, just because of lack of medical history of donor/family. It may be hypothetical, but very real. We need to stop the spread of this disease.

kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA ===========================================

Previous story--

Cadaver corneal transplants -- without family permission...


Sept. 15, 2000, 11:39PM

Slain woman's family sues over missing eyes

By BILL MURPHY Copyright 2000 Houston Chronicle

The family of a woman who was stabbed to death last year has filed a lawsuit accusing the Lions Eye Bank of Houston of removing the woman's eyes without permission and inserting plastic discs in their place.

Daisy Diaz's relatives were horrified when they saw her body and noticed her eyes were missing, said their lawyer, Duncan Neblett III.

"They're a Catholic family," Neblett said. "They have strong beliefs about the body and burial. They were really upset by this."

Dorey Zidrow, the eye bank's spokeswoman, said she could not specifically discuss the Diaz case because it was in litigation. But Zidrow said a state law allows doctors to remove corneas -- the dime-sized lens near the eye's surface -- from a corpse without the family's permission.

The eye bank's usual procedure calls for removing the corneas, Zidrow said, but not the entire eyes.

"There are an awful lot of people who benefit from this program in the state of Texas," she said.

Diaz, 25, was stabbed to death in her apartment in the 400 block of Thornton in October. Her brother-in-law, 30-year-old Raudel Quiroz, is charged in the killing but has not been caught.

Neblett said authorities have told him Quiroz may have returned to his native Guatemala.

Neither Diaz nor her family had given permission to donate any of her organs, Neblett said.

Although state law allows corneas to be removed from corpses without first gaining the family's permission, they cannot be removed over the family's stated objection.

The eye bank is located at, and staffed by, the Baylor College of Medicine, and receives part of its funding from the Lions Club.

The Diaz lawsuit is the second such suit to be filed against the eye bank in recent years.

The family of Levi Perry Jr., a Houston teacher shot to death in MacGregor Park in 1994, also alleged in their suit that Perry's eyes were removed. The family was awarded $345,000 from the eye bank in April 1999.




Sec. 693.012. Removal of Corneal Tissue Permitted Under Certain Circumstances.

On a request from an authorized official of an eye bank for corneal tissue, a justice of the peace or medical examiner may permit the removal of corneal tissue if:

(1) the decedent from whom the tissue is to be removed died under circumstances requiring an inquest by the justice of the peace or medical examiner;

(2) no objection by a person listed in Section 693.013 is known by the justice of the peace or medical examiner; and

(3) the removal of the corneal tissue will not interfere with the subsequent course of an investigation or autopsy or alter the decedent's postmortem facial appearance.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.012 -------------------------------------------------------- TEXAS STATUTES Sec. 693.003. Consent Required in Certain Circumstances.

(a) A medical examiner or a person acting on the authority of a medical examiner may not remove a visceral organ unless the medical examiner or person obtains the consent of a person listed in Section 693.004.

(b) If a person listed in Section 693.004 is known and available within four hours after death is pronounced, a medical examiner or a person acting on the authority of a medical examiner may not remove a nonvisceral organ or tissue unless the medical examiner or person obtains that person's consent.

(c) If a person listed in Section 693.004 cannot be identified and contacted within four hours after death is pronounced and the medical examiner determines that no reasonable likelihood exists that a person can be identified and contacted during the four-hour period, the medical examiner may permit the removal of a nonvisceral organ or tissue.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.003 -------------------------------------------------------- PLEASE NOTE; the bottom would only pertain to those who know of the law. if you don't know about it, you cannot dispute, so in four hours, they can legally remove body organs, as long as they don't disfigure. and who is to know the difference? makes me wonder of some of my dead relatives, and if they were burried with their eye's and or any of their organs. This is very disturbing, if not for moral reasons, but for the risk of dangerous pathogens (human TSE's, etc.) to be transmitted. only time will tell, but i am very disturbed. these laws are not morally correct. They should be re-written as to they cannot so easily take your organs, with no one knowing. The Family or Victim, must consent. There should be some kind of research on donor/family medical history...TSS --------------------------------------------------------

Sec. 693.013. Persons Who May Object to Removal.

The following persons may object to the removal of corneal tissue:

(1) the decedent's spouse;

(2) the decedent's adult children, if there is no spouse;

(3) the decedent's parents, if there is no spouse or adult child; or

(4) the decedent's brothers or sisters, if there is no spouse, adult child, or parent.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.013 ------------------------------------------------------- to cover one's butt....

Sec. 693.014. Immunity From Damages in Civil Action.

(a) In a civil action brought by a person listed in Section 693.013 who did not object before the removal of corneal tissue, a medical examiner, justice of the peace, or eye bank official is not liable for damages on a theory of civil recovery based on a contention that the person's consent was required before the corneal tissue could be removed.

(b) Chapter 104, Civil Practice and Remedies Code, applies to a justice of the peace, medical examiner, and their personnel who remove, permit removal, or deny removal of corneal tissue under this subchapter as if the justice of the peace, medical examiner, and their personnel were state officers or employees.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.014

[[[as you can see, they knew it was wrong when they wrote the laws. or they would not have covered the rear-ends so well...TSS]]] --------------------------------------------------------- thanks again, kind regards, Terry S. Singeltary Sr.

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CJD, they eye's have it and they could be stealing them from your loved one

Subject: RE-The Eyes Have It (cjd) and they could be stealing them from your loved one... "pay back time" Date: Sat, 16 Sep 2000 10:04:26 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To:

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

I hate to keep kicking a madcow, but

CJD and Ophthalmology* May 4, 2004

Subject: RE--[Docket No. 03D-0118] Guidance for FDA Staff on Sampling or Detention Without Physical Examination of Decorative Contact Lenses (Import Alert 86-10)

Date: Mon, 07 Apr 2003 15:18:04 -0500

From: "Terry S. Singeltary Sr." To:

TSS SUBMISSION TO [Docket No. 03D-0118]

I would kindly like to submit to [Docket No. 03D-0118]

Guidance for FDA Staff on Sampling or Detention Without Physical Examination of Decorative Contact Lenses (Import Alert 86-10); Availability.

My concerns relate to human/animal TSEs Transmissible Spongiform Encephalopathies and all variants and the potential risks from the cosmetic RE-USE of these products IF re-use takes place in the USA. i am aware of such practices in the UK and recently ask where i received my new glasses if this practice of re-use of _trial_ contact lenses takes place. he was aware of only one type lens that this practice takes place with. i kindly informed him that this practice could potentially spread this agent and hoped he would look into it. other concerns of mine are with children and the _sharing_ of such contact lenses. if regulation are lax to the point of say (nutritional supplements), where there really are no regulations, the potential for many pathogens via the eye's are a very real threat, especially since the titre of infectivity for TSEs has recently been lowered to .1 gram for being LETHAL. i hope that the data below will provide enough information for further investigations into my concerns of RE-USE OF Contact lenses and potential exposure to human TSEs;

(Investigative Ophthalmology and Visual Science. 2003;44:342-346.) © 2003 by The Association for Research in Vision and Ophthalmology, Inc.

Prion Protein Accumulation in Eyes of Patients with Sporadic and Variant Creutzfeldt-Jakob Disease

Mark W. Head1, Victoria Northcott1, Kathleen Rennison1, Diane Ritchie1, Linda McCardle1, Tristan J. R. Bunn1, Neil F. McLennan1, James W. Ironside1, Andrew B. Tullo2 and Richard E. Bonshek2

1 From the National Creutzfeldt-Jakob Disease Surveillance Unit and Department of Pathology of the University of Edinburgh, Scotland, United Kingdom; and the 2 Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom.

PURPOSE. Creutzfeldt-Jakob disease (CJD) primarily affects the brain. This study was conducted to assess the possible involvement of the eye in sporadic and variant CJD by testing for the presence of the disease-associated, protease-resistant isoform of the prion protein (PrPSc) in ocular tissue.

