Index

A history, 138 AB128, 258 infection and transmission, 140–142 AB129, 258 other species, 148 AB130, 258 sheep skin biopsy, 141, 145 Acanthamoeba, 73, 285 treatment, 146–148 Acaricidal drugs, 147 , 215, 243, 285, 467 Actin-based motility (ABM), 423, 424 family, 9, 10, 71–72 Acute fever, 126 pathogens, 215, 216 Acute illness, 47 , 6–7, 100–101, 103–104, 119, 120 Acute respiratory distress syndrome (ARDS), Ankyrin repeat proteins, 179, 230 127, 131, 351, 392 Anopheles gambiae (African malaria Adhesins, 141 mosquito), 407 Adhesion of rickettsiae (Adr) 1 protein, 414 Antibiotic treatment, clinical rickettsioses ADP ribosylation factors (Arfs), 430 HGA, 117, 118 Aedes albopictus (Asian tiger mosquitoes), 407 HME, 117 , 96, 97 murine , 116 Agrobacterium tumefaciens, 429 RMSF, 114, 115 Allophycocyanin (APC)-conjugated , 117 fluorotag, 209 SFGR, 115, 116 endosymbionts, 7 typhus, 116 Amblyomma americanum, 219, 232 Antibodies, polyclonal, 33 Amblyomma maculatum, 43 Antigenic variation, 142 Amblyomma ticks, 244, 245, 250 Antigen-presenting cells (APC), 419, 421 Amblyomma variegatum, 246, 247, 251, 253 Antimicrobial agents, , 111–114 Amino acid sequence Antimite fluid, 360 Ehrlichia Hsp60, 188 Anti-rickettsial serologic testing, 99 P28-19, 187 Anti-SFG IgM, 99 Anaplasma, 3, 215, 299 Anti-Wolbachia Consortium (A⋅WOL), 503 fatal human diseases, 216 Apoptosis, 423 mutagenesis, 216 Aquatic organisms, Rickettsiales, 59, 60, mutational analysis, 216, 217 64–82 pathogens, 215 aquatic Anaplasmataceae, 71–72 Anaplasma phagocytophilum in sheep Ca. Anadelfobacter veles, 79 clinical signs and pathogenesis, 142–144 Ca. Bandiella, 76, 77 diagnosis, 144–146 Ca. Cyrtobacter, 79 etiology and epidemiology, 139, 140 Ca. Defluviella procrastinata, 80

© Springer International Publishing AG 2016 513 S. Thomas (ed.), Rickettsiales, DOI 10.1007/978-3-319-46859-4 514 Index

Aquatic organisms, Rickettsiales (cont.) Biopsy Ca. Fokinia solitaria, 80 liquid, 48 Ca. Jidaibacter acanthamoeba, 77, 78 skin, 40 Ca. Lariskella, 76 Biosafety level 3 (BSL3) laboratory, Ca. Midichloriaceae, 72–76, 80–81 339, 392 Ca. Xanohaliotis californiensis, 71 Biphasic life cycle inside host cells, 229 Ca. Xenolissoclinum pacificiensis, 72 Black measles, 401 members of genus , 71 Blood-sucking arthropods, 297 aquatic , 65–70 Blue disease, 401 Ca. Arcanobacter lacustris, 70 Body lice, 16, 17, 29 Ca. Cryptoprodotis polytropus, 70 Bone marrow, 207 Ca. Gigarickettsia flagellata, 67 Booklouse, 407 Ca. Megaira, 67, 69, 70 Bos indicus, 252 Ca. Megaira polyxenophila, 68 Bovine aortic endothelial cells (BAECs), 271 Ca. Trichorickettsia mobilis, 67 Bovine-granulocytic anaplasmosis, 139 clades of Rickettsia, 66 Brain squash smears, 255, 257 endosymbionts of leeches, 66 Brill-Zinsser disease, 4, 9, 30, 405 diversity of, 59–65 Brown-staining rickettsial colonies, 257 Alphaproteobacteria class, 59 Bubulcus ibis, 251 Candidatus, 65 Candidatus Midichloriaceae, 60, 64 Candidatus Pelagibacter, 65 C genus-level clades, 60 Callosobruchus chinensis, 490 medically relevant, 64 Candidatus, 65 new genera of, 60 Candidatus Anadelfobacter veles non-hematophagous arthropods, 59 (Ca. Anadelfobacter veles), 79 obligate endosymbionts, 65 Candidatus Arcanobacter lacustris reorganized of, 59 (Ca. Arcanobacter lacustris), 70 symbiosis, 65 Candidatus Bandiella (Ca. Bandiella), 76, 77 perspectives, 81–83 Candidatus Captivus acidiprotistae (Ca. bacterial chemotaxis, 82 Captivus acidiprotistae)-related flagella, 82 bacterium, 80 type IV secretion systems, 82 Candidatus Cryptoprodotis polytropus Arboviruses, 7 (Ca. Cryptoprodotis polytropus), 70 Argasid ticks, 11 Candidatus Cyrtobacter (Ca. Cyrtobacter), 79 Atlantic Rainforest Rickettsia (ATRF), 43–44 Candidatus Defluviella procrastinata ATP-binding cassette (ABC) transporter, 429 (Ca. Defluviella procrastinata), 80 Autophagy, 343 Candidatus Ehrlichia khabarensis, 229 Autopsy specimens, 101 Candidatus Ehrlichia regneryi, 229 Avian influenza, 382 Candidatus Ehrlichia shimanensis, 229 Azithromycin, 113, 116–118, 132, 359 Candidatus Fokinia solitaria (Ca. Fokinia solitaria), 79, 80 Candidatus Gigarickettsia flagellata B (Ca. Gigarickettsia flagellata), Babesia bovis, 256 66, 67 Baby Hamster Kidney Cells (BHK), 244 Candidatus Jidaibacter acanthamoeba Bacciger sprenti, 305 (Ca. Jidaibacter acanthamoeba), 77, Bacteremia, 143 78, 286 –host–vector interactions, 242 Candidatus Lariskella (Ca. Lariskella), 76 Bacterial clearance, 181–183 Candidatus Lariskella arthropodarum Bacterial symbiont, 70 (Ca. Lariskella arthropodarum), Bergey’s Manual of Determinative 75, 286 Bacteriology, 387 to vertebrates, 288 Biomarkers of rickettsial infection, 47–49 Candidatus Megaira (Ca. Megaira), 67, 69, 70 Index 515

