WRML.Redux-drench combinations vs drench rotation.Contagious yawning in sheep

In this issue:

  • Redux: drench combinations vs drench rotations
  • Contagious yawning in sheep

Combinations vs drench rotation to delay resistance

Recently Dr Lewis Kahn (CEO of Paraboss; Assoc Professor at UNE), commented on results of modelling (Teladorsagia model) by Dr Yan Laurenson (ParaBoss Feature Article; reprinted in WormMail).

The article reported that, to delay the onset of anthelmintic resistance, using combinations (of unrelated drench actives) was vastly superior to using single active drenches sequentially (drench A for an extended time, then drench B)  or rotation, for example, annually. It was also stated that the results of this modelling broadly confirm the results of other models developed in Australia, New Zealand and elsewhere over the last 20 years. (In the following, emphases (bolding) are mine. – Ed.)

In June 2011, Dobson and others reported the results of a study which addressed the best ways of using the new active monepantel (Zolvix) as well as existing actives. A multi-species model (Haemonchus, Trichostrongylus and Teladorsagia) was used to simulate worm burdens and selection for drench resistance in sheep in two winter rainfall zones (Kojonup (Western Australia, WA), Hamilton (Victoria, VIC),) and two summer rainfall zones (Glen Innes and Armidale (New South Wales, NSW).

To test the effect of refugia, 0,1,4,7 or 10 % of sheep were left untreated (UT).   Drench regimens explored were (1) monepantel (MPL) + benzimidazole (BZ) + levamisole (LEV) +abamectin (ABA) used in combination/concurrently, or (2) MPL rotated with BZ+LEV+ABA, or (3) MPL rotated with moxidectin (MOX), or (4) MPL rotated with BZ+LEV+ABA and MOX. So, 20 different treatment regimens were modelled in each region.

For both WA and Vic, using MOX+COM 0%UT, i.e., using MOX+BZ+LEV+ABA in combination, and leaving none-untreated, scored the best in both worm control and resistance management. For northern NSW, MOX+COM 0%UT scored best on resistance management, but was narrowly beaten by 4 other regimens (each of which included MOX and also a combination) on worm control. (Resistance was assumed to be emerging for MOX and ABA (3% resistance alleles) (the situation now-2016-is different!-Ed) and common for BZ+LEV (40% resistance alleles).

Arguably MOX+COM 0%UT would have scored highest as well for worm control in northern NSW if worm control was optimised, as outlined in WormBoss-Your Program.

The authors concluded that “in general, the model predicted that leaving more than 4% of adults untreated did not sufficiently delay the development of anthelmintic resistance to justify the increased production risk from such a strategy.(But in other studies, leaving some undrenched – with caveats – gets a tick). The choice of a drug rotation strategy had an equal or larger effect on nematode control, and selection for resistance, than leaving 1–10% of adults untreated”. I might add it also showed the superiority of combinations.

Barnes and others (1995) used a model simulating Trichostrongylus colubriformis in sheep at Armidale NSW. They found that, using ‘mixtures’ (i.e. using two unrelated drugs simultaneously, with individual drug efficacies at either 10, 50 or 99%), little (further) resistance developed over 20 years, whereas substantial resistance developed with each of the rotation strategies. Resistance developed more rapidly if it was determined by a single rather than two or more genes Resistance developed fastest if it was dominant. Leaving a proportion untreated delayed resistance, but at the expense of worm control. Also in their simulation, it was found that, without grazing management, heavy reliance on drugs rapidly leads to very high levels of resistance and lamb death. (Sage advice from the Terrific Trio).

Sangster in 2001, in a general discussion (covering a range of hosts and parasites), outlined in Table 4 of that paper, lists these measures to slow or deal with resistance: monitor resistance and use effective drugs, reduce reliance on chemicals (especially where there are (parasite) survivors; reduce the number of infective stages (i.e. control exposure); use effective drugs at full dose rates; do not use suppressive treatment regimens; rotate between chemical groups; monitor and treat when thresholds are reached; maintain a refugium (e.g. by leaving some untreated; or delaying the move to a very clean paddock after drenching); use short-acting drugs;  and, finally: “ the use of combinations has been predicted to be the most effective way of delaying resistance”… evidence comes from models of parasites as  diverse malaria, ticks, helminths…   (so) use combinations of drugs with different modes of action, against which there is no resistance (optimal, but often unachievable in the real world. – Ed), and which have the same elimination half lives.”

