Guidelines for the Registration of Agents for the Control and Treatment of Non-benign Ovine Footrot
Introduction
Ovine footrot, caused by Dichelobacter nodosus (formerly Bacteroides nodosus), can be classified on clinical grounds into benign or non-benign footrot. These classifications were formerly known as non-progressive (or avirulent) and virulent (progressive) footrot, respectively. Non-benign footrot has also previously been subdivided into "intermediate" and "virulent" footrot on the basis of epidemiology and laboratory studies. These latter terms are no longer considered helpful in the classification of the disease.
These guidelines are applicable to products which are aimed at controlling non-benign strains of D. nodosus. At this stage it is not possible to produce a set of Guidelines to assess the efficacy of a product against benign strains of the organism.
Before embarking on a trial program to test the performance of a novel product in the control or prevention of ovine footrot, or to extend the claims for an existing product, the applicant should be familiar with the system for the classification of serotypes of D. nodosus which occur, together with the range of clinical manifestations of the disease which are likely to be encountered in the field.
Definitions
Benign footrot
With benign footrot there is a very low prevalence of under-running of the horn of the feet in affected sheep, even under conditions which are highly favourable for the spread of the disease.
Non-benign footrot
With non-benign footrot, there is an increasing proportion of sheep with severe under-running of the horn of the feet, and resultant lameness, under conditions which are favourable to the spread of the disease. Less favourable conditions can lead to less severe clinical signs, particularly with the less virulent strains of the organism.
Spread Period
That period (or periods) of the year when the combination of environmental factors makes it suitable for the spread of the disease within a mob of sheep. Note that irrigated pastures may give an artificial spread period.
Non-spread Period
That period (or periods) of the year when the combination of environmental factors makes it impossible for the disease to spread from infected to non-infected sheep.
Control
The incidence of infection in a flock is reduced to, or held at, a low level, even though the environmental conditions are favourable for spread.
Eradication
The infection has been completely removed from the flock. Eradication will normally be achieved by the combined use of an effective control or treatment agent and the rigorous culling of refractory individuals. Proof of eradication usually requires sheep to pass through a spread period without showing any signs of infection with non-benign footrot.
For the purposes of registration of a novel product, or a new claim for an existing product, eradication can be assumed if there are two consecutive inspections of all feet of all trial sheep during the non-spread period with no evidence of infection. These inspections should be at a minimum of 4 weeks apart to allow any latent infections to manifest themselves, if present. The timing of the initial inspection post-treatment must allow sufficient time to elapse to enable any infection to manifest itself and will be longer for products such as vaccines than for antibiotics or topical treatments.
Footscore
This is the classification of the severity of the lesions, based on the degree of damage done to the feet. The scoring system to be used is the one as determined by the Animal Health Committee's Working Party on Footrot, namely:
Score 0: Normal, dry interdigital skin.
Score 1: Limited mild interdigital dermatitis. Slight to moderate inflammation which is confined to the interdigital skin and involves erosion of the epithelium.
Score 2: More extensive interdigital dermatitis. A necrotising inflammation of the interdigital skin and involves part or all of the medial wall of the digit.
Score 3: Severe interdigital dermatitis and under running of the soft horn of the heel and sole. A necrotising inflammation with under running of part or all of the soft horn of the heel and sole which does not extend to the outer edge of the sole of the hoof. This is further subdivided into 3a, 3b and 3c to indicate the degree of under running:
3a Separation of the skin-horn junction, with under running extending no more than 5 mm.
3b Under running no more than halfway across the heel or sole.
3c More extensive under running of the heel or sole but not extending to the abaxial edge of the sole of the hoof.
Score 4: Under running extending to the outer edge of the sole of the hoof.
Score 5: Necrotising inflammation of the deeper layers of the hoof allowing separation of the hoof.
Serotype/Serogroup
This is the classification of any strain(s) of D. nodosus based on the serological reaction between the pilus antigens of the organism and specific antigens, as described by Claxton (1989). There are up to 18 serotypes within 10 serogroups which have been assessed as significant in the Australian context (Claxton, 1989; Chetwin et al, 1991).
Virulence
Virulence of field isolates is to be determined by forwarding the isolates to an approved laboratory for testing. The tests to be conducted are the Elastin Agar Test and the Protease Stability Test (Gelatin Gel Test). The methods for these tests are given in the Australian Standard Diagnostic Techniques for Animal Diseases (Stewart and Claxton 1979).
General Requirements
It is a general requirement that no trial should commence until the protocol has been evaluated by a suitably qualified biometrician to determine the statistical validity of the protocol.
A minimum of 5 properties in different environments are to be used. These properties are to be located in areas which are endemic for non-benign footrot.
The majority of the properties must run merinos, given the greater susceptibility of this breed to infection with footrot.
It is expected that the person responsible for the trials will be a veterinarian with experience in working with ovine footrot and who is familiar with the degree of scientific rigour required in the implementation of trials.
