Prion 2017 Conference

Transmissible prions in the skin of Creutzfeldt-Jakob disease patients

Prion 2017 Conference Transmissible prions in the skin of Creutzfeldt-Jakob disease patients

Dr. Wenguan Zou1, Dr. Christina Orru2, Jue Yuan1, Brian Appleby1, Baiya Li1, Dane Winner1, Yian Zhan1,3, Mark Rodgers1, Jason Rarick1, Robert Wyza1, Tripti Joshi1, Gongxian Wang3, Mark Cohen1, Shulin Zhang1, Bradley Groveman2, Robert Petersen1, James Ironside4, Miguel Quinones-Mateu1, Jiri Safar1, Qingzhong Kong1, Byron Caughey2

1Case Western Reserve University, Cleveland, United States, 2Rocky Mountain Laboratories, National Institutes of Health, Hamilton, United States, 3Nanchang University, Nanchang, China, 4Universitv of Edinburgh, Edinburgh, United Kingdom

Aims: Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is transmissible by neuroinvasive iatrogenic routes due to abundant prion infectivity in the central nervous system (CNS). The disease-associated prion protein (PrPSc) and its infectivity have never been detected in skin from sCJD patients; however, some epidemiological studies have associated sCJD risk with skin-involved non-CNS surgeries. The aims of our study were to explore potential prion seeding activity and infectivity of skin and the feasibility of skin-based CJD diagnosis.

Methods: Skin samples were collected at autopsy or biopsy from twenty-one sCJD, two variant CJD, and fifteen non-CJD patients and analysed by Western blotting and real-time quaking-induced conversion (RT- QulC) for PrPSc. Infectivity of skin from two sCJD patients was determined by bioassay using two lines of humanized transgenic (Tg) mice.

Results: Western blotting demonstrated PrPSc in the skin of one of five deceased sCJD patients examined. However, the more sensitive RT-QuIC assay detected prion-seeding activity in skin from all 23 CJD decedents but not in non-CJD controls, indicating preliminary ClD diagnostic sensitivities and specificities of 100% (95% confidence intervals of 85-100%, and 78-100%, respectively). Although sCJD skins contained ~102-105-fold lower RT-QuIC seeding activity than sCJD brains, ten out of twelve mice from two Tg mouse lines inoculated with skin homogenates of two patients with two different subtypes of sCJD succumbed to prion disease within 450 days after inoculation.

Conclusions: O sCJD patients' skin may contain both detectable prion seeding activity and transmissible prions. Our findings not only suggest a new basis for diagnostic sCJD testing, but also raise concerns about the potential for iatrogenic sCJD transmission via skin. (Funded by the CJD Foundation, the National Institute of Neurological Disorders and Stroke, the Centers for Disease Control and Prevention, as well as others)


*sCJD patients' skin may contain both detectable prion seeding activity and transmissible prions.

*Our findings not only suggest a new basis for diagnostic sCJD testing, but also raise concerns about the potential for iatrogenic sCJD transmission via skin.

Oral Session14:45~15:00O-12 Wenquan Zou

*** PrPSc in the skin of CJD patients

Unexpectedly, our latest preliminary study identified two types of PK-resistant PrP molecules [with gel mobility similar to the PrPSc types 1 and 2 from the brain of sporadic CJD (sCJD)] in the fibroblast cells extracted from the skin of clinical sCJD patients and asymptomatic subjects carrying PrP mutations linked to familial CJD (fCJD). We also detected PrPSc in the skin of humanized transgenic (Tg) mice inoculated intracerebrally with a human prion. Moreover, prion infectivity has been observed in the skin of infected greater kudu (Cunningham et al., 2004) and a murine prion inoculated to mice via skin scarification can not only propagate in the skin, but also spread to the brain to cause prion disease (Wathne et al., 2012). We hypothesize that the skin of patients with prion disease harbors prion infectivity and the presence of PK-resistant PrP in the skin is a novel diagnostic marker for preclinical CJD patients.

