Prions in humans and animals / edited by Beat Hörnlimann ; in collaboration with Detlev Riesner and Hans Kretzschmar.

Format:

Book

Contributor:

Hörnlimann, Beat, 1958-

Riesner, Detlev, 1941-

Kretzschmar, H. A. (Hans A.)

Language:

English

Subjects (All):

Prion diseases.

Prion Diseases.

Prions.

Medical Subjects:

Prion Diseases.

Prions.

Physical Description:

xxvii, 714 pages : illustrations (some color), maps ; 25 cm

Place of Publication:

Berlin ; New York : Walter de Gruyter, [2007]

Summary:

This comprehensive work, aimed at both students and researchers alike, systematically covers all aspects of prion diseases (transmissible spongiform encephalopathies), from their history, microbiology and pathology to their transmissibility and prevention. The book describes diseases such as Creutzfeldt-Jacob disease, kuru, mad cow disease (BSE), chronic wasting disease and scrapie, highlighting their biochemical, molecular biological, genetic, and clinical aspects.

A renowned editorial team, representing the fields of medicine, veterinary medicine, and molecular biology, brought together 80 internationally respected authors for this translation and new edition of the successful German publication, not only from relevant research fields, but also from industry and public health institutions. The book includes chapters by, among many other notable scientists, William J. Hadlow, who discovered the relationship between the human and animal forms of prion diseases and Michael P. Alpers, with 45 years of experience in Papua New Guinea investigating the first known human epidemic form, kuru. Further contributions from Gerald A. H. Wells, a veterinary pathologist who described BSE and recognized its similarity to scrapie, thus recording the first cases in 1986 of the most important animal epidemic of modern times, and Robert G. Will, a medical neurologist and epidemiologist who discovered the emergence of the variant form of Creutzfeldt-Jacob disease in 1996, underscore the strength of this author team. Carefully edited with numerous illustrations, this work offers a systematic approach committed to a clear presentation of the current knowledge of prion diseases. It aims to inspire and stimulate interdisciplinary cooperation, innovative research ideas and effective prevention.

Contents:

Topic I History

1 Historical Introduction / B. Hornlimann, D. Riesner, H. Kretzschmar, R.G. Will, S.C. MacDiarmid, G.A.H. Wells, M.P. Alpers 3

