Development of antiparasitic drugs in the 21st century

Prospects for discovering new antiparasitic drugs for veterinary medicine in the coming century will be determined by economic, social and scientific factors. Consolidation in the pharmaceutical industry in general, and the animal health industry in particular, changes the business conditions in which drug discovery for veterinary medicine occurs. Social pressures on traditional animal agriculture and companion animal ownership have shifted the interest of animal companies primarily to pet medicine. Antiparasitic drug discovery is more than ever targeted to the most lucrative market segments, but the excellence of available drugs, and the apparent lack of resistance in important parasites, reduces industrial motivation to invest in parasitology. Veterinary parasitologists in academia will still have the chance to interact with their industrial counterparts in the traditional ways of supporting drug discovery and development. Nonetheless, there are many new opportunities to expand the research horizons of veterinary parasitology to strengthen the case for retaining a significant presence in the animal health industry.     

Methods in the evaluation of antiparasitic drugs in the horse.

The critical test is the primary method used for the efficacy evaluation of drugs against the major internal parasites (bots, ascarids, large strongyles, small strongyles, and pinworms) of the horse. The critical test determines: (1) spectrum of activity, (2) effectiveness of removal, (3) pattern of discharge, and (4) physical condition of each species of these parasites. General characteristics of the major parasitisms of the horse are discussed briefly. Criteria of the critical test also are considered including: (1) number of tests, (2) strain variation and drug resistance, (3) selection of test horses, (4) diagnosis of parasitic species, (5) numbers of parasites, (6) minimal efficacy requirements, and (7) other parasitic species. The controlled test principally is used on a selected basis for the small nematodes in the proximal portion of the digestive tract which cannot be properly evaluated by the critical test, or for other limited objectives. Clinical trials are discussed briefly but are invaluable supplements to the critical and controlled tests in the total assessment of a drug as a new product or for continued effectiveness in clinical use. Experimental procedures used in the conduct of drug evaluations should not be rigidly prescribed but should reflect input by the individual investigatior.     

Individual intake and antiparasitic efficacy of free choice mineral and fenbendazole in range calves

The current study was conducted to assess the feasibility of fenbendazole (FB) administration to steers in a free choice mineral supplement. Provision of free choice FB reduces the need for handling of animals as well as decreases the level of animal parasitism. Two separate trials were conducted using 400 +/- 19 kg Holstein steers (n=14 and 17) during the months of July and August. Each steer was tagged with a unique electronic identification (EID) ear tag and randomly allocated into one of two groups. The tags worked in conjunction with a mineral feeder equipped with a load cell by registering the steer's EID number every time the animal entered the electromagnetic field. Individual daily mineral intake and feeding times were determined over two 8-day periods of non-medicated mineral (no FB), separated by a 14-day period of medicated mineral (0.55% FB). Fecal samples were collected at the beginning and end of each trial period and were analyzed for gastrointestinal nematode eggs and Giardia cyst. There was a consistently high level of attendance for the entire experimental period, with the exception of the first six days of the adaptation period. There were three preferential times for visiting the mineral feeder, approximately 07:00, 12:00 and 18:00 h. Individual daily mineral and FB intake was 229 +/- 27.21 g/day and 2 +/- 0.14 mg/kg BW/day, respectively, for the 14-day drug delivery period. The levels of fecal nematode eggs and Giardia cysts decreased significantly (<0.01) between pre- and post-sampling, with reductions of 92% for nematode eggs and 85% for Giardia cysts. Free choice medication for the control of gastrointestinal parasites is potentially effective, provided that the appropriate drug concentration, adaptation period, intake level and duration of treatment is utilized.     

Individual intake and antiparasitic efficacy of free choice mineral containing fenbendazole for grazing steers

