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The effect of route of administration on the anthelmintic efficacy of benzimidazole anthelmintics in sheep infected with strains of Haemonchus contortus and Trichostrongylus colubriformis resistant or susceptible to thiabendazole.

Observations of erratic anthelmintic activity of fenbendazole against known standardised thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep were investigated. Fenbendazole at a dose rate of 10 mg/kg body weight was administered by oral, intra-ruminal or intra-abomasal routes, and was most effective against both resistant strains following intra-ruminal administration. In addition thiabendazole, oxibendazole, fenbendazole, parbendazole and mebendazole plus two unrelated compounds, levamisole and morantel tartrate, were used at one and a half times their suggested or recommended therapeutic dose rate against thiabendazole-resistant strains of H contortus and T colubriformis in sheep; each drug being administered by the intra-ruminal or intra-abomasal routes. Fenbendazole was more effective against both strains following intra-ruminal administration. Parbendazole was more effective against the resistant strain of T colubriformis following intra-ruminal administration. At the dose rate chosen for the other benzimidazoles used against these resistant strains, there was no difference in anthelmintic efficacy due to route of administration. Levamisole was highly effective against both resistant strains, irrespective of the route of administration. In the groups treated with morantel tartrate, the results obtained were difficult to interpret due to mortalities and a highly variable response in the surviving sheep. Fenbendazole, thiabendazole and mebendazole when used at their suggested or recommended therapeutic dose rate in sheep, were highly effective against known thiabendazole-susceptible strains of H contortus and T colubriformis following both intra-ruminal or intra-abomasal administration.

Abomasum↗

Changes in pepsinogen, proteins and lipids in the serum during experimental haemoncosis in sheep.

To determine the relationship between the course of infection by parasites of the genus Haemoncus and variations in the level of serum pepsinogen, an experiment was done with three groups of five lambs. The first was a non-infested control group. The lambs of the second group were given one dose of 10,000 H. contortus infective larvae. The animals of the third group were given one dose of 50,000 larvae. Fluctuations of the level of serum pepsinogen were determined throughout the experimental period (88 days). Observations also included variations of protein and lipid levels. Our experimental results showed that the development of H. contortus larvae, even when in small numbers, can cause lesions comparable to ostertagiosis in abomasum and produce the same rise in the level of serum pepsinogen. This increase in serum pepsinogen appeared to be related to the amount of larvae which were given. The high level of serum pepsinogen persisted over a long period. Variations of the serum, total protein and albumin levels were the same as described by other authors. There was no decrease in serum lipids.

Animals↗

Economic value and course of infection after treatment of cattle having a low level of nematode parasitism.

To determine whether it is economically advantageous to treat calves having inapparent parasitism, we conducted experiments from 1971 to 1976, involving more than 1,800 calves from 30 pens or lots, using formulations of thiabendazole, levamisole, and crufomate (ruelene). Differential egg counts, cultured larvae, and cultured parasitic stages were used to estimate the kind and degree of nematode parasitism. Differentiation of infective larvae consistently established Cooperia as the predominating (%) genus in all fecal samplings. Bunostomum, when initially present, decreased or disappeared, whereas Trichostrongylus increased; other genera fluctuated less consistently. These qualitative generic fluctuations were not primarily the result of treatment, but more likely were seasonal variation. Judged by average daily gain (ADG), anthelmintic treatment was statistically advantageous at one or more points during the observation periods in 10 of 13 treated groups. In seven treated groups, the observation periods were concluded with statistical advantage in ADG, whereas in three groups, compensatory gain by corresponding controls had neutralized earlier advantages. The comparative influence of the various anthelmintics was not consistent from year to year. When total cost/kilogram gain was calculated from feed efficiency measuremnts and other costs, economic treatment advantage was evident in seven of 11 tests (7 of 10 treatment groups) from 1973 through 1976. This financial advantage, due primarily to feed efficiency and noted after 28 to 51 days, justified anthelmintic treatment. This advantage was not likely lost by the animals in subsequent periods (to 218 days) on pasture or in lots, since ADG indicated the treated calves performed either as well as, or better than, the nontreated controls. Considering all aspects of the study, the results indicate calves coming into Kansas from southern states and weighing 184 to 267 kg may possess a level of subclinical (symptomless) nematode parasitism that when treated will result in a response justifying expense for using anthelmintics.