METHODS. Human eyes from donors with CJD and non-prion neurodegenerative disease control eyes were studied. In situ hybridization and Western blot analysis were used to determine the normal pattern of cellular prion protein (PrPC) expression. Western blot analysis and immunohistochemistry were then used to determine the localization, abundance, and isotype of PrPSc in eyes in CJD.

RESULTS. PrPC was expressed in the nuclear layers of the retina. In both the sporadic and variant forms of CJD, PrPSc accumulated throughout the synaptic layers of the retina. The levels of PrPSc found in the retina were comparable with those found in the brain. Lower levels of PrPSc could be found in the optic nerve, but no PrPSc was detectable in other ocular tissues. The glycoform ratio of PrPSc in the retina did not correspond to that found in the brain.

CONCLUSIONS. Presumptive centrifugal spread of PrPSc from the brain through the optic nerve occurs in two major types of CJD. PrPSc is a marker of CJD infectivity. Given that routine decontamination may not remove PrPSc from surgical instruments, a careful risk assessment should be made of possible iatrogenic spread of sporadic and variant CJD after surgery to the retina or optic nerve.

Organ distribution of prion proteins in variant Creutzfeldt-Jakob disease


In this article we give an overview of the transmissible spongiform encephalopathies, with emphasis on the evidence for the distribution of abnormal prions in tissues. The normal prion protein is distributed ubiquitously throughout human body tissues. Endogenous expression of the normal prion protein, as well as auxiliary proteins, plays a part in accumulation of the abnormal prion protein. As exemplified by variant Creutzfeldt-Jakob disease (vCJD) the abnormal prion protein can accumulate in the host lymphoid system, in particular the follicular dendritic cells. The route for the disease-related prion neuroinvasion is likely to involve the peripheral nervous system. An alternative route may involve blood constituents. Both animal studies and studies on vCJD patients suggest a potential for abnormal prion distribution in several peripheral tissues other than the lymphoreticular system. In human beings the abnormal prion has been reported in the brain, tonsils, spleen, lymph node, retina, and proximal optic nerve. Infectivity, although present in peripheral tissues, is at lower levels than in the central nervous system (CNS). Animal models suggest that the growth of infectivity in the CNS is likely to be gradual with maximum values during the clinical phase of disease. That tissues may harbour the abnormal prion, at different levels of infectivity, during the incubation period of the disease raises concerns of iatrogenic transmission of the disease either after surgery, blood transfusion, or accidental organ transplantation from donors in the preclinical phase of the disease.

Affiliations: a IR and FB are at the Communicable Diseases and Environmental Health Branch, Department of Health, Canberra, Australia. b ML is at the National Centre for HIV Epidemiology and Clinical Research, Darlinghurst, Australia. c SC is at the Department of Pathology, University of Melbourne, Victoria, Australia.

Royal College of Ophthalmologists Guidelines Creutzfeldt-Jakob Disease (CJD) and Ophthalmology

Background In the Clinic In the Operating Theatre Surgical Procedures on the Posterior Eye Ocular Tissue Transplantation Action if exposure to contamination takes place Patient Risk Groups

1. Background

Patients with classical (sporadic) CJD are predominantly in their 60s and as such may come into contact with ophthalmologists because of cataract, glaucoma and macular degeneration, or because of visual symptoms caused by their condition1. Although there is no clear evidence of the transmission of spongiform encephalopathy from one patient to another by ophthalmic surgery other than through corneal transplantation2, it has been accepted for many years that instruments used on patients with known or suspected CJD undergoing any surgical procedure, should be destroyed3.

The number of individuals in the UK who may develop variant CJD (vCJD), believed to be the human form of BSE, is unknown but may yet number tens of thousands who may be infectious before their symptoms develop. The Department of Health (DH) has identified ophthalmology as an area of risk second only to neurosurgery, though other forms of surgery, e.g. on the gut and tonsils, could also lead to contamination of instruments by prions which routine decontamination does not eradicate. Research is in progress to establish the efficacy of current and improved methods of decontamination in removing prion protein.

The only certain way to avoid the as yet unquantifiable risks of ophthalmic devices and instruments being vectors of transmissible prions would be for them all to be disposable, though this is currently impossible without severely compromising patient care. In 1999, the Medical Devices Agency issued Advice Notes on contact lenses4 and on devices5 that touch the eye, though their full implementation at that time was not feasible. The College of Optometrists and the Association of British Dispensing Opticians have since agreed the case with the DH for a more pragmatic approach and have published practical guidance6 which was circulated to their members in October 2001.

There are, however, situations where improved awareness and changes in clinical practice can be implemented without compromising other standards or necessarily increasing costs, in order to minimise the risk of transmission of prion protein.

2. In the Clinic Back to top

2.1 A significant proportion of patients with classical CJD present with visual disturbance. Key features3 which should raise suspicion are:

2.1.1 Unexplained visual loss in the middle-aged and elderly.

2.1.2 Homonymous hemianopia in the absence of evidence of space-occupying lesion or CVA on MRI scan.

2.2 For any patient, including those being pre-operatively assessed for surgery, the possible onset of either form of CJD should be considered. The features of vCJD to date have not included visual symptoms until the late stages, though it should be noted that this form of disease occurs in much younger people (median age 29)7. Suspicion should be raised in any patient under the age of 50 years who, in the preceding year, has experienced new psychiatric or neurological symptoms sufficient to warrant referral to a psychiatrist or neurologist8.

2.3 Tonometry: disposable tonometer heads9, tonometer shields10 or Tonopens are essential for the patient who is known to have or is under suspicion of having CJD (see Table 1). One or more of these devices should be available in all departments11.

2.4 Re-usable tonometer heads: tonometer prisms should not be moved between clinical workstations, clinics and departments, to facilitate tracing and so that their life may be more readily determined for the purpose of regular replacement. Current methods of hygiene are acceptable, but it should be noted that the manufacturer Haag-Streit AG has determined12 that Goldmann tonometer prisms may be re-used 100 times following immediate cleaning and subsequent disinfection in sodium hypochlorite solution of (in Haag-Streit's own example, greater than) 2% for one hour at room temperature. If this method is used, tonometer heads should then be rinsed thoroughly in sterile saline or boiled water and wiped dry.

2.5 Soft and rigid contact lenses: ideally all contact lenses should be for the use of one individual only. Nowadays most contact lens wearers use disposable soft lenses. These, and some other soft and rigid lenses, can be fitted empirically and will never need to be re-used on other wearers. Exceptions have to be made for 'special complex diagnostic contact lenses6' in fitting sets and it has been established that these lenses (both corneal and scleral) may be decontaminated without damage using 20,000 ppm available chlorine from sodium hypochlorite solution (e.g. 2% Milton Sterilising Fluid) for 1 hour6 after which they must be thoroughly rinsed in sterile saline (e.g. 3 full rinses in a 10ml contact lens case is adequate to dilute residual chlorine to a safe level of 1 ppm) and then disinfected in the normal way, e.g. dry storage or disinfectant solution storage.

2.6 It is recommended that between patients examination (diagnostic) contact lenses (e.g. gonio, 3-mirror and fundus lenses) are wiped clean whilst moist before the face of the lens is immersed in the disinfection fluid normally used. At the end of each session they should be cleaned with detergent, rinsed thoroughly in sterile saline and then wiped dry. Work on the compatibility of such devices with sodium hypochlorite 2% solution is not yet complete. Diagnostic contact lenses should not be moved between clinics and departments.

3. In the Operating Theatre Back to top

3.1 All instruments and devices marketed as being disposable must be disposed of after single use13.

3.2 By March 2002, all personnel involved with any operation in any surgical discipline, including Ophthalmology, and the instrument trays, must be identifiable and traceable13.

3.3 The cleaning of surgical instruments is now recognised to be even more important than autoclaving in removing prion protein. Instruments should be cleaned in washer disinfectors of a modern and high standard14.