1.2 The cause of prion diseases 3

1.3 Scrapie: archetype of all prion diseases 4

1.4 Transmissible mink encephalopathy 7

1.5 Chronic wasting disease in North American cervids 7

1.6 Creutzfeldt-Jakob disease and other human prion diseases 8

1.7 The scrapie-kuru connection 11

1.8 Etiological variety of prion diseases 12

1.9 New prion diseases 14

1.10 Prion diseases and contagion 18

1.11 Summary: traits common to all human and animal prion diseases 18

1.12 Synopsis of events, discoveries and findings since 1732 19

2 History of Kuru Research / B. Hornlimann 28

2.2 From the stone age to the present: the Fore people 28

2.3 Discovery of kuru 29

2.4 The "Tukabu" ritual 32

2.5 The beginning of kuru research 32

2.6 A kuru hospital in Okapa 33

2.7 The spread of kuru 34

2.8 The pathological picture 35

2.9 The diet of the Fore 36

2.10 The geographical spread of the epidemic and the phylogenetic relations among kuru victims 37

2.11 The ancestral cult 38

2.12 Social impact 39

2.13 The discovery of transmissibility 40

2.14 The answers to the questions 41

3 History of Prion Research / S.B. Prusiner 44

3.2 Animals and humans affected 44

3.3 In search of the cause 46

3.4 Amazing discovery 46

3.5 Prion diseases can be inherited 47

3.6 One protein, two shapes 51

3.7 Treatment ideas emerge 51

3.8 The mystery of "strains" 52

3.9 Breaking the barrier 53

3.10 The list may grow 54

3.11 Striking similarities 54

Topic II Molecular Biology and Genetics

4 The Physical Nature of the Prion / D. Riesner 59

4.2 The prion model and its nomenclature 59

4.3 The virus hypothesis 60

4.4 The virino hypothesis 61

4.5 The nucleic acid problem 61

5 Folding of the Recombinant Prion Protein / R. Glockshuber, J. Stohr, D. Riesner 69

5.2 Folding of recombinant PrP[superscript C] 70

5.3 The role of the single disulfide bond of PrP 73

5.4 Influence of point mutations linked with inherited human prion diseases on the thermodynamic stability of recombinant PrP[superscript C] 74

5.5 Outlook 76

6 Structural Studies of Prion Proteins / S. Schwarzinger, D. Willbold, J. Ziegler 79

6.2 Structure of the globular domain of PrP[superscript C] 81

6.3 Structural studies of full-length PrP 86

6.4 NMR studies on isolated structural features of PrP 88

6.5 High pressure NMR 90

6.6 Structural studies of PrP[superscript Sc] 91

7 Function of Cellular Prion Protein in Copper Homeostasis and Redox Signaling at the Synapse / J. Herms, H. Kretzschmar 95

7.2 Cellular location of PrP[superscript C] 95

7.3 Protein interactions with PrP[superscript C] 96

7.4 PrP[superscript C] binds copper(II) ions 96

7.5 Functional relevance of copper binding of PrP[superscript C] at the synapse 97

7.6 Neuroprotective role of the prion protein in response to copper and oxidative stress 98

7.7 Redox signaling by PrP[superscript C] modulates intracellular calcium homeostasis and synaptic function 99

8 The Scrapie Isoform of the Prion Protein PrP[superscript Sc] Compared to the Cellular Isoform PrP[superscript C] / D. Riesner 104

8.2 Biological and immunological properties of PrP[superscript Sc] 104

8.3 Chemical, biochemical, and physical properties of PrP[superscript Sc] 105

8.4 Structure of PrP[superscript Sc] 108

8.5 In vitro conversion of PrP and the generation of infectivity 109

8.6 Models of prion replication 113

8.7 Infectious, sporadic, and familial etiology of prion diseases 116

9 The Phylogeny of Mammalian and Nonmammalian Prion Proteins / H.M. Schatzl 119

9.2 The organization of the PrP gene 119

9.3 Comparative analysis of PrP genes and prion proteins 121

10 Knockouts and Transgenic Mice in Prion Research / E. Flechsig, I. Hegyi, A.J. Raeber, A. Cozzio, A. Aguzzi, C. Weissmann 134

10.2 Generation and properties of PrP knockout mice 134

10.3 Transgenesis and gene replacement 140

10.4 Reverse genetics: studies on the structure-function relationship of PrP 141

10.5 Transgenic approaches to study intervention strategies against prion diseases 148

10.6 Investigating the mechanism of prion propagation by ectopic expression of PrP 150

11 Transplantation as a Tool in Prion Research / E. Flechsig, I. Hegyi, A.J. Raeber, A. Cozzio, A. Aguzzi, C. Weissmann 160

