AU2016253604A1 - Molasses Blocks - Google Patents

Abstract

A supplemented (medicated) molasses feed block containing a drench for treating or preventing parasitic infestations in ruminants, such as gastrointestinal nematode infestations. In some embodiments the feed block: is highly palatable, particularly to ruminants such as sheep and cattle, thereby encouraging self-medication; the drench (and other biological actives) are substantially uniformly dispersed throughout the block; the block releases the drench in a uniform and controlled manner; the block enables controlled consumption - low daily dose of drench, thereby minimising the risk of overdosing on drench or parasite-resistance occurring. 0,48 h o 25 9 144 h 0 1- 5-10 10- 15 15-20 2 0-30 30 Medicated feed block eaten (g/day) Figure 5

Description

MOLASSES BLOCKS 2016253604 03 Nov 2016

TECHNICAL FIELD

[0001] This invention generally relates to a supplemented molasses feed block for ruminants. In particular, the invention concerns a medicated molasses feed block containing a drench for treating or preventing parasitic infestations in ruminants.

BACKGROUND ART

[0002] Feed supplementation blocks are commonly used to supplement diets of ruminants for increased milk and meat production. The ingredients of such blocks will vary, depending on what nutrients are required for the particular need at hand, what types of ingredients are available or affordable to those manufacturing the block, what types of block-moulding equipment or processes are available or affordable to the block manufacturer, and the environmental conditions/climate that the block needs to withstand.

[0003] Manufacturing blocks to meet all necessary requirements is rarely straightforward. The choice of required, available or affordable ingredients, for example, may result in a block that cannot adequately withstand the environmental conditions/intended climate. The choice of required, available or affordable ingredients, for example, may result in more expensive blockmoulding equipment or process (e.g. hot moulding process) being required.

[0004] In many countries of the world ruminants are susceptible to infestation with gastrointestinal parasites such as giardia, roundworms, hookworms, whipworms, the Taenia genus of tapeworms, pinworms, aelurostrongylus, paragonimiasis, strongyles and strongyloides. Infestation can lead to reduced milk and meat production, as well as animal death. Although such infestations may be treatable with drenches, such as the broad spectrum anthelmintic benzimidazole, there are disadvantages with the current methods for administrating such drenches. For example, individual administration of a bolus/dosage to each animal by an animal handler is impractical, being both time consuming and expensive.

SUMMARY OF INVENTION

[0005] The present inventors have now developed a supplemented molasses feed block that can be used to deliver at least one type of drench to one or more ruminants in a controlled manner. 1 [0006] According to a first aspect of the present invention, there is provided a supplemented molasses feed block comprising at least one type of drench for preventing or treating a parasitic infestation of a ruminant. 2016253604 03 Nov 2016 [0007] According to a second aspect of the present invention, there is provided a method of preventing or treating a parasitic infestation of a ruminant, said method comprising the step of feeding said ruminant a supplemented molasses feed block comprising at least one type of drench for preventing or treating the parasitic infestation.

[0008] According to a third aspect of the present invention, there is provided a method of manufacturing a supplemented molasses feed block, said method comprising the steps of: [0009] combining ingredients, including molasses and at least one type of drench, to form a block mixture; [0010] pouring the block mixture into a mould; and [0011] allowing the block mixture to set to form a supplemented molasses feed block comprising the at least one type of drench substantially uniformly dispersed throughout the supplemented molasses feed block.

[0012] The block’s ingredient content, size and shape can be tailored for the particular ruminant type for which it is provided, or even for the geographic location of the ruminant. For example, grain versus grass fed ruminants many require different ingredient contents in their blocks, such as different mineral content. The block can also be tailored for the palate of the ruminant (e.g. molasses and salt content).

[0013] In addition to containing molasses and at least one type of drench, the block can for example comprise one or more of the following types of ingredients: a nitrogen source; a protein source; a carbohydrate source; minerals; vitamins; a solidifying, binding or gelling agent; a pH adjuster; a filler; a flavouring agent (to increase palatability of the block); a biological active; and general types of excipients.

[0014] The at least one drench can be used to treat or prevent any suitable parasitic infestation. Examples of infestations are caused by the following organisms: Ostertagia (brown stomach worm); Haemonchus (barberpole worm); Trichostrongylus (bankrupt worm); Cooperia (small intestinal worm); Nematodirus (threadneck worm); Oesophagostomum (nodular worm); 2

Haemonchus Bunostomum (hookworm); Strongyloides (threadworm); Trichuris (whipworm); Moniezia (tapeworm); and, Dictyocaulus (lungworm). 2016253604 03 Nov 2016 [0015] Any suitable type or types and quantity or quantities of drench can be used. For example, the drench content can be about 0.01, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95 or 10% weight/weight of each type of drench. A suitable drench is, for example benzimidazole, which is a broad spectrum anthelmintic used against gastrointestinal parasites including giardia, roundworms, hookworms, whipworms, the Taenia genus of tapeworms, pinworms, aelurostrongylus, paragonimiasis, strongyles and strongyloides. Suitable examples of benzimidazole include fenbendazole and triclabendazole.

[0016] Solidifying, binding or gelling agents help solidify the block/make the block a coherent mass. Suitable examples include calcium oxide, magnesium oxide, calcium hydroxide, di-ammonium phosphate, cement, bentonite and hydrated lime (quick lime). Any suitable solidifying, binding and/or gelling agent/s quantity can be used. For example, the solidifying, binding and/or gelling agent/s content can be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40% weight/weight.

