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Anthelmintic efficacy of complex solid dispersion based on Fenbendazole and Niclozamide against dictyocaulosis and trichuriosis of sheep
Abstract
The purpose of the research is to study the anthelmintic efficacy of complex solid dispersion of fenbendazole and niclozamide against dictyocaulosis and trichuriosis of sheep.
Materials and methods . The complex solid dispersion was obtained by mechanochemical processing of fenbendazole (FBZ), niclozamide (NZM) and polyvinylpyrrolidone (PVP) substances in the ratio of 2 : 20 : 78. The obtained samples of solid dispersion were studied for nematocidal activity on sheep naturally infected with Dictyocaulus filaria and Trichuris ovis. The solid dispersion was tested against dictyocaulosis of sheep at a dose of 2 mg/kg and against trichuriosis at doses of 2, 4 and 6 mg/kg according to FBZ.
Results and discussion . The complex dispersion based on FBZ, NZM and PVP showed 98.9% efficacy against dictyocaulosis of sheep at a dose of 2 mg/kg according to FBZ. The basic preparation – a mechanical mixture of FBZ and NZM at the same dose revealed 25.8% effect. Against trichuriosis of sheep, 98.7; 93.5 and 78.8% efficacy of complex solid dispersion was obtained at doses of 6, 4 and 2 mg/kg according to the active substance, respectively. The mechanical mixture of FBZ and NZM showed a 24.6% effect at a dose of 6 mg/kg according to FBZ. The dose of the complex solid dispersion – 6 mg/kg according to FBZ is recommended as therapeutic against trichuriosis of sheep.
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A combination of cross-sectional and experimental study was conducted from December 2014 to January 2015 with the objectives of determining the prevalence of gastrointestinal nematodes and evaluating the efficacy of commonly used anthelmintic drugs in different sheep breeds in Areka agricultural research center sheep breed improvement farm, Wolayita, Southern Ethiopia. Prevalence study was conducted on the total of 229 sheep on station, belonging to 3 different breeds and the fecal egg count reduction test (FECRT) was used to evaluate the efficacy of anthelmintics. For the anthelmintic efficacy trial, a total of 72 sheep; 24 sheep for each breed were selected based on their higher fecal egg count (FEC) (> 150 eggs).The sheep were randomly assigned in to four groups for each breed. Anthelmintics tested were Albendazole, Tetramizole and Ivermectin for each group of sheep breed. From the total 229 different sheep examined, the overall prevalence of one or more gastrointestinal parasites was 86.6%. Individual breed prevalence was 90% for pure dorper, 92.9% for cross bred and 84.2% for local indigenous breed Predominant worm species were strongyle (71.9%), Trichuris (1.5%) and 26% of the positive specimens were harboring multiple worm species. Evaluation of the efficacy of anthelmintic by using FECRT revealed that Ivermectin and Albendazole did show resistance while Tetramizole was 100% effective against parasite treatment in all sheep breeds. Therefore the farm should practice strategic deworming system to reduce the problem of anthelmintic resistance and more controlled experimental trials that consider different season, agro ecology and using more sensitive methods like egg hatch and larval motility assay with varieties of anthelmintic brands to complement and support this finding.
Background
Due to the fact that animal parasitic diseases often occur in the form of mixed infections, it is necessary to use complex drugs with a combination of active substances that act against different classes of helminths. Fenbendazole has a wide spectrum of nematocidal action and is less effective against cestodes. Considering that sheep are often infected with both gastro-intestinal nematodes and cestodes, a complex drug based on fenbendazole, niclosamide with polyvinylpyrrolidone polymer, was developed using mechanochemical technology in order to increase its solubility and bioavailability and reduce the dosages and side effects.
Objective
This study aimed to evaluate the influence of mechanochemical technology on the efficacy of complex solid dispersions of anthelmintics against cestodoses and nematodoses.
Methods
The influence of different types of mills (roller and planetary mills), levels of energy intensity (20, 40, 60 g), and component ratio (2:20:78; 3:30:67; 4:40:56) during mechanochemical processing was studied on the anthelmintic efficacy of complex solid dispersions of fenbendazole, niclosamide, and polyvinylpyrrolidone in laboratory models of trichinellosis and hymenolepiosis of white mice, and on sheep naturally infected with helminths.
Results
The efficacy of complex solid dispersions obtained in the planetary mill was higher than the activity of dispersions obtained in a roller mill. It showed 87.5, 96.36, 83.77, and 99.39% efficacy, respectively, against experimental trichinellosis, hymenolepiosis of white mice, gastrointestinal nematode infection and monieziosis of sheep at a ratio of 2:20:78. The basic drug – fenbendazole demonstrated 31.37 and 22.77% activity against experimental trichinellosis and gastro-intestinal nematode infection of sheep. The basic drug, niclosamide, showed 36.37% efficacy against hymenolepiosis in mice and 28.31% against monieziosis in sheep. It was established that with an increase in the energy intensity level of the planetary mill (20, 40, and 60 g), the decrease in the efficacy of solid dispersion occurred from 73.90 to 59.12% against T. spiralis and from 92.73% to 79.81% against H. nana.
Conclusion
The use of mechanochemical technology for the production of solid dispersions of fenbendazole and niclosamide with polyvinylpyrrolidone makes it possible to increase the anthelmintic efficacy by 2.7–3 times compared to the activity of basic substances. It was noted that the complex solid dispersions of anthelmintics obtained in a planetary mill had 7.51–10.17% greater activity in comparison with the samples obtained in a roller mill. The most optimal ratio of active substances was 2:20:78 at a 20 g level of energy intensity of the planetary mill.
The first edition of the W.A.A.V.P. anthelmintic guidelines for ruminants was published in 1982. Since then improved parasitological procedures have been developed, new therapeutic and prophylactic products have appeared requiring different test methods, and registration authorities are requesting more detailed record keeping and data validation. This second edition addresses these developments and fulfills the original goal of publishing guidelines for high quality, scientifically valid testing standards for trials that would be accepted as proof of efficacy by registration authorities regardless of country of origin.
This second edition includes updated guidance on standard parasitological procedures, dose titration, dose confirmation and clinical trials, and provides guidelines for evaluating products for efficacy against anthelmintic resistant parasites, persistence of activity and prophylactic activity. Tests for efficacy against nematodes, trematodes and cestodes are included.
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