Candidatus Megaira polyxenophila CD4+ T lymphocytes, 422 (Ca. Megaira polyxenophila), 67–69 CD8+ T lymphocytes, 421 Candidatus Midichloriaceae chemokines, 422 (Ca. Midichloriaceae), 60, 64, 72–80 Foxp3+ Treg cell, 422 Ca. Lariskella arthropodarum to Treg, 422 vertebrates, 288 Cell tropism, 215 Ca. Midichloria mitochondrii to Chemokines, 417 vertebrates, 286–287 Chemoprophylaxis, 261, 262 future perspective, 291–292 Chemotherapy, 261, 262 genera of, 73 Chigger, 5, 16, 125, 126, 388–391 Ca. Anadelfobacter veles, 79 Childhood, considerations, 118 Ca. Bandiella, 76, 77 Chinese Hamster Ovary cells (CHO), 244 Ca. Cyrtobacter, 79 Chlamydia spp., 342 Ca. Defluviella procrastinata, 80 Chlamydia trachomatis, 343 Ca. Fokinia solitaria, 80 Chloramphenicol, 117, 118, 132, 358 Ca. Jidaibacter acanthamoeba, 77, 78 Rickettsiales, 112 Ca. Lariskella, 76 toxin B (CTB), 175, 186 Ca. Midichloria mitochondrii, 73–76 c-Jun NH2-terminal kinase (JNK), MAPK potential pathogenicity, 285, 286 pathway, 417 red mark syndrome, 288–291 Clarithromycin, 113 Rickettsiales incertae sedis, 80–81 Complement fixation tests, 30 Candidatus Midichloria-like organism Concanavalin A (ConA), 175 (Ca. Midichloria-like organism), Contemporary genetic methods, 24 286, 288–291 Cowdria ruminantium, 243 Candidatus Midichloria mitochondrii , 341 (Ca. Midichloria mitochondrii), CpG-oligodeoxynucleotides (CpG-DNA), 235 73–76, 286, 287 Cross-reactive IFA, 32 to vertebrates, 286–287 Culex pipiens, 313 Candidatus Pelagibacter, 65 Cycloheximide, 389 Candidatus Rickettsia aesemboensis, 44 Cytokines, 390, 415, 417, 418, 420, 421, 423 Candidatus Rickettsia senegalensis, 44 Cytoplasmic incompatibility (CI), 473 Candidatus Trichorickettsia mobilis Cytotoxic T lymphocytes (CTL), 201 (Ca. Trichorickettsia mobilis), 66, 67 Candidatus Xenohaliotis, 10 D Candidatus Xanohaliotis californiensis Deer tick (blacklegged tick), 12, 15 (Ca. Xanohaliotis californiensis), 71 Dense-core cell (DC), 229 Candidatus Xenolissoclinum pacificiensis Ca( . Dermacentor variabilis, 231 Xenolissoclinum pacificiensis), 72 Deropegus aspina, 318 Canine pathogen, 216 Direct fluorescent antibody assay (DFA), 395 Carboxyfluorescein succinimidyl ester Disease incidence, 383 (CFSE), 168 Disulfide bond formation (Dsb), 179 Caribbean Amblyomma programme (CAP), 252 Diversity of Rickettsiales, 59–65 Carteria cerasiformis cells, 68 Alphaproteobacteria class, 59 Cat Ctenocephalides( felis), 18 Candidatus, 65 CD4 knock-out mice, 199, 206 Candidatus Midichloriaceae, 60, 64 CD8 knock-out mice, 199, 206 Candidatus Pelagibacter, 65 CD62L, evaluation, 200 genus-level clades, 60 CD4+ Th1, activation of, 421 medically relevant, 64 CD4+ T lymphocytes, 422 new genera of, 60 CD8+ T lymphocytes, 421 non-hematophagous arthropods, 59 Ceftriaxone, 359 obligate endosymbionts, 65 Cell-free DNA, sampling of, 48 reorganized taxonomy of, 59 Cell-mediated immune response, 421–422 symbiosis, 65 516 Index

Double-stranded RNA (dsRNA), 235 CD4 knock-out mice, 199 Doxycycline, 111, 112, 114–119, 131, 132, CD4+ T cells, 199, 201, 206 358–360 CD8 knock-out mice, 199 Drosophila C virus (DCV), 485 CD8+ T cells, 199 Drosophila melanogaster, 470, 471 cell-mediated immunity, 198 Drug susceptibility testing, 393 CTL, 201 DH82 macrophage cells, 199 E. chaffeensis-infected cells, 179 E effector memory T cells, 200 Ectoparasites, 16 EVSYETFDVKNQGNN (C2) peptide, 201 Effector memory T cells, 200 host immunity to Ehrlichia, 3, 160–172, 177, 197, 215, 229, Ehrlichia-specific CD8+ T cells using 230, 299 pentamer staining, 208, 209 antigenic proteins, 178–181 flow cytometry, 209 cellular and humoral immunity in bacterial in vitro cultivation, 207 clearance, 181–183 mouse strains, 206 culturing, 175 peptide synthesis and definition and phylogeny, 225–229 characterization, 208 dense cored cells, 161 proliferation assay, 208 exit strategy, 168, 174, 175 real-time quantitative RT-PCR, 207 fatal human diseases, 216 RNA isolation, 207 filopodia statistics, 209 actin polymerization in host cells, tissue collection and processing, 207 inhibition, 168–171 human monocytic , 197 infected DH82 cells, 160–168 idiotypes, 204 infected mouse macrophages, 171, 172 immune response, 198 molecular biology immunodominant proteins, 230 genome reduction, 229 infection, 198, 204 tandem and ankyrin repeat proteins, 230 mouse strain, 204 morphology, 158–160, 162 mutations, coding and/or non-coding mutagenesis, 216 regions, 219, 220 mutational analysis, 217 P120 and TRP47, 230 overlying host cell membrane, 167, 171, p120 (E. chaffeensis p120), 180 173, 174 p156 (E. chaffeensis p156), 181 p28-OMP 19 to IAb, 202 p28-OMP 14, 198 p28-OMP epitopes, 206 p28-OMP 19, 201, 203 pathogens, 215 p28-OMP 19-derived peptides, 203 penicillin-binding protein, 198 p28-OMPs, 198 16S rRNA gene, 226, 228 pentamer-binding T cells, 210 Ehrlichia canis (E. canis), 178, 179, 216, 225 peptides, 201 control, 182 peptide-specific CD8+CD19− T cells, 205 infection, 230, 231 -lysosome fusion, 234 p43 (E. canis p43), 181 spleen cells, 201 p140 (E. canis p140), 180 SYFPEITHI algorithm, 201 (E. chaffeensis), T-cell epitopes, 200 111–114, 178, 179, 197, 206–209, Tlr4, 198 216–221, 229 universal immunogens, 206 Ank protein, 230 VSMFEATNPKISY (C3) peptide, 201 attenuated mutants, protection against Ehrlichia-containing vacuole (ECV), 234 infection challenge Ehrlichieae, 243 future perspectives, 221 (E. ewingii), 216, 229, 232 tick-transmitted challenge, 221 clinical manifestations, 232 wild-type infection challenge in deer, infections, 232 220, 221 neutrophils, 236 Index 517

