Man died of CJD 30 years after brain surgery 36 years old DOD
Friday 24 January 2020
Man died of CJD 30 years after brain surgery
A man who contracted CJD during a brain operation when he was a child died more than 30 years later of the disease, an inquest at the Dublin Coroner’s Court heard.1 A man who contracted CJD during a brain operation when he was a child died more than 30 years later of the disease, an inquest at the Dublin Coroner’s Court heard. Louise Roseingrave
June 1 2016 2:30 AM
A man who contracted CJD during a brain operation when he was a child died more than 30 years later of the disease, an inquest heard.
Noel Kavanagh (36) from Ballyragget, Co Kilkenny, lived a full life until he became ill in 2013 and died on October 20, 2014.
In July 1983, he underwent an eight-hour brain operation at the old Richmond Hospital on North Brunswick Street in Dublin. The surgery followed a fall from a tractor in which Mr Kavanagh, then aged five, had sustained a serious head injury.
He had a difficult recovery initially, but subsequently improved and went on to live a full and busy life, Dublin Coroner's Court heard. He enjoyed running and played soccer and was involved in the Special Olympics. He was able to manage independently and worked in a garden centre, the court heard.
In May 2013 he began to feel tired, listless and drowsy. He was brought to St Luke's Hospital in Kilkenny and later transferred to Beamount Hospital in Dublin. CT scans and a lumbar puncture were carried out and Mr Kavanagh was treated for an infection, thought to be a bacterial infection or meningitis, with antibiotics and steroids.
However, his clinical condition did not improve. He developed epilepsy and Donncha O'Brien, consultant neurosurgeon at Beaumont Hospital, said a hemispherectomy - a rare surgical procedure where half of the brain is removed - was agreed as a treatment for persistent seizures.
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During this procedure, brain tissue slides were taken and sent for analysis, revealing the presence of Creutzfeldt-Jakob disease or CJD. Mr Kavanagh had contracted CJD 30 years previously due to contaminated donor graft tissue inserted during the neurosurgery performed at the old Richmond Hospital.
Coroner Dr Brian Farrell returned a narrative verdict setting out the circumstances of Mr Kavanagh's death. Dr Farrell said a variant of CJD emerged in the early 2000s related to burger meat but this case concerned infected donor tissue.
"This is a set of unfortunate circumstances. The initial head injury was not fatal, but during that treatment, Noel contracted the infection.
"A dura [brain membrane] donor graft was used and it seems that graft was infected with CJD at the time. And over the years, there were changes in Noel's brain which indicated this had been ongoing for a long time.
"The diagnosis was ultimately confirmed when he passed away," the coroner said.
Irish Independent
SATURDAY, MARCH 10, 2018 Dura Mater Graft–Associated Creutzfeldt-Jakob Disease — Japan, 1975–2017 Update Dura Mater Graft–Associated Creutzfeldt-Jakob Disease — Japan, 1975–2017 Update
Weekly / March 9, 2018 / 67(9);274–278
Ryusuke Ae, MD, PhD1; Tsuyoshi Hamaguchi, MD, PhD2; Yosikazu Nakamura, MD1; Masahito Yamada, MD, PhD2; Tadashi Tsukamoto, MD, PhD3; Hidehiro Mizusawa, MD, PhD3; Ermias D. Belay, MD4; Lawrence B. Schonberger, MD4 (View author affiliations)
Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder that, according to the most well accepted hypothesis (1), is caused by replicating, transmissible, abnormal forms of a host-encoded prion protein (prions). Most CJD cases occur spontaneously (sporadic CJD) or are inherited (genetic CJD). Iatrogenic CJD can occur after exposure to prion-contaminated instruments or products in medical/surgical settings. Cadaveric dura mater graft–associated CJD (dCJD) accounts for a common form of iatrogenic CJD. This report summarizes the epidemiologic features of 154 cases of dCJD identified in Japan during 1975–2017; these cases account for >60% of dCJD cases reported worldwide (1,2). The unusually high prevalence of dCJD in Japan was first reported in 1997 (3). In 2008, a single brand of graft (Lyodura [B. Braun Melsungen AG, Melsungen, Germany]), frequently used as a patch in neurosurgical procedures, was identified as the probable vehicle of transmission (4). No international recall of the implicated Lyodura occurred, the product had a relatively long shelf life, and the grafts were used frequently in Japanese patients with non–life-threatening conditions (4,5). Since 2008, additional cases have been ascertained, reflecting the identification of previously missed cases and the occurrence of new cases with longer latency periods (interval from exposure to symptom onset) for dCJD (up to 30 years), underscoring the importance of maintaining surveillance for dCJD.
In 1996, after the first report of variant CJD (the human prion disease caused by the agent of bovine spongiform encepathalopathy [“mad cow disease”]) in the United Kingdom (6), the nongovernmental Japanese CJD Surveillance Committee (J-CJDSC), with support from the Japanese Ministry of Health, Labour, and Welfare, conducted a preliminary nationwide mail survey to identify cases of human prion disease in Japan; since 1999, J-CJDSC has maintained a national CJD registry (7). J-CJDSC members investigate each reported suspected CJD case in cooperation with CJD specialists in each prefecture. The methods for identifying dCJD cases in Japan have been described previously (5,7,8). All identified CJD cases, including cases of dCJD, are entered into the J-CJDSC database, which contains demographic and clinical information, including a detailed history of any surgical procedures and international travel and CJD laboratory test results (including cerebrospinal fluid analyses and genetic testing) (7).
Among 829 identified physician-diagnosed cases of CJD during 1979–May 1996, a total of 43 (5%) patients had received a dura mater graft as part of a surgical procedure (typically a patch during neurosurgery); 41 (95%) of these dCJD patients had received a Lyodura graft (3). A 1987 U.S. investigation of a dCJD case found that Lyodura produced before May 1987 carried an unusually high risk for dCJD because of the contamination-prone method of production (9,10); after that report, the manufacturer reported revising its collection and processing procedures to reduce the CJD transmission risk.
By 2008, a total of 132 dCJD cases had been reported in Japan, and among 120 (91%), Lyodura was identified as the probable vehicle of transmission; the graft brand for the other 12 dCJD patients was unknown (4). By the end of 2017, the J-CJDSC database included 154 patients with dCJD, including an additional 22 patients identified since the last report (4).
Among 154 dCJD patients, receipt of a Lyodura graft was documented in 140 (91%); the brand of dural graft received by 14 patients was not identified. The most common medical conditions for which patients received the cadaveric dura mater grafts were brain tumors (including meningioma) (69; 45%), facial palsy or trigeminal neuralgia (26; 17%), and brain hemorrhage (25; 16%). Less common conditions included intracranial aneurysm (10; 6%), unspecified anomalies (eight; 5%), intracranial hematoma (seven; 5%), trauma (seven; 5%), and other (two; 1%). The median age at symptom onset among dCJD patients was 58 years (range = 15–81 years; mean = 56 years); 89 (58%) patients were female. All patients had received their dura mater graft during 1975–1993 (Figure 1) (Figure 2), and dates of illness onset ranged from 1985 to 2016.
Although the shelf life of Lyodura established by the manufacturer was 5 years, three dCJD patients had surgical procedures in 1993, at least 6 years after the company had changed their collection and processing procedures. J-CJDSC determined that all three patients had received a Lyodura graft, and that at least one of the grafts was processed before 1987, and had therefore expired (the processing date of the second and third patients’ grafts are unknown). Eleven (7%) dCJD patients identified by J-CJDSC received grafts during 1988–1993 (Figure 2), including eight during 1988–1991, indicating that they might have received unexpired Lyodura produced before the company changed its processing procedures in 1987. In 1997, a case occurred in a patient with a history of two neurosurgical procedures in 1991. Investigation by J-CJDSC revealed that the patient had received a graft produced before 1987 during the first procedure. None of the dCJD cases identified to date received a dural graft after 1993.
In Japan, it is estimated that 20,000 persons received a Lyodura graft each year during 1983–1987, approximately 50 times more than the estimated number of U.S. recipients (4). During this period, 123 Japanese patients who subsequently developed dCJD had surgical procedures, including 114 (93%) who had documentation of receipt of a Lyodura graft (the graft brand of the other nine patients was unknown), indicating that the risk for developing dCJD within 30 years of receiving a Lyodura graft in Japan was at least one per 877 (i.e., 114 dCJD cases per 100,000 Lyodura graft recipients). In this analysis, both the median and mean intervals from receipt of dural graft to illness onset (latency period) were 13 years (range = 1–30 years) (Figure 3). Since the update in 2008, 11 of the 22 newly reported dCJD cases have had latency periods exceeding 24 years, the longest interval reported in 2008 (4) (Figure 3). In three of these 11 cases, the latency period was 30 years, the longest reported to date.
Top Discussion
A comprehensive 2012 global summary of dCJD cases by country (2) reported that 142 (62%) of 228 cases of dCJD described worldwide occurred in Japan, and that at least one dCJD case was reported from 20 other countries. In the United States, four cases attributed to dura mater grafts have been identified; three were linked to a Lyodura graft produced before 1987, and one to a different commercially produced cadaveric dura mater graft. Lyodura grafts produced before 1987 were widely distributed to many countries, but most frequently to Japan.
During the U.S. investigation of the first Lyodura-associated CJD case in 1987 (9,10), investigators learned that the company mixed dura from multiple donors during batch processing of single lots and sterilized the grafts with gamma irradiation, a procedure that does not inactivate prions (10). A Lyodura representative also reported that the company did not maintain records identifying donors, so they could not be traced. Lyodura was only available to U.S. hospitals by mail if ordered from a non-U.S. distributor because the manufacturer did not produce the product for distribution in the United States.
Owing to Lyodura’s 5-year shelf life, it is likely that the eight dCJD patients in Japan who received Lyodura during 1988–1991 received grafts produced before the company changed its processing procedures in 1987. In addition, the three patients who received a graft in 1993 all received Lyodura grafts, one of which was documented to be an expired graft processed before 1987.
Age at onset of dCJD depends on the patient’s age at receipt of a dural graft and the latency period. Although the latency period varies among patients, currently available data indicate that the upper limit is at least 30 years, which is longer than has been reported previously (4). The most recently diagnosed case, for example, occurred in a patient who received Lyodura during surgery for a craniopharyngioma in 1985 at age 27 years and developed dCJD 30 years later in 2015.
The findings in this report are subject to at least four limitations related to ascertainment of dCJD cases. First, because it is possible that dCJD patients with an unknown brand of dural graft did, in fact, receive Lyodura, it is likely that one dCJD case per 877 Lyodura recipients is an underestimate of the proportion of dCJD patients with Lyodura-related CJD. Second, the risk for a Lyodura-related CJD infection among dural graft recipients is unknown because many infected patients likely died from other causes before developing CJD. Third, additional dCJD cases related to receipt of Lyodura might still occur. The increased use of Lyodura in Japan is the most likely reason for the unusually high number of dCJD cases in Japan (4), although only estimates of the numbers of recipients in Japan and other countries, including the United States, are available. Finally, the medical conditions for which dura mater grafts were used in Japan differed from those in other countries (5): patients with dCJD in Japan more frequently received dura mater grafts for non–life-threatening conditions than did patients in other countries (5).
