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1.
Bártíková, H., Křížová, V., Lamka, J., Kubíček, V., Skálová, L., Szotáková, B. Flubendazole metabolism and biotransformation enzymes activities in healthy sheep and sheep with haemonchosis. J. vet. Pharmacol. Therap . 33 , 56–62.
The aim of this project was to study the influence of haemonchosis, a common parasitic infection of small ruminants caused by Haemonchus contortus , on the activity of biotransformation enzymes and on in vitro flubendazole (FLU) biotransformation in liver and small intestine of lambs ( Ovis aries ). Twelve lambs were divided into three groups: non-infected animals, animals orally infected with larvae of H. contortus ISE strain for 7 weeks and for 11 weeks. At the end of the experiment, hepatic and intestinal subcellular fractions were prepared and used for assays of biotransformation enzymes activities and FLU metabolism testing. The activities of hepatic cytochromes P450, flavine monooxygenases and carbonyl-reducing enzymes were decreased in infected animals. UDP-glucuronosyl transferase activity was significantly lower (by 35%) in 11 weeks infected animals than that in control animals. When in vitro metabolism of FLU was compared in control and infected animals, significantly lower velocity of FLU reduction was found in infected animals. Slower FLU reduction may be beneficial for the haemonchosis treatment using FLU, because FLU will remain longer in the organism and could cause longer contact of parasites with FLU.  相似文献   

2.
Basal activities of certain pheasant hepatic and intestinal biotransformation enzymes and modulation of their activities by anthelmintics flubendazole (FLBZ) and mebendazole (MBZ) were investigated in subcellular fractions that were prepared from liver and small intestine of control and FLBZ or MBZ treated birds. Several oxidation, reduction and conjugation enzyme activities were assessed. In the liver, treatment of pheasants by FLBZ or MBZ caused very slight or no changes in monooxygenase activities and conjugation enzymes. More significative changes were detected in small intestine. Metyrapone and daunorubicin reductase activities were increased by both substances in the liver. This is the first evidence that certain benzimidazoles modulate reductases of carbonyl group. With respect to the relatively slight extent of the changes caused by FLBZ or MBZ we can assume that repeated administration of therapeutic doses of both FLBZ and MBZ has probably no serious influence on pheasant biotransformation enzyme system.  相似文献   

3.
Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.  相似文献   

4.
Drug entry into the body of a helminth is a key factor in the efficacy of anthelmintics. The present project was designed to study the ex vivo uptake and efflux of the benzimidazole anthelmintic flubendazole (FLU) in four strains of H. contortus: the ISE strain (fully susceptible to anthelmintics), the ISE-S strain (resistant to ivermectin), the BR strain (resistant to benzimidazoles) and the WR strain (multi-resistant). The transport of FLU between dead and living nematodes was also compared as well as the effect of verapamil, an inhibitor of the main efflux ABCB1 transporter (P-glycoprotein), on FLU accumulation in nematodes. The obtained results showed that FLU is able to effectively enter H. contortus adults due to high FLU lipophilicity. Passive diffusion is probably the only mechanism in both FLU import and efflux from nematodes. No differences in FLU transport were found among four H. contortus strains with different sensitivity to anthelmintics. No active FLU efflux from H. contortus and no effect of verapamil were observed, indicating that H. contortus cannot protect itself against FLU by the active removal of this anthelmintic from its body.  相似文献   

5.
The development of moxidectin resistance (MOX-R) in sheep parasitic gastrointestinal nematodes already carrying multiple resistances to other anthelmintic groups has made control of these strains very difficult. The anthelmintic resistance patterns of MOX-R strains of Trichostrongylus colubriformis and Haemonchus contortus were characterized to provide an insight into the remaining role of anthelmintics in the control of such strains. Homozygous MOX-R individuals of both genera were unaffected by moxidectin. For MOX-R heterozygotes a dose rate of 200 microg/kg abamectin (ABA) given orally removed 25% of H. contortus while 200 microg/kg MOX given orally achieved a 72% reduction. Doubling the dose rate of ABA improved the mean efficacy to 37%. Consequently, in H. contortus, the degree of dominance differs markedly between the two anthelmintics. A dose rate of 8 mg/kg levamisole and 185 mg/kg napthalophos achieved >95% reduction in worm count of the MOX-R homozygous H. contortus but only 85 and 7%, respectively against the MOX-R homozygous T. colubriformis.  相似文献   

6.
Multiple resistance to albendazole, thiophanate, levamisole and orally administered ivermectin 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.  相似文献   