Smith in 1990 modelled the evolution of anthelmintic resistance in a direct life cycle nematode parasite and reported that the model suggested that alternating or sequential use of  anthelmintics with different modes of action may be a less effective resistance management strategy than administering the same drugs simultaneously. Smith stated that there was general agreement that infrequent treatments which targeted just those animals at particular risk would impede development of resistance, but that there could be production penalties. As to various drug strategies, he said the literature was replete with conflicting opinions, with some advising the use of one drug until it became ineffective, then switching to another (sequential use); still others suggested slow rotation of alternate drugs; and finally some (including Dash in 1986, and Anderson, Martin and Jarrett, in 1989), recommending using mixtures of anthelmintics.

There has been a growing acceptance of the value of using drugs in combination, but at the same time the idea that rotation of drugs has significant value in delaying resistance in nematodes of sheep still enjoys considerable favour, despite the paucity of supporting evidence. Lewis Kahn has thought that one paper might have been thought to provide evidence. That reported a study by Donald and others (1980) in which oxfendazole-resistance Teladorsagia (Ostertagia) in sheep was then exposed to selection with levamisole. Progeny of survivors of levamisole treatment(s) showed reduced resistance to oxfendazole, suggesting that levamisole selected against benzimidazole resistance. From this it was suggested that alternation in the use of different drugs could delay the development of resistance.

It has also been suggested that the recommendation to rotate drugs when controlling nematodes in sheep has largely been extrapolated from studies in insects (??).

So, the recent article by Lewis Kahn is a salutary reminder.

To repeat his main points:

Rotation between different drench groups does relatively little to slow development of drench resistance and should not replace these three highly effective practices:

  • use products most effective on your property
  • use multi-active (combination) products
  • use short-acting products

Moving (rotating) to a different drench (or combination of drenches) as an ‘exit’ drench can be of value:

  • at the end of the protection period of a persistent drench.
  • when sheep are exiting a paddock which was a low worm-risk paddock into which the sheep were drenched and moved earlier, for example pre-lambing, ewes, or lambs at weaning.