3.4 If a patient is known to be suffering from, or is at risk of either form of CJD (see Table 1), all instruments and devices must be segregated and destroyed by incineration after use3.

3.5 If a patient is suspected to be suffering from any form of CJD, consideration may be given to deferring surgery in order to allow clinical signs to be observed or for a further opinion to be sought. If surgery is deemed urgent, then consideration should be given to the operation, if possible, being carried out entirely with single-use instruments. If this is not possible, at the end of the procedure:

3.5.1 Re-usable instruments should be placed in an impervious plastic container with a close-fitting lid and sealed with heavy-duty tape. The box must be labelled with the patient's identification details, the surgical procedure for which the instruments were used and the name of the responsible person (theatre manager).

3.5.2 The box must be stored indefinitely in a designated place until the results of further investigations are known.

3.5.3 If the patient is confirmed as suffering from any form of CJD, the sealed box and its contents must remain undisturbed and be incinerated.

3.5.4 If an alternative and confirmed diagnosis is established, the instruments may be removed from the box by the responsible person and be sent to CSSD for processing in the normal way. The CSSD must be informed of this decision before the instruments are transported.

3.6 Surgical Procedures on the posterior eye Back to top

3.6.1 Recent evidence from studies on the eyes of patients who have died from classical or vCJD show that prion protein is present in the retina and optic nerve, but not elsewhere in the eye, using the methods of Western blotting and peroxidase staining15.

3.6.2 All instruments that penetrate the optic nerve sheath, e.g. enucleation snares or scissors, and evisceration spoons, should be traceable to individual patients, or preferably disposed of after single use.

3.6.3 Some instruments used in vitreoretinal surgery are already for single use, and efforts are continuing to develop alternatives to those that are not currently disposable.

3.6.4 For each essential non-disposable instrument that enters the vitreous cavity or comes close to or touches the retina, e.g. membrane scissors, the patient on whom they are used should be identifiable.

4. Ocular Tissue Transplantation Back to top

4.1 Guidelines on donor exclusion criteria and the retrieval of human ocular tissue for transplantation and research are already available16 are regularly revised and are carefully utilised by eye banks. Currently the only way to exclude donors known or suspected to have CJD is through the medical and behavioural history.

4.2 Suggested information for transplant recipients that specifically mentions remote risk of disease transmission is also available16.

4.3 Eye retrieval is now possible and recommended using disposable instruments17.

4.4 Eye Banks are advised that disposable instruments are now also available for all stages of processing17.

4.5 During corneal transplantation, all trephines and trephine blocks should be disposed of after single use.

4.6 Eye banks in the UK will continue to provide sclera on request, though the proximity of the sclera to the retina and optic nerve, where prion proteins may be present15, suggests that if alternative methods and materials are available, and that these should be given due consideration by surgeons.

4.7 It is essential that records of all ocular donor tissue are kept by eye banks; details of surgery should be recorded on the Royal College/UKT Transplant Record Form (or similar), and returned to the UK Transplant Information Executive.

4.8 The ability to trace all recipients of ocular tissue transplants and to monitor outcome are key components of a surgeon's responsibility. Completion of the Royal College/UKT Follow-up Forms is strongly encouraged for at least 5 years following corneal transplantation for penetrating and lamellar keratoplasty.

4.9 Surgeons should, through their Hospital Manager, ensure that hospital records of transplant recipients should be kept for at least 8 years after the patient has died or been lost to follow-up.

NB: Ocular tissue transplant recipients are currently not accepted as blood donors.

5. Action if exposure to contamination takes place Back to top

The CJD Incidents Panel (established November 2000) has already received several reports of ophthalmic incidents since September 1999, concerning known or suspected sporadic CJD, mostly involving cataract surgery. If a patient undergoing ophthalmic surgery subsequently develops any form of CJD, it is desirable that all instruments and devices involved should be traceable and taken out of circulation, and that subsequent patients who may have inadvertently been put at risk can be identified. For further advice in such an event contact Dr Philippa Edwards, Department of Health, Skipton House, 80 House Road, London, SE1 6LH, tel: 0207 - 972 5324, e-mail: claire.mills@doh.gsi

NB: A consultation document from the CJD Panel is accessible on

References: Back to top

1 Lueck CJ, McIlwaine GC, Zeidler M. CJD and the Eye. II. Ophthalmic and Non-Ophthalmic Features, Eye 2000; 14: 291-301

2 Hogan RN, Brown P, Heck E, Cavanagh HD. Risk of Prion Disease Transmission from Ocular Donor Tissue Transplantation, Cornea 1999; 18: 2-11

3 HSC 1988 1 (Annex 1)

4 MDA AN1999 (03): Single patient use of contact lenses: implications for clinical practice. Medical Devices Agency, October 1999

5 MDA AN 1999 (04): Single patient use of ophthalmic medical devices: implications for clinical practice. Medical Devices Agency, October 1999

6 College of Optometrists and Association of British Dispensing Opticians, September 2001: Guidance on the Re-Use of Contact Lenses and Ophthalmic Devices

7 Will RG, Ironside JW, Zeidler M et al. A New Variant of Creutzfeldt-Jakob Disease in the UK, Lancet 1996; 347: 921-5

8 Will RG et al: Psychiatric features of new variant Creutzfeldt-Jakob Disease, Psychiatric Bulletin 1999: 23; 264-7

9 Clement Clarke International Limited, Edinburgh Way, Harlow, Essex, CM20 2TT (Fax. 01279-635232)

10. Kestrel Healthcare Ltd, Network House, Basing View, Basingstoke, Hampshire, RG21 4HG (Tel. 01256-307580, Fax. 01256-307590)

11. Desai SP, Sivakumar S, Fryers PT. Evaluation of a disposable prism for tonometry, Eye 2001; 15: 279-282

12. Haag-Streit Dok. Nr. 9202 9200066 01010, 1998: Desinfektion der Haag-Streit Kontacktgläser und Tonometermesskörper

13. MDA DB 2000(04): Single-use Medical Devices: Implications and consequences of reuse

14. HSC 2000/032 Decontamination of Medical Devices

15. Wadsworth JDF, Joiner S, Hill AF, et al. Tissue distribution of protease-resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay, Lancet 2001: 358; 171-80


17. AMG Medical Products, 48 Church Street, Shipston on Stour, Warwickshire, CV36 4AS (Tel: 01608 662029; Fax 01608 663222).

Further Reading: Back to top

HSC 1999/178: Variant Creutzfeldt-Jakob disease (vCJD): Minimising the risk of transmission, NHS Executive, August 1999

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection, Advisory Committee on Dangerous Pathogens, 1998

Tullo AB, Buckley RJ, Painter M. CJD and the Eye, Eye 2000; 14: 259-260

Anderson S, Kaye SB, Tullo AB, Hart CA. CJD and Optometry: What are the risks? Optometry Today 2001

Table 1 Patient Risk Groups Back to top Known or at-risk patients Suspected patients

Patients diagnosed as having CJD or a related disorder*

Asymptomatic patients who are potentially at risk of developing CJD or a related disorder, i.e. - recipients of hormone derived from human pituitary glands, e.g. growth hormone, gonadotrophin - recipients of human dura mater grafts; - people with a family history of an inherited form of CJD or related disorder, i.e. close blood line relatives (parents, brothers, sisters, children, grandparents and grandchildren); sometimes patients may be uncertain of the type of CJD of which their relative(s) dies; in such circumstances, if two or more family members have been diagnosed as CJD patients, this is a good indication that it is the inherited form of the disease. Patients suspected of having CJD or a related disorder* i.e. whose clinical symptoms are suggestive of CJD but where the diagnosis has not yet been confirmed. * i.e. classical sporadic CJD, vCJD, Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia and kuru

January, 2002

Optometric practice does not expose patients to potentially infective procedures except via mucus membrane contact or contact with the cornea. This would include the use of contact lens fitting sets and tonometer heads. It is as yet unknown how reliable a route of transmission this is likely to be. The Spongiform Encephalopathy Advisory Committee (SEAC) advised in June 1999 that optometrists should not reuse trial contact lenses. Used trial lenses should be safely disposed of after use71. However, the recent publication of a study shows that although the prion responsible for vCJD is present in significant quantities in the optic nerve and retina, it could not be detected in the anterior segment of the eye of a vCJD victim. This has led to new recommendations by SEAC published in July 2001. These have been adopted by the College of Optometrists that has issued guidelines for the reuse of contact lenses and ophthalmic devices73.

