WormMail Issue 20091126 Editor: Stephen Love
TO: WORMMAIL MAILING LIST
IN THIS ISSUE:
* Notes on monepantel (Tony Morton) * Managing the first drench in 25 years (Bruce Watt) * Pathology of round and tapeworms (Brown Besier) * Cydectin® LA, combinations etc (SL) * World’s Oldest Sheep? * Managing Flystrike – Sheep CRC * Sweet Poison (Gillespie) * Environment/Sustainability (Godwin)
NOTES ON MONEPANTEL
Dr Tony Morton, District Veterinarian, Hume LHPA
“Recently Bruce Watt and I attended a key opinion leader meeting organised by Novartis at Wagga regarding Zolvix® (monepantel). There was a range of DPI, CSU vets, consultants, leading resellers etc present. I attended as the southern internal parasites representative for NSW District Veterinarians. It was a fascinating meeting.
Bruce did an excellent press release from the meeting (pasted below).
A few dot points I noted (and have been commented on by Justin Bailey of Novartis) which you may find of interest include:
*works on all resistant nematodes
*aiming to develop a test that finds resistant alleles earlier than faecal egg count reduction test
*effective (higher) dose rate published re goats
*pre treatment fasting yielded no significant benefit (Refer to work of the late Des Hennessy showing benefits of feed restriction when treating with BZs, closantel, MLs (but not LEV, and should not restrict feed before/after OP drenches. Also where the drench gun is placed in the mouth. See DrenchPlan Primefact,
www.dpi.nsw.gov.au - Ed).
* as a quarantine treatment: zero worm eggs in faeces by about 48 hours (n.b. monepantel is not ovicidal)
* very safe, 800x normal dose = LD50
*Meat withholding period in New Zealand is 7 days
*It will be marketed (initially) as a single compound not as a combination (why? high efficacy and safety profile, new chemistry (takes time), global market- no combos registered in Europe).
*computer modelling for main roundworm (
Teladorsagia/Trichostrongylus) species at Hamilton, Victoria showed the best rotation was monepantel and a triple combo. The modelling also indicates the long acting effect of moxidectin promotes resistance. It also showed that at Hamilton not drenching 10% of the mob had little effect on the development of resistance (this was different from WA with its hot dry summer)
* work done by Dave Leathwick in NZ which showed that to achieve the same dilution of resistant alleles (when drenching onto identical pasture) attained by leaving 1% untreated with a 99.9% effective drench, would require leaving 5% untreated with a 99% effective drench or 34% untreated with a 95% effective drench.
*Nick Sangster’s (Charles Sturt Uni.) modelling (Sangster and Dobson) suggests that with the two new actives coming on the market if they are rotated it will take about 7.5 years for resistance to emerge, if used in combination there would no resistance after 20 years.
See the CSU web site for further details:
http://www.csu.edu.au/faculty/science/savs/research/whatsnew.htm (Also see:
http://paradak.wordpress.com/2009/08/26/managing-new-anthelmintics-sangster/ - Ed. ).
Nick commented: “The modelling makes some assumptions about ideal components of a combination which we can’t be sure occurs. Nevertheless it illustrates a principle. Dave Leathwick discusses it in his paper (referred to in the talk)”.
The latest AVJ (Nov 2009) has an excellent article on the efficacy of Zolvix (monepantel) in sheep”.
MANAGING THE FIRST NEW DRENCH IN 21 YEARS
Dr Bruce Watt, Senior District Veterinarian, Tablelands LHPA
(Article for local (Bathurst) newspaper. Republished with permission).
In 1988, Nick Greiner ousted Barry Unsworth in the NSW state election. Our Prime Minister Bob Hawke stood by (but didn’t touch) the Queen as she helped us commemorate the bicentenary of the landing of the First Fleet by opening the New Parliament House in Canberra. Duncan Armstrong won gold in Seoul but we lost the Bledisloe Cup 2-0. And the last drench from a new group, ivermectin, was launched in Australia.
A new drench group is therefore big news. I recently joined a group of vets, consultants and farmers in Wagga to hear Novartis company veterinarians lead a discussion on how we might best manage their new product, Zolvix® (monepantel), one of two completely new drenches to be released in the near future.
