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Veterinary Parasitology 112 (2003) 255–257 Letter to the Editor Comment on “A comparison of persistent anthelmintic efficacy of topical formulations of doramectin, eprinomectin, ivermectin and moxidectin against naturally acquired nematode infections of beef calves” and problems associated with mechanical transfer (licking) of endectocides in cattle We would like to comment on an article by Williams et al. (1999). In this article, describing a comparison of topical formulations of macrocyclic lactones (MLs) there is a dramatic decrease of 75% in the faecal egg count (FEC) of untreated animals 7 days after trial commencement. A reduction of >75% in faecal egg count was maintained for the remainder of the trial (112 days). In the discussion regarding the decrease in faecal egg count, it was suggested the most likely factor was a change in diet from dry hay to lush winter forage but also included the possibilities of handling procedures, host immune response and larval inhibition. The authors suggested that it was unlikely that the decrease in faecal egg count was due to mechanical transfer (rubbing, licking, etc.) of endectocides due to the uniform decrease in faecal egg count (presumably because mechanical transfer would be sporadic in nature). Serum levels of endectocides were not analysed by Williams et al. (1999). In a recent trial conducted in northeast Victoria, Australia we have analysed serum from cattle after ML administration (Barber et al., in preparation) and believe that our results may add some further information regarding transfer of “pour-on” products post-administration in standard grazing situations with cattle. This trial consisted of 160, 10-month-old cross-bred Angus, Murray Grey and Brangus female and male cattle with an average weight of 213 kg. The cattle were pastured in four groups and grazed over an area they had grazed for the previous 2 months. Treatments consisted of doramectin pour-on and injection (Dectomax ® , Pfizer); eprinomectin pour-on (Eprinex ® , Merial); ivermectin pour-on and injection (Ivomec ® , Merial); moxidectin pour-on and injection (Cydectin ® , Fort Dodge) and an untreated group. All groups consisted of 20 animals and these animals were split amongst the four paddocks (with males and females in separate paddocks). Average stock- ing density was approximately one animal per hectare with an average pasture height of 0304-4017/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. doi:10.1016/S0304-4017(02)00436-3

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Page 1: Comment on “A comparison of persistent anthelmintic efficacy of topical formulations of doramectin, eprinomectin, ivermectin and moxidectin against naturally acquired nematode infections

Veterinary Parasitology 112 (2003) 255–257

Letter to the Editor

Comment on “A comparison of persistentanthelmintic efficacy of topical formulationsof doramectin, eprinomectin, ivermectin and

moxidectin against naturally acquired nematodeinfections of beef calves” and problems

associated with mechanical transfer(licking) of endectocides in cattle

We would like to comment on an article byWilliams et al. (1999). In this article, describinga comparison of topical formulations of macrocyclic lactones (MLs) there is a dramaticdecrease of 75% in the faecal egg count (FEC) of untreated animals 7 days after trialcommencement. A reduction of >75% in faecal egg count was maintained for the remainderof the trial (112 days). In the discussion regarding the decrease in faecal egg count, it wassuggested the most likely factor was a change in diet from dry hay to lush winter foragebut also included the possibilities of handling procedures, host immune response and larvalinhibition. The authors suggested that it was unlikely that the decrease in faecal egg countwas due to mechanical transfer (rubbing, licking, etc.) of endectocides due to the uniformdecrease in faecal egg count (presumably because mechanical transfer would be sporadicin nature). Serum levels of endectocides were not analysed byWilliams et al. (1999).

In a recent trial conducted in northeast Victoria, Australia we have analysed serum fromcattle after ML administration (Barber et al., in preparation) and believe that our results mayadd some further information regarding transfer of “pour-on” products post-administrationin standard grazing situations with cattle. This trial consisted of 160, 10-month-old cross-bredAngus, Murray Grey and Brangus female and male cattle with an average weight of213 kg. The cattle were pastured in four groups and grazed over an area they had grazedfor the previous 2 months. Treatments consisted of doramectin pour-on and injection(Dectomax®, Pfizer); eprinomectin pour-on (Eprinex®, Merial); ivermectin pour-on andinjection (Ivomec®, Merial); moxidectin pour-on and injection (Cydectin®, Fort Dodge)and an untreated group. All groups consisted of 20 animals and these animals were splitamongst the four paddocks (with males and females in separate paddocks). Average stock-ing density was approximately one animal per hectare with an average pasture height of

0304-4017/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved.doi:10.1016/S0304-4017(02)00436-3

Page 2: Comment on “A comparison of persistent anthelmintic efficacy of topical formulations of doramectin, eprinomectin, ivermectin and moxidectin against naturally acquired nematode infections

256 Letter to the Editor / Veterinary Parasitology 112 (2003) 255–257

2.3 cm in early July when the trial commenced. Blood was collected the day before ML ad-ministration and 7 and 13 days after, while faeces were collected the day before and 13 dayspost-administration. Serum was analysed using a high performance liquid chromatography(HPLC) method previously validated (Alvinerie et al., 1995).

