how drenches work-wormfax-paraboss news-avermectin and artermisinin etc

In this issue of WormMail:

  • How drenches work
  • Anthelmintic resistance
  • WormFaxNSW-September issue
  • ParaBoss News
  • Lyssavirus and other bat health risks
  • Avermectin and Artemisinin – Revolutionary Therapies against Parasitic Disease
  • WHO report on meat and cancer
  • Hayfever and wattle
  • Shark tracking
  • Auditory transduction
  • Australian scientists make major quantum computing discovery
  • Halloween, Wallabies and Kiwis (Rugby World Cup)

How drenches work

While the precise mode of action of many anthelmintics is not fully understood, the sites of action and biochemical mechanisms of many of them are generally known. (Merck Vet.Manual).

  • inhibitors of tubulin polymerizationbenzimidazoles (BZs) and probenzimidazoles (which are metabolized in vivo to active benzimidazoles and thus act in the same manner). The first member of the group, thiabendazole, was used as an antifungal. The benzimidazoles inhibit tubulin polymerization, acting on the same receptor protein, β-tubulin. In resistant worms, BZs can no longer bind to the receptor with high affinity. Benzimidazoles progressively deplete energy reserves and inhibit excretion of waste products and protective factors from parasite cells; therefore, an important factor in their efficacy is prolongation of contact time between drug and parasite. (This perhaps explains why slow release devices prolong the useful life of BZs). BZs are strongly associated with particulate matter in the rumen, which may extend the period over which they are absorbed.
  • uncouplers of oxidative phosphorylation—’salicylanilides’ (e.g. rafoxanide (“Ranide”), closantel (which binds strongly to albumin, this fact determining its spectrum of activity)) “Seponver” etc.) and substituted phenols’ (e.g. nitroxynil (“Trodax” etc.)). Mostly flukicides (fasciolicides). Acting as protonophores, these cause hydrogen ions to leak through the inner mitochondrial membrane. Although isolated nematode mitochondria are susceptible, many fasciolicides are ineffective against nematodes in vivo, apparently due to a lack of drug uptake. Exceptions are the hematophagous (“blood eating”) nematodes, eg, Haemonchus and Bunostomum’.
  • inhibitors of enzymes in the glycolytic pathway—clorsulon (a sulphonamide). Present, with other actives, in ‘Ivomec Plus’, ‘Nitromec’ etc. When Fasciola hepatica ingest clorsulon (in plasma and bound to red blood cells), they are killed because glycolysis is inhibited and cellular energy production is disrupted.

Effects may occur by inhibiting the breakdown or by mimicking or enhancing the action of neurotransmitters. The resulting paralysis (spastic or flaccid) of an intestinal helminth allows it to be expelled by the normal peristaltic action of the host.

Categories include drugs that act via:

  • a presynaptic latrophilin receptor (emodepside). Emodepside (sold in combination with another anthelmintic (praziquantel) for topical application under the tradename Profender) is currently marketed only for cats, although it has been found to be effective against a range of nematodes in small and large animals. (Sutherland). The drug is derived from a metabolite of Mycelia sterile, a fungus that inhabits the leaves of Camellia japonica (Wiki).
  • various nicotinic acetylcholine receptors (agonists: imidazothiazoles (eg levamisole (LEV)), tetrahydropyrimidines (e.g. morantel); allosteric modulator: monepantel (‘Zolvix’); antagonist: spiroindoles (e.g. derquantel, as in ‘Startect’).

Derquantel causes flaccid paralysis of nematodes.

The receptors on which monepantel acts are unique in that they are found only in nematodes, which presumably explains the drug’s very favourable safety profile.

  • glutamate-gated chloride channels (macrocyclic lactones: avermectins, milbemycins).  The macrocyclic lactones (MLs) cause an influx of chloride ions, resulting in (flaccid) paralysis of the pharynx, the body wall, and the uterine muscles of nematodes. (Inability to move, feed or oviposit (Sutherland)).
  • GABA-gated chloride channels (piperazine). Causes flaccid paralysis. It also blocks succinate production by the worm. The parasites, paralysed and depleted of energy, are expelled by peristalsis.
  • inhibition of acetylcholinesterases (coumaphos, naphthalophos). Organophosphates block cholinergic nerve transmission, resulting in spastic paralysis. OPs inhibit other enzymes as well.

‘The mode of action of praziquantel is not certain, but it rapidly causes tegumental (‘skin’) damage and paralytic muscular contraction of cestodes (tapeworms), followed by their death and expulsion’.

Anthelmintic resistance

Resistance, a heritable trait, is present when there is a greater frequency of individuals within a population able to tolerate doses of a compound than in a normal population of the same species. (Slightly modified from Pritchard et al (1980), cited by Sutherland and Scott (p.117). See above).

