EFFICACY OF A BOLUS IN FIELD INFECTIONS OF BOVINE Taylor Sm, Mallon T, Green Wp

To cite this version:

Taylor Sm, Mallon T, Green Wp. EFFICACY OF A LEVAMISOLE BOLUS IN FIELD INFEC- TIONS OF BOVINE NEMATODES. Annales de Recherches Vétérinaires, INRA Editions, 1988, 19 (2), pp.111-118. ￿hal-00901813￿

HAL Id: hal-00901813 https://hal.archives-ouvertes.fr/hal-00901813 Submitted on 1 Jan 1988

HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. EFFICACY OF A LEVAMISOLE BOLUS IN FIELD INFECTIONS OF BOVINE NEMATODES

TAYLOR SM, MALLON T GREEN WP

Veterinary Research Laboratories, The Farm, Stormont, Belfast, BT4 3SD Northern lreland

received 07/04/87, accepted 15/07/87

Résumé

RECHERCHE DE L’EFFICACITÉ D’UN DIFFUSEUR DE LÉVAMISOLE AU COURS D’INFECTIONS SUR LE TERRAIN PAR , ONCOPHORA ET DICTYDCAULUS VIVIPARUS. - Quarante-quatre veaux indemnes de parasites ont été répartis en huit groupes, quatre de six veaux et quatre de cinq veaux. Deux des groupes de six veaux ont reçu un diffuseur contenant 22 g de lévamisole sous une forme conçue pour libérer l’anthelmintique pendant 90 jours. L’un des groupes de veaux traités a été mis à l’herbe début mai en même temps qu’un des groupes de veaux non traités sur un terrain contaminé avec 0 ostertagi et C oncophora, et l’autre groupe de veaux traités a été sorti avec les témoins sur une pâture connue pour avoir les mêmes espèces de parasites plus D viviparus. Mi-août, tous les veaux mis à l’herbe ont été abattus et leur nombre de vers a été compté. En même temps, les autres groupes (non traités) ont été amenés sur les mêmes pâtures et ont été utilisés comme traceurs du niveau d’infestation. Après être restés sur la pâture pendant un mois, ils ont été rentrés, abattus et leur nombre de vers compté. Les nombres d’oeufs dans les fecès des veaux traités ont été moins importants que ceux des témoins jusqu’à la fin du mois de juillet. Les veaux non traités, qui ont séjourné dans les enclos infestés par D viviparus, ont été sévèrement affectés par une bronchite d’origine parasitaire, tandis que les veaux traités, bien qu’étant infestés, n’ont pas présenté de symptômes cliniques. Chez les veaux mis à l’herbe, la charge parasitaire d’O ostertagi a été réduite de 65 à 67 % et celle de C oncophora de 97 % comparative- ment aux veaux non traités. Chez les veaux traceurs, il n’y a aucune différence dans les charges parasitaires d’O ostertagi et de D viviparus mais de grandes différences ont été établies dans le nombre de C oncophora. Il a été conclu que le traitement avec le diffuseur a supprimé efficacement la multiplication de Concophora mais que son efficacité sur O ostertagi et D viviparus n’a pas été suffisante pour empêcher une contamination des pâtures par ces nématodes à la fin de l’été. Une protection suffisante a cependant été observée contre les manifestations cliniques de la bronchite vermineuse malgré une contamination sévère.

