Index

Note: Page numbers in bold type refer to figures Page numbers in italic type refer to tables

AccuProbe^eCulture Identification Tests 71 acid-fast bacilli (AFB) 33, 120, 161-162, 177, 179, 190, 201, 267, 276, 285-286, 287 acid-fast pathogens 66 acid-fast staining 33, 38 acid-susceptible disruptions 125-126 acidic PH 125 acidification, phagosomal 126 adenovirus-based vaccine (Ad5) 220 adjuvanted LAV 388 adjuvants 111, 192, 220, 252, 367, 368-369, 380, 381, 387, 388-392, 399

Ag85 complex 389-392, 393, 396 agar disc elution protocol 145 agar gel immunodiffusion test (AGID) 164, 165, 180, 193, 355, 356

age, at testing 318 age-associated reduced susceptibility 22 7, 229 age-specific test sensitivity 340 alkyl hydroperoxide reductases (AhpC/AhpD) 6, 113 alpacas 193 analytes 334

Animal Health Law (AHL, EU) 349, 360-361 animal models see models animal waste, samples from 281-282 ante-mortem tests 164, 191, 306, 314, 339 see also antibody ELISAs; diagnosis PCR-based methods; faecal culture anti-mycobacterial therapy, in Crohn's disease 37 antibiotics 33, 3 7, 38, 141, 142, 145, 180, 222, 227, 229, 268, 269, 276, 280, 285 definition 140

in vivo 33

markers 385, 399 resistance 140, 309 triple combination, RHB104 143-144 antibodies 35, 36, 164, 256, 335-337 cross-reacting 338 generation, rabbits 211 antibody ELISAs (enzyme-linked immunosorbent assays) 2, 3-4, 45, 46, 47-48, 50-52, 104, 108-109, 155, 165, 180, 189, 207, 267, 343, 355 advantages/disadvantages 338 antigens tested by 112 bovine 223-226, 356, 356

commercial 193, 337 bulk tank milk (BTM) 4, 256 caprine 228, 230-231 cervid and/or exotic ruminants 191, 237-238

detection

of affected animals 339

of infectious animals 337, 339, 340, 342

of MAP-infected animals 338-339 goat-milk testing 180 IgG₁ 191

in known-infected herds 155 milk 314, 318, 337 pooled 3

Pourquier 337, 339, 340 ovine 233-235, 236 predictive values of 340, 341

antibody ELISAs (enzyme-linked immunosorbent assays) (continued)

sandwich 112 sensitivities and specificities 336 serum 6, 49, 53-54, 56, 57, 317, 337, 339, 356

single 340

tests, sensitivity 108 use of, results on ordinal scale 339-340, 341 antibody-detection-based tests 180, 191 antigens 180, 220, 335-337, 389

diagnostic 105 discriminating 105

M.

MAP 34-35, 108-112, 124

CMI stimulating 111-112 johnin PPD 109-110, 110 multi-antigen studies 108-109 tested by ELISA 112 tested in IFN-γ assay 110-111 protective, failure of 104 rabbits 211

recombinant 111

antihelminth medication 145 antimicrobial susceptibility test (AST)

definition 140

see also drug susceptibility test (DST) antimicrobials 69, 139, 144-145, 268-269 evaluation 282

novel 145

antimycobacterial agents 145 antimycobacterial therapy, for Crohn's disease 3 7 aquatic systems 69

Argentina 85 attenuated vaccines 367, 370

live vector subunit delivery 393-396 Australia

control measures 359

MAP

farm spread and survival 22 transmission 82

National Johne's Disease Program 193 sheep flocks 6

MAP studies 54, 55, 166-167 prevalence 160

vaccination 366

avian tubercle bacillus 65

avian tuberculosis 64, 69

B cell responses 255-256

B cells, subpopulations 256

BACTEC^tm 12B 273, 274, 283, 287, 290

BACTEC^tm 460 239

BACTEC^tm MGIT^tm 960 142, 271 bacterial culture see culture bacterial uptake 248-250

Bactiter GIo^tm 141

badgers 201

Battey bacillus 66-67

BCG 373-374, 381

M.

for MAP antigens delivery 393-396 bedaquiline 144

beef, MAP contamination of 20

beef cattle 20, 46, 350, 359

herd-level prevalence 6, 149, 161 benchmarked multi-antigen studies 108 benchmarking, international, diagnostic testing 316-317

between-herd prevalence/transmission 351, 352, 354, 358

biofilms 69

biomarkers 104, 179 biosecurity 353, 354, 361 birds 64, 65, 69, 201 bison 78, 80, 192, 274-275, 279, 381

BLAST 105

blood, culture 280-281, 315

Bos

indicus 227

taurus 227

bouquet 287

bovine models 221-228, 223-226

long-term 221-227 short-term 228

bovine tuberculosis, vaccination interference with 373, 374

British Royal Commission on Tuberculosis 65 brown hares 201

BTM PCR assay 318-319

bulk propagation 282

bulk tank milk (BTM) 318

ELISA tests 4, 180, 318, 355

MAP contamination 19

PCR-based diagnostics 318, 320

C¹⁴-labelled carbon dioxide 271

calf-to-calf transmission 1

calves 6

diagnostic methods 227

ileal cannulation model 228

intestinal loop model 228

invasion/surgical method 228 management, as control measure 353-354 seropositivity 150

susceptibility to infection 150-151 camelids 78, 80, 93, 105, 192, 193 Canada

dairy study 45

economic losses 7

MAP

isolates 83

prevalence 6-7, 160

candidate gene studies

cattle 49, 50-52

goats 56

sheep 54-55

candidates

for DNA delivery sub-unit vaccines 392-393, 394-395

for LAV 382-384, 385-389 caprine models 228-232, 230-231

goat model 371

long-term MAP challenge 228-229 short-term MAP challenge 229-232

everted intestine sleeve model 229-232 intestinal loop model 229 caprine tuberculosis see goats carnivores 206

transmission to 205 carriers 2, 209, 365, 366 cattle 80, 149-156

breeds 45-46

control measures, tests 356

diagnosis 153-156 diagnostic methods 149 early vaccines for 365-366 faecal shedding 22 faeces ingestion 206 feedlot 6

incubation period 32 infection 121

susceptibility 150-151

LAV testing 387-388 lesions 153, 154, 215 MAP-S group 167 mid-ileal tissues, immunohistochemical staining 257

pathogenesis and infection stages 151-153 pooled faecal culture 2 79 prevalence in 149, 350, 351

pure-bred 6

as reservoirs 32

review of control (2012-2018) 346, 347 risk factors 174

subunit vaccine for 370, 392 transmission, routes 149-150 vaccine trialling 396 see also beef cattle; bovine models; calves; dairy cattle; susceptibility

