Itraconazole and thiophanate-methyl fail to clear tadpoles naturally infected with the hypervirulent lineage of Batrachochytrium dendrobatidis.

The emerging infectious disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis, is a major driver pushing many amphibian species to the brink of extinction. Substantial efforts to develop effective protocols that use antifungal drugs have had notable success. Here, we used the antifungal agents itraconazole and thiophanate-methyl, singly and in combination, in an attempt to treat common midwife toad Alytes obstetricans larvae naturally infected with the globalized hypervirulent lineage of B. dendrobatidis. Despite the successful use of itraconazole in a closely related species (A. muletensis), our results show that these antifungal treatments are not always effective and that full clearance of animals cannot be assumed following treatment.

Multiple anthelmintic resistance on a goat farm in Kenya.

The anthelmintic efficacy of benzimidazoles, levamisole, rafoxanide and ivermectin was evaluated on an institutional farm in Kenya using faecal egg count reduction test, larval cultures and a controlled slaughter trial. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles, levamisole and rafoxanide and Trichostrongylus columbriformis and Oesophagostomum sp. against levamisole on the same farm. Injectable and orally administered ivermectin was effective against the benzimidazole and levamisole resistant H. contortus.

Multiple anthelmintic resistance in Haemonchus contortus on a sheep farm in Kenya.

Multiple resistance to albendazole, thiophanate, levamisole and orally administered invermectin was detected in an isolate of Haemonchus contortus in sheep on a farm where benzimidazole resistance had already been identified. Following a faecal egg count reduction test, this was confirmed by both critical and controlled anthelmintic tests. Different groups of sheep infected naturally or given an experimental infection with the benzimidazole-resistant isolate were treated with the recommended doses of various anthelmintics. Compared to the control group, the percentage reductions in the faecal egg counts of sheep treated with albendazole, thiophanate, levamisole and ivermectin varied between 38.2% and 79.1% and the residual worm counts between 27.3% and 57.5%. The results indicate the presence of multiple anthelmintic resistance in this isolate of H. contortus. Sheep treated with closantel showed 100% reductions in faecal egg and worm counts, indicating that this drug was very effective against the population of H. contortus on the farm.

Comparative efficacies of closantel, ivermectin, oxfendazole, thiophanate and levamisole against thiabendazole resistant Haemonchus contortus in sheep.

Forty-nine sheep artificially exposed to a thiabendazole (TBZ) resistant isolate of Haemonchus contortus were assigned to 7 groups of 7 animals each and used to conduct a controlled anthelmintic trial. One group of sheep served as untreated infected controls and 6 groups were treated as follows: closantel, 5.0 mg kg-1; ivermectin, 0.2 mg kg-1; oxfendazole, 5.0 mg kg-1; thiophanate, 50 mg kg-1, levamisole, 7.5 mgkg-1 and thiabendazole, 66 mg kg-1. Eggs per gram of faeces were determined on days 21, 24 and day 34 (10 days post-treatment) after infection and all animals were necropsied for residual worm counts. The calculated efficacies of the treatments against H. contortus as indicated by worm reduction were closantel (100%), ivermectin (99.3%), oxfendazole (35.2%), thiophanate (56.7%), levamisole (98.6%) and thiabendazole (24.3%). The data therefore indicate that the TBZ-resistant isolate of H. contortus used was highly resistant to the 2 benzimidazole (BZ) anthelmintics, oxfendazole and thiophanate. This is the first report in Kenya of a field strain of H. contortus resistant to thiophanate.

Critical controlled test to evaluate resistance of field strains of Haemonchus contortus to thiophanate.

Following reports of suspected gastrointestinal strongylid nematode resistance to thiophanate in sheep and goats at Sokoine University of Agriculture (SUA), Tanzania, field strains of Haemonchus contortus, one from SUA and another from Kimamba, Tanzania, were selected for a critical controlled test to evaluate the efficacy of thiophanate. The SUA H. contortus strain in goats showed a marked resistance to thiophanate at an oral dose of 50 mg kg-1 liveweight (efficacy = 24.1%), while the Kimamba H. contortus strain showed very marked susceptibility (efficacy = 99.7%) to thiophanate at the same oral dose. This is the first report from East Africa of a field strain of H. contortus resistant to thiophanate. The incidence of resistant strains of strongyloid parasites to benzimidazole anthelmintics in sheep and goats in East Africa is on the increase. The magnitude of this problem should be evaluated and remedial solutions sought.

Efficacy of thiophanate and albendazole against natural infections of Dicrocoelium dentriticum, Fasciola hepatica, and gastrointestinal nematodes and cestodes in sheep.