Dr Stephen Love (I&I, Armidale) told us that it usually takes about five years from the release of a new chemical group drench for the first signs of resistance to appear. Unusual exceptions however do occur. As I have mentioned previously worms have been very slow to develop resistance to the organo-phosphate drenches, just as lice have been very slow to develop resistance to OPs and flies to cyromazine (Vetrazin®, and now generics).
Nick Sangster, professor of veterinary pathobiology at Charles Sturt University, gave us a summary of management practices that are likely to enhance the development of chemical resistance in worms.
He listed the failure to administer a quarantine drench to newly purchased stock, the use of long acting products, drenching before moving to very clean pastures (especially stubbles), the treatment of ewes prior to lambing and finally under dosing and drenching excessively as the most likely factors.
However, internal parasite management is a juggling act between controlling worms in sheep for enhanced health and production and drenching sensibly to avoid resistance.
We all agreed that we would like to see Zolvix® used responsibly to delay resistance and to help in worm control. Extensive trial data from both Australia and elsewhere show that it is highly effective against a wide range of worms including those resistant to other drenches.
It is also non-toxic and easy to administer. For sheep producers the only bad news is that it will not be cheap. While Australian pricing has not been disclosed, I am told you can expect to pay a premium for Zolvix®.
So how might (NSW central) tablelands sheep producers use monepantel? As most still have at least three effective drench types to choose from (abamectin/moxidectin, the OP combinations and the triple combinations), they are not yet backed into a corner on resistance (unlike some of their New England counterparts).
However, I think many rely heavily on abamectin and moxidectin. Monepantel will be a useful alternative to the OP combinations for those who would like to extend the life of moxidectin on their farms.
The first summer drench, due now, would be an appropriate time to use monepantel, although perhaps not this season as it is not yet released. It would also be most useful as a drench for young sheep that require a lower and so less expensive dose and where its safety and effectiveness would be valuable.
PATHOLOGY OF ROUND- AND TAPE-WORMS (Dr Brown Besier, Principal Veterinary Parasitologist, Dept. Agric., WA)
An excerpt from a conversation among colleagues:
"I ... agree that there is no clear evidence that Moniezia are pathogenic and only anecdotal evidence that they have any effects in lambs, or in promoting enterotoxaemia. There have been a number of more or less inconclusive trials, but I have never talked to a parasitologist in any country who thought Moniezia was a problem in sheep.
This makes sense when you think of it: there is good evidence that the majority of the damage that nematodes do to sheep (apart from blood-sucking ones) is immune-mediated. If you abolish the hosts’ response to the worm burden (by using corticosteroids), there is little pathogenic effect such as appetite depression, local tissue damage or nitrogen metabolism impairment. The severe effects we see from Teladorsagia and Trichostrongylus result from thousands of contact points where an immune response is engendered, but typically, lambs carry only one or a few Moniezia. I imagine that although they are quite immunogenic (spontaneously expelled at a young age), the very low amount of antigenic exposure would result in relatively little overall immune-mediated physiological effect. (Although I readily admit I am not an immunologist!)
Regarding tapeworms in horses, Anoplocephala are considered quite pathogenic, and I have seen good trial evidence for this. "
Notes: Moniezia species are the common intestinal tapeworm of sheep and goats. Teladorsagia (Ostertagia) circumcincta: (small) brown stomach worm. Trichostrongylus spp (e.g. T. colubriformis, T. vitrinus): black scour worm. – Ed.
CYDECTIN® LA, COMBINATIONS ETC
A vet from northern NSW emailed me recently for my opinion regarding usage of Cydectin® LA and related matters. Some of the interaction appears below (personal identifiers removed; and ‘typos’ hopefully fixed).
“Hi Steve
Some advisers promote Cydectin® LA with a Levamisole primer and Lev / Rametin at day 80. I’m told this reduces resistance build up considerably on the computer models. The other thing is that, in the New England, they like to use it in the autumn so that any eggs that drop from surviving Haemonchus during the tail off of the sustained action (that is the point where resistance develops) are laid into the non-viable egg hatching winter months. A colleague has also I pointed out that in areas like Narrabri there is also a non-viable period due to high evaporation over Dec – Jan and so its use in Oct would fit in with the strategy of the tail going into non-viable periods. What are your thoughts? Regards ''Alphonse'' ================================ Hi 'Alphonse'
Some thoughts:
* In theory at least, to delay resistance it is better to use unrelated actives in combination, rather than singly in any sort of rotation. The 'perfect' combination contains unrelated actives (different modes of action/different genes for resistance) with the same length of action, the same spectrum of activity, and resistance to each is rare (ideally absent). (And of course, it doesn't cost any more than a single-active product, comes premixed, is a delight to use, and comes with a free Play Station etc).
