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Steffan P. (1,2), Fiel C. (1), Reggi J. (2), Riva E. (1, 3) y Guzmán M. (1,3)

(1) Area of Parasitology, Faculty of Veterinary Science, UNCPBA, Campus Universitario (7000) Tandil, Argentina; (2) Novartis Argentina, Animal Health; (3) Fellowship CONICET- Argentina. Tel: +54 02293 439850 Mail: steffan@vet.unicen.edu.ar

IntroductionResistance of gastrointestinal parasites of sheep to several broad-spectrum anthelmintics has been well documented in Argentina (1, 2) and in nematode populations of the subtropical area of this country in particular (3). Monepantel is the first compound (4) from the amino-acetonitrile derivative class of anthelmintics (5) to be developed as an anthelmintic for sheep (ZolvixTM, Novartis Animal Health). Its efficacy from controlled studies conducted in Latin America has been previously reported (6, 7). The results on the efficacy of monepantel against multiple anthelmintic resistant nematodes of sheep naturally infected in the subtropical area of Argentina are presented here.

Worm counts of animals from G1 and G2 are shown in Table 1 and 2respectively, and the efficacy of monepantel is presented in Table 3.

Table 1. Worm counts in lambs treated with monepantel (2.5 mg/k.b.w.) (G1)

Materials and methodsLocation of the trial and antecedents of anthelmintic resistanceThe trial was conducted in a sheep farm located at the Corrientes province in the subtropical area of Argentina. The nematode population had previously been tested for susceptibility to anthelmintics and results indicated a high level of resistance to ivermectin, benzimidazole derivates, levamisole and closantelwith Haemonchus spp and Trichostrongylus spp. mainly involved.

Experimental animals and treatmentsFourteen female weaned lambs, of Polwerth breed, weighing 29 kg on average were selected from the flock according to the number of nematode eggs in the faeces (e.p.g.) (8). The lambs were weighed, identified and divided into two comparable groups of seven animals each and treated as follows: G1 (e.p.g.: 2574) with monepantel orally at the dose rate of 2.5 mg/ kilo body weight (k.b.w.) and G2 (e.p.g.: 2520) as nontreated control group with saline solution in a volume equivalent (1 ml/ 10 k.b.w.). G1 and G2 remained separated on concrete floored pens and fed lucerne pellets and fresh water ad libitum up to necropsy.

Faecal samples, worm counts and determination of efficacyFaecal samples were collected on day 4 after treatment for epg counts and all animals were necropsied on day 8 after treatment. Digestive tracts were removed for worm recovery, identification and counting from treated and non treated lambs to determine the efficacy of monepantel following the Guidelines of WAAVP (9)Efficacy of the test compound was calculated by comparison of the parasite counts (geometric mean) from treated and control groups following this formule: Efficacy % = [(control - treated) control (-1)] . 100; the Wilcoxon test for statistic analysis was used (10).

References(1) Eddi C, Caracostantogolo J, Peña M, Schapiro J, Marangunich L, Waller PJ, Hansen JW (1996) The prevalence of anthelmintic resistance in nematode parasites of sheep in Southern Latin America: Argentina. Vet Parasitol 62:189–197(2) Caracostantogolo J, Castaño R, Cutullé Ch, Cetrá B, Lamberti R, Olaechea F, Ruiz M, Schapiro J, Martínez M, Balbiani G, Castro M (2005) Evaluación de la resistencia a los antihelmínticos en rumianatesen Argentina. ISBN: 92-5-305428-X; ISSN: 1014-1200, FAO Producción y Sanidad Animal, Estudio, Resistencia a los antiparasitarios internos en Argentina, 7–34(3) Romero J, Boero C, Vázquez R, Aristizabal T, Baldo A (1998) Estudio de resistencia a antihelmínticos en majadas de la mesopotamia argentina. Rev Med Vet 79:342 – 346.(4) Kaminsky R, Ducray P, Jung M, Clover R, Rufener L, Bouvier J, Schorderet Weber S, Wenger A, Wieland-Berghausen S, Goebel T, Gauvry N, Pautrat F, Skripsky T, Froelich O, Komoin-Oka C, WestlundB, Sluder A, Mäser P (2008) A new class of anthelmintics effective against drug-resistant nematodes. Nature 452:176–180(5) Kaminsky R, Gauvry N, Schorderet Weber S, Skripsky T, Bouvier J, Wenger A, Schroeder F, DesaulesY, Hotz R, Goebel T, Hosking BC, Pautrat F, Wieland-Berghausen S, Ducray P (2008) Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate. Parasitol Res 103:931–939(6) Bustamante M, Steffan P, Bonino Morlán J, Echevarria F, Fiel C, Cardozo H, Castells D. and Hosking B (2009). The efficacy of monepantel, an amino-acetonitrile derivative, against gastrointestinal nematodes of sheep in three countries of southern Latin America. Parasitol Res (2009) 106:139–144(7) Steffan P, Sánchez E, Entrocasso C , Fiel C, Lloberás M, Riva E y Guzmán M (2011). Eficacia de Monepantel contra Nematodes de Ovinos con Resistencia Antihelmíntica Múltiple en la Región Templada de Argentina. Vet. Arg., Vol XXVIII, N° 273(8) Roberts, F.; O'Sullivan P.; 1949. Methods for egg count and larval cultures for strongyles infesting gastrointestinal tract of cattle. Aust. J. Agric. Res., 1: 99-102.(9) Wood IB, Amaral NK, Bairden K et al. Second Edition of Guidelines for Evaluating the efficacy of Anthelmintics in Ruminants (Bovine, Ovine, Caprine); 1995. Vet. Parasitol. 58:181-213(10) SAS Institute Inc., SAS/STAT User’s Guide, Version 6, Foutrh Edition, Volumen 2, Cary, NC: SAS Institute Inc., 1989, 846 pp.

Efficacy of Monepantel against multiple anthelmintic resistant nematodes of sheep in the subtropical area of Argentina

aapavet

2,3500000G. mean5,7100000Average

00000021120000002012000000203000000216000000208000000205000000218

CooperiaTrichostrongTrichostrongTeladorsagHaemonche.p.g.SMALL INTESTINEABOMASUMLamb N°

Table 2. Worm counts in lambs of the nontreated control group (G2)

10095,712327,243968,391360,701102,342732,22G. mean12485,7126004428,57150012003071,43Average

2400270041002800150035002141620045006200170023002400202560022001900140013001300207840035005800160010003800209

210002600760015009004900213142008002600900700430020419600190028006007001300212

CooperiaTrichostrTrichostrTeladorsHaeme.p.g.SMALL IINTESTINEABOMASUMLamb N°

Table 3. Efficacy (%) of monepantel against multiple resistant nematodes

* P< 0.05

> 99*100*100*100*100*100*Efficacy(%)

CooperiaTrichostrongTrichostrongTeladorsagHaemonche.p.g.SMALL INTESTINEABOMASUM

The efficacy of monepantel was 100% against Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus axei, Trichostrongyluscolubriformis, Cooperia pectinata and Cooperia punctata (P< 0.05). E.p.g. counts in group G1 were negligibles at day 4 after treatment onwards (P< 0.05).

Conclusions

These results indicate that monepantel showed a high efficacy against multiple anthelmintic resistant nematodes of sheep of the subtropical area of Argentina, being specially recommended to be used in a rotational scheme of drugs. No adverse effects related to treatment with monepantelwere noted.

Results