The cases described in this report indicate that recipients of prion-contaminated grafts could remain at risk for CJD for at least 30 years after receiving grafts. Given the known potential for even longer latency periods for prion diseases, this outbreak is expected to continue. The dCJD cases underscore the importance of establishing measures to eliminate or greatly reduce the possibility of CJD transmissions (e.g., strict donor screening, appropriate record keeping, prevention of cross-contaminations, and ideally, the use of validated sterilization methods) whenever human tissues, particularly of cadaveric origin, might be used to treat other patients. In addition, a system of human disease surveillance to detect the possible emergence of new sources of prion disease transmissions is needed. Furthermore, physicians maintaining a high index of suspicion for unusual prion disease cases, as well as a system of human disease surveillance to detect the emergence of new sources of prion disease transmissions, is needed to enable the prevention of infections Finally, maintaining surveillance for CJD in Japan is important to better assess the impact of the outbreak of dCJD and to identify additional cases.
Ministry of Health, Labour and Welfare, Japan.
P81 Iatrogenic Creutzfeldt-Jakob disease related to dura mater grafts
Professor Masahito Yamada1, Dr. Tsuyoshi Hamaguchi1, Dr. Kenji Sakai1, Dr. Moeko Noguchi-Shinohara1, Dr. Ichiro Nozaki1, Yu Taniguchi1, Dr. Atushi Kobayashi2, Dr. Atsuko Takeuchi3, Prof. Tetsuyuki Kitamoto3, Prof. Yosikazu Nakamura4, Prof. Nobuo Sanjo5, Dr. Tadashi Tsukamoto6, Prof. Masaki Takao7, Dr. Shigeo Murayama8, Dr. Yasushi Iwasaki9, Prof. Mari Yoshida9, Dr. Hiroshi Shimizu10, Prof. Akiyoshi Kakita10, Prof. Hitoshi Takahashi10, Dr. Hiroyoshi Suzuki11, Prof. Hironobu Naiki12, Prof. Hidehiro MIzusawa6
1Kanazawa University, Kanazawa, Japan, 2Hokkaido University, Sapporo, Japan, 3Tohoku University, Sendai, Japan, 4Jichi Medical University, Shimotsuke, Japan, 5Tokyo Medical and Dental University, Tokyo, Japan, 6National Center of Neurology and Psychiatry, Tokyo, Japan, 7Saitama Medical University International Medical Center, Hidaka, Japan, 8Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan, 9Aichi Medical University, Nagakute, Japan, 10University of Niigata,, Niigata, Japan, 11National Hospital Organization Sendai Medical Center, Sendai, Japan, 12University of Fukui, Fukui, Japan
Aims: To elucidate epidemiological, clinicopathological, and molecular features of dura mater graft-associated Creutzfeldt-Jakob disease (dCJD), and deposition of pathogenic proteins of neurodegenerative diseases in dCJD.
Methods: We investigated dCJD patients identified in Japan, including epidemiological and clinicopathological features, genetic and molecular characteristics of prion protein (PrP), and transmission properties to mice expressing human PrP (Ki-HuPrP). Deposition of amyloid β protein (Aβ) and other pathogenic proteins in dCJD patients were analysed in comparison with age-matched patients with sporadic CJD (sCJD).
Results: Until September 2016, 152 patients with dCJD have been identified in Japan, comprising about two-thirds of the world cases. They received dura mater grafts between 1975 and 1993 at the ages of 1-70 (av. 43) years for the surgery of brain tumor, hemorrhage, hemifacial spasm, etc. After the incubation periods of 1-30 (av. 13) years, they had dCJD onset at the ages of 15-80 (av. 56) years in 1985-2015. The higher incidence of dCJD in Japan may be related to more frequent use of cadaveric dura mater for non-life-threatening conditions than in other countries. dCJD was classified to plaque and non-plaque types. Non-plaque type had clinicopathological features of classical CJD, while, plaque type was characterized by relatively slow progression, lack or late occurrence of periodic encephalogram, unique MRI findings, methionine homozygosity (M/M) at codon 129 of the PrP gene, intermediate type PrPres (type i), and kuru plaques in the brain (MMiK). Transmission studies with the plaque type dCJD to Ki-HuPrP mice showed properties identical to sCJD-VV2 and MV2, indicating that the origin of the plaque type would be VV2 or MV2 sCJD (V2 prion strain). Furthermore, we identified two atypical cases of MMiK type among patients with “sCJD”; the two MMiK cases showed same properties as sCJD-VV2 or MV2 in transmission and protein misfolding cyclic amplification (PMCA) studies, indicating transmission of the V2 prion prion to these cases in the absence of dura mater or other grafts. Compared with sCJD, dCJD showed significantly severe cerebrovascular Aβ deposition (CAA), especially meningeal CAA, and subpial Aβ deposition; the severity was correlated with incubation period from dura mater grafting to death.
Conclusions: We revealed epidemiological, clinicopathological, and molecular features of dCJD. Plaque type dCJD was characterized by MMiK, indicating cross-sequence transmission of the V2 prion strain to methionine homozygotes. MMiK could be a marker to identify acquired prion diseases. Cerebral β-amyloidosis could be transmitted from humans to humans via cadaveric dura mater grafting.
P119 Type-dependant diverse extension patterns of hyperintensity on diffusion-weighted MR images in dura mater graft-associated Creutzfeldt-Jakob disease
Dr Kenji Sakai1, Dr Tsuyoshi Hamaguchi1, Dr Nobuo Sanjo2, Dr Hiroyuki Murai3, Dr Yasushi Iwasaki4, Dr Tadanori Hamano5, Dr Mari Honma6, Dr Moeko Noguchi-Shinohara1, Dr Ichiro Nozaki1, Prof Yosikazu Nakamura7, Prof Tetsuyuki Kitamoto8, Dr Hidehiro Mizusawa9, Prof Masahito Yamada1 1Kanazawa University, Kanazawa, Japan, 2Tokyo Medical and Dental University, Tokyo, Japan, 3Kyushu University, Fukuoka, Japan, 4Aichi Medical University, Nagakute, Japan, 5University of Fukui, Fukui, Japan, 6Masu Memorial Hospital, Nihonmatsu, Japan, 7Jichi Medical University, Shimtsuke, Japan, 8Tohoku University, Sendai, Japan, 9National Center of Neurology and Psychiatry, Kodaira, Japan
Aims: Studies of dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) cases have proposed that abnormal prion protein may propagate directly from the contaminated dura mater graft to the adjacent brain regions and spread to other brain areas. We aimed to elucidate extension patterns of the hyperintense areas on diffusion-weighted images (DWI) in patients with dCJD.
Methods: We collected the MR images and the medical records of dCJD cases identified by CJD Surveillance Committee in Japan between April 1999 and September 2016. The dCJD cases were classified into two clinicopathological subtypes (non-plaque type and plaque type). We analyzed a relationship among the abnormal signals on DWI, the pathological classification, and the sites of grafting. Sequential images were also assessed.
Results: We collected MR images of 11 patients with dCJD. Lyodura® was transplanted in all proven cases. Four cases were female. The median with range of the age at onset, the age at dural grafting, and the incubation period were 41 (26–76) years, 19 (10–53) years, and 22 (16–29) years, respectively. The dCJD cases were classified into 8 cases of the non-plaque type and 3 cases of the plaque type. Four of the 8 non-plaque-type cases and all the plaque-type cases were pathologically confirmed. Brain MRI was performed 3 (1–22) months, reported as median (range), after the onset. Initial brain MRI was taken significantly earlier in cases with non-plaque type (non-plaque 2.5 months vs plaque 10 months; P = 0.012). Regarding non-plaque type, hyperintense cerebral cortex and basal ganglia (BG) were obvious in all cases. Abnormal signals were much brighter on the side of dural grafting. Subsequent MRI performed in 5 cases showed widespread hyperintense lesions in the brain. In contrast, the plaque type cases showed diverse patterns of hyperintensity on DWI. In one case, initial hyperintense areas were shown in the BG, frontal cortex, and thalamus. The other case demonstrated the lesion confined to the BG and thalamus. Sequential images presented with frontal lesions in addition to BG and thalamus. The third case showed no apparent abnormalities in the cerebral cortex or BG on DWI 7 months after the onset; however, serial images showed hyperintensity in the cerebral cortex, thalamus, and cerebellum.
Conclusions: In cases with non-plaque type dCJD, there could be a close relationship between the hyperintense signals on DWI and the sites of dural grafting. Plaque-type prions could have different patterns of propagation in human CNS.
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P126 Clinical and pathological characterization of “sporadic Creutzfeldt-Jakob disease” with histories of neurosurgery to identify iatrogenic cases
Dr. Tsuyoshi Hamaguchi1, Dr. Kenji Sakai1, Dr. Atsushi Kobayashi2, Professor Tetsuyuki Kitamoto3, Dr. Ryusuke Ae4, Professor Yosikazu Nakamura4, Professor Nobuo Sanjo5, Dr. Tadashi Tsukamoto6, Professor Hidehiro Mizusawa6, Professor Masahito Yamada1 1Department Of Neurology, Kanazawa University Hospital, Kanazawa, Japan, 2Laboratory of Comparative Pathology, Hokkaido University, Sapporo, Japan, 3Department of Neurological Science, Tohoku University, Sendai, Japan, 4Division of Public Health, Center for Community Medicine, Jichi Medical University, Shimotsuke, Japan, 5Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan, 6Department of Neurology, National Center of Neurology and Psychiatry, Kodaira, Japan
Aims: Recently, we revealed that patients with plaque-type dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) showed atypical molecular features characterized by methionine homozygote at codon 129 of the prion protein gene (PrP), intermediate type PrPSc, and Kuru plaques, called MMiK. Surprisingly, we discovered that 2 patients who had been diagnosed as having sporadic Creutzfeldt-Jakob disease (sCJD) showed clinical, pathological, and molecular features identical to MMiK type, suggesting possible iatrogenic transmission. In this study, the objective is to investigate the possibility of iatrogenic transmission of prion disease in patients who have been diagnosed as having sCJD.
Methods: We investigated 1836 patients who were diagnosed as having sCJD and 5 patients who were diagnosed as having unclassified type CJD because of insufficient information of dura mater grafting in the nationwide surveillance of CJD in Japan, and compared between those with and without histories of neurosurgeries.
