WRML.2014-11-24.Triclabendazole resistant liver fluke in New England NSW etc

WRML.2014-11-24. Triclabendazole resistant liver fluke in New England NSW etc

To WormMail (WRML) mailing list (~400 subscribers; recipients undisclosed)

In this issue:

Triclabendazole (TCBZ) resistant liver fluke in sheep – NSW New England (case report)

· TCBZ-resistant Fasciola in Australian cattle – and coproantigen ELISA –Brockwell et al 2014

· Update: monepantel resistant sheep worms – Australia

· Sheep WormTest results around the state (NSW)

· Don’t forget DrenchChecks on New and Old

· LiceBoss on-line learning now on-line!

· Cases of type 2 ostertagiosis in cattle on NSW North Coast

· Water for livestock

· What’s in name..? (Ostertagia etc)

· Canine Cognitive Dysfunction (CCD) and Alzheimer’s

· Your brain on beer vs coffee

· Add sugar to margarine to entice kids

Triclabendazole resistance liver fluke in sheep – New England region, New South Wales (NSW) Australia

Here, with permission, is information (slightly edited) from Dr Matt Ball, Technical Services Manager (Livestock), Virbac.

“A basic field trial using 60 sheep was conducted recently on a New England, NSW property to investigate poor responses to triclabendazole for fluke control.

Following are results from VHR (Veterinary Health Research) diagnostic testing. The graph was made for general communication so forgive the lack of detail.

The figure shows percent efficacies from a faecal egg count reduction test (fluke eggs counted using a sedimentation technique), which included an untreated control group, a Fasinex®(Novartis)-treated group (7% faecal egg count reduction (FECR)), a Flukazole® (Virbac) group (39% FECR) and a Closicare® (Virbac; closantel) group (100% FECR)”.

“The higher kill rate of Flukazole® (triclabendazole + oxfendazole) in the face of resistance is an interesting finding and somewhat consistent with Dr Joe Boray’s synergy work many years ago. Virbac will continue to recommend Flukazole® as the preferred product in sheep to help delay onset of resistance. Cattle of course have a Nitromec® (nitroxynil + clorsulon + ivermectin) option”.

“Virbac is working with Charles Sturt University and faecal antigen testing to learn more about this type of situation”.

Notes (SL):

Label claims regarding liver fluke:

Closicare (closantel): adult and immature liver fluke including 6 week old stages.

Fasinex (triclabendazole): For the treatment of triclabendazole-susceptible early immature, immature and mature liver fluke

Flukazole (triclabendazole + oxfendazole): For the control of … early immature, immature and, mature liver fluke in sheep.

Source: PubCRIS at www.apvma.gov.au

Also see Table 1 in Dr Boray’s PrimeFact on liver fluke:

http://www.dpi.nsw.gov.au/__data/assets/pdf_file/0004/114691/liver-fluke-disease-in-sheep-and-cattle.pdf

This table lists efficacies of various flukicides.

TCBZ-resistant Fasciola in Australian cattle (and the coproantigen ELISA) –Brockwell et al 2014

Virbac and others have been collaborating with Charles Sturt University, Wagga Wagga on investigations into liver fluke, including the use of a commercial coproantigen test kit (BIOX) which is available for use in ruminants.

Brockwell and others (2014) reported some of this work.

Here are some notes (interpretive summary) from that paper:

The cost of liver fluke and the numbers of cattle (>6 million) at risk in Australia is discussed.

Triclabendazole (TCBZ) is the preferred drug for Fasciola hepatica control (efficacy against immature and adult stages). (Although it seems to me another option in cattle – Nitromec® (Virbac; nitroxynil + clorsulon + ivermectin) has similar efficacy).

However there are reports of TCBZ-resistant F. hepatica from different regions around the world. TCBZ resistance was first reported (in the world) from sheep in Victoria, Australia (Overend and Bowen); ‘now occurs in several parts of Europe, with TCBZ resistance being reported in several countries in both cattle and sheep, and a human case reported in the Netherlands.

The authors investigated TCBZ resistance in F. hepatica in naturally infected Australian beef and dairy cattle herds and assessed methods of measuring the levels of resistance.

