Avian intestinal spirochaetosis: an emerging zoonosis

Abstract

Intestinal spirochetes are detected in a wide range of mammalian and avian host species. and cause enteric disease, especially in swine and poultry. Although avian intestinal spirocheosis (AIS) is considered a growing and underestimated problem in poultry production systems, its occurrence and economic burden cannot be neglected. The causative agent of AIS is Brachyspira spp., particularly Brachyspira pilosicoli (B. pilosicoli), B. intermedia, and B. alvinipulli. They are Gram-negative spiral motile, oxygen-tolerant, and fastidious slow-growing anaerobes of the order Spirochaetes. The bacterium colonizes the lower gastrointestinal tract of most domestic and free-living birds. Layer and breeder chickens are most susceptible to Brachyspira spp. infection and present signs of chronic diarrhea, a low growth rate, delayed or reduced egg production, and poor egg quality. The zoonotic potential of B. pilosicoli is increasingly recognized. Humans can become infected via contact with the feces or meat of infected animals or food contaminated by food handlers. Patients with colonic spirochaetosis exhibit signs of diarrhea, rectal bleeding, and abdominal pain. Diagnosis is usually carried out through conventional isolation and identification as well as recent molecular detection techniques. Tiamulin and other macrolides are considered the gold standard for treating AIS. Unfortunately, resistance of bacteria to such treatments has emerged owing to the urgent need for the development of new interventions. Non-antibiotic interventions such as probiotics show promising results in preventing Brachyspira infection. There are no commercially available vaccines to prevent AIS. However, a recombinant vaccine against B. pilosicoli was recently developed in layer chickens. Here, the review discusses AIS in terms of etiology and pathogenesis, susceptibility and transmission, clinical picture in poultry, human infection, laboratory diagnosis, and prevention and treatment.

Keywords

Brachyspira spp. / Human / Poultry / Treatment / Zoonosis

References

[1] Arnold, M., Swam, H., Crienen, A., Schüpbach-Regula, G., von Berg, S. and Nathues, H. 2023. Prevalence and risk factors for Brachyspira spp. in pig herds with a history of diarrhea in six European countries. Preventive Veterinary Medicine, 213:105862. https://doi.org/10.1016/j.prevetmed.2023.105862.

[2] BackhansA, JanssonDS, AspánA, FellströmC. Typing of Brachyspira spp. from rodents, pigs and chickens on Swedish farms. Veterinary Microbiology, 2011, 153: 156-162

[3] BernardeauM, GueguenM, SmithDG, Corona-BarreraE, VernouxJP. In vitro antagonistic activities of Lactobacillus spp. against Brachyspira hyodysenteriae and Brachyspira pilosicoli. Veterinary Microbiology, 2009, 138: 184-190

[4] BrookeCJ, HampsonDJ, RileyTV. In vitro antimicrobial susceptibility of Brachyspira pilosicoli isolates from humans. Antimicrobial Agents and Chemotherapy, 2003, 47: 2354-2357

[5] BurchDGS, HardingC, AlvarezR, ValksM. Treatment of a field case of avian intestinal spirochaetosis caused by Brachyspira pilosicoli with tiamulin. Avian Pathology, 2006, 35: 211-216

[6] CardRM, StubberfieldE, RogersJ, Nunez-GarciaJ, EllisRJ, AbuOunM, StrugnellB, TealeC, WilliamsonS, AnjumMF. Identification of a new antimicrobial resistance gene provides fresh insights into pleuromutilin resistance in Brachyspira hyodysenteriae, etiological agent of swine dysentery. Frontiers in Microbiology, 2018, 9: 1183

[7] CarpentieriDF, Souza-MoronesS, GardettoJS, RossHM, DowneyK, IngeboK, SiawE. Intestinal spirochetosis in children: Five new cases and a 20-year review of the literature. Pediatric and Developmental Pathology, 2010, 13: 471-475

[8] Casas, V., Rodríguez-Asiain, A., Pinto-Llorente, R., Vadillo, S., Carrascal, M. and Abian, J. 2017. Brachyspira hyodysenteriae and B. pilosicoli proteins recognized by sera of challenged pigs. Frontiers in Microbiology, 8:723. https://doi.org/10.3389/fmicb.2017.00723.