CD4 36, 129

CD8 129

CD40 signal transduction 124 CD40-CD154 binding 124-125

CD109 54-55

CD209 49

cell counts, microscopic 282-283 cell-mediated immune (CMI) response 111-112, 178, 180, 338

in vitro tests for 355

tests 191, 338, 343

cell-mediated tests 338, 342, 343

cells

B 255-256

bacterial, protein location 106, 106 dendritic cells (DCs) 112, 123 epithelial 107, 121-122 γδ T 129, 164, 178, 215-220, 251, 252 giant 85 monocytic myeloid-derived suppressor cells (M-MDSCs) 255 see also M cells; T cells

Centres for Disease Control and Prevention 142 centrifugation 276, 279, 280 certification 341-342, 349, 354 international trade 360

cervid models 236-239, 237-238 long-term MAP challenge model 236-239 cervids see deer

Cervus elaphus (red deer) 56, 57, 189, 257 models 236-239, 237-238

cheese 20, 22, 280

children 31, 34

Chile 2 76

clarithromycin (CLA) 143

classification, of MAP 121 infected/contaminated 333 re-classification 2

CLEC7A protein 49

Clinical Laboratory Standards Institute (CLSA) 139, 140, 142, 145

clofazimine 37

CMI see cell-mediated immune response colony

counts, on HEYM slopes 283 morphology 286 colostrum, contamination 127, 150 communication

control measures 353 lack 361

compensation, and control measures 352 complement fixation test (CFT) 355 complement receptors 250, 252 compulsory participation, in control measures 352 consensus promotor sequence 92 contact, with infected animals 32 contaminants

effect on MAP identification 288 faecal samples 276

contamination

of animal carcasses 20

BTM 19 colostrum 12 7, 150 faecal 205-206

cultures 290 raw milk 15-19 farm environment 22-23 of feed 205, 206 pastures 7, 23, 206 rates

cultivation 283-285, 284 faecal culture 283

water systems 31

control

deer 191-192

goats 180-181

control measures 346-361

current approaches communication 353 coordination 350-351 diagnostic tools 354-356 funding 351-352 goals, results and success 356-357 incentives 352 leadership 351

in low and middle income countries

357 manual 352 organisation and participation

350-353 participation 352 practices and tools 353-354, 355,

356 research 353 success indicators and outcomes

356-357

eradication 360

issues impeding future control 357-361 funding cessation 359 lack of adherence to movement controls and herd status certification 360-361 lack of communication 361 lack of control in LMICs 358 lack of holistic approach 359 lack of international animal health code 358

lack of performance indicators 358-359

lack of research 359-360 lack of true prevalence data 358 lack of resources in LMICs 357 legal conditions for handling 349-350 long-term 346 objectives 347-348, 349 reasons for having and not 347, 348 review (2012-2018) 346, 347 role of international organizations 348-349 control programmes 155, 156

Australia 166

costs 7-8

early 346

goats 181

Iceland 166

national 380

cooking 21

cow-calf herds 6

CRISPR-Cas-based molecular assays 320

CRISPRi system 98-99, 99

Crohn's disease 142

anti-mycobacterial therapy 37 immunosuppressive therapy 36-3 7

lesions 35

MAP link 29-38, 220, 267, 385 arguments against 31 arguments in favour 30 clinical and pathological comparison 29-30

MAP-C isolates 80

patients

MAP detection in 32-34

and RHB104 treatment 143-144, 145 therapies 143-144, 145

PCR assays 315 cross-species infection 175 crows 201

CTLA-4 253

cull dairy cattle 6 culling 354, 361

costs 8

test-and-cull approach 353, 354, 361, 373 wildlife 208

cultivation 266-291

contamination rate 283-285, 284 culture

media, contemporary 269-270 specific applications 2 75-282 egg yolk requirement 268 general principles, critical steps 170 historical perspective 267-268 in vitro propagation and stability of MAP 282 incubation period 2 75

MAP

enumeration 282-283

resuscitation and growth stimulation

269

sample storage and processing 285 strains and cultural requirements 2 73-2 75

mycobactin requirement 268

other chemical and physical aspects 268-269 quality control 290 tissue samples 2 79

see also culture

culture

blood 280-281

cheese 280

environmental samples 281 faecal 3, 46, 227, 275-279, 288

contamination 283, 290 decontamination 2 75-2 76, 277-278 environmental 281

MAP concentration from 2 76-2 78, 283

pooled 165, 179, 278-279, 318 as gold standard 267, 305, 314, 355, 372 identification of MAP in 285-288

colony morphology 286 effect of contaminants 288 molecular confirmation using IS900 286-287 mycobactin dependency 286 other methods 287-288

in vitro 282

MAP detection by 179, 191

meat 2 79-280

methods comparison 288-290 milk 280

mycobacterial 69

MAP detection by 33, 142, 165 positive 266 protocols 2 76, 277-278

international standards 290 yoghurt 280 culture filtrate proteins 112 culture media

contemporary 269-270

growth 288

liquid 271-273, 275, 287, 288, 290 sensitivity comparison 288, 289 ovine models 232

solid 269, 271, 271, 275, 283, 288, 290 growth rates 290 sensitivity comparison 288, 289 culture-based diagnosis 179

Cyprus 160

cysteine desulfurase 106 cytokines

expression 256-257 proinflammatory 257 regulatory 255 response 128-130, 163, 164, 178, 250-251 cytotoxic T lymphocyte (CTL) 123 Czech Republic 23 CZVaccines 366-367, 367 dairy cattle

control measures 353-354

cull 6

environmental samples 281 herd-level prevalence 4-6, 4, 149, 151 vaccination field studies 373

dairy processing 21-22

dairy products 20, 320 decision making 341-342 decontamination

faecal samples 275-286, 277-278 milk 280

solution 275-276, 285

tissue samples 279

deer 188-193

clinical syndromes 189

farmed 188-189

diagnosis 190-191 disease 189 epidemiology 190 MAP contamination of 20-21 pathology 189-190 prevention and control 191-192

species 188 susceptibility 56-57 wild and captive 188 see also cervid models dendritic cells (DCs) 112, 123 diagnosis 266-267

cattle 153-156

individual cows 355 challenge 108 culture-based 179 deer 190-191 goats 178-180 herd-level 360 immune-based 333-343