It may be necessary to pare to a significant degree to accurately determine the footscore on some sheep. It should be recognised that this paring itself may well contribute to an alleviation of the clinical manifestations of the disease, even during the spread period. Where no paring is anticipated in association with the use of a particular product, the scoring of lesions beyond score 3a will obviously not be as accurate. This is not necessarily important in the final assessment of the product where complete cure of any lesions is the ultimate aim.
Specific Requirements
Antibiotics and Antimicrobials
For the purposes of this document, the term "antibiotic" is taken to include "antimicrobial".
If the antibiotic is a new antibiotic for use in livestock, or this application represents a new use of an existing antibiotic, the applicant must seek approval of the NHMRC Expert Panel on Antibiotics, as set out on page 159 (Chapter II-9) of the Interim Requirements for the Registration of Agricultural and Veterinary Chemical Products.
Potency, sterility, pyrogen and freedom from abnormal toxicity tests are to be conducted in accordance with the methods as described in the British Pharmacopoeia (1993) and the British Pharmacopoeia (Veterinary) (1993).
Data must be presented to confirm the stability of the product in the proposed container.
Data must be presented which confirms the validity of the choice of the dose rate to be recommended for the product as marketed. These data may be generated in pen trials, using statistically valid group sizes of sheep (minimum of 5 per group recommended) which are exposed to artificial challenge with a number of non-benign strains of D. nodosus. Alternatively, the data can be generated in conjunction with the field trials to test the efficacy of the product.
Field trials to evaluate the efficacy and safety of the antibiotic must be carried out on a minimum of 5 properties in different areas, ie, they must not be adjoining properties.
Trial mobs must contain enough sheep to allow a minimum of 100 sheep per group, including an untreated control group. Applicants are advised to use more than this minimum number, if at all possible, to allow for losses during the trial.
The trial mob must have a minimum of 20% infection with non-benign footrot, with severe under-running of the horn (Score 3b or higher) of one or more feet. It is permissible to achieve this level of infection by introducing infected sheep from other mobs of the same class of sheep at the time the trial groups are being formed.
Sheep are to be randomly allocated to treatment and control groups, and must be individually identified by eartags. Double eartags are a decided advantage in reducing the number of sheep which might otherwise be lost from the trial. Care must be taken to ensure that there is an equal proportion of sheep with Score 3a or greater in each group. If this is not the case, adjustments to the groups must be made prior to the commencement of the trial.
It is recommended that the trials should be carried out at a time of year and under weather conditions which will allow the best assessment of the performance of the antibiotic. This means that treatment should be undertaken when the pastures are dry and there are no signs of rain. Green pasture and wet/humid conditions can compromise the performance of an antibiotic against D. nodosus (Egerton et al, 1968). If such conditions are unavoidable, sheep should be put on battens for a minimum of 24 hours following treatment. If the applicant believes that the new antibiotic will work under wet and humid conditions, data will need to be generated to substantiate that claim, using the same trial procedures (with the exception of a positive control using penicillin/dihydrostreptomycin). The following trial procedure presumes that treatment will only be effective under dry conditions.
While only infected sheep need to be treated with the antibiotic, the clean sheep should remain with the rest of the trial sheep in order to detect whether spread occurs during the time of the trial. All groups should continue to run as a single mob until the next inspection, at which time there should be segregation of infected and non-infected sheep (see 18, below). The clinical condition of the sheep is to be monitored on a daily basis by the owner of the property and any problems reported to the veterinarian in charge of the trial for appropriate action. Severely affected sheep from the control group will be removed from the trial and treated. If the control group sustains a high level of severe infection overall, the group will be treated with the trial formulation and the group will be monitored as according to the protocol for the treatment group.
It is strongly recommended that penicillin/dihydrostreptomycin, at a dose of 2.5 million units of penicillin and 2.5 g of dihydrostreptomycin sulphate, be used as a positive control on at least two of the trial properties. This would require a minimum trial mob size of 300 sheep on these properties, with at least 100 sheep per group.
Samples must be taken from at least 5 sheep from each property and submitted to an appropriate laboratory for testing of the degree of virulence of the representative strains of D. nodosus. Serotyping is not essential in this instance.
All sheep in the trial mob should be weighed on at least two occasions, namely at the start and end of the trial (prior to segregation for culling purposes). It is preferable to weigh the sheep at the time of each inspection. This data will permit the assessment of the value of the product in reducing production loss in those instances where the differences in clinical condition are not statistically significant. Bodyweight measurements must be taken where it is intended to make a claim for increased production as a result of the use of the product.
Sheep from each trial group must have every foot individually examined and scored prior to treatment, in accordance with the scoring system detailed above.
Infected sheep from each treatment group are to be treated in accordance with the proposed dosing schedule and route of administration for the antibiotic.
The treated sheep should be pared (trimmed) to allow drainage of the footrot lesion, unless the intention is to claim efficacy in the absence of paring. If the latter is the case, the infected sheep should be randomly allocated into "pared and treated" and "unpared and treated" groups. In such cases, particular care will need to be taken to ensure that the sizes of the respective groups are large enough to allow valid statistical analysis.