Ehrlichia Hsp60, 179, 183, 186, 189, 192 vaccination, 262–267, 269 amino acid sequence, 188 vector chemical control, 262 immunization, 190 as vaccines, 183 protection induced, 191 Ehrlichia ruminantium Gardel virulent Ehrlichia infection, 234–237 (ERGvir), 248 manipulating host immune system, 234 Ehrlichioses (Ehrlichiosis), 6, 100–101, dampening host cell immune response, 103–104, 119, 120, 157, 183–186, 236, 237 189, 192, 225, 230–233 evading host cell PRRs, 234, 235 development of vaccines, 183 evading lysosomal destruction, 234 E. ruminantium, attenuated inhibiting host cell apoptosis, strain, 183 235, 236 OMP P28, 183–185 invading host cell, 234 P29, 185 pathogenic mechanisms, 233 structure-based vaccines, 185, 186, 189 Ehrlichia muris (E. muris), 158, 160, 168, disease, 6 171, 175, 197, 229 epidemiology and clinical manifestations E. muris-like agent (EMLA), 104, 180 E. canis infection, 230, 231 E. muris-like (EML) organism, 233 E. muris infection in humans, 233 in humans, 233 human ewingii ehrlichiosis, 232 P29 (E. muris P29), 185 human monocytic ehrlichiosis, Ehrlichia P28-19, 186, 189 231, 232 amino acid sequence, 187 Electron microscopy, 144, 244, 391 Ehrlichia ruminantium (E. ruminantium), 178, ELISA-based tests, 129 216, 225, 229, 241, 243–247, 249, Elokomin fluke fever (EFF), 305, 311 250, 252, 254, 255, 257–267, 269 Endemic , 29 biology Endemic typhus, 5, 9 developmental cycle, 247, 249, 250 Endosymbionts, 288 tick transmission, 244, 246, 247 Endothelial cells diagnosis of heartwater, 254 activation and inflammatory response to brain squash smears, 255, 257 rickettsial infection, 416 clinical signs, 254, 255 rickettsial adherence and invasion of molecular diagnostics/diagnosis, host, 408 257–260 Enzyme-linked immunosorbent assays molecular tools, 260 (ELISA), 99, 254, 393 pathogenesis, 255 , 101, 401, 402, 451 serological tests, 257 controversy in origination, 405 suitable diagnostic for, 260, 261 mortality rate, 16, 405 epidemiology during World War II, 402 animal species affected, 252, 254 Epidemiological trends, scrub typhus, heartwater geographical distribution, 376–379 250, 252 Eradication programmes, 252 etiologic agent of heartwater Eschar, 126–129, 350–353, 357, classification, 243–244 390–393 colonies morphology in vivo and cigarette burn appearance on skin, 127 in vitro, 244, 245 neck region, 127 future perspectives, 274, 275 Eschar-associated rickettsial illness, 43 immune response and against heartwater, Eschar-associated rickettsioses, 102 269, 270 Eschar-associated SFG rickettsiae, 101 infection in the ruminants, 256 Eutreptiella, 77 life cycle, 249 Eutrombicula hirsti, 344 Omics approaches, 270, 271, 274 Exit strategy, Ehrlichia, 168, 174, 175 treatment, control and prevention, 261 External primers, 258 chemotherapy and chemoprophylaxis, Extracellular signal-regulated kinases 261, 262 (ERKs), 417 518 Index

F Glycoprotein (gp19), 179, 180 Fast-performance liquid chromatography gp200, 181 (FPLC), 270 Gram-negative bacteria, 8, 159, 180, 215, 218, Febrile syndromes, 96 225, 234 Female parthenogenesis (thelytoky), induction Gram-negative coccobacilli, 4 of, 473 Gray baby syndrome, 118 Ferric ion-binding protein (Fbp), 179 GroEL gene, 316, 322 Field diagnostic approach, 144 GroEL (Hsp60), 179, 183, 186 Filopodia, 175 Group II intron-based system, 411 formation and localization, 168–171 infected DH82 cells, 160–168 infected mouse macrophages, 171, 172 H Filopodium, 161, 163–174 Hanks buffered salt solution (HBSS), 209 Flea-borne infections, 17 Hard ticks (Ixodidae), 11, 13 Flea-borne murine typhus, 29 Heartwater, 241–245, 254, 255, 257–261 Flea-borne rickettsiae, 46 control, 242 Flock House virus (FHV), 485 diagnosis, 254 Flow cytometry, 189, 393 brain squash smears, 255, 257 Fluorescein isothiocyanate (FITC), 209, 355 clinical signs, 254 Fluorescence-based detection technology, molecular, 257–260 35–36 pathogenesis, 255 Fluoroquinolones, Rickettsiales, 112, 113 serological tests, 257 Focal adhesion kinase (FAK), 341 suitable diagnostic for, 260, 261 Formaldehyde-fixed and paraffin-embedded etiologic agent of (FFPE) tissue, 40 classification, 243–244 Formin homology 1 (FH1) domain, 425 colonies morphology in vivo and Foxp3+ Treg cell, 422 in vitro, 244, 245 geographical distribution, 250–252 immune response to Ehrlichia G ruminantium and against, 269, 270 Gamma interferon (IFN-γ), 236 vaccines, 272 Gel-shift mobility assays, 413 HeLa cells, 411 Gene expression, 219 High-passaged attenuated strain Genetic variants, 138, 139, 144, 145 (ERGatt), 273 Genome analysis, 35 Histoplama capsulatum, 237 Genome reduction, 229 Hong Kong, scrub typhus, 378 Genome sequencing method, 451 Horizontal gene transfer (HGT), 458–460 Genomes of Rickettsia species. See Rickettsia Host associations, 298, 305, 318 species Host cells Genomics, 432–437 apoptosis, 235 first rickettsial plasmid, 436 biphasic life cycle, 229 mean expression value (MEV), 436 evading PPRs, 234, 235 mobile genetic elements, 436, 437 immune response, 236, 237 noncoding DNA, 433 invading, 234 noncoding RNA, 433, 436 Host immunity to E. chaffeensis nucleus-encoded mitochondrial Ehrlichia-specific CD8+ T cells using proteins, 433 pentamer staining, 208, 209 ORF, 433, 436 flow cytometry, 209 small RNAs (sRNAs), 436 in vitro cultivation, 207 spotted fever group, 433 mouse strains, 206 Genotypes of , 36 peptide synthesis and characterization, 208 Gentamicin protection assays, 413 proliferation assay, 208 Genus Rickettsia, clades of, 66 real-time quantitative RT-PCR, 207 Gimenez method, 449 RNA isolation, 207 Index 519