According to the Laurenson modelling, a relatively small benefit (compared to using combinations) from drench rotation can also accrue if rotational grazing is practised as well.

~~~~~~~~~~~~~~

All of the above should part of a complete program, as outlined in WormBoss programs, for example, which also, apart from drenching, deal with:

  • controlling exposure to infective larvae – though grazing management.
  • reducing vulnerability of animals – through nutrition and genetics.
  • maintaining sufficient worms in refugia.

As Bartram and others (2012) say, using combinations is not a panacea.

References

Barnes EH, Dobson RJ, Barger IA, 1995. Worm control and anthelmintic resistance: adventures with a model. Parasitology Today. 1995 Feb;11(2):56-63.

(Also see Bartram and others, 2012.  The role of combination anthelmintic formulations in the sustainable control of sheep nematodes. Veterinary Parasitology.)

Dobson RJ, Barnes EH, Tyrrell KL, Hosking BC, Larsen JWA, Besier RB, Love S, Rolfe P and Bailey JN, 2011. A multi-species model to assess the effect of refugia on worm control and anthelmintic resistance in sheep grazing systems. Australian Veterinary Journal Volume 89, No 6, June 2011

(Also see this paper by Dobson et al in May 2011; Minimising the development of anthelmintic resistance, and optimising the use of the novel anthelmintic monepantel, for the sustainable control of nematode parasites in Australian sheep grazing systems. Australian Veterinary Journal Volume 89, No 6, June 2011).

(Also see:

Leathwick DM, 2011.Modelling the benefits of a new class of anthelmintic in combination

Vet. Parasitol. (2011) http://dx.doi.org/10.1016/j.vetpar.2011.11.050

Leathwick DM, Hosking BC, Bisset SA and McKay CH, 2009.Managing anthelmintic resistance: is it feasible in New Zealand to delay the emergence of resistance to a new anthelmintic class? N. Z. Vet. J., 57 (2009), pp. 181–192)

Sangster N, 2001. Managing parasiticide resistance. Veterinary Parasitology 98 (2001) 89–109.

(Also see: Sangster N and Dobson R, 2002. Anthelmintic resistance.  In: Lee, DL, ed. The Biology of Nematodes, London: Harwood Academic Publishers, 2002; 531-567).

Smith G, 1990. A mathematical model for the evolutions of anthelmintic resistance in a direct life cycle nematode parasite. International Journal of Parasitology. 1990 Nov;20(7):913-21.

Further reading:

David J. Bartram, Dave M. Leathwick, Mike A. Taylor, Thomas Geurdend, Steven J. Maedere, 2012. The role of combination anthelmintic formulations in the sustainable control of sheep nematodes. Veterinary Parasitology, Volume 186, Issues 3–4, 25 May 2012, Pages 151–158. http://dx.doi.org/10.1016/j.vetpar.2011.11.030 http://www.sciencedirect.com/science/article/pii/S030440171100762X

Abstract below, but read the full review:

Abstract

Combinations of anthelmintics with a similar spectrum of activity and different mechanisms of action and resistance are widely available in several regions of the world for the control of sheep nematodes. There are two main justifications for the use of such combinations: (1) to enable the effective control of nematodes in the presence of single or multiple drug resistance, and (2) to slow the development of resistance to the component anthelmintic classes. Computer model simulations of sheep nematode populations indicate that the ability of combinations to slow the development of resistance is maximised if certain prerequisite criteria are met, the most important of which appear to concern the opportunity for survival of susceptible nematodes in refugia and the pre-existing levels of resistance to each of the anthelmintics in the combination. Combinations slow the development of a resistant parasite population by reducing the number of resistant genotypes which survive treatment, because multiple alleles conferring resistance to all the component anthelmintic classes must be present in the same parasite for survival. Individuals carrying multiple resistance alleles are rarer than those carrying single resistance alleles. This enhanced efficacy leads to greater dilution of resistant genotypes by the unselected parasites in refugia, thus reducing the proportion of resistant parasites available to reproduce with other resistant adults that have survived treatment. Concerns over the use of anthelmintic combinations include the potential to select for resistance to multiple anthelmintic classes concurrently if there are insufficient parasites in refugia; the potential for shared mechanisms of resistance between chemical classes; and the pre-existing frequency of resistance alleles may be too high on some farms to warrant the introduction of certain combinations. In conclusion, anthelmintic combinations can play an important role in resistance management. However, they are not a panacea and should always be used in accordance with contemporary principles for sustainable anthelmintic use.

For those who like pictures:

love-s-powerpoint-slide-2015-02-value-of-combinations-adapted-from-kahn-citing-leathwick-2012

Contagious yawning in sheep

Now for something different, and in no way connected to the above:

http://onlinelibrary.wiley.com/doi/10.1111/asj.12681/abstract?campaign=wolearlyview

(Thanks Dr Hatcher)

SL, Armidale, 2016-10-28

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WRML. WormFax.cost of worms-UK.flotation fluids. a first for Armidale. quolls and trematodes.cows and choppers

WormfaxNSW – September 2016

The September issue is now online.
Below is some commentary:

Article for ParaBoss News – October 2016

