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PubMed1994

Anthelmintic resistance in Haemonchus contortus from sheep in Malaysia.

Albendazole, oxfendazole, fenbendazole, levamisole, closantel, ivermectin and febantel were administered to sheep on four farms and their efficacy assessed by faecal egg count reduction test. High level of resistance of Haemonchus contortus was found to benzimidazoles (albendazole, oxfendazole, fenbendazole) on all farms and to febantel on the one farm where it was tested. No resistance to closantel and levamisole was observed. Resistance to ivermectin was absent on the three farms examined under this study, but has been reported on the fourth farm in earlier work. It is concluded that anthelmintic resistance to benzimidazoles and the probenzimidazole, febantel, is a serious and widespread problem in H. contortus in sheep in Malaysia.

Animals↗
PubMed1994

Resistance to benzimidazole anthelmintics by Haemonchus contortus in goats in peninsular Malaysia.

A previous study had suggested that local strains of goat trichostrongyles, comprising largely Haemonchus contortus, might have developed resistance to benzimidazole anthelmintics. A trial involving 18 goats was conducted to confirm this. There was a significant (P < 0.01) reduction in worm burdens in goats given levamisole, but this was not so for those animals given albendazole, fenbendazole, oxfendazole and mebendazole (P > 0.05).

Albendazole↗
PubMed1994

Multiple and multigeneric anthelmintic resistance on a sheep farm in Malaysia.

The anthelmintic efficacy of benzimidazoles, levamisole, closantel, ivermectin and moxidectin was evaluated on an institutional farm in Malaysia using faecal egg count reduction tests, controlled slaughter trials and an in vitro egg hatch assay. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles and ivermectin and of Trichostrongylus colubriformis against benzimidazoles and levaminsole on the same farm. Moxidectin was effective against the ivermectin resistant H. contortus.

Animal Husbandry↗
PubMed1994

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of anthelmintics for dogs and cats.

Guidelines have been designed to assist in the planning, operation and interpretation of studies for the assessment of the efficacy of drugs against helminth parasites of dogs and cats. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on the selection of animals, housing, feeding, dose-titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities involved in the evaluation of anthelmintics to employ comparable and standard procedures and will have the added benefit of minimising the numbers of animals needed for such tests.

Animal Husbandry↗
PubMed1995

Evidence for multiple anthelmintic resistance in sheep and goats reared under the same management in coastal Kenya.

Four experiments, two with sheep and two with goats, were carried out to determine the efficacy of ivermectin, fenbendazole, levamisole, closantel and some of their combinations by faecal egg count reduction tests. In the first experiment, injectable ivermectin, oral ivermectin, fenbendazole and levamisole were tested in 6-month-old lambs, and their reduction percentages were 77%, 13%, 42% and 92%, respectively. In the second experiment, with yearling sheep, the reduction percentages were 35% for injectable ivermectin, 32% for fenbendazole, 99% for levamisole, 48% for closantel, 92% for injectable ivermectin combined with fenbendazole, 99% for injectable ivermectin combined with levamisole, and 100% for fenbendazole combined with levamisole. In the study with 18-month-old goats given the same dose rates as those recommended for sheep, the reduction percentages were 73% for injectable ivermectin, 25% for fenbendazole, and 78% for levamisole. Another group of 14-month-old goats was treated with dose rates 1.5 times those recommended for sheep and the reduction percentages were 93% for levamisole, 92% for injectable ivermectin, and 97% for a combination of levamisole and ivermectin. In all experiments with sheep and goats the gastrointestinal nematode parasites identified by larval cultures were Haemonchus contortus, Trichostrongylus spp. and Oesophagostomum spp. The gastrointestinal nematodes of both sheep and goats on this farm are resistant to ivermectin and fenbendazole, whereas levamisole is still effective in sheep, but not in goats. The results are discussed in relation to the farm as a source of breeding stock to smallholder farmers and its potential to spread anthelmintic resistance.

Animal Husbandry↗
PubMed1996

Anthelmintic resistant nematodes in goats in The Netherlands.