* So, the advice to use a primer and tail-cutter/exit drenches is employing 'combination theory'.
* The background, as you know, is that ML resistance in
Haemonchus contortus (Hc; barber’s pole worm) is escalating in macrocyclic lactone drenches (MLs) in northern New South Wales and south eastern Queensland, and this is also affecting the most potent of the Sheep MLs, moxidectin.
It is common now for Hc eggs to be appearing 'early' after Cydectin® (moxidectin) treatment, whether oral or LA, indicating that the period of protection is being eroded (as happened with closantel in the late 1980s/ early 1990s). Also there are cases, beginning with the one in the Warialda district (circa 2000), where Cydectin is not 100% effective against resident Hc. (Reported, with a view to sounding an alert, in the Australian Vet Journal several years ago).
* Early in the piece, Fort Dodge and others recommended Cydectin usage early in the season (e.g. pre-lambing, early Spring) and throughout the season, albeit with a lower frequency of treatment being required than if short-acting drugs were used (unless short-acting drugs were combined with good integrated parasite arrangement (IPM), including grazing management).
So, Cydectin pre-lambing and then later in the season gave great results all round. It really is an outstanding anthelmintic (but none of them are immortal). In fact once or twice I jokingly told F-Dodge area managers that they were superfluous: Cydectin sold itself. (I don't think my humour is always appreciated).
Cydectin of course filled the void left by the narrow-spectrum drench closantel (Seponver(R), Razar(R) etc), which worked like 'magic' in a rational program (WormKill 1 and 2) against Hc (at least from 1984 to the early 1990s). A down-side in some respects is that Cydectin is a broad-spectrum product. (Sometimes it is being used primarily to control one roundworm species, i.e. Hc).
Then there are the pros and cons of the long tail, which is a two-edged sword. The extent to which the potency of Cydectin ameliorates the negative aspects of a long tail (increased potential for selection for resistance) was hotly debated for a long time, without much benefit, and often detracting from more important issues. (e.g. ‘what drenches work on your property?’ ‘How can you protect them?’ ‘What IPM measures can you implement or improve?’ ‘How do you decide when to drench?’).
Ideally, like any other drench, Cydectin should have been used in an appropriate combination from day one. An imperfect 'combination' (remember there are no perfect combos) would be an efficacious non- ML drench as a primer then an efficacious non-ML as a ‘tail-cutter’ (‘exit’ drench). (The timing of the tail-cutter is a bit tricky and would best be determined by regular faecal worm egg count (FWEC) monitoring through the tail of Cydectin).
* The Achilles heel of Hc is its eggs. Freshly laid eggs are only viable for around 7 days. During that time they have to have adequate temperature and moisture for the eggs to develop and hatch. (In around 24 hours under optimal conditions). Then there needs to be adequate moisture for the third stage/infective larvae (L3s) to get out of the faecal pellet and go 'walk-about' in films of moisture on the grass.
From an ecological point of view, the biggest difference between the three important roundworms of sheep in Australia (
Haemonchus (barbers pole worm),
Ostertagia (
Teladorsagia; small brown stomach worm) and
Trichostrongylus spp (black scour worm)) is the eggs. The survivability of the L3 larvae of each species is broadly similar. But differences between the eggs are bigger.
In order of decreasing susceptibility (of eggs) to cold and desiccation; here is how they stack up:
Barber’s pole worm - black scour worm - small brown stomach worm.
(Nodule worm -
Oesophagostomum columbianum - thought to be extinct in the Northern Tablelands (but not the north west of NSW) is even less cold tolerant than
Haemonchus. (Interestingly barber’s pole worm and
Oesophagostomum are thought to be 'African' worms, whereas
Ostertagia and
Trichostrongylus are thought to have co-evolved with sheep in central Asia. But that is another story. See 'Le Jambre's Theory of Co-Evolution' in one of the ‘Turning the Worm' newsletters on-line).
