Creutzfeldt-Jakob Disease in Mexico (1990-2023): Survival analysis, population characteristics and the first bioinformatics analysis database
Fabricio Cruz-Lópeza, b, c, Gustavo Reyes-Teránd, Petra Yescas-Gómezb, Sergio Iván Valdés-Ferrerc, e, f, Miguel Ángel Ramírez-Garcíab, Óscar Arias-Carrióng, Marie Catherine Boll-Woehrlenb, Carlos Alberto Gómez-Pérezb, Pablo Eduardo Irigoyen-Ruízh, i aFacultad de Medicina, Benemérita Universidad Autónoma de Puebla, H. Puebla de Zaragoza, Mexico; bGenetics Department, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico; c Department of Neurology and Psychiatry, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico; dCoordinating Commission of the National Institutes of Health and High Specialty Hospitals, Ministry of Health, Mexico City, Mexico; eInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA; f Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico; gUnidad de Trastornos del Movimiento y Sueño, hHospital General Dr. Manuel Gea González, Mexico City, Mexico; i Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
Aims: Create the first database of Mexican patients with Creutzfeldt-Jakob Disease (CJD) from 1990 to 2023, to describe survival and presenting clinical features.
Materials and Methods: We performed a systematic scoping review from all published reports of Mexican patients with CJD following the PRISMA methodology. The quality was evaluated through the scale of The Joanna Briggs Institute. Likewise, we included new patients from INCMNSZ and INNN centers. Nonparametric estimation of Kaplan-Meier survival analysis was performed in R.
Results: Seventy-five Mexican patients with CJD were identified between 1990 and 2023; the median of age was 54 yo (ranges 20-90 yo). The main reported manifestations were: cerebellar or visual alterations (n=57), followed by myoclonus (n=43) and extrapyramidal alterations (n=41). The KaplanMeier curves show no differences in mean survival by gender (≈275 days); however, those patients reporting cerebellar and visual alterations (≈275 days) have longer survival compared to those who do not (≈125 days); Likewise, when grouping the Definite or Probable diagnosis (>400 days) in comparison to those with Possible diagnosis (200 days) of CJD; and patients with Familial etiology (≈325 days) versus patients with Sporadic etiology (≈275 days) we not found statistical differences.
Conclusions: The Creutzfeldt-Jakob Mexican cases show a longer survival than reported elsewhere; however, it could be due to classification bias (in the case of Possible diagnosis). Furthermore, the lack of application of diagnostic tools (such as 14-3-3, TAU, Biopsy, PRNP gene analysis, or RT-QUIC) does not allow the determination of Definitive or Probable diagnoses, which increases the uncertainty of misdiagnosed cases.
More information is available at: https://rpubs.com/MrKristarlx07/PrionMex_survival_analysis
Funded by: F.C.-L. has the support of the Consejo de Ciencia y Tecnología del Estado de Puebla, as well as the Vicerrectoría de Investigación y Estudios de Posgrado of the Benemérita Universidad Autónoma de Puebla (Autonomous University of Puebla).
''The Creutzfeldt-Jakob Mexican cases show a longer survival than reported elsewhere; however, it could be due to classification bias (in the case of Possible diagnosis). Furthermore, the lack of application of diagnostic tools (such as 14-3-3, TAU, Biopsy, PRNP gene analysis, or RT-QUIC) does not allow the determination of Definitive or Probable diagnoses, which increases the uncertainty of misdiagnosed cases.''
Prion 2023
Title: Diagnostic Journey of Patients with Creutzfeldt-Jakob Disease (CJD) in the United States: A RealWorld Evidence Study
Author list: Duncan Brown1 , Emily Kutrieb2 , Montserrat Vera Llonch1 , Rob Pulido1 , Anne Smith1 , Derek Weycker2 , Ellen Dukes2 , Brian S Appleby3-5
Affiliations: 1 Ionis Pharmaceuticals; 2Policy Analysis Inc. (PAI); 3National Prion Disease Pathology Surveillance Center; 4Case Western Reserve University; 5University Hospitals Cleveland Medical Center
Aims: Identification of clinical symptoms leading to a diagnosis of CJD from real-world evidence is limited. A new study using a United States (US) healthcare claims database was thus undertaken to address this evidence gap.
Materials and Methods: A retrospective cohort design and the Merative MarketScan Database (01/2012-12/2020) were employed. The study population comprised adults aged ≥18 years with ≥1 inpatient diagnosis or ≥2 outpatient diagnoses (≥3 days apart) of CJD, magnetic resonance imaging of the head or lumbar puncture, and no evidence of selected neurologic conditions after the last CJD diagnosis. Patients without healthcare coverage during the 12-month pre-diagnosis period were excluded; alternative pre-diagnosis periods (spanning 24 and 36 months, respectively) were also explored. Diagnostic journey was detailed based on diagnosis codes for selected symptoms and neurologic conditions during the pre-diagnosis period.
Results: Among the 61.8 million persons in the source population from 01/2013-12/2019, 215 CJD patients qualified for inclusion in the study population. CJD patients first presented with symptoms consistent with the diagnosis 5.0 (SD=4.0) months, on average, before the initial CJD diagnosis, and 80% had ≥3 symptoms, most commonly altered mental status (82%), gait/coordination disturbance (60%), and malaise/fatigue (44%). Most patients (63%) also had ≥1 differential (neurologic) diagnosis leading to the CJD diagnosis, most commonly cerebrovascular disease (49%), peripheral vertigo (11%), and Alzheimer’s disease (7%); mean duration from first differential diagnosis to initial CJD diagnosis was 2.4 (SD=3.1) months.
Conclusions: Study findings suggest that, in US clinical practice, CJD patients present with one or more clinical symptoms impacting motor, cognitive or other domains, and many are initially mis-diagnosed, prolonging the diagnostic journey. CJD should be considered in the differential diagnosis of those with rapidly progressing dementia or motor disturbance.
Funded by: Ionis Pharmaceuticals
Grant number: N/A
Acknowledgment: XXX
"Study findings suggest that, in US clinical practice, CJD patients present with one or more clinical symptoms impacting motor, cognitive or other domains, and many are initially mis-diagnosed, prolonging the diagnostic journey."
22 years ago;
2001 Singeltary on CJD
February 14, 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr
Author Affiliations
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
MONDAY, SEPTEMBER 11, 2023
Professor John Collinge on tackling prion diseases
“The best-known human prion disease is sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia which accounts for around 1 in 5000 deaths worldwide.”
There is accumulating evidence also for iatrogenic AD. Understanding prion biology, and in particular how propagation of prions leads to neurodegeneration, is therefore of central research importance in medicine.
FRIDAY, JANUARY 15, 2021
CJD TSE Prion Questionnaire USA, UK, and the history there from, have you filled out this questionnaire?
if not, why not?