[0017] pH adjusters help adjust the final pH of the block. Examples of suitable pH adjusters include organic acids such as citric, tartaric, boric and phosphoric acid. Any suitable pH adjuster quantity can be used. For example, the pH adjuster content can be about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10% weight/weight.

[0018] Fillers help bulk up the block, to get it to the correct volume. The filler can be digestible or not. Examples of suitable fillers include bran (digestible) and earth (not digestible). Any suitable filler/s quantity can be used. For example, the filler/s content can be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40% weight/weight.

[0019] Any suitable source or sources of nitrogen can be used. The nitrogen can derive from a source of protein or not. In an example, the source of nitrogen is urea (non-protein source). Any suitable quantity of nitrogen or nitrogen source can be used. For example, the nitrogen or nitrogen source content can be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% weight/weight. 3 [0020] Any suitable source or sources of protein can be used. Suitable sources of protein include cottonseed meal, fish meal, soybean meal and oilseed meal. Any suitable quantity of protein or protein source can be used. For example, the protein or protein source content can be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% weight/weight. 2016253604 03 Nov 2016 [0021] Any suitable source or sources of carbohydrate can be used. Suitable sources of carbohydrate include molasses. Any suitable quantity of carbohydrate or carbohydrate source can be used. For example, the carbohydrate or carbohydrate source content can be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% weight/weight.

[0022] The block can include any suitable type of mineral or minerals. Examples of suitable minerals include sodium, phosphorus, sulphur, calcium, sodium, iron, copper, manganese, zinc, iodine, selenium and cobalt. Any suitable mineral quantity can be used. For example, the mineral content can be about 0.5, 1.0, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 and 5% weight/weight.

[0023] The block can include any suitable type of vitamin or vitamins. Examples of suitable vitamins include vitamin A, B, C, D and E. Any suitable vitamin quantity can be used. For example, the vitamin content can be about 0.5, 1.0, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 and 5% weight/weight.

[0024] Any suitable type or types of flavouring agent can be used. Any suitable quantity of flavouring agent/s can be used. Examples of flavouring agents include molasses and salt.

[0025] Any suitable type of salt or salts can be used. Suitable types of salt include sea salt and sodium chloride. Any suitable quantity of salt can be used. For example, the salt content can be about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% weight/weight.

[0026] Any suitable type or types of biological actives (apart from the drench) can be used. Suitable types of biological actives include antibiotics, antimicrobials, rumen stimulants (to encourage the growth of rumen microbes), methane-reducing agents (e.g. 3-nitrooxypropanol), ionophores (compounds that alter rumen fermentation patterns, to increase feed efficiency and body weight gain), analgesic agents and anti-inflammatory agents. Any suitable quantity of biological active/s can be used. For example, the biological active/s content can be about 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1%, 4 1.5%, 2%, 2.5%, 3% , 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5% or 10% weight/weight. 2016253604 03 Nov 2016 [0027] Any suitable type of analgesic agent or combination of different types of analgesic agents can be used. Likewise, any suitable type of anti-inflammatory agent or combination of different types of anti-inflammatory agents can be used. Potentially suitable agents include one or more of the following: acetaminophen, aspirin, salicylic acid, methyl salicylate, choline salicylate, glycol salicylate, 1-menthol, camphor, mefenamic acid, fluphenamic acid, indomethacin, diclofenac, alclofenac, ibuprofen, ketoprofen, pranoprofen, fenoprofen, sulindac, fenbufen, clidanac, flurbiprofen, indoprofen, protizidic acid, fentiazac, tolmetin, tiaprofenic acid, bendazac, bufexemacpiroxicam, phenylbutazone, oxyphenbutazone, clofezone, pentazocine, mepirizole, hydrocortisone, cortisone, dexamethasone, fluocinolone, triamcinolone, medrysone, prednisolone, flurandrenolide, prednisone, halcinonide, methylprednisolone, fludrocortisone, corticosterone, paramethasone, betamethasone, naproxen, suprofen, piroxicam, diflunisal, meclofenamate sodium, carprofen, flunixin, tolfenamic acid and meloxicam.

[0028] In some embodiments, the biological active can be a non-steroidal antiinflammatory drug (NSAIDs). The NSAID can be a salicylate (e.g. aspirin (acetylsalicylic acid), diflunisal (dolobid), salicylic acid and other salicylates, salsalate (disalcid)), propionic acid derivative (e.g. ibuprofen, dexibuprofen, naproxen, fenoprofen, ketoprofen, dexketoprofen, flurbiprofen, oxaprozin, loxoprofen), acetic acid derivative (e.g. indomethacin, tolmetin, sulindac, etodolac, ketorolac, diclofenac, aceclofenac, nabumetone), enolic acid (oxicam) derivative (e.g. piroxicam, meloxicam, tenoxicam, droxicam, lomoxicam. ilsoxicam, phenylbutazone), anthranilic acid derivative (fenamate) (e.g. mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid), selective COX-2 inhibitor (e.g. celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib, etoricoxib, firocoxib), sulfonanilide (e.g. nimesulide), or other (e.g. clonixin, licofelone, H-harpagide in Figwort or Devil's Claw).