statistics, 209 metabolism, 431–432 tissue collection and processing, 207 ATP, 431 Host innate immune response, 419–421 biosynthetic pathways, 432 Host–symbiont interactions, Wolbachia, 480–483 coenzymes, 432 Aedes aegypti mosquitoes, 481 cofactors, 432 autophagy, 480, 481 eukaryotic and prokaryotic effects of diet, 482 organisms, 432 female wasps, 482 glutamine, 432 in filarial nematodes, 482 obligate intracellular organisms, 431 genomic analyses, 481 Orientia, 431 iron, 482 sequencing of R. prowazekii rapamycin-treated nematodes, 480 genome, 432 in terrestrial isopods, 481 transporter systems, 431 variation in dietary iron, 483 overview, 401–408 Host–vector–pathogen interactions, 270 ancestral group, 401 Hub tropism, 470 antigenically distinct groups, 401 Human ehrlichiosis, 6 association with arthropods, 405 Human ewingii ehrlichiosis, 232 human body louse, 405 Human granulocytic ehrlichiosis (HGE), 6 mosquito, 406 Human granulocytic/granulocytotropic Rickettsia-free ticks, 405 anaplasmosis (HGA), 6, 101, 110, RMSF, 401 117, 118, 216 spotted fever group, 401 Human microvascular lung endothelial cells ticks, 402 (HMVEC-L), 411 transmission method, 405, 406 Human monocytic/monocytotropic typhus group, 401 ehrlichiosis (HME), 101, 110, 117, rickettsial target cells, adhesion, and host 157, 177 invasion, 408–415 Human rickettsioses, 9, 100, 101, 103, 197, actin, 414 216, 231, 232, 401, 402, 405, 406, in cytoplasm, 412 411–414, 417–423, 426, 428–433, gel-shift mobility assays, 413 436, 437 genetic manipulation of endothelial interactions and inflammatory Rickettsia, 411 response, 415–426 gentamicin protection assays, 413 chemokines, 417 OmpA, 411 host innate immune response, 419–421 OmpB, 411, 412 humoral immune response, 422–423 phagosome lysis, 414 IL, 417 protein, 414 PRRs, 418–419 sca, 411–413 regulation of programmed cell death, 423 SDS-PAGE analysis, 412 rickettsial motility (see Rickettsial vinculin, 413 motility) secretion systems, 426–431 selectin molecules, 417 autotransporters, 428 signaling cascades, 417 immunofluorescence assays, 430 future directions, 438–439 in vitro analyses, 428 genomics, 432–437 membrane fusion protein, 429 mean expression value (MEV), 436 plasmids, 429 mobile genetic elements, 436, 437 RalF protein, 430, 431 noncoding DNA, 433 scaffold proteins, 430 noncoding RNA, 433, 436 sec-dependent pathways, 426, 428, 429 nucleus-encoded mitochondrial sec-independent pathways, 428 proteins, 433 T4SS, 429, 430 ORF, 433, 436 Tat pathway, 428 small RNAs (sRNAs), 436 TISS, 429 spotted fever group, 433 type I secretion system, 428 520 Index

Human umbilical vein endothelial cells 120-kDa protein, 180 (HUVECs), 417, 421 200 kDa protein (Ank200), 230 Humoral immune response, 422–423 Kedani fever, 331 Hyperemia, 126 Krebs cycle, 431

I L Ichthyophthirius multifiliis, 69 Laboratory criteria, Rickettsial disease, 128 IgG isotype, 99 imaging, 130 Immune suppression, 143 specific investigations, 129 Immunoblotting, 254 supportive laboratory investigations, 130 Immunochromatographic tests (ICTs), 358 Laboratory diagnosis of Rickettsiales, 98–104 Immunoglobulin M (IgM), 129, 393 culture, 97–98 Immunoglobulin therapy, 422 general principles, 96–97 Immunohistochemistry (IHC), 33, 101–102 immunohistochemistry, 101–102 Inactivated vaccine, 265 molecular detection, 102–104 Incompatible insect technique, 497 Ehrlichiosis and Anaplasmosis, 103–104 Indian tick typhus, 126, 130 scrub typhus, 103 Indirect immunofluorescence assay/antibody spotted fever and typhus group (IFA), 31–32, 98–101, 103, 128, rickettsioses, 102–103 129, 145, 254, 322, 335, 355, 356, overview, 95 376, 393, 395 serology, 98–101 Indirect immunoperoxidase (IIP) tests, 353 Ehrlichiosis and Anaplasmosis, Indirect immunoperoxidase assay (IPA), 100, 100–101 128, 129, 393 scrub typhus, 100 Infection and treatment method, 262, 265 spotted fever and typhus group Infectious disease, 177, 178, 184 rickettsioses, 98–100 Innate immune system, 418 Lateral gene transfer, Wolbachia, 490–493 Inner membrane component (IMC), 429 Callosobruchus chinensis, 490 Insertions or deletion events (INDEL), 36–40 Drosophila ananassae, 490 Intergenic regions, 36–40 F factor, 492 variations in sequences of, 36–37 filarial nematodes, 492 Interleukin (IL)-8, 250 lifestyle of Wolbachia, 490 Interleukins (IL), 417 Loa loa genome, 492 Internal primers, 258 mammalian immune response, 493–496 Intracellular bacteria, 334, 339, 343, 414, 415, pseudogenome, 490 419, 421, 423, 431 supergroup, 493 Intracellular pathogens, 157, 160, 185, 215, transcriptomic analysis of adult worms, 492 342, 343 Legionella pneumophilia RalF (LpRalF), 430 In vitro cultivation of E. chaffeensis, 207 Lepidopterans, 478 Ixodes ovatus ehrlichia (IOE), 171, 175, 178, Leptospirosis, 352 181, 182, 197, 233, 236 Leptotrombidium, 343, 345, 380 Ixodes ricinus, 286, 287 Leptotrombidium delicense (L. delicense), 381 Ixodes scapularis, 12 Leptotrombidium fletcheri (L. fletcheri), 381 IкB kinase (IKK), 417 Leptotrombidium imphalum (L. imphalum), 381, 382 Leptotrombidium scutellare (L. scutellare), 381 J Leukocytosis, 353 Japan, scrub typhus, 378 Lipid droplets, 343 Japanese river fever, 331 Lipopolysaccharide (LPS), 32, 159, 235, 451 Liquid biopsy, 48 Live attenuated vaccine, 265 K Louse infestation, 16 47-kDa antigen, 357 Lyme disease, 382 56-kDa antigen, 332, 335–339, 341, 356–358 Lymnaea stagnalis, 313 Index 521