[9] ChristodoulidesM, de OliveiraD, ClearyDW, HumbertMV, Machado-de-ÁvilaRA, La RagioneRM. An in silico reverse vaccinology study of Brachyspira pilosicoli, the causative organism of intestinal spirochaetosis, to identify putative vaccine candidates. Process Biochemistry, 2022, 122: 128-148

[10] Corona-BarreraE, SmithDG, MurrayB, ThomsonJR. Efficacy of seven disinfectant sanitizers on field isolates of Brachyspira pilosicoli. Veterinary Record, 2004, 154: 473-474

[11] DassanayakeRP, CaceresNE, SarathG, DuhamelGE. Biochemical properties of membrane-associated proteases of Brachyspira pilosicoli isolated from humans with intestinal disorders. Journal of Medical Microbiology, 2004, 53: 319-323

[12] Gan, J., Bryant, C., Arul, D. and Parmar, C. 2017. Intestinal spirochaetosis mimicking acute appendicitis with review of the literature. BMJ Case Reports, 2017, bcr2017221574. https://doi.org/10.1136/2Fbcr-2017-221574.

[13] GoodsallTM, TalleyNJ, RassamL, WoodNK, ZalaA, JonesM, WalkerMM. Unique pathology of colonic spirochaetosis characterized by mucosal eosinophilia is linked to diarrhea and IBS. Gut, 2017, 66: 978-979

[14] GoulartT, GruchouskeiL, GonçalvesJ, CavasinJP, MatosMR, FaccinM, ViottAM. Diagnosis of Brachyspira pilosicoli, Brachyspira hyodysenteriae and Brachyspira intermedia in hens and laying hens in the western region of Paraná through bacterial isolation and identification in qPCR. Pesquisa Veterinária Brasileira, 2019, 39: 476-480

[15] Günther, U., Epple, H.J., Heller, F., Loddenkemper, C., Grünbaum, M., Schneider, T., Zeitz M. and Bojarski, C. 2008. In vivo diagnosis of intestinal spirochaetosis by confocal endomicroscopy. Gut, 57:1331–1333.

[16] HaleemA, Al-HindiH, Al HusseiniH, JubouryM. Appendiceal spirochetosis: A light and electron microscope study of two cases. Annals of Saudi Medicine, 2003, 23: 216-219

[17] HampsonDJ. The spirochete Brachyspira pilosicoli, enteric pathogen of animals and humans. Clinical Microbiology Reviews, 2018, 31: e00087-e117

[18] HampsonDJ, AhmedN. Spirochaetes as intestinal pathogens: Lessons from a Brachyspira genome. Gut Pathogen, 2009, 1: 10

[19] HampsonDJ, WangP. Colonic spirochetes: What has genomics taught us?. Current Topics in Microbiology and Immunology, 2018, 415: 273-294

[20] HampsonDJ, RobertsonID, LaT, OxberrySL, PethickDW. Influences of diet and vaccination on colonization of pigs by the intestinal spirochaete Brachyspira (Serpulina) pilosicoli. Veterinary Microbiology, 2000, 73: 75-84

[21] HampsonDJ, OxberrySL, StephensCP. Influence of in-feed zinc bacitracin and tiamulin treatment on experimental avian intestinal spirochaetosis caused by Brachyspira intermedia. Avian Pathology, 2002, 31: 285-291

[22] HampsonDJ, PhillipsND, PluskeJR. Dietary enzyme and zinc bacitracin reduce colonization of layer hens by the intestinal spirochaete Brachyspira intermedia. Veterinary Microbiology, 2002, 86: 351-360

[23] HampsonDJ, StephensCP, OxberrySL. Antimicrobial susceptibility testing of Brachyspira intermedia and Brachyspira pilosicoli isolates from Australian chickens. Avian Pathology, 2006, 35: 12-16

[24] HampsonDJ, LaT, PhillipsND. Emergence of Brachyspira species and strains: Reinforcing the need for surveillance. Porcine Health Management, 2015, 1: 8

[25] HampsonDJ, LugsomyaK, LaT, PhillipsND, TrottDJ, AbrahamS. Antimicrobial resistance in Brachyspira - An increasing problem for disease control. Veterinary Microbiology, 2019, 229: 59-71

[26] Hampson, D.J., Oxberry, S.L. and La, T. 2006a. Potential for zoonotic transmission of Brachyspira pilosicoli. Emerging Infectious Diseases, 12:869–870. https://doi.org/10.3201/2Feid1205.051180.

