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RPCV (2015) 110 (593-594) 65-68

Summary: The administration of oral anthelmintics with the head of small ruminants raised above the topline results in direct deposition in the abomasum and with head aligned with the top-line the drug first reaches the rumen. Deposition of certain active principles directly into the abomasum results in faster absorption and clearance with drug efficiency reduction. The aim of this ex-periment was to evaluate the effect of esophageal groove stimu-lation in oral anthelmintic efficiency in sheep. The experiment consisted of two stages and 60 sheep were used. In stage 1, an efficacy test was performed with the active principles moxidec-tin, ivermectin, levamisol disofenolat, oxfendazol and levamisol hydrochloride. The levamisol disofenolat presented higher effi-cacy and it was used in stage 2. In T1, the anthelmintic was ad-ministered with the animal’s head raised, stimulating esophageal groove, in T2 it was administered with the animal’s head aligned with topline and T3 was not medicated. In both stages, it was performed the tests egg count per gram of feces and fecal culture on day 0, 7 and 14. Efficiency of T1 was 87 and 75% and T2 was 92 and 91% for 7 and 14 days, respectively, with no significant difference. Esophageal groove stimulation had no influence on active principle effectiveness.

Key-words: endoparasites, gastrintestinal parasites, parasite re-sistance, pharmacological

Resumo: A administração de antihelmínticos orais com a cabe-ça de pequenos ruminantes erguida acima da linha do dorso re-sulta em deposição direta no abomaso, enquanto e com a cabeça alinhada a linha do dorso o medicamento atinge primeiramente o rúmen. A deposição de determinados princípios ativos direta-mente no abomasso resulta em absorção e eliminação em menor período, com redução na eficácia do medicamento. O objetivo deste experimento foi verificar o efeito da estimulação da go-teira esofágica na eficácia de antihelmíntico oral em ovinos. O experimento foi constituído de duas etapas e foram utilizados 60 ovinos. Na etapa 1 foi realizado um teste de eficácia com os princípios ativos moxidectina, ivermectina, disofenolato de levamisole, oxfendazole e cloridrato de levamisole. O disofeno-lato de levamisole apresentou maior eficácia e foi utilizado na etapa 2. No T1, o antihelmíntico foi administrado com a cabeça do animal erguida, com estimulação da goteira esofágica, no T2 foi administrado com a cabeça alinhada ao dorso e o T3 não foi medicado. Em ambas etapas foram realizados os testes de con-tagem de ovos por grama de fezes e coprocultura nos dias 0, 7 e 14. A eficácia do T1 foi de 87 e 75% e do T2 foi de 92 e 91%

para os dias 7 e 14, respectivamente, sem diferença estatística. A estimulação da goteira esofágica não apresentou influência sobre a eficácia do princípio ativo.

Palavras-chave: endoparasitas, farmacologia, parasitas gastrin-

testinais, resistência parasitária

Short communication

Shortly after the beginning of animal’s domestica-tion, mankind recognized the need to combat unwant-ed endoparasites due to its devastating nature inside the organism (Molento, 2004). The pharmaceutical industry has solved this problem by manufacturing anthelmintic drugs for oral, injectable and intra-ru-minal administration. The injectable form, despite the advantages as practical application and faster method, yet it is not commonly used by most traditional farm-ers. In the state of Rio Grande do Sul, the preference for oral anthelmintic administration is mainly due to the culture of farmers and because of the elimination of abscess formation risk at the site of application. Studies indicate that the route of administration (oral, injectable or intraruminal) does not change the active principle efficiency (Mingardo, 2005), determining just preference of each owner, farmer or professional. However, there are variables with few studies that can change the products efficiency even in population of susceptible parasites, such as: rumen repletion, fast-ing, alimentation type and esophageal groove stimu-lation.

The esophageal groove is a tube formed by the smooth muscle of rumen and reticulum that when stimulated connects the esophagus directly to the abomasum, without passing through the rumen, which is a fermentation chamber of ruminants. The esophageal groove is activated when the animal’s head is extended above the horizontal line of the dorse (Molento, 2004), in other words with the head up. The activation reflex of the esophageal groove al-lows the anthelmintic to be delivered directly to the

Effect of esophageal groove stimulation in oral anthelmintic efficacy in sheep

Efeito da estimulação da goteira esofágica na eficácia de antihelmíntico oral em ovinos

Fernanda C.C. Santos1*; Fernanda S.F. Vogel1

1Laboratório de Doenças Parasitárias (LADOPAR), Universidade Federal de Santa Maria (UFSM), Avenida Roraima, 1000, Bairro Camobi, Santa Maria, Rio Grande do Sul (RS), Brasil.

*Correspondência: [email protected] Tel: +55 (55) 3220-8071

Santos F. et al. RPCV (2015) 110 (593-594) 65-68

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abomasum, which determines that the drug has no contact with ruminal chamber. In certain active prin-ciples, this activation results in faster absorption and clearance with reduction efficacy against endopara-sites (Prichard and Hennessy, 1981).

This study aims to evaluate the effect of esopha-geal groove stimulation in oral anthelmintic efficacy in sheep.