When I am talking about moisture, I am mainly referring to precipitation, and am implying 'effective' precipitation. The late Ian Barger long ago used to refer to precipitation/evaporation (P/E). (And I know that Shaun Slattery talks about the negative effects on Hc of high evaporation rates in summer in the Narrabri district, and the positive effects of heavy dews in autumn).
So a month of 100mm rainfall in summer in the Northern Tablelands might be different from the same rain in Narrabri.
* The strength of Hc is its fecundity, with females pumping out around 10 000 eggs per day, around 10-20 times as much as the scour worms. So, when the narrow window of opportunity arises (warm and moist), Hc is there in numbers, ready to go. (But liver fluke surpasses Hc in fecundity and certainly in longevity).
* Pondering the weaknesses of barber's pole worm, you can see why a good system of rotational grazing can work well in its control. Or, to put it another way, the worst thing you can do for barber’s pole worm control, in terms of grazing management, is set-stocking.
Hang in the 'Alphonse'; I'm getting there.
* So, the rationale for using Cydectin LA in autumn, as you have noted, is that when barber’s pole worm eggs appear post-treatment, it will be too cold for the eggs to develop and hatch (i.e. days consistently below 10 degrees C overnight), and resistant genes won't make it through to the next generation. A similar rationale is used in other areas: i.e. timing of the treatment so that, when eggs do appear post-treatment, the conditions are too hostile for eggs/larvae. Of course, all this comes unstuck if eggs appear a whole let earlier than you expected.
But, we focus on ML-resistant
Haemonchus in the Hc endemic areas. What about
Ostertagia and
Trichostrongylus? And their eggs can tolerate a wider range of environmental conditions than
Haemonchus. ML resistance in
Trichostrongylus so far appears to be somewhat less common than for Hc (summer rainfall areas) and
Ostertagia (winter and non-seasonal rainfall areas) but we know that ML-resistant
Trichostrongylus is more than a theoretical possibility (e.g. see Le Jambre and others (2005). Characterization of moxidectin-resistant
Trichostrongylus colubriformis and
Haemonchus contortus. Veterinary Parasitology)
*
Now, regarding the advice (
Haemonchus -endemic areas) favouring the use of Cydectin® LA with a levamisole primer and Lev / Rametin (MAP; naphthalophos) at day 80 etc:
In general, this seems quite logical to me. I think this can be seen as preventative and/or curative. I include 'curative' (in the sense of dealing with - if not fixing - an existing problem) because there are properties where Hc eggs are appearing quite early after treatment with moxidectin, including Cydectin LA. (See graph below, which I prepared some time ago from data by Bailey and Nielsen, 2005. No doubt this data will be updated some time).
It seems that giving a primer in these cases allows you to still get some mileage out of the moxidectin drench. FWEC monitoring of course would be mandatory. In fact FWEC is generally mandatory anyway, but especially with long-acting products, and most definitely if there are any suspicions of resistance.
Optimally, if any long acting product is used, even if apparently effective on it's own, an effective primer should be given at the beginning (to help reduce head selection) as well as towards 'the end' - i.e. a tail-cutter or exit drench.
The timing of the tail-cutter could be based on best guess (based on label claims for the product and on-property experience with the product) or, better, regular FWEC monitoring. Cultures may be required, as the protective period against susceptible worms in the case of moxidectin at least is shorter for
Trichostrongylus than for
Haemonchus (and
Ostertagia). The rationale for the recommendation on using a tail-cutter at day 80 I assume is roughly based on the claimed protective period against susceptible Hc less the prepatent period of 18-21 days for
Haemonchus (plus a bit). Also I guess as a bonus it, all going well, kills
Trichostrongylus, the eggs of which might be expected to appear around day 80 post treatment (earlier if resistance is present).
LEV is a good option as a primer for Cydectin LA in Hc-endemic areas because LEV is cheap and likely to work on it's own against Hc, and even more likely to work in company with moxidectin. But, we both know there are properties in the New England where Hc is resistant to MLs, including moxidectin, as well as levamisole (and also benzimidazoles and closantel).