[27] Hampson, D.J., 2013. Avian Intestinal Spirochetosis. In Swayne D.E., Glisson J.R., McDougald L.R., Nolan L.K., Suarez D.L., Nair V. (Eds.). Diseases of Poultry, 13^th ed., Ames: Wiley-Blackwell. pp. 995–1007.

[28] HarmsM, SchmidtV, HeydelT, HauptmannJ, AhlersC, BergmannR, BaumsCG. Differentiation of Brachyspira spp. isolated from laying hens using PCR-based methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Journal of Veterinary Diagnostic Investigation, 2018, 30: 545-553

[29] HelbingR, OsterheldMC, VaudauxB, JatonK, NydeggerA. Intestinal spirochetosis mimicking inflammatory bowel disease in children. BMC Pediatrics, 2012, 12: 163

[30] HerbstW, WillemsH, HeuserJ, EwersC. Isolation and antimicrobial susceptibility of Brachyspira species from feces of layer chickens in Germany. Tierärztliche Praxis Ausgabe G: Großtiere/Nutztiere, 2018, 46: 29-34

[31] HessC, ZlochA, BilicI, HacksteinerK, KuchlingS, HessM. High prevalence of Brachyspira spp. in layers kept in alternative husbandry systems associated with frequent species variations from end of rearing to slaughter. Avian Pathology, 2017, 46: 481-487

[32] HillenS, WillemsH, HerbstW, RohdeJ, ReinerG. Mutations in the 50S ribosomal subunit of Brachyspira hyodysenteriae associated with altered minimum inhibitory concentrations of pleuromutilins. Veterinary Microbiology, 2014, 172: 223-229

[33] JamshidiA, HampsonDJ. The eggs from laying hens infected with Brachyspira pilosicoli may not be a potential source of infection for human. Iranian Journal of Veterinary Research, 2005, 6: 28-34

[34] JamshidiA, HampsonDJ. Zinc bacitracin enhances colonization by the intestinal spirochaete Brachyspira pilosicoli in experimentally infected layer hens. Avian Pathology, 2002, 31: 293-298

[35] JamshidiA, HampsonDJ. Experimental infection of layer hens with a human isolate of Brachyspira pilosicoli. Journal of Medical Microbiology, 2003, 52: 361-364

[36] JanssonDS, PerssonM, ZimmermanU, JohanssonKE. Phenotypic and genetic diversity among intestinal spirochaetes (genus Brachyspira) in free-living wild mallards (Anas platyrhynchos) sampled in southern Sweden. Systematic and Applied Microbiology, 2011, 34: 566-575

[37] JensenTK, BoyeM, AhrensP, KorsagerB, TeglbjaergPS, LindboeCF, MøllerK. Diagnostic examination of human intestinal spirochetosis by fluorescent in situ hybridization for Brachyspira aalborgi, Brachyspira pilosicoli, and other species of the genus Brachyspira (Serpulina). Journal of Clinical Microbiology, 2001, 39: 4111-4118

[38] LaT, PhillipsND, ReichelMP, HampsonDJ. Protection of pigs from swine dysentery by vaccination with recombinant BmpB, a 29.7 kDa outer-membrane lipoprotein of Brachyspira hyodysenteriae. Veterinary Microbiology, 2004, 102: 97-109

[39] LaT, NeoE, PhillipsND, HampsonDJ. Genes encoding ten newly designated OXA-63 group class D β-lactamases identified in strains of the pathogenic intestinal spirochaete Brachyspira pilosicoli. Journal of Medical Microbiology, 2015, 64: 1425-1435

