Intestinal Spirochaetosis Research Articles

Antimicrobial treatment for human intestinal spirochaetosis: a systematic review

IntroductionThe antimicrobial treatment options for patients with intestinal spirochaetosis (caused by Brachyspira pilosicoli and Brachyspira aalborgi) are not well defined. We aimed to systematically review the literature to explore antimicrobial...

Molecular characterization of antimicrobial resistance in Brachyspira species isolated from UK chickens: Identification of novel variants of pleuromutilin and beta-lactam resistance genes

Brachyspira species are Gram negative, anaerobic bacteria that colonise the gut of many animals, including poultry. In poultry, Brachyspira species can be commensal (B. innocens, B. murdochii, ‘B. pulli’) or pathogenic (B. pilosicoli, B. intermedia, B. alvinipulli or rarely B. hyodysenteriae), the latter causing avian intestinal spirochaetosis (AIS). Antimicrobial therapy options for treatment is limited, frequently involving administration of the pleuromutilin, tiamulin, in water. In this study 38 Brachyspira isolates from chickens in the UK, representing both commensal and pathogenic species, were whole genome sequenced to identify antimicrobial resistance (AMR) mechanisms and the minimum inhibitory concentration (MIC) to a number of antimicrobials was also determined. We identified several new variants of blaOXA in B. pilosicoli and B. pulli isolates, and variations in tva which led to two new tva variants in B.murdochii and B.pulli. A number of isolates also harboured mutations known to encode AMR in the 16S and 23S rRNA genes. The percentage of isolates that were genotypically multi-drug resistance (MDR) was 16%, with the most common resistance profile being: tetracycline, pleuromutilin and beta-lactam, which were found in three ‘B. pulli’ and one B. pilosicoli. There was good correlation with the genotype and the corresponding antibiotic MIC phenotypes: pleuromutilins (tiamulin and valnemulin), macrolides (tylosin and tylvalosin), lincomycin and doxycycline. The occurrence of resistance determinants identified in this study in pathogenic Brachyspira, especially those which were MDR, is likely to impact treatment of AIS and clearance of infections on farm.

Factors and presenting symptoms associated with intestinal spirochaetosis in men who have sex with men: A systematic review.

The transmission dynamics and presenting symptoms of intestinal spirochaetosis (Brachyspira pilosicoli, Brachyspira aalborgi) are poorly understood but is seen more frequently in men who have sex with men (MSM) where sexual transmission may occur. We aimed to systemically review the literature to define the factors and presenting symptoms associated with intestinal spirochaetosis in MSM. We systematically searched three bibliographical databases (MEDLINE, EMBASE and Scopus) for manuscripts written in English up to November 2022. The primary author conducted an initial screen and three authors conducted independent reviews to determine the final eligible manuscripts. We only included manuscripts where there were specific data on factors and presenting symptoms associated with intestinal spirochaetosis in MSM. Fifteen manuscripts published between 1981 and 2022 met the inclusion criteria that included 188 MSM. Sexually transmitted intestinal spirochaetosis in MSM was associated with-living with HIV (including having a low CD4 count <200 mm3), having a concomitant sexually transmitted infection, a history of a sexually transmitted infection, co-infection with intestinal parasites; and sexual behaviour including oro-anal sexual contact, oro-genital contact, fisting, condom-less anal sex, receptive anal sex, multiple non-regular sexual partners and increased number of lifetime sexual partners. The presenting symptoms of MSM with intestinal spirochaetosis were diarrhoea, abdominal pain, constitutional symptoms and proctitis, including rectal pain, rectal bleeding rectal discharge, flatulence and tenesmus. We have highlighted some biological and behavioural factors and presenting symptoms associated with intestinal spirochaetosis in MSM which provide insight for clinicians, guidelines and future public health control strategies.