A suspected case of anthelmintic resistance on a farm with Angora and Anglo-Nubian goats was confirmed in a controlled test. Twelve lambs of sheep were infected with larvae cultured from faeces of the goats. The lambs were allocated to four groups: untreated controls and lambs treated 21 days after infection with 5 mg kg-1 oxfendazole, 0.2 mg kg-1 ivermectin or 7.5 mg kg-1 levamisole. The lambs were slaughtered 1 week later and post-mortem worm counts were performed. Benzimidazole resistance was found in Haemonchus contortus, Teladorsagia circumcincta, Cooperia curticei and Trichostrongylus colubriformis with the efficacy of oxfendazole being 68%, 31%, 21% and 48% respectively. No resistance was found against levamisole or ivermectin.

Abomasum↗
PubMed1978

Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin.

The binding and inhibitory properties of 11 benzimidazoles for bovine brain tubulin were investigated. The effects of the benzimidazoles on the initial rates of microtubule polymerization were determined by a turbidimetric assay. The median inhibitory concentrations (I50) for nocodazole, oxibendazole, parbendazole, mebendazole and fenbendazole ranged from 1.97 . 10(-6) to 6.32 . 10(-6) M. Benomyl, cambendazole and carbendazim had I50 values from 5.83 . 10(-5) to 9.01 .10(-5) M. Thiabendazole had an I50 value of 5.49 . 10(-4) M. Inhibitor constants (Ki) were determined by the colchicine binding assay. Oxibendazole, fenbendazole, and cambendazole had Ki values of 3.20 . 10(-5), 1.73 . 10(-5) and 1.10 . 10(-4) M, respectively. Oxibendazole and fenbendazole were competitive inhibitors of colchicine. In contrast, cambendazole was a noncompetitive inhibitor of colchicine. The ability of these benzimidazoles to inhibit microtubule polymerization and the mode of action for the anthelmintic benzimidazoles is discussed.

Animals↗
PubMed1989

Reduction potentials of anthelmintic drugs: possible relationship to activity.

Electrochemical data were acquired for several categories of anthelmintic agents, namely, iminium-type ions, metal derivatives and chelators, quinones and iminoquinones, and nitroheterocycles. Reductions usually were in the favorable range of +0.2 to -0.7 V versus normal hydrogen electrode. The drug effect is believed to result in part from either the catalytic production of oxidative stress or disruption of helminth electron transport systems. Relevant literature results are discussed.

Animals↗
PubMed2005

Tribendimidine: a promising, safe and broad-spectrum anthelmintic agent from China.

We review, for the first time, a 20-year Chinese story of research and development pertaining to tribendimidine, a promising anthelmintic agent that is safe and exhibits a broad spectrum of activity. Tribendimidine was first synthesized at the National Institute of Parasitic Diseases in Shanghai in the mid 1980s. In laboratory studies, tribendimidine showed high efficacy against Nippostrongylus braziliensis in rats, Necator americanus in hamsters, Ancylostoma caninum and Toxocara canis in dogs, and Syphacia mesocriceti in mice. Activity was also found against several species of cestodes in chicken. In clinical trials, a single oral dose of 400 mg tribendimidine, administered to patients infected only with N. americanus, or with N. americanus and Ancylostoma duodenalis, resulted in cure rates of 85.7% (132/154) and 89.8% (53/59), respectively. In comparison, a single oral dose of 400 mg albendazole resulted in significantly lower cure rates, namely 65.5% (91/139; chi(2) = 16.47, P < 0.001) and 71.7% (43/60; chi(2) = 6.29, P = 0.012), respectively. Single oral doses of tribendimidine (300 mg) and albendazole (400mg) were equally effective against Ascaris lumbricoides infections; cure rates were 96.0% (97/101) and 98.1% (101/103), respectively. In 5-14-year-old children with an Enterobius vermicularis infection, treated with a single oral dose of 200 mg tribendimidine, a cure rate of 81.6% (93/114) was observed. Tribendimidine was well-tolerated as only mild and transient side effects were observed. It would be of great public health significance if these findings are confirmed in other epidemiological settings, as more than one-quarter of the world population is currently affected by intestinal nematodes, with only very few drugs currently available on the market.

Animals↗
PubMed2005

Synthesis and anthelmintic activity of 7-substituted 3,4a-dimethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2-b]pyridine-6,8(7H)-diones.