Lymphatic filariasis/elephantiasis, 469 islands, 348, 382 Lyticum flagellatum, 78 Mite vectors for scrub typhus, 379–382 Lyticum genus, 78 Mitogen-activated protein kinases (MAPK) Lyticum sinuosum, 78 signaling cascade, 417 Mobile genetic elements (MGEs), 457–460 Modification-rescue model, 473–474 M Molecular detection, 102–104 Macrolides/ketolides, Rickettsiales, 113–114 Ehrlichiosis and Anaplasmosis, 103–104 Macrophages, 157, 158, 161, 163, 168, scrub typhus, 103 171–173 spotted fever and typhus group Major antigenic protein-1 (MAP-1), 256–257 rickettsioses, 102–103 Major histocompatibility complex class II Molecular diagnosis, heartwater, 257 (MHCII) knockout mice, 236 PCR and nested PCR, 257, 258 Mammalian immune response, Wolbachia quantitative real-time PCR, 259 in absence of neutrophils, 496 typing methods, 259, 260 abundant protein, 496 Molecular epidemiology, 23–45 filarial infection, 496 biomarkers of rickettsial infection and in filarial nematodes, 493 future directions for, 47–49 filarial-Wolbachia symbiosis, 496 molecular genetic tools in rickettsiology, live adult worms, 494 33–41 molecules, 495 intergenic regions, VNTR, INDEL, and neutrophil infiltration on, 493 SNP typing, 36–40 in ocular pathology of onchocerciasis, 493 PCR amplification and gene targets, PAL, 495 34–35 severity of stromal haze, 493 quantitative PCR and fluorescence-­ WSP, 493, 495 based detection technology, 35–36 Management, guidelines, 128 samples needed for investigations, case definition 40–41 confirmed case, 128 16S rRNA and 23S rRNA genes for probable case, 128 identification, 34 suspected/clinical case, 128 for surveillance, 45–46 laboratory criteria, 128 in outbreak investigations of rickettsial imaging, 130 diseases specific investigations, 129 challenges in identifying new supportive laboratory investigations, 130 pathogens and confirming treatment etiologies, 44–45 at primary level, 131, 132 R. parkeri and ATRF, 43–44 at secondary and tertiary care, 131, 132 Rickettsia massiliae, 41–42 Manifestations, 126–128 RMSF, 42–43 Matrix-assisted-laser desorption time-of-flight overview, 23–24 mass spectroscopy (MALDI-TOF/ concept of, 24 TOF), 208 contemporary genetic methods, 24 Mediterranean spotted fever (MSF), 10, 111 taxonomy, 23 Membrane fusion protein (MFP), 429 rickettsioses in the USA in pre-molecular Mesocricetus auratus, 313 era (see Rickettsioses in the USA, Metagonimoides oregonensis, 312 pre-molecular era) Mexican brown dog ticks, 42 Monocytes, 157, 158, 163, 168, 171, 173, 174 MHCI H-2Kb and MHCII IAb binding Montana State Board of Health, 26 peptides, 202 Montezuma, 288 Micro-IFA, 98 Morula (Morulae), 158, 297 Midichloriaceae, 3, 4 Mosquitoes, arboviruses, 7 Migratory birds, scrub typhus, 382, 383 Mugil cephalus, 310 Minocycline, 111, 112 Multi-locus genetic typing Mite, 16 Multi-locus sequence typing (MLST), 38, Mite bite fever, 331 259, 337 522 Index

Multi-locus variable number of tandem Neorickettsia elokominica, 311, 312 repeated sequence analysis Neorickettsia helminthoeca, 306–308 (MLVA), 259 Neorickettsia risticii, 308–310, 320 Multiplexed PCR assay, 103 , 298, 309, 311 Multispacer typing-MST approach, 36 Neorickettsiae, digenean and vertebrate hosts, Murine cycle, classic urban, 46 301–303, 316, 318 Murine flea-borne typhus, 126 Nested PCR, 257, 258 Murine typhus, 29, 96, 101, 116, 130, 352, Nested PCR pCS20, 260 451, 456 Nested primers, 258 rash in patient with, 96 Neuronal-WASP (N-WASP) signaling, 425 Mutagenesis, 221 Next-generation sequencing approaches, 34 in Ehrlichia and Anaplasma species, 216 NOD-like receptors (NLRs), 418, 419 random, 216–221 Non-model Rickettsiales, 285 targeted, 217, 218, 221 Non-synonymous SNPs, 38 transposon, 218, 221 Nuclear factor kappa-light-chain-enhancer of Mutations activated B cells (NF-kB), 235 coding and/or non-coding regions of Nuclear factor-кB (NF-кB) signaling cascade, E. chaffeensis, 219, 220 417, 418, 423 impacting gene expression, 219 Nucleus-encoded mitochondrial proteins, 433 targeted, 218 Nutrient-rich host cytosol, 414 Mutualism, 479, 480 Mycobacterium tuberculosis, 237 Mycoplasma pneumoniae, 352 O MyD88-dependent signaling, 182 amplified genetic elements (OtAGEs), 334 Octomom, 489 N Omics approaches, 269, 270, 273 Nanodrop Spectrophotometer, 207 OmpB protein antigens, 32, 36, 412 Nanophyetus salmincola, 306, 307, 312 domains of, 411 Natural killer (NK) cells, 419, 421 Onchocerciasis/river blindness, 469 Natural Tregs, 422 Oncorhynchus mykiss Walbaum, 288–291 Negative serology, 101 Open reading frames (ORFs), 433, 451, , 342 457, 458 Neorickettsia, 3, 215, 243, 297, 299, 300, Orientia, 3, 8, 16, 431 304–309, 311–313, 315, 316, organisms in, 97 319, 320 transmission of, 16 geographic distribution, 319–322 Orientia chuto, 388 members of genus, 71 Orientia tsutsugamushi, 100, 117, 332, 334, molecular detection and identification, 322 335, 337, 339, 341, 347, 350, 352, real time PCR detection, 322 355, 357–360, 375, 376, 380, 382, systematics and phylogeny, 299–305 383, 387, 390, 393 interrelationships within, 299, 300, antibiotics, 358 304, 305, 319, 320 antibodies against, 348 position among Rickettsiales, 299 antigenic diversity, 335 transmission biology, 305 antigenic types, 336 Neorickettsia elokominica, 311, 312 biology, 339–343 Neorickettsia helminthoeca, 306–308 cell wall, 388 Neorickettsia risticii, 308, 309 coinfections, 352, 359 Neorickettsia sennetsu, 309, 311 disease caused by, 5–6 Neorickettsia spp., 316 DNA of, 103 Neorickettsia sp. (PE agent), 312, doxycycline, 359 313, 315 eschar, 357 Neorickettsia sp. (SF agent), 311, 312 features, 334 Neorickettsia sp. rainbow trout agent, 312 feeding process, 388 Index 523