A 95-day study (June 25-September 27, 2001) was conducted using 120 steers (311.9+/-2.4 kg) randomly allocated to two treatments: (1) mineral containing 0.55% fenbendazole (FBZ) and (2) control, no FBZ in the mineral. Animals in the FBZ group were individually identified by an electronic tag that was read each time an animal attended the mineral feeder. The feeder was equipped with load cells that enabled individual mineral intakes to be estimated. The FBZ group was provided with non-medicated mineral during a 14-day adaptation period (July 23-August 5) and an 8-day post-medication period (September 17-24). The intake of FBZ was monitored for 14 days during each of the two treatment periods; August 6-19 and September 3-16, separated by a 14-day non-medicated period, August 20-September 2. Control animals had access to non-medicated mineral for the entire 95-day study period. All steers were grazed on alfalfa-grass pasture for the duration of the study and had free access to flocculated, filtered and chlorinated water via an automatic waterer. Fecal samples were collected from steers three times during the experiment July 23, August 27 and September 27, and analyzed for nematode eggs and Giardia sp. cysts. Seventy-five and 83% of the steers in the FBZ group visited the mineral feeder during the first and second treatment periods, respectively. Individual daily mineral and FBZ intake for the first and second treatment periods was 52.9+/-6.6g per day and 10.1+/-1.2mg/kg BW; 72.3+/-8.4 g per day and 11.8+/-1.4 mg/kg BW, respectively. FBZ animals were separated into three groups during each treatment period based on the recommended dose (RD) of FBZ (5 mg/kg/BW), those that received > the RD, those that received < RD but > 50% RD and those that received < 50% of RD. Nematode egg counts and the number of animals infected with nematodes was reduced (p < 0.05) in all cattle that consumed FBZ as compared to control animals. In contrast to nematode eggs, numbers of Giardia cysts was not reduced (p > 0.05) by FBZ as compared to controls in either treatment period. These results may be a reflection of Giardia re-infection occurring following treatment and highlight the need for variation in treatment regimes specifically targeted at the parasite of interest.     

Effect of the antiparasitic drugs fenbendazole and ivermectin on the soil nematode Pristionchus maupasi

Pristionchus maupasi, a soil nematode, was used to elucidate the potential ecotoxic effect of the two anthelmintics fenbendazole and ivermectin in cattle dung. The population growth of P. maupasi was greater in faeces from cattle harbouring active Panacur- or Ivomec-boli, which are releasing fenbendazole and ivermectin to the rumen, respectively, compared to the growth in control faeces. In dose-response experiments it could be shown that the pure chemical compound of fenbendazole was increasingly nematocidal to P. maupasi in concentrations from 10 to 20 microg/g faeces (ww, i.e. wet weight) and the pure compound of ivermectin was effective above 3 microg/g faeces (ww). The results indicate that neither fenbendazole nor ivermectin have any acute toxic effect on P. maupasi in naturally excreted concentrations of the pure drugs, together with their metabolites in faeces from bolus-treated cattle. Both drugs are excreted in concentrations that are non-toxic to P. maupasi.     

抗蠕虫药对人工感染豆状囊尾蚴家兔肌肉主要营养成分的影响

为分析不同驱虫药对感染豆状囊尾蚴肌肉营养成分含量的影响,本试验采用3种抗蠕虫药（甲苯咪唑、吡喹酮、丙硫苯咪唑）对人工感染豆状囊尾蚴家兔进行驱虫试验,并对感染豆状囊尾蚴后和驱虫后家兔肌肉营养成分（水分、灰分、脂肪和蛋白质）含量变化进行分析。结果表明,3种抗蠕虫药对家兔感染豆状囊尾蚴均有不同程度的驱虫效果,家兔肌肉营养成分含量有不同程度的升高。其中,甲苯咪唑和丙硫苯咪唑对家兔肌肉中的水分、脂肪和蛋白质含量影响较大,吡喹酮驱虫后家兔肌肉中灰分含量增加较明显。     

Comparative efficacy of drugs in bovine anaplasmosis

Summary Calves experimentally infected withAnaplasma marginale were subjected to chemotherapeutic treatment in groups, each group receiving one drug only. Observations were made on clinical signs, haematological changes, parasitaemias and levels of antibodies as measured by the complement fixation test. The most effective treatment was with imidocarb; other drugs which were apparently effective were steclin, terramycin and aureomycin in that order, while chloroquin diphosphate and camoquin gave little indication of therapeutic value.

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Eficacia Comparativa De Drogas En La Anaplasmosis Bovina

Resumen Diferentes grupos de terneros infectados conAnaplasma marginale se sometieron a tratamientos quimioprofilácticos con una droga específica cada uno. Se observaron los síntomas clínicos, cambios hematológicos, parasitémias y niveles de anticuerpos, estos últimos mediante la prueba de fijación de complemento. El tratamiento más efectivo fue con imidocarb y en orden decreciente con esteclin, terramicina y aureomicina. El difosfato de cloroquin y el camoquin no tuvieron valor terapéutico.

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Efficacite Comparee De Medicaments Contre L'anaplasmose Bovine

Résumé Des veaux expérimentalement infectés parAnaplasma marginale ont été soumis à des traitements chimiothérapiques de groupe, chacun de ces groupes ne recevant qu'un seul des produits essayés. Les observations ont parté sur les signes chimiques, les variations dans les formules hématologiques, la parasitémie et le niveau des anticorps mesurés par la réaction de fixation du complément. Le traitement le plus efficace a été obtenu avec l'imidocarbamide; les autres corps qui ont été apparemment efficaces ont été: steclin, terramycine et aureomycine dans cet ordre, alors que le diphosphate deichloroquine et al camoquine n'ont paru avoir qu'une action thérapeutique très limitée.