antibody ELISAs 338-341 cell-mediated tests 338 decision-making 341-342 establishment of 333-334, 334 immunity and immune-based tests 335-338

test characteristics and biases 334-335

PCR-based methods 179, 305-320 application and interpretation of findings 318-319

choice of target genes 308-309, 309 commercial kits 317

DNA extraction procedures 309-310 PCR techniques 306-308 quality control of assays 315-317 sample-specific techniques and challenges 310-315 sheep 164-165 test validation 316 diagnostic antigens 105, 106 diagnostic assays 153, 164, 165 diagnostic sensitivity (SE) 334-335, 336, 338-339, 342

low 108 values 317 diagnostic specificity (Sp) 334-335, 336, 338-339, 342

diagnostic tests 2, 3-4, 8, 46, 104, 179 AGID 164, 165, 180, 193, 355, 356 ante-mortem 164, 191, 306, 314, 339 cattle

calves 227

for eradication 156 for individual animals 156 in known-infected herd 155 strategies 154-155 to determine herd MAP status 155-156 cell-mediated 338 characteristics and biases 334-335 definitive, cultivation 266 evaluation 335

spectrum bias 335, 336 immunity and immune-based 335-338 diagnostic tests (continued)

immunodiagnostic 164, 165

international benchmarking 316-317 low accuracy 348-349

PDD in 109, 110

point-of-care 319

post-mortem 164, 314, 320

purposes 334, 354-355

results, actions 333-334

strategy 334

used in prevalence studies 2-3

see also individual assay names

diagnostics, PCR-based 308 diarrhoea 2, 6, 29, 149, 151, 152, 153, 156, 161, 175, 176, 193, 221, 339, 342, 347, 373

disruptions, acid-susceptible 125-126 diversity 65, 83

genetic 78, 83, 93, 228-229, 232, 282 strain 76, 290

DNA 314

amplification 306-307

by PCR 3 72

detection 308-309

extraction

dilution of extract 316

procedures 309-310 semi-automated methods 287

M.

magnetic bead-based purification method 310

MAP, PCR detection 305, 306, 308

sequencing 65, 67, 70, 76

vaccination 370

vaccines 399

delivery sub-unit 392-393, 394-395

DnaK 113

dormancy 269

DRB3 gene 56

droplet digital PCR (ddPRC) 307-308, 308

drug susceptibility test (DST) 139-146

definition and description 139-142 for MAP

present 142-145

purpose 142

molecular 143

mycobacterial 140

drug synergy 143-144

dye-based PCR assays 308

dyes 269, 270, 308

antimicrobial 276

economic consequences 7-8, 166 losses

deer 191-192

goats 174

egg yolk 267, 268, 269, 271, 287 see also HEYM

ELISAs see antibody ELISAs (enzyme-linked immunosorbent assays) embryo transfer, cattle 150

endemic disease 4, 8

enteric disease investigation model 236

enumeration, MAP 282-283 environment(al)

management 361

reservoir, MAC 68-69

samples, culture 281, 315

sampling 319

testing 155

enzyme-linked immunosorbent assays see antibody ELISAs

epidemiology 266

deer 190

sheep 166-167

epithelial cells 107, 121

intestinal 121-122

invasion 107, 122

epitope 105

Escherichia coli 108

ethanol-treated protoplasmic preparation 191

European Committee on Antimicrobial Testing (EUCAST) 140

European Food Safety Authority (EFSA) 349

Scientific Panel on Animal Health and Welfare

(AHAW) 150

European Medicines Agency (EMA) 399

European rabbit see rabbits

European Union (EU) 399, 400

Animal Health Law (AHL) 349, 360-361

everted intestine sleeve model 229-232, 236, 249

excreta

wildlife 203, 206

see also faecal entries; faeces

expression library 108 faecal contamination 15-19, 205-206, 290 faecal culture see culture

faecal PCR tests 318

faecal pooling 155-156

faecal samples

contaminants 276

environmental 155, 281 faecal shedding 22, 149, 165, 179, 310 faecal-oral transmission 1, 149-150 faeces

environmental samples 281

excretion, and vaccine effect 372

MAP detection in, qPCR assays 310-313, 311-312

molecular detection assays for 310

PCR-based diagnosis 310-313 rabbits 204

ruminant 310

faeces-avoidance behaviour 205-206 false-positive results 108, 338

FAP 113

farm

environment

contamination 22-23

MAP spread and survival 22-23 samples from 315

farmed deer see deer

farmed ruminants 358 farmers 32, 361 Faroe Islands 82 feed, contamination 206 feedlot cattle 6 ferric uptake regulator (FUR) 126-127 field-based PCR technology 319 financial support 352 flow cytometry 112 fluoroquinolones 144 follow-up testing 318 food

animal-derived 14, 16-18 safety 266 food chain 346, 348 foxes 201, 203

France, early vaccines 365-366, 381 funding

of control measures 351-352, 361 cessation 359

gallium 145

maltolate 144 nitrate 144

gamma radiation 22

γδ T cells 129, 164, 178, 215-220, 251, 252

gene expression programmes 125-127, 252

gene set enrichment analysis (GSEA) 53

gene set enrichment analysis-SNP (GSEA-SNP) 53-54 gene sets 53-54

genes

leading-edge 54

MAP 122, 123-124

unique 105

multicopy 309 mutants 125

mutations 35-36

and phenotypic antibiotic resistance 142, 143

silencing 99

target 309

for PCR 308-309, 309

virulence 107

genetic diversity 78, 83, 93, 228-229, 232, 282 genetic polymorphisms 78

genetic susceptibility to infection

cattle 151

goats 174

sheep 161

genetic variation 71

genetically modified attenuated vaccines 3 70 genetically modified organisms (GMOs) 399, 400

GeneXpert MTB/RIF assay 143

genome, MAP 105

genome sequence 130 genome sequencing 34, 66, 76-77, 105

benchtop next-generation platforms 93

see also whole genome sequencing (WGS) genome-wide association studies (GWAS)

cattle 46-49, 47-48

goats 56

sheep 54

genomic comparison of MAP strains 76-80, 81-82 genomic differences among MAP strains 78-79 genomic manipulation 386 genotyping 34, 38, 46, 83

bacterial 38

tools, limitations 83 geographical distribution, MAP strains 82 giant cells 85 glycolipids 106

glycopeptidolipids (GPLs) 70, 106, 107 goats 174-181, 220

attenuated live vector subunit delivery vaccines 396

breeds 55-56

control 180-181

diagnosis 178-180

culture-based 179 immunological methods 180 PCR-based methods 179

herd-level prevalence 5, 6-7, 55

host and pathogen factors animal risk 174-175 environment and management risk

172

pathogen risk 175

infection

and disease 175-177 route and transmission 177 stages 175

infection and disease characteristics clinical signs and pathology 175-176 pathology, gross and microscopic lesions 176-177