In essence, these suggest that wherever practicable contact lenses or devices that come into contact with the eye should be disposed of after use. If the practitioner judges that only a reusable item is suitable, for example where a special complex diagnostic contact lens is needed the patient should be advised of the risks and benefits of the use of this item. After use it should be soaked in 2% sodium hypochlorite for one hour in addition to the normal cleaning procedure. The device should then be thoroughly rinsed. The practitioner concerned should keep a full record of the use of each contact lens. If the patient is in a high-risk category for the development of CJD even reusable item should always be disposed of immediately after use. The full guidelines are available from the College of Optometrists.

Diagnostic and treatment contact lenses such as goniscopy and fundus view contact lenses are not available in a disposable form. Volk advises us that any contact with sodium hypochlorite or heat sterilisation will have detrimental effects on the lenses. They suggest either ethylene oxide or the STERIS process, neither of which has been shown to be effective in the destruction of prions. Haag-Streit has published that tonometer heads may safely be disinfected in 2% sodium hypochlorite up to 100 times. This would make it marginally cheaper to use the disposable type of tonometer (Tonosafe™) (Figure 1) if the practitioner did this procedure frequently as well as complying with the above guidelines. Unpublished data mentioned in the College of Optometrists’ guidelines suggests that a one-hour soak in 2% sodium hypochlorite at room temperature did not effect the physical characteristics of rigid contact lenses. While sporadic CJD is a very rare disease, the full scale of the variant CJD epidemic is still unknown. It seems extremely unlikely that either of these diseases would be passed on by routine optometric practice. Given, however, that the risk is unknown and many patients (especially those being fitted for contact lenses) are young and healthy, it is appropriate that guidelines are now available to further minimise any risks.

AGENTS FOUND TO BE INEFFECTIVE AGAINST CJD • Alcohol67 • Hydrogen peroxide67. • Sodium dichloroiocyanurate (e.g. Presept)68 • Moist heat at 121°C for 15 minutes67 • Formalin (actually increased resistance to disinfection with heat)60 AGENTS FOUND TO BE EFFECTIVE AGAINST CJD • 8,259ppm available chlorine/sodium hypochlorite for 1/2 hour68 • 2M sodium hydroxide for 1 hour (not fully effective)68 • Porous load steamer 134-137°C for 18 minutes (not fully effective)68 • Phenol60 • Guanidine thiocyanate60

Further reading • Lueck C, Ocular features of CJD. Optician2000; 220: 23-27 • Lueck C J, McIlwaine G G, Zeidler M. Creuzfeld-Jacob disease and the eye. 1. Background and patient management. Eye 2000; 14:263-290 • Lueck C J, McIlwaine, Zeidler M, Creutzfeldt-Jacob disease and the eye. II. Ophthalmic and neuro-ophthalmic features. Eye 2000; 14:291-301 • The College of Optometrists, The Association of British Dispending Opticians. Guidance on the re-use of contact lenses and ophthalmic devices October 2001. About the authors Sarah Anderson is a Specialist Registrar in Ophthalmology at the Royal Liverpool University Hospital. Stephen Kaye is a Consultant Ophthalmologist at the Royal Liverpool University Hospital. Andrew Tullo is a Consultant Ophthalmologist at Manchester Royal Infirmary. Charles Hart is a Professor of Medical Microbiology at the Royal Liverpool University Hospital. References For a list of references please fax 01252-816176 or e-mail: 26 ot October 19, 2001 OT


Subject: Trial Contact Lenses and RE-USE in the U.S. & CJD, no threat says FDA??? Date: Sat, 7 Oct 2000 10:27:03 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To:

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

It just never ceases to amaze me, that the FDA and the rest of the different political governmental bodies that are suppose to protect us, but instead, choose to protect their best interest$ the corporate industries that donate all the cash$ there has been plenty of warning and tests to prove of some sort of infectivity in the eyes. the fda speaks of no test for the tears, well hell, there is no test that will detect it period, but yet you still die from it. does not mean it is not there. when will they wake up? sporadic CJD is coming from somewhere and they had better start looking as to where it is coming from. this is just more typical B.S.eee. please read the ignorance, below....

thank you, Terry S. Singeltary Sr., Bacliff, Texas USA

Subject: 09-018 - gsc - - concern of CJD transmission with trial contact lenses Date: Fri, 06 Oct 2000 14:49:24 -0400 From: "Clark, Geoffrey S." To: "''" CC: "Warburton, Karen" , "CDRH Small Manu. Assistance"

Terry S. Singeltary Sr.:

I have discussed your concerns with our Device Evaluation staff who have provided the following information:

The risk of CJD transmission through the use of trial (fitting) contact lenses is extremely low and at present unmeasureable. There have been no documented cases of CJD transmission via a contact lens or contact lens solution. It is highly unlikely that the CJD agent would be present on the surface of the cornea or present in the tears of an infected person. Additionally, the use of trial lens sets has been declining in the US over the past 10 years as the soft contact lens market has shifted to lenses dispensed in non-reusable blister packs. Therefore, a formal recommendation against the use of trial lenses because of potential CJD transmission is not appropriate at this time.

Please feel free to contact me if I can be of additional assistance.

=<:"Geoff Clark from PC 5074275; Room 130H <> (HFZ-220) 1350 Piccard Dr., Rockville, MD 20850-4307 800.638.2041x122 fax.301.443.8818 =========================================================================

From: Winston, F. Blix Sent: Tuesday, September 05, 2000 5:00 PM To: Clark, Geoffrey S. Subject: 09-018 - Geoff,

This came into the DSMA account. Would you please respond?

Thanks, Blix

-----Original Message----- From: WEBO@CDRH.FDA.GOV [SMTP:WEBO@CDRH.FDA.GOV]

Sent: Friday, September 01, 2000 9:27 AM To: DSMA@CDRH.FDA.GOV Subject: DSMA Email Form Response

Name: Terry S. Singeltary Sr. Phone Number: Na Fax Number: Na Email Address: Mailing Address: P.O. Box 42 Bacliff, Texas USA 77518

Questions/Comments: P990072 *In relation to human Transmissible Spongiform Encephalopathy and Contact Lens

i think it would be to everyone's best interest, "IF" the practice of "RE-USING" _display_ contact lens in the commercial aspect takes place in the U.S., this practice must be stopped. Please allow me to explain. In the U.K., the practice of having display of different colors of contact lens on display, for the consumer to try on, and see how they look with the different colors. These contact lens were then re-used over and over. No standard cleaning cleaning solution and or auto-claving procedure will kill the TSE agent. This is known fact. Plus, the U.K. has 'BANNED' this practice due to vCJD and sCJD (if i am not mistaken), but regardless, both can transmit the TSE agent. I will not waste my time trying to explain this in this box, will post a few URLS and you will see what i speak of if you care. But the eyes, brain, pituitary are the most infectious parts, of an infective species. Trust me, i know what i speak of.......

thank you, Terry S. Singeltary SR. ======================= ISSUE 1490

Thursday 24 June 1999

CJD alert over contact lenses By David Brown, Agriculture Editor

PEOPLE risk catching the human form of mad cow disease from re-used contact lenses, scientists warned the Government yesterday. They urged the Department of Health to stop opticians re-using trial lenses among their clients to help prevent further outbreaks of the new variant Creutzfeldt-Jakob disease which has killed 41 people so far.