The methods: Faecal egg count test (FECRT), although this has not been validated for fluke (Coles et al, 2006), and coproantigen reduction test (CRT). Faeces (for both tests) collected pre-treatment and generally 21 days post-treatment. (My recollection is that Boray prefers 28 days for FECRT for liver fluke. Wood et al (WAAVP, 1995-guidelines for clinical trials with Fasciola), suggest 21 days. Reasons for this suggestion of 21 days: time for removal of adult fluke post-treatment and for removal of eggs in gall bladder, and time for immature fluke surviving treatment to mature to antigen production). The authors discuss the pros and cons of doing post-treatment collections for FEC and the coproantigen ELISA test (CT) earlier, e.g. 7 days and 14 days post-treatment. Brockwell et al (2013) found both FEC and coproantigen levels fell to negative values within 7 days of successful TCBZ treatment of artificially infected cattle. Flanagan et al (2011) reportedly used a 14 day interval for FEC and CT in sheep and found antigen levels generally fell to zero by 14 days post-treatment. However Novobilsky et al (2012) state a 7 day interval may not be appropriate when testing albendazole.

Brockwell et al (2013) state the coproantigen test (ELISA) (CT) reflects fluke burdens in cattle, allowing for intensity of infection to be measured (various say the threshold for production losses in cattle is 30-40 flukes), and also detects fluke that survive treatment (also demonstrated in sheep by others). The authors also showed (as stated above) that coproantigen falls with 7 days after successful treatment – elsewhere (in the discussion) they say within 14 days of successful treatment – so the post-treatment collection of faeces could be done at 14 days, in line with the 10-14 days for nematodes, allowing an FECRT for nematocides as well as TCBZ to be done

simultaneously.

The CT reportedly shows ‘moderate to good’ correlations with parasite burdens in cattle (R2 ranging from 0.239 to .871) (Brockwell et al 2013) and 0.899 in lambs (Mezo et al, 2014). Roblez-Peres et al (2013) found PCR to be more sensitive than the BIOX CT in detecting drug resistant fluke (and others found PCR and CT to be more sensitive than FEC), however the CT in that case was used at the BIOX recommended cut-off rather than a custom cut-off. Other characteristics: samples can be stored frozen for use at a later stage using the CT and transport delays have less adverse effects (c.f. FEC). ELISA technology – which the CT uses – is almost universal in diagnostic labs whereas skills necessary for ID/differentiation and counting of trematode eggs is not. Flanagan et al (2011) have already shown the FEC and CT are suitable for use resistance investigations in sheep.

This coproantigen test is the same as used by others (Well, it does come as a kit (BIOX)). The specificity of the CT ELISA has been determined in studies of natural infections of gastrointestinal nematodes, Moniezia, Dicrocoelium, Echinococcus; as well as Paramphistomum cervi.

Brockwell et al (2013) and also Palmer et al (2013; see WormMail Sept 15, 2014) improved the test’s sensitivity by removing false negatives, achieving this by using a revised or custom (lower) cut-off point c.f. the kit’s recommended cut-off.

The farms: FECRT and CRT were done on six south-eastern Australian beef properties where TCBZ failures were suspected (three in north eastern NSW – Irvington, Caniaba, Parrots Nest; two in south eastern NSW – Gireke and Numbugga; and one in north eastern Victoria – Tallangatta Valley) and one dairy property (Maffra, Vic.). The CRT was conducted on an additional beef property (Nimmitabel, south eastern NSW).

Protocol: 15 animals were treated on each farm with an oral preparation of TCBZ at the recommended dose; 15 animals remained as untreated controls. Fluke eggs in faeces were counted and coproantigen levels were measured before treatment and 21 days after treatment and in the untreated control animals.

Data: ‘evaluated using three different methods to calculate % reductions (in the FECRT and CRT) compared with controls. Resistance was defined as <90% reduction, the standard used for Australian flukicide efficacy trials. (Others define resistance to flukicide as <95% reduction, as with nematodes). Of the 3 methods, the authors favoured the RESO technique (recommended by the World Assoc Advanc Vet Parasitol (Coles et al 1992), which compares post-treatment arithmetic means of treated and control groups because it generates less statistical error, relies on post-treatment results only and is, accordingly, cheaper. (It seems most authors, including Coles et al, do not state what the acronym ‘RESO’ (a method, software and Excel spreadsheet for analysing FECRT data) stands for. My hunt for (the) meaning continues).

Results: Resistance was detected on the dairy property using both FEC and CRT, and on 3/6 beef properties using FECRT and 4/7 beef properties using CRT.