LAV testing 387, 388

pathogenesis 177-178

raw milk 17, 19

study of recombinant proteins in 111 treatment 180

see also caprine models

Golgi apparatus 56

good manufacturing practice (GMP), regulations 400 granulomatous lesions 121, 177, 256 grazing livestock 281

gut-associated lymphoid tissue (GALT) 248

Haemophilus influenzae 105

Hain Lifescience 71

heat shock protein 70 6, 256, 391 herd-level prevalence 4-7, 350

cattle

beef 6, 149, 161 dairy 4-6, 4, 149

deer 189

goats 5, 6-7, 55 sheep 5, 6-7

wildlife 7

within-herd 6, 93, 149 herd-level testing 108, 318 herds

classification programmes 349 prevalence reduction in 348 heritability

cattle 45-46

deer 57 goats 56 sheep 54 hexadcyl pyridinium chloride (HPC) 2 76, 277-278,

279, 285, 288

HEYM (Herrold's egg yolk medium) 271, 271, 275, 276, 288, 290

Hidden Markov Model 100 high income countries (HIC) 359 high-performance liquid chromatography (HPLC) 70 high-resolution melt method 70

high-temperature, short-time (HTST) pasteurization 21 Himlar 1-derived transposons 96, 97 histopathological lesions

deer 190

goats 177

holistic approach, lack of 359 homogenization 21

host

cells, MAP effects on 127

immunity 248

preference, MAP 80 reservoir 206 susceptibility 45 to MAP infection

alternative response 129-130 non-ruminant wildlife 200-204, 202-203

host-pathogen interactions 120-130 hot spots 204, 208

HPC 276, 277-278, 279, 285, 288 human disease 347

and M.

management 142

and MAP 347

see also Crohn's disease human exposure 23, 31-32, 68-69 humans, MAC epidemiology in 68 humoral immune responses 178 humoral immunodiagnostics 343 hydrostatic pressure 22 hygiene 19, 175 iceberg phenomenon 2-3, 151, 151

Iceland

MAP in sheep study 166 sheep-cattle cross-transmission 82 vaccination 366

IdeR 126

IFN-γ release assay 4, 105, 165, 178, 180, 252, 255, 337, 338, 342

in vitro 338, 355-356

MAP antigens tested in 110-111 sheep 251

IgG1 antibody ELISA 191 reactivity 335-337

IL-1α 128

IL-4 253-254

IL-10 129, 178, 250, 254, 255

IL-12 125, 251-252, 254

IL-17 129-130, 253

IL-18 252

IL-22 129

IL-23 129, 130

ileal cannulation model 228, 236

ileal loop model 254

ileal Peyer's patches, in sheep 162 ileum 249

immune responses 333 adaptive 220 cell-mediated 111-112, 178 in Crohn's patients 34-36 host, polarizing 84 immune-based diagnosis see diagnosis immune-based diagnostic tests 337-338, 343 immunity

host 248

and immune-based diagnostic tests 335-338 advantages and disadvantages 338 antigens and antibodies 335-337 immunological responses 335 types of test and sample material 33 7 trained 381-385 by vaccine 365

immunocapture techniques 310 immunodiagnostic tests 164, 165 immunohistochemical staining 257 immunohistochemistry (IHC) 180 immunological responses 335 stimulating 385

immunology 248-257 bacterial uptake 248-250 early infection, macrophage-T-cells interactions 251-252

early-to late infection transition 252-253 innate response to infection 250-251 late infection

B cell responses 255-256

T regulatory cells 255 T-cell responses 253-254 of MAP infection 38 immunopathogenesis, of MAP, study 220-221 immunopathology 256-257 immunosuppressive therapy 36-37, 38 impacts of paratuberculosis 347 in vitro assays 386

in vitro growth, MAP 139, 145, 146, 267, 269 in vitro propagation, and stability of MAP 282 in vitro tests, for CMI response 355 inactivated vaccines 367

incentives, control measures 352 incubation period 4, 32, 69, 149, 156, 167, 275,

285, 334

in cultivation 179, 268, 270, 274, 275, 277-278, 280-281, 288, 290 double 277-278, 285 outcomes 334

shorter 142, 149

India

goats susceptibility study 55 river water 23

riverine buffalo 192 sheep susceptibility study 54 transmission 82

Indian Bison type genotype 78, 80, 192,

274-275, 381

infant formula 20 infected animals, contact with 32 infection

alternative host response 129-130 bovine models 221-228, 223-226 caprine 228-232, 230-231 cattle 149-150, 151-152 susceptibility 150-151 cervid models 236-239, 237-238 cross-species 175 detection 45 early 251-252

early-to late transition, T-cell subpopulations 252-253

experimental, lambs 85

fetal 150

free of 342

goats 177-178 innate response 250-251 late

B cell responses 255-256

T regulatory cells 255 T-cell response 253-254 macrophage responses 121, 122, 124 multibacillary 55

in sheep 55, 161-162, 163-164, 165 murine models 214-220, 216-219, 222 ovine models 225-227, 232-236 paucibacillary 55

persistence, non-ruminant wildlife 206-208 progression between 335, 337 protocol, MAP strains 123-124 route

limitation 353

in sheep 162

ruminants 380

spread 373

sheep 166-167 stages 2-3, 151, 151

I (silent) 152, 175, 177

II (infection progresses/subclinical)