WormFaxNSW – September

A new of WormFaxNSW, a monthly summary of sheep WormTests from around the state, is up on the DPI website:

 

Except from ParaBoss news – have you subscribed?

From the Editor

Summer is certainly on the way. Temperatures are up and in many regions across the country rainfall is down.

As users of this site, we all acknowledge that parasites and research into their control is of paramount importance. It was therefore pleasing to see the 2015 Nobel Prize for Physiology or Medicine awarded for the development avermectin (the parent of ivermectin) and artemisinin, drugs that are now instrumental in the control of roundworm diseases and malarial blood parasites of humans.

The precursors of these drugs were sourced from the natural environment: Avermectin from fungi in soil samples and Artemisinin from the wormwood bush, Artemisia annua not A. absinthium typically grown in Australia. The impetus to develop these drugs was to better control resistant parasites and to delay further drug failure (see page 6). And these drugs are best used in combination with other drugs and non-drug strategies. Now that sounds like a WormBoss message!

Maxine Murphy

Feature articles in ParaBoss News

Liver fluke on the NSW Central Tablelands

by Bruce Watt, Regional Veterinarian, Central Tablelands Local Land Services, Bathurst NSW

Watt-Bruce dinkus 201108 - cropped

Liver fluke infestation is a widespread problem for sheep, cattle and goat producers in the NSW Central Tablelands. We know from on-farm surveys and from abattoir surveillance that at least 80% of Central Tablelands properties have fluke. >> Read more.

Breech strike practice change

by Deb Maxwell, ParaBoss Operations Manager

The marketability of Australian wool will be dependent on progress made toward a breech strike resistant national flock. >> Read more.

Keep your flock lice-free

by Deb Maxwell, ParaBoss Operations Manager

Whether you’ve long had a lice-free flock and haven’t treated for many years or you’ve recently treated your sheep, hoping to eradicate lice, the threat of lice is ever present. >> Read more.

Eperythrozoon

by Maxine Murphy, ParaBoss News Editor

Eperythrozoonosis (ep-pur-rith-ro-zo-on-nosis) is the disease produced by the bacterium Mycoplasma ovis. M. ovis inhabits red blood cells of sheep and causes their destruction leading to anaemia, jaundice, and in heavy infections, deaths of susceptible sheep. >> Read more.

State Outlooks for October 2015

The quick quiz

This 3-question quick quiz tests your knowledge of sheep parasites and their control.
>> Take the quiz.

Lyssavirus and other bat health risks | NSW Department of Primary Industries

http://www.dpi.nsw.gov.au/biosecurity/animal/humans/bat-health-risks

Avermectin and Artemisinin – Revolutionary Therapies against Parasitic Diseases

As mentioned by ParaBoss News editor, Maxine Murphy, above:

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/advanced-medicineprize2015.pdf     It’s a good read.

” Malaria alone is responsible for the death of 500,000 individuals each year; with the majority (90%) residing in Africa and tragically, 80% are children predominantly under the age of 5. Artemisinin-based therapy has contributed to the significant reduction in mortality, particularly for children with severe malaria (>30%) (Dondorp et al., 2010). The overall global death toll from Malaria during the last 15 years has declined by 50% (WHO, 2015). “

“Roundworm infection often occurs during childhood and gives rise to lifelong suffering and disability. Among the multiple diseases caused by roundworm infection, River Blindness and Lymphatic Filariasis stand out, with 25 million and 120 million individuals inflicted for these diseases, respectively. These diseases are included in the Neglected Tropical Diseases, 7 which totally amount to between 46–57 million disability adjusted life-years (DALYs) lost annually. Thus, this group of diseases represents one of the most significant global causes of illness and disability. “

WHO report on meat and cancer

See here for an example of one of the news stories:

http://www.smh.com.au/world/processed-meats-cause-cancer-and-red-meat-probably-does-too-world-health-organisation-20151026-gkj2pf.html

Other views:

http://www.zoeharcombe.com/2015/10/world-health-organisation-meat-cancer/

http://www.theshovel.com.au/2015/10/27/vaping-sausages-may-be-safer-word-health-organisation-says/#more-5786

Hayfever? don’t blame the wattle?

http://www.abc.net.au/news/2015-09-23/dont-blame-the-wattle/6791396

Shark tracking

http://www.dpi.nsw.gov.au/fisheries/info/sharks/tips-to-reduce-your-risk-of-shark-attack/north-coast-shark-tracking

Auditory transduction – Brendon Pletsch

How auditory transduction works. This Youtube video is short (6:44) and it is fabulous. A must see (and hear).