Live adult flukes were recovered at slaughter following TCBZ treatment of 6 cattle from 3 of the beef properties, confirming the TCBZ resistance status of F. hepatica in these cattle. This showed the test positives were not

false positives. The correlation between FEC and fluke number was R2 = 0.1801 and for coproantigen R2 = 0.3542, but note small sample size. (See above (under methods) for other comments on correlations).

I tabulated the summary results (any errors are mine) to aid (my) comprehension:

Table – Summary of FECRT and CRT results – Efficacy of TCBZ (% reduction; using RESO method)

Farm/location Test result – efficacy (%)
North-eastern NSW CRT FECRT
Parrots Nest 100 93.4
Irvington 100 99.9
Caniaba 99.8 99.1
South-eastern NSW
Nimmitabel 89.9 (no test)
Numbugga 37.4 88.4
Gireke 64.6 19.9
Victoria
Tallangatta Valley 56.4 78.9
Maffra (dairy cattle) 63.7 18.7

There was discussion as to the origins of the resistant isolates (on-farm selection +/- importation/translocation from other farms) and it was noted resistance was not found in the NE NSW cattle farms. (Genetic studies are underway (Elliott et al, 2013) and may shed light on this).

Resistance may not be the only reason for treatment failures. Other reason include: maladministration of drug, reduced drug quality (from poor handling etc) and hepatopathies which may affect metabolising of drugs. The example of the Leon isolate is cited. It was reported to be resistant but subsequently FECRT, CRT and necropsy findings showed it was susceptible.

The authors state this is the first report of F. hepatica resistant to TCBZ in cattle in Australia (although I thought it was already known to occur on dairy farms in the Goulburn Valley of Victoria) and the results suggest that resistance is widespread in the south-eastern region. (Perhaps the Goulburn Valley cases are not regarded as ‘confirmed’ or were not published??)

The authors see the CRT as a robust alternative to the FECRT for evaluation of TCBZ resistance in F. hepatica in cattle.

Brockwell YM, Elliott TP, Anderson GR, Spithill TW, and Sangster NC. (2014). Confirmation of Fasciola hepatica resistant to triclabendazole in naturally infected Australian beef and dairy cattle. International Journal for Parasitology: Drugs and Drug Resistance.Volume 4, Issue 1, April 2014, Pages 48–54.

As always, read the paper and check the references for yourself. (…verify). (But I think my summary is almost as long as the paper…).

Update: monepantel (MPL) resistant sheep worms – Australia

​I have updated this WRML (October 28, 2014):

https://wormmailinthecloud.wordpress.com/2014/10/28/wrml-monepantel-resistance-confirmed-in-sheep-in-australia-two-genera-two-states/

It turns out the suspected MPL-resistant Teladorsagia (brown stomach worm) isolate is not from sheep, but is from a goat property. In fact, it is from the goat farm in NSW which was the source of the first reported confirmed* case of MPL resistance in Australia. (WRML June 11, 2014).

More information is being collected on the isolates mentioned in the 28 October 2014, so further updates (more detail, property histories are likely).

*Confirmed by faecal egg count reduction test and slaughter study.

Sheep WormTest results around the state (NSW)

I was just quickly perusing the summary of WormTest results for October from Veterinary Health Research. (By the way, all identifying data in these summaries is deleted).

The highest worm egg counts (WECs) were generally in the New England region of northern NSW, ‘though overall WECs are much lower than normal because of the near record dry conditions, especially in the north of NSW.

As Lewis Kahn has noted elsewhere, we (New England region) have now had three failed Springs in a row. Nearby regions are in a similar situation.

Despite this, there is still the occasional flock with relatively high WECs, e.g up to 3000 eggs per gram (with some individual sheep up to 2-3 times higher than the WormTest group average).

In most cases these higher WECs are mostly Haemonchus but I noted one which was mostly Trichostrongylus.

There was a WormTest average WEC in Tamworth district of just under 6000 epg (again, Haemonchus). Elsewhere in the state WECs were generally low, although there was one at Yass with an average WEC of ~ 2000 epg. But, a DPI colleague from Yass (Phil Graham) tells me they had an excellent season this year leading into winter with frosts coming much later than usual.

With relatively high WECs, especially under dry conditions, you can usually bet that the unwitting use of ineffective drenches is part of the problem.

Don’t forget DrenchChecks on New and Old

Assume nothing. Do regular DrenchChecks, including checks of newer drenches (Zolvix® (monepantel) and Startect® (derquantel+abamectin).

