Financial modelling of the potential cost of ovine Johne's disease and the benefit of vaccinating sheep flocks in southern New South Wales

OBJECTIVE: To develop an enterprise gross margin (GM) model that predicts the on-farm financial impact of ovine Johne's disease (OJD) for various sheep enterprises in Australia. In addition, to estimate the benefits and costs of control through the use of the Gudair vaccination, including a breakeven point. DESIGN AND POPULATION: Data for the model was gained from an observational study conducted over a 3-year period from 2002 to 2004 using sheep from 12 OJD-infected flocks from southern New South Wales. Flocks ranged between 3500 and 20,000 sheep, with owner estimates of 5% or greater OJD mortality at the start of the study. PROCEDURE: A GM model was developed to predict the on-farm financial impact of OJD for various sheep enterprises in Australia, comparing non-infected, infected (status quo) and infected (vaccination) disease scenarios. RESULTS: Vaccination breakeven points are achieved within 2 to 3 years for breeding enterprises if OJD mortalities are high, rising towards 7 years for a Merino ewe enterprise if OJD mortalities are low. CONCLUSION: The GM model demonstrates the returns to investment of vaccination for Australian sheep producers with OJD-infected flocks.     

Lesions attributed to vaccination of sheep with Gudair for the control of ovine paratuberculosis: post farm economic impacts at slaughter

OBJECTIVE: To determine i) the prevalence of lesions at the site of vaccination with Gudair, and ii) the incidence of discounting of slaughtered sheep carcasses due to the presence of these lesions. DESIGN: A survey of the prevalence of injection lesions and actual discounts applied to 20 consignments of vaccinates slaughtered in abattoirs in New South Wales. PROCEDURE: Consignments of sheep previously vaccinated against ovine Johne's disease (OJD) were assessed on the slaughter chain for the prevalence of vaccination site lesions and any costs associated with carcass trimming were estimated. In addition a telephone survey was conducted to determine the experiences and risk attitudes of 8 abattoirs in south east New South Wales likely to have previously processed vaccinates. RESULTS: The prevalence of lesions observed was 18% for adult (mutton) and 65% for lamb carcasses. The value of the trim removed was insignificant, the labour cost of its removal was nil and no carcass was downgraded to a lower value grade. CONCLUSION: Under the market conditions existing at the time the study was conducted, in sheep vaccinated at the recommended site high on the neck, it is unlikely that OJD vaccination site lesions will be a significant cost to producers or the processing industry and will represent only a very small proportion of the total cost of OJD control by vaccination.     

Thalidomide pharmacokinetics in sheep

AIM: To determine the half life (T_1/2), time taken to reach maximum plasma concentration (T_max) and maximum plasma concentration (C_max) of thalidomide in sheep following I/V, oral and topical treatment with a single dose of thalidomide.

METHOD: Three groups of 4–6-month-old ram lambs were treated with thalidomide dissolved in dimethylsulphoxide (DMSO). The first group (n=10) was treated I/V with 100?mg thalidomide in 2?mL DMSO; the second group (n=8) received 400?mg thalidomide in 2?mL DMSO orally, and the third group (n=8) had 400?mg thalidomide in 4?mL DMSO applied topically. Plasma samples were collected up to 36 hours after treatment, snap-frozen at ?80°C and analysed for concentrations of thalidomide using high performance liquid chromatography.

RESULTS: Following I/V administration, T_1/2 was 5.0 (SEM 0.4) hours, volume of distribution was 3,372.0 (SEM 244.3) mL/kg and clearance was 487.1 (SEM 46.1) mL/hour.kg. Topical application of 400?mg thalidomide did not increase plasma concentrations. Following oral administration, thalidomide bioavailability was 89%, with T_1/2, T_max, and C_max being 7.2 (SEM 0.8) hours, 3.0 (SEM 0.4) hours and 1,767.3 (SEM 178.1) ng/mL, respectively.