11.2 Prion-infected neurografts fail to cause neuropathological changes in PrP knockout mice 160

11.3 Spread of prions in the central nervous system requires PrP[superscript C]-expressing tissue 161

11.4 Spread of prions from extracerebral sites to the CNS 162

12 Prion Strains / M.H. Groschup, A. Gretzschel, T. Kuczius 166

12.2 Definition of the term "prion strain" 166

12.3 Characteristics of prion strains 167

12.4 Adaptation and selection 173

12.5 Known prion strains in different species 174

12.6 Explanatory approaches with regard to the development and existence of prion strains 179

Topic III Portraits of Prion Diseases

13 Portrait of Kuru / B. Hornlimann, M.P. Alpers 187

13.1 History 187

13.2 Forms or variants 187

13.3 Incubation period, transmissibility, and susceptibility 187

13.4 Clinical signs and course of disease 188

13.5 Differential diagnoses 190

13.6 Epidemiology 190

13.7 Pathology 191

13.8 Is kuru a new disease? 191

13.9 Risk factors 191

13.10 Surveillance, prevention, and control 192

14 Portrait of Creutzfeldt-Jakob Disease / H. Budka 195

14.1 History 195

14.2 Forms or variants 195

14.3 Incubation period, transmissibility, and susceptibility 196

14.4 Clinical signs and course of disease 197

14.5 Differential diagnoses 197

14.6 Epidemiology 198

14.7 Pathology 198

14.8 Is CJD a new disease? 198

14.9 Risk factors 199

14.10 Surveillance, prevention, and control 199

15 Portrait of Variant Creutzfeldt-Jakob Disease / R.G. Will, J.W. Ironside 204

15.1 History 204

15.2 Forms or variants 204

15.3 Incubation period, transmissibility, and susceptibility 204

15.4 Clinical signs and course of disease 205

15.5 Differential diagnoses 205

15.6 Epidemiology 205

15.7 Pathology 206

15.8 Is vCJD a new disease? 207

15.9 Risk factors 208

15.10 Surveillance, prevention, and control 208

16 Portrait of Gerstmann-Straussler-Scheinker Disease / H. Budka 210

16.1 History 210

16.2 Forms or variants 211

16.3 Incubation period, transmissibility, and susceptibility 211

16.4 Clinical signs and course of disease 212

16.5 Differential diagnoses 213

16.6 Epidemiology 213

16.7 Pathology 213

16.8 Is GSS a new disease? 213

16.9 Risk factors 213

16.10 Surveillance, prevention, and control 213

17 Portrait of Fatal Familial Insomnia and Sporadic Fatal Insomnia / H. Budka, E. Gelpi 216

17.1 History 216

17.2 Forms or variants 216

17.3 Incubation period, transmissibility, and susceptibility 216

17.4 Clinical signs and course of disease 217

17.5 Differential diagnoses 218

17.6 Epidemiology 218

17.7 Pathology 218

17.8 Are FFI and SFI new diseases? 220

17.9 Risk factors 220

17.10 Surveillance, prevention, and control 220

18 Portrait of Scrapie in Sheep and Goat / B. Hornlimann, L. v. Keulen, M.J. Ulvund, R. Bradley 222

18.1 History 222

18.2 Forms or variants (scrapie agent strains) 223

18.3 Incubation period, transmissibility, and susceptibility 223

18.4 Clinical signs and course of disease 225

18.5 Differential diagnoses 226

18.6 Epidemiology 226

18.7 Pathology 227

18.8 Is scrapie a new disease? 227

18.9 Risk factors 227

18.10 Surveillance, prevention, and control 228

19 Portrait of Bovine Spongiform Encephalopathy in Cattle and Other Ungulates / B. Hornlimann, J. Bachmann, R.

Bradley 233

19.1 History 233

19.2 Forms or variants 234

19.3 Incubation period, transmissibility, and susceptibility 236

19.4 Clinical signs and course of disease 239

19.5 Differential diagnoses 239

19.6 Epidemiology 240

19.7 Pathology and pathogenesis 240

19.8 Is BSE a new disease? 243

19.9 Risk factors 243

19.10 Surveillance, prevention, and control 246