152, 156, 175, 177, 189, 266

III (clinical disease) 152-153, 175,

176, 189

IV (advanced clinical disease) 153, 176 studies 31-32

see also incubation period; resistance; susceptibility; transmission; virulence

Ingenuity Pathway Analysis (IPA) 53, 55 innate response, to infection 250-251 Inno-LiPA® MYCOBACTERIA V2 71 inocula

bovine 212

caprine 229

inoculation

bovine 212

oral 211, 214 rabbits 211 iNOS 125 insertion sequences

PCR-based detection 33, 70

see also IS entries

integrin receptors 249

interferon-γ assays see IFN-γ release assay internal amplification control (IAC) 315-316 internal extraction control 315 international animal health code 358 International Association for Paratuberculosis, guidelines 349, 360 international organizations, control measures' role 348-349

international trade, certification in 360 International Working Group on Mycobacterial Taxonomy (IWGMT) 67

interspecies transmission 205 intestinal epithelial cells 121-122 intestinal lesions 176-177, 176 intestinal loop model 228, 229, 236 intestinal mucosal cells 153, 153 intestinal tissues, culture 314 intra-peritoneal injection (IP) 214 intracellular metal homeostasis 126 intracellular signalling, in MAP-infected macrophages 127-128 intracellular survival, of MAP 121-125, 127-129 intradermal tuberculin test 338 intrauterine transmission, deer 190 iron

homeostasis 145

MAP requirements 126, 127

15900 33, 70, 179, 308-309, 316 molecular confirmation using 286-287

IS900-based PCR 287, 288

15901 70 IS1245 70

isolates 64, 65, 84, 275 bovine 93 from goats 175, 228-229 human and bovine-derived 34 human origin 83

MAP-C and MAP-S 80

isothermal assays 319

Italy 32

ITS sequevars 70 jackdaws 201

jejunal Peyer's patches 162

jejuno-ileal loop model 128

jejunum 249

Johne's disease 65, 149

qPCR test standardization 317

Johne's Disease Integrated Project (JDIP, AMSC) 213 johnin 109-110, 110, 110, 337

skin test 180 knockout vaccines 3 70

knockouts, single/double gene 386

knowledge gaps 8, 353 laboratory-based diagnostics 319 lambs

experimental infection 85 for experimental studies 236 intratonsillar route 162 latent TB infection (LTBI) 256 LAV see live-attenuated vaccine (LAV) leadership, of control measures 351, 361 leading edge genes 54 legislation 399 legislative document 352 Leishmania major 125 leporid model 214, 220-221, 222 leprae reactions 35 leprosy 35, 36 lesion grading system 236 lesions 85, 127, 153, 154

camels 193

cattle 153, 154, 215

Crohn's disease 35 deer 190-191 early 129 goats 176-177, 176 granulomatous 121, 177, 256 histopathological 177 intestinal 176-177, 176 macroscopic 176 non-ruminant wildlife 201 rabbits 201 sheep 161-162, 163, 165 grading system 162

spectrum 177

line probe assays (LPAs) 71

lipid antigens 105, 112 lipids 55, 105, 106-107, 110, 124, 144 lipoarabinomannan molecule 107 lipopeptides 106, 107 lipoproteins 106-107 lipotripeptide (L3P) 107

live vector subunit vaccines 399

tested in animals 393-396, 397-398 live-attenuated vaccine (LAV) 220, 370, 381, 385-389, 399

adjuvanted 388

tested in animals 382-384

testing 399 whole-cell 385-389

livestock, movement control measures 360 livestock-to-wildlife transmission 205 LJ medium 271, 271, 276, 290

llamas 193

loci identification 45-49, 54

low and middle income countries (LMICs)

control measures 357, 358

resources need 361

LuxR transcriptional regulator 107 lymph nodes 55, 85, 121, 12 7

carnivores 205

cattle 152

cultures 314

contamination 283

deer 189-190

goats 176-177, 179 mesenteric 179, 189, 192, 193, 201, 221, 227 sheep 163-164, 283

supramammary 320

lysis 309-310

M cells 121-122, 122, 152, 248-249

goats 177

in sheep 162-163 M7H9C medium 273, 274 macaques 201 macrophages 36, 122, 123, 152, 162, 175, 250

genetic responses of MAP strains 84

local 257

MAP-infected 125, 127, 128-129, 177 intracellular signalling in 12 7-128 murine 124

studies 215

receptors 123

responses 121, 122, 124, 178 macrophage-T-cells interactions 24, 251-252 Madin-Darby bovine kidney cells (MDBKs) 121, 122 magnetic bead-based DNA purification method 310 major histocompatibility complex (MHC) see MHC major membrane protein (MMP) 122-123 MALDI-TOF MS 70, 287

ManLAM 123

ManLAM-DC-SIGN interaction 123

manual, control measures 352 manure 282

sampling 155

MAP 65

definition 267

DNA 32

freedom from 349

gene expression programmes 125-127 genome 105

genomic epidemiology 80-83

host preference 80 transmission 82-83

sequencing project 93, 94-95

strains 2 73-2 74

bison 70, 80, 192, 274-275, 279, 381 bovine K-10 221-222, 239 diversity 76, 290

genetic response to macrophages 84, 123-124

genomic comparison of 76-80 genomic differences among 78-79 geographical distribution 82 infection protocol 123-124

LAV candidates 382-384, 385-389 libraries for LAV vaccines 386-387 non-ruminant 201

phylogenetic relationships among

77-78

316F 313, 367

typing assays 306

virulence and pathogenicity comparison 83-85

virulence and pathogenicity insights 80, 81-82

see also MAP-C group; MAP-S group see also molecular genetics

MAP 185 143

MAP 0403 107

MAP 825 105

MAP 1203 105, 107

MAP 2609 108

MAP 282 7 126

MAP 2942c 108-109

MAP 3464 122

MAP-C group 66, 76, 77-78, 80, 84, 273-274 annotated genome sequence 76-77 deer 190, 239 goats 175 immune responses, in vitro and in vivo 85 open reading frame (ORF) clusters 78, 79 sheep 161, 167 sub-lineage 78

Indian Bison type 78, 80, 192, 274-275, 381

virulence 84

MAP-S group 66, 76, 77-78, 84, 273-275 cattle 167

cross-species transmission 82

culture media 288

goats 175

host preference 80

in vitro 224

open reading frame (ORF) clusters 78, 79 sheep 161, 166, 167 sub-lineages 78 virulence 84

whole genome sequence 76-77

MAPK (mitogen-activated protein kinase) pathway 124, 128, 250

markers 95, 98

Treg 255

Market Assurance Progams 352

MarP 126

master seed stocks, storage 399 mathematical modelling 208 vaccines 3 71-3 72

meat

culture 2 79-280 products 20-21

PCR tests for 320 medicine 266 metabolic pathways 84 metabolism 141

metal homeostasis, intracellular 126 metalloregulators 126

MGIT^tm (Mycobacteria Growth Indicator Tube) 141, 142, 273, 274, 288

MHC 163, 250

Class II molecules 55

molecules, mutations 50-52, 55

MIC (minimum inhibitory concentration) 141, 141 to RIF 142, 143, 143

mice (mouse) 124, 126, 255 attenuated live vector subunit delivery vaccines 396

knockout strains 215

LAV testing 387, 388 models 213-214, 222, 3 71, 396

MAP infection 215-221 purified protein vaccine testing 389 Michigan State Laboratory 99