A Kiss of a Prion: New Implications for Oral Transmissibility

The transmissibility of scrapie among sheep (intraspecies) is well recognized. It must be emphasized that horizontal transfer (from one individual to another) of scrapie is the main route of infection, because vertical transmission of disease from mother to offspring via milk or placental tissue occurs infrequently. Thus, in view of the report by Maddison et al, the oral transmissibility of prions among sheep may serve as a major route for horizontal scrapie transfer. This occurrence is plausible because sheep often lick each other. Maddison et al [10] indicate that, because of the similarities in prion tissue distribution, their implications for the oral transmission of ovine scrapie might be true for other prion diseases, such as cervid chronic wasting disease and human vCJD. If this is true for humans, a kiss of a prion may sometimes have lethal consequences.


PERSON TO PERSON TRANSMISSION OF THE TSE PRION DISEASE, never say never. as the disease mutates, it becomes more virulent in some cases, and cwd is efficiently transmitted from cervid to cervid. there are now multiple strains of CWD in cervids, as with the TSE prion disease in bovine, sheep and goats, and we now have the atypical TSE in these species, that have mutated, and some strains _have_ become more virulent. we now have younger humans dying from the TSE prion disease, with shorter incubation period, and that are much younger. human to human casual transmission of the TSE prion disease...again, never say never. ...TSS

see more here;


The occurrence of the disease in a patient who had contact with cases of familial C.J.D., but was not genetically related, has been described in Chile (Galvez et al., 1980) and in France (Brown et al., 1979b). In Chile the patient was related by marriage, but with no consanguinity, and had social contact with subsequently affected family members for 13 years before developing the disease. The contact case in France also married into a family in which C.J.D. was prevalent and had close contact with an affected member. In neither instance did the spouse of the non-familial case have the disease. The case described in this report was similarly related to affected family members and social contact had occurred for 20 years prior to developing C.J.D. If contact transmission had occurred, the minimum transmission period would be 11 years. Contact between sporadic cases has not been described and it is remarkable that possible contact transmissions have all been with familial cases. No method of transmission by casual social contact has been suggested.

***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent.

snip...see full text here;


-----Original Message-----

From: Terry Singeltary <>

To: Sent: Thu, Nov 23, 2017 10:22 am

Subject: re-NIH scientists and collaborators find infectious prion protein in skin of CJD patients

>>>Although sCJD patient skin contained ~103- to 105-fold lower prion seeding activity than did sCJD patient brain tissue, all 12 mice from two transgenic mouse lines inoculated with sCJD skin homogenates from two sCJD patients succumbed to prion disease within 564 days after inoculation<<<

for something to be 103 to 105 fold lower prion seeding, yet still be 100% fatal in all test subjects, very disturbing...terry


NIH scientists and collaborators find infectious prion protein in skin of CJD patients



Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease


PRION 2018

17:00 Wen-Quan Zou (Case Western Reserve University): Preclinical detection of prions in skin samples of scrapie-infected animals by serial PMCA and RT-QuIC assays.

THURSDAY, MAY 24, 2018

Prion 2018 May, 22-25 2018 Santiago de Compostela


Skin as a Potential Source of Prion Infectivity Mammalian skin is composed of different strata and cell types, which are both innervated and carry blood vessels. There is therefore the potential for skin to harbor prions and facilitate its excretion into the environment. Cunningham and coworkers demonstrated the presence of prion infectivity in the skin of BSE-affected kudu.87 Subsequently, Thomzig et al. used a rodent model to demonstrate that skin-associated prions could be identified from late preclinical stages of disease for both scrapie and BSE,88 estimating that there is likely to be 5,000–10,000 times less prion in the skin of hamsters challenged with scrapie than in the brains of those same animals. This study also demonstrated the presence of prions in the skin of sheep during the late stages of naturally acquired scrapie where PrPSc was generally associated with small nerve fibers within the dermis. More recently, PrPSc was found within the skin of a vCJD patient.89 In addition, cervine CWD prions have been found within antler velvet,90 a vascularized skin layer covering the developing antler of male deer, which is shed after the ossification of antlers.

Skin may therefore represent another route by which prions contaminate the environment. Mechanisms of prion shedding from this organ could include natural sloughing of skin, abrasions of the skin and, in the case of sheep, skin cuts and nicks that are introduced during shearing.