20 Portrait of Prion Diseases in Zoo Animals / J.K. Kirkwood, A.A. Cunningham 250

20.1 History 250

20.2 Forms or variants 250

20.3 Incubation period, transmissibility, and susceptibility 251

20.4 Clinical signs and course of disease 251

20.5 Differential diagnoses 251

20.6 Epidemiology 252

20.7 Pathology 253

20.8 Are prion diseases of zoo animals new? 253

20.9 Risk factors 253

20.10 Surveillance, prevention, and control 254

21 Portrait of Chronic Wasting Disease in Deer Species / E.S. Williams, M.W. Miller 257

21.1 History 257

21.2 Forms or variants 257

21.3 Incubation period, transmissibility, and susceptibility 258

21.4 Clinical signs and course of disease 259

21.5 Differential diagnoses 261

21.6 Epidemiology 261

21.7 Pathology 262

21.8 Is CWD a new prion disease? 262

21.9 Risk factors 262

21.10 Surveillance, prevention, and control 262

22 Portrait of Transmissible Mink Encephalopathy / W.J. Hadlow 265

22.1 History 265

22.2 Forms or variants 265

22.3 Incubation period, transmissibility, and susceptibility 265

22.4 Clinical signs and course of disease 266

22.5 Differential diagnoses 267

22.6 Epidemiology 267

22.7 Pathology 268

22.8 Is TME a new disease? 268

22.9 Risk factors 268

22.10 Surveillance, prevention, and control 268

23 Portrait of Transmissible Feline Spongiform Encephalopathy / M. Hewicker-Trautwein, R. Bradley 271

23.1 History 271

23.2 Forms or variants 271

23.3 Incubation period, transmissibility, and susceptibility 271

23.4 Clinical signs and course of disease 271

23.5 Differential diagnoses 272

23.6 Epidemiology 272

23.7 Pathology 272

23.8 Is FSE a new disease? 272

23.9 Risk factors 273

23.10 Surveillance, prevention, and control 273

24 Portrait of Experimental BSE in Pigs / G.A. H. Wells, S.A.C. Hawkins, J. Pohlenz, D. Matthews 275

24.1 History 275

24.2 Forms or variants 275

24.3 Incubation period, transmission, and susceptibility 275

24.4 Clinical signs and course of disease 276

24.5 Differential diagnoses 276

24.6 Epidemiology 276

24.7 Pathology 276

24.8 Is there a TSE of pigs? 277

24.9 Risk factors 277

24.10 Surveillance, prevention, and control 277

25 Portrait of a Spongiform Encephalopathy in Birds and the Transmissibility of Mammalian Prion Diseases to Birds / G.A.H. Wells, J. Pohlenz, S.A.C. Hawkins, D. Matthews 279

25.1 History 279

25.2 Avian prion diseases? 279

25.3 Transmission studies 280

25.4 Clinical signs and course of the SE of ostriches 280

25.5 Differential diagnoses of the SE of ostriches 280

25.6 Epidemiology of the SE of ostriches 281

25.7 Pathology of the SE of ostriches 281

25.8 What is the significance of the SE of ostriches? 281

25.9 Risk factors and prevention 281

25.10 Surveillance 282

Topic IV Pathology

26 Pathology and Genetics of Human Prion Diseases / H. Kretzschmar, P. Parchi 287

26.2 Neuropathologic features of prion diseases in humans 288

26.3 PrP[superscript Sc] in non-neuronal tissues 294

26.4 The human prion protein and prion protein gene (PRNP) 294

26.5 Neuropathological phenotypes of human prion diseases 299

26.6 Genetics of human prion diseases: phenotypes of familial (genetic) prion diseases 305

27 The Pathology of Prion Diseases in Animals / G.A.H. Wells, S.J. Ryder, W.J. Hadlow 315

27.2 Pathology of scrapie in sheep and goats 315

27.3 Pathology of transmissible mink encephalopathy 318

27.4 Pathology of chronic wasting disease 318

27.5 Pathology of bovine spongiform encephalopathy 319

27.6 Pathology of BSE in non domestic captive ungulate species 323

27.7 Pathology of feline spongiform encephalopathy 323

28 Pathophysiology of Prion Diseases Following Peripheral Infection / W.J. Schulz-Schaeffer, H. Kretzschmar, M. Beekes 328