CONCLUSION: Topical administration using DMSO as a solvent did not increase concentrations of thalidomide in plasma. The mean pharmacokinetic parameters determined following oral treatment with 400?mg of thalidomide were similar to those reported in humans receiving a single 400?mg oral dose (T_1/2 7.3 hours; T_max 4.3 hours and C_max 2,820?ng/mL). There is potential for thalidomide to be used as a model for the treatment of chronic inflammatory conditions in sheep, such as Johne's disease, where tumour necrosis factor alpha plays a pathogenic role.     

SHORT CONTRIBUTION: Needle-free vaccination in sheep

Multi-dose vaccinators have been in use for many years to vaccinate livestock. A number of needle-free vaccinators that use compressed gas to drive the vaccine through intact skin have been recently introduced to the market. We recently examined the efficacy of a needle-free vaccinator to induce antibodies to tetanus toxoid in sheep. The result indicates that needle-free vaccination can stimulate antibody responses comparable to conventional needle vaccination.     

Investigation of Johne's disease in Tasmanian fallow deer (Dama dama)

In 2012 when many sheep flocks in northern‐central Tasmania were experiencing a high prevalence of ovine Johne's disease, 34 wild adult fallow deer shot on or near infected properties were negative to microscopic Mptb lesions of the ileo‐caecal valve, terminal ileum and ileo‐caecal lymph nodes. This study demonstrated 95% confidence of detecting Johne's disease in this fallow deer population if ≥10% of animals were shedding Mycobacterium avium subsp. paratuberculosis in their faeces, or if ≥21% of animals were sub‐clinically infected.     

The effect of Johne's vaccination on tuberculin testing in farmed red deer (Cervus elaphus)

AIM: To assess the degree of interference with bovine tuberculin testing in farmed red deer that vaccination of young deer with an oil-adjuvanted vs aqueous formulation of live attenuated Mycobacterium paratuberculosis Strain 316F vaccines would be likely to cause, and to compare immunological responses between vaccine formulations.

METHODS: Five-month-old red deer (n=45) were randomly allocated to three treatment groups of 15 animals, which received either no vaccine, a single 2-ml dose of an oil-adjuvanted formulation or two 2-ml doses, 6 weeks apart, of an aqueous formulation of live attenuated M. paratuberculosis Strain 316F vaccine injected subcutaneously (S/C) in the neck (Control, Oil-adjuvant Ptb, and Aqueous Ptb groups, respectively). Injection-site reactions were described and measured on Weeks 3, 6 and 9. Animals were weighed and lymphocyte transformation tests (LTT) and antibody enzyme-linked immunosorbent assays (ELISA) using avian, bovine and Johnin tuberculin were conducted on blood samples collected at Weeks 0, 6, 12, 15, 24, 27, 36 and 39. A bovine mid-cervical skin test (MCT) was applied at Week 12, and comparative cervical skin tests (CCTs) at Weeks 24 and 36. At Week 42, the animals were slaughtered at a commercial deer slaughter premises and subjected to rigorous meat inspection.

RESULTS: Two animals were eliminated at the start of the trial due to a positive cross-reaction with bovine tuberculin in the initial LTT. Almost all animals reacted to the MCT at Week 12, with mean skin thicknesses of 3.9, 2.9 and 1.0 mm for the Oil- adjuvant Ptb, Aqueous Ptb and Control groups, respectively. When the CCT was conducted at Week 24, 2/15 Oil-adjuvant Ptb, 2/14 Aqueous Ptb and 1/14 Control animals were classified as CCT-positive to bovine tuberculin. By Week 36, all animals were CCT-negative. The Oil-adjuvant Ptb vaccination resulted in high persistent levels of antibody that reacted with bovine tuberculin, compared with negligible levels in the Aqueous Ptb group.