Sheep should be observed for any adverse reactions, which must be recorded. Every effort must be made to have a post-mortem conducted on any sheep which die during the trial.
All sheep from the trial mob should be re-examined, with paring as necessary, and scored 4-6 weeks after treatment. Infected sheep should be removed and the owner advised to cull them. Uninfected feet act as the Controls for evidence of spread.
Further inspections should be undertaken at intervals of at least 4 weeks (with infected sheep being removed) until there have been two 100% clean inspections of the trial mob.
Cure rate for the antibiotic is determined by application of the following formula:
Cure rate (%) = 100-(100 x TSI)
CSI
Where:
TSI = Number of Treated animals which were originally infected and are still infected.
CSI = Number of Control animals which were originally infected and are still infected.
Note: An "infected" animal is one with Score 2 or higher.
A minimum of 20 sheep from a single property, which have been treated with the antibiotic at or above the recommended dose rate, must be sent for slaughter under supervision at an approved abattoir. These sheep should be separate from the trial mob, but it would be preferable for them to be infected at the time of treatment to allow for any interaction between the condition and health of the animal on the metabolism and rate of excretion of the antibiotic. Time of slaughter should coincide with the proposed withholding period for the antibiotic for sheep meat. A post-mortem examination must be made of the site of injection and the degree and nature of any reaction recorded. Samples must be taken from the site and surrounding tissues and sent for analysis to determine the residues in the tissues.
The Directions for Use as proposed for the product and as included on the draft label, must make it clear as to the conditions for the optimal performance of the product under field conditions.
Individual Topical Treatment/Control Agent:
Data must be presented which confirms the validity of the choice of the dose rate and frequency of treatment which are to be recommended for the product as marketed. These data may be generated in pen trials, using statistically valid group sizes of sheep (minimum of 5 sheep per group is recommended) which are exposed to artificial challenge with a number of non-benign strains of D. nodosus. Alternatively, the data can be generated in conjunction with the field trials to test the efficacy of the product.
Field trials to evaluate the efficacy and safety of the preparation must be carried out on a minimum of 5 properties in different areas, ie, they must not be adjoining properties.
The timing of the trials will depend upon the intended claim and Directions for Use of the product. The trial requirements will vary accordingly.
Treatment during the spread period:
Trial mobs must contain enough sheep to allow a minimum of 100 sheep per group, including an untreated control group. Applicants are advised to use more than this minimum number, if at all possible, to allow for losses during the trial.
The trial mob must have a minimum of 20% infection with non-benign footrot, with severe under-running of the horn of one or more feet. It is permissible to achieve this level of infection by introducing infected sheep from other mobs of a similar class of sheep at the time the trial groups are being formed.
Sheep are to be randomly allocated to treatment and control groups, and must be individually identified by eartags. Double eartags are a decided advantage in reducing the number of sheep which might otherwise be lost from the trial. Care must be taken to ensure that there is an equal proportion of sheep with Score 3a or greater in each group. If this is not the case, adjustments to the groups must be made prior to the commencement of the trial.
Samples must be taken from at least 5 sheep from each property and submitted to an appropriate laboratory for testing of the degree of virulence of the representative strains of D. nodosus.
Serotyping is not essential in this instance.
All sheep in the trial mob should be weighed on at least two occasions, namely at the start and end of the trial (prior to segregation for culling purposes). It is preferable to weigh the sheep at the time of each inspection. This data will permit the assessment of the value of the product in reducing production loss in those instances where the differences in clinical condition are not statistically significant. Bodyweight measurements must be taken where it is intended to make a claim for increased production as a result of the use of the product.
Sheep from each trial group must have every foot individually examined and scored prior to treatment, in accordance with the scoring system detailed above.
If treatment to obtain cure is the aim of the product, only the infected sheep (Score 1 or greater) would need to be treated in accordance with the proposed Directions for Use of the product. If this is the case, the clean (uninfected) sheep should remain with the rest of the trial sheep to detect whether spread has occurred during the time of the trial. All groups should continue to run as a single mob for the duration of the trial. The clinical condition of the sheep is to be monitored on a daily basis by the owner of the property and any problems reported to the veterinarian in charge of the trial for appropriate action. Severely affected sheep from the control group will be removed from the trial and treated. If the control group sustains a high level of severe infection overall, the group will be treated with the trial formulation and the group will be monitored as according to the protocol for the treatment group.
If the aim of the treatment is to prevent as well as cure, all sheep in the trial mob would have to be treated in accordance with the proposed Directions for Use of the product.
Unless the claim for the product is that it is effective in the absence of paring, sheep to be treated must be pared to expose pockets of infection. It is not acceptable to have to pare the feet to such an extent that the welfare of the animal is compromised by the paring. If the product requires this degree of paring to be effective it will be refused registration on welfare grounds, as there are effective alternative products available which do not require this radical level of paring.