Australian scientists make major quantum computing discovery

http://www.industry.nsw.gov.au/business-and-industry-in-nsw/news-and-events/news/australian-scientists-make-major-quantum-computing-discovery

But, can the Aussies beat the All Blacks in the Rugby World Cup on 2015-10-31 (GMT/UTC) (Halloween)? Will history repeat?

 

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Startect resistance?-NO. ParaBoss News. Reduced efficacy of new drenches?-be alert, not alarmed. Canid pest ejector. Brucella suis. Rabies etc

In this issue

  • Resistance to Startect? – NO!
  • ParaBoss News – September 2015
  • Reduced efficacy of new drenches? Be alert, not alarmed – Love
  • August WormFax NSW-now online
  • Canid Pest Ejector- A new tool to protect threatened Rock Wallabies
  • Swine, brucellosis, hunting dogs and humans
  • World rabies day – 28 September
  • Interesting x-rays of native fauna
  • Behavioural economics for better decisions
  • Drive safe (sic) this long weekend
  • Upcoming  release of the K5 variant of RHDV
  • New free App for mapping pest animals

Resistance to Startect? – NO!!

Already some are getting this wrong.  Dead wrong.

Detectable resistance in practice means  reduced efficacy. However reduced efficacy does not necessarily mean resistance.

Along with other colleagues I have been at pains to point out that that reduced efficacy of Startect is not, at this point in history, resistance. In particular I am referring to recent articles in this blog and in the September 2015 ParaBoss News which, among other things, mention that Startect on two farms had an efficacy of ~ 90% against Haemonchus.  On both farms, abamectin, one of the two active ingredients in Startect, had zero efficacy (severe resistance!) against Haemonchus.

We know that derquantel on its own is not innately highly effective against Teladorsagia, or against Haemonchus L4 larvae.  This is not unusual. Consider, for example, naphthalophos, also a mid-spectrum drench (when used on its own). Also consider narrow spectrum drenches, triclabendazole for example: a very good flukicide, but naturally ineffective against roundworms. Is the latter resistance?  No.

In the fullness of time resistance to derqunatel will almost certainly develop. It has with naphthalophos, and all or most other sheep and cattle drench actives (that I know of).

So, do we have evidence of resistance to Startect? NO!  Can Startect have reduced efficacy (e.g. ~ 90% or so) in certain circumstances? Yes – if abamectin resistance is severe, and many Teladorsagia and/or immature Haemonchus are present.

Whether new or old, regularly check the efficacy of drenches you use. Find out what works on your farm (evidence), then make best use of all the available options. Don’t guess; ignore the spin; rely on the evidence.

ParaBoss News – September

The September issue is out.

If you don’t get ParaBoss News, you can subscribe here: http://www.paraboss.com.au/subscriptions.php

ParaBoss is the umbrella (parasol?) under which WormBoss, FlyBoss and LiceBoss live.

In this month’s issue:

From the Editor

Early spring was dominated by high temperatures with a return to more usual levels later in the month. Good rains fell over much of the coastal and subcoastal temperate regions while the pastoral zones remained very dry.

While not all worms ‘disappear’ when temperatures drop, neither do all worms disappear when conditions become dry. The difference between worms is how they wait out the dry times. For instance, Haemonchus (barber’s pole worm) eggs and larvae are not at all dry-tolerant, so the adults find a quiet spot inside the sheep. When areas of green pick around leaky watering points encourage sheep activity, these adults respond by producing spectacular numbers of eggs resulting in hotspots of infection in an otherwise dry landscape. In contrast, the scour worms such as Trichostrongylus spp (scour worms) and Teladorsagia (small brown stomach worm) find the drier conditions not quite so taxing and the relatively few eggs produced wait stoically on pasture for rain before continuing on.

In the State Outlooks this month, conversation is all about the weaners, fresh low worm-risk paddocks and efficient drenches.

Maxine Murphy

Feature articles

Reduced efficacy of new drenches? Be alert, not alarmed

By Stephen Love, Veterinarian / Research Officer (Parasitology), NSW DPI

Recently there have been a small number of confirmed reports of reduced efficacy, including resistance, involving new sheep drenches in Australia. What should sheep producers do? >> Read more.  Or see here: Love S.2015-09 Reduced efficacy of new drenches_ Be alert, not alarmed ParaBoss Newspdf

Barber’s pole worm in winter, non-seasonal and Mediterranean rainfall areas

by Deb Maxwell, ParaBoss Operations Manager

Barber’s pole worm (Haemonchus contortus) occurs in all sheep production areas of Australia, even in arid areas. With the introduction of the Barbervax® vaccine it is timely to clarify the areas of Australia in which it is recommended for use and how to manage barber’s pole worm where it is sporadic. >> Read more.