Prevalence and risk factors of Brachyspira spp. in pig herds with a history of diarrhoea in six European countries

Swine dysentery and porcine intestinal spirochaetosis caused by Brachyspira (B.) hyodysenteriae and B. pilosicoli, respectively, are important diseases in swine production worldwide. The aim of this study was to assess the prevalence of both pathogens in farms with a history of diarrhoea within the last 12 months in Denmark, France, Germany, the Netherlands, Spain, and United Kingdom. In addition, risk factors for their prevalence and correlations between presence of different Brachyspira spp. and Lawsonia intracellularis were investigated. Therefore, faecal samples of 6355 nursery to finishing pigs out of 144 herds were sampled in 2017/2018 during a prevalence study on Lawsonia intracellularis, followed by polymerase chain reaction analysis for Brachyspira spp. detection. Herd prevalence differed significantly between countries, from 4.2% to 45.8% for B. hyodysenteriae and 8.3–87.5% for B. pilosicoli, respectively (p < 0.01). For the within-herd prevalence (in positive herds), these values ranged from 2.2% to 27.0% for B. hyodysenteriae and 3.3–50.8% for B. pilosicoli. Mixed infections occurred in 34.1% and 58.7% of B. hyodysenteriae positive samples with Lawsonia intracellularis or B. pilosicoli, respectively. In 43.2% of B. pilosicoli positive samples, Lawsonia intracellularis was detected simultaneously. Overall, nursery pigs were significantly less often positive for one of the pathogens than growing or finishing pigs (p < 0.001). The absence of gastrointestinal problems like diarrhoea, routine use of antimicrobials and well performed biosecurity measures were some of the factors associated with lower detection rate of Brachyspira spp. Surprisingly, deworming of different age categories also showed associations with the detection of Brachyspira spp. which, however, were not always equally directed, and therefore require further investigations. The only risk factor significant for both Brachyspira spp. was the median number of ≥ 30 nursery pigs per pen after weaning, compared to smaller group sizes. Both pathogens were detected with varying frequency between the six European countries. This should be considered in the probability of disease and in case of transnational transport, to prevent spread of pathogens. In addition, the frequent presence of mixed infections in some countries should be taken into account in diagnostics. The most important protective factors against Brachyspira spp. presence on farm are biosecurity measures, while potential new factors such as deworming still require further investigation.

Intestinal spirochaetosis in an immunocompetent host: case report and review of literature

Intestinal spirochaetosis in an immunocompetent host: case report and review of literature

JMM Profile: Brachyspira species: the causative agent of Avian Intestinal Spirochaetosis.

The genus Brachyspira includes nine officially recognised species, several of which are pathogenic to mammals and birds. B. pilosicoli, B. intermedia, and B. alvinipulli are the causative agents of avian intestinal spirochaetosis (AIS), a gastrointestinal disease in poultry caused by the colonisation of the caeca and/ or colo-rectum by Brachyspira. AIS primarily affects layer hens and broiler breeders over the age of 15 weeks. The severity of symptoms can vary but typically presents as reduced growth rates, delayed onset of lay, reduced egg production, faecally stained eggs, and diarrhoea. This disease is estimated to cost the UK laying industry £18 million per annum. Brachyspira colonisation in humans is common in populations from developing countries and HIV-positive patients; however, it is rarely investigated as a human pathogen.

An in silico reverse vaccinology study of Brachyspira pilosicoli, the causative organism of intestinal spirochaetosis, to identify putative vaccine candidates

Brachyspira pilosicoli is a zoonotic bacterium that can cause intestinal spirochaetosis (IS) in avian species (AIS), pigs (PIS) and humans (HIS). In the absence of vaccines to prevent infections, we used genome-based reverse vaccinology (RV) to identify putative B. pilosicoli vaccine candidates. Genome sequence of B. pilosicoli strain B2904, an AIS isolate, was analysed with PSORTb3, CELLO, SOSUIGramN, LipoP, SignalP-5.0, TMHMM, BLAST 2.12.0 + , PDB database, SEED Viewer, eggNOG-mapper, UniProt, VaxiJen and Vaxign2, and Tblastn to generate a RV list of putative vaccine candidates. We also generated a linear B-cell chimera antigen using Blast-p, Emini Surface Accessibility Prediction, ABCpred, Expasy ProtParam and PepCalc programs. RV defined a list of 162 proteins containing 48 Outer Membrane (OM), 27 OM/Extracellular, 27 Extracellular, 4 Periplasm, 2 Surface, 2 Cytoplasm and 52 Unknown proteins. The list was characterised by an abundance of SPII lipoproteins. We found that genes encoding amino acid sequences of 146/162 (90%) proteins were present in 19 other B. pilosicoli genomes. A linear B-cell chimera antigen was generated from the amino acid sequences of 18 OM and Extracellular proteins. Our contemporary RV study represents a starting point for a comprehensive vaccine development strategy for preventing intestinal spirochaetosis.