fluoroquinolones against, 359 Pediculus humanus corporis (human body HIV-1 replication, 352 louse, 405 horizontal gene transfer, 335 Peptidoglycan-associated lipoprotein (PAL), 495 IFA, 355 Phalloidin, 161 infected , 345 Phenotypic analysis, 209 infection with, 345, 347, 353, 393 Phospholipase D (pld), 414 larvae from, 345 Plagiorchis elegans, 312, 314, 315 larval acquisition, 346 pLbaR plasmid, 456 mammals as reservoir, 388 p38 MAPK pathway, 417, 418 in mice, 392 , 127 microbiology, 389, 390 Polar actin tail formation, 424 molecular detection, 356, 357 Polyclonal antibodies, 33 morphology, 340–341 Polymerase chain reaction (PCR), 102, 129, pathogenicity, 390, 391 231, 257, 258, 356, 357, 393 pathology, 351 amplicons of VNTR sites, 37 phenotypic differences, 333 amplification and gene targets, 34–35 phylogenetic analysis, 339 assays, 104 prevalence of antigenic types, 337 quantitative, 35–36 RAGE, 459 testing of , 46 risk factors, 348 Wolbachia infections, 467, 469 strains, 393, 394 Polymorphonuclear leukocytes (PMNL), 390 transovarial transmission, 345, 388 p28-OMP 14, 198 uninfected mites, 346 p28-OMP 19, 198 Weil Felix test, 393 Population replacement technique, 497 Ostrinia scapulalis, Wolbachia in, 478 Potomac horse fever (PHF), 305, 308, 309, Outer membrane protein A (OmpA), 32, 312, 322 102, 411 Pregnancy, considerations, 118 Outer membrane protein (OMP) P28, 183–185 pRF, rickettsial plasmid, 436, 456, 458 Outer membrane proteins (OMP-1/P28), 179 Primers, 258, 322 Outer membrane proteins (OMPs), 179, Primorye region, scrub typhus, 381 180, 236 Programmed cell death, regulation of, 423 Ovine granulocytic anaplasmosis, 139 Proimmune, 209 Oxytetracyclines, 147 Prompt antibiotic therapy, 127 Oxytrema silicula, 306 Prophylaxis, 138, 146 , 393 Prototypes, 395 P P29, 180, 185 Panola Mountain Ehrlichia (PME), 216 Q Paramecium, 67, 78, 80 Qualitative real-time PCR, 102, 103 Parasite, 69 Quantitative PCR assays, 35–36 Passenger domain, OmpB, 411 Quantitative real-time PCR (qPCR), Pasture fever, 139 259, 314 Pathogen-associated molecular patterns assays, 103 (PAMPs), 418, 419 Questing position, 14 Pathogenesis, 220, 221 Pathogen protection, 485 Pathological alteration, 285 R Pattern recognition receptors (PRRs), 234, R1 symbiont, 80 235, 418–419 Rainbow trout agent, 288–291, 312 NLRs, 418, 419 Random mutagenesis, 218 TLRs, 418, 419 RankPep program, 201 Pediculosis, 16 Rash, 126 Pediculus humanus, 4 Real-time PCR pCS20, 261 524 Index

Real-time polymerase chain reaction macrolides/ketolides, 113–114 (RT-PCR), 168 rifamycins, 114 Recombinant FliD protein, 287 tetracyclines, 111, 112 Recombinant P28-19, 183, 184 childhood and pregnancy, Recombinant vaccine, 266, 267 considerations, 118 Recrudescent typhus, 405 evolutionary relationships within families, Red mark syndrome (RMS), 288–291 60–61 Regional lymphadenopathy, 391 families of organisms, 95 Regulatory T-cells (Treg), 422 general principles, 110 Restriction fragment length polymorphism laboratory diagnosis of (see Laboratory (RFLP) analysis, 103, 258, 395 diagnosis of Rickettsiales) Reticulate body (RB), 247–248 negative staining transmission electron Reticulate cell (RC), 229 microscopy images of, 64 Reverse line blot (RLB), 261 new genera of, 62–63 Rhipicephalus microplus, 262 position of Neorickettsia, 299 Rhipicephalus sanguineus, 119, 230, 231 prevention, 119 RickA protein, 424 Rickettsiales amplified genetic element (R. akari), 29, 408 (RAGE), 459 Rickettsiaceae, 215, 243, 285 Rickettsiales Anaplasma marginale, 242 , 115 Rickettsiales endosymbiont of T. adhaerens Rickettsia conorii in host cells, 402 (RETA), 77 Rickettsia conorii (R. conorii)-infected Rickettsiales infections, 3–5, 7, 8, 11–18, 125 macrophages, 420 biomarkers of, 47–49 Rickettsia endosymbiont of Ixodes scapularis disease caused by (REIS), 433, 457 Anaplasma, 6–7 genome from, 459 Ehrlichia, 6 Rickettsia-free ticks, 405 Neorickettsia, 7 Rickettsia helvetica, 34 Orientia tsutsugamushi, 5–6 Rickettsia-infected endothelial cells, 423 Rickettsia, 4–5 Rickettsial disease, 128–132, 401 epidemiology, 9–10 classification, 126 innate and adaptive immune response to, 420 diagnosis of, 30 overview, 3–4 management, guidelines, 128–132 ectoparasites, 3 confirmed case, 128 families, 3 laboratory criteria, 128–130 features of, 3 probable case, 128 risk of infections, 4 suspected/clinical case, 128 rRNA gene, 3 treatment, 130–132 pathobiology, 10–11 manifestations, 126–128 prevention of, 8 molecular methods, 31 Rickettsia conorii, 9 molecular typing methods and outcomes, 39 , 9 Rickettsiales, 95, 109, 111–118, 215, 229, , 9 285, 332 significance ofWolbachia , 7–8 antibiotic treatment of clinical rickettsioses arboviruses, 7 HGA, 117, 118 nematode hosts, 8 HME, 117 Wolbachia-harboring mosquitoes, 7 murine typhus, 116 Zika virus, 8 RMSF, 114, 115 taxonomy, 8–9 scrub typhus, 117 vectors of, 11–18 SFGR, 115, 116 body lice, 16 typhus, 116 cat flea, 18 antimicrobial agents, 111–114 flea-borne infections, 17, 18 chloramphenicol, 112 other vectors, 16–18 fluoroquinolones, 112, 113 tick feeding, 13 Index 525