The racemic 7-substituted 3,4a-dimethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2-b]pyridine-6,8(7H)-diones represent novel tricyclic compounds with strong in vivo efficacy against the parasitic nematode Haemonchus contortus Rudolphi in sheep. Here we report on the synthesis of tricyclic endo-2,3-dihydro[3,2-b]pyridine-type cycloadducts and describe the separation of the racemic 3,4a-dimethyl-7-ethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2]pyridine-6,8(7H)-dione into the enantiomers by HPLC. The absolute configuration of the most anthelmintically active (4aS,5aS,8aS,8bR)-enantiomer was determined by single crystal X-ray analysis using its stable (4aS,5aS,8aS,8bR)-enantiomer-CuCl2 (2:1)-complex.

Animals↗
PubMed2005

Synthesis and anthelmintic properties of arylquinolines with activity against drug-resistant nematodes.

2,4-Disubstituted quinolines with additional substituents in positions 5-8 have been found to have anthelmintic properties. A number of 2,4-dimethoxy-6- or 8-arylquinolines have potent activity against the sheep nematode Haemonchus contortus, with LD99 values of the same order of magnitude as levamisole. These arylquinolines maintain their activity against levamisole-, ivermectin- and thiabendazole-resistant strains of H. contortus.

Animals↗
PubMed2006

Synthesis and anthelmintic activity of substituted (R)-phenyllactic acid containing cyclohexadepsipeptides.

The substituted (R)-phenyllactic acid containing cyclohexadepsipeptides (CHDPs) represent novel enniatin derivatives with strong in vivo activities against the parasitic nematode Haemonchus contortus Rudolphi in sheep. 2D NMR spectroscopic analysis revealed for the substituted (R)-phenyllactic acid containing CHDPs one major conformer with an unsymmetrically folded conformation lacking a cis-amide bond. A correlation between the substitution pattern and its anthelmintic activity was found. Here we report on a simple total synthetic pathway of the precursor for this particular type of CHDPs and an efficient modification of the benzylic side chain (R-PhLac(2)).

Animals↗
PubMed2006

Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans.

Emodepside, a cyclooctadepsipeptide, is a broad-spectrum anthelmintic previously shown to paralyse body wall muscle and pharyngeal muscle in the model nematode Caenorhabditis elegans. We demonstrate that wild-type C. elegans L4 are less sensitive than adults to emodepside in two independent assays of locomotor behaviour: body bend generation on agar (adult IC(50) 3.7 nM, L4 IC(50) 13.4 nM) and thrashing behaviour in liquid (thrashing behaviour as a % of controls after 1h in 10 microM emodepside: adults 16%, L4 worms 48%). We also show that continuous exposure of wild-type C. elegans to emodepside throughout the life-cycle from egg onwards, slows worm development, an effect that is emodepside concentration-dependent. The rate of worm-hatching from eggs on agar plates containing emodepside was not significantly different from controls, suggesting that it is development post-hatching rather than hatching itself that is affected by the drug. Emodepside also inhibits wild-type C. elegans egg-laying, with acute exposure to the drug at 500 nM resulting in an almost total inhibition within the first hour. However, the rate of egg production was not inhibited and therefore emodepside-treated worms became bloated with eggs, eventually rupturing. This suggests that the effect of emodepside on reproduction is not due to an inhibition of egg production but rather a paralytic effect on the egg-laying muscles. These results, when coupled with previous research, suggest that emodepside interferes with signalling at the neuromuscular junction on the body-wall muscles (Willson et al., 2003), pharynx (Willson et al., 2004) and egg-laying muscles and thus inhibits three important physiological functions: locomotion, feeding and reproduction.

Animals↗
PubMed2005

Reevaluation of risks with the use of Ficus insipida latex as a traditional anthelmintic remedy in the Amazon.

The anthelmintic remedy oje, prepared latex of Ficus insipida, is still used by indigenous and local people in the Amazonian regions. However, overdosage leading to toxic reactions occurs despite the broadcasting of a clinically accepted dosage that is effective and safe. The intoxication of a 10-year-old girl in Pucallpa, who had received oje in a dose close to the recommended one, led us to study retrospectively the records of all hospitalized patients with toxic reactions to oje over a 12-year-period. The use of oje in and around Pucallpa was estimated. Most cases with toxic reactions, out of a total of 39 for the 12-year-period, were probably due to an overdose, defined as more than 1.5 cm(3)/kg; the recommended dose being 1 cm(3)/kg. In only five cases did toxic reactions occur at doses up to 1.5 cm(3)/kg, which were interpreted as idiosyncratic reactions; all of them occurred in children, and in two cases it was a severe reaction. One fatal outcome was noted among the 37 hospitalized patients. Two other fatal outcomes were observed in the 12-year-period but they occurred outside the hospital. The mortality rate is estimated to have been 0.01-0.015% among patients supposedly treated with oje in the area. Severe intoxication led to symptoms of cerebral edema. The main treatment was osmotic diuresis with mannitol which started in 1996. Although hypersensitivity reactions have been observed with other Ficus spp., there was apparently no such reaction in our cases. Recommendations are given so as to avoid toxic reactions from an expected continued use of oje.