“Sheep worm egg counts are on the rise in most areas of New South Wales, which is not surprising given above average seasonal conditions. If it’s good for grass, it’s good for worms.  And good for snails as well, which includes lymnaeid snails, the intermediate host for liver fluke.

It is critical to do regular worm egg counting (WECs), probably every 4 weeks while worm-risk remains high. Using ineffective drenches exacerbates worm-risk, so it is more important than ever to do DrenchChecks – with a WEC on the day of drenching and again ~ 10 days later (in sheep). With organophosphate (OP) drenches – and therefore OP-based combinations – no longer available in AUS (possibly Napfix will make a comeback ???), then drench choices are more limited, which might increase the chance that farmers will inadvertently use ineffective drenches – unless they do regular check drenches.

Don’t forget that we also have some resistance to flukicides.  To test their efficacy, against adults at least, do a fluke worm egg count on the day of treatment and again 3 weeks later.  There is also the ‘copro-antigen test’ aka ‘faecal fluke antigen test’: ask your adviser. As with round worms, combinations have also been advocated by experts for treating liver fluke, notably Fairweather and Boray (1999), and more recently Kelley and others (2016). The ones that I can think of, and which we have in Australia as off-the-shelf products, are triclabendazole + oxfendazole and, for cattle only, combination products containing the flukicides nitroxynil and clorsulon. Interestingly, according to Boray, synergism has been claimed for triclabendazole + oxfendazole, but not for triclabendazole + albendazole, even though albendazole on its own has some claim as a flukicide (against adults, when used at a higher dose rate), unlike oxfendazole. The situation is the same with closantel + oxfendazole (once available as ‘Closicomb’, effective against 6+ week old fluke) vs closantel + albendazole (once available as ‘Closal’, effective against 8+ week old fluke).

A lot more people will be considering Barbervax, at least in young sheep, including in central and southern NSW which have been seeing higher numbers of Haemonchus, which is a regular occurrence in the northeast of NSW, ‘Haemonchus heaven‘.

If it all possible, prepare a low-worm risk paddock for young sheep that will be weaned in mid-summer. It’s not too late. Check out the WormBoss program for your area.(WormBoss.com.au)

Do your weaner cattle, weaned in autumn, need a drench?   In many areas, numbers of larvae on pasture of  that most important cattle roundworm in temperate regions, i.e. Ostertagia, peak in late winter – early spring. These larvae, exposed to cold conditions, also tend to become inhibited for 3-6 months, sitting in the abomasum with development on hold, then resuming development in summer – autumn when the cattle are around 16-18 months of age, possibly producing ‘type 2 ostertagosis’. Macrocyclic lactone (ML) drenches are the best for Ostertagia in cattle, including inhibited stages.   But remember that resistance of cattle roundworms to drenches is now common too. If drenching weaners this spring, an ML-based one is a good option, even better, a combination containing an ML and one or more other unrelated broad-spectrum actives. The two options in Australia are Eclipse (pour-on) and Trifecta (oral). Consider a DrenchCheck when treating cattle as well, but remember that the egg count post-treatment is done at 14 days.”

Cost of worms in Wales, Northern Ireland, Scotland and the other place…oh yeah…England

http://liveuk-livestockfarming.ztsaccess.com/posts/sheep/cost-of-worm-resistance-in-sheep-infographic.aspx

OK, this is partly an advertorial for a particular drench, but it’s interesting nonetheless. (Thanks SAJ).

Flotation fluids –parasitology- RVC / FAO

Accessed Oct., 2016: http://www.rvc.ac.uk/Review/Parasitology/Flotation/Flotation_fluids/General.htm

‘Might be of use/interest.

The first tertiary institution in Australia outside a capital city was in Armidale

The first tertiary institution in Australia founded outside a capital city was in Armidale, NSW. It was not Armidale Teacher’s College nor the New England University College.

It was St John’s Theological College, established in 1898.

Architect Horbury Hunt, in what would be his last Armidale commission, drew up plans for a permanent building for the college.

http://newenglandhistory.blogspot.com.au/2014/05/history-revisited-college-capital-idea.html

FNQ Cows more dangerous than Brisbane Broncettesos

http://www.brisbanetimes.com.au/queensland/helicopter-destroyed-after-runin-with-cow-20160919-grjh3l.html

Quoll – who is monitoring whom?

quoll-with-collar-photo-trent-forge-posted-by-guy-ballard-2-facebook-at-work-2016-10-03

Photo posted with permission. Originally posted by wild dog researcher, Dr Guy Ballard, in Facebook at Work (NSW DPI), with this comment:

“Monitoring collared quolls’ responses to wild dog & fox control programs is a two-way street: sometimes they monitor us too.”    Photo by researcher, Trent Forge.

And here is a gastrointestinal fluke (trematode) (Mehlisia acuminata) from a quoll. (Guts supplied by Dr Ballard et al; ID and photo by Dr Tommy Leung, UNE)

quoll-trematode-mehlisia-acuminata-gi-tract-t-leung-une

Photo: T Leung

And I just rediscovered this from Dr Joe Boray:

Mehlisia – REDUX
‘Remember the fluke/trematode found in the quoll? See WormMail.201103251500 – Tapes and Trematodes http://wormmailinthecloud.posterous.com/wormmail-tapes-and-trematodes Fluke guru Dr Joe Boray comments:

Dear Steve,
Yes, I was delighted to see the lovely Mehlisia. Obviously the researchers found it either in the duodenum or in the small intestine , (not mentioned). They probably were looking for adult hydatid worms. In the Armidale area there are plenty of Lymnaea tomentosa and some bulinid snails possibly serving as intermediate hosts . I found several species of Echinostomes in those snails, which are trematodes of the duodenum of ducks . With patience and time, somebody could find the intermediate host of Mehlisia . I don’t believe that anybody would provide a grant, but it would be a delightful hobby . A fenced in area for a few Quolls will be necessary. I would be happy to help in the protocols of the work .
Hoping to find a few applicants,
With kindest regards,
Joe    (2011)

(Joe turns 90 next Monday, 31 October, 2106 – Ed.)

(The Posterous platform – where WormMail once was – is no more. It was bought by Twitter then killed off).

SL, Armidale 2016-10-25

 

 

 

 

 

WRML: efficacy and plasma profiles in cattle of abamectin plus levamisole combination as oral or pour‐on

David Leathwick and colleagues recently published the results of this research.

A related paper is this one: Efficacy of oral, injectable and pour-on formulations of moxidectin against gastrointestinal nematodes in cattle in New Zealand D.M. Leathwick ,C.M.Miller  http://www.sciencedirect.com/science/article/pii/S0304401716302904

From comments I have heard, you might say the latest peer-reviewed paper at least is contentious, with some saying the conclusions have reasonable supporting evidence and others saying the opposite.

Comments are not usually enabled on this blog for various reasons. Seeing this paper has evoked disparate responses on this important issue, I thought I would enable comments for this post, so that different points of view can be aired in a constructive and helpful way. Comments will be open for 20 days.

HOWEVER…. I have gone with the default settings for comments, which are designed to prevent spamming etc (e.g. no more than one hyperlink in a comment is allowed), and also require moderation.

Also you will be required to give your name, email address and log into WordPress. (If you are serious, these won’t be onerous conditions). On the right hand side of the post, you will see a heading, ‘META’, and below that ‘register’ and ‘log in’. (I have just removed the ‘register’ and ‘log in’ requirements, but will reinstate if need be. Sl, 2016-10-21T1030).

I won’t allow comments apart from those that are logical, dispassionate, and where possible, provide supporting evidence. Any ad hominem arguments, impugning of motives, slander, rants and the like will go straight to the bin.

Below is the abstract and the highlights. I am not free (copyright) to send you the paper. Please access and read the paper yourself, especially if you wish to comment. It would be difficult to make worthwhile comments/judgements without looking at the detail, e.g., the design. data, indications of statistical significance etc.

http://www.sciencedirect.com/science/article/pii/S0304401716302904

Research paper

 The efficacy and plasma profiles of abamectin plus levamisole combination anthelmintics administered as oral and pour‐on formulations to cattle

Highlights

Oral and pour-on combination anthelmintics were compared.

Combination pour-ons showed variable efficacy in the absence of resistance.

Abamectin levels in plasma were lower for combination cf single-active pour-ons.

Abamectin levels in plasma were higher for combination cf single-active orals.

Formulation issues probably affect the performance of combination pour-ons.

Abstract

“In phase I, faecal egg count reduction tests (FECRT) were conducted on six commercial cattle farms to compare the performance of two pour‐on and one oral combination anthelmintic. Groups of 12–15 calves were sampled for faecal nematode egg count (FEC) before treatment with either abamectin oral, levamisole oral, an abamectin + levamisole oral combination or one of two abamectin + levamisole combination pour‐ons. Samples were collected again 14 days after treatment to calculate the percentage reduction in FEC. The proportions of infective stage larvae (L3) in faecal cultures were used to apportion egg counts to, and calculate efficacy against, the main parasite genera.

Abamectin oral was effective against Ostertagia except on one farm where resistance was indicated, but had reduced efficacy against Cooperia on four farms. Levamisole oral was effective against Cooperia on all farms, but had variable efficacy against Ostertagia. The abamectin + levamisole oral was effective against both species on all farms. The abamectin + levamisole pour‐ons were effective on some farms but not on others. In particular, pour‐on 2 failed to achieve 95% efficacy in 45% of evaluations, 4/6 against Cooperia and 1/5 against Ostertagia. On some farms the combination pour‐ons were less effective than their constituent actives administered alone as orals.

In phase II, 8 groups of 6 calves, grazing parasite-free pasture, were infected with putatively ML‐resistant isolates of Cooperia oncophora and Ostertagia ostertagi. Once infections were patent groups were treated with oral or pour‐on formulations of abamectin alone, levamisole alone, abamectin + levamisole (two pour‐ons) or remained untreated. Blood samples were collected for analysis and after 8 days all calves were euthanized and abomasa and intestines recovered for worm counts.