[40] LaT, PhillipsND, HampsonDJ. Vaccination of chickens with the 34 kDa carboxy-terminus of Bpmp72 reduces colonization with Brachyspira pilosicoli following experimental infection. Avian Pathology, 2019, 48: 80-85

[41] LamJKS, RabuszkoL, FitzpatrickC, WilliamsD, RichardsonD. Antimicrobial treatment for human intestinal spirochaetosis: A systematic review. Frontline Gastroenterology, 2024, 15: 408-416

[42] Le RoyCI, MappleyLJ, La RagioneRM, WoodwardMJ, ClausSP. Brachyspira pilosicoli-induced avian intestinal spirochaetosis. Microbial Ecology on Health and Disease, 2015, 26: 28853

[43] Ludwig, W., Euzeby, J. and Whitman, W.B., 2008. Draft taxonomic outline of the Bacteroidetes, Planctomycetes, chlamydiae, spirochaetes, Fibrobacteres, Fusobacteria, Acidobacteria, Verrucomicrobia, Dictyoglomi and Gemmatimonadetes. Bergey Vol 4 〈www.bergeysorg/outlines/2008〉, p. Outlinepdf01/05/12 2008.

[44] MappleyLJ, BlackML, AbuOunM, DarbyAC, WoodwardMJ, ParkhillJ, TurnerAK, BellgardMI, LaT, PhillipsND, La RagioneRM, HampsonDJ. Comparative genomics of Brachyspira pilosicoli strains: Genome rearrangements, reductions and correlation of genetic compliment with phenotypic diversity. BMC Genomics, 2012, 13: 454

[45] MappleyLJ, TchórzewskaMA, NunezA, WoodwardMJ, La RagioneRM. Evidence for systemic spread of the potentially zoonotic intestinal spirochaete Brachyspira pilosicoli in experimentally challenged laying chickens. Journal of Medical Microbiology, 2013, 62: 297-302

[46] MappleyLJ, TchórzewskaMA, NunezA, WoodwardMJ, BramleyPM, La RagioneRM. Oral treatment of chickens with Lactobacillus reuteri LM1 reduces Brachyspira pilosicoli-induced pathology. Journal of Medical Microbiology, 2013, 62: 287-296

[47] MappleyLJ, TchórzewskaMA, CooleyWA, WoodwardMJ, La RagioneRM. Lactobacilli antagonize the growth, motility, and adherence of Brachyspira pilosicoli: a potential intervention against avian intestinal spirochetosis. Applied and Environmental Microbiology, 2011, 77: 5402-5411

[48] Martínez-LoboFJ, HidalgoÁ, GarcíaM, ArgüelloH, NaharroG, CarvajalA, RubioP. First identification of “Brachyspira hampsonii” in wild European waterfowl. PLoS One, 2013, 8: e82626

[49] McFadzeanH, SchockA, StubberfieldE, CardRM, ThomsonJ, RohdeJ, MurrayL, Velo-RegoE, AinsworthH, BarlowAM, WelchmanD. Retrospective analysis of necrotizing typhlitis cases associated with Brachyspira spp. in British rheas. Avian Pathology, 2021, 21: 1-11

[50] MikoszaAS, LaT, de BoerWB, HampsonDJ. Comparative prevalences of Brachyspira aalborgi and Brachyspira (Serpulina) pilosicoli as etiologic agents of histologically identified intestinal spirochetosis in Australia. Journal of Clinical Microbiology, 2001, 39: 347-350

[51] MirajkarNS, PhillipsND, LaT, HampsonDJ, GebhartCJ. Characterization and recognition of Brachyspira hampsonii sp. nov., a novel intestinal spirochete that is pathogenic to pigs. Journal of Clinical Microbiology, 2016, 54: 2942-2949

[52] MovahediA, HampsonDJ. Evaluation of recombinant Brachyspira pilosicoli oligopeptide-binding proteins as vaccine candidates in a mouse model of intestinal spirochaetosis. Journal of Medical Microbiology, 2010, 59: 353-359

