1 / 142

Transmissible Spongiform Encephalopathy

margarita-vargas
Télécharger la présentation

Transmissible Spongiform Encephalopathy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. MEDICAL DEVICES ADVISORY COMMITTEEMEETING OF THE GENERAL HOSPITAL AND PERSONAL USE DEVICES PANELTransmissible Spongiform Encephalopathy (TSE)September 27, 2005Infection Control Devices BranchDivision of Anesthesiology, General Hospital, Infection Control and Dental DevicesCenter for Devices and Radiological Health

  2. Transmissible Spongiform Encephalopathy Introduction Sheila A. Murphey, MD Branch ChiefInfection Control Devices Branch Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Center for Devices and Radiological Health HHS/FDA/CDRH

  3. General Hospital and Personal Use Devices Panel • The Advisory Panel is asked to address the scientific issues surrounding the evaluation of products/processes intended to reduce the bioburden of the Creutzfeldt-Jakob transmissible agent on contaminated surgical instruments. HHS/FDA/CDRH

  4. General Hospital and Personal Use Devices Panel • In July 2003, DAGID asked the Transmissible Spongiform Encephalopathies Advisory Committee (TSEAC) to address the issue of reprocessing medical devices contaminated or potentially contaminated by TSE agents. HHS/FDA/CDRH

  5. General Hospital and personal Use Devices Panel • The questions on instrument decontamination asked of TSEAC were general and received general responses. • TSEAC pointed out that little of the experimental literature on TSE inactivation is directly applicable to hospital settings. HHS/FDA/CDRH

  6. General Hospital and Personal Use Devices Panel • TSEAC stated that “there is no threshold value below which exposure to a TSE agent should be considered safe. • TSEAC stated that “use of existing methods cannot assure complete removal of TSE agents from all materials under all circumstances”. HHS/FDA/CDRH

  7. General Hospital and Personal Use Devices Panel • The Division of Anesthesiology, General Hospital, Infection Control and Dental Devices (DAGID) believes that it needs more guidance on the issues of TSE contamination of surgical instruments HHS/FDA/CDRH

  8. General Hospital and Personal Use Devices Panel • The number of scientific articles addressing the reduction/removal of TSE from instrument proxies is increasing • Public interest in and concern about variant Creutzfeldt-Jakob disease and its potential for causing infections in the US is increasing HHS/FDA/CDRH

  9. General Hospital and Personal Use Devices Panel • DAGID believes that it should prepare for the possibility that products or processes intended to reduce TSE infectivity on surgical instruments will be submitted to FDA for premarket evaluation. HHS/FDA/CDRH

  10. General Hospital and Personal Use Devices Panel Presentations by FDA Sheila A. Murphey, MD Elaine S. Mayhall, PhD Estelle Russek-Cohen, PhD Ronald Brown HHS/FDA/CDRH

  11. General Hospital and Personal Use Devices Panel Guest Speaker Allan Hidderley Senior Medical Device Specialist Medicines and Healthcare Products Regulatory Agency (Devices) Device Technology and Safety-Biologics and Implants United Kingdom HHS/FDA/CDRH

  12. HHS/FDA/CDRH

  13. Transmissible Spongiform Encephalopathy Introduction Elaine Schalk Mayhall, Ph.D. Infection Control Devices Branch Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Center for Devices and Radiological Health HHS/FDA/CDRH

  14. Transmissible Spongiform Encephalopathy • Transmissible spongiform encephalopathies (TSE) are rare, progressive neurodegenerative diseases which affect both humans and animals. • TSEs result from the accumulation of the abnormal isoform of a normal host cell protein which causes progressive neuronal dysfunction. HHS/FDA/CDRH

  15. Human Transmissible Spongiform Encephalopathies HHS/FDA/CDRH

  16. Animal Transmissible Spongiform Encephalopathies HHS/FDA/CDRH

  17. Pathogenesis of Human Transmissible Spongiform Encephalopathy PrPc Prion protein (cellular) - also called PrPsen • Encoded by PRNP • Normal protein isoform, expressed on the surface of neurons, glial cells, other cells • Function uncertain Prion stands for proteinaceous infectious particle HHS/FDA/CDRH