[0029] Suitable general excipients include antioxidants, colourants, emulsifiers, preservatives, solvents, solubilisers, viscosity increasing agents, diluents, carriers and so forth. Any suitable quantity of water can be used. For example, the water content can be about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% weight/weight.

[0030] The molasses of the block provides the following: improves palatability (flavouring 5 agent); provides minerals/trace elements such as sulphur; provides carbohydrates/fermentable sugars; and, functions as a binding agent. Molasses also makes the block easier to manufacture. Any suitable source and quantity of molasses can be used. For example, the molasses content can be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 and 60% weight/weight. In other embodiments, molasses can be used to balance the ingredient content to 100%. The molasses can be produced from sugarcane, for example. 2016253604 03 Nov 2016 [0031] Preferably the block has a toffee-like consistency, able to withstanding wet weather as well as temperatures ranging from about -20°C to 50°C.

[0032] Preferably the drench is substantially uniformly dispersed throughout the supplemented molasses feed block.

[0033] The supplemented molasses feed block can be fed to any suitable type of ruminant. Suitable ruminants include sheep, cattle, horses, buffalo, goats and yak.

[0034] Preferably, the method comprises the ruminant self-medicating. That is, the ruminant consumes as much of the supplemented molasses feed block as it desires, as often as it desires.

[0035] Preferably, the supplemented molasses feed block provides a drench dose to the ruminant in the order of about 10, 15, 20, 25, 30, 35, 40, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 and lOOmg/ruminant/day (depending on the size of the animal).

[0036] Preferably the supplemented molasses feed block is fed to the ruminant for a period of 0.5, 1, 1.5, 2, 2.5, 3, 3.5 or 4 weeks. More preferably, the supplemented molasses feed block is fed to the ruminant for a period of 1 to 3 weeks, and even more preferably 1 to 2 weeks.

[0037] The method may comprise a step of feeding to the ruminant a first supplemented molasses feed block containing a first type of drench for a first period of time, then a second supplemented molasses feed block containing a second type of drench for a second period of time, so as to lessen the risk of drench-resistance occurring. The first and second periods of time could, for example, each be 1 to 2 week periods. If required, the method may comprise a step of feeding to the ruminant a third (or fourth) supplemented molasses feed block containing a third (or fourth) type of drench for a third (or fourth) period of time. 6 [0038] Regarding sheep, in one embodiment, the supplemented molasses feed block provides a fenbendazole dose in the order of about 25-30mg/sheep/day. 2016253604 03 Nov 2016 [0039] Regarding sheep, in one embodiment, the supplemented molasses feed block enables a consumption rate of about 5-7mg of fenbendazole/g block for an about 50 kg sheep consuming the supplemented molasses feed block at the daily rate of about 15g.

[0040] The block can be manufactured using a hot process (requiring heating of one or more ingredients) or cold process. Preferably, the block is manufactured using a cold process. More preferably, the block is manufactured using a cold moulding process.

[0041] A body of the block can be of any suitable size and shape. The block body can comprise a top surface, a bottom surface and at least one side surface. Potential shapes for the block body include a rectangular, hexagonal or octagonal prism or cylinder/disc, for example.

[0042] The block body can be of any suitable weight but preferably has a weight of between about 5 and 1000 kg, and more preferably about 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 and 1000 kg.

[0043] Particularly preferred embodiments of supplemented molasses feed block are described below.

[0044] Preferably, the supplemented molasses feed block comprises about 40 to 50% weight/weight molasses.

[0045] Preferably, the supplemented molasses feed block comprises about 5 to 10% weight/weight salt.

[0046] Preferably, the supplemented molasses feed block comprises at least one type of phosphate. Any suitable type or types and quantity of phosphate can be used. For example, the phosphate content can be about 5-10% weight/weight. A suitable phosphate is di-calcium phosphate.

[0047] Preferably, the supplemented molasses feed block comprises at least one type of hydrated lime. Any suitable type and quantity of hydrated lime can be used. For example, the hydrated lime content can be about 0-5% weight/weight. 7 [0048] Preferably, the supplemented molasses feed block comprises magnesium oxide. Any suitable quantity of magnesium oxide can be used. For example, the magnesium oxide content can be about 10-20% weight/weight. 2016253604 03 Nov 2016 [0049] Preferably, the supplemented molasses feed block comprises minerals such as copper, cobalt, zinc and selenium. Any suitable mineral quantity can be used. For example, the mineral content can be about 1-2% weight/weight.

[0050] Preferably, the supplemented molasses feed block comprises up to about 10% weight/weight water.

[0051] Preferably, the supplemented molasses feed block comprises about 0.5-1% weight/weight of each type of drench. A preferred type of drench is fenbendazole.

[0052] Optionally, the supplemented molasses feed block comprises about 5-10% weight/weight of phosphoric acid.

[0053] Optionally, the supplemented molasses feed block comprises at least one type of protein source/meal. Any suitable type or types and quantity or quantities of meal can be used. For example, the meal content can be up to about 2% weight/weight. Suitable meal is, for example, cottonseed meal, fish meal, soybean meal and oilseed meal.

