In this issue
- Mox in your milkshake? – WAAVP 2015 papers – Doyle, Leathwick and others
- Moxidectin LA in ewes – Kelly et al (WAAVP 2015).
- Macrocyclic lactones – lipophilia and secretion into milk
- Medications in milk
- Zolvix Plus (MPL+ABA) for cattle
- ParaBoss incl. WormBoss – cool new logos (outdone only by the content)
- Protein, energy, resistance and resilience – from WormBoss
- Liver fluke – a discussion – SL
- Congenital/ectopic fluke infections?
- Wet and dry ewes?
- NSW DPI digital publications
- The K5 variant of rabbit calicivirus
- Feral photos
- Snake envenomation-domestic animals-Australia
- Animal health surveillance – NSW and Australia
- Inimitable; wasabi; stop
Mox in your milksake?
Frivolous headings aside, I first became aware of the ‘moxidectin in milk’ story when listening to a talk by Michelle Dever (Sheep CRC-supported PhD candidate, University of New England, Armidale; now with MSD) on some MLA-funded research (by Michelle and others) into worm control in prime (‘meat breed’) lambs and their mothers. In short, they found a reduction in the worm egg counts of untreated prime lambs born to ewes treated with moxidectin pre-lambing. (This was just one of the findings). A quick search at the time found papers by the likes of Alvinerie and others reporting moxidectin in calves born to mothers treated with moxidectin. With the benefit of 20/20 (6/6 in the metric world) hindsight, this really shouldn’t come as a surprise.
Michelle Dever and colleagues presented some of those findings at WAAVP, Perth (2013), flagging that excretion of moxidectin in the milk of ewes could have untoward consequences (“the decreased effectiveness of the … treatments in lactating ewes may be attributed to moxidectin due to its extreme lipophilic nature and excretion in milk”). See poster here: Dever M et al WAAVP_Aug13 (poster) decreased drench efficacy during lactation-ewes. frm MD nov15
In 2014, at the Australian Society for Parasitology meeting, Michelle and colleagues presented more information, including the observation that “the consequence of treating lactating ewes with long-acting anthelmintics excreted in milk could be that worms in lambs may be exposed to sub-lethal doses of the active which could hasten development of anthelmintic resistance” [Dever, M. L., Kahn, L. P., Doyle, E. K., & Walkden-Brown, S. W. (2014). Worm egg counts in lambs decreased after administration of long acting anthelmintics to ewes. Australian Society for Parasitology, Canberra, Australia]. See poster here: Dever M et al ASP_Jun14 (poster) M Dever_17Jun14_Final (1)-WECs in lambs lower after ewes drenched-frm MD nov15
Subsequently Dever and Kahn published this paper in the journal, Veterinary Parasitology: Dever, M. L., & Kahn, L. P. (2015). Decline in faecal worm egg counts in lambs suckling ewes treated with lipophilic anthelmintics: Implications for hastening development of anthelmintic resistance. Veterinary Parasitology, 209(3-4), 229–234. doi:10.1016/j.vetpar.2015.02.018)
Matt Playford and colleagues at Dawbuts saved me time by summarising some of the papers from the recent WAAVP conference in the UK. Here, with permission, are excerpts (italicised) from the Dawbuts spring newsletter regarding moxidectin given to lactating ewes finding its way into the lambs.
‘Moxidectin given to lactating ewes finds its way into the lambs – This is understandable given the lipophilic nature of moxidectin, but detailed trials on the phenomenon had not been conducted until recently. What did these trials show?’
‘* Emma Doyle from the University of New England measured the moxidectin levels in the blood and milk of LA -injected ewes. Lambs had detectable levels of moxidectin in their bloodstream up to 35 days after treatment, resulting in a sub-lethal dose being applied to all lambs. In the short term this resulted in lower worm burdens in lambs from treated ewes compared to those from untreated ewes, but in the long term it is expected that this will lead to faster onset of resistance’. (‘LA’ = moxidectin long-acting injection. Doyle et al not only measured the concentration of mox. in milk, but also the volume of milk produced as well. – Ed.) Doyle Dever Kahn.WAAVP 2015. Moxidectin transfer via milk and sub-lethal dose of the active to suckling lambs
‘* In a study that sampled milk from ewes dosed with controlled release capsules or long-acting (LA) formulation of moxidectin prior to lambing, Leathwick et al. from New Zealand came up with the following conclusions. “Treatment of ewes pre-lambing with long-acting ML anthelmintics resulted in the persistent transfer of active to the lambs via milk and in the case of moxidectin, this resulted in a significant reduction in the establishment of ML-susceptible, but not ML-resistant larvae.” These studies have answered the knowledge gap in understanding moxidectin resistance when using long-acting treatments’.