Treatment should be repeated at intervals as in the proposed Directions for Use of the product for as long as the spread period continues.
Sheep should be observed for any adverse reactions, which must be recorded. Every effort must be made to have a post-mortem conducted on any sheep which die during the trial.
All sheep from the trial mob should be re-examined and scored 4-6 weeks after the final treatment. Infected sheep should be removed and the owner advised to cull them.
Further inspections should be undertaken at intervals of at least 4 weeks (with infected sheep being removed) until there have been two 100% clean inspections of the trial mob.
Cure rate for the preparation is determined by application of the following formula:
Cure rate (%) = 100-(100 x TSI)
CSI
Where:
TSI = Number of Treated animals which were originally infected and are still infected.
CSI = Number of Control animals which were originally infected and are still infected.
Note: An "infected" animal is one with Score 2 or higher.
If any level of prevention is to be claimed for the preparation, the following formulae are to be applied:
Protection Rate (%) = 100-(100 x TI)
CI
Where:
TI = Number of Treated animals presently infected.
CI = Number of Control animals presently infected.
Adjusted Protection Rate (%) = 100-[100 x (TI/CI)]
(TOI/COI)
Where:
TI and CI have the same meaning as above.
TOI = Number of Treated animals originally infected.
COI = Number of Control animals originally infected.
Note: An "infected" animal is one with Score 2 or higher. Also, for protection rates, 30% of infected sheep in the untreated group must be infected at the time the protection rate is measured, ie, spread must have occurred.
In this instance the Protection Rate and Adjusted Protection Rate may simply indicate the appropriate time interval between successive treatments during the spread period.
The Directions for Use as proposed for the product and as included on the draft label, must make it clear as to the conditions required for optimal performance of the product under field conditions.
Treatment during the non-spread period:
Trial mobs must contain enough sheep to allow a minimum of 100 sheep per group, including an untreated control group. Applicants are advised to use more than this minimum number, if at all possible, to allow for losses during the trial.
The trial mob must have a minimum of 20% infection with non-benign footrot, with severe under-running of the horn of one or more feet. It is permissible to achieve this level of infection by introducing infected sheep from other mobs of a similar class of sheep at the time the trial groups are being formed.
Sheep are to be randomly allocated to treatment and control groups, and must be individually identified by eartags. Double eartags are a decided advantage in reducing the number of sheep which might otherwise be lost from the trial. Care must be taken to ensure that there is an equal proportion of sheep with Score 3a or greater in each group. If this is not the case, adjustments to the groups must be made prior to the commencement of the trial.
All sheep in the trial mob should be weighed on at least two occasions, namely at the start and end of the trial (prior to segregation for culling purposes). It is preferable to weigh the sheep at the time of each inspection. This data will permit the assessment of the value of the product in reducing production loss in those instances where the differences in clinical condition are not statistically significant. Bodyweight measurements must be taken where it is intended to make a claim for increased production as a result of the use of the product.
Samples must be taken from at least 5 sheep from each property and submitted to an appropriate laboratory for testing of the degree of virulence of the representative strains of D. nodosus.
Serotyping is not essential in this instance.
Sheep from each trial group must have every foot individually examined and scored prior to treatment, in accordance with the scoring system detailed above.
While only infected sheep need to be treated with the preparation, the clean sheep should remain with the rest of the trial sheep in order to detect whether spread occurs during the time of the trial. All groups should continue to run as a single mob for the duration of the trial. The clinical condition of the sheep is to be monitored on a daily basis by the owner of the property and any problems reported to the veterinarian in charge of the trial for appropriate action. Severely affected sheep from the control group will be removed from the trial and treated. If the control group sustains a high level of severe infection overall, the group will be treated with the trial formulation and the group will be monitored as according to the protocol for the treatment group.
Infected sheep from each treatment group are to be treated in accordance with the proposed treatment schedule for the preparation.
Sheep should be observed for any adverse reactions, which must be recorded. Every effort must be made to have a post-mortem conducted on any sheep which die during the trial.
All sheep from the trial mob should be re-examined and scored 4-6 weeks after the final treatment. Infected sheep should be removed and the owner advised to cull them.
Further inspections should be undertaken at intervals of at least 4 weeks (with infected sheep being removed) until there have been two 100% clean inspections of the trial mob.
Cure rate for the preparation is determined by application of the following formula:
Cure rate (%) = 100-(100 x TSI)
CSI
Where:
TSI = Number of Treated animals which were originally infected and are still infected.
CSI = Number of Control animals which were originally infected and are still infected.
Note: An "infected" animal is one with Score 2 or higher.
The Directions
for Use as proposed for the product and as included on the draft label,
must make it clear as to the conditions required for optimal performance
of the product under field conditions.