Middlebrook 7H9 271

Middlebrook liquid and solid media 271, 272-273 milk 320

contamination 19, 127, 150 control measures in 352 culture 280

contamination 285

sensitivity 288 decontamination 280 diagnosis from 313-314, 313, 314 economic losses 7

ELISA tests in 3, 112, 180, 337

MAP evidence in 17, 19-20, 21, 30-31

on-farm 313-314

raw 14-19, 15

pasteurized 17, 19-20, 21, 31

milk (continued)

processing techniques 21-22 raw

faecal contamination 15-19

MAP evidence in 14-19, 15 PCR 19 sampling 338

minimum inhibitory concentration (MIC) see MIC miRNA biomarkers 320

MIRU-VNTR 76 modelling

dairy cattle control measures 354 mathematical 208, 371-372

models 213-239

bovine 221-228, 223-226 caprine 228-232, 230-231 cervid, red deer 236-239, 237-238 goat 371

herd-level monitoring 360-361, 360 mouse 371, 396

rabbit 214, 220-221, 222, 371

rodent 213-221

ruminant 215, 371, 396 simulation 3 73

vaccine 216-219, 220, 370-372, 373

in vitro and ex vivo 3 71

in vivo 371

see also murine model; ovine models molecular detection assays 310, 314, 319 molecular genetics

of MAP 92-100

CRISPRi 98-99

genome sequence 93

isolation of deletion mutants 97-98 key tools (1993-2008) 92-93, 94-95 mutant complementation studies 98 transposon mutagenesis 93-97 molecular tools 93 monetary losses 7-8 monitoring

after herd-level diagnosis 360-361 suggested model 360-361, 360 disease progression 385

monocyte-derived dendritic cells (MoDCs) 123 monocytes 371

monocytic myeloid-derived suppressor cells

(M-MDSCs) 255

Moredun Research Institute 366 Morocco 82 mortality

disease-induced, primates 201 reduction 374

mouse models see mice

movement controls, guidelines for 360 mptG gene 107

multibacillary infection, in sheep 55, 161-162, 163-164, 165

multicopy genes 309 multiple RNA 320 multiplex bead-based immunoassay 109 multiplex qPCR assays 307 murine macrophages 124, 215

murine model 214-220, 216-219, 222 disadvantages 214-215 key features 214-215

mutagenesis, transposon 93-97, 99, 107 mutants 92, 107, 125, 146, 214, 215, 220, 370, 388 deletion 97-98

gene 125

libraries 96-97, 96, 125 transposon 92, 93, 97, 215

mutations, MHC molecules 50-52, 55 mycobacteria 35, 120, 309

Group III taxonomy 67 pathogenic complexes 120

Mycobacteria Growth Indicator Tube (MGIT^tm) 141, 142, 273, 274, 288

mycobacterial acid resistance protease (MarP) 126 mycobacterial interspersed repetitive units-variable- number tandem repeats (MIRU-VNTR) 76 Mycobacterium

avium, subsp. hominissuis 65, 127, 128 avium avium 64-66, 122

and human disease 65

M.

bovis 65, 93, 120, 167

BCG 387

intracellulare 66-67, 69

johnei 221 leprae 36, 177 Iepraemurium 66 smegmatis 126 tuberculosis 126, 255, 256

attenuation 385-386

complex 120

DST 140, 141-142, 145

protein array 108-109 resistance 141

vaccination in non-human primates study 385

vacuoles 123

see also MAP

Mycobacterium avium Complex (MAC) 64-71, 120 classification 69-70

diagnostics 69-71

commercial assays 71

culture and traditional methods 69-70 DNA sequencing 70

other molecular assays 70 environmental reservoir 68-69 M. intracellulare 66-67, 69 in molecular era 67-68 taxonomy 67, 68

Mycobacterium avium-intracellulare complex 67 mycobactin 268, 271

dependency 286

Mycoplasma agalactiae 108 myeloid regulatory cells (MRCs) 255 n-arylpiperazine 144 nanoparticles 319-320 NaOH-OA protocol 276, 278, 285 national regulation authorities (NRAs) 399 neonates 248

Netherlands 352

New Zealand 6, 82, 167, 189, 400

New Zealand White Rabbit 213

Nocardia intracellularis 66

NOD2 49

non-denaturing (native) gel electrophoresis 106 non-ruminant model 387 non-ruminants see wildlife

non-tuberculosis mycobacteria (NTM) 140 Norway 6

notifiability 349-350

nuclear factor kappa beta (NFKB) 53

pathway 124

nucleic acid amplification-based tests (NAATs) 305 occupational risk 32, 38

oedema 161

OIE see World Organization for Animal Health (OIE) oleic acid 269 opsonization 250

oral inoculation 214, 229, 232

ovine models 225-227, 232-236

long-term MAP challenge 232-236 short-term MAP challenge 236 ovine paratuberculosis 167

Para-LP-01 106-107

Parachek™ ELISA 165

Paralisa test 191

participation

in control methods 352

and organisation of control methods

350-353

pasteurization 21, 150

pasteurized milk, MAP evidence in 17, 19-20, 21, 31 pastures, contamination 7, 23, 206 pathogen recognition receptors (PRRs) 249 pathogenesis

cervids 189

models 211

pathogenicity

of MAP strains 80, 81-82

comparison 83-85

pathogens

acid-fast 66

detection by qPCR 307

host-, interactions 120-130

success traits 121

pathology

deer 189-190, 239

non-ruminant wildlife 201

sheep 161-162

pathway analysis

cattle 53-54

deer 57 sheep 55 pattern recognition receptors (PRRs) 163 paucibacillary infection 55

in sheep 161-162, 163

PCR (polymerase chain reaction) 3, 83, 165, 355 confirming identification 316 diagnosis by 179, 305-320 faecal tests 318 field-based technology 319

IS detection 33, 70 IS900-based 287, 288 MAP tests, dairy and meat products 320 nested 306 target genes choice 308-309 techniques

conventional 306 droplet digital (ddPCR) 307-308, 308 real-time/quantitative (qPCR) 306-307 viable MAP detection 308

PCR-based assays

diagnosis, using milk 313, 314, 314 gold standard for diagnosis accuracy 316 PCR-based methods

diagnosis 179

faeces 310-313

quality control of assays, assay validation 316 PD-1 expression 253 penalties, avoidance of 352 performance indicators, lack of 358-359 peripheral blood mononuclear cells (PBMCs) 111 Peyer's patches 162, 248-249