The warning came from the Spongiform Encephalopathies Advisory Committee, the independent team of scientists advising the Government on BSE and CJD. Ministers are expected to ban the re-use of these lenses as a precaution, which could mean higher prices for consumers.

In a statement, the committee said: "Any potential risk is probably very low, but the committee felt strongly that the Department of Health should encourage opticians to adopt, as a matter of best practice, the single use of trial lenses followed by safe disposal." Sir John Pattison, the committee's chairman, said it was surprised to learn that it was common practice among opticians to try the same contact lenses on several clients.

It was known that the classical variety of CJD, the kind which was known before the new variant (vCJD) was announced in 1996 and linked to BSE, had been spread in the past by transplants of infected corneas.

The committee noted that the eyes are directly connected to the brain, the main seat of BSE and CJD. The warning applied to vCJD and the classical variety of the fatal brain disease.

Testimony of Bess Believeaux, Lions Eye Bank of Central Texas (Submission to the Jan. 18/19 meeting of the TSE Advisory Committee)

TSS Submission to the same Committee;

Tissue Banks International (TBI), Gerald J Cole

"1st", i wrote this in Nov. 1999, came through BSE-L, then tom posted; Cadaver corneal transplants -- without family permission...

then JAMA came out with this on Dec. 15, 1999 from some doctor in dallas??? just a coincidence???

Preventing Prion Transmission in Corneal Transplants

WE must not forget the obvious;

BEFORE going further, this has always disturbed me, please read carefully, 3 important factors to think about before using Xenotransplantation Products;

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8 Related Articles, Links

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.

PMID: 8006664

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__.

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone.

Croes EA, Roks G, Jansen GH, Nijssen PC, van Duijn CM.

1: EMBO J 2002 Dec 2;21(23):6358-66

BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein.

Asante EA, Linehan JM, Desbruslais M, Joiner S, Gowland I, Wood AL, Welch J, Hill AF, Lloyd SE, Wadsworth JD, Collinge J.

MRC Prion Unit, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK.

Variant Creutzfeldt-Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrP(Sc) type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

PMID: 12456643


Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD Date: Thu, 28 Nov 2002 10:23:43 -0000 From: "Asante, Emmanuel A" To: "''"

Dear Terry,

I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention. Thank you for your interest in the paper.

In respect of your first question, the simple answer is, yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD.

It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.

I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.

Emmanuel Asante

<> ____________________________________

Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 ===========================

a person can look perfectly healthy but still pass the agent;


MRC-43-00 Text only version of this sitePrint this page Issued: Monday, 28 August 2000 NEW EVIDENCE OF SUB-CLINICAL PRION INFECTION: IMPORTANT RESEARCH FINDINGS RELEVANT TO CJD AND BSE

A team of researchers led by Professor John Collinge at the Medical Research Council Prion Unit1 report today in the Proceedings of the National Academy of Sciences, on new evidence for the existence of a ‘sub-clinical’ form of BSE in mice which was unknown until now.

The scientists took a closer look at what is known as the ‘species barrier’ - the main protective factor which limits the ability of prions2 to jump from one species to infect another. They found the mice had a ‘sub-clinical’ form of disease where they carried high levels of infectivity but did not develop the clinical disease during their normal lifespan. The idea that individuals can carry a disease and show no clinical symptoms is not new. It is commonly seen in conventional infectious diseases.

Researchers tried to infect laboratory mice with hamster prions3 called Sc237 and found that the mice showed no apparent signs of disease. However, on closer inspection they found that the mice had high levels of mouse prions in their brains. This was surprising because it has always been assumed that hamster prions could not cause the disease in mice, even when injected directly into the brain.

In addition the researchers showed that this new sub-clinical infection could be easily passed on when injected into healthy mice and hamsters.

The height of the species barrier varies widely between different combinations of animals and also varies with the type or strain of prions. While some barriers are quite small (for instance BSE easily infects mice), other combinations of strain and species show a seemingly impenetrable barrier. Traditionally, the particular barrier studied here was assumed to be robust.

Professor John Collinge said: "These results have a number of important implications. They suggest that we should re-think how we measure species barriers in the laboratory, and that we should not assume that just because one species appears resistant to a strain of prions they have been exposed to, that they do not silently carry the infection. This research raises the possibility, which has been mentioned before, that apparently healthy cattle could harbour, but never show signs of, BSE.

"This is a timely and unexpected result, increasing what we know about prion disease. These new findings have important implications for those researching prion disease, those responsible for preventing infected material getting into the food chain and for those considering how best to safeguard health and reduce the risk that theoretically, prion disease could be contracted through medical and surgical procedures."




Professor Collinge is a consultant neurologist and Director of the newly formed MRC Prion Unit based at The Imperial College School of Medicine at St Mary’s Hospital. He is also a member of the UK Government’s Spongiform Encephalopathy Advisory Committee (SEAC). The MRC prion unit is was set up in 1999, and its work includes molecular genetic studies of human prion disease and transgenic modelling of human prion diseases.

Prions are unique infectious agents that cause fatal brain diseases such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie and BSE (mad cow disease) in animals. In some circumstances prions from one species of animals can infect another and it is clear that BSE has done this to cause the disease variant CJD in the UK and France. It remains unclear how large an epidemic of variant CJD will occur over the years ahead.

The strain of prion used here to infect the mice is the Sc237 strain (also known as 263K) which infects hamsters, and until now was assumed not to infect mice.

This research was funded by the Medical Research Council and Wellcome Trust.

The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC’s expenditure of £345 million is invested in over 50 of its Institutes and Units, where it employs its own research staff. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.

The Wellcome Trust is the world's largest medical research charity with a spend of some £600 million in the current financial year 1999/2000. The Wellcome Trust supports more than 5,000 researchers, at 400 locations, in 42 different countries to promote and foster research with the aim of improving human and animal health. As well as funding major initiatives in the public understanding of science, the Wellcome Trust is the country's leading supporter of research into the history of medicine.

©2002 Medical Research Council

Views & Reviews Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and Lawrence B. Schonberger, MD

From the Division of Viral and Rickettsial Diseases (Drs. Belay and Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and National Prion Disease Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH.

Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600 Clifton Road, Mailstop A-39, Atlanta, GA 30333.

Transmissible spongiform encephalopathies (TSEs) attracted increased attention in the mid-1980s because of the emergence among UK cattle of bovine spongiform encephalopathy (BSE), which has been shown to be transmitted to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The BSE outbreak has been reported in 19 European countries, Israel, and Japan, and human cases have so far been identified in four European countries, and more recently in a Canadian resident and a US resident who each lived in Britain during the BSE outbreak. To monitor the occurrence of emerging forms of CJD, such as vCJD, in the United States, the Centers for Disease Control and Prevention has been conducting surveillance for human TSEs through several mechanisms, including the establishment of the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to maintain a high index of suspicion for vCJD and use the free services of the pathology center to assess the neuropathology of clinically diagnosed and suspected cases of CJD or other TSEs.

Post-Publication Peer Reviews:

Read all Post-Publication Peer Reviews

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States Terry S. Singeltary Neurology Online, 27 Jan 2003 [Full text]

Reply to Singletary Ryan A. Maddox, MPH, et al. Neurology Online, 26 Mar 2003 [Full text]

Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734.

Full Text

Tue, 13 Feb 2001 JAMA Vol. 285 No. 6, February 14, 2001 Letters

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor:

In their Research Letter in JAMA. 2000;284:2322-2323, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

To the Editor:

At the time of my mother's death, various diagnoses were advanced such as "rapid progressive Alzheimer disease," psychosis, and dementia. Had I not persisted and personally sought and arranged a brain autopsy, her death certificate would have read cardiac failure and not CJD.

Through CJD Voice1 I have corresponded with hundreds of grief-stricken families who are so devastated by this horrific disease that brain autopsy is the furthest thing from their minds. In my experience, very few physicians suggest it to the family. After the death and when families reflect that they never were sure what killed their loved one it is too late to find the true cause of death. In the years since my mother died I think that the increasing awareness of the nature of CJD has only resulted in fewer pathologists being willing to perform an autopsy in a suspected case of CJD.