[53] MushtaqM, ZubairS, RåsbäckT, Bongcam-RudloffE, JanssonDS. Brachyspira suanatina sp nov, an enteropathogenic intestinal spirochaete isolated from pigs and mallards: genomic and phenotypic characteristics. BMC Microbiology, 2015, 15: 208

[54] NakamuraS, AdachiY, GotoT, MagariyamaY. Improvement in motion efficiency of the spirochete Brachyspira pilosicoli in viscous environments. Biophysical Journal, 2006, 90: 3019-3026

[55] NareshR, HampsonDJ. Attraction of Brachyspira pilosicoli to mucin. Microbiology, 2010, 156: 191-197

[56] NareshR, HampsonDJ. Exposure to norepinephrine enhances Brachyspira pilosicoli growth, attraction to mucin and attachment to Caco-2 cells. Microbiology, 2011, 157: 543-547

[57] NareshR, HampsonDJ. Strains of the intestinal spirochaete Brachyspira pilosicoli attach to and aggregate erythrocytes. Letters in Applied Microbiology, 2014, 58: 65-69

[58] NeoE, LaT, PhillipsND, HampsonDJ. Multiple locus variable number tandem repeat analysis (MLVA) of the pathogenic intestinal spirochaete Brachyspira pilosicoli. Veterinary Microbiology, 2013, 163: 299-304

[59] NishiiS, HigashiyamaM, OgataS, KomotoS, ItoS, MizoguchiA, TeradaH, FuruhashiH, TakajoT, ShirakabeK, WatanabeC, TomitaK, NagaoS, MiuraS, HokariR. Human intestinal spirochetosis mimicking ulcerative colitis. Clinical Journal of Gastroenterology, 2018, 11: 145-149

[60] OgataS, HigashiyamaM, AdachiY, OharaI, NishiyamaJ, OkusaY, TakeoH, SatoK, NakanishiK, KawaiT. Imprint cytology detects floating Brachyspira in human intestinal spirochetosis. Human Pathology, 2010, 41: 249-254

[61] OgataS, ShimizuK, NakanishiK. Human intestinal spirochetosis: Right-side preference in the large intestine. Annals of Diagnostic Pathology, 2015, 19: 414-417

[62] Passey, J.L. and La Ragione, R.M., 2022. JMM profile: Brachyspira species: the causative agent of avian intestinal spirochaetosis. Journal of Medical Microbiology  71. https://doi.org/10.1099/jmm.0.001495.

[63] PhillipsND, LaT, PluskeJR, HampsonDJ. The wheat variety used in the diet of laying hens influences colonization with the intestinal spirochaete Brachyspira intermedia. Avian Pathology, 2004, 33: 586-590

[64] PhillipsND, LaT, HampsonDJ. A cross-sectional study to investigate the occurrence and distribution of intestinal spirochaetes (Brachyspira spp.) in three flocks of laying hens. Veterinary Microbiology, 2005, 105: 189-198

[65] PrimN, PericasR, EspañolM, RiveraA, MirelisB, CollP. Bloodstream infection due to Brachyspira pilosicoli in a patient with multiorgan failure. Journal of Clinical Microbiology, 2011, 49: 3697-3699

[66] PringleM, PoehlsgaardJ, VesterB, LongKS. Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase center are associated with reduced susceptibility to tiamulin in Brachyspira spp. isolates. Molecular Microbiology, 2004, 54: 1295-1306

[67] PringleM, FellströmC, JohanssonKE. Decreased susceptibility to doxycycline associated with a 16S rRNA gene mutation in Brachyspira hyodysenteriae. Veterinary Microbiology, 2007, 123: 245-248

[68] ProhaskaS, PflügerV, ZieglerD, ScherrerS, FreiD, LehmannA, WittenbrinkMM, HuberH. MALDI-TOF MS for identification of porcine Brachyspira species. Letters in Applied Microbiology, 2014, 58: 292-298

[69] Rebollada-MerinoA, Ugarte-RuizM, Gómez-BuendíaA, BárcenaC, GarcíaN, DomínguezL, Rodríguez-BertosA. Cecal reduction of Brachyspira and lesion severity in laying hens supplemented with fermented defatted ‘Alperujo’. Fermentation, 2022, 8: 550

