Vaccination against ovine foot-rot
Abstract
Sheep vaccinated in different ways or left unvaccinated, were challenged by the application of Fusiformis nodosus cultures after exposure of their feet to maceration and to faecal contamination as a source of F. necrophorus. Severe persistent foot-rot developed in 7 unvaccinated controls and 7 vaccinated with F. necrophorus only. Slight infections confined to the interdigital skin developed in 13 of 16 sheep vaccinated with the challenge strain of F. nodosus alone or in combination with F. necrophorus, but all except 3 of these had healed 30 days later. The F. nodosus vaccine was given to 6 sheep with severe foot-rot induced by the method of challenge. Eight weeks after the first dose they had healed completely, whereas 7 controls left unvaccinated were still severely affected. Six infected unvaccinated sheep were cured by parenteral chemotherapy and externally applied formalin. When challenged again they were still fully susceptible.
The superior resistance of the vaccinated sheep was associated with titres of circulating bactericidal antibody far higher than those in the sheep that had been infected only. It is suggested that their resistance was due to the destruction of F. nodosus by antibody and complement diffusing into the infected epidermis.
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Cited by (155)
Evidence of novel Treponema phylotypes implicated in contagious ovine digital dermatitis and association of treponemes with major lameness causing foot pathogens
2023, Microbial PathogenesisIn this study 269 swabs collected from 254 ovine foot lesions and 15 apparently healthy ovine feet were screened by PCR for the presence of major lameness causing foot pathogens viz. Treponema species, D. nodosus, F. necrophorum and T. pyogenes with the presumption that ovine foot lesion positive for Treponema species alone or in association with other three pathogens were categorized as contagious ovine digital dermatitis (CODD). While samples positive for D. nodosus alone or its combination with F. necrophorum and T. pyogenes were considered as footrot (FR) and samples in which F. necrophorum or T. pyogenes was found either alone or in combination were considered as interdigital dermatitis (ID). The overall occurrence of Treponema sp. in ovine foot lesions was 48.0%, and ranged from 33 to 58%. In Treponema positive samples D. nodosus, F. necrophorum and T. pyogenes were present in 34 (27.4%), 66 (54.4%) and 84 (68.5%) in contrast to Treponema negative samples in which these were present in 15 (11.1%), 20 (14.12%) and 17 (12.6%) samples, respectively. The data signifies that Treponema sp. are significantly associated with these foot pathogens and their different combinations with Treponema sp. influence the severity of CODD lesion. The identification of Treponema phylotypes was done by sequencing the 16S rRNA gene fragment of ten representative samples. Out of ten sequences, four (Trep-2, Trep-4, Trep-7 and Trep-10) were identical to Treponema sp. phylotype 1 (PT1) that belongs to phylogroup T. refringens-like, one sequence (Trep-1) was genetically close (90% sequence homology) to Treponema brennaborense while five sequences (Trep-3, Trep-5, Trep-6, Trep-8 and Trep-9) matched with uncultured bacterium clones of treponemes forming separate monophyletic group in phylogenetic tree and could represent new digital dermatitis phylogroup presently containing five ovine specific phylotypes. This is the first report on the presence of Treponema phylotypes other than three digital dermatitis (DD) Treponema phylogroups viz. T. phagedenis-like, T. medium/T. vincentii–like, and T. pedis-like that are frequently detected in CODD lesions. Metagenomic analysis of two representative samples revealed the abundance of genus Treponema in CODD lesion while this genus was absent in swab collected from clinically healthy foot suggesting that it might play primary role in producing CODD. These findings may further aid in understanding the etiopathogenesis of CODD and could help to develop appropriate treatment and mitigation strategies to combat the disease.
The role of foot conformation in susceptibility of Merino sheep to footrot
2022, Small Ruminant ResearchFootrot is an important cause of lameness in small ruminants. It exists in most countries and is a significant cause of production losses. While sheep with persistent footrot may develop misshapen hooves due to inflammation affecting the germinal tissues, the role of foot conformation as a factor affecting the susceptibility to footrot is unknown. Consequently, this study was undertaken to determine whether there is an association. The foot conformation of Merino sheep (n = 44) was assessed prior to infection with Dichelobacter nodosus in an experimental pen infection model. Associations between pre-infection foot conformation parameters and foot lesions that developed as a result of the infection were evaluated using univariable and multivariable logistic regression. Heel height (lateral digit), sole width (lateral digit) and interdigital skin height were significant in univariable models (P < 0.05) but lost significance in multivariable models. Foot conformation may affect the microenvironment and hence the microbial community on the interdigital skin; further studies are warranted with increased sample sizes to better understand the relationship between foot conformation parameters and the susceptibility to footrot in order to assess the potential for genetic selection.