[0054] A particularly preferred supplemented molasses feed block comprises the following ingredients (all weight/weight): [0055] 40 to 50% (or to balance) molasses [0056] 5 to 10% salt [0057] 5 to 10% phosphate (e.g. di-calcium phosphate) [0058] Up to 5% hydrated lime [0059] 10 to 20% magnesium oxide [0060] 1 to 2% minerals (including copper, cobalt, zinc, selenium) [0061] 10% water [0062] 0.5-1% of each type of drench (e.g. fenbendazole) 8 [0063] Such a supplemented molasses feed block can be suitable for treating gastrointestinal nematodes in ruminants, particularly sheep. 2016253604 03 Nov 2016 [0064] Any of the features described herein can be combined in any combination with any one or more of the other features described herein within the scope of the invention.

[0065] The reference to any prior art in this specification is not, and should not be taken as an acknowledgement or any form of suggestion that the prior art forms part of the common general knowledge.

[0066] Preferred features, embodiments and variations of the invention may be discerned from the following Detailed Description (including Figures) which provides sufficient information for those skilled in the art to perform the invention. The Detailed Description is not to be regarded as limiting the scope of the preceding Summary of the Invention in any way.

BRIEF DESCRIPTION OF FIGURES

[0067] Figure 1 - Frequency distribution of wethers (n=30) to estimates of daily intake of a medicated feed block (the block being as described in Example 1).

[0068] Figure 2 - Intake of medicated feed block (MFB) (+ 68% confidence intervals) by Merino wethers infected with worms or uninfected. The corresponding change in mean worm egg count (WEC) in the infected animal is also provided.

[0069] Figure 3 - Frequency distribution of infected and uninfected sheep (n=24) to estimates of mean daily intake of a medicated feed block during first week of access.

[0070] Figure 4 - Frequency distribution of lactating Merino ewes (n=52) to estimates of daily intake of a medicated feed block (MFP) after two, four and six days of access.

[0071] Figure 5 - Frequency distribution of Merino wethers (n=60) to estimates of daily intake of a medicated feed block (MFP) on days two, four and six after access.

DETAILED DESCRIPTION

[0072] Example 1 - Manufacture of a supplemented molasses feed block [0073] This example describes the manufacture of a supplemented molasses feed block (“medicated feed block”) containing a drench, manufactured using a cold moulding process. 9 [0074] Molasses and hydrated lime were mixed together in water using a high-speed mixer. Other ingredients, including salt, di-calcium phosphate, magnesium oxide, minerals and drench were added in turn, and the mixture was poured into a mould and allowed to set for about 48 hours. 2016253604 03 Nov 2016 [0075] The block consisted of the following ingredients (all weight/weight): [0076] 40 to 50% molasses [0077] 5 to 10% salt [0078] 5 to 10% di-calcium phosphate [0079] Up to 5% hydrated lime [0080] 10 to 20% magnesium oxide [0081] 1 to 2% minerals (including copper, cobalt, zinc, selenium) [0082] 10% water [0083] 0.5% fenbendazole [0084] When set, the block had a toffee-like consistency.

[0085] The block had a weight of 20 kg. The drench was substantially uniformly dispersed throughout the block. The consistency of the block was like toffee.

[0086] Example 2 - Self-prescribed control of gastrointestinal nematode parasites of grazing sheep through medicated feed blocks [0087] Summary [0088] This trial was undertaken to assist a better understanding on the intake by sheep of a medicated feed block containing the anthelmintic fenbendazole (as described in Example 1) for control of worm infection. A technique to determine block intake by free-ranging sheep over a prolonged period, with minimal disturbance of grazing behaviour, did not exist and was developed as part of this trial. The results of the trial gave an indication as to the best use of medicated feed blocks in the field to provide good worm control for sheep while managing development of anthelmintic resistance. 10 [0089] Fenbendazole incorporated into a feed supplement, in a role independent of its anthelmintic activity, was confirmed as an excellent marker for estimating intake by grazing sheep. Plasma concentrations of its hepatic metabolites could be used to estimate individual supplement (block) intake in grazing livestock. The proportionality to fenbendazole dose of these plasma metabolites was confirmed when single, multiple and daily doses were given. Pooling plasma samples offered an effective and analytically efficient way of analysis and allowed detection of differences in supplement intake that minimised animal disturbance. 2016253604 03 Nov 2016 [0090] Intake of medicated block by sheep was observed to be regulated by behavioural responses to worm infection. Intake by a group of animals was a function of the proportion of animals in a group that consumed the medicated block and the magnitude of block intake by individual sheep. Infection with gastrointestinal worms generally resulted in a reduction in the proportion of animals that did not eat a medicated block and it is proposed that this is a consequence of worm infection reducing behavioural phobia. The amount of medicated block consumed by animals was increased by worm infection whenever the medicated block provided a positive post-ingestive consequence, providing a curative treatment for worm infection. If the curative benefit diminished, or did not exist, intake of medicated block was unlikely to be increased by worm infection.

[0091] The results from this trial allowed comment on the use of medicated blocks to provide good worm control for sheep while managing development of anthelmintic resistance. The level of inclusion of fenbendazole in a medicated block was an important factor to minimise the chance of under-dosing by animals that consumed only small amounts of block. Level of inclusion needed to account for the existence of benzimidazole-resistant worms across much of Australia and the negative feedback loop (on intake) derived from the curative consequence of consuming a medicated block. Extrapolating from the trial results and being cognisant of these other factors, led to the suggestion of an inclusion rate of 5-7 mg fenbendazole/g block for a 50 kg sheep consuming block at the daily rate of 15 g.