[70] RohdeJ, Habighorst-BlomeK. An update on the differentiation of Brachyspira species from pigs with nox-PCR-based restriction fragment length polymorphism. Veterinary Microbiology, 2012, 158: 211-215

[71] RojasP, PetrichA, SchulzeJ, WiessnerA, LoddenkemperC, EppleHJ, SterlacciW, ViethM, KikhneyJ, MoterA. Distribution and phylogeny of Brachyspira spp. in human intestinal spirochetosis revealed by FISH and 16S rRNA-gene analysis. Anaerobe, 2017, 47: 25-32

[72] RubinJE, HarmsNJ, FernandoC, SoosC, DetmerSE, HardingJC, HillJE. Isolation and characterization of Brachyspira spp. including “Brachyspira hampsonii” from lesser snow geese (Chen caerulescens caerulescens) in the Canadian Arctic. Microbial Ecology, 2013, 66: 813-822

[73] Se, C.Y., Yong, F.F., Tan, H.M., Yeo, W.M. and Teo inventors, A.Y.L., 2008. Broad-spectrum antibacterial and antifungal activity of Lactobacillus Johnsonii D115. United States patent.

[74] SmithJL. Colonic spirochetosis in animals and humans. Journal of Food Protection, 2005, 68: 1525-15134

[75] SongY, HampsonDJ. Development of a multiplex qPCR for detection and quantitation of pathogenic intestinal spirochaetes in the feces of pigs and chickens. Veterinary Microbiology, 2009, 137: 129-136

[76] SongY, LaT, PhillipsND, HampsonDJ. Development of a serological ELISA using a recombinant protein to identify pig herds infected with Brachyspira hyodysenteriae. Veterinary Journal, 2015, 206: 365-370

[77] StantonTB, HumphreySB, SharmaVK, ZuernerRL. Collateral effects of antibiotics: Carbadox and metronidazole induce VSH-1 and facilitate gene transfer among Brachyspira hyodysenteriae strains. Applied and Environmental Microbiology, 2008, 74: 2950-2956

[78] StephensCP, HampsonDJ. Experimental infection of broiler breeder hens with the intestinal spirochaete Brachyspira (Serpulina) pilosicoli causes reduced egg production. Avian Pathology, 2002, 31: 169-175

[79] StephensCP, HampsonDJ. Evaluation of tiamulin and lincomycin for the treatment of broiler breeders experimentally infected with the intestinal spirochaete Brachyspira pilosicoli. Avian Pathology, 2002, 31: 299-304

[80] StubberfieldE, PringleM, LandenA, VeldmanKT, GeurtsY, JouyF, Le DevendecL, RubinJE, KulathungaD, KristensenKA, ChanterJ, BollardA, JohnsonP, MaycockJ, Habighorst-BlomeK, RohdeJRM. Card Validation of an antimicrobial susceptibility testing protocol for Brachyspira hyodysenteriae and Brachyspira pilosicoli in an international ring trial. Veterinary Microbiology, 2020, 244: 108645

[81] StubberfieldE, SheldonJ, CardRM, AbuOunM, RogersJ, WilliamsonS, KayGL, PallenMJ, AnjumMF. Whole-genome sequencing of Brachyspira hyodysenteriae isolates from England and Wales reveals similarities to European isolates and mutations associated with reduced sensitivity to antimicrobials. Frontiers in Microbiology, 2021, 12, 713233

[82] StubberfieldE, AbuOunM, CardRM, WelchmanD, AnjumMF. Molecular characterization of antimicrobial resistance in Brachyspira species isolated from UK chickens: Identification of novel variants of pleuromutilin and beta-lactam resistance genes. Veterinary Microbiology, 2024, 290 ArticleID: 109992

[83] TessonJR, FontaineaR, FumeryM, FontaineR, GaudetLV, AttencourtC, ChatelainD. Immunohistochemical diagnosis of colonic spirochetosis with anti-treponema antibody in patients consulting for chronic diarrhea. The results of a prospective study conducted in 137 patients. Ann Pathology, 2019, 39: 280-325