Distribution, genetic heterogeneity, and antimicrobial susceptibility of Brachyspira pilosicoli in Swiss pig herds

Brachyspira (B.) pilosicoli is a bacterium causing porcine intestinal spirochaetosis, a disease characterized by diarrhoea and depressed growth rates especially in nursery and fattening pigs. Knowledge of the epidemiology and antimicrobial susceptibility of this pathogen is limited. Therefore, the aim of this study was to analyse the distribution, genetic heterogeneity, and antimicrobial susceptibility of B. pilosicoli field isolates from Swiss pig farms. Faecal swabs of 693 animals originating from 156 herds were analysed for the presence of Brachyspira spp. using culture and polymerase chain reaction identification. Further characterisation was performed using multilocus sequence typing (MLST) and broth dilution antimicrobial susceptibility testing. With 52.6% positive herds, B. pilosicoli could be frequently isolated from herds with animals suffering from diarrhoea. In herds with animals without clinical signs of diarrhoea, detection was significantly less frequent with only 10.5% positive herds (p 0.001). Among 80 isolates used for typing, genetic heterogeneity was observed with 44 different sequence types (ST) which often differed from herd to herd. No predominant ST was observed. More than 73.0% of the 41 B. pilosicoli isolates analysed, showed minimal inhibitory concentration values above the wild type cut-off values for lincomycin, tylvalosin and/ or tylosin. For tiamulin, valnemulin and doxycycline, this was the case in 48.8%, 43.9% and 36.6%, respectively. In conclusion, a diverse population of B. pilosicoli exhibited decreased susceptibility to antimicrobials used against Brachyspira infections. Monitoring of resistance in Brachyspira spp. is highly recommended to support targeted use of antimicrobials in pigs.

Avian intestinal spirochaetosis

This datasheet on avian intestinal spirochaetosis covers Identity, Overview, Associated Diseases, Pests or Pathogens, Distribution, Hosts/Species Affected, Diagnosis, Pathology, Epidemiology, Prevention/Control, Further Information.

A Case of Intestinal Spirochaetosis with Weight Loss and Diarrhea Treated with Metronidazole

A Case of Intestinal Spirochaetosis with Weight Loss and Diarrhea Treated with Metronidazole

Intestinal spirochaetosis mimicking acute appendicitis with review of the literature

Human intestinal spirochaetosis is a well-established micro-organism existing in the colon. It is less commonly seen in the appendix, and rarely presents as acute appendicitis. We present a case of...

Brachyspira hyodysenteriae and B. pilosicoli Proteins Recognized by Sera of Challenged Pigs.

The spirochetes Brachyspira hyodysenteriae and B. pilosicoli are pig intestinal pathogens that are the causative agents of swine dysentery (SD) and porcine intestinal spirochaetosis (PIS), respectively. Although some inactivated bacterin and recombinant vaccines have been explored as prophylactic treatments against these species, no effective vaccine is yet available. Immunoproteomics approaches hold the potential for the identification of new, suitable candidates for subunit vaccines against SD and PIS. These strategies take into account the gene products actually expressed and present in the cells, and thus susceptible of being targets of immune recognition. In this context, we have analyzed the immunogenic pattern of two B. pilosicoli porcine isolates (the Spanish farm isolate OLA9 and the commercial P43/6/78 strain) and one B. hyodysenteriae isolate (the Spanish farm V1). The proteins from the Brachyspira lysates were fractionated by preparative isoelectric focusing, and the fractions were analyzed by Western blot with hyperimmune sera from challenged pigs. Of the 28 challenge-specific immunoreactive bands detected, 21 were identified as single proteins by MS, while the other 7 were shown to contain several major proteins. None of these proteins were detected in the control immunoreactive bands. The proteins identified included 11 from B. hyodysenteriae and 28 from the two B. pilosicoli strains. Eight proteins were common to the B. pilosicoli strains (i.e., elongation factor G, aspartyl-tRNA synthase, biotin lipoyl, TmpB outer membrane protein, flagellar protein FlaA, enolase, PEPCK, and VspD), and enolase and PEPCK were common to both species. Many of the identified proteins were flagellar proteins or predicted to be located on the cell surface and some of them had been previously described as antigenic or as bacterial virulence factors. Here we report on the identification and semiquantitative data of these immunoreactive proteins which constitute a unique antigen collection from these bacteria.

Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition

Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a 1H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development.

A novel multiplex qPCR targeting 23S rDNA for diagnosis of swine dysentery and porcine intestinal spirochaetosis.

BackgroundA multiplex qPCR targeting a 128 bp region on the 23S rDNA gene was developed for detection of Brachyspira (B.) hyodysenteriae and B. pilosicoli, the agents of swine dysentery (SD) and porcine intestinal spirochaetosis (PIS), together with a triplet of apathogenic Brachyspira spp. (B. innocens, B. intermedia, B. murdochii) in porcine feces. The multiplex qPCR was evaluated against a duplex PCR (La et al., J Clin Microbiol 41:3372–5, 2003).ResultsUsing DNA extracted from fecal culture, the multiplex qPCR showed excellent agreement with the duplex PCR (κ = 0.943 and 0.933). In addition, thanks to the three probes whereof one detecting the apathogenic Brachyspria spp., a more diversified overview of the brachyspiral flora in porcine fecal samples can be delivered as a part of the routine diagnostic. The multiplex qPCR with a limit of detection of 5–10 genomic equivalents (GE) per reaction (6 × 102 GE per gram) allows reliable detection of Brachyspira species directly from fecal swab DNA. In line with this, analysis of 202 fecal swabs in comparison with culture-based qPCR showed a high agreement for the causative agents of SD (B.hyodysenteriae: κ = 0.853, sensitivity 87% specificity 98%).ConclusionThe novel multiplex qPCR is robust and has a high analytical sensitivity and is therefore suitable for high-throughput screening of porcine fecal swabs for the causative agents of SD. This assay can therefore be used for the direct proof of the pathogenic B. spp. in fecal swabs within the scope of a monitoring program.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0939-6) contains supplementary material, which is available to authorized users.

Intestinal Spirochaetosis in a Patient with Crohnʼs Disease on Use of Immunosuppressive Drug

Intestinal Spirochaetosis in a Patient with Crohnʼs Disease on Use of Immunosuppressive Drug

Intestinal spirochaetes (Brachyspira species) in pheasants in Great Britain

AVIAN intestinal spirochaetosis (AIS) is characterised by colonisation of the caecum of birds with spirochaetes of the genus Brachyspira (formerly Serpulina ). In chickens the effects of colonisation vary from...

Brachyspira pilosicoli-induced avian intestinal spirochaetosis.

Avian intestinal spirochaetosis (AIS) is a common disease occurring in poultry that can be caused by Brachyspira pilosicoli, a Gram-negative bacterium of the order Spirochaetes. During AIS, this opportunistic pathogen colonises the lower gastrointestinal (GI) tract of poultry (principally, the ileum, caeca, and colon), which can cause symptoms such as diarrhoea, reduced growth rate, and reduced egg production and quality. Due to the large increase of bacterial resistance to antibiotic treatment, the European Union banned in 2006 the prophylactic use of antibiotics as growth promoters in livestock. Consequently, the number of outbreaks of AIS has dramatically increased in the UK resulting in significant economic losses. This review summarises the current knowledge about AIS infection caused by B. pilosicoli and discusses various treatments and prevention strategies to control AIS.