(The ML-resistant Teladorsagia isolate used by Leathwick et al (“SOL-ivm-resistant”) was resistant to ivermectin (efficacy 42%), but susceptible to abamectin (96%) and moxidectin (>99%). Moxidectin levels in milk began at ~ 45 ng/ml, declining to low levels (~1-2 ng/ml) by day 80. Abamectin fluctuated in the range 1-3 ng/ml. Reference: Leathwick, D.M., Miller, C.M., Fraser, K., Selection for anthelmintic resistant Teladorsagia circumcincta in pre-weaned lambs by treating their dams with long-acting moxidectin injection, International Journal for Parasitology: Drugs and Drug Resistance (2015), doi: 10.1016/ j.ijpddr.2015.11.001.
Paper highlights: ”  Long-acting anthelmintics were administered to pregnant ewes.  Moxidectin and abamectin were detected in ewe’s milk for >60 days.  Moxidectin and abamectin were detected in plasma of lambs for >60 days.  Abamectin treatment had no effect on establishment of larvae in the lambs.  Moxidectin treatment reduced establishment of susceptible, but not resistant larvae.” – Ed.)
‘* Gareth Kelly, also from the University of New England, studied LA moxidectin in ewes and found that ewes treated with the injection alone had high worm egg counts (WEC) of approximately 480 eggs per gram over the subsequent 112 days. In contrast, ewes treated with an effective primer (in this case Zolvix (monepantel)) at the time of the LA injection had an average WEC of only 50 epg. The consequences of this are that ewes treated without a primer will contaminate pastures with high numbers of moxidectin-resistant larvae (see Figure 1)’.
Figure 1. From Dr Gareth Kelly’s presentation at WAAVP, 2015.
Notes for figure 1: Mox LA= single dose of long-acting moxidectin injection on day 0; MPL D0 = single dose of monepantel on day 0; MPL D0, 49 = two doses of monepantel given on days 0 and 49; MPL D0, 70 = two doses of monepantel given on days 0 and 70; Mox LA/MPL D0= primer of monepantel given on day 0 at the same time as the long-acting moxidectin; Mox LA/MPL D0,49 = long-acting moxidectin on day 0 + two doses of monepantel given on days 0 and 49; Mox LA/MPL D0, 70 = long-acting moxidectin on day 0 + two doses of monepantel given on days 0 and 70.
(Note: Moxidectin-resistant Haemonchus occurs on about 80% of farms in the New England region of NSW, where this trial was conducted. In the trial, there was severe resistance of Haemonchus to moxidectin – Ed.) Kelly G Kahn L WAAVP 2015.Managing resistance to long-acting injectable moxidectin in sheep nematodes – co-admin of unrelated actives
“Further studies by Gareth Kelly with Lewis Kahn showed that long acting moxidectin alone did have a benefit in terms of weight gain but that a primer was required to reduce worm egg counts. The bigger question is now that we have scientific evidence of the ‘lamb effect’ with moxidectin long-acting treatments how do we combat this to prevent further rapid onset of moxidectin resistance.”
Also from Dawbuts:
” ZOLVIX PLUS (monepantel + abamectin) for cattle! More exciting news to come from the WAAVP conference in Liverpool, UK was details about Zolvix Plus the latest cattle oral drench. Trials have been conducted at Elanco’s research site Yarrandoo, NSW. This was the first public presentation of results of trials where Zolvix Plus was used in cattle. Dose rate of monepantel is the same as in sheep (2.5mg/kg). Efficacy appears to be similar to the two compounds used in sheep, with greater than 99% efficacy reported to the common nematode species in slaughter studies”.
Why ‘Dawbuts’? Well, Matt , who hails from Cowra, NSW, has Japanese connections. (Cowra itself has Japanese connections). For example, his doctoral thesis, on Echinococcus multilocularis, and done in Hokkaido, was in Japanese. However, this article, by Playford and Kamiya, is in English: http://www.ncbi.nlm.nih.gov/pubmed/1297005. The lab at Dawbuts is called the ‘Kamiya Laboratory’.
‘Dawbuts’ sounds like the Japanese word (dobutsu) for animal(s).
Macrocyclic lactones – ‘lipophilicity’ and secretion into milk
From Hennessy and Alvinerie:
“A most significant characteristic of MLs is their lipophilicity”.
“Ivermectin is arguably the least lipophilic ML, with the possible exception of eprinomectin”.
“Moxidectin is about 100 times more lipophilic than ivermectin”.
Doramectin is “less lipophilic than moxidectin, but more than ivermectin or eprinomectin..”