Results: Among 1841 patients with sCJD, 51 had histories of neurosurgery, but 13 patients were excluded from the study because they underwent neurosurgeries within 1 year before or after the onset of CJD. Between the patients with and without histories of neurosurgery, positive rate (84.2%, 32/38 patients) of periodic sharp-wave complexes (PSWCs) on electroencephalogram (EEG) in the patients with histories of neurosurgery were significantly less than that (94.4%, 1677/1776 patients) in the patients without histories of neurosurgery, although age at onset of CJD, sex distribution, distribution of polymorphism at codon 129 of PrP, disease duration of CJD (duration between the onset of CJD and the appearance of the akinetic mutism or death in the patients who died without akintic mutism), and positive rate of 14-3-3 protein and total tau (cut off 1200 pg/ml) in cerebrospinal fluid were not significantly different. Among 38 sCJD patients with histories of neurosurgery, 9 (23.7%) had atypical CJD features that showed no PSWCs on EEG or had disease duration longer than 1 year. Three of the 9 atypical patients with histories of neurosurgery were autopsied, and one patient was MM2-thalamic form, one patient was MM2-cortical form, and another one patient was MMiK.
Conclusions: Among the patients who were diagnosed as sCJD or unclassified type CJD, some patients with histories of neurosurgery, but without dura mater grafting, had atypical clinical and neuropathological features similar to plaque type dCJD. Neuropathological study with PrP typing is essential to identify iatrogenic cases in patients with prion disease and history of neurosurgery.
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Iatrogenic CJD after human cadaver-sourced growth hormone treatment in France: identifying risk factors associated with susceptibility
Ms Laurene Peckeu1, PhD Dominique Costagliola4, MD Jean-Philippe Brandel1,2, MD, PhD Stephane Haïk1,2,3 1Institut Du Cerveau Et De La Moelle Épinière (ICM) - Team "alzheimer's And Prion Diseases "inserm Umr-1127/cnrs Umr 7225, Paris, France, 2AP-HP, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, Paris, France, 3AP-HP, Laboratoire de Neuropathologie R Escourolle, Groupe Hospitalier Pitié-Salpêtrière, Paris, France, 4Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Universités, Inserm et UPMC Univ Paris 06 (UMR_S 1136), Paris, France
Background: Human growth hormone (hGH) treatment is the main cause of iatrogenic CJD (iCJD-hGH) in France. Among the 1443 patients who received cadaver-sourced hGH during the high-risk period from December 1983 to July 1985, 119 patients developed Creutzfeldt-Jakob disease. In this study, risk factors associated with the susceptibility of developing iCJD-hGH were analysed.
Methods: Two multivariate cox analyses were performed on the 1443 subjects. The first one (Bonferroni correction, level of significance for univariate analysis at 0.0008) aimed to determine, among all the 63 batches dispensed during this period, those significantly associated with the risk of developing CJD. The second model aimed to assess the association of sex, age at beginning of treatment, treatment duration and number of doses received from each batch with susceptibility. In this model all variables individually associated with susceptibility at a significant level of p<0 .1="" analysis="" in="" included="" level="" multivariate="" of="" p="" significance:="" span="" the="" then="" were="">
Results: Nineteen batches were identified after univariate analysis. Five of them were significantly associated with susceptibility after multivariate analysis. The number of doses delivered from batches identified at risk was statistically different (mean=55.3 for hGH-CJD group and 16.1 for non hGH-CJD group). iCJD-hGH was significantly more frequent in males (10%) compared to females (5%). Median age at the beginning of treatment was 12.0 years in non hGH-CJD group, and 12.1 in hGH-CJD group. Treatment duration was significantly higher in hGH-CJD group. Risk factors associated with the susceptibility identified by the second model were gender (HR, 1.70; 95%CI, 1.08-2.67) and the number of doses from the batches identified at risk by the first analysis (HR, 2.90; 95%CI, 2.22-3.79).
Discussion: In the final model, among the five batches that were significantly associated with susceptibility, four were previously reported as at risk (Huillard d’Aignaux et al., 1998). Of the 1443 patients, 550 were exposed to at least one of these five batches and only 18% (n=100) of them developed iCJD-hGH suggesting that additional risk factors were involved. The second model showed a significant association between sex, doses and susceptibility of developing iCJD-hGH. While the relationship between infectious dosis and attack rate is a well known phenomenon in experimental infectious models of prion diseases, this is the first evidence, to our knowledge, that it also applies in humans. Surprinsingly, we observed an effect of gender with a two-fold higher proportion in male that could not been explained by a difference in exposure.
THURSDAY, MAY 17, 2012
Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment
Volume 18, Number 6—June 2012
Paul Brown , Jean-Philippe Brandel, Takeshi Sato, Yosikazu Nakamura, Jan MacKenzie, Robert G. Will, Anna Ladogana, Maurizio Pocchiari, Ellen W. Leschek, and Lawrence B. Schonberger Author affiliations: Centre à l’Energie Atomique, Fontenay-aux-Roses, France (P. Brown); Institut National de la Santé et de la Recherche Médicale, Paris, France (J.-P. Brandel); Nanohana Clinic, Tokyo, Japan (T. Sato); Jichi Medical University, Yakushiji, Japan (Y. Nakamura); Western General Hospital, Edinburgh, Scotland, UK (J. MacKenzie, R.G. Will); Istituto Superiore de Sanità, Rome, Italy (A. Ladogana, M. Pocchiari); National Institutes of Health, Bethesda, Maryland, USA (E.W. Leschek); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (L.B. Schonberger)
Abstract
The era of iatrogenic Creutzfeldt-Jakob disease (CJD) has nearly closed; only occasional cases with exceptionally long incubation periods are still appearing. The principal sources of these outbreaks are contaminated growth hormone (226 cases) and dura mater grafts (228 cases) derived from human cadavers with undiagnosed CJD infections; a small number of additional cases are caused by neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infection with variant CJD transmitted by transfusion of blood products. No new sources of disease have been identified, and current practices, which combine improved recognition of potentially infected persons with new disinfection methods for fragile surgical instruments and biological products, should continue to minimize the risk for iatrogenic disease until a blood screening test for the detection of preclinical infection is validated for human use.
I hope and pray that Paul Brown et al rosey outlook is correct, and the end of iatrogenic Creutzfeldt Jakob Disease is truly over, bbut, I have my doubts. ...TSS
5.3.3 The greatest risk, in theory, would be from parenteral injection of material derived from bovine brain or lymphoid tissue. Medicinal products for injection or surgical implantation which are prepared from bovine tissues, or which utilise bovine serum albumin or similar agents in their manufacture, might also be capable of transmitting infectious agents. All medicinal products are licensed under the Medicines Act by the Licensing Authority following guidance, for example from the Committee on Safety of Medicines (CSM), the Committee on Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing Authority have been alerted to potential concern about BSE in medicinal products and will ensure that scrutiny of source materials and manufacturing processes now takes account of BSE agent.
EXPORT OF BRITISH BIOLOGICAL PHARMACEUTICALS
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Update: Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts, Japan, 1978-2008
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Creutzfeldt-Jakob disease (CJD) is the most common of the human prion diseases (also known as transmissible spongiform encephalopathies), which, according to the leading hypothesis, are caused by an abnormal protein (that is, prion) that is able to induce abnormal folding of normal cellular prion proteins. Annual worldwide incidence of these always fatal neurodegenerative diseases is estimated at 0.5-2.0 cases per million population. CJD can occur sporadically, or as a genetic disease, or can be transmitted iatrogenically. In 1996, a new human prion disease, variant CJD (vCJD), was 1st described in the United Kingdom. This disease was believed to have resulted from human consumption of cattle products contaminated with the prions responsible for bovine spongiform encephalopathy (BSE, commonly known as mad cow disease). That year, in part to check for possible vCJD cases, a national survey was conducted in Japan; 821 CJD cases were identified, including 43 cases associated with receipt of cadaveric dura mater grafts (1). A single brand of dural graft (Lyodura) produced by a German manufacturer before May 1987 was identified as the most likely vehicle of transmission in all but one case (2,3). By 2003, continued surveillance in Japan had identified a total of 97 such cases (2). Since then, an additional 35 cases have been identified. This report updates previous reports and summarizes the investigation of all 132 cases to date linked to dural grafts. The results suggest that, because of the long incubation period between graft receipt and symptom onset (possibly greater than 24.8 years), continued surveillance in Japan might identify additional CJD cases associated with dural grafts. Since 1996 in Japan, a nongovernmental CJD surveillance group supported by the Ministry of Health and Welfare (later renamed the Ministry of Health, Labour, and Welfare) has conducted a national survey seeking cases of human prion disease. The survey is mailed to neurologic, psychiatric, and neuropathologic departments of hospitals with a minimum bed capacity of 100 (overall response rate: 74 per cent) (1,2). A case of CJD associated with a dura mater graft is defined as physician-diagnosed CJD in the recipient of a cadaveric dura mater graft whose disease was reviewed and accepted as CJD by the surveillance system's panel of neurologists.
During 1996-2008, as clinicians reported additional CJD cases to the surveillance system sponsored by the Ministry of Health and Welfare, the number of persons identified with CJD associated with cadaveric dura mater grafts increased from 43 initially to 132. All 132 patients had received dura mater grafts during 1978-1993. Three patients received more than one dural graft during this period, including one patient reported previously. For purposes of analysis, the 1st graft was assumed to be the source of infection in all 3 patients. Of the 132 patients, the most common medical conditions leading to the use of dural grafts were tumor (60 patients, 45 per cent), brain hemorrhage (21, 16 per cent), Jannetta procedure for facial palsy (18, 14 per cent) and for trigeminal neuralgia (7, 5 per cent), and intracranial aneurysm (9, 7 per cent). The other conditions were unspecified anomalies (6 patients), hematoma (6), injury (4), and ossification of the spinal posterior longitudinal ligament (one).
Illness onset for the 132 CJD patients ranged from September 1985 to October 2006. The mean age of the 132 patients at onset was 55 years (range: 15-80 years); the median age was 57 years. A total of 79 (60 per cent) patients were female. Neuropathologic confirmation of CJD diagnosis was obtained from 31 (23 per cent) patients; 81 (80 per cent) of the other 101 patients with physician-diagnosed CJD had an electroencephalogram with a periodic synchronous discharge pattern characteristic of CJD.
Incubation periods ranged from 1.2 years (receipt in 1987 and onset in 1989) to 24.8 years (receipt in 1981 and onset in 2006). The median and mean incubation periods were 12.4 years and 11.8 years, respectively.
A total of 120 of the 132 patients (91 per cent) were documented to have received Lyodura dural grafts; investigators were unable to identify the lot numbers of the grafts used. For the 12 other patients, the brand name of the dural graft was unknown. A total of 109 (83 per cent) patients received their dural grafts during 1983-1987, when an estimated 100 000 persons received Lyodura grafts in Japan (2,4).