28.2 Administration of the pathogen in animal experiments 328

28.3 Cell culture experiments 328

28.4 Peripheral paths of infection 328

28.5 Significance of the hematopoetic system, in particular the spleen 329

28.6 Species-specific differences 330

28.7 Neuronal spread of infection to the central nervous system 331

Topic V Surveillance, Clinical Aspects and Diagnostics

29.2 Surveillance of patients on an out-patient and in-patient basis 339

29.3 Surveillance in neuropathological laboratories and diagnostic laboratories 341

29.4 International cooperation and the importance of national health authorities 344

29.5 Epidemiological surveillance and case control studies 345

29.6 The problem of possible phenotypic variation of disease caused by BSE prions in humans 345

30 Clinical Findings in Human Prion Diseases / M. Sturzenegger, R.G. Will 347

30.2 Differential diagnosis and additional paraclinical investigations 349

30.3 Clinical features of Creutzfeldt-Jakob disease 352

30.4 Clinical features of variant CJD 355

30.5 Clinical features of Gerstmann-Straussler-Scheinker disease 356

30.6 Clinical features of fatal familial insomnia 357

30.7 Clinical features of sporadic fatal insomnia 359

30.8 Clinical features of kuru 359

30.9 Annex: historical classification 359

31 Methods for the Clinical Diagnosis of Human Prion Diseases / I. Zerr 363

31.2 Electroencephalogram 365

31.3 Analysis of cerebrospinal fluid 366

31.4 Imaging techniques 371

31.5 Sensitivity of clinical diagnostic tests in distinct molecular CJD subtypes 375

31.6 Diagnostic procedure 377

32.2 Passive surveillance for animal prion diseases 383

32.3 "Active" surveillance for animal prion diseases 386

33 Clinical Findings in Bovine Spongiform Encephalopathy / E. Schicker, U. Braun, B. Hornlimann, T. Konold 389

33.2 Clinical history and course of the disease 389

33.3 Differential diagnosis of BSE 390

33.4 General clinical examination findings 390

33.5 Neurological examination findings 390

33.6 Laboratory findings 395

33.7 Examination at abattoirs - a diagnostic challenge 396

34 Clinical Findings in Scrapie / M.J. Ulvund 398

34.2 Case history 399

34.3 Findings of the general clinical examination 401

34.4 Differential diagnoses 401

34.5 Course of the disease 403

34.6 Findings of the neurological examination 404

34.7 Laboratory findings 405

35 Diagnosis of Bovine Spongiform Encephalopathy by Immunological Methods / A.J. Raeber, M. Moser, B. Oesch 408

35.2 Properties of the normal and disease-associated form of the prion protein 408

35.3 Rapid tests approved by European authorities 408

35.4 Ante mortem TSE test development 414

35.5 Identification of atypical BSE strains 416

Topic VI Epidemiology

36 Epidemiology and Risk Factors of Creutzfeldt-Jakob Disease / I. Zerr, S. Poser 423

36.2 Descriptive epidemiology 423

36.3 Risk factors for sporadic CJD 425

36.4 Epidemiology and risk factors of acquired forms of CJD 427

37 Creutzfeldt-Jakob Disease in Germany / I. Zerr, S. Poser, H. Kretzschmar 433

37.2 German CJD surveillance study 433

37.3 CJD epidemiology in Germany 434

37.4 Prognostic factors in sporadic CJD 438

38 The Epidemiology of Kuru / M.P. Alpers, B. Hornlimann 440

38.2 Frequency of cases and progression of the epidemic 440

38.3 The geographical spread and related cultural events 442

38.4 Distribution according to sex and age 444

38.5 Sociocultural background of the sex- and age-specific distribution 445

38.6 Explanation for the survival time curve (time of infection and infectious dose) 445

38.7 Explanation of kuru cases among children (modes of infection) 446

38.8 Conclusion and present significance of kuru 447

39 The Course of the BSE Epidemic-Retrospective Epidemiological Considerations / B. Hornlimann, J.B. Ryan, S.C. MacDiarmid 449