  18. Pathogenesis of Human TSE PrPres (PrPsc) • Abnormal isoform of the normal prion protein, PrP • Induces the conversion of PrPc to PrPres • Accumulation of the abnormal isoform PrPres causes fatal neurodegenerative disease with a long incubation period HHS/FDA/CDRH

  19. Pathogenesis of Human TSE HHS/FDA/CDRH

  20. Pathogenesis of Human TSE Conversion of PrPsen to PrPres • Acquisition of abnormal isoform • “Sporadic” (Idiopathic) (?somatic mutation) • Ingestion • Iatrogenic transmission • Inheritance of an abnormal isoform at least 30 mutations described HHS/FDA/CDRH

  21. Transmission of Human TSE • When PrPres is present, it can be transmitted to another host • Transmission requires prion transfer, usually in tissue. • While central nervous system (CNS) tissue is the most effective vehicle, other tissues can also transfer prions • Efficiency of transmission is dose-related HHS/FDA/CDRH

  22. Transmission of TSE Risk of TSE transmission will be determined by • Availability of a TSE source • Likely frequency of a “transmissible” encounter with a TSE source • Effective TSE “dose” • Larger doses are more efficient in transmission HHS/FDA/CDRH

  23. Iatrogenic Transmission of Creutzfeldt-Jakob disease Source # Incubation period Neurosurgery 5 17 months (12-28 m) EEG Electrodes 2 16-20 months Cornea Transplant 3 16-320 months Dura mater grafts 114 6 yrs (1.5 – 18 yrs) Growth Hormone 139 12 yrs ( 5-30 yrs) Gonadotropin 4 13 yrs ( 12-16 yrs) P Brown et al, Neurology 2000, 55:1075-1081 HHS/FDA/CDRH

  24. Iatrogenic Transmission of CJD by Contaminated Surgical Instruments • All 7 reported cases of CJD transmission by contaminated surgical instruments/EEG electrodes occurred between 1954 and 1980 • All 7 reported cases of CJD transmission by contaminated surgical instruments/EEG electrodes occurred in Europe (UK 4, Switzerland 2, France 1) HHS/FDA/CDRH

  25. Preventing Iatrogenic TSE Transmission by Contaminated Instruments • Human forms of TSE can be transmitted • Transmission by materials and instruments contaminated by CNS tissue from CJD patients has occurred • CJD patients are not always promptly diagnosed in the early stages of disease HHS/FDA/CDRH

  26. Preventing Iatrogenic TSE Transmission by Contaminated Instruments Currently Recommended Clinical Practice • Precautions to prevent the transmission of TSE by contaminated surgical instruments should be taken for invasive CNS procedures in patients with dementia of uncertain origin and patients known or suspected of having TSE. • Precautions to prevent instrument transmission should also be taken for extraneural procedures although the risk of transmission is lower. HHS/FDA/CDRH

  27. Preventing Iatrogenic TSE Transmission by Contaminated Instruments Currently Recommended Clinical Practice • Surgical instruments may be discarded • Surgical instruments may be quarantined until a diagnosis is confirmed • Surgical instruments may be treated with processes shown to have some in-vivo effect in reducing TSE transmission and recommended by CDC HHS/FDA/CDRH

  28. Preventing Iatrogenic TSE Transmission by Contaminated Surgical Instruments • Studies at the National Institutes of Health have identified several methods of instrument treatment which reduce TSE transmission. • These have been recommended for clinical consideration by the CDC and other authorities. HHS/FDA/CDRH

  29. Preventing Iatrogenic TSE Transmission by Contaminated Instruments Currently Recommended Clinical Practice • Prevacuum steam sterilization at 1340C for 18 min • Gravity steam sterilization at 1210C for 1 hr • Immersion in 1 N NaOH for 1 hr HHS/FDA/CDRH

  30. Preventing Iatrogenic TSE Transmission by Contaminated Instruments • NaOH immersion and TSE sterilizer cycles have been used together • Sodium hypochlorite immersion has been recommended by some authorities • Currently recommended decontamination procedures are corrosive and unsuitable for heat-sensitive materials HHS/FDA/CDRH