People with CJD may die with incorrect diagnoses of dementia, psychosis, Alzheimer disease, and myriad other neurological diseases. The true cause of death will only be known if brain autopsies are suggested to the families. Too often the physician's comment is, "Well, it could be CJD but that is so rare it isn't likely."

Until CJD is required to be reported to state health departments, as other diseases are, there will be no accurate count of CJD deaths in the United States and thus no way to know if the number of deaths is decreasing, stable, or increasing as it has recently in the United Kingdom.

Dorothy E. Kraemer Stillwater, Okla

In Reply:

Mr Singeltary and Ms Kraemer express an underlying concern that our recently reported mortality surveillance estimate of about 1 CJD case per million population per year in the United States since 1985 may greatly underestimate the true incidence of this disease. Based on evidence from epidemiologic investigations both within and outside the United States, we believe that these national estimates are reasonably accurate.

Even during the 1990s in the United Kingdom, where much attention and public health resources have been devoted to prion disease surveillance, the reported incidence of classic CJD is similar to that reported in the United States.

In addition, in 1996, active US surveillance for CJD and new variant (nv) CJD in 5 sites detected no evidence of the occurrence of nvCJD and showed that 86% of the CJD cases in these sites were identifiable through routinely collected mortality data.

Our report provides additional evidence against the occurrence of nvCJD in the United States based on national mortality data analyses and enhanced surveillance. It specifically mentions a new center for improved pathology surveillance. We hope that the described enhancements along with the observations of Singeltary and Kraemer will encourage medical care providers to suggest brain autopsies for more suspected CJD cases to facilitate the identification of potentially misdiagnosed CJD cases and to help monitor the possible occurrence of nvCJD.

Creutzfeldt-Jakob disease is not on the list of nationally notifiable diseases. In those states where surveillance personnel indicate that making this disease officially notifiable would meaningfully facilitate collection of data that are needed to monitor the incidence of CJD and nvCJD, including the obtaining of brain autopsy results, we encourage such a change. However, adding CJD to the notifiable diseases surveillance system may lead to potentially wasteful, duplicative reporting because the vast majority of the diagnosed cases would also be reported through the mortality surveillance system.

Furthermore, making CJD a notifiable disease may not necessarily help identify undiagnosed CJD cases. The unique characteristics of CJD make mortality data a useful surrogate for ongoing surveillance. Unlike many other neurologic diseases, CJD is invariably fatal and in most cases rapidly progressive and distinguishable clinically from other neurologic diseases.

Because CJD is least accurately diagnosed early in the course of the illness, notifiable disease surveillance of CJD could be less accurate than mortality surveillance of CJD. In addition, because death as a condition is more completely and consistently reported, mortality surveillance has the advantage of being ongoing and readily available.

The absence of CJD and nvCJD from the list of nationally notifiable diseases should not be interpreted to mean that they are not important to public health; this list does not include all such diseases. We encourage medical caregivers to report to or consult with appropriate public health authorities about any diagnosed case of a transmissible disease for which a special public health response may be needed, including nvCJD, and any patient in whom iatrogenic transmission of CJD may be suspected.

Robert V. Gibbons, MD, MPH Robert C. Holman, MS Ermias D. Belay, MD Lawrence B. Schonberger, MD, MPH Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, Ga




My Submission will be on the 'slides' of the Jan. 19, meeting...tss

PDF]Freas, William TSS SUBMISSION File Format: PDF/Adobe Acrobat - Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary Sr. [] Monday, January 08,200l 3:03 PM freas ...

Transmissible Spongiform Encephalopathy Advisory Committee February 20, 2003 (SLIDES)

EPA Comment Number: 550-2 Received: October 26, 1998 Subject: DOCKET # opp-00550 FEDERAL FOOD AND SAFETY PLAN!!!

Docket No: 01-064-1 Title: Animal Disease Risk Assessment, Prevention, and Control Act Contact Person: Mr. William Macheel, (301) 734-4420 Comments Due: October 9, 2001 Received on E-comments 24. Terry S. Singeltary Sr. 8/22/01






IF THERE is one categorical pronouncement you can safely make about prion diseases like BSE or CJD, it is that one should not make categorical pronouncements. "British beef is safe" and "there is no BSE in Germany" come to mind. Now there are two more: "scrapie is safe", and "people don't catch sporadic CJD". Scrapie is the most widespread prion disease, infecting untold numbers of sheep worldwide. Sporadic CJD is the old-fashioned pre-BSE kind that is supposed to happen spontaneously in unlucky people. But a surprise observation in France suggests some sCJD cases--though by no means all--may be linked to scrapie after all (see p 4).

For years, British authorities asserted that BSE was harmless because it was a form of scrapie. In fact, the only evidence scrapie is safe is some broad-brush epidemiology, good as far as it goes but unable to reveal occasional risks for some people from some sheep. Alarm bells should have rung in 1980 when researchers gave monkeys scrapie by feeding them infected brains. But that research, like so much other work on prion diseases, was never followed up. We still have little idea what BSE does in pigs and chickens. The Queniborough vCJD outbreak (see p 5) would be easier to understand if we knew how much brain we must eat to be infected. As for scrapie, it shouldn't take a chance finding to tell us that there may be dangerous sheep out there.

Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

Exclusive from New Scientist magazine

Four years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease.................

full text url follows By Debora MacKenzie

Suspect Symptoms

if url dead, go here for 'SUSPECT SYMPTOMS'

you can access article here also;

Then follow up with PNAS studies from which new scientist article written from;

Published online before print March 20, 2001 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.041490898

Neurobiology Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt- Jakob disease: Implications for human health Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger ] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [] , Dominique Dormont*, and Jean-Philippe Deslys*

* Commissariat à l'Energie Atomique, Service de Neurovirologie, Direction des Sciences du Vivant/Département de Recherche Medicale, Centre de Recherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc, BP 6, 92 265 Fontenay-aux-Roses Cedex, France; [Dagger ] Hôpital Neurologique Pierre Wertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and [] Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, United Kingdom

Edited by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000 (received for review October 16, 2000)


There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.


The recognition of a variant of the human transmissible spongiform encephalopathy (TSE) Creutzfeldt-Jakob Disease (vCJD) in the U.K. in 1996 raised the major concern that it would correspond to human infection with the agent responsible for bovine spongiform encephalopathy (BSE; ref. 1). Transmission of BSE to macaques provided the first experimental evidence as it produced a disease close to vCJD in humans (2). Strain typing in inbred mice (consisting of measuring the incubation period and establishing lesion profiles corresponding to the strain-specific distribution of brain vacuolation) allows reliable identification of TSE strains (3). This method, together with biochemical methods, has revealed a single phenotype for the agents of BSE and the British cases of vCJD (4-6). Mice expressing only the bovine prion protein (PrP) were highly susceptible to vCJD and BSE, which induced the same disease (7). Thus, it is now well established that BSE has caused vCJD, probably by alimentary contamination. In this respect, the finding of abnormal PrP labeling in the gastrointestinal tract and lymphatic tissues of orally BSE-contaminated lemurs shows that the BSE agent can infect primates by the oral route (8). About 1 million contaminated cattle may have entered the human food chain, and the future number of vCJD cases could range from 63 to 136,000 depending on the incubation period of BSE in humans (9). Unlike sporadic CJD (sCJD) and iatrogenic CJD (iCJD) linked to the administration of contaminated growth hormone extracted from human hypophyses, in vCJD, the infectious agent seems to be widely distributed in lymphoid organs, as pathological PrP (PrPres) can be detected in tonsils, lymph nodes, spleen, and appendix even in the preclinical phase of the disease (10, 11). This raises a public health issue with regard to the risk of iatrogenic transmission of vCJD through surgical instruments, grafts, blood transfusion, or parenteral administration of biological products of human origin. However, this risk is difficult to assess, because it largely depends on factors such as the virulence of the BSE agent adapted to primates and the efficiency of secondary transmission to humans by a peripheral route such as the i.v. one. A further issue is whether vCJD accidentally acquired from humans would be recognized. The latter poses the question of a phenotypic variation of the BSE agent after successive transmissions in humans: does it retain its strain characteristics, and does it induce a pathology similar to that observed in the previous host? A 9-year history of transmission of BSE to primates and mice enables us today to clarify a number of these important points.