Drinking water application of Denagard® Tiamulin for control of Brachyspira pilosicoli infection of laying poultry

Avian intestinal spirochaetosis (AIS) caused by Brachyspira spp., and notably Brachyspira pilosicoli, is common in layer flocks and reportedly of increasing incidence in broilers and broiler breeders. Disease manifests as diarrhoea, increased feed consumption, reduced growth rates and occasional mortality in broilers and these signs are shown in layers also associated with a delayed onset of lay, reduced egg weights, faecal staining of eggshells and non-productive ovaries. Treatment with Denagard® Tiamulin has been used to protect against B. pilosicoli colonisation, persistence and clinical presentation of AIS in commercial layers, but to date there has been no definitive study validating efficacy. Here, we used a poultry model of B. pilosicoli infection of layers to compare the impact of three doses of Denagard® Tiamulin. Four groups of thirty 17week old commercial pre-lay birds were all challenged with B. pilosicoli strain B2904 with three oral doses two days apart. All birds were colonised within 2days after the final oral challenge and mild onset of clinical signs were observed thereafter. A fifth group that was unchallenged and untreated was also included for comparison as healthy birds. Five days after the final oral Brachypira challenge three groups were given Denagard® Tiamulin in drinking water made up following the manufacturer's recommendations with doses verified as 58.7ppm, 113ppm and 225ppm. Weight gain body condition and the level of diarrhoea of birds infected with B. pilosicoli were improved and shedding of the organism reduced significantly (p=0.001) following treatment with Denagard® Tiamulin irrespective of dose given. The level and duration of colonisation of organs of birds infected with B. pilosicoli was also reduced. Confirming previous findings we showed that the ileum, caeca, colon, and both liver and spleen were colonised and here we demonstrated that treatment with Denagard® Tiamulin resulted in significant reduction in the numbers of Brachyspira found in each of these sites and dramatic reduction in faecal shedding (p<0.001) to approaching zero as assessed by culture of cloacal swabs. Although the number of eggs produced per bird and the level of eggshell staining appeared unaffected, egg weights of treated birds were greater than those of untreated birds for a period of approximately two weeks following treatment. These data conclusively demonstrate the effectiveness of Denagard® Tiamulin in reducing B. pilosicoli infection in laying hens.

Bibersteinia trehalosi infection in cattle and sheep

Bibersteinia trehalosi infection reported in both calves and lambsBracken poisoning in cattleCopper deficiency in four-month-old pigsAvian intestinal spirochaetosis in free-range layer chickensHaemonchosis, gastric ulceration and coccidiosis in alpacasThese are among...

Intestinal spirochaetes (Brachyspira spp.) colonizing flocks of layer and breeder chickens in Malaysia

Avian intestinal spirochaetosis causes problems including delayed onset of lay and wet litter in adult chickens, and results from colonization of the caecae/rectum with pathogenic intestinal spirochaetes (genus Brachyspira). Because avian intestinal spirochaetosis has not previously been studied in South East Asia, this investigation was undertaken in Malaysia. Faecal samples were collected from 25 farms and a questionnaire was administered. Brachyspira species were detected by polymerase chain reaction in 198 of 500 (39%) faecal samples from 20 (80%) farms, including 16 (94%) layer and four (50%) breeder farms. Pathogenic Brachyspira pilosicoli was identified in five (29%) layer and two (25%) breeder farms whilst pathogenic Brachyspira intermedia was detected in nine (53%) layer and one (12.5%) of the breeder farms. Twelve (80%) layer farms had egg production problems and 11 (92%) were positive for Brachyspira: three (25%) for B. pilosicoli and six (50%) for B. intermedia. Of three breeder farms with egg production problems, one was colonized with B. pilosicoli. Three of ten layer farms with wet litter were positive for B. pilosicoli and six for B. intermedia. Of four breeder farms with wet litter, one was colonized with B. pilosicoli and one with B. intermedia. No significant associations were found between colonization and reduced egg production or wet litter, perhaps because so many flocks were colonized. A significant association (P = 0.041) occurred between a high prevalence of colonization and faecal staining of eggs. There were significant positive associations between open-sided housing (P = 0.006), and flocks aged >40 weeks (P < 0.001) and colonization by pathogenic species.