7.
Two controlled tests were performed to investigate the benzimidazole resistance of a nodular worm isolate "GIBZ" from a pig breeding farm in Germany. In Trial I, groups of five pigs, artificially infected with Oesophagostomum larvae isolated from that farm were treated with flubendazole at a single dose of 5 mg kg(-1) bodyweight (BW) or remained untreated. In Trial II, three groups of three pigs each infected with larvae after a further laboratory passage of this isolate were treated with flubendazole either at a single dose of 5 mg kg(-1) BW or at a divided dose of 1.5 mg kg(-1) BW daily for 5 consecutive days, or with fenbendazole at a single dose of 5 mg kg(-1) BW, the fourth infected group remained untreated. The respective doses of anthelmintics were mixed with a small amount of feed and administered to individual pigs in both trials. Fecal egg counts before and after treatment and post-mortem worm burdens 7 days after (last) treatment were examined to assess the anthelmintic efficacies. Only infections with Oesophagostomum dentatum were found in both trials. In Trial I, the mean worm count reduction by flubendazole was 30% as compared to the untreated controls. In Trial II, flubendazole administered at a single or divided dose reduced the mean worm burden by 0 and 85%, respectively, whereas fenbendazole was 100% effective. These results establish resistance to flubendazole in the isolate "GIBZ" of O. dentatum. The failure to reveal side resistance to fenbendazole may be explained by that the currently recommended dose rate of this compound is supra-optimal for porcine nodular worms.  相似文献   

8.
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.  相似文献   

9.
A strain of Haemonchus contortus resistant to the benzimidazoles, ivermectin and salicylanilides was used to study the effect of exposure to ivermectin or oxfendazole on the number of eggs produced by adult female parasites. After anthelmintic administration there was a reduction in the faecal egg count of the infected lambs. Ivermectin caused a reduction in the number of eggs within adult parasites for up to 72 hours but this returned to higher than pre-treatment levels at 168 hours after treatment. After oxfendazole treatment there was an increase in the number of eggs stored in the adult parasites at 24 hours and then a significant reduction in the number of eggs for over 168 hours. This suggested that both ivermectin and oxfendazole have a deleterious effect on the reproductive potential of female H contortus although the parasites are resistant to these drugs. These results confirm the importance of allowing up to 10 days to elapse between the time of administration of an anthelmintic and the collecting of faecal samples when using the faecal egg count reduction test to identify anthelmintic resistance, especially when using benzimidazoles. The more prolonged effect on fecundity produced by oxfendazole may reflect the antimitotic action of the benzimidazole anthelmintics.  相似文献   

10.
Groups of 10 goats, harbouring both naturally acquired and experimental infections of gastrointestinal nematodes, were drenched with either levamisole (5 mg kg-1), albendazole (3.8 mg kg-1) or parbendazole (15 mg kg-1), or remained untreated. Haemonchus contortus was the numerically dominant infection, with Strongyloides papillosus, Trichostrongylus colubriformis and Oesophagostomum columbianum also present. At 5-6 days post-treatment, goats were killed and necropsied. Post-mortem worm counts showed that the reduction in mean total worm burdens was 57.4% in levamisole-treated animals, 71.1% in the albendazole group and 85.1% in the parbendazole group. Reductions for H. contortus were 80.2, 87.9 and 83.9% in the levamisole-, albendazole- and parbendazole-treated groups, respectively. These data indicate that the anthelmintics in question are not being applied at an adequate dose rate for goats, and/or resistance to anthelmintics is occurring in the field in Pernambuco State, northeast Brazil.  相似文献   

11.
The prevalence of drug-resistant ovine parasites in the United States has not been widely reported. Thirteen flocks, typical of commercial sheep production units, were selected for survey. Four anthelmintics (fenbendazole, ivermectin, pyrantel pamoate, and levamisole) were tested for their ability to reduce herd mean pretreatment fecal egg count. If a properly dosed and administered drug failed to reduce herd mean pretreatment fecal egg count by 80%, it was considered ineffective in that flock, and the presence of parasites resistant to that drug was inferred. Fenbendazole administration changed pretreatment fecal egg counts by +9% to -100%. On the basis of the aforementioned definition, drug resistance existed in 6 of 13 flocks. Posttreatment larval culture indicated that Haemonchus contortus survived administration of fenbendazole. Levamisole, pyrantel pamoate, and ivermectin reduced pretreatment fecal egg count by -83% to -100%; resistance to these products was not evident in the flocks surveyed.  相似文献   