Disruption of the normal spring and summer core (Morgan and Rowlands, 1986, Proc l4th World pattern of multiplication of gastro-intestinal parasi- Cong Dis Cattle, 1:136-140). In general these devi- tes of cattle in temperate areas can be achieved by ces are arranged to be effective in minimising the regular administration of (Pott et al establishment and egg laying capacity of the com- 1974, Proc 3rd Int Cong Parasitol 2:747). The mon pathogenic nematodes for a minimum of anthelmintics can be given by a series of conven- sixty and a maximum of one hundred and thirty tional single doses, by periodic addition to drinking days. The method used for the prolonged adminis- water (Downey and O’Shea 1977) or by the use of a tration depends on the chemical characteristics, device which after a single application to individual pharmacokinetics, potential toxicity and the possi- will release at a predetermi- bility of undesirable tissue residues as well as the ned rate. The methods of release of active ingre- efficacy as an anthelmintic. Of the common anthel- dient have been shown to be either continuous mintic compounds (Morgan and slow release with gradual decay of the quantity of Rowlands, 1986, Proc 14th World Cong Dis Cattle, anthelmintic released (Armour et al 1981, Jacobs 1:136-1401, pyrimidines (Armour et al 1981) and et al 1981), continuous administration with an (Baggot et al 1986, Proc 14th World abrupt cut-off (Laby 1978 Australian Patent Appli- Cong Dis Cattle, 1 :160-165) have been shown to be cation 35908/78, Baggot et al 1986, Proc 14th World capable of adaptation to this form of use, but untill Cong Dis Cattle, 1:160-165) or periodic pulsed now there have been no reports using release of a therapeutic dose of anthelmintic trig- imidothiazoles such as levamisole. This paper gered by the rate of corrosion of a central alloy reports on the effectiveness of a bolus which gives continuous release of levamisole for approximately Experimental design ninety days on experimental field infections of Forty-four calves of Friesian type were purchased shortly calves with onco- Ostertagia ostertagi, Cooperia after birth from dairy farms and reared on milk, milk phora and Dictyocaulus viviparus. substitute, concentrates hay and silage until approximately twelve weeks of age. At that time, the calves were divided into two groups, the first group of twenty-four to go to Materials and Methods grass on 1 May and graze until 15 August, the second (untreated) to go to grass on 15 August and graze for one month which time would act as tracers of the Slow release bolus (Chronomintic Mk III-Virbac Ltdl. The during they level of infection propagated by the original calves. bolus consists of a 22.2 g of levamisole hydrochloxide moulded with ethylene vinyl acetate copolymer and iron The first group was further divided into four groups of fillings. The total weight is 152 g and the bolus is cylindrical six. Groups 1 and 3 acted as untreated controls and the with a height of 105 mm and base diameter 27 mm ; a calves in groups 2 and 4 were given a bolus on 29 April, two central cylindrical core of diameter 10 mm is removed from days before they went to grass for the first time. They were its entire length which leaves an open tube from one end to X-rayed on the following day to ensure that all had a bolus the other. It is greenish-gray in colour and has a plastic in position. At that time, groups 1 and 2 were placed on appearance. adjoining paddocks separated by a ten metre space. The paddocks were part of a field on which cattle inf ’cted with propagation of each parasite on the grazing areas. After O ostertagi and C oncophora had grazed during the pre- grazing for one month they were brought indoors, retained vious year. Groups 2 and 4 were placed on two similar for ten days to allow maturation and hence easier counting paddocks approximately six hundred metres from the and identification of the nematodes present, and then others, on which calves infected with O ostertagi, C onco- slaughtered. phora and Dictyocaulus viviparus had grazed during the the first two weeks at in order previous year. During grass Autopsy procedures to ensure adequate infections were initiated in addition to those naturally present, the calves in groups 1 and 2 were Calves were euthanised with intravenous sodium pento- given oral doses of 0 ostertagi and C oncophora infective barbitone. The carcases were carefully opened and the larvae on five occasions, so that in toto each calf received abomasa and small intestines isolated and ligatured. The approximately 2 000 larvae of each species. The same num- viscera and lungs were then removed and the worms in ber of larvae of these species was given to the calves in each organ counted using standard parasitologicaltechni- groups 3 and 4 which in addition were given 25 infective ques, including that for D viviparus larvae where appro- larvae of D viviparus with each dose of the intestinal priate. The number of worms in intestines and abomasa species, so that in toto they received 125 lungworm larvae. was estimated by counting these observed in a five per cent of the total contents. During the period at grass, the calves were weighed aliquot organ monthly and had faeces and blood samples taken every two weeks for estimation of worm egg count (Dunn 1978) Statistical techniques and plasma pepsinogen (Mylrea and Hotson 1969). Grass samples for estimation of numbers of infective larvae were The mean worm counts and faecal egg output for each taken monthly and examined using the technique of Parfitt group were obtained using the logarithm of (count + 1) and (1958). On 15 August, the original calves were brought in, compared by Student’s test adjusted for small groups using retained for ten days and euthanised. On the day that they the logarithmic values. For plasma pepsinogen concentra- were brought in from the paddocks, five calves from the tions absolute arithmetic values were used. Weight changes original division and which had been retained indoors were estimated by calculating percentage increase, in rela- under parasite free conditions were put on to each paddock tion to weight at the start of the grazing period and compa- to act as non-immune tracers for estimation of the level of red after arc sin transformation. Results culty other than a slight cough. They were treated with antibiotic from 16 July and 30 July for 1. Field observations 1.5 weeks to avoid the possibility of superimposed bacterial pneumonia which might exacerbate the (a) Resident calves 1/5-15/8/86). (grazing condition and seriously interrupt the investigation. The progress and growth of the calves in groups 1 and 2 were uneventful. No clinical disease was noted. There were marked differences between groups 3 and 4. The calves in group 3 (control) were affected by lungworm infection after approxi- mately five weeks grazing. Three were seriously affected and despite constant antibiotic treatment (anthelmintic was not given) to reduce the effect of secondary bacterial pneumonia, they died. The first died on 26 June (Day 58) another on 16 July (Day 78) and the third on 29 July (Day 911. Because they were fairly near the end of their grazing period and had excreted both gastro-intestinal worm eggs and lungworm larvae they were not replaced, as the replacements would not have had time to excrete further infection. Group 4 (Bolus- treated), although infected with lungworm did not display clinical symptoms. (b) Tracer calves (grazing 11/8-15/9). A similar pattern followed-fairly normal health in groups 1, 2 and 4 but severe lungworm infection in group 3, which caused the death of one calf. The tracers in group 4 paddock also developed lungworm infection.