Hc-resistant LEV are still relatively uncommon, but I think it would be best not to use LEV on its own, cost considerations aside. As to the tail-cutter, I think a NAP+BZ+LEV combination would be better than Rametin®/LEV. The greatest part of the cost of any NAP(thalophos) combination is the NAP (Combat®, Rametin®), so going for a three way rather than a two way NAP combination has increased benefits that outweigh the marginal increase in cost. As an aside, for ML-based combinations, NAP-ML is one that should be considered. And again, it would be better (from a resistance point of view) to only use MLs in combination (e.g. abamectin+NAP, or ML-based triple or quadruple drenches). Yes, cost is a consideration.
It goes without saying that any drench option, including 3 or 4 way combinations, should be tested on a property, whether by way of a DrenchTest (faecal worm egg count reduction test (FECRT); best) and /or through ongoing monitoring (DrenchCheck: post treatment FWEC monitoring). There are cases in the New England of resistance to 'triple' combinations.
‘A long winded answer, 95% or more of which your probably already new, but hopefully it was helpful.
Regards
Steve”
WORLD’S OLDEST SHEEP?
http://au.news.yahoo.com/a/-/odd/6510526/big-sleep-for-lucky-sheep/
MANAGING FLYSTRIKE
New area on Sheep CRC website:
http://www.sheepcrc.org.au/industry-tools-and-information/managing-flystrike.php
SWEET POISON – by David Gillespie
Although experts in the field may feel that Gillespie has oversimplified the fructose story (and thus made it more digestible?), it is nonetheless an interesting book. Sweetpoison.com.au
By the way, the whole fresh fruit you eat is not the villain. Most metabolisable fructose in western diets comes from elsewhere.
The problem in a nutshell? We are not designed to consume large amounts of fructose. Fructose pretty much bypasses intake control (appetite regulation), unlike other carbohydrates, protein and fat, and also sidesteps regulation of metabolism. The end result of fructose excess, according to Gillespie, is increased fatty acids (and adipose tissue), and increased LDL cholesterol. We consume massive amounts of fructose, much of it invisible, and much of as sugar (which is 50/50 glucose and fructose) and, in the US in particular, as high fructose corn syrup.
ENVIRONMENT AND SUSTAINABILITY – Dr Ian Godwin-UNE
(I found this in my archives. Permission to use this in my newsletter was obtained from IG 17/12/2004 and again 26/11/09. Note this was written in 2004; some of the details may have changed since then. Ian is no longer the man he used to be, having put into practice his own expertise on fructose metabolism, just as Gillespie (Sweet Poison) put into practice findings from his own reading on the subject. Ian researches fructose metabolism and is currently Assoc. Professor, Animal Physiology - Environmental and Rural Science W28, UNE, Armidale, NSW AU). Date: Tue, 14 Dec 2004 14:29:20 +1100
To: unesci-all
Dear All,
We have been asked for feedback on the university's new environment and sustainability policy. I have a suggestion outlined below.
Whilst walking to work this morning I pondered the consequences of losing the 5kg of extra body weight that I carry around.
Human adipose tissue contains approximately 2% myristic, 26% palmitic, 14% stearic, 44% oleic and 10% linoleic acids (the remaining few percent is structural proteins etc which we will ignore). To lose this weight by exercising will require the conversion of this fat to carbon dioxide.
This means for each mole of oleic acid (C18H34O2) 18 moles of CO2 will be produced. Each mole of CO2 will occupy 22.4 Litres at 25 degrees C. Each kg of fat will produce 64.6 moles of CO2.
As there are currently 60% of Australians overweight or obese (lets say by an average of 5kg), then loss of this weight would generate 87,858,708,754 litres or 172,580 tonnes of CO2.
This is why we cannot ratify the Kyoto protocol as it has too great a health consequence for the nation. We can also add in further direct increases to global warming, if we take into account the 37KJ (8.84 Calories) of energy liberated for each gram of fat oxidized. This would yield enough heat to raise the temperature of 5,363,183Litres of water to boiling point.
I will be applying for carbon credits for my spare tyre, although MacDonalds is disputing ownership.
This should be considered in the university's new environment and sustainability policy. I think that the university should provide free Pizza lunches, to reduce the greenhouse emissions from the campus.
So all you skinny types out there make sure you eat up big over Christmas to save our environment.
Kind regards,
Ian G.
Ian Godwin
University of New England
Armidale, N.S.W.