All treatments were effective against O. ostertagi and all treatments containing levamisole were effective against C. oncophora. Animals treated with the oral combination had higher Cmax and AUC values for abamectin in plasma than animals treated orally with abamectin alone. In contrast, animals treated with the combination pour-ons tended to have lower plasma levels for abamectin than those treated with abamectin alone as a pour-on, with differences in the Cmax and AUC values approaching statistical significance (p-values ≤0.07). There were no differences detected in plasma concentrations of levamisole.

The inconsistent and sometimes poor efficacy of the combination pour‐ons on-farm is likely due to reduced levels of abamectin in the plasma and hence less active reaching the target worms in the gut.”

 

SL, Armidale.    2016-10-21

 

 

WRML.2016-10-13.[1] drench rotation-any good? [2]wormboss for goats

WormBoss for Goats – 1st November 2016

Those of you who subscribe to ParaBoss News will know  -from yesterday’s update from ParaBoss – that the launch date for Wormboss for Goats is 1st November.

http://www.wormboss.com.au/news/articles/general/wormboss-is-now-australias-goat-worm-control-resource.php

And also, that Lewis Kahn has written an interesting article on drench rotation and resistance.

http://www.wormboss.com.au/news/articles/drench-resistance/drench-rotation-does-little-to-combat-drench-resistance.php

Here is the teaser…(included in the email sent to ParaBoss News subscribers):

“Drench rotation does little to combat drench resistance 

by Lewis Kahn, ParaBoss Executive Officer

Rotation between different drench groups does not slow development of drench resistance and should not be used at the expense of the other highly effective practices. >> Read more.   “

Interestingly, back in 1999, Fairweather and Boray, when discussing management of resistance to flukicides, emphasised use of combination flukicides (combinations of (generally) unrelated flukicide actives) as a means of managing resistance. This has been picked up by others, including Kelley and others (2016).

Excerpt from Fairweather and Boray (1999):

“A number of strategies have been proposed that may help to avoid or at least slow down the development and spread of anthelmintic resistance.
They include limiting the number of anthelmintic treatments; strategic dosing at particular times of the year, based on epidemiological data; correct dosage; and the annual rotation of anthelmintics, using drugs from different chemical groups. The latter strategy is designed to prevent the build-up of resistance to a particular class of anthelmintic and to minimize the passage of resistance genes early in the selection process. However, a more effective approach is to use combinations of drugs. It is particularly useful when development of resistance reduces the efficacy of an individual drug, but it retains its efficacy in synergistic combinations.”

(I say ‘generally unrelated’ above, as not all of the combinations which Boray et al found to be synergistic were entirely unrelated: eg triclabendazole and oxfendazole).

It would be best to read Lewis Kahn’s article at ParaBoss, because it puts you right in the thick of lots of other good information, but -what the heck – I will paste the article below as well. (First get a cup of  coffee, or other preferred stimulant…. not that the article isn’t interesting!)

Drench rotation does little to combat drench resistance

by Lewis Kahn, ParaBoss Executive Officer

October 2016

Rotation between different drench groups does not slow development of drench resistance and should not be used at the expense of these three highly effective practices:

  • use products most effective on your property
  • use multi-active (combination) products
  • use short-acting products

However, there are times when using a drench group that is different from the previous treatment is important and this is discussed later in this article.

Drench rotation is the practice where consecutive drenches are used from different drench groups.  A simple example of a drench rotation is for the first drench to be from the BZ group and the next time a drench is given, a product from the levamisole group is used.

It’s tempting to think that rotation, once considered to be drench best practice, would slow the development of drench resistance on the basis that using a different drench group would kill any worms that were resistant and survived the previous treatment.  While this is true, and this effect can still provide value under certain circumstances (discussed later), advances in the understanding of drench resistance indicate that the practice of rotation itself will not delay the development of drench resistance.

To provide context to the scenarios below, a treatment with resistance at 10–20% (in other words, the drench is 80–90% effective) will result in a large loss of production from worm infection.

Development of drench resistance

At the ParaBoss Technical Forum held in March 2016, Dr Yan Laurenson of the University of New England presented the output of a model that predicts development of drench resistance.

This model broadly confirms the results of other models developed in Australia, New Zealand and elsewhere over the last 20 years.

Two scenarios from the presentation are relevant to this article and are provided in the figures below.

The first scenario is sequential drench use (no drench rotation), where drench A was the only drench group used for 15 years before being replaced by drench B as the only group for the next 15 years.