2. Faecal worm egg output (a) From the day of going to grass until the end of July (Day 92) the faecal egg counts of the calves which had received an intra-ruminal bolus were significantly less than the untreated control calves. Group geometric means are shown in table 1. For the last two weeks of their grazing period although the results from treated calves were better there were no statistical differences between treated and untreated cattle. This was not necessarily an indica- tor that the same numbers of worms were present in both as it is well known that there is an inversely proportional relationship between worm numbers present and individual female egg output. (b) Lungworm larvae (table 2). Control calves were first observed to excrete larvae on Day 27. Excretion was intermittent although three suffered fairly heavy infections, from which 3/6 subsequently died. In contrast only one of the treated calves excreted larvae early in the grazing period (Day 33). However, the other calves subsequently underwent autoinfection pre- sumably from larvae excreted by that calf or from previous infection on the paddock, and by late July and early August all were infected to the extent that they were observed to excrete larvae but not to become clinically affected by respiratory diffi- 3. Weight changes (Resident calves) (fig 1) increase in contamination took place earlier in the control than in the bolus paddocks, and resulted in Although there were similarities between the higher worm counts in the resident calves grazing pattern of weight changes between groups 1 and 2 on them. The number of larvae increased around and groups 3 and 4, the presence of D viviparus in the beginning of August and by September there the latter had serious repercussions on group 3 : was little difference between control and bolus to 34) controls Initially (up Day grew slightly areas either in grass larvae or in the resultant more than treated the difference calves, although tracer worm counts. was not statistically significant. Thereafter, lung- worm infection had a significant effect, firstly in (b) Cooperia oncophora (table 4) group 3 calves which lost weight and of which There were marked differences between the three died. At that time, group 4 (treated) calves areas grazed by control and bolus-treated calves, showed an increase in weight at a significantly with the former having much higher counts until greater rate. After Day 93 however, the survivors in the last sampling. The differences were reflected in group 3 which were then immune to lungworm the tracer worm burdens. grew more quickly than those in 4, which at group (c) Dictyocaulus viviparus (table 5) that time were infected by lungworm the advent of which had been delayed but not prevented by the A similar pattern was observed except that the activity of the bolus. larval contamination which was higher in the con- trol paddock during August and September was not reflected in differences in the numbers of 4. Infective larvae on paddocks any lungworms picked up by the tracer calves. The numbers of larvae recovered were lower than normal and did not accurately reflect the quantity present as picked up by the calves. This 5. Observations at autopsy phenomenon has been observed before in very (a) Bolus recovery wet years such as this was, and may reflect that All six boluses were recovered from 2, but larvae may be washed down onto the soil, that group five out of six from 4. All boluses were increased grass growth may dilute the concentra- only group recovered from the reticulum which showed no tions and that the techniques employed are not sufficiently sensitive under these conditions. abnormalities. The from which no bolus was retrievable had, as the others, been shown to (a) Ostertagia ostertagi (table 3) have the bolus in position by X-ray photography The infective larvae contamination followed a on the day after administration. A search of the similar pattern to the faecal egg output, in that the field failed to find the missing bolus. The recovered boluses were washed to remove and reduced the viability of any subsequently ruminal contents which were tightly packed within ingested. On the contrary, the burdens of D vivi- the central cylindrical space. They were lightly parus recovered from the three dead calves were dried and then weighed. Their original mean high. weight was 146.2 g, but on recovery they had an (c) Worm burdens of tracer calves increase of 8.45 % to 158.5 ± 0.9 g. (1 ) Abomasa (table 8). As it can be observed, there Worm burdens of resident calves (b) was no statistical difference between the burdens (1) Abomasa (table 8). It can be seen from table 8 of groups 1 and 2, 3 or 4, or groups 1 and 3 that the numbers of 0 ostertagi in the abomasa of combined and groups 2 and 4, the calves with one untreated control calves were considerably larger exception all picking up moderate numbers of than those in the bolus treated calves. The diffe- O ostertagi. rence when all abomasal results are combined was (2) Small intestines (table 9). There were large a reduction of 59.6 % in treated to