Lamb’s tails; how long is long enough?

from the FlyBoss web site

Docking the tail to the correct length at lamb marking time is crucial in minimising stain around the breech and reducing flystrike risk throughout the sheep’s life. >> Read more.

Stripping, topping up and all the other jargon

from the LiceBoss web site

If you sometimes struggle with the jargon on lice product labels, you’re not the only one. See our product label terminology page to make sense of those terms. >> Read more.

The quick quiz

This 3-question quick quiz tests your knowledge of sheep parasites and their control.
>> Take the quiz.

This month’s polls

Click the question to open the page then go to the poll at the top right hand corner of each web site.

WormBoss: Did you prepare a low worm-risk paddock during the last 12 months?

FlyBoss: Do you apply a flystrike preventative treatment each year? If so, what deterines the time it is appplied?

LiceBoss: Between your most recent main shearing and the main shearing before that, did you apply a lice treatment, and if so, how long after shearing?

>> View results of previous polls

August Wormfax NSW-now online

Canid Pest Ejector- A new tool to protect threatened Rock Wallabies

Excerpt from this story:
“The Canid Pest Ejector is a mechanical device that delivers a dose of 1080 poison into the mouth of the target animal when it attempts to remove the attached bait,” explained Senior Local Land Services Officer, Huw Evans.”

Swine, brucellosis, hunting dogs and humans

“Swine Brucellosis” is found in feral pigs in northern NSW and Queensland and can be transmitted to pig hunting dogs through infected pigs or from being fed raw, infected pig meat or by-products. Brucellosis can potentially be fatal for humans and there is no known guaranteed cure for dogs. NSW DPI have prepared an information sheet for hunting dog owners and guidelines for veterinarians.

Source: Tablelands Telegraph, Sept 2015 issue.

World rabies day – 28 September  world rabies day

https://rabiesalliance.org/world-rabies-day/

Excerpt: ‘During the next 10 minutes, at least one person will die from rabies. There’s a good chance that person will be a child, let’s imagine she’s a girl. She will almost certainly be from Africa or Asia, and there’s little chance she will have access to palliative care which might have made her final hours less anguished. Instead, she might be strapped to a bed or locked in room until death releases her. To die of rabies is not a gradual slipping from the world, it is a tortuous exit. And death is certain. Rabies is 99.9% fatal, the highest fatality rate of any known disease.  However, there is hope for the 2 billion people who live at risk of rabies because it is also preventable.

(Emphases mine. – SL)

From a NSW DPI blog (Peter Fleming and Jessica Sparkes):

wild dog being tracked -source-P Fleming and J Sparkes 2015-09-28 DPI Active blog world rabies day

Image source: Peter Fleming and Jessica Sparkes, NSW DPI.  GPS-collared wild dog being tracked.

Rabies: prevention is key.

‘Rabies is a preventable viral disease that impacts upon most countries. With the highest fatality rate of any known disease affecting humans, more than 65,000 people die of rabies annually.

Today, this deadly disease is being thrown into the spotlight for World Rabies Day. Hundreds of events are being held globally to raise awareness of the disease and its prevention.

Thankfully, through vigilance, quarantine and distance, we still don’t have the disease in Australia. To keep it that way, NSW DPI researchers, in conjunction with staff and students at the University of New England, are working to safeguard Australia from a potential rabies incursion.

GPS logging collars, like the one on the old bloke in the picture, are deployed on dingoes and other free-roaming wild and domestic dogs to track their movements and quantify interactions between them.

We also use camera monitoring stations to help estimate numbers of dogs in the wild and the contacts they make with other dogs.

Information collected through this collaboration will feed directly into strengthening Australia’s response strategy for a rabies incursion (AusVetPlan).

Interesting x-rays of native fauna

http://www.abc.net.au/radionational/programs/offtrack/echidna-innards-and-wombat-bones/6777744

Although designated ‘Homo sapiens‘, apparently people don’t always behave rationally.

“‘Economists model creatures that are hyper rational, have no self-control problems, no emotions and are extremely selfish,’ says Prof. Richard Thaler, University of Chicago. ‘Behavioural economics is ‘really just economics with people instead of these fictional creatures that pop up in economics textbooks.’

How does this relate to ‘agricultural extension’ and adoption rates of ‘best practice’? Of course the ‘experts’ could be as much a problem as the ‘end -users’.

Drive safe this long weekend

Thus says a message I got by email. So, we don’t drive safely any more?   Or, do we drive safes instead of cars?

Or, as a friend quipped, “Adverbs are on the way out. Or, should I say adverbs are dying out quick.”

Upcoming  release of the K5 variant of RHDV

See here.

New free App for mapping pest animals

http://www.feralscan.org.au/