Flock Topical Treatment (Footbathing)
Data must be presented which confirms the validity of the choice of the dose rate and/or concentration and frequency of treatment which are to be recommended for the product as marketed. These data may be generated in pen trials, using statistically valid group sizes of sheep (minimum of 5 sheep per group is recommended) which are exposed to artificial challenge with a number of non-benign strains of D. nodosus. Alternatively, the data can be generated in conjunction with the field trials to test the efficacy of the product.
Field trials to evaluate the efficacy and safety of the preparation must be carried out on a minimum of 5 properties in different areas, ie, they must not be adjoining properties.
The timing of the trials will depend upon the intended claim and Directions of Use of the product. The trial requirements will vary accordingly.
Treatment during the spread period (residual activity):
Data must be presented which confirms the validity of the choice of the dose rate and/or concentration and frequency of treatment which are to be recommended for the product as marketed. These data may be generated in pen trials, using statistically valid group sizes of sheep (minimum of 5 sheep per group is recommended) which are exposed to artificial challenge with a number of non-benign strains of Dichelobacter nodosus. Alternatively, the data can be generated in conjunction with the field trials to test the efficacy of the product.
For this purpose, "non-benign" strains are defined as those which are Gelatin Gel positive and have been shown to be associated with clinical expression in the field to at least the level specified in Point 4, below.
Field trials to evaluate the efficacy and safety of the preparation must be carried out on a minimum of 5 properties in different areas, ie, they must not be adjoining properties.
Trial mobs must contain a minimum of 100 sheep. Applicants are advised to use more than this minimum number, if at all possible, to allow for losses during the trial. Where only one product is being tested at one rate, there must be at least four (4) replicates of both the treated and control groups, using similar classes of sheep, on each property on which trials are to be conducted. Should there be more than one chemical or formulation or more than one rate, then three (3) replicates of each group would suffice.
The trial mob must have a minimum of 20% sheep with lesions consistent with non-benign footrot, with severe under-running of the horn of one or more feet (Score 3a or higher). It is permissible to achieve this level of infection by introducing infected sheep from other mobs of a similar class of sheep at the time the trial mob is being formed.
Sheep must be individually identified by eartags. Double eartags are a decided advantage in reducing the number of sheep which might otherwise be lost from the trial.
The clinical condition of the sheep is to be monitored on a daily basis by the owner of the property and any problems reported to the veterinarian in charge of the trial for appropriate action. Severely affected sheep must be removed from the trial and treated in accordance with veterinary directions.
Severely affected sheep are those in poor condition, or those which are down on their knees and are unable to graze.
All sheep in the trial mob should be weighed on at least two occasions, namely at the start and end of the trial (prior to segregation for culling purposes). It is preferable to weigh the sheep at the time of each inspection. This data will permit the assessment of the value of the product in reducing production loss in those instances where the differences in clinical condition are not statistically significant. Bodyweight measurements must be taken where it is intended to make a claim for increased production as a result of the use of the product.
Samples must be taken from at least 5 sheep from each property and submitted to an appropriate laboratory for testing of the degree of virulence of the representative strains of D. nodosus. The test to be used is the Gelatin Gel test. Serotyping is not essential in this instance.
Sheep from each trial group must have every foot individually examined and scored prior to treatment, in accordance with the scoring system detailed above.
All sheep in the trial mob would have to be treated in accordance with the proposed
Directions for Use of the product. It would be expected that these Directions for Use would include detailed instructions for the management of infected sheep (during the spread period) which had not responded to treatment within a specified period of time. Treatment may involve standing sheep in a footbath for a specified period of time, or may require sheep to be walked through a trough containing the diluted preparation. Where walk through troughs are used they should be a minimum of 8 metres in length to ensure adequate wetting of the feet of the sheep.
If the product has nil or negligible residual protection, the Directions for Use must include directions as to the management of the total flock on a property with a view to minimising cross-infection.
Unless the claim for the product is that it is effective in the absence of paring, sheep to be treated must be pared to expose pockets of infection. It is not acceptable to have to pare the feet to such an extent that the welfare of the animal is compromised by the paring. If the product requires this degree of paring to be effective it will be refused registration on welfare grounds, as there are effective alternative products available which do not require such radical paring.
Sheep should be observed for any adverse reactions, which must be recorded. Every effort must be made to have a post-mortem conducted on any sheep which die during the trial.
Treatment should be repeated at intervals as in the proposed Directions for Use of the product for as long as the spread period continues.
All sheep from the trial mob should be re-examined and scored 4-6 weeks after the final treatment, with a further inspection 4-6 weeks later. Note that the presence of infected sheep at this stage would mean that the claim for eradication during the spread period would not have been substantiated.
Cure rate for the preparation is determined by application of the following formula:
Cure rate (%) = 100-(100 x TSI)
CSI
Where:
TSI = Percentage of Treated animals which were originally infected and are still infected.
CSI = Percentage of Control animals which were originally infected and are still infected.
Note: An "infected" animal is one with Score 2 or higher.
The Directions
for Use as proposed for the product and as included on the draft label,
must make it clear as to the conditions required for optimal performance
of the product under field conditions.