P_f 342

phage-based assays 24, 308 phagocytes 250, 255 phagocytosis 12 7 phagosomal acidification 126 phagosomes 250 phagosome-lysosome fusion 123 phenotypes 46 phenotypic antibiotic resistance, and gene mutations 142, 143

pigmentation 78

plasmids 370, 392-393, 399, 400 point-of-care (POC) diagnostic tests 319 polymerase chain reaction see PCR polymorphisms, genetic 78, 80 polyoxyethylene stearates (POES) 269 pooled faecal culture 165, 179, 278-279, 318 Portugal 23 post-mortem tests 164, 314, 320 Pourquier milk ELISA 337, 339

Pourquier serum ELISA 339 PPD-P 337 predators 205 prevalence

between-herd 351

in cattle 149, 350, 351 global 4, 4, 5 in goats 174

in herds, reduction 348

non-ruminant wildlife 203-204, 209

in sheep 160 true data 358 within-herds 350, 358 see also herd-level prevalence prevention

in deer 191-192

see also control measures; control programmes, vaccination prey species 203, 205 primaquine 144-145, 145 prime-boost vaccination 3 70 processed food 7 processed meat 280 production parameters 342 promotor upstream sequence 92-93 prophylaxic vaccines 399 protein expression, profiling studies 79, 85 protein-based vaccines

sub-unit 389-392, 390-391 purified 389-392

tested in animals 389, 390-391 proteins 389

complexes 105-106 MAP 105-107 cell location 106, 106 functional characterization 105-106 lipoproteins 106-107 PDD 110, 110 virulence 107

recombinant 111 proteomic advances 104 proteomic research 104, 105, 109, 110, 112-113 proto-spacer adjacent motifs (PAMs) 98 PtpA 112, 113 public health 266

authorities 347 concerns 7 pulsed electric fields 21 purified protein derivative (PPD) 104

johnin 109-110, 110, 110

MAP 110

qPCR (real-time/quantitative) 306-307, 318, 319 assays

multiplex 307

to detect MAP in faeces 310-313, 311-312

assessment 317

commercial diagnostic kits 317

and MAP extraction 317

tissue 314-315

quality control

of assays

confirming PCR identification 316 international benchmarking 316-317 validation 316

cultivation 290

quantitative faecal PCR tests 191

quarantine 161

quinolones 144

Rab7 function 12 7

rabbits

faeces 204

farmed 21

histopathology 201

infection

levels after cattle control 206-208, 207 risk from 207-208, 209

models 214, 220-221, 222, 371

population management 208

transmission by 204-205, 206

as wildlife host 200

radiometric BACTEC^tm 12b medium 283

radiometric growth indicator 2 71

recombinant antigens 111, 112

red deer 56, 57, 189

models 236-239, 237-238

Treg gene expression 257

RedHill Biopharma 37

RHB-104 3 7, 38, 143-144, 145 regulations, GMP 400 regulatory cytokines 255 regulatory issues

in vaccines 399-400

zero-risk compliance 400

Resazurin Microtiter Assay (RMA) 141 research

into control measures 353

lack 359

reservoir host 206

reservoirs 385

cattle 32

environmental, MAC 68-69

infection 208

wildlife 7

resistance 141

in cattle 150-151

in deer 190

definition 139-140

in goats 174

in sheep 164

RHB-104 3 7, 38, 143-144, 145

ribosomal inhibitors 143

rifabutin (RFB) 142

rifampicin (RIF) 142

risk

from rabbit infection 207-208, 209 goats 174-175 status 360

river water 23

riverine buffalo 192-193

RNA sequencing 178

rodent models 213-221 leporid models 214, 220-221, 222 MAP infection models 215-220 MAP vaccine 220

see also mice (mouse); murine model rodents 205, 206

RPA assays 319 ruminant models 215, 371, 396 ruminants 310, 359 farmed 358 infection 350, 380 running-free 350 runoff 23

Salmonella enterica 396 samples, viability 285 sampling, environmental 319 Sanitary and Phytosanitary Agreement (SPA, WTO)

349 scavenging 205, 206 Scotland 192, 204, 205 screening, in vitro 104 SDS-PAGE separation and immunoblot study 109 sedimentation 276, 277-278 semen, cattle 150 sensitivity, low 108 sequencing

DNA 65, 67, 70, 76 genome 66, 76-77 project, MAP 93, 94-95 see also whole genome sequencing (WGS) seropositivity 35, 150 seroprevalence 175 serotyping 70 serum ELISA 33 7, 339 shedding 165, 340, 341

after inoculation 227

faecal 22, 149, 165, 179, 310

patterns 3

rates, non-ruminant wildlife 204 sheep 160-167

breeds 54-55

cytokine gene expression in 257 disease pathology, strain-specific differences 85

DNA vaccine delivery 393 early vaccine for 366 faeces ingestion 206 herd-level prevalence 5, 6-7 host and pathogen characteristics 160-161 breed, age and sex 160-161

MAP strain 161

IFN-γ responses 251-252 immunodiagnosis 165 infection characteristics and disease

161-164

clinical signs and clinical pathology 161 immunopathobiology 163-164 infection route and transmission

162-163

pathology, gross and microscopic lesions 161-162 infection spread (epidemiology) 166-167 LAV testing 388

MAP

dissemination and propagation 163 strain 161

microbiological diagnosis 164-165

culture 165

PCR 165

pooled faecal culture 2 78-2 79

raw milk 19

see also lambs; ovine models; susceptibility shuttle plasmid vectors 93, 94-95, 96 SigE 125 SigH 97, 107, 125