39.2 Basic epidemiological data on BSE in the UK 449

39.3 The factors that determined the course of the epidemic 452

40 The Causes of the BSE Epidemic / S. Dahms, B.

Hornlimann 464

40.2 The case-series study: development of the feed-borne hypothesis 464

40.3 The case-control study: investigations on the feed-borne hypothesis 465

Topic VII Transmissibility

41 The Experimental Transmissibility of Prions and Infectivity Distribution in the Body / M.H. Groschup, M. Geissen, A. Buschmann 473

41.2 Brief historical overview 473

41.3 Design of experimental transmission studies 473

41.4 Experimental transmissibility of human prion diseases 475

41.5 Experimental transmissibility of animal prion diseases 476

41.6 Infectivity distribution in peripheral organs 477

41.7 Pathegonesis studies 478

42 Iatrogenic and "Natural" Transmissibility of Prion Diseases / M.H. Groschup, B. Hornlimann, A. Buschmann 483

42.2 Natural transmission within one species 486

42.3 Natural transmission of scrapie to other species 489

42.4 Natural transmission of BSE to other species 489

42.5 Iatrogenic transmission in human and veterinary medicine 490

42.6 Genetically determined susceptibility 491

Topic VIII Agent Inactivation

43 Inactivation in Practice - Risk Assessment and Validation for Food Gelatin / S.C. MacDiarmid 499

43.2 Raw materials 499

43.3 Dilution 500

43.4 Acid treatment 501

43.5 Alkaline treatment 501

43.6 Further acid treatment 502

43.7 Extraction of gelatin 502

43.8 Experimental studies 502

44 Chemical Disinfection and Inactivation of Prions / B. Hornlimann, W.J. Schulz-Schaeffer, K. Roth, Z.-X. Yan, H. Muller, R.C. Oberthur, D. Riesner 504

44.2 Basic knowledge regarding the chemical inactivation of prions 505

44.3 Prerequisites for the efficiency of chemical disinfectants 506

44.4 Testing for prion depletion and inactivation efficiency 506

44.5 Chemical disinfectants suitable for the inactivation of prions 508

44.6 Chemical disinfectants unsuitable or less suitable for the inactivation of prions 511

45 Thermal Inactivation of Prions / R.C. Oberthur, H. Muller, D. Riesner 515

45.2 Physical chemistry of heat inactivitation of complex biological structures 515

45.3 Kinetics of thermal denaturation and inactivation 516

45.4 Experimental setup for the thermal inactivation of a specimen 517

45.5 Results of inactivation studies 519

45.6 Inactivation of prions under oleochemical conditions 522

45.7 Practical and theoretical implications 523

Topic IX Prevention

46 Prevention of Prion Diseases in the Production of Medicinal Products, Medical Devices and Cosmetics / M. Ruffing, H. Windemann, J. Schaefer 529

46.2 Regulations to prevent the transmission of prion diseases by medicinal products and cosmetics 529

46.3 Evaluation of the risk of medicinal products transmitting prion diseases 533

46.4 Regulations for specific materials used in the production of medicinal products 538

46.5 Regulations to prevent the transmission of prions by medical devices 541

47 Prevention of the Transmission of Prion Diseases in Healthcare Settings / B. Hornlimann, G. Pauli, K. Lemmer, M. Beekes, M. Mielke 546

47.2 Patient care 547

47.3 Risk of accidental occupational transmission in nosocomial and other healthcare settings 547

47.4 Iatrogenic transmission of human TSEs: retrospective findings and current risk assessment 547

47.5 Preventive measures for handling CSF and tissue samples 550

47.6 Transmission through blood and blood products 550

47.7 Precautionary measures to minimize the risk of transmission via surgical interventions on patients with an evident or potential risk of CJD or vCJD 551

47.8 Disinfection and sterilization of instruments and materials 552

47.9 Decontamination of instruments following surgery on patients without any specific signs or symptoms pointing to a risk of transmission 552