Treatment during the spread period (no residual activity):
Trial mobs must contain enough sheep to allow a minimum of 100 sheep per group, including an untreated control group. Applicants are advised to use more than this minimum number, if at all possible, to allow for losses during the trial.
The trial mob must have a minimum of 20% infection with non-benign footrot, with severe under-running of the horn of one or more feet. It is permissible to achieve this level of infection by introducing infected sheep from other mobs of a similar class of sheep at the time the trial groups are being formed.
Sheep are to be randomly allocated to treatment and control groups, and must be individually identified by eartags. Double eartags are a decided advantage in reducing the number of sheep which might otherwise be lost from the trial. Care must be taken to ensure that there is an equal proportion of sheep with Score 3a or greater in each group. If this is not the case, adjustments to the groups must be made prior to the commencement of the trial.
The clean (uninfected) sheep from each group should remain with the rest of the trial sheep to detect whether spread has occurred during the time of the trial. All groups should continue to run as a single mob for the duration of the trial. The clinical condition of the sheep is to be monitored on a daily basis by the owner of the property and any problems reported to the veterinarian in charge of the trial for appropriate action. Severely affected sheep from the control group will be removed from the trial and treated. If the control group sustains a high level of severe infection overall, the group will be treated with the trial formulation and the group will be monitored as according to the protocol for the treatment group.
All sheep in the trial mob should be weighed on at least two occasions, namely at the start and end of the trial (prior to segregation for culling purposes). It is preferable to weigh the sheep at the time of each inspection. This data will permit the assessment of the value of the product in reducing production loss in those instances where the differences in clinical condition are not statistically significant. Bodyweight measurements must be taken where it is intended to make a claim for increased production as a result of the use of the product.
Samples must be taken from at least 5 sheep from each property and submitted to an appropriate laboratory for testing of the degree of virulence of the representative strains of D. nodosus. Serotyping is not essential in this instance.
Sheep from each trial group must have every foot individually examined and scored prior to treatment, in accordance with the scoring system detailed above.
All sheep in the trial mob would have to be treated in accordance with the proposed Directions for Use of the product. . Such treatment may involve standing sheep in a footbath for a specified period of time, or may require sheep to be walked through a trough containing the diluted preparation. Where walk through troughs are used they should be a minimum of 8 metres in length to ensure adequate wetting of the feet of the sheep
Unless the claim for the product is that it is effective in the absence of paring, sheep to be treated must be pared to expose pockets of infection. It is not acceptable to have to pare the feet to such an extent that the welfare of the animal is compromised by the paring. If the product requires this degree of paring to be effective it will be refused registration on welfare grounds, as there are effective alternative products available which do not require such radical paring.
Sheep should be observed for any adverse reactions, which must be recorded. Every effort must be made to have a post-mortem conducted on any sheep which die during the trial.
Treatment should be repeated at intervals as in the proposed Directions for Use of the product for as long as the spread period continues.
All sheep from the trial mob should be re-examined and scored 4-6 weeks after the final treatment. Infected sheep should be removed and the owner advised to cull them.
Further inspections should be undertaken at intervals of at least 4 weeks (with infected sheep being removed) until there have been two 100% clean inspections of the trial mob.
Cure rate for the preparation is determined by application of the following formula:
Cure rate (%) = 100-(100 x TSI)
CSI
Where:
TSI = Number of Treated animals which were originally infected and are still infected.
CSI = Number of Control animals which were originally infected and are still infected.
Note: An "infected" animal is one with Score 2 or higher.
If any level of prevention is to be claimed for the preparation, the following formula is to be applied:
Protection Rate (%) = 100-(100 x TI)
CI
Where:
TI = Number of Treated animals presently infected.
CI = Number of Control animals presently infected.
Adjusted
Protection Rate (%) = 100-[100 x (TI/CI)]
(TOI/COI)
Where:
TI and CI have the same meaning as above.
TOI = Number of Treated animals originally infected.
COI = Number of Control animals originally infected.
Note: An "infected" animal is one with Score 2 or higher. Also, for protection rates, 30% of infected sheep in the untreated group must be infected at the time the protection rate is measured, ie, spread must have occurred.
In this instance the Protection Rate and Adjusted Protection Rate may simply indicate the appropriate time interval between successive treatments during the spread period.
The Directions
for Use as proposed for the product and as included on the draft label,
must make it clear as to the conditions required for optimal performance
of the product under field conditions.
Treatment during the non-spread period:
Trial mobs must contain enough sheep to allow a minimum of 100 sheep per group, including an untreated control group. Applicants are advised to use more than this minimum number, if at all possible, to allow for losses during the trial.
The trial mob must have a minimum of 20% infection with non-benign footrot, with severe under-running of the horn of one or more feet. It is permissible to achieve this level of infection by introducing infected sheep from other mobs of sheep of the same class at the time the trial groups are being formed.