[Reported by: Y Nakamura, MD, R Uehara, MD, PhD, M Watanabe, MD, PhD, A Sadakane, MD, Dept of Public Health, Jichi Medical Univ, Shimotsuke; M Yamada, MD, Dept of Neurology, Kanazawa Univ Graduate School of Medical Science, Kanazawa; H Mizusawa, MD, Dept of Neurology, Tokyo Medical and Dental Univ School of Medicine, Tokyo, Japan. R Maddox, MPH, J Sejvar, MD, E Belay, MD, L Schonberger, MD, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC]
MMWR editorial note:
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New cases of CJD associated with dural grafts continue to be reported in Japan, and Lyodura grafts remain the most likely vehicle for transmission. Similar to other allogeneic dura mater grafts, Lyodura grafts were derived from cadaveric dura mater and used by surgeons for soft-tissue reconstruction of damaged, missing, or impaired tissues (primarily dura mater). According to the manufacturer, the grafts were gradually absorbed in situ, colonized by fibroblasts and stem cells, and eventually replaced by endogenous connective tissue.
In 1987, the 1st identified case of CJD associated with a Lyodura graft was reported in the United States (5). During the US investigation of that case, the manufacturer reported revising collection and processing procedures for Lyodura to reduce the risk for CJD transmission (6). Only 6 of the 132 patients in Japan received their dural grafts after 1987, and only one of these 6 patients is known to have received a Lyodura graft that was most likely produced after 1987. This patient had received 2 dura mater grafts in 1991 at a hospital that reported using only Lyodura or another brand of dural grafts, Tutoplast (3). No cases have been reported in Japan among patients who received their 1st dural graft after 1993.
The substantial number of CJD cases associated with dural grafts in Japan likely reflects the widespread use in that country of Lyodura grafts produced before May 1987. During 1983-1987, an estimated 20 000 persons in Japan received Lyodura grafts each year, about 50 times higher than the estimated number of recipients in the US (2,4). Although Lyodura was then available to US hospitals through the mail, the German manufacturer produced Lyodura for distribution in Japan and other countries but not for distribution in the US (7). In June 1987, after the company learned of the 1st CJD case associated with a Lyodura graft, the manufacturer reported revising procedures for the collection and processing of its dura mater grafts after 1 May 1987, to reduce the risk for CJD transmission (6). The key reported processing changes included conversion from batch to individual processing of dura mater and treatment of each dura mater graft with 1.0 normal sodium hydroxide (NaOH); no practical final screening test of the product for prion contamination is available. However, the change to individual processing of dura mater greatly limited the number of grafts that could be contaminated by a single infected donor. In addition, 1.0 normal NaOH is known to be highly effective for inactivating prions (3).
In the US, after report of the 1st Lyodura-associated CJD case, the Food and Drug Administration (FDA) issued a recall in late April 1987 of Lyodura that was packaged in 1982, the year the graft used in the initial US case had been packaged. In addition, after receiving report of a 2nd Lyodura-associated CJD case in a patient in New Zealand, CDC advised avoiding Lyodura grafts produced before May 1987 (6). However, no international recall of Lyodura produced before May 1987 occurred. Therefore, the implicated Lyodura with its potential contaminant might have remained in use at Japanese hospitals for several years.
Cases of dural graft-associated CJD in Japan have occurred since 1985, peaking during 1995-1999, when 51 of the 132 patients became ill. As this outbreak has continued, the median incubation period has increased to 12.4 years, and the longest period between graft surgery and onset of illness is now 24.8 years. In the US, 2 more patients with Lyodura-associated CJD have been identified since the 1st reported case in 1987. Most recently, a patient aged 26 years died in 2006 from autopsy-confirmed CJD (7). The incubation period in this case was 18.7 years.
The long incubation period and always fatal outcome of CJD and other transmissible spongiform encephalopathies underscore the importance of efforts to minimize potential exposures of persons to prions. However, implementing timely preventive measures against these diseases can be difficult because the public health significance of certain actions might not become apparent for years, if at all. For example, in 1987, the producer of Lyodura revised collection and production measures without knowing at the time that these actions likely would prevent many future deaths from Lyodura-associated CJD. Similarly, in 1997, a feed ban was instituted to prevent BSE in the United States, even though no endemic BSE had been recognized in North America. In addition, to prevent potential cases of vCJD in the United States, prospective blood donors who might have been exposed to BSE in the United Kingdom were deferred, even before transmission of the vCJD agent via blood transfusion had been documented in that country (8).
In 1997, the FDA's Transmissible Spongiform Encephalopathy Advisory Committee recognized that use of human dura mater carries an inherent risk for transmitting CJD. However, the committee recommended that the use of such grafts be left to the discretion of the treating neurosurgeon, provided that the human dura mater is procured and processed according to additional safety measures outlined by the committee (9). After the committee's recommendations were issued, the number of dural grafts distributed for use in the US declined from an estimated 4500 in 1997 to an estimated 900 in 2002, to a documented 389 in 2006, and 368 in 2007 (2) (BE Buck, MD, Miami Tissue Bank, personal communication, August 2008).
CDC continues to conduct surveillance for cases of CJD in the US through various mechanisms, including 1) receipt and investigation, in collaboration with local and state health departments, of case reports from physicians and patient support groups; 2) analysis of national multiple cause-of-death data; and 3) review of prion disease cases confirmed by the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University (Cleveland, Ohio). During 1996-1997, CDC established NPDPSC in collaboration with the American Association of Neuropathologists to help maintain and enhance US human prion disease surveillance. NPDPSC provides, free of charge, advanced neuropathologic and biochemical prion disease diagnostic services to US physicians and other appropriate health personnel, including local and state health officials. Patients with a rapidly progressive dementia consistent with CJD and a history of dural graft implantation should be reported through local or state health departments to CDC, telephone 404-639-3091.
References --------- 1. Nakamura Y, Yanagawa H, Hoshi K, Yoshino H, Urata J, Sato T. Incidence rate of Creutzfeldt-Jakob disease in Japan. Int J Epidemiol 1999; 28: 130-4. 2. CDC. Update: Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts--Japan, 1979-2003. MMWR 2003; 52: 1179-81. 3. CDC. Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts---Japan, January 1979--May 1996. MMWR 1997; 46: 1066-9. 4. Brown P, Preece M, Brandel JP, et al. Iatrogenic Creutzfeldt- Jakob disease at the millennium. Neurology 2000; 55: 1075-81. 5. CDC. Epidemiologic notes and reports update: Creutzfeldt-Jakob disease in a patient receiving a cadaveric dura mater graft. MMWR 1987; 36: 324-5. 6. Janssen RS, Schonberger LB. Creutzfeldt-Jakob disease from allogeneic dura: a review of risks and safety [Discussion]. J Oral Maxillofac Surg 1991; 49: 274-5. 7. Blossom DB, Maddox RA, Beavers SF, et al. A case of Creutzfeldt- Jakob disease associated with a dura mater graft in the United States. Infect Control Hosp Epidemiol 2007; 28: 1396-7. 8. Zou S, Fang CT, Schonberger LB. Transfusion transmission of human prion diseases. Transfus Med Rev 2008; 22: 58-69. 9. Food and Drug Administration. Class II special controls guidance document: human dura mater. Guidance for industry and FDA. Rockville, MD: Food and Drug Administration; 2002. Available at
Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone
E A Croes, G Roks, G H Jansen,PCG Nijssen, C M van Duijn .............................................................................................................................
J Neurol Neurosurg Psychiatry 2002;72:792–793
A 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic CJD. This is the longest incubation period described so far for iatrogenic CJD. Furthermore, this is the first report of CJD after diagnostic use of hGH. Since the patient was one of the first in the world to receive hGH, other cases of iatrogenic CJD can be expected in the coming years.
snip...
An incubation period as long as 38 years had never been reported for iatrogenic CJD. Huillard d’Aignaux et al7 studied the incubation period in 55 patients with hGH related CJD in a cohort of 1361 French hGH recipients. The median incubation period was between 9 and 10 years. Under the most pessimistic model, the upper limit of the 95% confidence interval varied between 17 and 20 years. Although the infecting dose cannot be quantified, it can be speculated that the long incubation period in our patient is partly explained by the administration of a limited amount of hGH. This hypothesis is supported by experimental models, in which higher infecting doses usually produce shorter incubation periods.6 Since our patient was one of the first in the world to receive hGH, this case indicates that still more patients with iatrogenic CJD can be expected in the coming years. Another implication of our study is that CJD can develop even after a low dose of hGH. This case once more testifies that worldwide close monitoring of any form of iatrogenic CJD is mandatory.
Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years
Peter Rudge,1,2 Zane Jaunmuktane,3 Peter Adlard,4 Nina Bjurstrom,1 Diana Caine,1,5 Jessica Lowe,2 Penny Norsworthy,2 Holger Hummerich,2 Ron Druyeh,2 Jonathan D. F. Wadsworth,2 Sebastian Brandner,3 Harpreet Hyare,1,2 Simon Mead1,2 and John Collinge1,2
Patients with iatrogenic Creutzfeldt-Jakob disease due to administration of cadaver-sourced growth hormone during childhood are still being seen in the UK 30 years after cessation of this treatment. Of the 77 patients who have developed iatrogenic CreutzfeldtJakob disease, 56 have been genotyped. There has been a marked change in genotype profile at polymorphic codon 129 of the prion protein gene (PRNP) from predominantly valine homozygous to a mixed picture of methionine homozygous and methioninevaline heterozygous over time. The incubation period of iatrogenic Creutzfeldt-Jakob disease is significantly different between all three genotypes. This experience is a striking contrast with that in France and the USA, which may relate to contamination of different growth hormone batches with different strains of human prions. We describe the clinical, imaging, molecular and autopsy features in 22 of 24 patients who have developed iatrogenic Creutzfeldt-Jakob disease in the UK since 2003. Mean age at onset of symptoms was 42.7 years. Gait ataxia and lower limb dysaesthesiae were the most frequent presenting symptoms. All had cerebellar signs, and the majority had myoclonus and lower limb pyramidal signs, with relatively preserved cognitive function, when first seen. There was a progressive decline in neurological and cognitive function leading to death after 5–32 (mean 14) months. Despite incubation periods approaching 40 years, the clinical duration in methionine homozygote patients appeared to be shorter than that seen in heterozygote patients. MRI showed restricted diffusion in the basal ganglia, thalamus, hippocampus, frontal and the paracentral motor cortex and cerebellar vermis. The electroencephalogram was abnormal in 15 patients and cerebrospinal fluid 14-3-3 protein was positive in half the patients. Neuropathological examination was conducted in nine patients. All but one showed synaptic prion deposition with numerous kuru type plaques in the basal ganglia, anterior frontal and parietal cortex, thalamus, basal ganglia and cerebellum. The patient with the shortest clinical duration had an atypical synaptic deposition of abnormal prion protein and no kuru plaques. Taken together, these data provide a remarkable example of the interplay between the strain of the pathogen and host prion protein genotype. Based on extensive modelling of human prion transmission barriers in transgenic mice expressing human prion protein on a mouse prion protein null background, the temporal distribution of codon 129 genotypes within the cohort of patients with iatrogenic Creutzfeldt-Jakob disease in the UK suggests that there was a point source of infecting prion contamination of growth hormone derived from a patient with Creutzfeldt-Jakob disease expressing prion protein valine 129.