tick life cycle and behavior, 13–16 influenzae, 451 tick vectors, 11–13 Mycoplasma genitalium, 451 Rickettsial genomes and associated plasmids, pLbaR plasmid, 456 434–435 pRF plasmid, 456 Rickettsia-like organisms (RLO), 64 protein-coding genes, 451 Rickettsial motility, 423–426 R. bellii genome, 457 ABM, 423–425 R. conorii genome, 458 acquisition of, 423 R. felis genome, 456 actin polymerization, 426 Rickettsia symbiont of Ixodes immunofluorescence assays, 425 scapularis, 457 N-WASP, 425 sequencing of genome, 451 polar actin tail formation, 424 MGEs and HGT, 458–460 RickA protein, 424, 425 organisms in, 97 VCA, 425 overview, 449–451 WASP, 424, 425 phylogenomic tree of, 450 Rickettsial plasmids (RPs), 437 secretion systems, 427 characteristic of, 458 Wolbachia, 314 determining origin of, 437 Rickettsia tsutsugamushi, 332, 387 genes, 458, 459 Rickettsia typhi, 18 study of evolutionary history, 458 Rickettsioses in the USA, pre-molecular era, , 5, 28–29 24–33, 450 Rickettsial proteins, mammalian host, 409–410 and epidemiological concepts Rickettsia massiliae, 41–42 murine typhus, 29 Rickettsia orientalis, 332 rickettsialpox, 28–29 Rickettsia palindromic elements (RPEs), 451 RMSF, 26–28 (R. parkeri), 32, 43–44 sylvatic typhus, 29–30 Rickettsia rickettsii (R. rickettsii), etiological agents and primary genotypes of, 36 vectors, 26 , 407, 430 serological tools and their role, 30–33 Rickettsia-rich biopsy tissues, 49 IFA, 31–32 Rickettsia ruminantium, 225 IHC, 33 Rickettsia species, 197, 333, 335, 387, 389, western blotting, 32–33 390, 449, 451, 456–458, 461 Rifampin, 114, 117, 118, 359 conjugation genes in, 459 Rifamycins, Rickettsiales, 114 degree of synteny, 456 Rocky Mountain spotted fever (RMSF), 5, disease caused by, 4–5 25–28, 45, 97, 101, 109, 114, 115, R. africae, 5 177, 231, 401 R. akari, 5 Amblyomma americanum, 28 R. conorii, 5 antibiotics for treatment of, 27 R. prowazekii, 4 case definitions for reporting (1990 and R. rickettsii, 5 2010), 25 R. typhi (murine typhus), 5 early days, 27 disease, in vivo model, and transmission molecular epidemiology of, vector associated with, 403–404 42–43 dissemination in tissues, 415 national incidence and case-fatality rate in features of, 452–455 the USA, 28 genomes on rickettsial pathogenesis, prevalence in Wyoming, 1913–1926, 27 460–462 symptoms of, 26 F-type T4SS, 461 untreated fatality rate, 402 P-type T4SS, 461 Rodent eradication programs, 29 TA modules, 461 Rodents, 388 genomic characteristics of, 451–458 rOmpA protein, 460 degree of synteny, 457 rOmpB protein, 411, 460 evolutionary analysis, 458 Russia, scrub typhus, 380 526 Index

S immunofluorescence assays, 430 Salmon poisoning disease (SPD), 297, in vitro analyses, 428 305–309, 311, 312, 317 integral membrane proteins, 426 Salmonella heterologous system, 415 membrane fusion protein, 429 Scanning electron microscope (SEM), 165, plasmids, 429 175–176 RalF protein, 430, 431 Scrub typhus, 5, 6, 10, 16, 100, 103, 112, 114, scaffold proteins, 430 117–120, 125–131, 331, 332, sec-dependent, 426, 428, 429 334–335, 337, 339, 341–343, 375, sec-independent, 428 387, 393 T4SS, 429, 430 background, 331–332 Tat pathway, 428 causative agent, 375 TISS, 429 biology of O. tsutsugamushi, 339, type I secretion system, 428 341–343 Selective Capture of Transcribed Sequences classification, 332 (SCOTS) methodology, 271 genomics, 334–335 Senegalese tick, 245 strain variation, 335, 337, 339 Sennetsu fever, 4, 297, 305, 309, 312, 318 chest X-ray, 355 Serological tests, 257 clinical features, 391, 392 Serology, 27, 95, 97–101 clinical manifestations, 350–353, 375 Ehrlichiosis and Anaplasmosis, 100–101 control, 383 scrub typhus, 100 diagnosis, 353, 355–358 spotted fever and typhus group disease transmission, 343, 345, 346 rickettsioses, 98–100 distribution and trends of annual Serotypes, 335, 337, 339, 355, 357 incidences, 347, 377 Sheep, Anaplasma phagocytophilum distribution of mite vectors, 379–382 clinical signs and pathogenesis, 142–144 epidemiological characterization, 395 diagnosis, 144–146 epidemiological study on, 377 etiology and epidemiology, 139, 140 epidemiological trends and spatiotemporal history, 138 pattern, 376–379 infection and transmission, 140–142 eschars, 351, 391 other species, 148 features, 375, 376 sheep skin biopsy, 141, 145 habitat and epidemiology, 346–350, treatment, 146–148 388–389 Shell vial technique, 98 history, 387, 388 Short-acting tetracyclines, 261 laboratory and radiographical findings, 354 Signal peptide, OmpB, 412 laboratory diagnosis, 392–393 Single nucleotide polymorphisms (SNPs), drug susceptibility testing, 393 36–40, 460 IFA, 393 Skin biopsy, 40 IgM and IgG ELISA, 393 Skin biopsy specimens, 101 IPA, 393 Skovsyge condition, 138 PCR, 393 Small non-coding RNAs (sRNAs), 461 Weil Felix test, 393 Smart Cycler system, 207 microbiology, 389, 390 Soft ticks, 11, 13, 14 migratory birds in spread of, 382, 383 Solid-phase peptide synthesis, 208 pathogenicity, 390–391 Soluble TNF-α (sTNF-α) receptor, 421 phenotypic differences, 333 South Korea, scrub typhus, 378 prevalence of antigenic types, 337 Species-specific assays, 36 prevention, 394, 395 Spotted fever group (SFG), 95, 98, 100, 102, 125, seasonal prevalence, 379 401, 402, 405, 412, 418, 424, 450 treatment and control, 358–360, 393 transmission cycle for natural Scrub typhus infection criteria (STIC), 358 maintenance of, 406 Secretion systems, 426–431 Spotted fever group rickettsiae (SFGR), 10, autotransporters, 428 25, 27, 29, 111, 115, 116, 118, 119 Index 527