Overall, a single dose of the Oil-adjuvant Ptb vaccine in deer stimulated a vigorous, cross-reactive immune response, evidenced by high LTT, skin-test and antibody reactions to bovine tuberculin, with both cell-mediated and humoral characteristics. By comparison, two doses of the Aqueous Ptb vaccine produced less cross-reactivity and a bias towards a cell-mediated response. The Oil-adjuvant Ptb vaccine resulted in moderate injection- site lesions that were quite persistent, whereas the Aqueous Ptb vaccine resulted in smaller nodules that regressed more quickly.

CONCLUSIONS: Vaccination of farmed deer with an oil-adjuvanted Johne's vaccine has the potential to cause significant interference with routine tuberculin skin testing. The cross-reactivity should decline with time and the CCT should be able to clear MCT-positives, but there is a risk of false-positives to the blood test for tuberculosis (BTB), due to high persistent levels of antibody. The CCT could be used as a primary skin test in vaccinated deer on some farms.

The Aqueous Ptb caused fewer problems with skin testing and produced significantly less bovine antibody than the Oil-adjuvant Ptb, but stimulated persistent cell-mediated immune responses that may provide some protection against Johne's disease.     

Detection of Mycobacterium avium subsp. paratuberculosis in skeletal muscle and blood of ewes from a sheep farm in New Zealand

Abstract

AIM: To determine whether viable Mycobacterium avium subsp. paratuberculosis (Map) is present in skeletal muscle and blood in ewes with and without Johne's disease confirmed histologically.

METHODS: A total of 51 mixed-aged ewes in poor body condition from a farm with a history of clinical Johne's disease were culled and examined at necropsy. BACTEC radiometric culture was performed on samples of skeletal muscle from the biceps femoris, mononuclear cells in peripheral blood (hereafter referred to as blood), and ileum. Histological sections and Ziehl-Neelsen (ZN)-stained impression smears of terminal ileum and mesenteric lymph nodes were examined. Ewes were defined as having confirmed Johne's disease if there was histopathological evidence typical of the disease within the ileum and adjacent lymph nodes.

RESULTS: Eighteen of 21 (86%) ewes with confirmed clinical Johne's disease were culture-positive for Map from sites peripheral to the alimentary tract, comprising 15 from skeletal muscle and 13 from blood. Five of 30 (17%) ewes that did not have Johne's disease were culture-positive, with four from skeletal muscle and one from blood. The likelihood that ewes with confirmed Johne's disease had systemic Map infection compared with ewes without was determined as OR=30 (95% CI=6.3–142.0; p<0.001).

CONCLUSION: The prevalence of Map infection of skeletal muscle and blood in ewes with confirmed Johne's disease was 71% and 62% respectively, and in unaffected ewes was 13% for muscle and 3% for blood.

CLINICAL RELEVANCE: Skeletal muscle and blood are potential sources of exposure of humans to Map, and the risk appears higher from sheep with Johne's disease.     

Xylaxine

Extract

In reply to the correspondence from Beasley⁽¹⁾, may I heartily endorse his request for any factual or anecdotal reports of the effects of xylazine in humans.     

Interferon gamma responses to proteome-determined specific recombinant proteins: Potential as diagnostic markers for ovine Johne's disease

Johne's disease (JD), or paratuberculosis is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). There may be a long subclinical phase with no signs of clinical disease.     

Financial effect of bovine Johne's disease in beef cattle herds in Australia

Objective To assess the financial effect of programs for controlling bovine Johne's disease (BJD) in beef herds. Design A spreadsheet simulation model of a self‐replacing beef herd in south‐eastern Australia selling 400‐kg steers at 15 months old. Methods The model calculated the monthly cash flow, and net present value (NPV) of cumulative cash flow, over 10 years. Four main control options were compared: (1) a base herd (no action to control the disease), (2) test and cull, and (3) partial and (4) total destocking. It was assumed that BJD was eradicated after 3 and 5 years with total and partial destocking, respectively, and not eradicated with a test and cull program. Scenarios were compared for both commercial and stud enterprises. Results If there was no discount on the sale price of cattle in commercial herds, deaths from BJD had to exceed 5% before the NPV of partial or total destocking was similar to taking no action to control the disease over a 10‐year period. When cattle sales incurred a 10% discount, deaths had to exceed 1% before the destocking strategies would break even after 10 years. Conclusion Control options for BJD should be carefully planned on an individual herd basis, as significant production and financial risks accompany destocking programs. Eradication will only be more profitable in the longer term, compared with living with the disease, when discounts on the sale of stock from infected herds are high. This can occur with the selling of store cattle or breeders. In stud herds, BJD will usually cause the total failure of the business.     