In the second scenario (annual drench rotation), drench A was used in an annual rotation with drench B for 30 years.  For example drench group A in year one, group B in year two, group A in year three and so on.

Although producers have more drench groups than this at their disposal, the concepts shown here will still apply.

Complete resistance is predicted to have developed to both drench groups A and B after 30 years regardless of whether a rotation was practiced or not; but let’s look more closely at these scenarios.

When the drenches are used alone (sequential), resistance to drench A increased after 10 years to about 80% (shown as the blue circle on the Figure 1), but when rotated with drench group B, resistance had only increased to about 30% (grey circle on Figure 2).

Figure 1: ‘Sequential’—Development of drench resistance when drenches are used sequentially.
Figure 2: ‘Annual Rotation’—Development of drench resistance when drenches are used in rotation.
The main reason for this apparent benefit at this stage is that only half the number of doses of drench group A were given when used in a rotation and so there was less opportunity for sheep worms to develop resistance.

At the 10 year-mark of the simulation a drench rotation looks highly effective at slowing the development of resistance, but remember, in the sequential use situation, while resistance to drench A is 80%, drench B is still 100% effective because it has not been used.

Now let’s look at the predicted situation after 20 years. By then, drench group B had only been used alone (sequential) for 5 years and resistance had developed to about 30%, see the red circle on Figure 1, (andresistance to Drench A is 100%). When used in rotation, resistance to both drench groups had increased to about 80% (black circle on Figure 2).  A complete reversal of the situation that was predicted at the 10-year mark.

On average, across the entire 30-year period, there was no predicted advantage from a drench rotation.

Use drench groups in combination

In contrast, using drench groups in combination has a much greater effect in slowing the development of drench resistance.

Using two drench groups in combination at each treatment reduced resistance after 10 years to 20% and when using three drench groups in combination, resistance had only developed to the level of 5% over the same period (see orange oval in Figure 3). Once again, a closer look at this figure is informative.

In a situation where you had three drench groups at your disposal and you decided to use only one until resistance to that drench group developed to 20% (purple circle on figure 3) (when major production loss would be occurring due to the drench being only 80% effective), then each of the three drench groups could be used for about 4 years each, giving 12 years before major production loss was likely to occur from poorly controlled worm infection.

In contrast, if you used all three drench groups in combination (green line on Figure 3), it is predicted that major production loss from drench resistant worm infections would not occur until after 30 years (green circle, Figure 3):  this is an 18 year advantage over the singular use of drench groups.

 

Figure 3: ‘Combinations’—Development of drench resistance when one, two or three drench groups in a treatment.

What is important from these model predictions is the superiority of multi-active combinations for delaying drench resistance. Regardless of whether the development of drench resistance occurs more slowly or rapidly on your property to that presented here, the relative benefit from using combination treatments will remain the same.

WormBoss recommendations

This is why WormBoss highlights the importance of using drenches in combination or using more than one product concurrently (up the race with one and then the other/s) to combine different drench groups.

But remember, these models started with fully effective drenches. Use combinations before each of the single actives in them become ineffective on your property.

The higher the efficacy (effectiveness) of each drench group used in a combination and the more drench groups included in the combination, the greater the benefit for slowing drench resistance.

This is why it is important to test the efficacy of each drench group (that is, you should test the single active products, even if you know they are no longer fully effective) to know how protective each drench group is in a combination product. For example, if you use a triple combination, where two of the drench groups in it are already very ineffective (say 30-40% effective or less) it will be more like using a single active product and drench resistance won’t be slowed a great deal, even though the combination product might still be effective at killing worms.

Just because a product is a combination drench, doesn’t mean it is effective on your property. You need to do a DrenchTest to find out.

When does a drench rotation provide value?

There are specific situations when using a different drench group/s from the previous treatment can have a major benefit.

The first of these situations is the choice of an exit or tail-cutter drench used at the end of the protection period of a mid- or long-acting drench. Under this situation WormBoss recommends that you use an exit drench and that it is from a different drench group/s to the persistent treatment.