[0092] The existence of non-eaters, even during the presence of worm infection, is an important and potentially positive finding from this trial. Non-eaters provide a source of worms that are unselected for anthelmintic (fenbendazole) resistance and eggs deposited in faeces onto pasture from this unselected population (when developed to infective third stage larvae) will slow development of resistance within worm populations. There is a strong argument that a medicated block should be used tactfully for short periods. Access to a medicated block should 11 be targeted for a period of one to 2 weeks, which should be sufficient to eliminate a fenbendazole-susceptible worm burden. If, however, continue protection was required the medicated block could be left available for longer periods but this would accelerate development of drench resistance. 2016253604 03 Nov 2016 [0093] The major threat against the use of medicated blocks containing fenbendazole is the endemic nature of benzimidazole resistance among different genera of gastrointestinal worms. A secondary threat is a general perception that continual exposure of a worm population to an anthelmintic will worsen the level of resistance. The results from this trial suggest that the latter of these threats can be mitigated and that self-medication by sheep in response to worm infection provided the potential for voluntary targeted selective treatment.

[0094] Background [0095] The experiments conducted during this trial were designed for two purposes. The first purpose was to develop a technique to estimate intake of a medicated (anthelmintic) feed block by grazing animals over a prolonged period. The second purpose was to use this technique to investigate if grazing sheep displayed the ability for self-medication, induced by worm infection, and thereby achieve a voluntary targeted selective treatment. Targeted selective treatment is the administration of anthelmintic to those animals with the greatest need, leaving a proportion of the mob untreated so as to provide an unselected source of worms to slow development of anthelmintic resistance.

[0096] Experiments [0097] Technique to estimate intake of a medicated feed block [0098] Experiments were designed to examine the potential of fenbendazole (FBZ) as a marker of intake by grazing sheep. FBZ is a member of the benzimidazole anthelmintic class, and its two metabolites in sheep, oxfendazole (OFZ) and fenbendazole-sulfone (SUL) have been reported to have a prolonged appearance in plasma following oral administration. The longer appearance of the metabolites in plasma suggested they are likely to be more useful marker of intake than FBZ itself. A possible dose dependent relationship between FBZ dose and OFZ and SUL concentration in plasma and the long half-life of the metabolites in plasma suggested that FBZ may be useful marker of supplement intake over the long term in a way that is independent of its anthelmintic activity and allows avoidance of faecal collection and 12 frequent animal disturbance. FBZ is stable over a range of temperatures and climates, has a very low toxicity in mammals, has no reports of induced aversion and, together with OFZ and SUL, can be readily and accurately detected in plasma with high pressure liquid chromatography. 2016253604 03 Nov 2016 [0099] Five experiments were conducted to determine the relationship between oral ingestion of FBZ and the plasma concentrations of FBZ, OFZ and SUL after single, multiple and daily doses both in housed and grazing sheep and sheep infected with internal parasites (worms). Extraction recovery of OFZ+SUL standards added to plasma (n=12) was 72.4%, with a precision of 8.8%. The accuracy of the HPLC analysis (n=9) was 96.2% and precision was 3.9%. The repeatability of the HPLC analysis for individual samples (n=3) processed three times was 1.2%. In other words, the technique was both highly accurate and precise.

[00100] The results from these experiments indicated that FBZ and plasma concentrations of OFZ+SUL could be used to estimate individual supplement intake in grazing livestock. The proportionality to dose of OFZ+SUL plasma concentrations when single, multiple and daily doses were given made it a useful and reliable indicator of FBZ intake. Pooling plasma samples taken at 48 h intervals also gave an effective and analytically efficient way of detecting differences in FBZ intake that minimised animal disturbance. While there is increased variation of OFZ+SUL concentration in grazing animals, difference in intake were still indicative of dose rate. Few, if any, other methods for estimating intake in sheep have relied on inference of statistical difference as has been demonstrated for this technique. When FBZ was incorporated into a feed block the linear relationship between FBZ dose and metabolite concentration in plasma also remained though concentrations were higher than equivalent pure FBZ treatments. Finally gastrointestinal parasitism at commercially-relevant rates did not affect OFZ-SUL concentrations in plasma.

[00101] In summary, the FBZ technique provided an excellent tool for estimating intake for a medicated feed block by grazing sheep. The technique was sufficiently robust to use to investigate how grazing sheep consume mediated blocks when exposed to worm infection and this is described in the next section.

[00102] Intake of medicated fee blocks bv grazing sheep [00103] Three experiments were conducted to determine intake of medicated feed blocks by grazing sheep, variability of intake among sheep within the same mob, and provide comment on 13 the strategic use of medicated feed blocks. 2016253604 03 Nov 2016 [00104] In the first experiment, Merino wethers were given access to a molasses-based feed block (no FBZ) for at least four weeks while grazing at pasture. Replacement of the feed block with a medicated block containing FBZ allowed estimation of block intake by individual sheep, using the methods developed through this trial. Intake of the medicated feed block averaged 7g/head/day in the first week of being offered and this increased to 19g/head/day in week 2 of offering (Figure 1). The range in intake was 0-42g/head/day with 73% of animals consuming more than lOg/day in the second week of offering. The concentration of FBZ in the block was approximately lOmg/g which provided a mean daily FBZ dose of 190mg/head during the second week of offering. A therapeutic dose against FBZ sensitive strains of worms is likely to be in the order of 25-30mg/head/day for the sheep in this experiment. Intake of block as low as 3g/head/day would have achieved this dose.