CJD TSE Prion Questionnaire USA, UK, Singeltary
CJD FOUNDATION Questionnaire
UK CJD Questionnaire
cjd questionnaire 1979
CJD Questionnaire
F. MEDICATIONS, has Subject taken any medications regularly, (if yes, record the date, name of the medication, the reason for taking it, and route of administration) prompt for prescription drugs, including insulin and type. Prompt for hormone therapy or nutritional supplements including oral contraceptives and hormone replacement therapy: Prompt for homeopathic/herbal therapy: Prompt for eye drops SUMMARY OF ABOVE RESPONSES; HAS THE SUBJECT BEEN EXPOSED TO ONE OF THE MEDICATIONS OF BOVINE OR OVINE ORIGIN, AND OR ANY DESICCATED ANIMAL ORIGIN? G. Has Subject ever been tested for allergy using needles? H. Has Subject ever received a treatment involving a course of injections? (If yes, record year, name of therapy, frequency, reason)
NOT to open up old wounds, but here is my 23 years of endeavors to get the USA to have a CJD Questionnaire for every family of a person whom died of cjd tse prion in the USA in every State, pertaining to real questions of all the potential routes of CJD in that questionnaire. seems i have failed terribly. there was great debate, much anguish, and i did take it personally, when others took credit for what i had been trying to get done. but this was long ago, and today the CJD Foundation seems to be working hard to change there old ways, and seem to be looking to find the routes of sporadic cjd as well. this is just that history, like it or not...kind regards, terry
THE MAKING OF THE USA CJD QUESTIONNAIRE
seems to be a colossal waste of time on my part, 23 years and nothing, were still talking about the same failures, imo...
wasted days and wasted nights...Freddy Fender
SOME HISTORY ON MEXICO, BSE, SCRAPIE, CWD, CJD, TSE, PRION
MEXICO BSE GBR
Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE-Risk (GBR) of MEXICO Question N° EFSA-Q-2003-083
Adopted July 2004
Summary
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in Mexico, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in Mexico. This scientific report addresses the GBR of Mexico as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into Mexico and could have reached domestic cattle. These cattle imported could have been rendered and therefore led to an internal challenge in the mid to late 1990’s. It is possible that imported meat and bone meal (MBM) into Mexico reached domestic cattle and leads to an internal challenge around 1993.
It is likely that BSE infectivity entered processing at the time of imported ‘at - risk’ MBM (1993) and at the time of slaughter of imported live ‘at - risk’ cattle (mid to late 1990s). The high level of external challenge is maintained throughout the reference period, and the system has not been made stable. Thus it is likely that BSE infectivity was recycled and propagated from approximately 1993. The risk has since grown consistently due to a maintained internal and external challenge and lack of a stable system.
EFSA concludes that the current geographical BSE risk (GBR) level is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSEagent. The GBR is likely to increase due to continued internal and external challenge, coupled with a very unstable system.
http://www.efsa.europa.eu/en/efsajournal/doc/4r.pdf
Key words: BSE, geographical risk assessment, GBR, Mexico, third countries
SNIP...
Annex to the EFSA Scientific Report (2004) 4, 1-13 on the Assessment of the Geographical BSE Risk of Mexico
- 7 -
2.3 Overall assessment of the external challenge
The level of the external challenge that has to be met by the BSE/cattle system is estimated according to the guidance given by the SSC in its final opinion on the GBR of July 2000 (as updated in January 2002).
Live cattle imports:
According to the CD the country imported in total over the period 1980 to 2003, approximately 3.2 million live cattle from BSE - risk countries, of which conclusively none came from the UK. The numbers shown in table 1 are the raw import figures and are not reflecting the adjusted imports for the assessment of the external challenge. Broken down to 5 - years periods the resulting external challenge is as given in table 3. This assessment takes into account the evidence that certain imported cattle did not enter the domestic BSE/cattle system, i.e. were not rendered into feed. In the case of Mexico, it is assumed that “cattle still alive” (imports from Spain) did not enter the rendering system.
MBM imports:
According to the CD the country imported in total over the period 1980 - 2003 approximately 826,000 tons MBM from BSE - risk countries (according to “other data”: ~ 919,000 tons), of which none came from the UK. The numbers shown in table 2 are the raw import figures and are not reflecting the adjusted imports for the assessment of the external challenge. Broken down to 5 - years periods the resulting external challenge is as given in table 3. This assessment takes into account the evidence that certain imported MBM did not enter the domestic BSE/cattle system or did not represent an external challenge for other reasons. However, in the case of Mexico, there was not sufficient evidence to remove any quantities of MBM from the external challenge.
SNIP...
Annex to the EFSA Scientific Report (2004) 4, 1-13 on the Assessment of the Geographical BSE Risk of Mexico
- 12 -
would harbour, while being pre - clinical, as much infectivity as a clinical BSE case. Hence cattle imports could have led to an internal challenge about 3 years after the import of breeding cattle (that are normally imported at 20 - 24 months of age) that could have been infected prior to import. In case of Mexico this implies that an internal challenge caused by live cattle imports (predominantly from USA or Canada) first occurred in the mid to late 1990’s and continued to the present.
On the other hand imports of contaminated MBM would lead to an internal challenge in the year of import, if fed to cattle. The feeding system is of utmost importance in this context. If it could be excluded that imported, potentially contaminated feed stuffs reached cattle, such imports might not lead to an internal challenge at all. In case of Mexico this implies that an internal challenge caused by MBM imports (predominantly from USA or Canada) first occurred around 1993 and continued to the present.
In view of the above - described consideration the combination of the very / extremely high external challenges with a very unstable system makes the occurrence of an internal challenge likely in Mexico from approximately 1993 onwards.
4.2 Risk that BSE infectivity entered processing
It is likely that BSE infectivity entered processing at the time of imported ‘at - risk’ MBM (1993) and at the time of slaughter of imported live ‘at - risk’ cattle (mid to late 1990’s). The high level of external challenge is maintained throughout the reference period, and the system has not been made stable, leading to increased internal challenge.
4.3 Risk that BSE infectivity was recycled and propagated It is likely that BSE infectivity was recycled and propagated from approximately 1993. The risk has since grown consistently due to a maintained internal and external challenge and lack of a stable system.
5. CONCLUSION ON THE GEOGRAPHICAL BSE – RISK
5.1 The current GBR as function of the past stability and challenge The current geographical BSE risk (GBR) level is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent.
5.2 The expected development of the GBR as a function of the past and present stability and challenge
• The GBR is likely to increase due to continued internal and external challenge, coupled with a very unstable system.
SNIP...
http://www.efsa.europa.eu/en/efsajournal/doc/4r.pdf
The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.
http://www.oie.int/boutique/extrait/06heim937950.pdf
Subject: Mexico SAGARPA Assessment of BSE VS EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of Mexico
Date: February 5, 2007 at 1:11 pm PST
Empresa solicitante: SAGARPA
Tipo del análisis efectuado: Cuantitativo
Temática: “Análisis de riesgo sobre la ocurrencia de la encefalopatía espongiforme bovina en México”
INTRODUCTION:
The bovine spongiform encephalopathy (BSE), it is a neurological disease, invariably fatal and with long period of incubation, that affects cattle. Its etiologic agent is the prion. General consensus exists with respect to that the feeding of contaminated meat and bone flours, it is the most significant source in the dissemination and transmission of this etiologic agent. At this time there is no exist evidence that BSE is transmitted by means of embryos, their semen and in case of existing maternal transmission, if this could happened it would be in a so extremely low rate that it could not be considered like a trigger or leading factor of an epidemic. Controversy in respect to other probable ways of transmission remains. The BSE was diagnosed for the first time in 1986 in the United Kingdom. At this time it exists in 26 countries, including a Canada and the United States of North America (USA).
