To WormMail list (recip. undisclosed). WRML.20130213. Drenches – sundry and various
Drenches – sundry and various
The only new active we have on the market in Australia (AU) is of course the broad-spectrum anthelmintic for sheep, monepantel (‘Zolvix’, Novartis), which belongs to the AADs (amino-acetonitrile derivatives).
The release of ‘Startect’, already available in the southern hemisphere in South Africa and New Zealand, and the UK (where it is the first dual-active wormer), is still awaited in AU. SA and NZ are currently ahead in rugby as well. (Hope springs eternal (for macropod supporters)).
‘Startect’ (Pfizer) is composed of the novel anthelmintic derquantel (a spiroindole), combined with abamectin (an avermectin, a subgroup within the macrocyclic lactones (MLs). (Moxidectin is in the milbemycin sub-group)).
By they way, you can get up-to-date info on sheep drenches in AU at the newly released (21.11.12) and revamped WormBoss: www.wormboss.com.au (Did I mention 21.11.12 is a palindrome? 🙂
Other newcomers to the Australian (AU) sheep drench market are older drugs ‘repackaged’, albeit using fancy chemistry, but are nonetheless welcome and useful additions.
These include ‘Napfix’ (Jurox) which was released a few months ago. Napfix is a combination of naphthalophos+abamectin+albendazole.
‘Sequel’ (abamectin+levamisole; Ancare) is about to be released. While using a triple broad-spectrum would arguably be more desirable, Sequel apparently will be positioned, and at quite a competitive price I believe, to get more farmers (who baulk at the price of triples) off ‘singles’ (single active broad-spectrum drenches) and onto a combination.
Competition is good: I believe the price of ‘triples’ has gone down of late by up to 10-20% per 50kg sheep dose. e.g. from roughly the 40-45 cents down to 35-40 cents. For a list of ‘triples’, see WormBoss.
Still, the most expensive drench is the one that doesn’t work.
Drench resistance is steadily getting (even) worse. The biggest changes I think over the last decade have been increasing resistance of sheep nematodes to the MLs, and increasing resistance (once uncommon) of Haemonchus to levamisole. (In Australia, resistance of the ‘scour worms’ (Trichostrongylus and Teladorsagia(Ostertagia)) species in small ruminants to LEV has been common for 20+ years).
ML resistance was once common only in places like the New England region of north eastern NSW (Haemonchus), or the south western part of Western Australia (Ostertagia/Teladorsagia), and some other winter rainfall areas (e.g. Kangaroo Island).
But recent work by District Veterinarians (DVs) in NSW has shown that resistance, including resistance of the MLs (avermectins as well as the milbemycin, moxidectin) is now common in many if not most areas. This includes the Wagga Wagga area (work by DVs Amy Shergold and Tony Morton and others ), the south west slopes (more or less) of NSW ( DVs Eliz. Braddon (Young), Belinda Edmonstone (Forbes) and Katharine Marsh (formerly of Condobolin) ) and the central west (Dubbo area; DV Evelyn Walker and others ).
A recent analysis by Rad Nielsen of VHR has shown that resistance in the New England is worsening . See also Love, 2011 . (An update by Playford and others is pending).
You could argue that, as a general rule, all sheep producers in Australia should be using multi-active broad-spectrum sheep drenches. Of course, from a theoretical point of view, such combinations have the greatest effect in delaying selection for resistance if used from day one, when resistance to each of the component actives is rare or non-existent. From a (short-term) economic point of view, this could be a hard sell.
Still, a somewhat less than perfect combination can still be a good thing. e.g. a combination of say drench A (say 95% effective (optimal is >99%), drench B (say 80% effective) and drench C (say 50% effective), all unrelated actives with similar spectra of activity and persistency, will theoretically give an overall efficacy of (95% + 4% + 0.5%=) 99.5% . ‘Better than a poke in the eye with a blunt stick.
However, we are now at the stage that many farmers, need to use ‘multi-actives’ just to achieve moderately high efficacy. Added to that is the fact that most producers do not accurately know what drenches work on their properties. So, from a best bet point of view, in the absence of data, multi-actives are a good option. (But even they are not always a sure thing, given the state of resistance).
If you wanted Zolvix alive (high efficacy) for as long as possible, a good option would be to use it in rapid rotation with combinations that are still highly effective on your farm . Lets say ML and organophosphate (OP) based combinations were still highly effective. A plan might be to use Zolvix, then (at the next drench) naphthalophos (NAP) + benzimidazole (BZ) + levamisole (LEV), then an ML-based triple eg ML+BZ+LEV. Other combinations could be used of course. Even better – short-term economics (and increased work load) aside ! – you would not use even Zolvix on its own, but you would use it concurrently with other unrelated active(s).
A word on organophosphate drenches
I think we are lucky in Australia to have OP drenches, despite the extra care they require (lower safety index). They, and their combinations, have provided an alternative to the MLs, and now an extra alternative to Zolvix.
