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).
Several classes of anthelmintics impair cell structure, integrity, or metabolism:
- inhibitors of tubulin polymerization—benzimidazoles (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’.
- Merck Vet. Manual. http://www.merckvetmanual.com/mvm/pharmacology/anthelmintics/mechanisms_of_action_of_anthelmintics.html?qt=macrocyclic&alt=sh
- Sutherland and Scott, 2010. Gastrointestinal nematodes of sheep and cattle. Wiley-Blackwell. ISBN 978-1-4051-8582-0 (Hardback; ~242 pp).
More information on drenches:
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!
Feature articles in ParaBoss News
Liver fluke on the NSW Central Tablelands
by Bruce Watt, Regional Veterinarian, Central Tablelands Local Land Services, Bathurst NSW
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.
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.
The quick quiz
This 3-question quick quiz tests your knowledge of sheep parasites and their control.
Lyssavirus and other bat health risks | NSW Department of Primary Industries
Avermectin and Artemisinin – Revolutionary Therapies against Parasitic Diseases
As mentioned by ParaBoss News editor, Maxine Murphy, above:
” 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:
Hayfever? don’t blame the wattle?
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
But, can the Aussies beat the All Blacks in the Rugby World Cup on 2015-10-31 (GMT/UTC) (Halloween)? Will history repeat?