This document summarizes the analyzed elements and the results of the study of the evaluation of the risk factors, of the epidemiology surveillance and related activities, as well as the quantitative estimation of the risk with respect to the probability of introduction of the disease to the Mexican herd.
EVALUATED ELEMENTS:
Demography and characteristics of the Mexican cattle industry: Cattle is one of the main activities in the Mexican farming sector, due to its contribution in the supply of meat (beef) products, dairy, among others; as well as its participation in the international trade on cattle exports, mainly to the United States of North America. According to data of the 2001, cattle population is of 30.620.933 of heads, of which 28.480.803 are beef cattle and 2.140.130 dairy cattle. The main cattle production states are located in the center-north, where its operation is intensive and its feeding is based on grains; as well as in the coast of the Gulf of Mexico and the south-southeastern, with intensive programs and feeding is based mainly on the pasturing (grass). The national dairy herd, is calculated as specialized or technified that represent 17,44% of the herd, semi-specialized 14,90% of the herd, double-purpose herd (beef and dairy) 59,68% and the small family-run herd or the referred as “backyard” (traspatio) 7,98%.Previous numbers are to be considered as an estimation of the dairy livestock inventory by production units. Nevertheless, it is necessary to consider that all races of pure breed can be found in anyone of those groups.
Legal grounds: Mexico counts on a normative frame that covers (deals with) the relevant aspects of the Epidemiology Surveillance of the BSE, like the Federal Law of Animal Health, the Federal Law of Metrology and Regulation, the General Law of Health and several Mexican Official Norms (NOM-009-Z00-1994, Sanitary process of the meat, NOM-030-ZOO-1995, Specifications and procedures for the import of beef, carcasses, viscera and offal at zoo-sanitary inspection points, NOM-061-ZOO-1999, Zoo-sanitary specifications of nutritional products destined for animal feed and NOM-060-ZOO-1999, Zoo-sanitary specifications for the transformation of animals offal and its use in animal feeding). Wider and extended covertures of these regulations were evaluated. Veterinary infrastructure: The veterinary services in the country are structural and normative organized by the Mexican State through the Secretariat of Agriculture, Livestock, Rural Affairs, Fishery and Alimentary (SAGARPA) Federally Empower, that is to say, that has the capacity and authority to negotiate an to come to agreement with the States Governments that integrate the Republic; to coordinate itself with the other Secretariats of State; to deal with organizations of the Private and Social sector as well as with the rest of the Civil Society as a whole.
The National Service of Health, Food Safety and Ag-alimentary Quality (SENASICA), it is an organism of this Secretariat, which has attributions in the matter of vegetable health, animal health and ag-alimentary safety and is conformed by the following main directorates: Sanidad Vegetal, Salud Animal, Inocuidad Agroalimentaria, Acuícola y Pesquera, Inspección Fitozoosanitaria, (equivalent to U.S. APHIS, FSIS and VS –Veterinary Services) Jurídica, Administración e Informática. In accordance with the assigned attributions, it corresponds to central offices the substantive part and the operative part, to the personnel assigned to the State Delegations of the SAGARPA and other instances of the SENASICA.
Consequently, the four main areas are assigned to the Main directorate of Salud Animal-Animal Health (DGSA) and to the Main directorate of Inspección Fotozoosanitaria-Plant Inspection (DGIF) and Veterinary Services (SV) in Mexico are in charge of: surveillance, epidemiology, animal movement, zoo-sanitary campaigns and emergencies.
Imports This is perhaps one of the medullar points, in the sense that it represents the information of the imports made during the risk periods and therefore, it provides the fundamental information for the risk assessment. In 1991, Mexico implemented measures to avoid the appearance of BSE, as the disease had become a serious worldwide problem, reason why, live bovines imports were prohibited, beef, beef products and by-products and in 1994 flour of meat and bone from countries affected by this disease was also prohibited and in the 2000 MBM feeding ban was imposed. In order to mitigate the risk of transmission of the EEB, a revision of the established requirements for import for ruminants’ products began.
Cattle imports and its products and by-products, as well as specific risk materials played a very important role in this study, where considerable amounts of cattle imports from countries now affected by BSE were identified, countries that at the time of the import they remained clean and therefore just some preventive risk measures were in place.
Slaughter, Cattle disposition and Offal.- Different cattle slaughter schemes were analyzed as well as the processes in use, finding some significant differences among them, being the most important the sanitary jurisdiction of the organizations that regulate us.
In Mexico, the slaughter is divided in three different systems, Federal Inspection Type Plants (TIF), which has been increased in the past years; in 1992 they participated with the 13,5%, in 1997 with the 19,40% and in 2002 with the 26,60% of the national total. In the case of the municipal slaughterhouses from 1992 to 1997, their slaughtered animals corresponded to the 49,5% and for 2002 it was increased to 73,4%, whereas the slaughter in private plants decreased of 37,10% in 1992 to 31,10%, in 1997 and from 1998 to date, we have no information.
The procedures to be followed by the establishments in the animal slaughter and those that industrialize, process, packing, chilled/froze beef products or by-products for human consumption, in order to obtain products of optimal hygienic quality, are written in the NOM-009-ZOO-1994 “sanitary Process of Beef”.
The direct consumption of beef can be stratified in three great destinies, differentiated by the market that are destined to, the rural one, the one of small centers of population, (and) the one of the big cities, characterized each one of them by its consumption and the partial or integral industrialization by direct consumer and by means of commercialization or points of sale, as well as for the origin of the own supplier.(?) Rendering of Cattle Products.
The processes applied by the rendering plants for obtaining the protein from inedible offal, were evaluated. Food elaboration and its use for animal feeding.- This analysis was focused in the processes of food elaboration for animal consumption.
In Mexico, the control in the production of food from animal origin, as much as the elaboration of the meat flour as that of the balanced food manufacture it is regulated by the Mexican Official Norm NOM-061-ZOO-1999, “Zoo-sanitary Specifications of nutritional products for animal consumption”, which bans the use of MBM flours of ruminant origin or any mixture that contains it for the elaboration of balanced meals for ruminants, and the Mexican Official Norm NOM-060-ZOO-1999, “Zoo-sanitary Specifications for the transformation of animal offal and its use in the animal feeding”.
In accordance with the Section of Manufacturers of Balanced Food for Animals of the National Camera of the Industry of Transformation (CANACINTRA), there are 396 balanced food plants registered, same that have the capacity to produce more than 20 million tons a year, according to the numbers registered during 1999-2002. 63% of such plants are integrated and produce 64% of the animal feed produced nationwide, the rest corresponds to commercial plants.
The animal feed produced by the integrated plants, that is the most significant part, during the 2002 it produced the 58,7% of the products destined for raising of poultry, the 16,5% for swine, the 14,3% for dairy and 9,2% for feedlots (cattle) and 1,3% for other species.