47.10 Prevention in specific areas 555

47.11 Handling of corpses prior to interment 557

47.12 Waste disposal in hospitals and laboratories 557

48 Precautionary Measures for Autopsies Performed in Cases of Suspected Prion Disease / W.J. Schulz-Schaeffer, A. Giese, H. Kretzschmar 561

48.2 Performing the autopsy 562

48.3 Decontamination and resistance of the infectious agent 563

49 Prevention of Prion Diseases in Research Laboratories / A.J. Raeber, A. Aguzzi 565

49.2 Risk categorization of prions 565

49.3 Risk assessment for work with prions and prion proteins 566

49.4 Risk classification for work with prions and prion proteins 566

49.5 Containment of laboratory work with prions 567

49.6 Inactivation of prions in research laboratories 567

49.7 Post-exposure prophylaxis following spills and accidents 568

49.8 Further useful information 569

Topic X Risk Assessment

50 Evidence for a Link between Variant Creutzfeldt-Jakob Disease and Bovine Spongiform Encephalopathy / M.E. Bruce, R.G. Will, J.W. Ironside, H. Fraser 573

50.2 TSE strain discrimination in mice 573

50.3 Transmissions of Animal TSEs to mice 574

50.4 Transmissions of vCJD and sCJD to mice 576

51 Risk Assessment of Transmitting Prion Diseases through Blood, Cornea, and Dura Mater / J. Lower, T.R. Kreil 579

51.2 Blood 579

51.3 Cornea 594

51.4 Dura mater 595

52 BSE Risk Assessment and Minimization / R.C. Oberthur, A.A. de Koeijer, B.E.C. Schreuder, S.C. MacDiarmid 601

52.2 Definition of the term "risk" 603

52.3 Dose-response relationship in BSE 604

52.4 Reproduction number 607

52.5 Reproduction number in Great Britain over time 610

52.6 BSE risk minimization within the cattle population 614

52.7 BSE risk minimization from cattle to humans 616

52.8 Control of the efficiency of BSE risk minimization 617

53 BSE control - Internationally Recommended Approaches / S.C. MacDiarmid, P. Infanger, B. Hornlimann 620

53.2 Measures in response to the first case of BSE in a country 620

53.3 Measures for surveillance, prevention, and control of a BSE epidemic 622

54 Atypical Scrapie-Nor98 / S.L. Benestad, B. Bratberg 630

54.2 TSE surveillance program launched for small ruminants 630

54.3 Particularity of clinical signs of atypical scrapie 630

53.4 Particularity of genetics 631

54.5 Particularity of the pathology 631

54.6 Particularity of the diagnosis 632

54.7 The origin of atypical scrapie 633

55 Scrapie Control - Internationally Recommended Approaches / M.G. Doherr, N. Hunter 635

55.2 Criteria to assess the scrapie status of a country or region 636

55.3 Disease monitoring 636

55.4 Measures to control scrapie in a country or region 637

55.5 Historical scrapie situation and potential import routes 638

55.6 National animal identification and tracing system 638

55.7 Genetic influences 638

56 The PrP Genotype as a Marker for Scrapie Susceptibility in Sheep / N. Hunter, A. Bossers 640

56.2 Sheep PrP gene (Prnp) and its variantions 640

56.3 Sheep PrP genotypes and association with susceptibility to TSEs 642

56.4 Methods of genotyping sheep 643

57 Scrapie Control at the National Level: The Norwegian Example / K.R. Alvseike, I. Melkild, K. Thorud 648

57.2 Number of scrapie cases in Norway 648

57.3 Scrapie surveillance 649

57.4 Control and eradication of scrapie 650

57.5 Scrapie prevention 652

Appendix 1 Major Categories of Infectivity (WHO) 657

Appendix 2 Bovine Spongiform Encephalopathy (OIE) 665

Appendix 3 Scrapie (OIE) 671.

Notes:

Includes bibliographical references and indexes.

ISBN:

3110182750

9783110182750

OCLC:

70929266