Paratuberculosis (Johne's Disease) in Cattle and Other Susceptible Species

Paratuberculosis (Johne's disease) is a widespread and costly disease. This consensus statement will summarize recommendations regarding diagnosis, control, and treatment of Johne's disease in cattle and other species. Each section of recommendations is followed by a statement that subjectively characterizes the strength of the supporting evidence. The role played by Mycobacterium avium subsp. paratuberculosis (MAP) in the pathogenesis has been a matter of controversy for many years. This statement concludes with an assessment of the evidence in favor of MAP as a potential zoonotic pathogen.     

Antimicrobial activity of gallium nitrate against Mycobacterium avium subsp. paratuberculosis in neonatal calves

Background: Mycobacterium avium subsp. paratuberculosis (MAP), the agent of Johne's disease in cattle, is a facultative intracellular bacterium that is dependent on ferric iron for its survival and replication. Gallium (Ga), a trivalent semimetal that shares many similarities with ferric iron and functions as an iron mimic has been shown to have in vitro antimicrobial activity against several microorganisms, including MAP. Objectives: (1) To investigate the antimicrobial activity of Ga in calves experimentally infected with MAP; and (2) to monitor for potential adverse effects of Ga on calf health. Animals: Twelve Holstein calves. Methods: Randomized blind controlled experiment. Beginning at 10 days of age (study day 1), the experimental calves (n = 6) were treated with 20 mg/kg gallium nitrate daily for 45 days. On study days 4 and 5, all calves were challenged with a PO dose of a live field strain MAP. Treated calves were monitored daily for adverse effects. Calves were euthanized on study day 100, and 29 tissue samples and 1 fecal sample were collected from each calf. Samples were cultured for MAP by MGIT liquid culture system, Herrold's Egg Yolk Medium culture, or both. Results: No adverse effects were observed in the treated calves. Treatment was associated with a significant reduction in MAP tissue burden when compared with control calves (P = .017). Conclusions and Clinical Relevance: Chemoprophylactic treatment of calves with Ga before and during the period of high susceptibility decreased MAP tissue colonization in experimentally infected neonatal calves.     

Lesions in sheep following administration of a vaccine of a Freund's complete adjuvant nature used in the control of ovine paratuberculosis

CASE HISTORIES: Occurrences of adverse reactions in seven sheep flocks in Australia following vaccination against paratuberculosis where veterinary attention was requested are reviewed. All cases occurred within the 3-year period following commencement of use of a vaccine of a Freund's complete adjuvant nature, at a time when approximately six million doses of vaccine had been administered.

CLINICAL FINDINGS: In the first case, 26/58 (45%) Merino sheep vaccinated as adults had palpable tissue reactions at or near the site of vaccination; enlarged prescapular lymph nodes were palpated in 17 (29%), and nine (16%) sheep had both palpable lesions at the site of vaccination and enlarged prescapular lymph nodes. The reactions included caseous nodules up to 5.5 cm in diameter. In the other cases, fistulating or granulomatous wounds were occasionally found at the recommended site of injection behind the ear, and myiasis was rare. Occurrences of inappropriate choice of injection site were recorded, including injection into the axilla of two Merino rams, and lesions in the tissues of the maxilla and nose of almost 50% of 350 Border Leicester lambs. Four outbreaks of progressive paralysis due to injection into cervical musculature were reported, described as ‘OJD staggers’ by producers.