As far as the composition of the main raw materials to produce balanced foods, these mainly correspond in 45% to domestic sorghum and 55% sorghum concentrated; 16% to domestic yellow maize and 84% imported; 91% domestic protein pastes and 9% imported; 80% of other domestic forage grains (broken maize, wheat, barley, oats, etc.) and 20% imported and other ingredients (wheat by-products, maize, vitamins, minerals, oils, etc.).
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Neuropathies in Mexico, Epidemiology Surveillance Program.- For this analysis, the legal elements related to the notification of the BSE were taken into account, in Mexico, as well as the activities made by the Commission Mexico - United States for the Prevention of the Aftosa Fever and Other Exotic Diseases of Animals (CPA), official entity in charge of carrying out this activity and other connected activities as training, taking of samples and the diagnosis of laboratory.
BSE Diagnosis.
Veterinary Services diagnoses capacity was evaluated as well as its adherence to the international standards, according to what is indicated by the International Organization of Animal Health (OIE), as well as the processes of taking and shipping of samples.
For the diagnosis of the BSE, the OIE recommends five laboratory tests: Histopathology (HP), Immunohistochemistry (IHQ), Western blot (immunotransferency), ELISA (enzimoinmunoassay) and Bio-assay in mouse. At this time Mexico counts with two laboratories of diagnosis for this disease: the National Center of Services of Diagnosis in Animal Health (CENASA) and the Laboratory of high security of the CPA. The CENASA performs the histopathology test and at the CPA the Immunohistochemistry test is carried out.
The reception of samples at CPA, it depends to a great extent on the economic resources which are accounted for this activity, expense that is approximately of $400,00 ($ 36.50 USD.) per sample received (includes the material for conservation, packing and shipping), reason for what, have to wait for the collection of several to be sent at the same time and in order to reduce costs, but delaying the result. As the CPA does not have a certified pathologist to carry-out the HP test technique, these samples are sent to the CENASA for their diagnosis; this implies that such samples are stored by approximately one week, since it doesn’t have the human resources for its transfer.
The main problem at CENASA, for the right operation of the diagnosis of the BSE, it is the lack of coordination on shipping and receiving of samples, which is not done accordingly to the calendar of the laboratory and the operative area, because in a short period of time the expected/projected number of samples is exceeded, resulting in delays in accomplishment of the tests and the disposition in excess of material and human resources.
At this moment, the techniques are being standardized, Immunohistochemistry at the CENASA and the western blot (immunmotransferency) at the CPA, which will allow us to have more tools for the diagnose in Mexico; in addition, the WB allow us to count on another technique of the higher sensitivity and specificity, that guarantees optimal result in less time (approximately 8 hours).
It must be mentioned that, we have had contemplated the formation of a network of laboratories of diagnosis of TSE´s to specialized on the HP technique, where we will have 6 regional laboratories and 4 universities involved, this will in the future allow the processing and diagnosis of the sample from its place of origin and only its confirmation by other techniques at central level. For this, we already count with the procedure for the authorization and verification of a laboratory of histopathology for the diagnosis of the BSE.
Monetary Compensation to cattle dealers: Because the BSE is considered as an exotic disease, a contingency fund that could be put to work in case the disease appears, does not exist at this time.
In the case of the contingency funds, the national campaign for diseases relies on a section on this subject. Nevertheless, for the exotic diseases official norms do not exist and article 36 of the Federal Law of Animal Health only establishes that will be due to create, but it does not explain the mechanism to be considered for its creation.
The pre-established form to compensate the possible producers that are themselves affected by the presence of BSE in their cattle, it will be from the federal budget that is agreed upon the program Alliance for the Country for the corresponding fiscal year.
In this sense, it is necessary to pinpoint that the minimum amount to consider for this budget will be a 4% of the total assigned to the Fito-zoo-sanitary Contingencies Plan on behalf of the Federal Government.
This will have a distribution by federal entity, which a specific amount will be able to be assigned to joint, if necessary, to the DINESA against the BSE. Also, the State Governments will proportionally contribute an equal amount to the federal to be incorporated to the compensation funds of the Device of Emergency. As for the cattlemen, they will have to come-up with resources equivalent to the third part of the total amount assigned by the Federal and State governments.
Animal identification and traceability of cattle products.- Different elements were considered with which Mexico counts on to carry out the traceability of animals and its products upon a sanitary problem, including the animal identification and the organizations related to this activity.
Actually, the identification system of the cattle in Mexico is organized in two forms, one State-ID with aims of demonstration of property and control of cattle rustling and another Federal-ID, with aims of identification for the development of the zoo-sanitary campaigns against the bovine tuberculosis and brucellosis, first it is based on the registry and recognition of the Hot-Brands of each producer, and the second in addition to the previous system, one is based on a metallic earring of blue color with a number of identification, which is described in the NOM-031-ZOO-1995, Campaña Nacional Contra la Tuberculosis Bovina (Mycobacterium bovis), National Campaign Against Bovine Tuberculosis.
This procedure assigns a number to an animal, which is used during zoo-sanitary surveillance campaigns, these activities are registered along with an identification number, in a document called test-opinion, in which it is written down, in addition to the test results applied to the animals, the identification and data of the cattle herd and ranch of origin of the animal for its later traceability. This test-opinion is along with the certificate of “Herd free of bovine tuberculosis” as described in the same Mexican Official Norm.
According to the procedure previously described, in Mexico, there were around 3.291 registered herds with 282.932 heads of bovines identified in 2003, that represents 0,94% of the total population in this country. Nevertheless, in the same NOM, it’s expressed in point 11 referring to mobilization that the animals coming from disease-free herds, they will be able to be mobilized to any destination within the national territory with no need to be tested for tuberculosis before its mobilization, if the following requirements are met: obtain a zoo-sanitary certificate, and for the zoo-sanitary certificate to be issued, certification that they come from a disease-free herd and that the animals must have a disease-free herd identification.
Considering that in order to mobilize the animals it is necessary to have a valid disease-free zoo-sanitary certificate, we can estimate that there are more than 3,431,022 identified animals, according to the information obtained from the Statistical Report of the Cattle Mobilization of FY2000, with information captured up to the 24 of August of 2001 by the National Organism of Herd Certification, A.C., that represents the 11,4% of the bovine total population on which we can observe that more than 50% of these mobilizations are directed to slaughterhouses, 17% to feedlots, 15% for export and 11% for pasturing.
Based on the above, experience of a suitable animal traceability is shown specially in the case of the animals destined to be exported, where the USDA when finding a positive animal reactor to the tests of tuberculosis in the United States, it has been possible to trace it back to its the original herd; on the other hand, the identification system used on dairy cattle, which counts on a homogenous system of identification for production and genetic improvement control, nevertheless, this mechanism although is available for the federal government, it would make use of, only in the presence of a serious epidemiology event.
Educational Programs, Awareness and Training.- The CPA, one of its activities, is to maintain a permanent program of training courses on exotic diseases of the animals, on a national context. In 1994, BSE awareness programs were incorporated , with the diffusion of information, talks and courses on the following areas: disease history, economic consequences, etiology, transmission mechanisms, clinical signage, histopathology injuries, differential diagnosis, measures of prevention and activities of epidemiologist surveillance, supported by audio-visual means, these programs are taken to a diverse audience, including the students of the last semesters of Veterinary Medicine, to the personnel that conforms the Quarantine National System, as well as Veterinary Doctors, government, private and to other specialists.