Discussion
This study, covering the period from 2000–14, shows that iatrogenic CJD due to cadaver-sourced pituitary growth hormone, a treatment that was discontinued in 1985 in the UK, continues to occur in the UK at a frequency of 0–6 cases per annum. Incubation periods are now extraordinarily long, with estimates ranging from 18–40 years, the uncertainty based on clinical onsets and lengths of treatment with potentially infected batches. In this paper we have reviewed the clinical features, progression, imaging abnormalities, prion protein genotype, PrPSc type by western blot and preliminary neuropathology data.
THURSDAY, DECEMBER 08, 2011
A case of Iatrogenic Creutzfeldt Jakob Disease (iCJD) in a patient who had received a German-manufactured human dura mater graft 23 years ago
Monday, February 01, 2010
Import Alert 57-20 and 84-03 Human Dura Mater and risk factors there from due to Creutzfeldt Jakob Disease (CJD)
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral ...
Thursday, March 8, 2018
Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein
Subject:
CJD * Lyodura-B.Braun Melsungen AG, Germany
From:
"Terry S. Singeltary Sr."
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Bovine Spongiform Encephalopathy
Date:
Mon, 27 Sep 1999 10:35:09 -0500
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Terry S. Singeltary Sr., Bacliff, Texas USA -- Greetings, I was hoping Roland or someone, could tell me if this Company (Lyodura-B.Braun Melsungen AG, Germany) is still paying out settlements for the medical deaths from CJD and their product? How far back, has their product been found to be infected and or, was it found to be deadly in 1982? Was the material in 1982 taken from cows or humans or both?
Many Thanks, Terry
Subject:
Re: CJD * Lyodura-B.Braun Melsungen AG, Germany
From:
Jennifer Cooke
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Bovine Spongiform Encephalopathy
Date:
Wed, 29 Sep 1999 00:24:32 +1000
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Cear Terry,
I devoted most of one chapter in my book, Cannibals Cows & the CJD Catastrophe (Random House Australia) to CJD deaths from dura mater including Lyodura, that have been reported in the literature since the initial FDA warning about Lyodura in 1987.
Several cases related to 1982 - either because the Lyodura was manufactured in that year, or the operation of the victim took place in that year. One confidential settlement I know of was to the family of a British man who died of CJD in 1989 following a Lyodura graft in 1985.
There have now been four deaths in Australia from CJD after Lyodura grafts - all of which related to operations carried out in 1982. The latest death occurred in June this year - which means that the incubation period has now blown out to more than 17 years for this type of peripheral infection. Quite horrifying. I believe the family intends to sue ...
Regards,
Jennifer Cooke
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Subject:
Japan releases bad Lyodura lot numbers
From:
tom
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Bovine Spongiform Encephalopathy
Date:
Wed, 20 Sep 2000 14:53:39 -0800
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This is hot, they actually published the bad lot numbers on the Lyodura in the newspaper. NIH has fought off US residents for years. on the growth hormone lot numbers, to protect their crazy man in North Carolina who insisted on injecting crude pituitary extracts. Some recipients do want to know whether they got an injection from a bad lot; some don't -- but I never heard from anyone who wanted Big Brother making the decision for them.
There is a staggering amount of this Lyodura implanted in people: Japan alone imported "12,545 boxes of the dura mater, manufactured in 1982 by B. Braun Melsungen AG." It doesn't say how many uses per box or how many boxes comprise a serial number, or how many individuals were pooled per serial number.
It would be so cool if some serial number 2105 or so is still around -- then we could test it to see what species it came from (I say sheep, given that is what their contract surgeon, who died of CJD a few years thereafter, was removing as dura mater source).
tom
CJD-linked product banned in U.S. was imported to ... Kyodo World Service Wed, Sep 20, 2000
TOKYO, Sept. 21 (Kyodo) -- The government on Wednesday admitted to the likelihood that Japan imported German medical products which reportedly caused Creutzfeldt-Jakob Disease (CJD) even after the United States had warned of the danger in 1987, contradicting its previous claims.
Kazuo Maruta, a senior official at the Health and Welfare Ministry, said the German-made dried dura mater used for brain surgery produced in 1982 was likely to have been imported before 1997.
The U.S. Food and Drug Administration (FDA) in 1987 issued a domestic advisory not to use such dura mater made in that year, after learning about a report that it could cause CJD.
Symptoms of the disease include rapidly progressive dementia, loss of cerebral functions, and paralysis of limbs, with parts of the brain becoming sponge-like.
Maruta, chief of the ministry's Pharmaceutical and Medical Safety Bureau, told members of the Health and Welfare Committee at the House of Representatives that it is "likely" that the product, Lyodura with serial numbers 2000 to 2999, was imported into Japan.
He cited a report by Tokyo importer Nihon B.S.S. which said 12,545 boxes of the dura mater, manufactured in 1982 by B. Braun Melsungen AG, were imported that year.
Health and Welfare Minister Yuji Tsushima also told the committee, "It was impossible (for the government) to foresee the dangers of the product."
Previously, the ministry has denied the possibility of any imports, insisting that Lyodura with the serial number 2105, which the U.S. government said caused the first-discovered case of CJD, was not imported into Japan.
The German firm recalled the 2105 Lyodura in early 1987 and the FDA advised domestic medical facilities to abandon the product with serial numbers from 2000 to 2999.
It was only 10 years later that the Japanese ministry prohibited use of the product.
More than 40 people, including CJD victims and their relatives, have filed two damages suits with the Tokyo District Court and the Otsu District Court, Shiga Prefecture, accusing the Japanese companies involved and the German firm of negligence, as well as the Japanese government.
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Subject:
Re: Japan releases bad Lyodura lot numbers
From:
"Bossers, A."
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Bovine Spongiform Encephalopathy
Date:
Thu, 21 Sep 2000 08:44:59 +0200
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Tom,
Sorry but I don't get it.
> It would be so cool if some serial number 2105 or so is still > around -- > then we could test it to see what species it came from (I say > sheep, given > that is what their contract surgeon, who died of CJD a few years > thereafter, was removing as dura mater source). > > tom >
You think that Lyodura grafts were made of other origin than human? Do you have references to that? Thought they were of human origin solely and that only animal products were used for ie. catgut / sutures?
Alex
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Subject:
Re: Japan releases bad Lyodura lot numbers
From:
tom
Reply-To:
Bovine Spongiform Encephalopathy
Date:
Thu, 21 Sep 2000 06:36:13 -0800
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######### Bovine Spongiform Encephalopathy #########
>> It would be so cool if some serial number 2105 or so is still >> around -- >> then we could test it to see what species it came from (I say >> sheep, given >> that is what their contract surgeon, who died of CJD a few years >> thereafter, was removing as dura mater source).
>You think that Lyodura grafts were made of other origin than human? Do you >have references to that? Thought they were of human origin solely and that >only animal products were used for ie. catgut / sutures? >
I was surprised to find that xenotransplants have been going on for decades on a truly massive scale in many countries. It is not just cowgut surgical sutures, but anything and everything that doesn't set off too bad an immune response. One of the more insiduous aspects of the BSE epidemic is the large number of bovinebiologicals that came onto the international comodity markets. We saw just one British company selling 40,000 bovine pericardium patches at year for use in human heart valve replacements.
I posted many months back all the species used previously for dura mater transplants in human, as seen in simple Medline searches. I also posted some ideas on how to experimentally determine the species of origin for a given piece of dura mater, be it still in the box or removed from a iatrogenic CJD cadaver (there are a couple of intrinsic proteins that could be seen with IgG).
I also posted a newspaper account of the German orthopedic surgeon employed by this dura mater company to remove dura mater from sheep brain. The cause of his CJD was never determined (though the diagnosis was not in doubt); it could have been anything from handling sheep scrapie dura mater to inherited. I don't know if he also handled human dura mater for the company. Scrapie is only uncommonly reported in German sheep.
The idea here is not to make assumptions about the species origin of Lyodura, but rather to test the species origin experimentally. The purpose here is not to investigate the company.
Rather, Japan may have inadvertently done the scrapie-to-human intra-cerebral injection experiment that medical ethics prevents us from doing directly today. This would complement the successful in vitro conversion experiments that you and your colleagues have published.
Given the scale of dura mater use in Japan, there may still be boxes left of dura mater in the 2000-2999 serial number range. Or there may be material recoverable from 2105 recipients. Given the low incidence of CJD compared to scrapie, I would say that if any of the dura mater is sheep, the whole episode can be probably be attributed to scrapie.
tom
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Subject:
Re: Japan releases bad Lyodura lot numbers
From:
tom
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Bovine Spongiform Encephalopathy
Date:
Thu, 21 Sep 2000 08:48:32 -0800
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######### Bovine Spongiform Encephalopathy #########
Alex,
Mon, 19 Jul 1999 was when this came up. Here is the relevent Lancet article.
Transmission of Creutzfeldt-Jakob disease by handling of dura mater.
The Lancet Volume 341(8837) January 9, 1993 pp 123-124 Weber, Thomas; Tumani, Hayrettin; Holdorff, Bernd; Collinge, John; Palmer, Mark; Kretzschmar, Hans A.; Felgenhauer, Klaus
Sir,- Creutzfeldt-Jakob disease (CJD) can be transmitted iatrogenically by human pituitary growth hormone, corneal transplants, and dura mater grafts (1). Possible accidental transmission has been reported in only four people-a neurosurgeon (2), a pathologist (3), and two laboratory technicians (4,5) . We have encountered an unusually rapid case of CJD probably acquired through handling of sheep and human dura mater.
In May, 1992, a 55-year-old orthopaedic surgeon developed paraesthesia of the left arm. A few days later he had spatial disorientation, apraxia, and gait ataxia. In June he was admitted and a neurologist suspected CJD on the basis of the clinical signs, typical electroencephalogram (EEG) pattern, and history. An EEG in June revealed a typical pattern of periodic biphasic and triphasic sharp wave complexes.
We saw the patient in July, 1992. He was awake and oriented, with dyscalculia, dysgraphia, disturbed vision, apraxia mainly of the left side, rigidity of wrists, spasticity of all muscles, myoclonus of the left arm, increased tendon reflexes, ataxia of limbs and trunk, and incoordination of left arm. Within 3 weeks he had impaired consciousness and attention, mildly impaired memory, and threatening visual hallucinations with restless turning. He had periodic states with movements of his head and eye-bulbs resembling tonic adversive seizures. During sleep these motor disturbances stopped. 2 1/2 months later the patient died.
This patient had worked with sheep and human dura mater from 1968 to 1972. He handled about 150 specimens of ovine origin and at least a dozen human preparations for research. Handling involved opening skulls with a band saw, removing dura, and testing them either fresh (usually), preserved, or lyophilised for mechanical qualities.
These specimens were sent to a company that has sold dura mater preparations by which CJD was transmitted in six instances. No information was available from the company about a possible connection with this patient's disease and the earlier cases of transmitted CJD.