Sheep are to be randomly allocated to treatment and control groups, and must be individually identified by eartags. Double eartags are a decided advantage in reducing the number of sheep which might otherwise be lost from the trial. Care must be taken to ensure that there is an equal proportion of sheep with Score 3a or greater in each group. If this is not the case, adjustments to the groups must be made prior to the commencement of the trial.
All sheep in the trial mob should be weighed on at least two occasions, namely at the start and end of the trial (prior to segregation for culling purposes). It is preferable to weigh the sheep at the time of each inspection. This data will permit the assessment of the value of the product in reducing production loss in those instances where the differences in clinical condition are not statistically significant. Bodyweight measurements must be taken where it is intended to make a claim for increased production as a result of the use of the product.
Samples must be taken from at least 5 sheep from each property and submitted to an appropriate laboratory for testing of the degree of virulence of the representative strains of D. nodosus.
Serotyping is not essential in this instance.
Sheep from each trial group must have every foot individually examined and scored prior to treatment, in accordance with the scoring system detailed above.
While only infected sheep need to be treated with the preparation, the clean sheep should remain with the rest of the trial sheep in order to detect whether spread occurs during the time of the trial. All groups should continue to run as a single mob for the duration of the trial. The clinical condition of the sheep is to be monitored on a daily basis by the owner of the property and any problems reported to the veterinarian in charge of the trial for appropriate action. Severely affected sheep from the control group will be removed from the trial and treated. If the control group sustains a high level of severe infection overall, the group will be treated with the trial formulation and the group will be monitored as according to the protocol for the treatment group.
Infected sheep from each treatment group are to be treated in accordance with the proposed treatment schedule for the preparation.
Sheep should be observed for any adverse reactions, which must be recorded. Every effort must be made to have a post-mortem conducted on any sheep which die during the trial.
All sheep from the trial mob should be re-examined and scored 4-6 weeks after treatment. Infected sheep should be removed and the owner advised to cull them.
Further inspections should be undertaken at intervals of at least 4 weeks (with infected sheep being removed) until there have been two 100% clean inspections of the trial mob.
Cure rate for the preparation is determined by application of the following formula:
Cure rate (%) = 100-(100 x TSI)
CSI
Where:
TSI = Number of Treated animals which were originally infected and are still infected.
CSI = Number of Control animals which were originally infected and are still infected.
Note: An "infected" animal is one with Score 2 or higher.
The Directions
for Use as proposed for the product and as included on the draft label,
must make it clear as to the conditions required for optimal performance
of the product under field conditions.
Vaccines
Sterility, pyrogen and freedom from abnormal toxicity tests are to be conducted in accordance with the methods as described in the British Pharmacopoeia (1993) and the British Pharmacopoeia (Veterinary) (1993).
If the vaccine is derived from genetically manipulated organisms, advice must be sought from the Genetic Manipulation Advisory Committee.
Vaccines will need to demonstrate efficacy against representative strains from each of the major serogroups encountered in the field in Australia.
Data should be presented to show that antigenic competition does not compromise the performance of the vaccine.
Data must be presented to confirm the stability of the product in the proposed container.
Applicants must submit details as to the quality control measures which will be applied to the vaccine, with details as to the rationale for particular procedures, particularly in relation to efficacy.
With new vaccines and with amended formulations to existing vaccines, efficacy of the vaccine needs to be demonstrated in the face of heterologous challenge in which the vaccine is challenged by a wide range of serotypes of non-benign D. nodosus which may be encountered in the field.
With new vaccines and with amended formulations to existing vaccines, efficacy may be demonstrated by the use of artificial challenge of sheep in pen trials, using statistically valid numbers of sheep ( minimum of 5 sheep per group recommended).
With new vaccines, efficacy data generated in pen trials must be supported by safety and, if environmental conditions permit, efficacy data generated in field trials. These trials are to be carried out on a minimum of 5 properties in different environments, ie, they must not be adjoining properties.
Trial mobs on these properties must contain enough sheep to allow a minimum of 100 sheep per group, including an untreated control group. Applicants are advised to use more than this minimum number, if at all possible, to allow for losses during the trial.
The trial mob must have a minimum of 20% infection with non-benign footrot, with severe under-running of the horn of one or more feet. It is permissible to achieve this level of infection by introducing infected sheep from other mobs of sheep of the same class at the time the trial groups are being formed.
Sheep are to be randomly allocated to treatment and control groups, and must be individually identified by eartags. Double eartags are a decided advantage in reducing the number of sheep which might otherwise be lost from the trial. Care must be taken to ensure that there is an equal proportion of sheep with Score 3a or greater in each group. If this is not the case, adjustments to the groups must be made prior to the commencement of the trial.
All groups should continue to run as a single mob until the next inspection. The clinical condition of the sheep is to be monitored on a daily basis by the owner of the property and any problems reported to the veterinarian in charge of the trial for appropriate action. Severely affected sheep from the control group will be removed from the trial and treated. If the control group sustains a high level of severe infection overall, the group will be treated with the trial formulation and the group will be monitored as according to the protocol for the treatment group.