ESTIMATION OF RISK (Risk Assessment)
According to the qualitative estimation in this assessment, it was determined that the risk of occurrence of the disease in the bovine population, is low.
The quantitative estimation index was located at 5.268908E 08 of the risk of disease exposure of the national herd, number that represents numerically like a low probability of occurrence of the problem in Mexico.
CONCLUSIONS AND RECOMMENDATIONS
Conclusions
The BSE is a disease that was described for the first time in 1986, nevertheless, today, epidemiologists have many unanswered questions on how is transmitted.
The introduction of the BSE in Mexico would cause a serious socioeconomic impact, commercial, political and probably of public health concern, because the presence of the disease would restrict sanitarily and commercially, disrupting the actual distribution of meat products at national level and to other countries, independently of the impact in the consumption of the inhabitants with respect to the beef consumption and products of bovine origin.
Considering the way of transmission, in case of a breakout, the native animals that are at greater risk of being infected in Mexico, those are the dairy cattle in specialized systems and the bovines at feedlots in the arid and tropical regions.
In Mexico, we got Laws, Mexican Official Norms and Agreements, that cover relevant aspects of the epidemiology surveillance of the BSE, same that must be fortified in its operative phase, mainly in its application and enforcement.
The Mexican Official Norm NOM-030-ZOO-1995, Specifications and procedures for the import of beef, carcasses, viscera and offal at zoo-sanitary inspection points, prohibits the import of cattle products, however, fresh beef has been imported, chilled, frozen and beef preparations, as long as it comes from animals smaller of thirty months of age, which diminishes the risk but does not exclude it.
The evaluation showed that the four great areas of concern are assigned to the Main Directorate of Animal Health (DGSA) and to the Main Directorate of Fito-zoo-sanitary Inspection (DGIF); responsibility of the Veterinary Services in Mexico, in relation to the BSE are: epidemiology surveillance, animal movement control, zoo-sanitary campaigns and emergencies; functionality and capability of communicating among them was evaluated as we as the capacity of response before a sanitary emergency caused by the BSE.
It is necessary to increase and to better coordination of the surveillance activities, particularity between the areas of diagnoses and operational, for the correct execution of the surveillance activities in the field. The imported bovines (1996-2003) have been slaughtered and those destined to improve genetics, once they conclude their productive life and are discarded, will also be slaughtered.
The actions of detection of downer-cows need to be reinforced for its processing at TIF plants, till now a deficient activity, where the majority of the animals with such clinical characteristics, regularly are not taken this plants but rather are slaughtered at same ranch/location and consumed regionally or they are taken to slaughterhouses without supervision and sanitary inspection.
Ante mortem inspections need to be reinforced at Federal Inspection Type Plants, municipal and private slaughterhouses, mainly in these two last ones, with the purpose of detecting bovines clinically affected by BSE. There is commercial interest to incorporate flours of meat and bone of ruminants in the rations destined to the feeding of the bovines, like an alternative source of protein matter, reason why official mechanisms must be reinforced in preventing this type of illegal practices.
One of the tools in preventing the BSE is to avoid the exposure of the native bovines to the consumption of presumably contaminated feed with the pathological agent or unless is processed by means of a thermal process that guarantees its inactivation. However, the heat treatment that the flours of meat and bone are put under in
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during 20 minutes), even though this one, it does not guarantee the destruction of the prion either, but it reduces its infectivity significantly.
The Country counts on regulations, in respect to the transformation of offal (NOM-061-ZOO-1999), there still are deficiencies as to the number and qualification of the personnel responsible in supervising their fulfillment through inspection and verification.
Deficiencies in the availability of technical information at official and private levels were detected, crucial information necessary for the elaboration of the present assessment, such as the case of the information on product imports and on rendering plants, were not available for the study.
Blood was not considered as a potential source of transmission of the BSE, by-product in form of flour (dry blood), that is also produced by the rendering plants and is used in animals feeds.
The BSE epidemiology surveillance program in Mexico must be reinforced by focusing on a target animal study (bovine suspected of BSE and with suggestive clinical signs of the disease). On the other hand, as a result from this study, we found that a percentage of the obtained samples for BSE testing have been inadequately collected and among other causes were: absence of cerebral stem, incomplete cerebral stem, over-manipulated samples, advanced changes (decompose) postmortem, not enough tissue to work on, low concentration of conservative (solution) or samples taken from inadequate age of animal (too young); showing all of these, a necessity to review these procedures.
It was also detected the fact that, as a routine practice the samples sent for the diagnosis of bovine rabies, whenever they come out positive to this disease, they are no longer processed for the BSE testing, discarding with this, the possibility of finding both diseases in a same animal, rabies virus and the BSE prion. It is also concluded that with the loss of diagnosis material, it prevented us from obtaining valuable epidemiology information useful in restructuring our surveillance program.
The identification of the cattle, as well as the traceability of its products and by-products, presents serious deficiencies at national level, which is important in case the BSE is detected in the Country, given its importance like a primordial component to trace, to prevent and to eradicate this and other animal diseases, turning out to be an additional vital tool to determine the dissemination degree in case of break-out in the country, that would immediately allow us to be able to establish its origin (native or imported) and to take the appropriate counter-epidemic measures.
From 1994, the Commission Mexico - United States for the Prevention of Foot-and-Mouth Disease (FMD) and other Exotic Diseases (CPA), it has carried out activities of awareness and training on BSE, however, this has been centered to certain zones of the country, leaving some other zones, particularly the rural zones without cover, same that can provide with valuable epidemiology information and some cases for diagnosis of neuropathy in ruminants.
According to the analysis made on the risk assessment in its qualitative modality, it is considered like low-risk, the risk of introduction of the BSE to the national herd, whereas the quantitative study locates it in values of 5.268908E-08.
Recommendations:
We ought:
to reinforce the inspection and supervision activities by the sanitary authority of the SAGARPA over all of those involved in the cattle production chain, in respect to the fulfillment and application of the established technical regulations expressed on the official norms on the monitoring of BSE, specially the NOM-060-ZOO-1999, Zoo-sanitary specifications for the transformation of animals offal and its use in animal feeding and the NOM-061-ZOO-1999, Zoo-sanitary specifications of nutritional products for animal consumption; to increase the number of inspectors (Vet Doctors) as much as governmental as private, with a vision of having a better supervision of the rendering plants and feed factories. It is recommendable that such inspectors have a veterinary doctor’s degree. to reinforce the active epidemiology surveillance subsystem, having special attention to aim at target animals and the size of the statistical test, as well as its stratification at national level; to review, to update and to homologate the criteria and definitions of the Mexican official norms related to the monitoring of the BSE and the requirements of import, according to norms NOM-008, NOM-030 and NOM-060; to provide technical and legal elements in the official norms, that may allow to optimize the use of financial and human resources (federal, state and private), with the purpose of that the material and human infrastructure, the installed diagnoses and the potential, can be used with greater efficiency, in the prevention activities, diagnosis and surveillance of the BSE in Mexico; to homologate the mechanism of training in the obtaining of the samples for the BSE, using the technique of the teaspoon, by means of a national program; to have a certified pathologist for the high security laboratory of the CPA, because this situation of not having one, causes the delay in the processing of samples, as well as the loss of economic resources by requiring the support of the CENASA; to plan the taking of samples at a national level and to coordinate its shipment to the CPA for its processing in the laboratory of high security or its re-expedition to the CENASA, with the purpose of optimizing the diagnosis; to obtain funds and allocate them at each state, in order to compensate cattle dealers affected by the animal culling at risk by BSE, in case of BSE showing up in Mexico, the same or similar mechanism are to established for the handling of monetary compensation, like the one used on the Alliance for the Country or to extend the already existing state government faculties, by means of an exclusive and specific account for the implementation of BSE comp payment.
to implement a national animal identification and traceability system, its products and by-products, that it may allow us to apply prevention measures and control of diseases, as it would be the case of the BSE.