[00105] In the second stage of this experiment, Merino wethers were selected based on previous block intake (from the first stage), thereby excluding animals that consumed the most or least block. The wethers received a single oral dose of 3,000 Haemonchus conforms (third stage larvae, anthelmintic susceptible) and 10,000 Trichostrongylus colubriformis (third stage larvae, anthelmintic susceptible) or remained uninfected. After 34 days of infection (during which animals had continuous access to a non-medicated feed block) they were offered a medicated block (1.48±0.08mg fenbendazole/g block) for 2 weeks.

[00106] Mean worm egg count was 2165 epg on day 0 (prior to access to medicated block) and declined to 120 epg by day 6 after access to the medicated block and then to 45 epg by day 14 (Figure 2). Worm eggs were not detected in the faeces of uninfected animals at any stage. The number of animals not eating the medicated block (non-eaters) was significantly lower in the worm infected group (5%) than the uninfected (21%) group. Intake of medicated block was increased by worm infection at 2 and 4 days after access (Figure 2).

[00107] Mean block was 32g/day for the infected sheep and 21g/day for the uninfected sheep during the first 6 days of access. The distribution of intake differed between these groups (Figure 3) indicating a minimum daily block intake in the range 10-20g/head for infected sheep which at the level of FBZ in the block provided a therapeutic dose against sensitive worms.

[00108] In the second and third experiments the aim was to determine if self-medication against worms was observed in lactating Merino ewes and Merino wethers grazing at pasture. 14 [00109] Animals either remained uninfected or were given an infection of T. colubriformis and H. contortus (Table 1). Animals had access to non-medicated blocks for the next 35 days and were then offered a medicated block at the start of the measurement period. 2016253604 03 Nov 2016 [00110] Table 1. Animal class, infection rate of Trichostrongylus colubriformis and Haemonchus contortus and number of animals in each treatment group in the ewe and wether experiments.

Ewe experiment groups Wether experiment groups Infection rate (L3) Number of animals T. colubriformis H. contortus E0 WO 0 0 20 El Wl 10 000 3 333 10 E2 W2 20 000 6 666 10 E3 W3 30 000 10 000 20

Note: Number of animals in each experimental group indicates 20 ewes in group E0 and 20 wethers in group W0 and so forth.

[00111] Mean worm egg count for the infected ewe groups (El, E2 and E3) was 1138 epg on day 0 and this increased to 1674 epg by day 14. The mean worm egg count for the infected wether groups (Wl, W2 and W3) was 578 epg on day 0 and 524 epg on day 14. T. colubriformis was the dominant species in the coproculture from most infected treatment groups (approx. 60%) with H. contortus accounting for 37% of larvae. Worm egg count did not reflect the infection levels with no differences among infected treatment groups. The uninfected groups maintained a zero worm egg count throughout the experiment.

[00112] Positive worm egg counts at day 14 indicated that the FBZ in the medicated block may not have been effective against the experimental worm infection which was surprising given that the worms given to animals were known to be FBZ sensitive. This indicated considerable infection must have occurred from infective larvae resident on the experimental paddocks. In confirmation of this, the mean efficacy of fenbendazole was tested following these experiments and determined to be 21% (i.e. 21% reduction in worm egg count due to oral dose of 5mg FBZ/kg weight).

[00113] The percentage of ewes not eating the block was significantly lower for infected groups being 18% for infected and 40% for uninfected ewes. Amongst those sheep eating the block, intake was unaffected by worm infection and ranged from 0-58g/day with an overall 15 mean intake of 13g/day (Figure 4). 2016253604 03 Nov 2016 [00114] The wethers ate less medicated block than the ewes (mean intake = 6g/day) and there was less variation in intake with a range of 0 - 32g/day. The proportion of wethers not eating the medicated block was unaffected by worm infection and fluctuated throughout the week from 2-13% (Figure 5).

[00115] Regardless of the resistance status of the worms, ewes and wethers did not consume enough mediated block to provide a therapeutic dose for fenbendazole-sensitive worms.

[00116] Intake of FBZ was 13 and 6mg/day as the block had FBZ included at lmg/g. Inclusion level of FBZ was deliberately set to a low level so that curative benefits would only be achieved with higher rates of block intake by infected sheep. This was established to allow better discrimination in block intake between infected and uninfected sheep. A therapeutic dose would have been in the range 18-25mg FBZ/day for the sheep in these experiments. This indicates that the inclusion level of FBZ in the block would need to have been in the order of 3.0-4.0mg/g.

[00117] Discussion [00118] The trial was designed to develop methods which allow the quantification of intake by sheep of a medicated (i.e. containing anthelmintic) feed block and determine the animal and parasite characteristics that are associated with block acceptance or refusal. The specific aims were: [00119] 1. Develop a method to measure the intake of a block containing anthelmintic drug over 1-7 days of continuous access by grazing sheep. Feed blocks containing anthelmintic drug (as described in Example 1).

[00120] 2. Assess the variability of the block intake of sheep grazing parasite contaminated pasture.

[00121] 3. Examine the strategic access of sheep to such a medicated block for control of parasite egg shedding from sheep on a year-round basis and consequent effects on anthelmintic resistance.