“Partitioning into milk is a complex process relating to physico-chemical characteristics and membrane interactions … The high lipophilicity of the MLs is highly conducive for partitioning into milk… ‘(there is) considerable partitioning of ivermectin into milk” (e.g., around 5% of the dose) .. “the higher lipophilicity of moxidectin will facilitate even great partition into milk.. (but) residual concentrations (of moxdectin) in milk are below toxic limits, resulting in nil withholding periods in many countries … Shoop reported that saturation of the C-22,23 portion of the ML molecule* facilitated partition into milk ….this observation led to the development of eprinomectin which is used in lactating dairy cattle with zero milk withholding time …. Alvinerie confirmed … only 0.1% of the dose (of eprinomectin partitions into the) milk of dairy cattle…”
Hennessy DR and Alvinerie MR, 2002. ‘Pharmacokinetics of the macrocyclic lactones..”, In “Macrocyclic lactones in antiparasitic therapy”, edited by Vercruyse and Rew. ISBN 0 85199 617 5
*So, does this effect (‘saturation of the C-22,23 portion of the ML molecule* facilitated partition into milk’ ) work through increasing ‘lipophilicity’ and/or other means?
Lipophilicity? I see lipophilic (‘tending to combine with or dissolve in lipids or fats’) in the dictionaries (Macquarie, Oxford), but I don’t see lipophilicity? So, coprophilia, or other ‘-phila’, should be coprophilicity?
From Websters: -philia |ˈfɪlɪə| combining form denoting fondness, especially an abnormal love for a specified thing:paedophilia.• denoting undue inclination: spasmophilia.DERIVATIVES -philiac |-lɪak| combining form in corresponding nouns and adjectives.,-philic combining form in corresponding adjectives.,-philous combining form in corresponding adjectives.ORIGIN from Greek philia ‘fondness’.
Medications in milk
Further to the above (moxidectin in the milk of ewes, passing then to lambs), I was wondering: is the presence of moxidectin in milk at higher levels than, say, abamectin, entirely due to the greater lipophilicity of moxidectin?
In short, I don’t know the answer, although this article, albeit relating to human milk, is interesting: http://www.medsmilk.com/pages/introduction
From this article:
Drugs transfer into human milk if they:
- Are highly lipid soluble.
- Attain high concentrations in maternal plasma.
- Are low in molecular weight (< 500 ).
- Are low in protein binding.
- Pass into the brain easily.
In addition to relative ‘lipophilia’, possibly another reason for MOX being present at higher concentrations than say ABA (as in Leathwick et al above) is due to large differences in maternal plasma levels, if only due to the typically lower plasma levels of drugs when delivered by controlled release devices, especially compared to the relatively high initial blood levels achieved by long-acting injectable moxidectin.
‘Cool new logos at ParaBoss, including WormBoss
(Logos designed by Ros Kelly from ‘Pictures+Words’).
Even better than the logos, as good as they are, is the content. On the worm front, a good place to start is ‘Your Program” at wormboss.com.au
Protein, energy, resistance and resilience
‘The resistance and resilience of sheep to worms is affected by different aspects of nutrition. It is the supply of protein that is most important for regulating the resistance of sheep to worms. This is largely because worm infection results in sheep diverting protein from muscle and wool growth to the immune response and the need to repair the damaged gut. In contrast, both protein and energy are equally important in improving resilience to infection.’
Read more at: http://www.wormboss.com.au/tests-tools/management-tools/nutrition.php
A discussion regarding liver fluke
A discussion (not prescriptive or perfect!) I had with some colleagues (LLS vets) regarding liver fluke treatments:
Hi ……………. ,
closantel) have been identified on Australian farms (Boray 1990). In
addition, strains of F hepatica resistant to luxabendazole and
triclabendazole have been selected in the laboratory (Boray 1990).
A field isolate of F hepatica resistant to triclabendazole has now been
identified on a Victorian sheep farm’.
Congenital/ectopic fluke infections?
A veterinary colleague (Matt Ball, Virbac) raised this recently. Can calves be born with liver fluke infections? In short, I don’t know for sure, but logically it would seem possible. If ingested larval fluke find their way through the intestine, then the peritoneal cavity, thence to the liver, presumably by some sort of chemotaxis??, then it may be that some could happen onto a foetal liver instead.
A quick search found these:
On page 125 ff there was this on ectopic localization of liver fluke:
“Whilst the liver is the typical tissue sought by the young liver fluke, numerous instances are known of the parasite establishing itself and growing in other locations in the mammalian body. Incidentally, such cases cannot be detected by the demonstration of eggs in the faeces. The most usual place is the lung and the presence of flukes there has been recorded as the cause of acute pneumonia and peribronchial inflammation in sheep (Mychlis, 1959) and cattle (Catellani, 1952; Kochnev, 1950). The parasite has also been found in lymph nodules (Dziekonski, 1947), and even in the uterus of cattle, causing sterility and endometritis (Thom, 1956 – 4 cases). It is conceivable that in this way the young flukes may even come to settle in the foetus in utero. The possibility of pre-natal infection was suggested by Raillet et al. (1913) and confirmed by Bugge (1935). Enigk and Duwel (1959) found liver flukes in 50 out of 661 calves aged under 3 months. Although post-natal infection at that age is not expected normally, it cannot be excluded in principle.”