With foundation in Article 14, fraction VI, of the Federal Law of Transparency and Access to the Governmental Public Information, the following paragraphs have been blocked: Justification of the blockade (p. 6, paragraph 1): Gallinaza and pollinaza- feather meal (hay bed or substrate on which birds grow up, constituted by rice husk, straw or another type of hay, agriculturist, that at the end of the raising cycle of young hens or chicken, contains the feces of the animals that were bred on it, as well as rest of non-consumed food by the birds), it has been considered in multiple occasions, like an element of potential risk in the transmission of the bovine spongiform encephalopathy (BSE), when it is used to feed ruminants. The risk is generated, as it is common, the bird feed, contains flours of meat and bone of ruminant like source of protein. In this way, in theory, if some of the bovines with which the meat and bone flour was prepared as bird feed were infected with the BSE prion and given the high resistance of the agent (prion) to high temperatures, in the industrial process as the making of the flour, like the making of the nutritional concentrated feed for birds, and even the passage by digestive-tract of the bird, it would not guarantee the destruction of the BSE prion, reason why the possibility would exist, when gallinaza or pollinaza is used in the feeding of ruminants, this could infect susceptible ruminants.
With foundation in Article 14, fraction VI, of the Federal Law of Transparency and Access to the Governmental Public Information, the following paragraphs have been blocked: Justification of the blockade (p. 6, paragraph 2): As much gallinaza as pollinaza, they can contain up to a 3% of wasted food, independently of bird feces that could also contain the prion, all implying that the flours of meat and bone of bovine origin, can be consumed by other bovines and by doing this, constituting a possible situation of BSE risk.
Norma NOM-060-ZOO-1999 Zoo-sanitary specifications for the transformation of animal’s offal and its use in animal feeding and the NOM-061-ZOO-1999 Zoo-sanitary Specifications of nutritional products for animal consumption, they clearly indicate the prohibition to feed ruminants with flours of meat and bone of ruminant origin, however, the prohibition to feed ruminants with gallinaza or pollinaza, is not contemplated in these norms. With foundation in Article 14, fraction VI, of the Federal Law of Transparency and Access to the Governmental Public Information, the following paragraphs have been blocked: Justification of the blockade (p. 6, paragraph 3): Other elements to consider are the production cycles of the farms of birds in Mexico, a common practice is that when a cycle is reached (ended) “all inside, all outside”, and the pollinaza and gallinaza are destined to feed the cattle. Depending on the type and the characteristics of the bed, it is possible to calculate an approximated weight of 13,9 kg. by square meter of bird farm surface.
With foundation in Article 14, fraction VI, of the Federal Law of Transparency and Access to the Governmental Public Information, the following paragraphs have been blocked: Justification of the blockade (p. 6, paragraph 4): In the Mexican market, two types of products are accepted: pollinaza and gallinaza, which has been consolidated as a production system, considering that near 90% of the feces are used as ruminant’s feed, with prices reaching near those of cereal grains, the rest is used in agriculture.
With foundation in Article 14, fraction VI, of the Federal Law of Transparency and Access to the Governmental Public Information, the following paragraphs have been blocked: Justification of the blockade (p. 6, paragraph 5): The use of the animal feces like source of high nutrients supply, it obeys mainly to its high content of mineral matter and non-protein nitrogen. In general, nitrogen is concentrated in greater amount in bird feces. What is doubtless, it is that the feces are raw material available all the year long for animal feeding, especially bovines. The FAO (1980) made a description of the physical composition of pollinaza as it is detailed next:
Feces 62%
Bed 31%
Wasted Feed 3%
Feathers 2%
Unknown ingredients related to fresh matter 2%
Source: The FAO. Feed from Wastes Animal: State of knowledge, Production animal and Health, to paper 18. Rome, Italy 1980.
Conclusion:
Making public the information that has been eliminated of the report, it would open the door for those in the grain business to use it for their benefit and by pressing the government/the authority to establish a NOM banning such products as ruminant feed. This would bring/cause an important alteration in the commercialization of these products nationwide, which in turn would remarkably increase the production costs of the cattle in feed lots. Today, we foresee escalating grains prices at medium term, originated by its use in the ethanol production; this would aggravate the situation and force a NOM as described before, which in addition, if our sanitary status with respect to the BSE is considered low, it would be obviously excessive cost and highly harmful for the producer of birds and cattle. It is why, that it was decided to block the reference information.
With foundation in Article 14, fraction VI, of the Federal Law of Transparency and Access to the Governmental Public Information, the following paragraphs have been blocked: Justification of the blockade (p. 12, paragraph 3): During the period between 1996 to 2003 years in which, considering the long period of incubation of the BSE, the disease was already present in the United States of America and Canada, Mexico as usual, imported considerable amounts of calves destined for dairy production. In the same term “bullfight” bulls from Spain were imported once Europe reached a free status from FMD, same that allowed the import of some cattle for reproduction from other European countries, with exception of the United Kingdom and Ireland, countries in which BSE already existed.
In all the cases these imports were immediately stopped even before the confirmation of BSE in those countries, nevertheless, as already indicated, the ample period of incubation of the disease, those imports are looked as of certain risk, even though in that moment they were not.
The nonexistence of a national animal identification and traceability system at that time made it impossible to establish the destiny of most of those animals and to even know if they have been eliminated at the end of its productive life. It is possible to indicate that the recent imports of heifers coming from the United States of America and in the near future from Canada, new requirements and actions that guarantee their traceability and other measures to mitigate the BSE risk, are in place.
Even though during the administration of the Lic. Vicente Fox, the SAGARPA made a concerted effort to establish the National System of Individual Cattle Identification (SINIIGA), the magnitude, cost and coverage of the project, its conclusion in the short and medium term are way far distant, what implies that it will be long time before Mexico can count on a suitable (working) national system of identification and traceability of animals and products of origin animal.
The blockade of the above paragraph obeys to the convenience of not exposing to the Federal Government to unnecessarily critics that even though funded, it would not contribute to the solution of a problem that, although is of urgent attention, by its magnitude and cost, it exceeds in much, the present capacities as much of the Government, like of the National Cattlemen Sector. The critic would sustain in that what it is said in such paragraph is purely speculative, without possibility of corroborating it documentarily.