See here:

http://www.wormboss.com.au/tests-tools/tests/checking-for-drench-resistance.php

LiceBoss on-line learning now on-line!

http://www.liceboss.com.au/about-lice/liceboss-online-learning.php

Cases of type 2 ostertagiosis in cattle on NSW North Coast

From Dr Phil Kemsley, Local Land Services, Lismore writes:

“Hi Steve,

‘Seeing a lot of Type 2 Ostertagiasis at present.

‘Have been through a tough winter and spring and individual cow’s immune system down.

Cases confirmed by plasma pepsin, at autopsy and histopathology on abomasal wall’.

Kind regards,

Phillip Kemsley

District Veterinarian, Lismore.

Phil further said they get cases in most years (Spring), but there have more cases this year. . Some are 1st calf heifers; also individual older cows in a mob. The main differential diagnosis in that area is bovine Johnes disease.

About 80% of herds in the area have poor cattle; a reflection of prevailing dry conditions in northern NSW. Conditions are also very dry in Queensland.

See this map at BOM: http://www.bom.gov.au/climate/drought/archive/20141106.2.col.gif

Water for livestock

Ed Joshua (NSW DPI, Dubbo) writes (slightly edited):

‘I have been dealing with inquiries about water quality and quantity. SheepconnectNSW has been providing information to sheep producers on this. Sixty two % of the SheepConnectNSW newsletter recipients clicked on the provided links to PrimeFacts on water’.

‘Below are links to PrimeFacts on livestock water. More than usual, producers may find water a critical issue this summer. It is interesting to note that research into water storages at Yanco NSW by Dr Harnam Gill shows that 50% of stored water evaporates over summer. This may be important in some situations so regular monitoring of the resource and consideration of what the livestock have to drink is important and more so in hot and windy conditions’.

http://www.dpi.nsw.gov.au/agriculture/resources/water/animals

An audit of stock water using is a useful start to knowing the situation.

http://www.dpi.nsw.gov.au/agriculture/resources/water/animals/publications/stockwater-limited-resource

What’s in a name…?

· Ostertagia –after German veterinarian, Robert von Ostertag

· Salmonella – after USDA veterinarian, Daniel E Salmon (not Daniel Salmon, LLS veterinarian at Deniliquin, NSW).

· Brucella – after Bendigo-born Scottish pathologist and microbiologist Major-General Sir David Bruce who investigated Malta fever (B melitensis) in British soldiers.

· Johnes disease – after Heinrich A. Johne, a German bacteriologist and veterinarian.

Canine Cognitive Dysfunction (CCD) and Alzheimer’s

From a recent AVA newsletter:

‘The DOGS+CELLS Trial aims to discover whether brain engraftment of ‘patient specific’ stem cells derived from a dog’s own skin can help treat the dementia-like syndrome, Canine Cognitive Dysfunction (CCD)’.

‘If successful this world-first study will pave the way for similar clinical trials in humans with dementia’.

‘What is canine cognitive dysfunction (CCD)?

CCD is a dementia-like syndrome that occurs in approximately 12-14% of dogs more than 10 years of age.

Typical features include

– Wall staring

– Not recognising owners

– Pacing and circling

– Getting lost

– Incontinence’

CCD is a progressive and ultimately fatal disorder with no proven effective treatment. It is devastating to the human-animal bond. CCD also has clinical, epidemiological, pathological and pharmacological similarities to human Alzheimer’s dementia’.

For more information go to http://www.rng.org.au/canine-cognitive-dysfunction/

http://www.ava.com.au/sites/default/files/AVA_website/News/A4%20Client%20Information%20Sheet%20SEPT%202014.pdf

Your brain on beer vs coffee

http://en.ilovecoffee.jp/posts/view/79

‘Meadow Lea adds sugar to margarine to entice kids’ ?

According to Gillespie, the sugar content of the product ranges from 17.8% to 20.5% depending on the flavour.

But, sugar is natural so, no worries regardless of the total dose, right?? 😉

http://davidgillespie.org/meadow-lea-adds-sugar-margarine-entice-kids/

Do you remember when they used to add sugar to toothpaste? I think they just use artificial sweeteners now. But, a new brand of toothpaste contains special stuff that neutralises acids from sugar, so there is no need to moderate your intake of sugar. Whew! We westerners can still consume our average of 0.6 kg or so of sugar ( = ~ 0.3 kg fructose) per week – not including fruit juices (which are typically ~ 10% sugar).

SL

Monday, 24 November 2014

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