Animals↗

Studies on Haemonchus contortus. IX. The effect of Trichostrongylus axei in Merinos on natural pasture.

Four groups of 6-7-month-old Merino lambs were each dosed with 40 000 infective larvae of Trichostrongylus axei on 2 November 1976 and subsequently exposed to challenge with Haemonchus contortus on natural grazing at the University of Pretoria's Experimental Farm in the eastern suburbs of Pretoria. One of these groups and one group of controls were killed every 8 weeks from the end of December 1976-June 1977. Predosing with T. axei was greater than 50% effective against 5th stage and adult H. contortus in greater than 50% of sheep for 164 days (Class C), improving to greater than 60% in greater than 60% of sheep (Class B) 220 days after dosing T. axei. The numbers of retarded 4th stage larvae (L4) of H. contortus in the undosed controls as well as in the sheep predosed with T. axei rose from a low level in summer (December) to a peak in late Autumn (June).

Animals↗

Studies on Haemonchus contortus. X. The effect of Trichostrongylus axei in Merinos on artificial pastures.

A recently established Eragrostis curvula pasture 1,1 ha in size at Hennops River in the Transvaal Highveld was contaminated from 6 October 1976 until 20 May 1977 by 30 weaned Merinos, each infested with 7 000 infective larvae of H. contortus. On 2 November 1976 3 groups of weaned Merinos and again on 10 January 1977 a further group of Merinos were infested with 40 000 infective larvae of Trichostrongylus axei. From 19 November a single group of sheep, predosed with T. axei, and a control group grazed with the seeders for 8 weeks. After 6 weeks another group of sheep dosed with T. axei grazed with them, thus ensuring a 2-week overlap. This continued until autumn, when the last groups were removed. Efficacy against challenge reached Class C (greater than 50% effective against total worm burdens of H. contortus in greater than 50% of sheep) in early summer and autumn, but only reached significant levels of either P less than 0,01 or P less than 0,05 in summer. Peak worm burdens in controls were recorded in early autumn.

Animals↗

Studies on Haemonchus contortus. XI. The effect of a bovine strain of Trichostrongylus axei in Merinos on natural pastures heavily infested with H. contortus.

Sheep grazed on natural pastures heavily infested with infective larvae of Haemonchus contortus. Sixty-eight weaned Merinos were divided into 6 groups on Day 0 (23 November 1977), and on Day +14 (7 December) 79 Merinos were divided into 7 groups. There were 2 groups of undosed controls and other groups were either dosed with infective larvae of Trichostrongylus axei (bovine strain) only on Days 0 and +14, or in combination with H. contortus, or with subsequent doses of H. contortus, 28 days later. One group (Group 12) was dosed with T. axei and treated with a subcutaneous injection of di-iodonitrophenol (DNP) on Day +14. With the exception of 2 sheep, the sheep of the first 6 groups survived until slaughter in March and April 1978, while many sheep (43) of the latter 7 groups died or were killed in extremis from March-May. T. axei dosed on 23 November (Day 0) protected Group 2 by greater than 50% in greater than 50% of sheep. In the latter 7 groups the best results were achieved when DNP was combined with predosing with T. axei. The poor results were probably due either to delayed predosing with T. axei or a massive challenge in the wettest summer on record.

Animals↗

Studies on Haemonchus contortus. XII. Effect of Trichostrongylus axei in Dorper lambs on natural pasture lightly infested with H. contortus.

