WRML.2015-09-24.Reports of resistance are not drench buying guides!

The last two WormMails were reports of drench resistance or reduced drench efficacy, relating to ‘Zolvix’ (monepantel) and/or ‘Startect’ (abamectin+derquantel)  The first was a statement from Elanco letting the industry know of confirmed resistance of Haemonchus to Zolvix (monepantel) on two commercial sheep farms in the New England region of NSW. I thought the Elanco statement was timely, balanced and put the matter into perspective. I am sure other companies would have done likewise.

Also in the other WormMail, which reported multi-drug including monepantel resistance of Haemonchus on a sheep farm in the Greater Sydney region – and reduced efficacy of Startect – the authors were likewise at pains to put the matter into perspective.  Following is the last section of that article:

“Resistance to the older broad-spectrum actives (benzimidazoles, levamisole, macrocyclic lactones) is now quite common on Australian sheep farms. However, confirmed cases of reduced efficacy are still rare for the newer drenches (Startect, Zolvix).

As each farm has a different resistance profile, sheep producers should test to determine which drenches are effective and utilize all available options in line with best practice. See WormBoss (wormboss.com.au).”

Reports of resistance? – what do they mean?

Confirmed field cases of drench resistance are usually reported to inform others of something unusual. Often these reports are about early cases of resistance to a new drench active. The take home message generally is that producers should be aware and that they should monitor the efficacy of the product on their farm. It certainly does not constitute ‘buying advice’ along the lines of, “Resistance to Drench X has been reported, so it is no longer an option!” Or, “In this case report, drench A was better than drench B, so A is what I should use!”

Other reports are about resistance surveys.   Many of these surveys do not test enough farms to reliably say that the prevalence of  resistance of worm A to drench X in region Z is W% of farms. The New England (NSW) Closantel Resistance Survey conducted 15 years or so ago (senior investigator: Dr Joan Lloyd) is one of the few surveys ( that comes to mind) that tested sufficient farms to give a good estimate of the prevalence of resistance in the region. (As an aside: the results of that survey were in the same ballpark of lab data from the former Armidale Regional Veterinary Laboratory (Dept. of Agriculture, NSW). Also the late Dr Peter Greentree, a former Tenterfield District Vet, reliably predicted the prevalence in his district). So, lab data and observations of experienced people in the field may be biased, but sometimes it’s not too bad.

Another recent survey in NSW that had a good number of farms in the study, was that done by District Vet Dr Eliz. Braddon and colleagues in the former Lachlan Livestock Health and Pest Authority (Young, Forbes etc., New South Wales). Also see here.   But smaller surveys  (e.g.  Walker E et al; Central West NSW, 2011 – see here) also yield valuable information,

Most surveys however give an idea of the likely prevalence, if not robust estimates, which is usually good enough. A recent one is the study published by Playford and others in the Australian Veterinary Journal in 2014.

Here is Table 1 from that paper:

To get the context and full information, read the paper.

The results in the table should of course be interpreted with due care. For example, note that for some drench products, there are only a small number of tests.

Also, the results summarised in table 1 are Australia wide. In the New England region of New South Wales (NSW), Haemonchus resistant to abamectin, moxidectin and closantel occur on roughly 80+% of farms (generally more than the figures in table 1). Likewise, the table shows that in 30% of tests, Haemonchus was resistant to levamisole. In the New England, however, data from Veterinary Health Research, Armidale suggests around 60% of farms now have Haemonchus resistant to levamisole. Other tables in the paper by Playford and others (2014) show the different results for each state.

In short, the situation varies from region to region and from farm to farm, even neighbouring farms.

Also, we know from recent tests that Zolvix and Startect are no longer operating at or near high efficacy (say, >98%) 100% of the time. Reduced efficacy is still rare, but it’s there.

So, when you look at results such as that displayed in Table 1, what you get is a rough idea of how likely a particular drench active or combinations of actives will be effective.  But on your farm, sooner or later you have to test. Either that, of ‘fly in the dark’. The resistance profile of your property may be quite different from what is more or less likely on a more or less average Australian sheep farm.

And, given that resistance evolves, you have to keep on monitoring the drenches you use.

And, it’s not just about drenches. See ‘Your Program’ at wormboss.com.au .

Reference

Playford MC, Smith AN, Love S, Besier RB, Kluver P and Bailey JN, 2014. Prevalence and severity of anthelmintic resistance in ovine gastrointestinal nematodes in Australia (2009-2012). Aust Vet J 2014; 92: 64-71.