The day before administration of all products the geometric mean FEC of the untreatedgroup was 180 eggs per gram (epg) and 13 days post-treatment this had reduced to 120 epg.This decrease could not be explained by a change in pasture as animals had grazed the samepasture for the previous 60 days. It was also unlikely that it was entirely due to handlingprocedures given the calves had been through the yards every month for the past 3 monthsand were accustomed to the procedure. This change could not be attributed to a change inparasite species present as the counts for the 2 days were very similar with major parasitespresent beingCooperia species (70%) andOstertagia ostertagi (20%) with a small numberof Nematodirus, Oesophagostomum andTrichostrongylus axei. It is possible host immuneresponse or larval inhibition were responsible but given the FEC did not drop any furtherover the following 2 months this also seems an unlikely explanation for the observed effects.

Seven days after treatment 80% of the animals in the untreated group had detectableamounts of ML in their serum with 55% of animals in the group having two or more MLsdetected. By 13 days after treatment, 60% of the untreated animals had ML in serum.This was observed across all paddocks (in both sexes) with the highest serum level of0.851 ng total ML/ml serum. This low serum level may represent sufficient levels of MLin the gastrointestinal tract for anti-parasitic efficacy given the poor bio-availability ofMLs when administered orally. Considerable care was exercised with the application ofpour-on products so it is unlikely that contamination occurred within the yards. Transfercontinued well after administration as some animals had higher levels at day 13 than at day7 post-treatment suggesting further intake occurred post or just prior to day 7. ML transferwas evident in all groups, including those groups treated with pour-on and administrationby injection. The most likely explanation for this amount of endectocide in the serum is dueto mechanical transfer by self or allo-grooming.

It has been recently demonstrated (Laffont et al., 2001) that there can be considerabletransfer of endectocide by licking in housed animals and results from this trial stronglysuggest this situation also occurs in range animals although it was not possible to producea pharmacokinetic profile given the limited time points available. We believe that thereare several areas of the methodology in the trial by Williams et al. to suggest that transferof endectocides may have been important in reduction of FEC as well as the change innutrition. These points are given as follows:

• The change in herd structure from one large herd to multiple small herds (five animalsper herd) contained in limited area (2 ha) is likely to lead to significant increases in socialinteraction including licking and rubbing resulting in increased transfer of MLs. In theAustralian trial females and males were separated into two groups (four groups in total)and pastured in approximately 40 ha per group. Under these extensive conditions, 80%of animals demonstrated mechanical transfer of MLs.

• The increase in available forage is very likely to lead to reduced time grazing and increasedtime for self and allo-grooming hence increased opportunity for transfer of MLs in thetrial by Williams et al. in comparison to the Australian trial.

Page 3: Comment on “A comparison of persistent anthelmintic efficacy of topical formulations of doramectin, eprinomectin, ivermectin and moxidectin against naturally acquired nematode infections

Letter to the Editor / Veterinary Parasitology 112 (2003) 255–257 257

• As all animals (except untreated) were treated with pour on there is an increased likelihoodof grooming leading to ML intake compared to the Australian trial as only half the animalsin the Australian trial were treated with pour-on ML.

We agree with the finding of Williams et al. in terms of the change in nutrition having themajor impact on faecal egg count but believe that more account should be taken of transferof MLs post-administration by a mechanical transfer or ‘licking affect’. This may have im-portant ramifications for future trial design and be important for observance of withholdingperiods where treated animals are kept close to cattle yards after ML administration andmixed with animals for sale resulting in detectable levels of endectocide in beef products.As the calculation of FEC reduction relies on the untreated group remaining free from alltreatments, transfer of MLs is also very important in the calculation of this index and mayartificially reduce the performance of the products used in an experiment where transferoccurs.

References

Alvinerie, M., et al., 1995. J. Chromatogr. 674, 119–124.Laffont, C.M., et al., 2001. Int. J. Parasitol. 31 (14), 1687–1692.Williams, J.C., et al., 1999. Vet. Parasitol. 85, 277–288.

Stuart BarberCentre for Animal Biotechnology

University of Melbourne, Parkville 3052, AustraliaCorresponding author. Tel.:+61-3-8344-4440; fax: 61-3-9347-4083

E-mail address: [email protected] (S. Barber)

Michel AlvinerieLaboratoire de Pharmacologie-Toxicologie

INRA, Toulouse, France

Received 24 July 2002