[00122] Development of FBZ as a marker of intake has been an original outcome from this 16 trial. The technique is highly accurate and precise and has a number of advantages not offered by other markers. For example, FBZ has few (if any) occupational health issues, has a wide safety margin in livestock, does not create feed aversions at high levels of intake, has metabolites with long apparent plateau which allow sampling (of blood) to be conducted with a maximum frequency of every 2 days which minimises animal disturbance and the chance of affecting animal behaviour, is efficiently analysed through the use of composite plasma samples and is able to discriminate intake across a wide range. The work conducted through this trial has provided a statistical basis for the value of FBZ as a matter of supplement intake such as medicated blocks. 2016253604 03 Nov 2016 [00123] There was large variability in medicated block intake between sheep but worm infection generally reduced the number of non-eaters and, under some circumstances, temporarily increased intake of a medicated block.

[00124] It is proposed there are two behavioural aspects that lead to consumption of a medicated block by sheep. The first aspect is the proportion of animals in a group that consume the medicated block and the second aspect is the magnitude of block intake. It is suggested that consumption of a medicated block is a consequence of sheep overcoming suspicion of a block and that worm infection reduces this phobia. Put simply, it is proposed that worm infection increases an animals’ preparedness to sample foods within its environment. In the context of a medicated block, this is measured as a reduction in the number of animals not eating the block. Such an effect was observed in two of the experiments described in this trial.

[00125] It is suggested that the magnitude of block intake is motivated by factors other than phobia and more closely related to the post-ingestive consequence of consuming a medicated block. Where the medicated block provides a positive post-ingestive consequence, through providing a curative treatment for worm infection, intake of medicated block is expected to be higher. As the curative benefit diminishes, through removal of a worm infection, intake of medicated block is expected to reduce. Similarly, if the medicated block provided no curative value, because of (say) drug-resistant worms, no effect on block intake would be expected. This suggestion is broadly supported by the experiments conducted as part of this trial.

[00126] While these factors may account for intake of a medicated block, the level of inclusion of FBZ is also very important to minimise the chance of under-dosing by animals that consume small amounts of block. When determining the inclusion level for FBZ, the factors 17 that are proposed motivate block intake by sheep are important to consider. For example, block intake needs to be associated with a curative benefit to encourage greater intake until the infection is cured. If a minimum daily FBZ dose if 0.5mg/kg weight is required to treat FBZ-sensitive worms, it is likely that a greater dose - perhaps 1.5-2.0mg/kg weight - may be required to provide a useful treatment in the field. Existence of benzimidazole-resistant worms is endemic across much of Australia with mean efficacy often estimated at 60-70%. For a 50kg sheep consuming block at the daily rate of 15g this would require an FBZ inclusion rate of 5-7mg/g block. 2016253604 03 Nov 2016 [00127] The existence of non-eaters, even during the presence of worm infection, is an important and potentially positive finding from this trial. Non-eaters provide a source of worms that are unselected for anthelmintic (FBZ) resistance and eggs deposited in faeces onto pasture from this unselected population (when developed to infective third stage larvae) will slow development of resistance within worm populations. Such strategies, referred to as targeted selective treatment (TST) have been the focus of active research in sheep producing countries. If for example, FBZ was 80% effective and there were 10% non-eaters, then 36% of eggs deposited onto pasture would derive from unselected adult worms. If non-eaters did not suffer debilitating loss from infection, this would be a very useful outcome for slowing the development of resistance by worms to FBZ.

[00128] The length of time that a medicated block needs to be provided can be surmised from this trial. Where FBZ was effective, worm egg counts declined to negligible levels by six days after animals had access to a medicated block. On this basis, it would seem that access for a period of 1-2 weeks would be sufficient to eliminate an FBZ-susceptible worm burden. If however, continued protection was required the medicated block could be left available for longer periods but this would accelerate development of drench resistance. There is a strong argument that a medicated block should be used tactically for short periods, thus avoiding the expense of labour to muster and drench animals which may amount to AU 20 cents per head for each treatment.

[00129] The medicated block could also be used in strategic ways as an aid to slow development of resistance to unrelated drench actives. For example, modelling has confirmed that effective multi-active combinations used in rotation are most effective at slowing development of drench resistance. It is possible that providing access to a medicated block immediately after (or before) drenching, with an unrelated active, would play a similar role to 18 multi-active combinations. A possible fit for this purpose would be drench actives that are not sold as multi-active combinations and most notable is the recently released Zolvix™ from Novartis. 2016253604 03 Nov 2016 [00130] The major threat against the use of medicated blocks containing fenbendazole is the endemic nature of benzimidazole resistance among different genera of gastrointestinal worms. A secondary threat is the general perception that continual exposure of a worm population to an anthelmintic will worsen the level of resistance. The results from this trial suggest that the latter of these threats can be mitigated and that self-medication by sheep in response to worm infection provides the potential for voluntary targeted selective treatment.

[00131] It is to be appreciated that the block of this trial could have been used to treat ruminants other than sheep, and that the block could have used a different type of drench, such as a different type of benzimidazole.

[00132] Some the advantages of the block as described in Example 1 are stated below: [00133] 1. It is rain-resistant in that it will not readily dissolve in rain.

[00134] 2. It is stable within the following temperature range: -20 to 50°C. Therefore, the block is suitable for use in Australia as well as countries having similar climates/environmental conditions such as South-East Asia, including New Zealand, Indonesia, Laos, Vietnam, Malaysia, Cambodia, China, India and Myanmar.

[00135] 3. It is highly palatable, particularly to ruminants such as sheep and cattle.