compared differences in the numbers of C oncophora recove- untreated calves. The overall geometric means red from treated and control calves, with the latter were 14 774 and 5 968 and this diffe- respectively, having significantly greater worm counts (p < 0.001).). rence is < On com- statistically significant (P 0.05). This was further proof of the efficacy of the bolus parison of group 1 and group 2 separately, the against this parasite. reduction was 67.6 %, but the result was just below at the 95 % level. In the significance group 3, only (3) Lungs (table 7). There were no differences results from the survivors were used as at their between the worm counts of D viviparus from both time of death abomasal burdens were still low. groups 3 and 4. With the exceptions of one calf in When to 4 had a reduc- compared group 3, group group 4 the burdens were all very high and produ- tion of 56.1 but it must be out that calf %, pointed ced severe clinical symptoms which necessitated no. 29 from which no bolus was recovered had by the slaughter in extremis of two of group 3 and far the abomasal worm burden in that largest one in group 4. group. If the results from that animal is excluded, it seems reasonable to assume therefore that calves 6. Serum pepsinogen concentrations in which the bolus was retained a reduction of There were small in the O ostertagi of approximately, 65 % could be expec- differences concentra- tions in a ted during a grazing season. the resident calves, reflection of the fact that the abomasal worm counts in control (2) Small intestine (table 9). From examination of although groups were significantly higher, they were not table 9, it is obvious that the presence of the bolus so to produce overt clinical disease. exerted a marked effect on the establishment of sufficiently Cooperia oncophora. Both treated groups had negligible burdens which were highly significantly (P < 0.001) less than those recovered from the Discussion control calves, the overall combined reduction being 99.3 %. Apart from demonstrating the efficacy of this (3) Lungs (tables 6 and 7). The burdens of D vivi- levamisole bolus under experimental conditions in parus recovered from the surviving resident calves the field, this investigation also gave more informa- tion on the differential some nema- of group 3 and 4 were small, presumably because susceptibility of they had developed immunity to the infection and tode species to levamisole. the reaction had removed those worms present The O ostertagi burdens in the resident calves grazing from 1 May until mid August were reduced dose rate at Day 0 was therefore 1.9 mg/kg. At Day overall by 60.7%, although the faecal egg counts 34, the maximum dose would have reduced to 1.57 of combined 0 ostertagi and C oncophora of trea- and 1.69 mg/kg and 1.49 mg/kg. It appears from ted calves were low until Day 103. the results of this experiment that the release rate was too low to be totally effective against O oster- This apparent anomaly may be explained by the but was sufficient to remove all C oncophora. effect of the bolus on C oncophora, which were tagi, of reduced by 97.6 % in the resident and by 96.9 % in Examination of the excretion D viviparus 2) would indicate that a similar effect had the tracer calves, and which is known to be a more (table taken as with prolific egg layer than O ostertagi spp in calves place O ostertagi. and Lancaster Smith Levami- (Mvchel 1970, 1970). These effects were verified in the worm burdens sole in doses of 8 given single therapeutic mg/kg observed in the tracer calves, in which there were et al 1975) removed between 0 and 64 % of (Lyons no difference between the numbers of 0 ostertagi and between 83 O ostertagi fourth stage larvae and D viviparus, but highly significant differences and 93 % of adult O The same treatment ostertagi. between Concophora burdens in treated and con- remove adult C onco- 100 % of both immature and trol calves. phora, indicating that levamisole is more effective against C oncophora than O ostertagi. Further evi- One other interesting observation was made in dence of the moderate effect on 0 ostertagi at this experiment with the levamisole bolus. The 1.5 mg/kg was reported by Hart et al (19691. calves which had been given the levamisole bolus The bolus in this experiment contained 22.2 g of increased in bodyweight at a much greater rate levamisole and was designed for continuous than the controls during the period in which the release for ninety days. The weight of calf for bolus was presumed to be releasing levamisole. In intended use is 100 kg upwards. In this experiment, the absence of any parasitological or other husban- the mean liveweights of treated groups at the dry explanation, the conclusion was reached that it beginning of the grazing period were 129.3 and might be attributable to the immunomodulating 128.5 kg respectively, rising to 156.8 and 145.7 kg effects of levamisole (Symoens and Rosenthal on day 34, 179.7 and 65.3 kg on day 63 and 202.5 1977), and might result in an unexpected benefit and 177.7 kg at Day 93. The maximum theoretical from its use.