Naphthalophos is the most famous. Bayer brought out NAP in one form or another many years ago. The first brand perhaps was Bayer Summer Management Drench, back around the time thiabendazole was released (and that was in the 1960s). Then there was Rametin H ( a 7.5 ml of the made-up drench for all sheep). H stood for Haemonchus I believe. Then there was Rametin HLV (Haemonchus-low volume); a 5 ml dose for all sheep if memory serves. (I still remember mixing up the drench from the powder (trying not to inhale) from plastic bags inside a tin (I am sure I have no nasal bot ;-)). We knew of course that with all these flat dose rates, there was also useful efficacy against ‘scour worms’ (as defined above) in sheep up to say 20-25 kg. In the 1980s, using information from Dr Keith Dash (‘father of WormKill’) I started including Rametin HLV at a dose rate of 30-35 mg/kg bodyweight in drench resistance trials (and only killed one sheep. I think my off-sider did it :-).
NAP on its own is highly effective (~100%) against adult Haemonchus, and has lower but useful activity (~ 70-90%, but variable ) against Trichostrongylus and Teladorsagia (Ostertagia) spp and immature Haemonchus. This is one reason why it should be used in combination with unrelated actives.
To my knowledge the two recorded (peer reviewed journals) cases of confirmed NAP-resistant Australian worm isolates are Green (Haemonchus), and Le Jambre et al (NAP-resistant Trichostrongylus (inferred) . From time to time, and more often in recent years, lower than expected efficacy of OPs, alone or in combination, has been seen in the field. This is mentioned for example by Love (2011; ‘Declining efficacy of NAP+BZ (against Trich) sometimes observed, some below 30% WECR ‘) and recently Nielsen indicated that low efficacy (lower than previously seen) of NAP against Trich/Ost is now common in NSW’s New England .
Rametin in its current form (the powder now comes in the mixing drum) of course is given at approximately a 35 mg/kg. Most often these days it is used in combination with other broad-spectrum drenches, which is a good idea.
Other manufacturers now have NAP-based products, including Virbac (‘Combat’), Jurox (‘Napfix’), and Agvantage, who market ‘Pole-Vault’ (presumably it gets the sheep air-borne).
The other OP-based sheep drench on the market in Australia is ‘Colleague’ (Coopers), a proprietary mix of pyraclofos and albendazole.
There was a permit until recent years for the use of ‘Neguvon’ (trichlorfon, Bayer) in Australia against Haemonchus in goats.
I understand that OP drenches are not available in NZ nor are likely to be.
Things are afoot here too.
Firstly there is increasing evidence that resistance is an issue in cattle nematodes in Australia. (There are cases of flukicide (triclabendazole) resistance too).
Added to that is evidence that route of administration can make a difference to efficacy (and possibly therefore selection of drench resistance). The recently published work of Leathwick and Miller (NZ)  is a case in point, with oral moxidectin being significantly more efficacious than injectable or pour-on (topical) moxidectin.
Just when you thought cattle drenches couldn’t get any more persistent, ‘Long Range’ (eprinomectin injectable, Merial) has hit the scene and there was a recent special edition of Veterinary Parasitology on this drench. Long Range apparently has an extended activity of 100-150 days depending on the parasite species. Interestingly the product produces two peaks of the drug in the animal, apparently by way of special polymers. The company says the product will be produce no more selection for resistance than other products because the times when drug levels are sub-therapeutic are relatively short. Whether the comparison is to other long-acting products on the market, or to relatively short-acting products as well, is unclear to me. Also, what is sub-therapeutic depends on the resistance status of target parasite populations. Once resistance begins to merge, there presumably will be increasingly longer periods of time when this (or any other drug) has sub-therapeutic levels in the animal.
If Long Range comes to Australia, perhaps it will be marketed here as ‘Long Reach’ (after the iconic town in regional Queensland. Ford named one of its utes ‘Longreach’). ‘Long Reach Two Peaks’ might be another option. (I expect to be head hunted by marketing departments of large pharmacos any time now; or perhaps just hunted).
Further to resistant cattle nematodes and the question of route of administration, my colleagues in NZ inform me that oral multi-active cattle drenches are not only available in that country, but very popular as well. (They not only do rugby well).
(To understand combinations, mixtures or both, see here: http://www.wormboss.com.au/news/articles/drenches/understanding-drenches-mixtures-combinations-and-both.php)
Here is some information from NZ veterinarian Andrew Dowling (PGG Wrightson), used with permission:
“…Our biggest selling triple drench for sheep and cattle (1ml/10kg) (over here) is called Alliance.” “Alliance is the biggest selling triple for PGW, 27% of our oral doses sold are now triples, up from 18% last year.”
“Here are some resent price comparisons.