Persistent treatments provide a long period when only resistant worms (if present) can establish and reproduce in the sheep, with only their eggs contaminating the pasture and developing into resistant infective larvae.  Removal of these resistant worms from the sheep will require the use of a product containing different drench groups to those in the persistent treatment, and importantly, that product itself must be highly effective.

The second situation is when using a different drench group/s from the previous treatment can have a major benefit  for managing animals that have been drenched into a low worm-risk paddock (such as a prepared lambing or weaning paddock).  Under this situation, there are few worms in refugia meaning there will be few worms on the pasture to dilute those that develop from the eggs laid by any resistant survivors of the treatment of the sheep going into the paddock.  While, this is a good outcome for worm control, it does create the situation where drench resistance may develop more rapidly.

WormBoss recommends two actions to deal with the resistant worms now in the sheep and on the paddock. Firstly, drench the sheep as they leave that paddock with a product containing different drench group/s to that used on these sheep when they were drenched into this low worm-risk paddock. For example, drench groups AB into the paddock and groups CD out of the paddock.

Secondly, the paddock potentially has a high proportion of resistant worms and should now be spelled or grazed with cattle for as long as practical prior to being grazed with sheep that have a moderate worm egg count.  The spelling or cattle grazing will allow for some of the infective larvae to die, making it easier for the worms that develop from the next grazing of sheep to dilute the resistant population and reduce the level of resistant worm larvae on the paddock.

The third situation is when rotational grazing management is practiced. A small benefit for slowing the development of drench resistance can be gained by rotating drench groups providing you also rotationally graze stock across the property. This creates situations where the drench resistance status of worms in the sheep differs from those on the pasture.

Despite being a useful practice, it is important to keep in perspective that drench rotation practiced with rotational grazing management might slow development of resistance by 15–20%.  In practical terms, this will add 2–3 years to the expected period of useful efficacy for a drench group.  In contrast, using a combination product with three efficacious drench groups will add an extra 18 years over the singular use of drench groups.

Conclusion

Rotation between different drench groups does not play a significant role in slowing the development of drench resistance. The three principles for choosing drenches to slow the development of drench resistance are:

  • Use drenches most effective on your property. Drenches that reduce worm egg count by at least 98% are preferred.
  • Use an effective combination of two or more drench groups, either in a multi-active product or using more than one product concurrently (up the race with one and then the other) to combine different drench groups. The higher the efficacy of each drench group and the more drench groups included in the combination, the greater the benefit for slowing drench resistance.
  • Use short-acting treatments and restrict the use of persistent products for specific purposes and high worm-risk times of year.

 

SL, Armidale 2016-10-13

 

paraboss-news-oct-2016

 

 

WRML.2016-10-05. tapeworms revisited incl. reduced efficacy of praziquantel. Mason. NZ.Overview-NSW DPI Agric

In this issue:

Tapeworms revisited – Paul Mason et al

Overview – NSW DPI Agriculture

Tapeworms revisited – Paul Mason et al

With permission, here is a paper from 2002 by New Zealand parasitologist, Dr Paul Mason and colleagues.

mason-p-et-al-2002-tapeworms-in-sheep-revisited-proc-32nd-sem-socy-sheep-beef-cattle-vets-nzva-wellington-may-2002

Some of the authors’ findings/conclusions:

“These two productivity trials involving over 400 lambs failed to show any response to tapeworm treatment. Neither albendazole nor praziquantel produced a production benefit over the control group. So rather than demonstrating that albendazole is as effective as praziquantel in reducing production losses from tapeworm, we have shown that there was no production loss associated with tapeworm infection on the two trial properties”.

“What does all this mean? The trials of Elliot (1984), the six trials of Mason (pers comm), and these two productivity trials have shown no productivity response to the removal of tapeworms. Now why do these results differ from those of Southworth et al. (1996)? Is it pure chance, or does tapeworm only become a problem when you get up into the north of New Zealand? “

“Albendazole was as effective as praziquantel against Moniezia in this study.” (Southworth et al, 1996, found praziquantel was 99-100% effective compared to albendazole (3.8mg/kg) which was 19-75% effective – Ed).“This is the first report of lack of efficacy (resistance) of Moniezia to praziquantel. We have no idea how widespread this situation is…”

Mason, P; Moffat, J; Cole D. 2002. Tapeworm in sheep revisited. Proceedings of the 32nd Seminar of The Society of Sheep & Beef Cattle Veterinarians NZVA, Wellington, 22-24 May 2002. Pp. 147-51.

I have yet to find other reports of resistance to, or reduced efficacy of praziquantel, with respect to Moniezia spp. tapeworms.

Overview – NSW DPI Agriculture

1-nsw-dpi-agricult-key-stats-2016-10-05

More info ( 3 PPT slides):

1-template-dpi-presentation-frm-dougal-gordon-2016-10-05-pdf-slides-2-4

 

SL, Armidale NSW, 2016-10-05