12.
An experimental study to investigate the susceptibility pattern of Haemonchus contortus to commonly used anthelmintics (albendazole, tetramisole, ivermectin, and triclobendazole) was conducted between June and September 2009. Adult H. contortus parasites were collected from a total of 30 sheep slaughtered at Jimma municipal abattoir. The anthelmintics were assessed for egg hatch inhibition ability against H. contortus eggs. The eggs (500 eggs/ml) were incubated with different concentrations (0.25, 0.125, 0.0625, 0.03125, and 0.015625?μg/ml) at 26°C for 48?h. Egg hatching inhibition of different anthelmintics at different concentrations was recorded. The overall mean percent inhibition showed that there was a significant difference (p?相似文献   

13.
The efficacy of two recently introduced benzimidazole anthelmintics, albendazole and fenbendazole, was determined for six-day, 10-day and adult stages of resistant strains of Haemonchus contortus and Trichostrongylus colubriformis. Albendazole, at 3.8 mg/kg reduced H contortus worm counts by 92.4, 70.8 and 67.1 per cent while fenbendazole, at 5.0 mg/kg, reduced worm burdens by 51.7, 95.5 and 93.4 per cent against six-, 10- and 25-day-old parasites respectively. For T colubriformis, the corresponding reductions with albendazole were 97.7, 95.8 and 64.9 per cent and for fenbendazole 29.0, 66.3 and 33.4 per cent. Compared with susceptible strains of H contortus and T colubriformis, for which therapeutic doses of benzimidazole anthelmintics are generally highly active against all stages of development, the present results show that these drugs do not have a uniform level of activity against all developmental stages of resistant strains.  相似文献   

14.
Surveys to determine the prevalence and degree of resistance of Haemonchus spp. of sheep and goats to the available anthelmintics in South Africa indicate that small ruminant production is entering a crisis situation. Three surveys employing the faecal egg count reduction (FECR) test to determine resistance were conducted in some of the main sheep-producing areas in the summer rainfall region of South Africa, where H. contortus is the principal worm species in sheep. After analyzing the data recorded in the surveys by six different methods, including the RESO test at two different levels of confidence, the results obtained in the least stringent one (geometric mean reduction of the worm egg counts of drenched, vs untreated group of sheep) are reported in this paper, so that if any bias was obtained it would be in the favour of the anthelmintic. In Mpumalanga and KwaZulu-Natal there was anthelmintic resistance in Haemonchus spp. on all the 52 farms surveyed. Sixteen percent of the strains of H. contortus were < 60% susceptible to three of the four anthelmintics tested, and 8% of the strains were < 40% susceptible to all four of the anthelmintics. FECR tests of sheep in six localities in the Lebowa district of Northern Province indicated that even in previously disadvantaged communities where anthelmintic treatment is less intensive, anthelmintic resistance is developing, and is possibly at the level at which the situation on commercial sheep and goat farms in South Africa was 25 years ago. From the data it appears that the level of anthelmintic resistance of H. contortus in South Africa is possibly the highest that has so far been recorded in the world and that strains of it are emerging that may soon not be controllable by treatment with any of the existing anthelmintics. Farmers in the summer rainfall region, if not the whole country, must be alerted to the immediate need for testing the parasite burdens of their sheep for susceptibility to preparations in all four groups of anthelmintic compounds currently available. Alternative methods of integrated worm control, including biological, must be sought and implemented with urgency, to reduce further selection for resistance and to induce reversion of the resistance that has already developed.  相似文献   

15.
During the past decade in South Africa there has been a continual increase in sheep of strains of gastrointestinal helminths resistant to the modern anthelmintics. Five strains of Haemonchus contortus are described in this paper. Despite the fact that 2 of the 5 strains were tested for susceptibility only to ivermectin, a total of 10 instances of resistance were found. Four of the 5 strains were resistant to ivermectin, 2 to closantel, 2 to rafoxanide and 2 to the benzimidazoles. One of these strains was concurrently resistant to 3 different anthelmintic groups, namely, the ivermectins, the benzimidazoles and the salicylanilides. Resistance to ivermectin developed in 2 strains of H. contortus after a history of only 3 treatments with this compound in one instance and 11 treatments in the other. In the latter case drenching with ivermectin was well interspersed with that of other anthelmintics. This rapid development of resistance suggests that there may be cross-resistance between ivermectin and another anthelmintic group. Two of the ivermectin resistant strains were recovered from separate properties in the south-western Cape Province, where Ostertagia circumcincta, which is usually the dominant parasite in this region, was virtually eliminated by the anthelmintic treatment. On each of these properties it was apparently replaced by a resistant strain of H. contortus. A serious threat to control is the dissemination of worm strains with multiple resistance to anthelmintics. The strain of H. contortus resistant to 3 anthelmintic groups has already been widely dispersed, as the farmer concerned suddenly decided to give up farming with sheep and to sell his flock.  相似文献   