OM el-Azazy. Suspected congenital fasciola infection in a buffalo calf. Vet. Rec. 1988;122:520 doi:10.1136/vr.122.21.520
‘Congenital infections with S. japonicum have been described numerous times for different hosts, including humans, dogs, goats, cattle, sheep, rabbit and pigs’ Parasite Immunology, 2005, 27, 289–295 Blackwell Publishing, Ltd. (Vercruysse et al?)
Wet and dry ewes
The inimitable Dr Refshauge shows you how:
NSW DPI Digital Publications
The facts about the K5 variant of rabbit calicivirus (from the AVA)
Snake envenomation in domestic animals in Australia
Free virtual issue of the Australian Vet Journal:
“Welcome to the FREE Virtual Issue from the Australian Veterinary Journal
Published: 29 October 2015
Introduction: Australia has some of the world’s most venomous snakes. With summer approaching, pets and other domestic animals are particularly susceptible to snake bites and subsequent envenomation as snakes emerge from hibernation to seek out the summer sun.
Numerous case reports published in the Australian Veterinary Journal have identified snake bites from brown snakes, tiger snakes, red-bellied black snakes, taipans, and death adders in domestic animals, including sheep, horse and cattle. A snake bite survey conducted in a 1998 issue of the AVJ reported dogs and cats to be the most common victims of snake bite, with brown snakes the most common species contributing to envenomation of domestic animals. Despite this survey, it is difficult to quantify the frequency of snake bite in animals in Australia, because of the many unreported and undiagnosed cases of snake envenomation.
As a consequence, pet owners and veterinarians need to be vigilant in not only preventing snake bites, but also in recognising and treating animals at all stages of envenomation. Importantly, past reports in the AVJ have stressed the difference in the action of venom from Australian snakes compared with American snakes and, as such, treatment strategies vary greatly and may not be interchangeable.
Given the unique nature of Australian snakes, Australia is not only at the forefront of research into snake envenomation, antivenene and treatment, but also in the treatment of snakes themselves, as they can also suffer from cancers and infection. This virtual issue provides free, full text access to a range of papers published in the AVJ concerning snakes, from case reports on envenomation to scientific articles on blood coagulation and anitvenene kits, to the treatment of snakes with infection and adenocarcinoma. We have also included a guide to venomous snakes, as well as a link to the first of our papers on snake envenomation by Max Henry, in 1935.
Animal Health Surveillance Quarterly
The latest issue of Animal Health Surveillance Quarterly (April – July 2015) is now available for download from the Animal Health Australia website by following the web link:
This issue contains the following articles:
- Message from the Australian Chief Veterinary Officer
- Approaches to support early detection of FMD in Australia
- Australia’s official freedom from classical swine fever
- Veterinary laboratory diagnosticians symposium
- Wildlife Health Australia
- Aquatic Animal Health
- State and territory reports
- Quarterly statistics
- NAHIS contacts
Animal Health Surveillance – NSW
so good or unusual as to be impossible to copy; unique.“they took the charts by storm with their inimitable style”
synonyms: unique, distinctive, individual, special, idiosyncratic, quirky, exclusive,rare; Gordon Refshauge, etc.
Yummy- all that wasabi!
English evolves: the meaning of STOP
We may not like it, but language is ever changing (‘going forward, evolving synergies’). One example might be the word STOP.
Surveys show that a declining number of car drivers come to a complete halt at STOP signs.
A young-ish policeman (as opposed to a cranky, curmudgeonly old coot) recently told me that drivers are getting worse. But when it comes to stopping, perhaps language has changed?
I heard of a lawyer who drove slowly through a STOP sign and was immediately swept upon by a police officer who wanted to book the lawyer for failing to stop at a stop sign. The lawyer explained to the police officer that he was a very important lawyer, and a good friend of the local judge, and that he, being an eminent lawyer, could cogently and successfully argue in a court of law that the meaning of ‘stop’ is now somewhat nuanced and could well mean ‘to slow down’ or ‘roll slowly forward’, thus fulfilling the spirit if not the letter of the law. All the while, the lawyer politely refused to produce his driver’s license, then politely declined to step from the vehicle. Eventually the officer impolitely hauled the lawyer from the car, and proceeded to vigorously beat him with his truncheon. The lawyer screamed in pain and pleaded with the policeman to stop, whereupon the policeman, sweating with exertion, asked the lawyer if he would like him to stop or merely slow down.
Editor (Ed.): SL. ~ 2015-11-27
E&OE (including stray apostrophes, various typos and errors in fact).