END...
Hola Amigo Terry,
Finally, here is a translation - if you can call it that - i'm not happy with it but guess that some paragraphs are very literally translated (poorest job i have ever done translating a document), please read it and if something is not clear enough or not right just let me know it and i'll correct it...
If you don't find anything of importance; if it is to vague and shows that they have done nothing about it; if somehow it gives you the impresion that they don't know a thing and are trying to cover their butts in a very stupid way;...yea! you got the right impression!!
All they are saying it's a "mea culpa" and we ought to do this and that; we don't know how they came in or where they are; we are looking into it; we screwed up all the BSE testing and we don't know how to do it right; it is too costly and we don't have the money; we didn't do it, past administration did it; we are trying to fix it; etc., All of the above and more, but we are following OIE rules, we have NO BSE anywhere and risk is extremely low or null, but CATTLEMEN WIL BE COMPENSATED!!
Conclusion- they are a bunch of murderers and me a national security threat for having them to admit it!! .....Oh my Lord!
snip...end (tss)
Have a wonderful weekend and our best regards,
xxxxxxxxxxxxxxxxxxxxxxx
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EEB BSE MAD COW IN MEXICO ???
CHRONIC WASTING DISEASE CWD TSE PRION IN MEXICO
Note: Effective September 2023 Mexico has placed a ban on all shipments of cervids from the entire United States due to Chronic Wasting Disease (CWD).
Captive Wild Ruminants - Health Certificate — Available Upon Request Only Note: Includes all camelids, excludes bovines and wild cervids
CERVID CWD SHIPPED TO MEXICO FROM USA???
''TPWD records indicate that within the last five years, the seven CWD-positive facilities transferred a total of 2,530 deer to 270 locations in 102 counties and eight locations in Mexico (the destinations included 139 deer breeding facilities, 118 release sites, five Deer Management Permit sites, and three nursing facilities).''
Special Work Session Chronic Wasting Disease -Disease Detection and Response Request Permission to Publish Proposed Rules in the Texas Register October 5, 2022
I. Executive Summary: Staff seek authorization to publish proposed amendments to the comprehensive Chronic Wasting Disease (CWD) rules in the Texas Register for public comment.
II. Discussion: CWD, a fatal neurodegenerative disorder that affects cervid species such as white-tailed deer, mule deer, elk, red deer, sika, and others (which will be referred to as susceptible species), has been detected in seven permitted deer breeding facilities since March 23, 2021. Texas Parks and Wildlife Department (TPWD), along with Texas Animal Health Commission (TAHC), has been engaged in an ongoing battle with CWD in Texas since 2002. Regarding the current situation involving CWD in permitted deer breeding facilities, TPWD records indicate that within the last five years, the seven CWD-positive facilities transferred a total of 2,530 deer to 270 locations in 102 counties and eight locations in Mexico (the destinations included 139 deer breeding facilities, 118 release sites, five Deer Management Permit sites, and three nursing facilities). Emergency rules were filed on June 22, 2021, intended to address significant concerns for CWD being transferred from deer breeding facilities where the disease may exist undetected, but those rules expire after 180 days, and amendments to the comprehensive rules are necessary to mitigate risks not currently addressed in the current rules.
Texas CWD Surveillance Positives
Counties where CWD Exposed Deer were Released
Number of CWD Exposed Deer Released by County
Chronic Wasting Disease CWD Captive Herds updated April 2023
Chronic Wasting Disease CWD Captive Herds updated April 2023
Chronic Wasting Disease CWD TSE PrP in Texas
Características clínicas de la enfermedad de Creutzfledt-Jakob en México: un análisis retrospectivo
José A. Choreño-Parra1 2
Francisco J. Pacheco-Sánchez1 3 4
Alberto I. Rodríguez-Nava1 3 4
Gabriela García-Quintero1 3 4
Patricia E. Rodríguez-Muñoz1
Parménides Guadarrama-Ortiz1 *
1Department of Neurosurgery, Centro Especializado en Neurocirugía y Neurociencias México (CENNM). Mexico City, Mexico
2Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Mexico City, Mexico
3Internado Médico de Pregrado, CENNM. Mexico City, Mexico
4Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional. Mexico City, Mexico
ABSTRACT
Background:
Little is known about the clinical characteristics and significance of Creutzfeldt-Jakob disease (CJD) in Mexico.
Objective:
This study aimed to conduct a retrospective revision and analysis of the clinical cases of Mexican patients with CJD available in the literature.
Methods:
We systematically searched electronic databases for studies in English and Spanish conducted in Mexico over the period of 1990-2020 that involved Mexican patients with any of the clinical forms of CJD. Clinical variables were extracted from the selected studies that met eligibility criteria. Descriptive statistics were used to characterize the study population.
Results:
A total of seven studies were included in the analysis. From these, 29 cases were revised, and their clinical characteristics analyzed. The median age at the time of diagnosis was 54 years (range 23-75 years). CJD was more frequent among females than male patients (male:female ratio 1:1.41). Most patients resided in Mexico City and the State of Mexico, and 93% attended public hospitals. The most frequent form of CJD was sporadic, with only two probable cases of familiar disease. The most common clinical symptoms observed in order or frequency were rapidly progressive dementia (68.9%), cerebellar signs (51.7%), neuropsychiatric symptoms (51.7%), akinetic mutism (51.7%), myoclonus (44,8%), extrapyramidal signs (44.8%), visual disturbances (41.3%), pyramidal signs (31%), and sleep disorders (17.2%). Only 20% of the cases were confirmed by histopathological analysis of brain biopsy or autopsy specimens.
Conclusions:
Our study provides an overview of the main clinical characteristics of CJD in Mexican patients.
Key words Creutzfeldt-Jakob disease; Prion; Cognitive decline; Rapidly progressive dementia; Spongiform encephalopathy
SNIP...
DISCUSSION
The knowledge about the incidence, clinical characteristics, and epidemiological significance of CJD in Mexico is limited. Our study aimed to retrospectively revise and analyze available reports about the main manifestations of CJD in Mexican patients. A striking finding of our analysis was the low amount of cases from Mexico formally described in the literature. Indeed, only 29 patients with CJD have been reported over the past three decades in our country, which is <1 case/year. This finding undoubtedly reflects a high grade of underreporting and sub-diagnosis of CJD cases in Mexicans. For instance, if we took the global incidence of sCJD as a reference (1 case per million people per year)3, then the expected number of CJD cases occurring in Mexico would be much higher.
These data are in part due to the rarity and unspecific manifestations of CJD. In this sense, it is well recognized that rapidly progressive dementia is not a unique characteristic of this disease. In fact, many other neurological disorders can be confused with CJD, including some variants of Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), viral, bacterial, parasitic, or autoimmune meningoencephalitis (e.g., Hashimoto’s encephalitis, and limbic encephalitis), corticobasal degeneration, progressive supranuclear palsy, paraneoplastic encephalomyelitis, and even vascular dementia18,19. Furthermore, a wide range of other clinical manifestations, such as pyramidal/extrapyramidal dysfunction, ataxia, cerebellar signs, psychiatric symptoms, visual disturbances, sleep disorders, akinetic mutism, and persistent painful sensory symptoms, may be present among patients with CJD1, adding complexity to the clinical spectrum of the disease. This fact led physicians to subclassify various forms of CJD according to the mean symptoms, including the classic (dyskinetic), Heidenhain (visual), myoclonic, cerebellar (ataxic), thalamic, amyotrophic, and panencephalopathic forms4,7.