Sri Lanka, scrub typhus, 378 Rickettsia-free ticks, 405 16S rRNA gene of Rickettsia, 34 soft, 13, 14 23S rRNA gene of Rickettsia, 34 species, 15 23S-5S intergenic spacer (IGS), 34 tick feeding, 14 Staphylococcus aureus, 143 to remove, 15 StatMost Statistical Package, 209 vectors, 11–13 Stellantchasmus falcatus, 306 Tick-transmitted pathogens, 177 Stimulation index (SI), 208 Tick-transmitted rickettsial diseases, 11 Structural vaccinology, 178, 186 TIR-domain-containing adapter-inducing Structure-based vaccines, 178, 185, 186, interferon-β (TRIF), 418 189, 193 TolC protein, 429 Surface cell antigen (sca), 408, 411, 412, 451 Toll-like receptors (TLRs), 234, 418, 419 mutant, 426 Toxin–antitoxin (TA) modules, 461 sca0, 408, 411 Transmission, 306–309, 311–313, 315, 316 sca1, 412 biology of Neorickettsia, 305 sca2, 412, 413, 425 Neorickettsia elokominica, 311, 312 sca3, 413 Neorickettsia helminthoeca, 306–308 sca4, 413 Neorickettsia risticii, 308, 309 sca5, 411 Neorickettsia sennetsu, 309, 311 sca16, 408 Neorickettsia spp., 316 Swan Ganz catheterization, 110 Neorickettsia sp. (PE agent), 312, SYBR Green assays, 35 313, 315 SYFPEITHI algorithm, 201 Neorickettsia sp. rainbow trout agent, 312 Sylvatic typhus, 29–30 Neorickettsia sp. (SF agent), 311, 312 complement fixation tests, 30 Ca. Lariskella arthropodarum to Rickettsia prowazekii, 30 vertebrates, 288 Symbiosis, 65, 469, 476, 478–480, 482, 490, Ca. Midichloria mitochondrii to 496, 504 vertebrates, 286–287 Synonymous SNPs, 38 Transposable elements (TEs), 334 Syzygium aromaticum, 360 Transposon mutagenesis, 216–218, 221 Treatment, Rickettsial disease at primary level, 131, 132 T at secondary and tertiary care, 131, 132 Tandem repeat proteins (TRP), 179, 230 Tricarboxylic acid cycle, 389, 431 Tandem repeats (TR), 37 Trifluoroacetic acid (TFA), 208 Targeted mutagenesis, 218 TRIF-related adaptor molecule (TRAM), 418 Targeted mutations, 216–218, 221 Tri-reagent RNA isolation kit, 207 T-cell idiotypes, 198 Trombiculid mite, 16, 331, 343, 346, 349, 380, Tetracyclines, 261, 476, 480, 499, 503 382, 388 Theileria tsutsugamushi, 387 larval (chigger) stage, 344 Thrombocytopenia, 130, 353 life cycle, 344 Tick-borne disease, 140, 221, 241, 271, 274 misnomer as, 347 Tick-borne fever (TBF), 138, 139, 141–144, primary hosts, 346 146, 147 species, 345, 347 Tick-borne pathogen, 271 Tropheryma whipplei, 341 Tick-borne /rickettsioses, 44, 288 Tsutsugamushi triangle, 346, 347, 381 Ticks, 177, 180, 225, 226, 229–233, 402 Twin-arginine-translocation (Tat) pathway, 428 African tick bite fever, 96 Type I secretion system (T1SS), 429 feeding, 13 Type IV secretion system (T4SS), 334, 429, hard, 13 430, 459, 461 life cycle and behavior, 13–16 Typhus, 116 life stages, 12 Typhus group rickettsiae (TGR), 10, 111, Mexican brown dog ticks, 42 119, 451 questing position, 14 Typhus islands, 388 528 Index

U Wild ruminants, 254 Unidirectional CI, 473 Wiskott–Aldrich Syndrome Protein The United States, incidence of SFR, 402 (WASP), 424 Universal immunogens, 206 Withering syndrome, 71 Wolbachia, 10, 299, 318, 467, 469–490, 492–497, 500, 503, 504 V compounds against, 501–502 Vaccination, Ehrlichia ruminantium, genomics and MGEs, 487–490 262–267, 269 genetic selection study, 489 comparative analysis, 267 phage WO, 488 identification of best, 267, 269 projects, 487 inactivated vaccine, 265 prophage genes, 488 infection and treatment method, 262, 265 strains, 488 live attenuated vaccine, 265 supergroup, 488–490 recombinant vaccine, 266, 267 of tsetse fly Glossina morsitans strategies, 263, 264 morsitans, 487 Vaccines, ehrlichiosis, 138, 147, 177, 178, wBm genome, 487 183–186, 189 wMel genome, 487 E. ruminantium, attenuated strain, 183 host range and distribution, 467–470 OMP P28, 183–185 DNA sequences, 469 P29, 185 in filarial nematodes, 469 structure-based vaccines, 185, 186, 189 infected terrestrial arthropod species, 467 Variable numbers of tandem repeat (VNTR) invertebrate hosts of, 467 sites, 37 neglected tropical diseases, 469 Vector-borne rickettsioses, 438 PCR screening, 467, 469 Vector chemical control, 262 phyla, 470 Vector map, 379–382 surveys in parasites, 469 Vectors of Rickettsiales, 16–18 in terrestrial isopods, 469 other vectors, 16–18 Wolbachia pipientis, 467 body lice, 16 host–symbiont interactions (see Host– cat flea, 18 symbiont interactions, Wolbachia) flea-borne infections, 17, 18 insect host and, 485 tick feeding, 13 interactions with co-infecting organisms, tick life cycle and behavior, 13–16 483–486 tick vectors, 11–13 blockage of dengue transmission, 485 Venezuelan human Ehrlichia (VHE), 231 strains, 483–486 Verprolin, cofilin, and acidic domain (VCA) on viral infections in insects, 483 mutants, 425 viral protection phenotypes, 483 Vertebrate hosts, 287 viruses and, 486 Vinculin, 413 wMel-like variants, 486 Viral syndromes, 96 wMelPop, 483, 484 VirB system, 82 in vector control, 496–499 Virulent strain (ERGvir), 273 Aedes polynesiensis, 497 Volvox, 67 strain, 497 wMelPop, 497 lateral gene transfer (see Lateral gene W transfer, Wolbachia) Weil–Felix test, 128, 129, 353, 376, 387, 393 mammalian immune response Western blotting, 32–33, 254 (see Mammalian immune response, Wheat germ agglutinin (WGA), 175 Wolbachia) White band disease, 69 obligate dependencies, 476–480 Whole genome sequences of Rickettsia. affecting sexual behaviour, 479 rickettsii, 38 in arrhenotokous species, 479 Whole Genome Shotgun (WGS) projects, 334 in arthropods, 479, 480 Index 529

Asobara japonica populations, 479 arthropods, 472 A. tabida system, 478 in filarial nematodes, 472 biotin biosynthetic cluster, 479 phylogeny, 472 in filarial nematodes, 476 strains, 472 genome sequencing of strain, 476 supergroups, 472, 473 heme auxotrophy, 476 Wolbachia melophagi, 472 hijacking sex determination Wolbachia persica, 472 system, 478 transmission, 470–472 lepidopterans, 478 Drosophila melanogaster, 470, 471 obligate haematophagous germline stem-cell niche, 470 arthropods, 479 horizontal transmission, 472 in Ostrinia scapulalis, 478 hub tropism, 470 removal from bedbugs, 479 in nematode oocytes, 470 removal of strain, 478 phylogenies, 471 supergroup, 477–479 targeted migration of, 470 symbiosis in bedbugs, 479 with mammalian immune system, 494 reproductive manipulations, 473–476 Wolbachia–host associations, 477 ankyrin-repeat proteins, 475 Wolbachia-induced CI, 498 CI, 473–475 Wolbachia bacteria, 7–8 eggs, 474 arboviruses, 7 feminisation, 473 nematode hosts, 8 H. bolina system, 476 Wolbachia-harboring mosquitoes, 7 in infected arthropod, 475 Zika virus, 8 in male killing, 473 Wolbachia pipientis, 243 sex ratio distortion, 473 Wolbachia surface protein (WSP), 493 strains, 475 Wolbachieae, 243 supergroup, 489 World Health Organization, 332, 379, 496 susceptibility to antibiotics, 499–504 World Trade Organization, 349 A⋅WOL, 503 clinical trials of doxycycline, 500 in filarial hosts, 503, 504 X human trials, 500 Xenopsylla cheopis, 17 in lymphatic filariasis, 500 taxonomy, 468, 472–473 analyses using orthologous gene Z clusters, 472 Zika virus, 7, 8, 497