Although BSE has mainly affected the U.K., two definite cases and one probable case of vCJD have now been reported in France in people who have never resided in the U.K. (12, 13). We strain-typed the first of these cases to establish its origin. Strain typing in C57BL/6 mice of BSE, French, and British vCJD was compared with that of BSE passaged in nonhuman primates, thus allowing us to study the effect of serial passages in primates. Comparisons were also made with French cases of sCJD and iCJD and two strains of scrapie (one of French and one of U.S. origin). Our findings provide experimental demonstration that the same agent, namely that responsible for the cattle disease BSE, has caused vCJD both in France and in the U.K., in line with biochemical data and with the fact that, until 1996, about 10% of the beef consumed in France was imported from the U.K. We found that the BSE agent in nonhuman primates is similar to that causing vCJD in humans and tends to evolve rapidly toward a primate-adapted variant. Furthermore, we showed that the strain responsible for iCJD is closely related to that of one patient with sCJD, and, more unexpectedly, that these agents were similar to the French scrapie strain studied (but different from the U.S. scrapie strain). This finding requires a cautious interpretation for several reasons, not least because of the inevitably limited number of TSE strains that can be studied by such a cumbersome method as strain typing. Nonetheless, it also prompts reconsideration of the possibility that, in some instances, sheep and human TSEs can share a common origin.




CWD to CJD in humans (why not?), as easy as BSE/Scrapie;

The EMBO Journal, Vol. 19, No. 17 pp. 4425-4430, 2000 © European Molecular Biology Organization

Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease

G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O?Rourke3, L.E. McHolland4, P.K. Bryant III4, M.W. Miller5, E.S. Williams6, M. Smits2 and B. Caughey1,7

1NIAID/NIH Rocky Mountain Laboratories, Hamilton, MT 59840, 3USDA/ARS/ADRU, Pullman, WA 99164-7030, 4USDA/ARS/ABADRL, Laramie, WY 82071, 5Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526-2097, 6Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA and 2ID-Lelystad, Institute for Animal Science and Health, Lelystad, The Netherlands 7Corresponding author e-mail: Received June 7, 2000; revised July 3, 2000; accepted July 5, 2000.


Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/genotypes. Furthermore, the efficiency with which the protease-resistant PrP (PrP-res) of one species induces the in vitro conversion of the normal PrP (PrP-sen) of another species to the protease-resistant state correlates with the cross-species transmissibility of TSE agents. Here we show that the CWD-associated PrP-res (PrPCWD) of cervids readily induces the conversion of recombinant cervid PrP-sen molecules to the protease-resistant state in accordance with the known transmissibility of CWD between cervids. In contrast, PrPCWD-induced conversions of human and bovine PrP-sen were much less efficient, and conversion of ovine PrP-sen was intermediate. These results demonstrate a barrier at the molecular level that should limit the susceptibility of these non-cervid species to CWD.


Clearly, it is premature to draw firm conclusions about CWD passing naturally into humans, cattle and sheep, but the present results suggest that CWD transmissions to humans would be as limited by PrP incompatibility as transmissions of BSE or sheep scrapie to humans. Although there is no evidence that sheep scrapie has affected humans, it is likely that BSE has caused variant CJD in 74 people (definite and probable variant CJD cases to date according to the UK CJD Surveillance Unit). Given the presumably large number of people exposed to BSE infectivity, the susceptibility of humans may still be very low compared with cattle, which would be consistent with the relatively inefficient conversion of human PrP-sen by PrPBSE. Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity as has been recommended for other animal TSEs.


Scrapie to Humans?

Houston Chronicle article Aug. 5, 2001

MAD COW DISEASE: Could It Happen Here?


go here for chronicle article;

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 CJD WATCH ==========

[Federal Register: April 4, 2003 (Volume 68, Number 65)] [Notices] [Page 16520-16522] From the Federal Register Online via GPO Access [] [DOCID:fr04ap03-80]



Food and Drug Administration

[Docket No. 03D-0118]

Guidance for FDA Staff on Sampling or Detention Without Physical Examination of Decorative Contact Lenses (Import Alert 86-10); Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.


SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance document entitled ``Guidance for FDA Staff on Sampling or Detention Without Physical Examination of Decorative Contact Lenses (Import Alert 86-10).'' The guidance document includes FDA's guidance to FDA district offices for sampling or detention without physical examination of plano (zero-powered or noncorrective) contact lenses intended solely to change the appearance of the normal eye in decorative fashion, when these products are presented for importation into the United States.

DATES: Submit written or electronic comments on the guidance by June 3, 2003.

ADDRESSES: Submit written requests for single copies of the Import Alert 86-10, to the Division of Import Operations and Policy (HFC-170), Office of Regulatory Affairs, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Send two self-addressed adhesive labels to assist that office in processing your request. You may fax your request to 301-594-0413. Submit written comments on this guidance to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to See the SUPPLEMENTARY INFORMATION section for information on electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Thaddeus J. Poplawski, Division of Import Operations and Policy (HFC-170), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-443-6553.


I. Background

FDA has been receiving reports that certain commercial entities are planning to distribute or may already be distributing plano (zero- powered or noncorrective) contact lenses intended solely to change the normal appearance of the eye in decorative fashion (decorative contact lenses). FDA understands that these products are intended to be distributed without a prescription, without fitting by a qualified eye care professional, and without ongoing professional supervision. FDA believes that, like other contact lenses, decorative contact lenses can cause a variety of eye injuries and conditions. Lens wear has been associated with corneal ulcer, for example, which can progress rapidly, leading to internal ocular infection if left untreated. Uncontrolled infection

[[Page 16521]]

can lead to corneal scarring, which can lead to vision impairment. In extreme cases, corneal ulcer can result in blindness and eye loss. Other risks include conjunctivitis; corneal edema; allergic reaction; abrasion from poor lens fit; and reduction in visual acuity, contrast sensitivity, and other visual functions, resulting in interference with driving and other activities. FDA believes that these risks cannot be sufficiently controlled unless: (1) The wearer obtains advice from an eye care professional; (2) the lenses are fitted by or under the supervision of such a professional; and (3) the wearer remains under appropriate professional supervision. Eye care professional involvement is legally required (21 CFR 801.109) for contact lenses intended for medical purposes (i.e., prosthetic use or vision correction). These products are regulated by FDA as medical devices under the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301 et seq.). \1\ Such control is not available for decorative contact lenses because these products are cosmetics under section 201(i) of the act (21 U.S.C. 321(i)). ---------------------------------------------------------------------------

\1\There are some lenses currently on the market under cleared 510(k)s covering contact lenses intended for both vision correction use and for solely decorative purposes.The sponsors in these cases voluntarily included a plano lens in the range of corrective powers described in the 510(k) submissions. ---------------------------------------------------------------------------

Section 201(i) of the act defines ``cosmetic'' to include ``articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance * * * '' (21 U.S.C. 321(i)(1)). Decorative contact lenses are articles intended to be introduced into the eye, which is a part of the body, to beautify the wearer, promote the attractiveness of the wearer, or alter the wearer's appearance. They are claimed to achieve this cosmetic result by changing the apparent color of the iris; by appearing to add a design to the iris (e.g., a professional sports team insignia); or by imparting a nonhuman or otherwise nonnormal appearance to the eye (e.g., cat's eye). Provided they are not marketed with claims\2\ that they effect physical or physiological change, decorative contact lenses are properly regulated as cosmetics under the act (cf. United States v. An Article * * * ``Sudden Change,'' 409 F.2d 734 (2d Cir. 1969) (``claiming to affect the structure of the skin in some physiological way'' makes a product a ``drug''); 21 CFR 700.35 (``sunscreen'' claims make a product a drug)). ---------------------------------------------------------------------------