Immunological response of lame sheep to clinical interdigital dermatitis and footrot: Procalcitonin, acute phase proteins, and pro-inflammatory cytokines
2022, Comparative Immunology, Microbiology and Infectious DiseasesCitation Excerpt :An AUC of 0.7–0.9 was considered moderately accurate, an AUC of > 0.9 highly accurate, and an AUC of 1 perfect. The selected sheep with clinical lameness in this study scored 2 (N = 28), scored 3 (N = 19) and scored 4 (N = 6) according to Egerton and Roberts [21,22] scoring system. All samples collected from lame sheep (N = 53) were positive for D. nodosus (100%), whereas F. necrophorum was detected in 19 out of 53 samples in real PCR analysis (35.84%).
In many countries, sheep lameness is a cause of economic concern and a contributing factor to a declining economy. This study aimed to investigate changes in procalcitonin (PCT), acute phase proteins (APPs), and cytokines (CYTs) in response to interdigital dermatitis and footrot in sheep under field conditions, to emphasize their role in the disease pathogenesis, diagnosis, as well as monitoring treatment response. Fifty-three sheep with foot diseases (26 clinical cases with interdigital dermatitis and 27 clinical cases with footrot) and 20 clinically healthy naemi sheep were used in this study. Real time PCR for detection of Fusobacterium necrophorum (F. necrophorum) and Dichelobacter nodosus (D. nodosus) revealed that, all samples collected from lame sheep (N = 53) were positive for D. nodosus (100 %), whereas F. necrophorum was detected in 19 out of 53 samples (35.84 %). The virulent D. nodosus was detected in 48 lameness cases where non-virulent D. nodosus were identified in 5 cases (in concurrent with F. necrophorum). The mean serum levels of PCT, C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (HP), fibrinogen (Fg) and CYTs (IL1-β, IL-1α, IFN-γ, IL-6 and TNF-α) in sheep with clinical interdigital dermatitis and footrot were remarkably higher than those detected in control healthy sheep. The serum levels of PCT, CRP, SAA, HP, Fg, and CYTs markers in lame sheep pre- and post-treatment were measured. A substantial decline was detected in serum levels of tested biomarkers of lame sheep after 14 days of treatment. The ROC curves were created. The AUC was assessed to evaluate the accuracy of each variable in distinguishing diseased and healthy sheep. Based on the ROC curves and AUCs; PCT, CRP, SAA, HP, and CYTs were highly diagnostic and predictive for the treatment response of sheep with clinical interdigital dermatitis and footrot. Moreover, all tested biomarkers had a noteworthy role in disease immuno-pathogenesis. Nevertheless, PCT and CRP are better than other tested APPs and CYTs as diagnostic markers for interdigital dermatitis and footrot. However, PCT only has the ability to differentiate sheep with different lameness score.
Genetic evaluations utilising footrot scores from industry flocks in their essence, incorporate data from a wide range of challenge environments, resulting in potentially large differences in means, variances and distribution of scores across challenges. The date that commencement of infection occurs is generally unknown, and progression of the infection varies with the prevailing environmental and management conditions, virulence of the bacterium Dichelobacter nodosus, as well as the genetic potential and (permanent) environmental ability of animals to resist footrot. In practice, animals are unlikely to be repeatedly scored to identify the best time for comparison, or monitor development of disease progression. Furthermore, field challenges are limited by the need to treat animals before their welfare is compromised. Therefore, the duration and intensity of infection varies and this affects comparisons between animals for their susceptibility. Diseases such as footrot are characterised by multiple categorical scores reflecting clinical stages that describe the progression and relative impact of the disease. This provides the opportunity for the transformation of the data to a standardised prevalence. Scoring events from multiple footrot field challenges under a standardised protocol were used to establish a series of transition matrices to describe disease progression between scores over time. These transition matrices were used to standardise challenge events to the more severe scoring events, observed later in the challenge. The accuracy of the transition technique was tested by comparing the ranking of animals and sires against the observed scores. Transitioning the data from low disease prevalence to the higher prevalence at the subsequent scoring event improved the correlations between the scoring events, at the animal level, by upwards of 0.10 across challenges. The utilisation of a transition matrix to transform low prevalence disease challenges by taking into account the natural biological rate of progression through the clinical stages of the disease provides a more accurate technique to account for variation in disease prevalence. The transition technique increases the acceptable range of disease expression targeted by producers when scoring virulent footrot challenges reducing the need for repeat scoring and allowing earlier treatment and reducing the impact of the disease on the host animal.