Adolescent↗
PubMed2003

A survey of anthelmintic resistant nematode parasites in Scottish sheep flocks.

The state of anthelmintic resistance in Scottish sheep flocks was evaluated during April-August 2000 using in vitro bioassays, egg hatch assays for detecting thiabendazole (TBZ) resistance and larval development assays for levamisole, ivermectin and TBZ resistance. Anaerobic sampling kits and detailed questionnaires outlining farm demographics and current management practices were mailed to 227 Moredun Foundation member farms, replies were received from 98 farms. Kits received from 90 farms contained sufficient material to conduct one or more of the assays. A majority of the farms examined (64%) exhibited TBZ resistance but there were both farm locality and regional variations in the percentage of resistant farms. Teladorsagia was the predominant genera detected from farms. No resistance to levamisole or ivermectin was detected in any of the samples. There was no strong evidence from this survey that any of the management practices examined greatly affected TBZ resistance.

Animal Husbandry↗
PubMed2003

The anthelmintic efficacy of five plant products against gastrointestinal trichostrongylids in artificially infected lambs.

Forty-eight helminth-free lambs were divided into eight groups (A-H) of six animals. Groups A-G were infected artificially with 10,000 third stage larvae of Haemonchus contortus and 20,000 third stage larvae of Trichostrongylus colubriformis, whereas group H remained uninfected. Thirty days post-infection the lambs were treated orally with a single dosage of one of the following products: group A with 3 mg/kg body weight (BW) of an aqueous ethanol extract (70%, v/v) of the seeds of Azadirachta indica A. Juss syn. Melia azedarach L. (Meliaceae); group B with 1 g/kg BW of a raw powder of the leaves of Ananas comosus (L.) Merr. (Bromeliaceae); group C with 0.3 mg/kg BW of an aqueous ethanol extract of a 1:1 mixture (g/g) of Vernonia anthelmintica (L.) Willd. (Asteraceae) seeds and Embelia ribes Burm (Myrsinaceae) fruits; group D with 183 mg/kg BW of an aqueous ethanol extract of the whole plants of Fumaria parviflora Lam. (Fumariaceae); group E with 28 mg/kg BW of an aqueous ethanol extract of the seeds of Caesalpinia crista L. (Caesalpiniaceae); group F with 25 mg/kg BW of pyrantel tartrate and group G with 50% ethanol. Group H remained untreated. Only the ethanol extract of F. parviflora caused a strong reduction of the faecal egg counts (100%) and a 78.2 and 88.8% reduction of adult H. contortus and T. colubriformis on day 13 post-treatment. The extract was as effective as the reference compound pyrantel tartrate. Therefore, the ethanol extract itself or single constituents of F. parviflora could be a promising alternative source of anthelmintic for the treatment of gastrointestinal trichostrongylids in small ruminants.

Administration, Oral↗
PubMed2004

Faecal egg count reduction test for assessing anthelmintic efficacy: average versus individually based estimations.

The faecal egg count reduction (FECR) in faeces is the most widely used method to assess the efficacy of anthelmintics against gastrointestinal strongyles. Several methods are used and they yield different efficacy values. They give important weight to those animals which excrete the majority of eggs, before or after treatment. We propose using individual animal FECR tests that give equal weight to every tested host. The first method is based on a before and after treatment without untreated controls, whereas the second one takes into account the use of non-treated control hosts. Confidence interval at P = 0.95 were established on bootstrap resamples for both individual-based methods. The individual-based FECR presented lower values than the average-based FECR in most cases. The individual FECR provided reliable evaluation when egg counts were over 300 eggs/g and when at least 10 animals were tested.

Animals↗