Regards,

SL      2015-09-24

Multi-drug including monepantel (Zolvix®) resistant Haemonchus confirmed in sheep on a farm in Greater Sydney region

 

Multi-drug including monepantel (Zolvix®) resistant Haemonchus confirmed in sheep on a farm in Greater Sydney region

Narelle Sales and Stephen Love, Research Officers, NSW Department of Primary Industries. 16^th September 2015

Summary

In summer 2014/2015 there were signs of haemonchosis in a sheep flock in the Greater Sydney Local Land Services region, soon after treatment with Zolvix^® (monepantel). In August 2015, pre- and post-treatment faecal worm egg counts revealed little reduction in egg counts after drenching with monepantel at the recommended sheep dose rate of 2.5mg/kg. Various anthelmintic drenches were tested with less than 95% reduction in Haemonchus egg counts found for monepantel, abamectin, moxidectin, and a derquantel/abamectin combination. An efficacy greater than 95% was achieved by a four-way combination containing abamectin, albendazole, levamisole and closantel. All tested drenches were highly effective (>98%) against Trichostrongylus sp.

Background

Mild to warm temperatures, high humidity and frequent light showers produced a very challenging worm season throughout summer 2014 and autumn 2015 in the Greater Sydney region. Decreased efficacy of monepantel was indicated when routine inspections found signs of  haemonchosis  after drenching a mob of weaners and moving to pasture adjudged to be ‘low worm-risk’.

The climate in the area is generally quite favourable for sheep worms, including free-living stages, which suggests lack of worms in refugia may not have been a significant factor. Both median and mean annual rainfall is approximately 770 mm, suggesting rainfall is not highly variable, and mean monthly rainfall ranges from a low of 40mm (July) to 100mm (February).  Only July to September averages below 50mm of rainfall per month. The average daily temperature ((max+min)/2) ranges from approximately 23°C in summer to 12°C in mid-winter (July), and is generally only substantially below 15°C in June to August. It’s likely that in average years Haemonchus completes its lifecycle in all months except for four months over winter.

Sheep and cattle, but not goats, are grazed on the property.

Prior to the initial suspicion of decreased efficacy, monepantel had only been used once a year at shearing (2011-2014) across the entire flock of approximately 1500. Monepantel was also reserved for use as a quarantine drench, however new stock were not brought onto the property during these 4 years. At drenching, sheep were weighed and dosed according to the product label and drench guns were calibrated before use.

Methodology

Faecal egg count reduction tests (FECRTs) were undertaken using the following drenches:  abamectin (WSD Abamectin®), moxidectin (Virbac, Cydectin ®), derquantel + abamectin (Zoetis, Startect®), monepantel (Novartis now Elanco, Zolvix®) and a combination drench containing abamectin, albendazole, closantel and levamisole hydrochloride (Jurox, Q-drench®).

Fifteen yearling wethers were used in each treatment group, sourced from a single mob, as younger sheep were not available. Each sheep was sampled, weighed and drenched with the dose recommended for 35-40Kg dose. The monepantel recommended dose rate for sheep is 2.5mg/kg.

Faeces were homogenised prior to subsampling for faecal worm egg counts (FECs) using the McMaster technique. Double chambers were counted (detection level of 20 eggs per gram faeces (epg)) to determine the FECs at day 0 (the day treatments were given) and 10 days post-treatment.

Larval differentiation of a pooled pre-drench culture estimated 63% Haemonchus and 37% Trichostrongylus. Larvae cultured from faeces from each treatment group at Day 10 post-treatment were 100% Haemonchus.  The Day 0 and Day 10 FECs and larval differentiations were added to the RESO Excel-based calculator (A Cameron, modified by R Dobson, 2013). RESO calculated the percentage reduction in FECs, and the 95% confidence limits, and generated the resistance statuses seen in Table 1.

Table 1. The mean pre- and post-drench egg counts, the percentage reduction in egg counts post-treatment and the resistance status for 5 drenches used in FECRTs as calculated by RESO.

Drench	Arith- metic Mean Day 0 Pre-Drench (epg)	Arith- metic Mean Day 10  Post-Drench (epg)	Egg count reduction (All ‘strongyle’)	Egg count reduction (Haemo-nchus)	Status (Haemo-nchus)	Egg count reduction (Trichost-rongylus)	Status (Trichost-rongylus)
Abamectin	1760	2147	-22%*	-94%*	Resistant	100%	Susceptible
Moxidectin	971	675	30%	-11%*	Resistant	100%	Susceptible
Derquantel + Abamectin	1310	87	93%	90%	‘Resistant’**	100%	Susceptible
Monepantel	2156	1497	31%	-10%*	Resistant	100%	Susceptible
4-way Combination	1267	20	98%	97%	Susceptible	100%	Susceptible

* Represents an increase in FEC between Day 0 and Day 10.       ** See Conclusion for comment.

Note: 4-way combination=abamectin + albendazole + levamisole + closantel.

To maintain scientific rigour, a second FECRT was performed as the monepantel drench used in the first FECRT was from a drum that had been opened for approximately 13 months. The label states the product should be used within 12 months of opening. The second FECRT commenced 7 days after the first was completed.