Office of Environment, Health and Safety (EH&S)

Prion Exposure Protocol

Organism or Agent:
Exposure Risk:
Human Prion Disease (Creutzfeldt-Jakob Disease/New variant CDJ, BSE, etc.)
UCSF Occupation Health:
415-885-7580 (work hours, 8am to 5pm)
Exposure Hotline Pager:
415-353-7842 (24 hours)
Environment, Health & Safety:
415-476-1300 (work hours)
UCSF Police Department;
415-476-1414 or 9-911 (In case of emergency, 24 hours)
EH&S Public Health Officer:
415-514-3531 (work hours)
Campus Bio-Safety Officer 415-514-2824
California Poison Control: 800-222-1222
SFDPH Emergency Number
CDC Emergency Operation
Occ Hlth Proto Button
************************************************** ***************************************
In the event of an accidental exposure or injury, the protocol is as follows:
1. Modes of Transmission:
Skin puncture or injection
Contact with mucous membranes (eyes, nose, mouth)
Contact with non-intact skin
Exposure to aerosols
2. First Aid: There is no evidence of occupational transmission of prion disease to healthcare workers. Perform first aid as self-care according to the type of exposure/ injury.
a. First Aid for an unbroken Skin Exposure: Wash with soap and abundant quantities of warm water (avoid scrubbing), rinse, and dry. Apply for 1 minute, 0.1N Sodium Hydroxide (NaOH) or a 1:10 dilution of bleach (sodiumhypochlorite).
When decontaminating with 0.1N NaOH or sodium hypochlorite, a face shield and eye goggles or eye goggles with mask should be worn for protection. It is important to decontaminate the wound with the appropriate agent for the appropriate length of time in order to denature the protein as soon as possible. See the special precautions for NaOH below.
After decontamination, rinse well with soap and water to neutralize the base.
Bring the 0.1N sodium hydroxide SDS to the ED
b. First Aid for lacerations or needlestick injuries: Gently encourage bleeding; wash (avoid scrubbing) with warm soapy water, rinse, dry and cover with a waterproof dressing. Further treatment (e.g. sutures) should be appropriate to the type of injury.
c. First Aid for splashes to the Eye, Nose or Mouth: Immediately flush the area with running water or normal saline. Continue washing for 15 minutes. Do not use sodium hydroxide or sodium hypochlorite in or around your eyes. Do not rub or keep eyes closed.
d. Following the administration of first aid, the employee will:
Inform your supervisor of the exposure.
Remove any garments that may have become soiled/contaminated with prions or NaOH, and place them in a double plastic bag. Close the bag securely, label it as contaminated, and wash your hands thoroughly.
Identify any equipment involved in the exposure and the mechanism of exposure. Make sure that the area has been secured and that notification of contamination has been posted to prevent other individuals from entering the area.
If you need immediate care for your injury, proceed to the Emergency Department(ED). When you injury is stable, Contact the Needlestick Exposure Hotline (415-353-7842) to report the exposure. The injured employee will need to follow up in the UCSF Occupational Health Clinic. Be sure to go to the clinic for medical evaluation and complete all necessary workers’ compensation paperwork.

e. Splash Affecting Garments, remove garments that may have become soiled or contaminated and place them in a double biohazard red plastic bag. Disposable gloves and gowns should dispose of by incineration, according to World Health Organization guidelines.
3. Treatment

Prion 2017 Conference
Transmissible prions in the skin of Creutzfeldt-Jakob disease patients

never say, never...

Terry S. Singeltary Sr.

Sent: Tue, Jun 5, 2018 3:02 pm

Subject: Prion Scientific Advisors and Consultants Staff Meeting Singeltary Submission Freas Monday, January 08,2001 3:03 PM

Sent: Monday, January 08,2001 3:03 PM

WOW, my submission held up on the www for 17 years, and was proven to be true, and now, it has been removed from the www, the same url does not work anymore and it was just working this year. nothing like the FDA et al cleaning up any evidence of truth with their mad cow debacle and sporadic cjd cover up sad$$$

let's review the truth about sporadic cjd shall we;

SUNDAY, JUNE 3, 2018

Clinical, pathological, and molecular features of classical and L-type atypical-BSE in goats