[84] TrottD, DavidP, ZuernerRL, BularchD, WannemuehlerM, StaskoJ. Identification and cloning of the gene encoding BmpC: An outer-membrane lipoprotein associated with Brachyspira pilosicoli membrane vesicles. Microbiology, 2004, 150: 1041-1053

[85] TsinganouE, GebbersJO. Human intestinal spirochetosis–a review. German Medical Science, 2010, 8: Doc01

[86] Umeda, S., Serizawa, H., Kobayashi, T., Toyonaga, T., Saito, E., Nakano, M., Higuchi, H., Tsunematsu, S., Watanabe, N., Hibi, T. and Morinaga, S., 2017. Clinical significance of human intestinal spirochetosis: a retrospective study. Nihon Shokakibyo Gakkai Zasshi, 114, 230 –237. https://doi.org/10.11405/nisshoshi.114.230

[87] VerlindenM, BoyenF, PasmansF, GarmynA, HaesebrouckF, MartelA. Antimicrobial susceptibility pattern of Brachyspira intermedia isolates from European layers. Microbial Drug Resistance, 2011, 17: 485-488

[88] VerlindenM, PasmansF, GarmynA, De ZutterL, HaesebrouckF, MartelA. Occurrence of viable Brachyspira spp. on carcasses of spent laying hens from supermarkets. Food Microbiology, 2012, 32: 321-324

[89] VerlindenM, PasmansF, MahuM, Vande MaeleL, De PauwN, YangZ, HaesebrouckF, MartelA. In vitro sensitivity of poultry Brachyspira intermedia isolates to essential oil components and in vivo reduction of Brachyspira intermedia in rearing pullets with cinnamaldehyde feed supplementation. Poultry Science, 2013, 92: 1202-1207

[90] Walker, M.M., Talley, N.J., Ingana¨s, L., Engstrand, L., Jones, M.P., Nyhlin, H., Agréus, L., Kjellstrom, L., Öst Å. and Andreasson A. 2015. Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden. Human Pathology 46:277–283. https://doi.org/10.1016/j.humpath.2014.10.026.

[91] Wanchanthuek, P., Bellgard, M.I., La, T., Ryan, K., Moolhuijzen, P., Chapman, B., Black, M., Schibeci, D., Hunter, A., Barrero, R., Phillips, N.D. and Hampson D.J. 2010. The complete genome sequence of the pathogenic intestinal spirochete Brachyspira pilosicoli and comparison with other Brachyspira genomes.PLoS One 5:e11455. https://doi.org/10.1371/2Fjournal.pone.0011455.

[92] WeissenbockH, MadernerA, HerzogAM, LussyH, NowotnyN. Amplification and sequencing of Brachyspira spp. specific portions of nox using paraffin-embedded tissue samples from clinical colitis in Austrian pigs shows frequent solitary presence of Brachyspira murdochii. Veterinary Microbiology, 2005, 111: 67-75

[93] WestermanLJ, StelHV, SchipperME, BakkerLJ, Neefjes-BorstEA, van den BrandeJH, BoelEC, SeldenrijkKA, SiersemaPD, BontenMJ, KustersJG. Development of a real-time PCR for identification of brachyspira species in human colonic biopsies. PLoS ONE, 2012, 7 e52281

[94] WoodEJ, SeviourRJ, SiddiqueABM, GlaisherRW, WebbRI, TrottDJ. Spherical body formation in the spirochaete Brachyspira hyodysenteriae. FEMS Microbiology Letters, 2006, 259: 14-19

[95] WoodwardMJ, MappleyL, Le RoyC, ClausSP, DaviesP, ThompsonG, La RagioneRM. Drinking water application of Denagard® tiamulin for control of Brachyspira pilosicoli infection of laying poultry. Research in Veterinary Science, 2015, 103: 87-95

[96] ZuernerRL, StantonTB, MinionFC, LiC, CharonNW, TrottDJ, HampsonDJ. Genetic variation in Brachyspira: Chromosomal rearrangements and sequence drift distinguish B. pilosicoli from B. hyodysenteriae. Anaerobe, 2004, 10: 229-237

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