Furthermore, it is, currently, well known that, in the specific case of sCJD, the clinical heterogeneity is also associated with some genetic and molecular features of the pathogenic PrPSc. Specifically, methionine (M) or valine (V) polymorphism at codon 129 of the PRNP gene20, as well as the type of electrophoretic mobility pattern of PrPSc after protease digestion (type 1 and 2), are used to classify patients into several phenotypes separated into three categories: sCJD cognitive subtypes (MM1, MV1, MM2, and VV1), ataxic subtypes (VV2 and MV2), and other non-sCJD subtypes (types 3 and 4 electrophoretic mobility for sporadic fatal insomnia (sFI) and variably protease-sensitive prionopathy (VPSPr), respectively)4,7. Each category has unique characteristics differing from the others in age at onset, duration of the disease, dominant neurological findings, and among others. However, the age at onset of all CJD cases ranges from 50 to 70 years with no predilection for any gender.
The polymorphisms in the PRNP gene that determine the susceptibility for the development of sCJD are differentially distributed among various populations around the world21-24. However, the frequency of M129V genotypes and alleles in the Mexican population has not been addressed. Our results confirm that sCJD is the most frequent variant of this disease in Mexicans. Furthermore, there are only two cases of probable fCJD not confirmed by the demonstration of an inherited mutation in the PRNP gene. There is no registry of any case of acquired CJD through iatrogenic exposure or contagion, but there are cases in very young patients, and the wide range of interval between disease onset to hospital admission opens the possibility of the occurrence of vCJD/iCJD among Mexican individuals. We also observed that rapidly progressive dementia, akinetic mutism, and myoclonus were among the most common symptoms observed in Mexican CJD patients. Furthermore, neuropsychiatric symptoms were frequently reported, although only one case was formally categorized as a Heidenhain variant of CJD15. These data indicate that the sCJD cognitive subtypes are common in Mexicans with this disease. Thus, we can predict that the underlying genetic and molecular traits of these phenotypes (MM1, MV1, MM2, and VV1) would be frequent in our population.
Interestingly, we found a high number of patients with CJD that presented cerebellar symptoms (51.72%), including ataxia. The frequency of cerebellar affection in CJD patients from other regions has not been comprehensively estimated. In a study conducted in the United Kingdom, cerebellar ataxia occurred as the only clinical manifestation in 5% of patients with CJD25. In contrast, in a study of Chinese patients with CJD, up to 51.9% of affected individuals presented cerebellar ataxia26, which coincides with our findings. Thus, based on our results, we also predict that the genetic and molecular characteristics of the PrPSc underlying ataxic subtypes of sCJD (VV2 and MV2) may have a high incidence in Mexico.
The variable clinical characteristics of CJD complicate the diagnostic approach and opportune detection of positive cases. Furthermore, the low level of clinical suspicion among physicians and the absence of a formal surveillance strategy may further contribute to the underestimation of the burden of CJD in the Mexican population. To improve the diagnosis and global surveillance of CJD, the CDCs have established several diagnostic criteria that classify each case according to the likelihood of the disease based on clinical features and the results of different laboratory and imaging tests9. Possible and probable categories are based on clinical symptoms and positive results in EEG, MRI, and CSF 14-3-3. Most such studies have high specificity but low sensitivity, and it is important to mention that their diagnostic reliability varies according to the CJD form and even to the sCJD subtype27.
EEG recording in patients with sCJD typically shows pseudo-periodic sharp-wave complexes (PSWC) with diffuse slowly background activity at the middle and late stages of the disease. The diagnostic value of EEG is due to its 64% sensitivity and 91% specificity28. On the other hand, MRI has shown to have better diagnostic performance due to improvements in the DWI sequence29. MRI does not allow to distinguish between clinical forms of CJD, but in cases of vCJD, a posterior thalamus involvement (pulvinar sign) supports the diagnosis30. CSF levels of neuron-specific enolase (NSE) and T-tau protein have also been proposed as biomarkers of CJD. From these, T-tau protein has the highest sensitivity and specificity with a cutoff of 1150pg/mL31. However, CSF levels of T-tau protein have not been integrated into the 2018 CDC’s diagnostic criteria for CJD.
Notably, in the last decade, RT-QuIC has emerged as a novel alternative for premortem diagnosis of CJD with better performance compared with other CSF tests. This assay relies on the in vitro template conversion of recombinant PrPC into PrPSc, evidenced through a fluorescent indicator, allowing to detect minute amounts of PrPSc in biological samples with high sensitivity and specificity17. Indeed, we recently reported the first case of a Mexican patient with sCJD confirmed by a complete battery of diagnostic tests, including EEG, MRI-DWI, CSF levels of T-tau, and 14-3-3 protein, as well as CSF RT-QuIC, which allowed us to detect this case premortem (16). In such a report, we demonstrated an excellent correlation between the results of the RT-QuIC test and other clinical and laboratory parameters. Despite this, RT-QuIC is not considered as a diagnostic tool that can classify a patient as a definitive case of CJD by the CDCs. Thus, the definitive diagnosis of CJD is still based on the histopathological analysis of brain biopsy and autopsy specimens.
Our study reveals concerning data about the diagnostic approach to CJD in our country. First, we observed that only 20% of cases were confirmed by histopathology. The definitive confirmation of CJD in Mexicans was exclusively performed in public health-care institutions. More specific and sophisticated imaging and CSF tests were rarely performed in public hospital care, and they were carried out in laboratories outside Mexico, even in cases diagnosed at private hospitals. These facts must claim the attention of national health-care authorities to make the efforts needed to create laboratories with the technical capacity to perform special CSF studies and to introduce new tests that allow confirming CJD in Mexico, such as the RT-QuIC test.
CONCLUSIONS
Our study provides an overview of the main clinical characteristics of CJD in Mexican patients. Also, our study reveals that the incidence of CJD in our country could be higher than supposed. Finally, we remarked several deficiencies in the diagnostic approach to this neurological disorder in our country that needs the attention of the Mexican authorities of health. Our findings should motivate Mexican physicians and researchers to get involved in the surveillance and improvement of diagnosis of the disease
MEXICO CREUTZFELDT JAKOB DISEASE CJD
THURSDAY, NOVEMBER 9, 2023
EFSA Annual Report of the Scientific Network on BSE-TSE 2023
Professor John Collinge on tackling prion diseases, sCJD accounts for around 1 in 5000 deaths worldwide
MONDAY, SEPTEMBER 11, 2023
Professor John Collinge on tackling prion diseases “The best-known human prion disease is sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia which accounts for around 1 in 5000 deaths worldwide.”
There is accumulating evidence also for iatrogenic AD.
Understanding prion biology, and in particular how propagation of prions leads to neurodegeneration, is therefore of central research importance in medicine.
Terry S. Singeltary Sr.