The anthelmintic efficacy of thiophanate and albendazole was compared in sheep with heavy infestations of Dicrocoelium dentriticum. The effectiveness of each drug was determined by counting the numbers of D. dentriticum in animals killed 21 days after treatment. In one group, the dose of thiophanate recommended for use against gastrointestinal (GI) nematodes (50 mg kg-1 live weight) was found to be 74.4% effective against D. dentriticum. Two tablets (each containing 76 mg of active ingredient) of albendazole per 30 kg live weight were given to a second group and the dose repeated after 1 week. Under this regime, albendazole was found to be 12.7% effective against D. dentriticum. The effect of each drug on other parasites was as follows; thiophanate had no effect against Fasciola hepatica or cestodes, while albendazole was 71.5% effective against F. hepatica and 100% effective against cestodes. Both drugs were highly effective against GI nematodes.

Helminthosis in goats in southern Tanzania: investigations on epidemiology and control.

Investigations were conducted in naturally infected goats to determine the main epidemiological factors related to gastro-intestinal nematode infections in southern Tanzania with a view to making appropriate recommendations for control. Faecal worm egg counts rose during the single rainy season and then fell to remain low during the dry season. The beneficial effect of an anthelmintic treatment after the rains was demonstrated in weaner goats under traditional management and this should form the basis of rational control.

[Pharmacokinetics and anti-Dicrocoelium activity of thiophanate and its major metabolite in ruminants]. / Pharmacocinétique et activité dicrocoelicide du thiophanate et de son métabolite majeur chez les ruminants.

After a single oral dosage of 40 mg thiophanate/kg in cattle, sheep and goats, the parent compound and its main metabolite: ethyl benzimidazol-1H-yl-2-carbamate (EBC) are evidenced in plasma by HPLC analysis for 60 to 72 hours. The rate of metabolic change of thiophanate into EBC is 34% in sheep, 52% in goats and 57% in cattle. At this dosage, thiophanate seems to be effective against Dicrocoelium in sheep. On the contrary, EBC is uneffective at 15 mg/kg while it seems undetectable in plasma at any time.

Field studies with in-feed medication of pigs in the Netherlands using the anthelmintic thiophanate with particular reference to efficacy against Ascaris suum.

Studies on the efficacy in pigs of low level in-feed medication with the anthelmintic thiophanate at a minimum intake of 6 mg/kg/day for fourteen days are reported. A trial was conducted to compare a group of medicated fattening pigs with a similar unmedicated group on premises known to have a high challenge of Ascaris spp. Daily growth rate was improved whilst feed conversion ratio and the liver condemnation rate were reduced in the treatment group. Routine medication of a whole herd using this regime contributed to a great improvement of the herd production when assessed by the above criteria. User studies in various geographical areas of the Netherlands involving 1500 adult pigs and 1200 fattening pigs medicated with thiophanate in-feed for fourteen days demonstrated that the compound eliminated the faecal worm egg output and was readily accepted and tolerated by pigs.

Resistance of Haemonchus contortus to thiophanate.

The occurrence of a field strain of Haemonchus contortus which was resistant to thiophanate and susceptible to thiabendazole and levamisole is reported. The LD95 of thiophanate for the strain was found to be 156.1 mg/kg and its resistance factor was 6.7. In possessing specific thiophanate resistance it differed from previously reported thiophanate resistant strains of H contortus which have been benzimidazole resistant worms that have possessed cross resistance to thiophanate.

Efficacy of thiophanate and thiabendazole against inhibited trichostrongylid larvae in sheep.

In a trial with natural infections of trichostrongyles in sheep, thiophanate and thiabendazole at 100 mg/kg and 200 mg/kg bodyweight were highly effective in removing all stages of development of the helminths including the inhibited stages. At 50 mg/kg bodyweight however, both drugs were only capable of reducing helminth load.

Thiophanate as a low daily dosage anthelmintic in sheep.

Thiophanate administered daily at low dosages reduced nematode faecal egg output, egg hatchability and parasitic worm burdens in treated lambs and ewes. Six daily doses of 1 or 3 mg per kg thiophanate (approximately 1/25th to 1/75th of the median therapeutic dose), given to lambs experimently infected with Trichostrongylus colubriformis, were partially effective in suppressing faecal egg output and egg hatchability. Six doses of 5 mg per kg per day were effective in lambs infected with Haemonchus contortus and Nematodirus spathiger. Daily doses of thiophanate (50 or 200 mg per head) given over 14 weeks to lambs grazing contaminated pasture resulted in improved productivity (the higher dosage) and suppression of output of viable eggs and reduced worm burdens (both dosages). Reduced output of viable eggs was also obtained in housed, lactating ewes receiving 5 or 7 mg per kg thiophanate dispersed daily in the feed for 11 or nine weeks respectively after lambing.