Brain biopsy was consistent with diagnosis of CJD. Cerebrospinal fluid obtained in July showed neuron-specific enolase (NSE) at 82.0 ng/mL, compared with 16.7 ng/mL in serum of other cases (6). Proton magnetic resonance spectroscopy of parieto-occipital and temporal grey matter, parietal white matter, and thalamus revealed a 20-30% reduction of N-acetylaspartate, as described (7). DNA was genotyped with allele-specific oligonucleotides (8) and was homozygous for methionine at the polymorphic codon 129. Subsequent direct DNA sequencing for the PrP gene open-reading frame demonstrated normal sequence on both alleles, excluding known or novel pathogenic PrP mutations.
It is tempting to speculate that prions were transmitted to this patient from sheep or human dura mater through small lacerations of his skin, but the patient and his wife did not remember any significant injury during his four years of working with these samples. It cannot be excluded that this was a case of sporadic CJD although this assumption is unlikely in view of the clinical course which was similar to iatrogenic CJD transmitted by peripheral inoculation, such as with human pituitary growth hormone or gonadotropin or to kuru (1). Iatrogenic cases resulting from intracerebral inoculation with the transmissible agent, for instance following dura mater grafts (2-5), present with a dementing picture, as is usual in sporadic CJD, rather than with ataxia as in this case.
=-==-=-=- Iatrogenic scrapie from sheep dura mater?
Mon, 19 Jul 1999 Listserve and Lancet January 9, 1993 pp 123-124
An orthopaedic surgeon employed by the Lyodura company [Braun Melsungen] extracted dura mater from sheep and human cadavers and came down with fast CJD 22 years later. The ratio of sheep to human dura mater he collected was150 sheep to 12 humans. Apparently the surgeon and the sheep were German. Scrapie has long been present in Germany but reported levels are very low, about a flock a year has to be destroyed. I am not aware of any high sensitivity tests or random screening every being used in Germany to assess the levels of preclinical animals.
This raises the question, what did the lyodura company do with so much dura mater from sheep? The market for specialty surgical products was overwelmingly in humans in 1968. Are there companies today that sell sheep dura mater for research? The Lancet article only says it was for research -- but in what species? Perhaps dura mater gives an immune response across species after processing, ruling out its use in humans. But blood type or other genetic differences do not matter within humans, ie, there is no tissue matching with dura mater.
How CJD could show up from a handful of human dura mater donations with sporadic CJD supposedly so rare -- this would be extraordinary bad luck that any of 150 sheep + 12 humans could have carried the disease. On the other hand, there would be no surprise at all if a case of subclinical scrapie showed up in 150 sheep. [While Germany only reports one case a year of scrapie and destroys the flock, the disease nonetheless persists, indicating under-reporting.]
This raises the question, have dura mater recipients or the surgeon subsequently been strain-typed? This might give a very different outcome than other forms of iatrogenic CJD or simply co-classify with pituitary growth hormone if route of infection (injected, oral, hereditary, etc.) is more important than strain source.
Otherwise, iatrogenic scrapie (like cwdCJD) is somwhat unpredictable in its gel pattern (though strains of scrapie in other primate species might be re-examined). The original scrapie strain is not be identifiable directly because material was not likely retained. Strain-typing was not available at the time of the article -- but Collinge was one of the authors.
There is little doubt that scrapie could be transfered to humans by intracerebral injection (based on lack of species barrier in primates) and that processed pooled (human?) dura mater can carry sufficient infectivity to cause CJD. Animal experiments have not commonly used sheep dura mater as experimental dose source.
If any humans received sheep dura mater, it is doubtful that this will be disclosed or that specific recipients will be identified to their doctors. It is probably better to trace backwards from affected recipients -- see if they strain-type out to be sheep.
Japan has been particularly hard hit by dura mater CJD (curious in itself) and researchers there might be motivated to find out what happened. I am not aware of agricultural agencies that would impede research over there.
############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
snip...see full text;
85%+ of all human TSE prion, i.e. sporadic CJD, does NOT happen spontaneously, as some would wish you to think. never say never with the TSE Prion disease. ...terry
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Volume 2: Science
4. The link between BSE and vCJD
Summary 4.29 The evidence discussed above that vCJD is caused by BSE seems overwhelming. Uncertainties exist about the cause of CJD in farmers, their wives and in several abattoir workers. It seems that farmers at least might be at higher risk than others in the general population. 1 Increased ascertainment (ie, increased identification of cases as a result of greater awareness of the condition) seems unlikely, as other groups exposed to risk, such as butchers and veterinarians, do not appear to have been affected. The CJD in farmers seems to be similar to other sporadic CJD in age of onset, in respect to glycosylation patterns, and in strain-typing in experimental mice. Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD.
***>It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people...end
BSE INQUIRY
SATURDAY, JUNE 23, 2018
CDC
***> Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification
Volume 24, Number 7—July 2018 Dispatch
SATURDAY, SEPTEMBER 21, 2019
National Variability in Prion Disease–Related Safety Policies for Neurologic Procedures
Friday, September 27, 2019
Prion disease and recommended procedures for flexible endoscope reprocessing – a review of policies worldwide and proposal for a simplified approach
FRIDAY, SEPTEMBER 06, 2019
Disinfection of Multi-Use Ocular Equipment for Ophthalmological Procedures: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines
Sent: Wed, Nov 13, 2019 9:52 am
Subject: Moncton Hospital A third person who had cataract surgery has been diagnosed with the fatal Creuztfeld-Jakob disease
Subject: Moncton Hospital A third person who had cataract surgery has been diagnosed with the fatal Creuztfeld-Jakob disease
Woman is 3rd person this year diagnosed with Creutzfeldt-Jakob disease at the Moncton Hospital
Shepody woman is 3rd person diagnosed with fatal disease at the hospital this year
Tori Weldon · CBC News · Posted: Nov 12, 2019 5:00 AM AT | Last Updated: 7 hours ago
Diana Paterson first showed signs of Creutzfeldt-Jakob disease in April. Since her diagnosis in June, her husband Art Paterson has become her full-time caregiver. (Tori Weldon/CBC)
Diana Paterson is not sure how much longer she has to live.
In June, she was diagnosed with Creutzfeldt-Jakob disease, known as CJD, after showing signs of the fatal illness for several months.
Art Paterson, speaking with his wife's permission, said Diana now suffers symptoms of dementia, which came on quickly.
"It's like all of a sudden you walked into a nursing home and you don't know the person you're with," Art said.
When the couple went to Toronto to see a baseball game in April, it was the first time he noticed something was off.
Art and Diana Paterson have been married for 29 years. Only a few months after her diagnosis of CJD, Diana uses a walker and can't be left alone. (Pierre Fournier/CBC) Diana became agitated and couldn't sit still, and they ended up leaving part way through the game, despite Diana's love of the Blue Jays.
Thirteen falls, a six-week hospital stay and numerous tests later, the couple received the diagnosis. Art can't pronounce Creutzfeldt-Jakob, but he knows its prognosis well.
"It's downhill and you're never going back up," he said.
In the seven months since she first started showing symptoms, Diana has lost her short-term memory and can no longer walk unassisted.
"I do everything for her that I can, get her mad, make her laugh, do all the laundry, cook all our meals, whatever," Art said. "That's what husbands and wives are about."
Information Morning - Moncton Another Creuztfeld-Jakob case diagnosed at Moncton Hospital 25:19
A third person who had cataract surgery has been diagnosed with the fatal Creuztfeld-Jakob disease. 25:19 'What the heck is going on?'
While CJD is said to occur at a rate of only one in a million people, Diana is the third person to be diagnosed with the deadly degenerative brain disease at the Moncton Hospital in less than a year.
"You just kind of throw your hands up in the air and say, 'What the heck is going on?'" said Art.
Dr. Gordon Dow is the division head of infectious diseases at the Moncton Hospital. (Pierre Fournier/CBC) After his wife's diagnosis, Art went online looking for more information. He found two other CJD cases had made the news earlier in the year.
Like Diana, both underwent cataract surgery at the Moncton Hospital before their diagnoses. She had her surgery in December 2016. The other two patients had their surgeries in December 2018 and January 2019.
2 cases of Creutzfeldt-Jakob disease at Moncton Hospital not cause for concern, officials say Frustration mounts over Horizon's response to deadly disease But unlike Diana, both were already showing signs of the disease at the time of surgery.
Dr. Gordon Dow, division head of infectious diseases at the Moncton Hospital, said even he was shocked when another case of CJD was discovered.
'Flabbergasted'
"I was flabbergasted initially when I saw that we had three cases of this rare disease in a small city the size of Moncton," Dow said.
He immediately contacted the Public Health Agency of Canada, which runs a national surveillance system for the disease. He said the agency scrutinized each case, and he believes there is no need for people to panic.
Three years before showing signs of CJD, Diana Paterson went on a trip to Italy with her husband.(Submitted/Art Paterson) "I think even though there's the overwhelming weight of evidence suggesting that we've had a cluster of sporadic cases, there is no need for public alarm," Dow said.
"This is not an indication that there's been an outbreak of CJD."
Dow said he found several factors that could explain why Moncton is seeing an increase in CJD diagnoses.
Testing has improved
"Up until now, the only definitive diagnosis was [done through an] autopsy or brain biopsy," said Dow.
He said within the last two years a new method of testing for CJD has been making it much easier to diagnose living patients.
"It has literally revolutionized our ability to diagnose this disease, which is probably more common than we realized," said Dow.
He points to national numbers that show an increase in CJD cases in the last 21 years in Canada, with the mortality rate rising steadily from 0.79 in 1998 to 2.09 in 2018.
As well, Dow said, the city has the largest cohort of neurologists in the province at its two hospitals. With neurologists and geriatricians best equipped to diagnose the disease, a diagnosis that might be missed elsewhere would get picked up in Moncton, he said.
With all three CJD patients having had cataract surgery at Moncton Hospital, Dow said the first concern he had was whether there was any chance that could have caused CJD. He turned to Public Health for information and looked at studies done around the world. He found there is no evidence of a link.
"There's no scientific evidence that cataract surgery can cause CJD," he said.
CJD is most often found in older people, and the elderly receive most cataract surgeries, Dow said. A symptom of CJD is blurred vision and blindness, issues that lead to people receiving cataract surgery.
Types of CJD
According to Dow there are four kinds of CJD:
Iatrogenic (through hospital or medical procedures). Familial (through hereditary link). Sporadic (spontaneously occurring for no apparent reason). Variant CJD (BSE or "mad cow" disease). He said the two earlier cases of CJD were determined to be sporadic, and for confidentiality reasons he would not discuss Paterson's results.
Dow said he doesn't see a reason for the public to be concerned but, "if we keep seeing further rates of CJD rising in the Moncton area we're going to treat every case as a unique and important case," he said.
"There's going to be a lot of scrutiny."