Weaned Dorper lambs on natural pasture were predosed with 40 000 infective larvae (L3) of Trichostrongylus axei, irradiated (0,3 kGy) L3 of T. axei or closantel at 10 mg/kg either in September or November 1978 and were compared with Merino yearlings predosed with 40 000 L3 of T. axei in November 1977. The following summer (December-March) only 178,6 mm of rain fell and very few H. contortus were present on pastures. Artificial challenge with 20 000 L3 of Haemonchus contortus with the local strain from the University of Pretoria's experimental farm was given 6-7 months after predosing with T. axei. When compared with the controls, significant reductions occurred only in Group 11 (T. axei irradiated at 0,3 kGy on Day +63) (P = 0,025); Group 2 (T. axei on Day 0) (P = 0,003) and Group 4 (T. axei and closantel on Day 0) (P = 0,049). We concluded that predosing with T. axei was unsuccessful in Dorpers and Merinos artificially challenged 6-7 months later with H. contortus.

Animals↗

The importance of endoparasite counts at necropsy.

In a 2-year study of 49 Oklahoma cattle with a typical history of clinical endoparasitism, 12 animals had Ostertagia only, and Ostertagia was the predominant endoparasite in 21. Only 1 animal had a pure Haemonchus population. Though primary endoparasitism was diagnosed antemortem in 32 animals, postmortem worm counts confirmed the diagnosis in only 19. Worm counts documented inapparent disease in 8 animals. In 21 cases of suspected of toxicosis, 12 animals had endoparasitism none was poisoned.

Animals↗

[Kinetics of the population of worms in various developmental stages, Haemonchus contortus in sheep after a single experimental infection] experimental infection].

This work was performed to study, in 147 month-old male lambs experimentally infected with 14000 Haemonchus contortus infective larvae and slaughtered at 6, 12, 18 and 24h and at 2, 6, 8, 11, 15 and 39 days post-infection (pi): 1, the importance, localisation and nature (with or without sheath) of the worms during the first 24 h pi; 2, the kinetics of the total worm population and of each evolutionary stages from the first to the 39th day pi: 3, the period of emergence of the fourth-stage larvae from the mucosae; 4, the topographic distribution of the different evolutionary stages of the parasite in the abomasum. During the first 24 h pi, the total worm population and that of the intramucosal larvae increase in lineary function to time (r = 0.98). After a maximum value, reached between 24 and 48 h pi, the total worm population decreases in lineary function to time (r = -0.94). Only 52% approximately of the larvae administered develop. One of the reasons is the fact that a proportion of 3rd stage larvae cannot leave their sheath during the rumino-omasal transit. Other limiting factors are discussed. The fourth-stage larvae appear in the mucosae 24 h pi. Their emergence from the mucosae starts between day 1 and 2 pi and increases in intensity from days 2 to 6 pi. The immature adults and the adults are encountered from days 6 and 14 pi respectively, and the prepatent period is on average 16 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Abomasum↗

[2-(Guanidino)-anilides and related compounds. Synthesis and anthelmintic effect. 3. Anthelmintics].

Anilides bearing a guanidino, thioallophanato, isothioallophanato or amidino group in the ortho position were synthesised (6) for investigations of their anthelmintic effects, and tested against sheep trichostrongylides. The most active anilides are those containing a 5-alkylthio, 5-alkylsulphinyl (alkyl = C3H7, C4H9), 5-phenylthio, 5-phenylsulphinyl or 4-phenylsulphonyloxy group, and a guanidino group substituted at both nitrogen atoms by a methoxycarbonyl group. The most active anthelmintic anilides are the form-, propion-, butyr- and methoxy-acetanilides (e.g. 60, 61, 66, 95, 100, 110). Of the guanidines unsubstituted at N' and N", the 2-guanidino-5-phenylthio-2-methoxyacetanilide (123) and the 2-guanidino-5-phenylsulphinyl-2-methoxyacetanilide (152) were more active than parbendazole. From the class of bismethoxycarbonylguanidines (6 alpha), which are also the most interesting products in terms of stability, febantel (110, Rintal) has been introduced into veterinary practice for the treatment of nematode infections in horses, cattle, sheep and swine.