All sheep in the trial mob should be weighed on at least two occasions, namely at the start and end of the trial (prior to segregation for culling purposes). It is preferable to weigh the sheep at the time of each inspection. This data will permit the assessment of the value of the product in reducing production loss in those instances where the differences in clinical condition are not statistically significant. Bodyweight measurements must be taken where it is intended to make a claim for increased production as a result of the use of the product.
Sheep to be vaccinated must have the vaccine applied subcutaneously high up on the neck and below the ear, unless a valid argument and evidence can be provided to substantiate an alternative route or site of injection.
It is expected that the recommended timing of the vaccination will allow maximum immunity to be achieved at the time to coincide with the greatest challenge from the disease. It is recognised that this will not always be possible to achieve in the field trial situation.
Samples must be taken from at least 5 sheep per property and submitted to an appropriate laboratory for testing of the degree of virulence and serotyping of the representative strains of D. nodosus.
Any concurrent treatments which it may be proposed to recommend, such as paring and/or footbathing, need to be specified and the number of trial groups adjusted accordingly.
Sheep from each trial group must have every foot of every sheep individually examined and scored prior to the initial vaccination, in accordance with the scoring system detailed above.
A minimum of 20 sheep from both the vaccinated and control groups must have blood samples taken prior to the initial vaccination, prior to the second vaccination and at the time of each subsequent inspection, with the same sheep being sampled on each occasion.
Sheep from each trial group must have every foot of every sheep individually re-examined and scored at the time of the second vaccination.
Any site reactions to the vaccine must be recorded with respect to both size and nature of the reaction.
Any other adverse reactions should also be recorded. Wherever possible, a post-mortem should be undertaken on any sheep which die during the trial.
Sheep from each trial group must have every foot of every sheep individually re-examined and scored 6 weeks and 12 weeks after the second vaccination. Data should be presented to indicate the length of protection achieved following a course of vaccination under severe challenge conditions (field or pen trials) with highly virulent strains of D. nodosus. Where a claim is intended to show protection beyond 12 weeks following the second vaccination, inspections need to be taken at these later times. Such a claim may be difficult to generate using field data, given the uncertain duration of the spread period in any year. Pen trials may be used to substantiate such claims, where appropriate.
All sheep from each trial group are to be re-examined and scored 4-6 weeks after the pastures have dried off and there is no further spread, with paring as necessary. Infected sheep are to be removed from the mob and the owner advised to cull them.
Further inspections should be undertaken at intervals of at least 4 weeks (with infected sheep being removed) until there have been two 100% clean inspections of the trial mob.
Cure rate for the vaccine is determined by application of the following formula:
Cure rate (%) = 100-(100 x TSI)
CSI
Where:
TSI = Number of Treated animals which were originally infected and are still infected.
CSI = Number of Control animals which were originally infected and are still infected.
Note: An "infected" animal is one with Score 2 or higher.
Protection rate for the vaccine is determined by application of the following formulae:
Protection Rate (%) = 100-(100 x TI)
CI
Where:
TI = Number of Treated animals presently infected.
CI = Number of Control animals presently infected.
Adjusted Protection Rate (%) = 100-[100 x (TI/CI)]
(TOI/COI)
Where:
TI and CI have the same meaning as above.
TOI = Number of Treated animals originally infected.
COI = Number of Control animals originally infected.
Note: An "infected" animal is one with a Score 2 or higher. Also, for protection rates, 30 % of infected sheep in the unvaccinated group must be infected at the time the protection rate is measured, ie, spread has occurred.
Serological data should be analysed to determine the serological response to the major serogroups, using geometric mean titres. It is inappropriate to attempt to evaluate the response of individual animals to vaccination, as some animals may have a low titre but be fully protected. Likewise, it is possible for an individual animal to have a high titre, but to still be susceptible to infection.
Serological data should only be used as supportive evidence to confirm efficacy as assessed in the clinical pen and/or field trials and is not a substitute for clinical data in such instances.
References
Chetwin, D.H., Whitehead, L.C. and Thorley, S.E.J. (1991). "The Recognition and Prevalence of Bacteroides nodosus Serotype M in Australia and New Zealand," Aust. Vet. J., 68: 154-155.
Claxton, P.D. (1989). "Antigenic Classification of Bacteroides nodosus," in Footrot and Foot Abscess of Ruminants, edited by J.R. Egerton, W.K. Yong and G.G. Riffkin, CRC Press, p.155-165.
Egerton, J.R., Parsonson, I.M. and Graham, N.P.H. (1968). "Parenteral Chemotherapy of Ovine Footrot", Aust. Vet. J., 44:275-283.
Stewart, D. G. and Claxton, P. D. (1979). "Ovine Footrot - Clinical Diagnosis and Bacteriology" in Australian Standard Diagnostic Techniques for Animal Disease.