Although the product used initially was almost certainly still within the manufacturer’s specifications, a new container was purchased to conduct the second FECRT.  The sheep used on this occasion were those that had been treated with either abamectin or moxidectin 17 days earlier during the first FECRT. These 30 sheep were weighed (23-41 kg), sampled and drenched with monepantel at the label-specified dose for 41-50Kg sheep. Eleven sheep, treated with monepantel in the first FECRT, were kept as untreated controls.

Larval differentiation on cultures pre- and post-monepantel drench in the second FECRT showed 100% of larvae were Haemonchus. Ten days after the two groups of 15 sheep were drenched with monepantel, the FEC was reduced by 51% in the sheep previously treated with moxidectin, which has a label claim of 14 days persistent activity against susceptible Haemonchus. There was a 29% reduction in egg counts in the sheep previously treated with abamectin, which does not have a claim of persistent activity. At day 10 of the second FECRT the untreated controls, treated 27 days before with monepantel, had a 103% increase in epg. Overall, there was a 36% reduction in Haemonchus epg in the 30 sheep drenched with monepantel in the second FECRT, 17 days after being drenched with abamectin or moxidectin in the first FECRT. In comparison, there was a 10% increase in the Haemonchus epg measured in the first FECRT after a single drench with monepantel. The results from both FECRTs confirm Haemonchus resistance to monepantel.

Conclusion

This is an early case of confirmed monepantel resistant sheep worms on a farm in Australia. In this case there was marked resistance of Haemonchus to this drench. Other anthelmintics – moxidectin, abamectin and also the derquantel+abamectin combination – displayed reduced (<95%) efficacy against Haemonchus. The four-way combination, with a FEC reduction of 97%, was effective (>95%) but not highly effective (>98%).

The reduced efficacy of the derquantel/abamectin combination against Haemonchus is likely due to the zero efficacy of abamectin against Haemonchus in this case, and the fact that derquantel on its own is not innately highly effective against 4^th stage Haemonchus larvae.   This is distinct from resistance resulting from a rare genetic mutation allowing worms to survive anthelmintic treatment and increasing in frequency because of continued selection pressure.

At the time of writing (September 2015), and as far as we are aware, previous published reports of confirmed field cases of monepantel resistance in sheep or goats in Australia are:

• July 2014. This was the first confirmed case in Australia, and possibly the second in the world, the first being in goats in NZ (Scott et al, 2013). In this Australian case, which involved goats in NSW, Haemonchus contortus (barber’s pole worm) was susceptible, monepantel being highly effective (>98%). Trichostrongylus colubriformis (black scour worm) displayed emerging resistance and Teladorsagia circumcincta and trifurcata (small brown stomach worm) showed severe resistance to monepantel. (Love S, 2014)

• This is the first case reported in sheep on farm in Australia. Goats were also involved. The location was the James Cook University farm at Townsville, Queensland. In both sheep and goats, reduced efficacy (i.e. resistance) was reported for both Haemonchus contortus and  Trichostrongylus. (Constantinoiu C and De Cat S, 2015).

Resistance to the older broad-spectrum actives (benzimidazoles, levamisole, macrocyclic lactones) is now quite common on Australian sheep farms. However, confirmed cases of reduced efficacy are still rare for the newer drenches (Startect, Zolvix).

As each farm has a different resistance profile, sheep producers should test to determine which drenches are effective and utilize all available options in line with best practice. See WormBoss (wormboss.com.au).

 References

Cameron A, ‘Anthelmintic Resistance’:  Report of the Working Party for the Animal Health Committee of the SCA.  CSIRO, 1989.

Constantinoiu C and De Cat S, 2015. Lack of efficacy of monepantel against Haemonchus contortus and Trichostrongylus spp in small ruminants. Proceedings of the 4th AVA/NZVA Pan Pacific Conference, Brisbane, 24-29 May, 2015.

Dobson RJ, Hosking BC, Jacobson CL, Cotter JL, Besier RB, Stein PA, Reid SA 2012. Preserving new anthelmintics: A simple method for estimating faecal egg count reduction test (FECRT) confidence limits when efficacy and/or nematode aggregation is high. Vet. Parasitol. 186:79-93.

Love S, 2014. Monepantel (Zolvix®) resistance confirmed in goats in NSW Australia. WormMail Newsletter, 6 June 2014. https://wormmailinthecloud.wordpress.com/2014/06/11/wrml-monepantel-zolvix-resistance-confirmed-in-goats-in-nsw-australia/ Accessed September 2015.

Scott I, Pomroy WE, Kenyon PR, Smith G, Adlington B, Moss A. Lack of efficacy of monepantel against Teladorsagia circumcincta and Trichostrongylus colubriformis, Vet Parasitol 2013;198(1-2)166-171.

Acknowledgements

The authors thank Greg Glasgow, Dorothy Sargent and Kim Koeford for their assistance.