Aniline Compounds↗

Resistance to Haemonchus contortus transferred between genetically histocompatible sheep by immune lymphocytes.

The pattern of faecal egg counts after infection with 10,000 Haemonchus contortus larvae was similar within but not between, four pairs of monozygous twin sheep. Transfer of whole lymph or washed lymph cells from three immune donor sheep to their identical co-twin recipients reduced the susceptibility of the recipients to challenge with 10,000 larvae as measured by faecal egg counts. Cells from a nonimmune donor did not have this effect. In a final experiment, washed cells from an immune triplet sheep, which was actively responding to a repeated challenge infection, transferred a secondary local IgA response to a second recipient triplet and resulted in a marked reduction in worm count when compared with that of a third infectivity control triplet.

Animals↗

Anthelmintic efficacy of avermectin B1a and dihydroavermectin B1a against ovine gastrointestinal nematodes in 1977.

In a critical study, 40 female mixed-breed lambs with experimental infections of Cooperia spp, Trichostrongylus colubriformis, Ostertagia circumcincta, T axei, and Haemonchus contortus were allocated to 8 groups in 1977. Groups 1 and 5 served as controls. Groups 2 to 4 were treated orally with avermectin B1a at dosage levels of 25, 50, and 100 micrograms/kg of body weight, respectively. Groups 6 to 8 were given oral dihydroavermectin B1a at dosage levels of 50, 100, and 200 micrograms/kg, respectively. The lambs were euthanatized and necropsied 6 days after treatment. The compounds were greater than 99% effective at all dosage levels.

Animals↗

Erythrocyte potassium concentration: a simple parameter for erythropoiesis in sheep infected with Haemonchus contortus.

A number of haematological parameters were monitored in eight-month-old Merino wethers, six infected with 10,000 Haemonchus contortus and 13 controls. Blood loss caused by infection was reflected in a decrease in packed cell volume (r = -0.78; P less than 0.001), and was correlated with faecal egg excretion (r = 0.89; P less than 0.001). Infected animals showed a decline of serum iron content and increased serum transferrin levels. Erythrocyte potassium concentration showed a high correlation with erythropoiesis as measured by iron59 clearance from blood (r = 0.79; P less than 0.001). As potassium assays are quick, inexpensive and samples can be stored for long periods, this parameter seems particularly useful in large experiments.

Animals↗

Stimulatory effects of prostaglandin F2 alpha on faecal egg production in Haemonchus contortus infected sheep.

The effect of prostaglandin F2 alpha on the pattern of faecal egg count was tested in 10- to 12-month-old sheep infected with 20,000 Haemonchus contortus larvae. Prostaglandin was infused intravenously 25, 50 and 75 days after infection for four hours at a rate of 5 micrograms/kg/minute and the egg counts in the faeces were determined daily for 110 days. Treatment on days 50 and 75 was followed by a significant rise in egg count lasting 19 and 12 days respectively. This observed rise seems to be related to a resumption of development of arrested larvae induced by prostaglandin treatment, and a hypothesis is proposed to explain its initiation.

Animals↗

Immune exclusion, a mechanism of protection against the ovine nematode Haemonchus contortus.

The fate of exsheathed Haemonchus contortus larvae injected directly into the abomasal lumen was studied in groups of naive and hyperimmune sheep. Within 48 hours of challenge, more than 90 per cent of the larvae were lost from hyperimmune sheep. The larvae had a propensity to associate with the superficial mucus in both groups and, in naive sheep, approximately 50 per cent of the larvae entered glandular tissue within four hours of challenge. By contrast, although initially associated with the mucosal surface, larvae in immune sheep were excluded from the glandular tissues. It is postulated that the rapid loss of worms from the hyperimmune abomasum is a consequence of 'immune exclusion' and the possible mechanisms underlying this process are discussed.

Abomasum↗