     

Comparative efficacy of drugs in bovine anaplasmosis

Calves experimentally infected with Anaplasma marginale were subjected to chemotherapeutic treatment in groups, each group receiving one drug only. Observations were made on clinical signs, haematological changes, parasitaemias and levels of antibodies as measured by the complement fixation test. The most effective treatment was with imidocarb; other drugs which were apparently effective were steclin, terramycin and aureomycin in that order, while chloroquin diphosphate and camoquin gave little indication of therapeutic value.     

抗寄生虫药物的正确使用

动物寄生虫病给养殖业造成很大的损失,抗寄生虫药物能消灭动物体内的寄生虫,治愈或减轻病情,促进畜体健康。合理地使用抗寄生虫药物,规范地治疗各种寄生虫病,在取得最佳疗效的同时,最大限度地避免不良反应的发生,还能有效消灭传染源,切断传播途径,预防寄生虫的感染。因此,正确使用抗寄生虫药非常重要。     

5种麻醉药对牛的麻醉效果比较

在临床实践中 ,用于牛的全身麻醉的药物很多 ,为研究这些药物的不同特性 ,从中选出用于牛临床麻醉的最佳药物 ,我们用眠乃宁、846合剂、静松灵、保定 号、酒精 5种麻醉药对牛的比较试验。1　材料与方法1 .1　试验动物　虎林市太和乡平原村王振恒家即将捕杀的 1 8头黄牛。临床手术牛 1 7头。1 .2　试验药品　眠乃宁 :中国人民解放军军需大学军事兽医研究所生产 ,批号 931 0 1 2 ;846合剂 :中国人民解放军军需大学军事兽医研究所生产 ,批号931 0 0 4 ;静松灵 :浓度 2 % ,河北省荣城县兽药厂生产 ,批号 85 0 72 6;保定 号 :北京科技协作中心…     

The antiparasitic activity of ivermectin in horses

Parenteral administration of ivermectin (22,23-dihydroavermectin B₁) significantly reduced the numbers of adult large and small strongyles, the immature stages of small strongyles, pinworm and ascarid, the microfilariae of Onchocerca cervicalis and gastrophilid bots from naturally infected horses. Strongylus vulgaris, S. edentatus and S. equinus were effectively removed by 0.02 mg/kg. Adult small strongyles, Cyathostomum pateratum, C. catinatum, Cylicocyclus nassatus, C. leptostomus, Cyliostephanus minutus, C. longibursatus and C. goldi, were effectively removed by 0.1 mg/kg. Fourth stage small strongyles (cyathostomes), 4th stage Oxyuris equi, 5th stage Parascaris equorum and the microfilarie of Onchocerca cervicalis were significantly reduced by 0.1 mg/kg also. The stomach bots, Gastrophilus intestinalis and G. nasalis, were effectively removed by 0.02 mg of ivermectin/kg. Analysis of the dose response curves obtained for the nematode and larval dipteran parasites found in these naturally infected horses suggests that a parenteral dose of 0.2 mg/kg ivermectin would produce 95% or more removal of these parasites. The antiparasitic efficacies observed for ivermectin in this controlled trial were equivalent to the efficacies found in an abbreviated critical trial contained within the controlled trial. However, it was calculated that the man—day effort required for data collection from one critical trial horse was the same as for 6 controlled-trial horses.     

三种鸡抗球虫药的效力比较试验

鸡球虫病是养禽业中常见的一种疾病,它对养鸡生产的危害十分严重,分布很广。在我国抗球虫药物的种类很多,但由于球虫耐药性的普遍存在,抗球虫应用效果不是很理想。试验通过挑选健康雏鸡随机分组,在人工感染鸡柔嫩艾美耳球虫条件下,评估3种抗球虫药物(磺胺氯吡嗪钠、马杜拉霉素、盐酸氯丙嗪)的抗球虫效果,并对3种抗球虫药物进行比较,以抗球虫指数(ACI)作为药物治疗效果的综合评定指标,为规模化养鸡场提供试验依据,以适应生产实际需要。     

Effect of antiparasitic treatment in beef replacement heifers

Two studies were conducted in western Canada to evaluate the impact of antiparasitic treatment on weight gain and reproductive performance in beef replacement heifers from weaning to first breeding. Treatment of heifers at weaning with ivermectin increased the rate of weight gain in comparison to treatment with fenthion. The feed efficiency of ivermectin-treated animals was also significantly better than those treated with fenthion. Increased weight was associated with an increased number of animals in estrus at the end of the feeding period for heifers receiving ivermectin. We concluded that treatment with ivermectin improved feed efficiency and weight gain in heifers from weaning to breeding. In turn, this weight gain appeared to be associated with an increased number of heifers in estrus.     