The new thing here are injectable combinations for those farmers that do not want to orally drench (and there are plenty of them!) ”
Indicative prices in NZ (courtesy of Andrew Dowling):
||dose per 250kg
||retail per 250kg
|EDGE , doramectin plus levamisole inj
|Cydectin PO 17L
|Cydectin PO 5.5L
|Alliance 10L oral triple
|Converge 10L, oral abamectin plus levamisole
|Scanda 10L oral bz lev
|Combi Cattle PO; oxfendazole plus levamisole
‘Outlaw’/ ‘Eclipse’ are abamectin+ levamisole cattle POs (pour ons/topical drenches) in NZ.
Meanwhile in Australia…
The last time I checked, the only ML cattle drenches in AU available as oral drenches were ivermectin-flukicide (triclabendazole) mixtures (Fasimec, Triclamec). Oral formulations of BZ and LEV-based drenches are somewhat easier to find.
The one combination cattle drench I know of in AU is Eclipse (Merial), which is a pour-on containing abamectin + levamisole.
Perhaps oral formulations of combination cattle drenches are in the pipeline (possibly vying with Startect to see daylight….?)
 (Walker E et al. Pending). To be presented at the District Veterinarians’ Conference, Armidale, NSW. March 2013. May appear in a later WormMail.
 (Nielsen). https://wormmailinthecloud.wordpress.com/2012/11/02/wrml-update-drench-resistance-of-sheep-worms-new-england-region-nsw-au/
 (Love, 2011). https://wormmailinthecloud.wordpress.com/2011/11/07/update-prevalence-of-drench-resistant-sheep-worms-australia-asv-conference-paper-2011/
 “a combination of say drench A (say 95% effective (optimal is >99%), drench B (say 80% effective) and drench C (say 50% effective), all unrelated actives with similar spectra of activity and persistency, will theoretically give an overall efficacy of (95% + 4% + 0.5%=) 99.5% ” i.e. (100-5) + (5 x .80) + (1 x o.5) = 99.5
 (Dobson et al) https://wormmailinthecloud.wordpress.com/2011/07/22/wrml-dobson-papers-resistance-monepantel-and-refugia/
 Green PE, Forsyth BA, Rowan KJ and Payne G (1981). The isolation of a field strain of Haemonchus contortus in Queensland showing multiple anthelmintic resistance. Australian Veterinary Journal 57(2): 79–84.
Le Jambre LF, Geoghegan J and Lyndal-Murphy M (2005). Characterization of moxidectin resistant Trichostrongylus colubriformis and Haemonchus contortus. Veterinary Parasitology 128: 83–90.
 Leathwick DM and Miller CM, 2013. Efficacy of oral, injectable and pour-on formulations of moxidectin against gastrointestinal nematodes in cattle in New Zealand. Veterinary Parasitology 191 (2013) 293– 300. doi: 10.1016/j.vetpar.2012.09.020. Epub 2012 Sep 24
NSW DPI e&oe.
“One day a florist went to a barber for a haircut. After the cut, he asked about his bill, and the barber replied, ‘I cannot accept money from you; I’m doing community service this week.’ The florist was pleased and left the shop. When the barber went to open his shop the next morning, there was a ‘thank you’ card and a dozen roses waiting for him at his door.
Later, a cop comes in for a haircut, and when he tries to pay his bill, the barber again replied, ‘I cannot accept money from you; I’m doing community service this week.’ The cop was happy and left the shop. The next morning when the barber went to open up, there was a ‘thank you’ card and a dozen doughnuts waiting for him at his door.
Then an MP came in for a haircut, and when he went to pay his bill, the barber again replied, ‘I cannot accept money from you. I’m doing community service this week.’ The MP was very happy and left the shop. The next morning, when the barber went to open up, there were a dozen MPs lined up waiting for a free haircut.
And that illustrates the fundamental difference between the citizens of our country and the politicians who run it.
Both politicians and nappies need to be changed often and for the same reason?
If you don’t forward this you have no sense of humour. Nothing bad will happen, however, you must live with yourself knowing that laughter is not in your future. Now send it to everyone you know….”
(Don’t send it. We all hate chain emails)
(The views above do not necessarily reflect that of the editor and certainly not of his/her employer. The situation may be different in your country: it is here… (<cough>)).
BBC News – Coca-Cola drinking ‘linked to New Zealander’s death‘
Up to 10 litres per day ( = 1 kg sugar and approx 1000 mg caffeine, per day (Soft drinks and fruit juices typically are ~ 10% sugar)) The average westerner has ~ 1 kg sugar per week(~50 kg per year), and this is ~ 30 times the consumption of people ~ 100 years ago. That’s progress.
For an interesting read on sugar, the book (‘Pure White and Deadly”) by the late Prof Yudkin, with a foreword by Prof Robert Lustig, has recently been republished. (And for South African readers, your very own Prof Tim Noakes now holds similar views).
I think I need a chocolate thick-shake.
Palindrome : literally ‘again way’