CBC's Journalistic Standards and Practices|About CBC News Report Typo or Error|Send Feedback
See history;
Statement on low risk of transmitting CJD through cataract surgery
(Moncton) April 8, 2019 - We would like to confirm Horizon's The Moncton Hospital has identified two separate cases where a patient with probable Creutzfeldt-Jakob disease (CJD) had cataract surgery in our facility. After careful review it was determined that these two cases are totally unrelated. CJD is a rare degenerative brain disorder that leads to dementia.
Patients who received the same procedure in the following weeks have no significant risk of contracting the protein from the same medical instruments being used.
Horizon is confident the risk of transmitting CJD from using the same instruments is not significant. Horizon uses modern cleaning and sterilization processes that make the transmission nearly impossible.
Horizon notified 103 patients of the risk by letter upon discovering the first case of CJD on January 15, 2019. We notified an additional 601 patients on February 14,2019 following the discovery of the second probable case.
Patients were encouraged to call Horizon to speak with either their ophthalmologist or a member of Horizon's team. We can confirm that 43 patients contacted Horizon to learn more about their potential risk.
The transmission of CJD by surgical instruments has only been documented on seven occasions worldwide, occurring more than 20-40 years ago, and none of the CJD cases have been linked to cataract surgery.
Even though the risk of one of our patients contracting CJD is extremely low, Horizon is committed to being transparent and wanted to share this information with patients that received cataract surgery at Horizon's The Moncton Hospital.
We also shared this information with the family physicians for each patient.
Due to the rarity of having two separate CJD cases identified, we have disclosed this information to the Public Health Agency of Canada.
April 8, 2019 7:10 pm Updated: April 9, 2019 8:57 am
N.B. health authority contacts over 700 patients after detecting rare degenerative brain disease
By Alexander Quon
File - The Horizon Health Network has notified more than 700 patients after two cases of Creutzfeldt-Jakob disease were diagnosed. Both patients had undergone cataracts surgery before being diagnosed.
File - The Horizon Health Network has notified more than 700 patients after two cases of Creutzfeldt-Jakob disease were diagnosed. Both patients had undergone cataracts surgery before being diagnosed.
New Brunswick’s Horizon Health Network has identified two separate cases in which a patient with a probable case of a degenerative brain disease had cataract surgery at the Moncton Hospital — spurring them to contact 700 patients who underwent similar procedures at the facility.
The health authority confirmed to Global News on Monday evening that two cases of Creutzfeldt-Jakob disease (CJD) were detected at the facility but are unrelated.
Horizon directed Global News to a video that they published on their YouTube channel earlier on Monday about CJD when asked for information on incidents. The video is narrated by Dr. Gordon Dow, the chief of infectious diseases at Moncton Hospital.
READ MORE: Young Edmonton mother with rare form of dementia passes away
In the video, Dow says that the first case of CJD was diagnosed after a patient was admitted to hospital in December. Six weeks later another man was diagnosed with the same degenerative brain disease.
Both of the patients had undergone surgery before being diagnosed with CJD.
“We could not find any reason for this but statistical probability. It just so happens that two rare events happened at once,” said Dow.
Dow stresses in the video that the risk of transmission of CJD is “very low.”
What is CJD
According to the Alzheimer Society of Canada, CJD is a rare and fatal brain disease that is caused by a protein in the brain called prion.
In its natural form, prion is harmless. But when it is abnormal it becomes toxic to brain cells.
The disease is difficult to diagnose and it can be several years before a person who is exposed to CJD has the abnormal prions form.
The society says CJD can affect everyone differently but that the disease progresses quickly once symptoms appear. People with CJD rarely live beyond a year.
CJD can be “accidentally transmitted during a medical procedure involving human tissues” but can also be transmitted from exposure to a cattle infected with a variant of CJD known as mad cow disease.
CJD can also happen sporadically, often in elderly people without warning, or be the result of a genetic mutation.
READ MORE: What is mad cow disease? Quick facts about BSE
Informing patients
Dow stresses in the video that the risk of transmission of CJD is “very low” during cataract surgeries because the protein that results in the disease is not significantly present in the area of the where the surgery is carried out.
The chief of infectious diseases also says that modern sterilization methods used on surgical tools reduce the likelihood of transmission.
In the video — which, as of 7:30 p.m. Monday, has not been shared on Horizon’s official social media accounts — Dow says that transparency is important in medicine, even when there is low to no risk.
As a result, Dow says after detecting the first case, the cataract surgeon notified “each and every one” of 103 patients by phone who had “potentially been exposed” to the medical instruments used during the surgery.
WATCH: Families continue to come forward after Moncton nurse fired for administering labour-inducing drugs
The patients also received a letter informing them of the low risk of transmission.
The second incident prompted Horizon to notify 601 patients who had been potentially exposed. Dow says they couldn’t call all of the patients but they were informed through a letter.
A note has also been placed on all of the patient’s charts in order to flag that they warrant extra attention.
“The risk looks like zero and if its not zero it’s too low to measure,” Dow said in the video.
“So wouldn’t it be appropriate to be vigilant with the patients who had been exposed to the instruments.”
Dow says that the incident has made the hospital stress the importance of keeping track of tools used during surgeries.
Any patient who has questions or concerns are urged to contact 1-844-225-0220
If you’ve received a letter as a result of the incident and are interested in talking to Global News please email us at newbrunswick@globalnews.ca.
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery. ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
O17 Evaluation of iatrogenic risk of CJD transmission associated with corneal transplantation
Douet JY. (1), Cassard H. (1), Huor A. (1), Lacroux C. (1), Haïk S. (2), Lugan S. (1), Tillier C. (1), Aron N. (1), Ironside J.W. (3), Andreoletti O. (1)
(1) UMR INRA-ENVT 1225, Ecole Nationale Vétérinaire de Toulouse, France.(2) Université Pierre et Marie Curie, UMR-S 1127, CNRS UMR 722, Institut du Cerveau et de la Moelle Epinière, G.H. PitiéSalpêtrière, Paris, France.(3) National CJD Research and Surveillance Unit Centre for Clinical Brain Sciences, University of Edinburgh, UK.
Sporadic Creutzfeldt–Jakob disease (sCJD) has been documented to be accidentally transmitted by contaminated corneal transplants. To date, only one case is considered as definite, while 5 other suspect cases are classified as probable or possible. However, the specific transmission risk associated with this widely-performed transplantation procedure has never been studied.
In this study, bioassays in transgenic mice expressing the human PrP confirmed the presence of infectivity in the cornea of 2 sCJD patients. Infectivity was also detected in other ocular tissues (optic nerve, retina, vitreous body, choroid and lacrymal gland) from one of these patients.
Based on these results, we investigated the presence of infectivity in the cornea of different TSE animal models. In conventional mice (RML strain) as well as in sheep (PG127 scrapie), infectivity could only be detected in the corneas collected at the late stage of the disease incubation phase.
In parallel to these experiments, corneas collected at different stages of the incubation period in infected mice and sheep were grafted into healthy recipients.
Our results showed that corneas collected during the late asymptomatic phase or in affected animals were able to transmit TSE infectivity. Importantly, after the death of the recipients (up to 2.5 years after surgery) infectivity could still be detected in the grafted cornea.
These data confirm the potential for sCJD transmission by corneal grafts. They also provide crucial data for the assessing the TSE transmission risk associated with various other ophthalmologic procedures.
PRION2018CONFERENCE ABSTRACT
JUST OUT CDC;
Tuesday, November 20, 2018
Eyes of CJD patients show evidence of prions Finding could help early diagnosis, raise concern for eye exams and transplants.
Singeltary 1999
***> THE EYES HAVE IT, CJD, AND THEY COULD BE STEALING THEM FROM YOUR LOVED ONE!...year 1999
i said that 20 years ago about this very thing. but did anyone listen...no!
prepare for the storm...terry
year 1999 to 2000
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
######### 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...
Cadaver corneal transplants -- without family permission Houston, Texas channel 11 news 28 Nov 99
Reported by Terry S. Singeltary Sr.son of CJD victim
"It was a story about how the Lions eye bank were harvesting corneas from victims in the Morgue, without their consent. Under Texas law, this appears to be legal (remember Texas has the Veggie liable law). Even if Family says no, this appears to happen, from what the news story said.
They said the only way to prevent this, is to fill out a form, stating not to have this done. So if you don't fill out the form, they can do this. How many people don't know about the form?
This is not only disgusting and appalling, it could be highly infectious. Without proper background checking of the donors, on their physical history, checking on past dementia, and/or family history, some of these unfortunate victims, could be passing a human TSE.
Response Jill Spitler Clevelland Eye Bank:
"No, we are not stealing.........Yes, you do have such a law in the state of Texas, but not all your state Eye Banks utilize the law. The Eye Bank that you're speaking of is only one of 43 certified Eye Bank throughout the USA.
And there are measure taken per the Medical Standards of the Eye Bank Association of America, the certifying body for eye banks and per FDA regulations to address those concerns that you speak of.
I would suggest that those interested/concern with transplant contact their local agencies. The Eye Bank Association of America has a web. site . Further if anyone has problems contacting or finding out about their local organization(s), call me or e-mail me I would be glad to help. My e-mail address is jill@clevelandeyebank.org"
Terry Singeltary responds:
"Explain this to the family in Houston who went to their loved ones funeral, only to find out that the loved one that was in the casket, had their corneas removed without their permission, without the consent of the victim or it's family. They would not have known it, only for the funny look the victim had. So, they questioned, only to find out, the corneas, had in fact, been removed without consent.
I call that stealing, regardless what the law states. This type of legal grave robbing is not a logical thing to do without knowing any type of background of the victims medical past, which really will not prove anything due to the incubation period. Eye tissue being potentially a highly infective source, there are risks here.
Should they not at least know of the potential ramifications of TSE's (the person receiving the corneas)?
Should there not be some sort of screening?
Should there be some sort of moral issue here?
If this is the case, and in fact, they can come take your corneas, without your consent, then what will they start taking next, without your consent?
Lets look at a hypothetical situation:
What would happen if my Mom (DOD 12-14-97 hvCJD) would have gotten into a car wreck and died, before the symptoms of CJD appeared. Not much money, so there was no autopsy. What would have happened to that recipient of those infecting corneas?"
Comment (webmaster): Actual transmission of CJD by means of corneal transplant may or may not be rare. The incidence of infectivity in older people could be fairly high; this is not to be confused with the lower incidence of symptomatic (clinical) CJD. It is very unlikely that familial CJD would have been diagnosed in earlier generations; however, without interviewing the family even known kindreds would not be excluded.
In blood donation, a much stricter policy is followed, even though corneal transplant may be far more dangerous (being a direct link to the brain and not going through purification steps).
Since highly sensitive tests for pre-clinical CJD are now available, it would make sense to screen corneas for CJD, just as they are screened for AIDS, hepatitus, and a host of other conditions.
Eye procedure raises CJD concerns
BySTEVE MITCHELL, Medical Correspondent
WASHINGTON, Nov. 18 (UPI) -- 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 cases of 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.