\2\American Health Prods Co. v. Hayes, 574 F. Supp. 1498, 1505 (S.D.N.Y. 1983), aff'd on other grounds, 744 F.2d 912 (2d Cir. 1984) (The courts ``have always read the * * * statuatory definitions employing the term `intended' to refer to specific marketing representations.''). ---------------------------------------------------------------------------

The fact that contact lenses are ``devices'' in the colloquial sense does not preclude cosmetic status under the act. FDA has previously determined that section 201(i) of the act applies to appearance-enhancing devices such as wigs, hair brushes, stockings and toothpicks (Refs. 1 through 3). Moreover, the fact that a product is intended to come into contact with the eye does not make it ineligible for cosmetic regulation (Ref. 4). Indeed, the legislative history accompanying the original 1938 act demonstrates that Congress enacted the cosmetic adulteration provisions to address the risk to users presented by cosmetic products that may cause blindness and other serious injuries (S. Rept. 74-361 at 21 (1935)). On October 22, 2002, FDA issued Import Alert 86-10, with respect to decorative contact lenses. We are now publishing a revised Import Alert 86-10 in the Federal Register. The Import Alert 86-10 does not cover contact lenses that are intended for vision correction or for prosthetic or other medical use. Section 801(a) of the act (21 U.S.C. 381(a)) authorizes FDA to refuse admission to articles that appear to be adulterated or misbranded. Based on the available evidence, FDA believes that decorative contact lenses presented for importation may appear to be adulterated under section 601(a) of the act (21 U.S.C. 361(a)), in that they contain a deleterious substance that is dangerous to wearers of the lenses when they are put to a labeled, customary, or usual use. The deleterious substance is the matrix in which colorants are embedded. This material can cause the potentially vision-threatening eye conditions discussed previously, particularly if the wearer fails to obtain appropriate professional counseling, fitting, and ongoing supervision; if the wearer trades lenses, fails to use proper disinfection and other care techniques; or if the wearer wears lenses for longer than the recommended period. Consequently, FDA believes that decorative contact lenses appear to be adulterated under section 601(a). Decorative contact lenses may also be subject to refusal if they appear to contain unsafe color additives (21 U.S.C. 381(a) and 361(e)). FDA understands that certain overseas manufacturers or distributors might have selected color additives for use in decorative contact lenses intended for U.S. distribution based on the fact that they have been approved by FDA for use in medical devices. To be used lawfully in decorative contact lenses, a color additive must be approved by FDA for use in eye area cosmetics. Not all color additives approved for use in medical devices have been approved for eye area use in cosmetics. Consequently, decorative contact lenses may also appear to be adulterated under section 601(e) of the act. Finally, decorative contact lenses may be subject to refusal on the ground that they are misbranded under section 602(a) of the act (21 U.S.C. 362(a)) because their labeling is false or misleading ``in any particular.'' Under the act, labeling can be misleading by failing to disclose ``facts * * * material with respect to consequences which may result'' from use of a product under customary, usual, or labeled conditions (21 U.S.C. 321(n)). As noted previously, decorative contact lenses may cause serious health problems, including (in extreme cases) blindness. FDA believes these risks are material. If they are not disclosed in labeling, then the labeling would be misleading, and the product would appear to be misbranded under section 602(a) of the act and subject to refusal under section 801(a) of the act.

II. Guidance

FDA's district offices may sample or detain without physical examination decorative contact lenses presented for U.S. importation. The Import Alert 86-10 applies to contact lenses that are: (1) Intended to change the appearance of the normal eye in decorative fashion; and (2) intended for distribution directly to the wearer, without the involvement of a qualified eye care professional. It does not cover contact lenses that are intended for vision correction or for prosthetic or other medical or therapeutic use and that are, therefore, properly regulated as medical devices under the act.

III. Significance of Guidance

This level 1 guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the agency's current thinking on the sampling or detention without physical examination of decorative contact lenses that appear to be adulterated under section 601(a) and (e) of the act because they contain a deleterious substance that is harmful to users and/or contain an unapproved color additive, or appear to be misbranded under section 602(a) because their labeling is false or misleading. It does not create or confer

[[Page 16522]]

any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the applicable statute and regulations. This guidance is effective immediately because prior public participation is not feasible or appropriate due to the risks to the public health presented by these products.

IV. Comments

Interested persons may submit to the Dockets Management Branch (see ADDRESSES) written or electronic comments regarding this guidance. Such comments will be considered when determining whether to amend the current guidance. Two paper copies of any mailed comments are to be submitted, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. The guidance and received comments are available in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through Friday.

V. Electronic Access

Persons with access to the Internet may obtain the guidance at

VI. References

The following references have been placed on display in the Dockets Management Branch (see ADDRESSES) and may be seen by interested persons between 9 a.m. and 4 p.m., Monday through Friday. 1. Food and Drug Administration (FDA), Compliance Policy Guide (CPG) 7128.04 (revised August 1996) (hair brushes); ( ). 2. FDA, CPG 7128.05 (revised September 1, 1986) (wigs); ( ). 3. Hutt, Peter Barton, ``Reconciling the Legal, Medical, and Cosmetic Chemist Approach to the Definition of a `Cosmetic,' '' Cosmetic, Toiletry, and Fragrance Association Cosmetic Journal'', vol. 3, 1971 (excerpted in Peter Barton Hutt & Richard A. Merrill, Food and Drug Law: Cases and Materials, p. 824-825 (2d ed. 1991)). 4. FDA, CPG 7128.03 (revised August 1996) (mascara is an eye- contact cosmetic); ( ).

Dated: April 1, 2003. John R. Marzilli, Acting, Associate Commissioner for Regulatory Affairs. [FR Doc. 03-8315 Filed 4-2-03; 11:42 am]




>>> "the biochemical signature of PrPres in the BASE-inoculated animal was
found to have a higher proteinase K sensitivity of the octa-repeat
region. We found the same biochemical signature in three of four human
patients with sporadic CJD and an MM type 2 PrP genotype who lived in
the same country as the infected bovine." <<<

NOT to forget ;

Thursday, June 05, 2008 Review on the epidemiology and dynamics of BSE epidemics Vet. Res. (2008) 39:15 DOI: 10.1051/vetres:2007053 c INRA, EDP Sciences, 2008 Review article


And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17]. These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.


Cases of atypical BSE have only been found in countries having implemented large active surveillance programs. As of 1st September 2007, 36 cases (16 H, 20 L) have been described all over the world in cattle: Belgium (1 L) [23], Canada (1 H)15, Denmark (1 L)16, France (8 H, 6 L)17, Germany (1 H, 1 L) [13], Italy (3 L)18, Japan (1 L) [71], Netherlands (1 H, 2 L)19, Poland (1 H, 6 L)20, Sweden (1 H)21, United Kingdom (1 H)22, and USA (2 H)23. Another H-type case has been found in a 19 year old miniature zebu in a zoological park in Switzerland [56].

It is noteworthy that atypical cases have been found in countries that did not experience classical BSE so far, like Sweden, or in which only few cases of classical BSE have been found, like Canada or the USA. And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17].

These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.

full text 18 pages ;

please see full text ;

***Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.***

Progress Report from the National Prion Disease Pathology Surveillance Center An Update from Stephen M. Sergay, MB, BCh & Pierluigi Gambetti, MD April 3, 2008

Sunday, March 16, 2008

MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE

HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008


Tissue infectivity and strain typing of the many variants Manuscript of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...


Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate

Creutzfeldt Jakob Disease









> Sunday, April 20, 2008
> Progress Report from the National Prion Disease Pathology Surveillance
> Center April 3, 2008


to be continued. ...TSS

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