DIAGNOSIS: Granulomatous cellulitis and lymphadenitis associated with oil droplets typical of ‘oil granulomata’. Injection of vaccine into the dorsal cervical area resulted in progressive paralysis due to myonecrosis and suspected granulomatous leptomeningitis.

CLINICAL RELEVANCE AND CONCLUSIONS: Although lesions at and near the site of injection are common, adverse reactions to vaccination were rare and included mortality from cervical spinal injection, production losses from injection in the maxilla or axilla or if myiasis resulted, and potential marketing losses if animals or carcasses are discounted as a result of the lesions. Risk factors for adverse reactions included inadequate restraint of sheep, breed of sheep, experience of the operator, poor injection technique, and inappropriate placement of vaccine. Increasing attention to the proper restraint of animals, restricting vaccination to the recommended site behind the ear, careful placement of the vaccine into subcutaneous tissue to avoid drainage of vaccine material into tissues such as the spinal cord, and post-vaccination supervision to address welfare concerns should adverse reactions occur are recommended.     

Risk management of paratuberculosis in dairy herds

Risk management of paratuberculosis (Johne's disease) in a dairy herd requires an assessment of the likelihood of paratuberculosis occurring in the herd, the economic impact of paratuberculosis on the herd and an evaluation of measures that can be taken to reduce this likelihood and impact.The likelihood of paratuberculosis occurring in the herd is related to the regional herd-level prevalence of paratuberculosis and the herd management (e.g., introducing animals from other herds). The economic impact of paratuberculosis includes production losses due to subclinical and clinical cases, losses due to increased replacement of animals and costs of control measures. Furthermore, a reduction of the price of milk from infected herds might result from consumer concerns about the zoonotic potential of paratuberculosis.Measures that reduce the likelihood of paratuberculosis occurring in a herd and its impact include preventive management measures (e.g., closed herd management and an effective separation of susceptible young stock from adult cattle), test-and-cull schemes for known infected herds and quality assurance schemes for test-negative herds. Quality assurance schemes for test-negative herds, such as schemes for 'low-Map bulk milk' and 'Map-free' herds, aim at safeguarding or increasing the profitability of these herds.Keys to success of risk management of paratuberculosis include realistic expectations of the results of paratuberculosis control, quality assurance and control programmes that are appreciated by farmers and incentives for farmers to participate in such programmes.     

Reversibility of the effects of GnRH‐vaccination used to suppress reproductive function in mares

Reasons for performing study: Active immunisation against gonadotrophin‐releasing hormone (GnRH) provides a reversible method for control of oestrous behaviour and fertility in mares. Previous reports failed to demonstrate the interval to resumption of cyclic ovarian activity after GnRH‐vaccination. Hypothesis: Administration of the GnRH‐vaccine Improvac in a large group of mares of various ages will result in effective, reliably reversible suppression of ovarian activity within a 2 year period. Methods: The mares, subdivided into 3 age categories, were vaccinated twice (with a 35 day interval) using 400 µg Improvac and monitored via blood samples until Day 720 after initial vaccination for serum progesterone concentration determination by radioimmune assay and anti‐GnRH antibody titre by enzyme immunoassay. Samples were collected until individuals resumed cyclic ovarian activity. Results: All mares showed suppression of cyclic ovarian activity by clinical examination and serum progesterone concentration (SPC) ≤1 nmol/l by Day 70 and 92.2% resumed cyclic activity by SPC at Day 720 with a mean interval = 417.8 days (s.d. ± 23.9; range 232–488 days, median 344 days). A significant age effect (P = 0.028) on the interval, but not on GnRH‐antibody titre response, was observed between the youngest (≤4 years) and oldest (≥11 years) categories. Conclusions: Immunising adult mares of all ages with Improvac resulted in a reversible suppression of cyclic ovarian activity in most mares. An age effect, with the youngest mares showing a longer interval to reversibility, was observed.