SigL 98, 107 signal amplification 320 simulation

model, vaccination versus testing and culling 3 73

studies, vaccines 3 71-3 72 single nucleotide polymorphism (SNP) assays 46,

78, 83

skin test 338, 355

SLC11A1 protein 49, 56 sodium pyruvate 268 soil 281

South Africa 352

Spain 82, 366

spatial clustering 204

Speed-Oligo® Mycobacteria Assay 71

SSR typing 83

staining

acid-fast 33, 38 immunohistochemical 257 stakeholder support 353, 359, 361 standardization, of assays 317 status, MAP 360 steam injection, direct 22 stoats 201 stock movement guidelines 349 strains see MAP stress-response sigma factors 125 stressors 125 String analysis 106 subunit vaccines see vaccines success indicators, control measures 356 supershedders 19, 22, 83 surveillance, herd-level 318-319

susceptibility 45

age-associated reduced 227, 229

cattle 45-55, 150-151

calves 150-151

deer 55-57, 189, 190

differences in cattle 45-55

candidate gene studies 49, 50-52, 55 genome-wide association studies 46-49 heritability 45-46

pathways and gene set analyses 53-54

differences in deer 55-57 heritability 57 pathway analysis 57

differences in goats 55-56 candidate gene studies 56 genome-wide association studies 56 heritability 56

differences in sheep 54-56 candidate gene studies 50-52, 54-55 genome-wide association studies 54 goats 55-56 heritability 54 pathway analysis 55

genetic 151

goats 55-56, 174, 175

sheep 54-56

see also drug susceptibility test (DST) sustainability, control by vaccination 3 73 swine 64

Switzerland 355

T cells 35, 110, 112

γδ T cells 129, 164, 178, 215-220, 251, 252 macrophage-, interactions 124, 178 regulatory (Tregs) 125, 253, 255 response, to late infection 253-254 subpopulations 252-253 target

conditions 334

genes, for PCR 308-309, 309

protein vaccine 389-392, 390-391

TB, human 256

temporal variation 204 test-and-cull approach 353, 354, 361

versus vaccination 3 73

testing

environmental 155

follow-up 318

herd-level 318

purpose 343

repeated 338

tests see diagnostic tests; drug susceptibility tests (DSTs); individual assay names

Tetracore VetAlert™ 317

TGFβ 125, 255, 257

Th1, immune response 110, 112, 129, 220, 253 Th2 129, 220, 253

Th17 130, 155

Th17-like response 129-130

tissue

culture 320

MAP detection in 314

infection 53

intestinal, contamination 283 qPCR 314-315

samples 227, 279, 285

Tn5367 93-96, 97

Tn5370 96

TNF α 36-3 7, 38

TNF receptors 128

Toll-like receptors (TLRs) 49, 249, 250

TRAF1 128

trained immunity 381-385

innate 374

transforming growth factor beta (TGFB) 54 transmission 1-2, 82-83, 121

animals-humans, BRCT study 65 between-herd 93, 354 in cattle, routes 149-150 cross-infection to domestic animals 175 cross-species 82

deduction 342

deer 190

epidemiological evidence 30-32 Europe 82

interspecies 205

intrauterine, deer 190 livestock-to-wildlife 205 non-ruminant wildlife 204-205 prevention 3 72

route 248

wildlife-to livestock 205-206, 209 within-herd tracking 93 transposons

Himlar 1-derived 9 mutagenesis 93-97, 99, 107 mutants 92, 93, 97, 215

Tregs 125, 253, 255

gene expression 257

markers 255

types 255

tuberculosis 68

turbidimetric estimates 283

Tween (polyoxyethylene sorbate) 269 ultraviolet light treatment 22

underreporting of MAP 350

United Kingdom (UK)

control measures 352

transmission 82

United Nations (UN), Development Program index 346 United States of America (USA)

bison 192

early vaccines 366

economic losses 7

GMO legislation 399

MAP spread and survival 22

National Animal Health Monitoring System (NAHS) 149

within-herd prevalence 6

urine shedding 204 vaccination 104, 179, 354, 358, 361, 365-3 74

Australia 6, 166

in bovine models 22 7

deer 192

general considerations and history 365-367 goats 181

Iceland 166

large-scale programme 380 particularities of field evaluation 372-374 clinical and productive indices 373 interference with bovine tuberculosis

diagnosis 3 73 microbiological variables 372 pathological variables 373 unspecific effects 373-3 74 versus testing and culling 3 73 prime-boost 370 studies 256

leporid (rabbits) 211

see also vaccines

vaccines 181, 192

adenovirus-based (Ad5) 220 adjuvants 111, 192, 220, 252, 367, 381,

387, 388-392, 399

assessing efficacy in animals models 396-399 attenuated 367, 370, 393-396

batch testing 400

delivery 385, 399

optimal live vector 393 toxicity towards vector 396 development goal 385 DNA delivery sub-unit 392-393, 394-395 early, France 365-366, 381 effect, failures 380-381 evaluation 3 72

protection criteria 372, 372

formulation 104

gold standard 385, 388, 399

history 381

immunity from 365

in vivo models 371

live vector subunit 393-396, 397-398 models 216-219, 220, 3 70-3 72 in vitro and ex vivo 371 mathematical modelling and simulation studies 3 71-3 72 new development 380-400 live-attenuated whole-cell vaccine (LAV) 220, 370, 382-384, 385-389

novel live 388-389

production 366-367, 367

prophylaxic 399

regulatory and production issues 399-400 sales 367

study, murine 214 sub-unit 3 70, 3 71, 381

protein-based 389-392, 390-391 trialling framework 386-387 types 367-370, 368-369

commercial 367

LAV 220, 3 70

vacuoles, M.

vancomycin 273

vectored DNA vaccine 369

venison 21

Veterans Administration-National Tuberculosis Association Cooperative Study of Mycobacteria 66

veterinarians 32

veterinary diagnostics, point-of-care in 319 virulence

factors, in murine models 215

MAP protein 107

of MAP strains 80, 81-82, 85 comparison 83-85

pathways 130

volatile emissions 287

volatile organic compounds 179

Wales 23

Walter-Reid medium 2 71, 272-273 waste, animal, samples 281-282 water

dam 22-23

drinking 23

samples from 315

systems, contamination 31

treatment 23

weaning weights 7

weasels 201

white-tailed deer 239

whole genome sequencing (WGS) 76, 83,

85-86, 93

study 77-78, 77

wildlife 93, 359

herd-level prevalence 7

MAP infection 350

MAP-S strains in 80

non-ruminant 200-209

control 208-209 epidemiology 204-208 host infection 200-204 host range 200-201, 202-203 infection persistence 206-208 pathology 201 prevalence and excretion rates 203-204 transmission 204-205 transmission by livestock to 205 within-herd prevalence 350, 351

wood mouse 201

wood pigeon bacillus 65

World Organization for Animal Health (OIE) 4, 316,

348

list of notifiable animal diseases 4 manual 316

tests overview 355

World Trade Organization (TWO) 349

Sanitary and Phytosanitary Agreement (SPA)

349

Xpert MTB/RIF 319 yoghurt 20, 22, 280

Ziehl-Neelsen (ZN) stain of faecal or tissue smears 356

Zwitterionic detergent CB-18 2 79