Friday, December 04, 2009
New guidance on decontamination of trial contact lenses and other contact devices has been revealed for CJD AND vCJD
SUNDAY, JANUARY 17, 2016
Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease
TUESDAY, NOVEMBER 20, 2018
CDC Eyes of CJD patients show evidence of prions concerns for iatrogenic transmission
THURSDAY, DECEMBER 12, 2019
Heidenhain Variant Creutzfeldt Jakob Disease hvCJD, sporadic spontaneous CJD and the TSE Prion December 14, 2019
22 years, rip mom dod 12/14/97 confirmed hvcjd, just made a promise to mom, and you don't break those promises, never forget, and never let them forget, before we all do...this pearl's for you! love terry
WEDNESDAY, DECEMBER 04, 2019
Three Cases of Creutzfeldt-Jakob Disease with Visual Disturbances as Initial Manifestation
WEDNESDAY, DECEMBER 25, 2019
Creutzfeldt-Jakob disease: a systematic review of global incidence, prevalence, infectivity, and incubation
We found that although CJD, particularly iatrogenic CJD, is rare, the incidence of sporadic CJD is increasing.
Saturday, November 23, 2019
Prion disease incidence in the United States, 2003–2015
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Article (citation):
. Prion disease incidence in the United States, 2003–2015. Neurology (2019); 10.1212/WNL.0000000000008680
https://n.neurology.org/content/early/2019/11/22/WNL.0000000000008680
The comment "RE: Prion disease incidence in the United States, 2003–2015" was submitted on 23 11 2019:
Greetings Neurology et al, I still find this hard to believe, especially with the new sporadic cjd called vpspr in humans, and the other new tse prion disease popping up in humans, along with the poor surveillance we have from state to state for human tse prion. with this continued belief of the UK BSE nvCJD only theory, meaning only those few tied to the typical C-BSE strain in cattle as nvCJD in humans, or what they call today vCJD, and that no other human tse on the globe is from any other animal tse prion like cwd tse prion in cervid, scrapie in sheep and goats, or the other atypical bse tse in cattle, and what about the outbreak of a new tse prion in a new livestock species, the camel. i think this belief, and continued statements of such (without reading the full study, i have no access as a peon), i believe helps continue to spread the tse prion around the globe, by ignoring the fact that all iatrogenic CJD is, is sporadic CJD, until the iatrogenic event is discovered, proven, documented, put in to the academic domain, and finally in the public domain. now we know that cwd in cervid and scrapie can transmit to pigs by oral route, and we also know out mad cow feed ban was a colossal failure. i also remember what some of these same scientist said long ago on this topic and cwd being zoonosis or not, and this was 2002, since then much science has come forth showing that cwd to humans not only is very probable, it most likely has already happened. we have doctors and scientist still claiming that 85%+ all human tse prion disease i.e. the sporadic cjd is a spontaneous event from nothing, just a funked out protein that twist wrongly, and that no other reason exist, and this is a dangerous precedent to set, without proof, and will continue to help spread the tse prion imo...
see;
Saturday, November 23, 2019 Prion disease incidence in the United States, 2003–2015
Terry S. Singeltary Sr. I am an Author of this Work, and the Work was prepared on my own time - not as part of my duties as an employee.
FRIDAY, OCTOBER 25, 2019
27th ANNUAL REPORT 2018 CREUTZFELDT-JAKOB DISEASE SURVEILLANCE
SUNDAY, MARCH 10, 2019
National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated Feb 1, 2019 Variably protease-sensitive prionopathy VPSPr
MONDAY, AUGUST 26, 2019
Creutzfeldt Jakob Disease CJD, TSE, Prion, Surveillance Update August 2019
SATURDAY, AUGUST 24, 2019
Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2018
SATURDAY, SEPTEMBER 21, 2019
National Variability in Prion Disease–Related Safety Policies for Neurologic Procedures
Friday, September 27, 2019
Prion disease and recommended procedures for flexible endoscope reprocessing – a review of policies worldwide and proposal for a simplified approach
FRIDAY, SEPTEMBER 06, 2019
Disinfection of Multi-Use Ocular Equipment for Ophthalmological Procedures: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
Wednesday, September 11, 2019
Is the re-use of sterilized implant abutments safe enough? (Implant abutment safety) iatrogenic TSE Prion
TUESDAY, APRIL 09, 2019
Horizon Health Network Moncton Hospital notified more than 700 patients after two cases of CJD were diagnosed both patients had undergone cataracts surgery before being diagnosed
THURSDAY, DECEMBER 19, 2019
The emergence of classical BSE from atypical/Nor98 scrapie
SUNDAY, AUGUST 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
TUESDAY, AUGUST 18, 2009
BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009
MONDAY, JANUARY 20, 2020
sporadic CJD one in a million, FAKE NEWS PEOPLE!
this myth has been incorrect for decades, and had been stated as such by a few, but again, the media is too lazy to do it's job and print the facts.
human tse prion is one in 5,000...just saying.
all iatrogenic cjd is, is sporadic cjd, until the iatrogenic event is discovered, traced back, proven, put into the academic domain, and then finally the public domain, which as you can see here, might take 30, 40, 50 years, but during that time period of sub-clinical tse prion, that person is a carrier and potential donor of the tse prion to others, by iatrogenic event...terry
Revisiting Sporadic CJD
It’s not hard to get Terry Singeltary going. “I have my conspiracy theories,” admitted the 49-year-old Texan.1 Singeltary is probably the nation’s most relentless consumer advocate when it comes to issues in prion diseases. He has helped families learn about the sickness and coordinated efforts with support groups such as CJD Voice and the CJD Foundation. He has also connected with others who are critical of the American way of handling the threat of prion diseases. Such critics include Consumers Union’s Michael Hansen, journalist John Stauber, and Thomas Pringle, who used to run the voluminous http://www.madcow.org Web site. These three lend their expertise to newspaper and magazine stories about prion diseases, and they usually argue that prions represent more of a threat than people realize, and that the government has responded poorly to the dangers because it is more concerned about protecting the beef industry than people’s health.
Singeltary has similar inclinations, but unlike these men, he doesn’t have the professional credentials behind him. He is an 11th-grade dropout, a machinist who retired because of a neck injury sustained at work. But you might not know that from the vast stores of information in his mind and on his hard drive. Over the years, he has provided unacknowledged help to reporters around the globe, passing on files to such big-time players as The New York Times, Newsweek, and USA Today. His networking with journalists, activists, and concerned citizens has helped medical authorities make contact with suspected CJD victims. He has kept scientists informed with his almost daily posting of news items and research abstracts on electronic newsgroups, including the bulletin board on www.vegsource.com and the BSE-listserv run out of the University of Karlsruhe, Germany. His combative, blunt, opinionated style sometimes borders on obsessive ranting that earns praise from some officials and researchers but infuriates others—especially when he repeats his conviction that “the government has lied to us, the feed industry has lied to us—all over a buck.” As evidence, Singeltary cites the USDA’s testing approach, which targets downer cows and examined 19,900 of them in 2002. To him, the USDA should test 1 million cattle, because the incidence of BSE may be as low as one in a million, as it was in some European countries. That the U.S. does not, he thinks, is a sign that the government is really not interested in finding mad cows because of fears of an economic disaster.
Singeltary got into the field of transmissible spongiform encephalopathy in 1997, just after his mother died of sporadic CJD. She had an especially aggressive version—the Heidenhain variant—that first causes the patient to go blind and then to deteriorate rapidly. She died just ten weeks after her symptoms began. Singeltary, who said he had watched his grandparents die of cancer, considered her death by CJD to be much, much worse: “It’s something you never forget.” Her uncontrollable muscle twitching became so bad “that it took three of us to hold her one time,” Singeltary recalled. “She did everything but levitate in bed and spin her head.” Doctors originally diagnosed Alzheimer’s disease, but a postmortem neuropathological exam demanded by Singeltary revealed the true nature of her death.
WEDNESDAY, MAY 29, 2019
Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures USDA HERE'S YOUR SIGN!
FRIDAY, JANUARY 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
Greetings Friends, Neighbors, and Colleagues,
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
Confucius is confused again.
I was just sitting and thinking about why there is no genetic link to some of these TSE prion sGSS, sFFi, and it’s really been working on my brain, and then it hit me today.
what if, vpspr, sgss, sffi, TSE prion disease, was a by-product from iatrogenic gss, ffi, familial type prion disease ???
it could explain the cases of no genetic link to the gss, ffi, familial type prion disease, to the family.
sporadic and familial is a red herring, in my opinion, and underestimation is spot on, due to the crude prehistoric diagnostic procedures and criteria and definition of a prion disease.
I say again, what if, iatrogenic, what if, with all these neurological disorders, with a common denominator that is increasingly showing up in the picture, called the prion.
I urge all scientist to come together here, with this as the utmost of importance about all these neurological disease that are increasingly showing up as a prion mechanism, to put on the front burners, the IATROGENIC aspect and the potential of transmission there from, with diseases/disease??? in question.
by definition, could they be a Transmissible Spongiform Encephalopathy TSE prion type disease, and if so, what are the iatrogenic chances of transmission?
this is very important, and should be at the forefront of research, and if proven, could be a monumental breakthrough in science and battle against the spreading of these disease/diseases.
sporadic CJD, along with new TSE prion disease in humans, of which the young are dying, of which long duration of illness from onset of symptoms to death have been documented, only to have a new name added to the pot of prion disease i.e. sporadic GSS, sporadic FFI, and or VPSPR. I only ponder how a familial type disease could be sporadic with no genetic link to any family member? when the USA is the only documented Country in the world to have documented two different cases of atypical H-type BSE, with one case being called atypical H-G BSE with the G meaning Genetic, with new science now showing that indeed atypical H-type BSE is very possible transmitted to cattle via oral transmission (Prion2014). sporadic CJD and VPSPR have been rising in Canada, USA, and the UK, with the same old excuse, better surveillance. You can only use that excuse for so many years, for so many decades, until one must conclude that CJD TSE prion cases are rising. a 48% incease in CJD in Canada is not just a blip or a reason of better surveillance, it is a mathematical rise in numbers. More and more we are seeing more humans exposed in various circumstance in the Hospital, Medical, Surgical arenas to the TSE Prion disease, and at the same time in North America, more and more humans are becoming exposed to the TSE prion disease via consumption of the TSE prion via deer and elk, cattle, sheep and goats, and for those that are exposed via or consumption, go on to further expose many others via the iatrogenic modes of transmission of the TSE prion disease i.e. friendly fire. I pondered this mode of transmission via the victims of sporadic FFI, sporadic GSS, could this be a iatrogenic event from someone sub-clinical with sFFI or sGSS ? what if?
REVIEW
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
Thursday, March 8, 2018
Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein
THURSDAY, JANUARY 23, 2020
USDA Consolidates Regulations for NAHLN Laboratory Testing USDA Animal and Plant Health Inspection Service sent this bulletin at 01/23/2020 02:15 PM EST
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
10:25 AM
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