The experiment consisted of two stages conducted in the Colégio Politécnico da Universidade Federal de Santa Maria (UFSM) installations, Rio Grande do Sul, Brazil. It was used 60 sheep, both sexes, aged from 2 to 4 years, crossbred Texel x Ilê de France.

Step 1 consisted of an anthelmintic efficacy test, to exclude the possibility that results about esophageal groove were related to parasite resistance. For this, the sheep were randomly divided into six groups of ten animals, each group representing an anthelmintic drug to be tested. The anthelmintics tested were mox-idectin (T1), ivermectin 1% (T2), levamisol disofeno-lat (T3), oxfendazol (T4) and levamisol hydrochloride (T5). In the control group (T6) no anthelmintic was administered to animals. The doses were used follow-ing the manufacturer’s recommendation (Table 1).

Table 1 - Dose and administration route of active principles tested according to group.

Treatment Active Principle Dose Administration

1 Moxidectin 1mL/10 kg BW Oral

2 Ivermectin 1% 2,5mL/10 kg BW Oral

3 Levamisol disofenolat 1mL/10 kg BW Oral

4 Oxfendazol 1mL/9 kg BW Oral

5 Levamisol hydrochloride 1mL/10 kg BW Oral

6 Control - -

BW: bodyweight.

In the second step, the most effectively anthelmintic identified in the preliminary study was used, being the disofenolat levamisol. The step 2 started approxi-mately 2 months after the first step. The sheep were randomly divided into three groups of 20 animals each. In T1, the anthelmintic was administered with the animal’s head in raised position, above the top-line. In T2 anthelmintic was administered with the animal’s head in normal position, aligned with the topline. The control group (T3) was the untreated group.

The animals received all treatments on same day, which is considered day 0. Fecal samples from all sheep were collected at day 0, 7 and 14 for the evalu-ation of egg counts per gram of feces (EPG) and fe-cal pool culture according to the methodology de-scribed by Gordon and Whitlock (1939) and Roberts and O’Sullivan (1950), respectively.

Treatment efficacy was calculated by the EPG re-duction test. Statistical analysis was performed using the Chi-square test.

The results of the EPG reduction performed in step 1 are shown in Table 2. All groups that received an-thelmintics presented a significant EPG reduction at the day 7 and day 14. It was observed statistical dif-ference between treatments in the same days, 7 and 14.

Table 2 - Percentage of reduction, minimum, average and ma-ximum values of EPG from sheep treated with moxidectin (T1), ivermectin (T2), levamisol disofenolat (T3), oxfendazol (T4), levamisol hydrochloride (T5) and control group.

TratamentDay

0 7 14

1 2800 A, a 1262 B, a 1044 B, a

% reduction 54% 62%

Mininum values 200 0 0

Maximum values 4500 4700 4400

2 3183 A, a 2483 B, b 2125 B, b

% reduction 21% 33%



3 2800 A, a 33 B, b 288 B, b

% reduction 98% 89%



4 2166 A, a 2150 B, b 3187 B, b

% reduction 1% 0%



5 3888 A, a 457 B, a 1212 B, a

% reduction 88% 68%



Control 2044 A, a 2787 A, a 3133 A, a

% reduction 0% 0%



Means followed by different capital letters in the same row differ sig-nificantly (p <0.05) by Chi-square test. Means followed by different lo-wercase letters in the same column differ significantly (p <0.05) by Chi-square test. The interaction between treatment and time was significant (p <0.001).

Although it was observed EPG reduction in all treated groups, moxidectin, ivermectin, oxfendazol and levami-sol hydrocloride presented low efficiency according to MAPA (1990). In this herd, the only active principle with high efficiency was levamisol disofenolat.


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In step 2, EPG reduction in the group treated with the head in raised position were 87% at day 7 and 75% at day 14. EPG reduction in the group treated with the head aligned with topline were 92% at day 7 and 91% at day 14 (Table 3). Both treatments presented a signifi-cant EPG reduction at day 7 and 14. There was no sta-tistical difference between T1 and T2 in the same days.

Table 3 - Percentage of reduction, minimum, average and ma-ximum EPG values of sheep treated with levamisol disofenolat being administered with the animal’s head raised (T1), aligned to topline (T2) and control group.

TratamentDay

0 7 14

1 1255 A, a 155 B, a 307 B, a

% reduction 87% 75%



2 2911 A, a 220 B, a 242 B, a

% reduction 92% 91%



Control 1433 A, a 1761 A, b 1330 A, b

% reduction 0% 7%



Means followed by different capital letters in the same row differ signifi-cantly (p <0.05) by Chi-square test. Means followed by different lowercase letters in the same column differ significantly (p <0.05) by Chi-square test. The interaction between treatment and time was significant (p <0.001).

Results of fecal culture of step 2 are demonstrated in Table 4.

Table 4 - Helminthes larvae genera identified in fecal cultures according to treatment, in percentage.