兽用抗寄生虫药克洛素隆的研究进展

克洛素隆 (4 氨基 6 三氯乙烯 1 ,3 苯二磺胺 )是经美国食品药物管理局 (FDA)批准最早用于治疗牛肝片吸虫 (Fasciolahepatica)病的磺胺类药物。本文主要从作用机理、药物代谢动力学、毒理学、药物残留及临床应用等方面追溯了国外对其研究概况     

The activity of closantel as an equine antiparasitic agent

Eighteen pony foals were experimentally infected with 500 third stage larvae of Strongylus vulgaris at 2 weeks, and at 2, 4, 6 and 8 months after birth. For the duration of the study, all foals were kept in the same pasture with their mothers to allow natural infection with other parasites by exposure to a contaminated environment. Twelve of the foals were utilized in groups of 3 and treated orally five times at two month intervals starting at one month of age with closantel at doses of 5, 10, 20 or 40 mg kg-1. Ten months after birth the foals were necropsied to determine the parasitic burdens in the gastrointestinal tracts and the cranial mesenteric arteries. The results indicate a high antiparasitic activity of closantel against larval stages of Gasterophilus intestinalis and S. vulgaris, as well as against adult S. vulgaris, S. edentatus, Anoplocephala perfoliata and Triodontophorus spp., when used at doses of 20 or 40 mg kg-1.     

The pharmacokinetics and antiparasitic activity of ivermectin in Hutsul and Toric horses

The aim of this study was to compare the pharmacokinetics of ivermectin and its antiparasitic activity in two horse breeds. Eight Hutsul and 14 Toric horses were administered ivermectin orally at a dose of 0.2 mg/kg body weight. Blood samples were collected for 96 hr, and faecal samples were collected one day before and on days 14 and 21 after drug administration. Ivermectin concentrations in plasma samples were determined by high‐performance liquid chromatography. Ivermectin concentration was significantly higher in Toric than in Hutsul horses 90 min after ivermectin administration and was maintained at higher level for up to 96 hr. The area under the concentration versus the time curve from 0 to the last sampling point (AUC_0→t) and the maximum plasma concentration (C_max) were significantly higher in Toric than in Hutsul horses (1792.09 ± 246.22 μg × hr/L vs. 716.99 ± 255.81 μg × hr/L and 62.72 ± 17.97 ng/ml vs. 35.34 ± 13.61 ng/ml, respectively). No parasitic eggs were found in the faecal samples collected from both groups of horses on days 14 and 21 after drug administration. The obtained results indicate that although the pharmacokinetics of ivermectin may differ significantly between horse breeds, these differences do not affect the effectiveness of therapy.     

Effect of antiparasitic medication in ponies on pasture.

Twenty Shetland ponies, 6 to 7 months old, were naturally infected with gastrointestinal nematodes and stomach bots. The ponies were allotted to 2 groups of 10 and were maintained on separate similar pastures that were free of infective larvae at the beginning of the study. The ponies in 1 group were treated monthly for 17 months with a therapeutic dose of a thiabendazole and piperazine mixture; those in the other group were not treated. During the 3rd and 5th months of the experiment, the ponies in the treated group were also given therapeutic doses of dichlorvos to remove bots. Various physical, hematologic, parasitologic, and blood chemical observations were made at weekly intervals. Each group of ponies was weighed at biweekly intervals. At the end of the experiment, the greatest differences between the treated and control ponies were in the mean number of worm eggs in fecal samples (0 vs 1,866 eggs/g), mean body weight (151.9 vs 117.0 kg), mean heart girth (126.5 vs 116.3 cm), mean packed cell volume (36.4 vs 30.8%), and mean serum protein content (8.47 vs 9.33 mg/100 ml), especially beta-globulin content (mean of 1.9 vs 3.4 mg/100 ml). The treated ponies remained clinically normal and were more spirited and more difficult to restrain for blood sampling and weighing than were the untreated controls. Parasitic nematode larvae were not recovered from grass samples from the pasture grazed by the treated ponies, but many such larvae (up to 500/300-g sample) were recovered from grass samples from the pasture grazed by the untreated ponies.     

药物驱除山羊消化道蠕虫的效果观察

本文报道三种药物驱除山羊消化道蠕虫的效果观察.选农民自养山羊20只,用丙硫苯咪唑、硫双二氯酚、伊维菌素驱除消化道蠕虫试验,表明应用丙硫苯咪唑、硫双二氯酚驱除线虫的效果前者优于后者,而对吸虫和绦虫则后者优于前者.伊维菌素对蠕虫和外寄生虫均有良好效果.