Gamithromycin in sheep: Pharmacokinetics and clinical evaluation against ovine footrot
2022, Research in Veterinary ScienceIn the context of a development program to obtain the market authorization of injectable gamithromycin 15% w/v solution (Zactran®, Boehringer Ingelheim) for use in sheep against footrot, the pharmacokinetic profile of gamithromycin was established and the safety and efficacy of the treatment were confirmed in a multicenter field study in Europe.
The basic pharmacokinetic parameters established in healthy young Merino sheep administered gamithromycin at 6 mg/kg body weight based on the analysis of plasma samples which were collected in intervals up to 12 days after subcutaneous injection were: area under the curve until last quantifiable concentration, 8.88 ± 2.33 μg*h/mL; maximum plasma concentration, 448 ± 180 ng/mL; terminal half-life, 42.5 ± 5.25 h.
The safety and clinical efficacy against footrot of gamithromycin 15% w/v solution were evaluated in comparison to tilmicosin 30% w/v solution (Micotil®, Elanco) treatment in 364 sheep of various breeds, sex and age from commercial farms in the United Kingdom (2 sites), Germany (3 sites) and France (1 site). Animals were enrolled based on lesions characteristic of footrot and lameness associated with the presence of footrot-related bacterial pathogens and were randomly allocated and treated in a 1:1 ratio with a single subcutaneous dose of gamithromycin or tilmicosin at label dosage (6 or 10 mg/kg body weight, respectively). Lameness and footrot lesions were evaluated at five and 21 days after treatment; the injection site in all animals was examined the day after treatment and followed up daily in the animals with injection site reaction until complete injection site reaction resolution.
Samples of 310 and 120 animals tested positive for Dichelobacter nodosus and Fusobacterium necrophorum, respectively, at inclusion, and data of 359 animals were included into the combined analyses (5 animals excluded for unintentional overdosing [1], lack of follow-up [1], concurrent antibiotic medication for non-footrot conditions [3]). Lameness scores at 21 days after treatment demonstrated a significantly (p = 0.0396) better success for the gamithromycin treatment compared to the tilmicosin treatment (97.8% vs. 93.3%). Post-dosing footrot lesion scores followed similar trends of rapid and marked decrease (improvement) for both treatments with similar (p = 0.127) treatment success for the gamithromycin and tilmicosin treatments (97.8% and 96.0%, respectively). Both treatments were safe; injection site reactions noted in 19 gamithromycin- and 25 tilmicosin-treated animals resolved within five days or six days of treatment, respectively.
Gamithromycin 15% w/v solution administered once to sheep by subcutaneous injection at 6 mg/kg body weight demonstrated a pharmacokinetic profile similar to that reported previously in sheep and cattle and was confirmed to be a safe and efficacious treatment for naturally occurring ovine footrot in a multicenter clinical field study conducted in Europe.
The association between foot temperature and hoof lesions in sheep
2021, Livestock ScienceLameness, predominantly caused by footrot and interdigital dermatitis, is a common issue in sheep flocks with negative consequences for animal welfare and productivity. Simple and cheap methods to prevent and monitor lameness are desirable to decrease prevalence within flocks. The aim of this study was to investigate whether a high foot temperature threshold can be used as an early warning for the development of hoof lesions and lameness in sheep. A flock of 47 pregnant ewes and seven non-pregnant ewe lambs were randomly allocated into two equal groups and placed in two different but similar permanent pasture fields for the duration of the study. Foot temperature was measured with a temperature probe placed on the interdigital skin on three dates over approximately 4 weeks. This study showed that increased foot temperature was associated with higher lesion scores (recorded lesions covered a scale of 0 to 3), with healthy feet having a mean temperature of 20°C and feet with severe lesion scores having a mean temperature of 31°C. Also, back feet had a higher foot temperature and lesion score than front feet (P<0.001). This study suggests that a threshold of 26.5°C in the back feet of sheep (mean foot temperature for a lesion score of 1 in back feet) could be used as an indication of when to foot bath or treat feet, and minimise hoof lesions in sheep.
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Present address: Wellcome Research Laboratories, Beckenham, Kent, England.