[00136] 4. The drench (and other biological actives) can be substantially uniformly dispersed throughout the block.

[00137] 5. The block releases the drench in a uniform and controlled manner.

[00138] 6. The block enables controlled consumption - low daily dose of drench, thereby minimising the risk of overdosing on drench or parasite-resistance occurring.

[00139] 7. The rate of cold production of the block is high, being about 50 tonnes of block per day.

[00140] 8. The block need not require urea as an ingredient. 19 [00141] In the present specification and claims (if any), the word ‘comprising’ and its derivatives including ‘comprises’ and ‘comprise’ include each of the stated integers but does not exclude the inclusion of one or more further integers. 2016253604 03 Nov 2016 [00142] Reference throughout this specification to ‘one embodiment’ or ‘an embodiment’ means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearance of the phrases ‘in one embodiment’ or ‘in an embodiment’ in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more combinations.

[00143] In compliance with the statute, the invention has been described in language more or less specific to structural or methodical features. It is to be understood that the invention is not limited to specific features shown or described since the means herein described comprises preferred forms of putting the invention into effect. The invention is, therefore, claimed in any of its forms or modifications within the proper scope of the appended claims (if any) appropriately interpreted by those skilled in the art. 20

Claims (20)

1. A supplemented molasses feed block comprising at least one type of drench for preventing or treating a parasitic infestation of a ruminant.

2. A method of preventing or treating a parasitic infestation of a ruminant, said method comprising the step of feeding said ruminant a supplemented molasses feed block comprising at least one type of drench for preventing or treating the parasitic infestation.

3. A method of manufacturing a supplemented molasses feed block, said method comprising the steps of: combining ingredients, including molasses and at least one type of drench, to form a block mixture; pouring the block mixture into a mould; and allowing the block mixture to set to form a supplemented molasses feed block comprising the at least one type of drench substantially uniformly dispersed throughout the supplemented molasses feed block.

4. The feed block of claim 1 or the method of claim 2 or 3, wherein the parasitic infestation is caused by a gastrointestinal nematode.

5. The feed block of claim 1 or claim 4, or the method of claim 2, 3 or 4, wherein the drench is capable of preventing or treating a parasitic infestation caused by one or more of the following organisms: Ostertagia (brown stomach worm); Haemonchus (barberpole worm); Trichostrongylus (bankrupt worm); Cooperia (small intestinal worm); Nematodirus (threadneck worm); Oesophagostomum (nodular worm); Haemonchus Bunostomum (hookworm); Strongyloides (threadworm); Trichuris (whipworm); Moniezia (tapeworm); and, Dictyocaulus (lung worm).

6. The feed block of claim 1, 4 or 5, or the method of claim 2, 3, 4 or 5, wherein the feed block comprises about 0.5-1% weight/weight of each type of drench.

7. The feed block of claim 1, 4, 5 or 6, or the method of claim 2, 3, 4, 5 or 6, wherein the at least one type of drench is benzimidazole.

8. The feed block of claim 7 or the method of claim 7, wherein the benzimidazole is fenbendazole or triclabendazole.

9. The feed block of claim 1, 4, 5, 6, 7 or 8, or the method of claim 2, 3, 4, 5, 6, 7 or 8, wherein the feed block comprises at least one analgesic agent.

10. The feed block of claim 9 or the method of claim 9, wherein the analgesic agent is a non-steroidal anti-inflammatory drug (NSAID).

11. The feed block of claim 1, or the method of claim 2, wherein the drench is substantially uniformly dispersed throughout the feed block.

12. The feed block of claim 1, 4, 5, 6, 7, 8, 9, 10 or 11, or the method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, wherein the feed block comprises about 40 to 50% weight/weight molasses.

13. The feed block of claim 1, 4, 5, 6, 7, 8, 9, 10, 11 or 12, or the method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, wherein the feed block has a toffee-like consistency, able to withstanding wet weather as well as temperatures ranging from about -20°C to 50°C.

14. The feed block of claim 1, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13, or the method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13, wherein in addition to said molasses and the least one type of drench, the feed block comprises one or more of the following ingredients (all weight/weight): 40 to 50% (or to balance) molasses; 5 to 10% salt; 5 to 10% phosphate; up to 5% hydrated lime; 10 to 20% magnesium oxide; 1 to 2% minerals; 10% water; and 0.5-1% of each type of drench.

15. The feed block of claim 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14, or the method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14, wherein the block is a substantially rectangular, hexagonal or octagonal prism, or substantially cylindrical or disc-shaped.

16. The feed block of claim 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, or the method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, wherein the ruminant is a sheep and the feed block provides a fenbendazole dose in the order of about 25-30mg/sheep/day.

17. The feed block of claim 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, or the method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, wherein the ruminant is a sheep and the feed block enables a consumption rate of about 5-7mg of fenbendazole/g block for an about 50 kg sheep consuming the supplemented molasses feed block at the daily rate of about 15g.

18. The method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17, wherein the method comprises the ruminant self-medicating.

19. The method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18, wherein the feed block is fed to the ruminant for a period of 1 to 3 weeks, and more preferably 1 to 2 weeks.

20. The method of claim 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19, wherein the method comprises a step of feeding to the ruminant a first supplemented molasses feed block containing a first type of drench for a first period of time, then a second supplemented molasses feed block containing a second type of drench for a second period of time, so as to lessen the risk of drench-resistance occurring.