Tratament GenresDay % Reduction

0 7 14 0-7 0-14Haemonchus 78 31 74 60 5

1 Cooperia 2 9 3 0 0

Trichostrongylus 20 27 3 0 85

Bunostomum - 33 8 0 0

Chabertia - - 11 - 0

Haemonchus 91 48 78 47 14

2 Cooperia 2 4 22 0 0

Trichostrongylus 4 48 - 0 100

Ostertagia 3 - - 100 100

Haemonchus 94 90 90 - -

Control Cooperia - 5 4 - -

Trichostrongylus 6 5 6 - -

According to the Brazilian legislation (MAPA, 1990), EPG reduction below 90% suggests the pres-ence of parasite resistance to the compound. In step 1, levamisol disofenolat was the only medicine with a value higher than 90%, suggesting the severity of the scenario in this herd, since most of the products tested are inefficient in endoparasites control and continue to be used by local farmers inadvertently.

Results from step 2 indicates that on day 7 there was no significant difference in the anthelmintics efficacy, however on day 14 the efficacy of the group with the head raised was less than expected. This could be ex-plained by passage through the rumen with a conse-quent increase in absorption rate and clearance of the drug, reducing the action time and the residual effect of this on endoparasites.

In goats, administration of certain compounds di-rectly into the abomasum results in faster absorption, metabolism and excretion with consequent efficacy reduction (Vázquez and Mañes, 2000). The shorter parasites are expose to the active principle, the lower treatment efficiency.

Some molecules do not suffer from biotransforma-tion in the rumen. Benzimidazol drugs do not toler-ate abomasal deposition and it is necessary to pass through the rumen, otherwise it may result in early product degradation, reducing elimination period of endoparasites (Molento, 2004). When the product re-mains in contact with the rumen flora it is biodegraded and metabolized by other gastrointestinal chambers, in order to be absorbed and reached the bloodstream. Trichlorfon is a drug indicated to be administrate prior to products that stimulates the closure of the esopha-geal groove, in order to present best antiparasitic ac-tion, in other words it needs to pass through the rumen (Xavier and Spinosa, 2008). However its use in sheep is limited due to high toxicity, being its use avoided by farmers.

In addition it has also been shown that oesophageal groove reflex operates to a greater extent in adult goats than in sheep and thus may influence drench uptake (Sangster et al., 1991). This phenomenon could re-duce the viability of oral anthelmintic and potentially increased the number of resistant parasites.

In relation to pharmacodynamics, levamisol cause a spastic paralysis in nematodes due to cholinesterase inhibition, determining a stable contraction muscular, which facilitates parasites removal (Kohler, 2001). Disofenol is a drug which interferes in the respiratory metabolism of helminths, blocking energy production due to inhibition of mitochondrial oxidative phospho-rylation, causing depletion of energetic reserves and resulting in death by starvation (Xavier and Spinosa, 2008). Both levamisol and disofenol are rapidly ab-sorbed after orally administration by the gastrointesti-nal system, and this experiment suggests that levami-sol disofenolat presents similar action when adminis-tered with or without esophageal groove stimulation.


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In this sheep herd, the anthelmintic which presented higher efficiency was levamisol disofenolat, a new mol-ecule in the market and therefore never been used in these animals. Levamisol disofenolat administered in sheep with or without esophageal groove stimulation presented similar efficiency. Regardless esophageal groove stimulation, it is important to perform a pre-vious evaluation of anthelmintic efficacy in the flock before any drug administration. In the present study, esophageal groove stimulation had no influence in the anthelmintic efficiency in sheep.

Acknowledgments

The authors thank the companies Ouro Fino, Ibasa, Biovet, Merial and Fort Dogde for antihelminth supply.

Bibliography

Ministério da Agricultura e Pecuária e Abastatecimento (1990). Portaria n. 90, de 04 dez. Normas para produção, controle e utilização de produtos antiparasitários. Diário Oficial, 1, 2.

Gordon HMCL, Whitlock HV (1939). A new technique for counting nematode eggs in sheep faeces. Journal of the Council for Scientific and Industrial Research, 12, 50.

Kohler P (2001). The biochemical basis of anthelmintic ac-

tion and resistance. International Journal for Parasitology, 31, 4, 336-345.

Mingardo M (2005). Vermifugação: planejamento garante eficiência. Revista Rural, 91, 1-5.

Molento MB (2004). Resistência de helmintos em ovinos e caprinos. Revista Brasileira de Parasitologia Veterinária, 13, 1, 82-85.

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Roberts FHS, O’Sullivan PJ (1950). Methods for egg counts and larval cultures for strongyles infecting the gastro-in-testinal tract of cattle. Australian Journal of Agricultural Research, 1, 99-102.

Sangster NC, Rickard JM, Hennessy DR, Steel JW, Collins GH (1991). Disposition of oxfendazole in goats and efficacy compared with sheep. Research in Veterinary Science, 51, 3, 258-263.

Vázquez FR, Mañes A (2000). Prevención y control de lãs principales helmintosis del ganado ovino. Revista Nuestra Cabaña, 5,14-15.

Xavier FG, Spinosa HS (2008). Toxicologia dos praguici-das anticolinesterásicos: organofosforados e carbamatos. In: Spinosa HS, Górniak SL, Palermo-Neto J. Toxicologia aplicada à medicina veterinária. 1st edn. Barueri: Manole, 291-311.

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