16.
Groups of four stag fawns, weighing 51 +/- 0.8 kg, were-infected with 30,000 larvae of one of three nematode parasites: O.circumcincta, O.ostertagia, or H.contortus. A further four remained as control. Individual feed intake, body-weight, faecal egg count and plasma pepsinogen concentration were measured during seven weeks after infection. Only infection with H.contortus caused significant elevation of pepsinogen concentration to 380ml/ L and consistent depression of feed intake (15%). Worm egg counts were below 300 e.p.g. in deer infected with all worm species. It is concluded that while resistance to development of parasites common to other species appears to be high further investigation of the susceptibility of deer to H. contortus infection would be justifiable.  相似文献   

17.
Two experiments were performed to determine whether previous infection of young lambs with Ostertagia circumcincta increased their resistance to the development of Haemonchus contortus and to explore alterations in the microenvironment of the abomasum related to the interaction. The parasitic infections were monitored with periodic fecal egg counts and by recovery and enumeration of parasites at necropsy of the lambs. Alteration of the microenvironment was examined by measurement of serum gastrin concentrations at critical times during both experiments. The results indicated that the numbers of H contortus were significantly (P less than 0.05) less in lambs which had O circumcincta infections before their exposure to H contortus. There was less reduction in lambs from which O circumcincta was removed (anthelmintic therapy) before their exposure to H contortus. Fecal egg counts also were significantly (P less than 0.05) less in the former group of lambs (exposed to both parasites) than those in lambs exposed only to H contortus. Serum gastrin values were significantly (P less than 0.05) increased in lambs infected with O circumcincta and indicated that the interaction observed could be due, in part, to alteration of abomasal pH.  相似文献   

18.
SUMMARY Following the apparent failure of levamisole to control infections of Haemonchus contortus in sheep at Lawes in south eastern Queensland, a strain of this parasite was isolated at the Animal Research Institute, Yeerongpilly. This strain was used to infect sheep at Yeerongpilly and the Merrindale Research Station, Victoria where four experiments to classify the resistance pattern of the parasite were carried out. Resistance to thiabendazole was first suspected in 1969, and these experiments confirmed that resistance to this drug was still present. They also showed that a strong degree of resistance had been developed to both levamisole and morantel tartrate. Other benzimidazole anthelmintics and also the organophosphorus compound naphthalophos were only moderately effective against the original isolate but rafoxanide, nitroxynil and phenothiazine were almost 100% effective. Other highly effective chemicals were disophenol and closantel. After passaging the strain for four generations with both levamisole and albendazole, resistance to both naphthalophos and the newer benzimidazole anthelmintics increased dramatically. This is the first report of a field strain of H. contortus exhibiting resistance to benzimidazole, non-benzimidazole and organophosphorus anthelmintics.  相似文献   

19.
Ivermectin resistance in the nematode Haemonchus contortus has been reported in many parts of the world and many ivermectin resistant isolates have been found to have reduced sensitivity to moxidectin. However, it is unclear whether parasites that are selected with moxidectin would demonstrate reduced sensitivity to ivermectin. In this study, the effects of moxidectin and ivermectin on an unselected strain and a strain of H. contortus derived from the unselected strain but selected over 14 generations with moxidectin, were compared in jirds. The recovery of adult worms and fourth stage (L4) larvae following treatment were compared between strains and anthelmintics. Moxidectin-selected H. contortus showed reduced sensitivity to ivermectin as well as to moxidectin. Doses of 0.1 mg/kg of moxidectin and 0.4 mg/kg of ivermectin were necessary to obtain an efficacy of 95% or above against the moxidectin-selected strain of H. contortus compared with 0.025 mg/kg for moxidectin and 0.1 mg/kg for ivermectin required for a similar efficacy in the unselected strain.  相似文献   

20.
A method of using commercially available benzimidazole anthelmintics in an egg hatch test, to record levels of resistance is described. The test shows that a side-resistance is present to all the benzimidazole anthelmintics tested against both Haemonchus contortus and Trichostrongylus colubriformis after selection with thiabendazole. Additional selection on the field resistant strain of H contortus with thiabendazole showed increased levels of resistance to all the compounds tested while similar selection of T colubriformis failed to change the level of resistance after 20 generations. The level of resistance recorded by the egg hatch test in vitro is greater than that recorded for adults in vivo for the CF strain of H contortus and T colubriformis. Problems associated with reading the test are mentioned as are the different levels for the threshold of activity.  相似文献   

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