  31. Preventing Iatrogenic TSE Transmission by Contaminated Instruments • Currently recommended procedures for treating CJD-contaminated surgical instruments have not been systematically studied for clinical efficacy HHS/FDA/CDRH

  32. Preventing Iatrogenic TSE Transmission by Contaminated Instruments • Iatrogenic transmission of CJD by CJD-contaminated surgical instruments has not been reported since 1980 • Small epidemiologic studies of risk factors for CJD have not consistently shown any statistically significant association between surgery and CJD HHS/FDA/CDRH

  33. Preventing Iatrogenic TSE Transmission by Contaminated Instruments • Exposures of patients to instruments used in invasive CNS procedures on patients with unrecognized CJD have been reported. • No cases of iatrogenic CJD resulting from these exposures have yet been reported. HHS/FDA/CDRH

  34. Transmission of TSE Availability of a TSE Source in the US • “Sporadic” CJD is the most common TSE in the US • Average annual US death rate from CJD is 0.95 per million persons • vCJD has been described only once in the US in a recent UK emigrant HHS/FDA/CDRH

  35. Does vCJD Increase the Risk of Iatrogenic TSE transmission? • Patients with variant CJD (vCJD) have greater extra-neural tissue burdens of PrPres • Patients with vCJD may have atypical and prolonged symptoms before diagnosis • The number of patients with presymptomatic vCJD may be increasing • There is concern that the risk of vCJD transmission by surgical instruments may be increasing in areas affected by the BSE epidemic and may involve other tissues besides CNS tissues HHS/FDA/CDRH

  36. Summary • TSEs are rare, fatal neurodegenerative diseases of man and animals • TSE has, very rarely, been transmitted by contaminated surgical instruments • Current clinical practice based on the CDC recommendations may reduce the risk of TSE transmission by contaminated instruments • Is it possible to further reduce the risk? HHS/FDA/CDRH

  37. HHS/FDA/CDRH

  38. In-Vivo Models of TSE Transmission Experimental Design Issues Sheila A. Murphey, MD Branch Chief Infection Control Devices Branch Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Center for Devices and Radiologic Health HHS/FDA/CDRH

  39. Experimental Methods for Studying TSE HHS/FDA/CDRH

  40. In-Vivo Models of TSE Transmission • Prion source • Susceptible host animal • CNS introduction • Observe host for symptoms of TSE or sacrifice asymptomatic survivors at predetermined endpoint • Confirm outcome by examination of CNS for evidence of TSE infection HHS/FDA/CDRH

  41. In-Vivo Models of TSE Transmission Prion Sources • Human CJD - sporadic - variant - genetic • Scrapie • Bovine Spongiform Encephalopathy (BSE) • Other Animal Prions HHS/FDA/CDRH

  42. In-Vivo Models of TSE Transmission • Most Common Hosts • Mice • Hamsters • Guinea Pig • Hosts may be genetically altered to carry other species’ PrPc • Host lifespan may differ from original host. Will this affect the natural history of infection or the interpretation of results? HHS/FDA/CDRH

  43. In-Vivo Models of TSE Transmission • Overcoming Species Barriers to TSE Transmission • Large infecting inoculum • Serial passage in new host • Genetic manipulation of the host by introducing a new PrPsen HHS/FDA/CDRH

  44. In-Vivo Models of TSE Transmission • Introduction of TSE Sources into CNS • Whole brain tissue • Homogenates of brain • Material may be diluted • Material may be pooled from several sources • Material may have been frozen before use HHS/FDA/CDRH

  45. In-Vivo Models of TSE Transmission • Introduction of Inoculum into CNS • Injection by needle • Coated stainless steel wire – may be left in-situ or removed after insertion • Coated stainless steel spheres HHS/FDA/CDRH

  46. In-Vivo Models for TSE Transmission HHS/FDA/CDRH

  47. HHS/FDA/CDRH

  48. HHS/FDA/CDRH

  49. HHS/FDA/CDRH

More Related