Abstract

Forty four parasite free calves were divided into eight groups, four of six and four of five calves. Two of the groups of six were given a bolus containing 22 g of levamisole in a formulation designed to release the anthelmintic for ninety days. One group of treated calves was put out to graze at the beginning of May with one of the untreated larger groups on a field contaminated with 0 ostertagi and C oncophora, and the other treated group grazed with controls on a field known to have the same species plus D viviparus. On mid August these resident calves were removed, slaughtered and worm counts estimated. At the same time, the other groups of untreated calves were put onto the same fields to act as tracers of the level of infection. After grazing for one month they were housed, slaughtered and worm counts carried out. The faecal egg counts of treated calves were much less than those of the controls until the end of July. Control calves on the paddock infected with lungworm were severely affected by parasitic bronchitis whereas treated calves although infected did not display clinical symptoms. In the resident calves, O ostertagi burdens were reduced by 65 and 67 % and C oncophora by 97 % compared to untreated controls. In the tracer calves, there was no difference in burdens of 0 ostertagi and D viviparus but large differences in the number of Concophora established. It was concluded that treatment with the bolus had effectively suppressed multiplication of C oncophora, but that its effectiveness on O ostertagi and D viviparus was not sufficient to prevent contamination of fields with these nematodes in late summer. However, sufficient protection was observed against clinical symptoms of parasitic bronchitis despite a severe challenge.

References

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