Evaluation of ivermectin paste in the treatment of ponies for Parascaris equorum infections

Twenty ponies less than 18 months of age and infected with Parascaris equorum were treated with either 0.2 mg of ivermectin/kg of body weight (n = 10) or a placebo (n = 10; controls). Five control and 5 ivermectin-treated ponies were euthanatized 14 and 35 days after treatment, respectively. At necropsy, the small intestinal contents, lungs, and liver were examined for larvae and/or adult P equorum. Significantly (P less than 0.02) higher mean total numbers of P equorum were found in the small intestinal contents of the controls on day 14 (51) and on day 35 (21) than in the ivermectin-treated ponies on days 14 (0) and 35 (3). The efficacy of ivermectin in removing adult and intestinal larvae of P equorum at 14 days after treatment was 100%. The efficacies of ivermectin in removing adults and intestinal larvae of P equorum at 35 days after treatment were 100% and 76.9%, respectively. Gross examination of liver and lung tissues revealed damage as a result of P equorum infections in all ponies. The Baermann technique used on liver and lung tissues did not yield any P equorum larvae. Adverse reactions attributable to treatment were not observed.     

Efficacy of an oxibendazole-trichlorfon paste formulation against third stage larvae of Gasterophilus intestinalis and its safety in horses

A paste formulation containing 14.3 per cent of oxibendazole and 44 per cent of trichlorfon was administered to 33 ponies and horses. The dose rate used was equivalent to 10 mg and 30 mg/kg bodyweight, of oxibendazole and trichlorfon respectively. After treatment 25 animals passed between one and 82 third stage larvae of Gasterophilus intestinalis in their faeces. Dosing with 0.2 mg ivermectin/kg bodyweight three weeks later resulted in six animals expelling between one and four bots. The efficacy of the oxibendazole-trichlorfon paste was on average 96.2 per cent. This drug combination given to 52 ponies and horses at the indicated dose rate and to six ponies at twice that dose was tolerated without side effects except transient softening of the faeces in several animals and mild symptoms of colic in two horses.     

Serum protein changes in ponies on different parasite control programmes

Serum protein responses were examined in 52 ponies divided into five groups and subjected to various control strategies that resulted in pasture infectivity ranging from 706 to 18,486 infective third stage, cyathostome and Trichostrongylus axei larvae per kilogram of herbage (L3/kg) by 17 September 1984. Major protein changes occurred only in young ponies (Groups 4 and 5) and were observed before exposure to maximum numbers of pasture larvae (Group 4; 10,210 L3/kg, Group 5: 10,042 L3/kg) on 17 September. It appeared that a primary infection of T axei was a greater stimulus to serum beta-globulin and immunoglobulin (Ig)G(T) responses that provided by continued infection with cyathostome (small strongyle) worms. The large strongyles (Strongylus vulgaris, S edentatus and S equinus) were not detected in any larval cultures or on pastures grazed by the young ponies. A fall in beta-globulin and IgG(T) concentrations of Group 5 ponies one month after treatment with ivermectin indicated a larvicidal action against T axei and/or the cyathostomes. A subsequent rise in serum albumin concentrations of Group 5 ponies suggested that a protein-losing gastroenteropathy had been alleviated by the larvicidal action of ivermectin. Mature control ponies (Group 1) showed little beta-globulin response and only a modest IgG(T) response in six of the 10 ponies after exposure to heavily infected lawns (18,486 L3/kg) in September 1984. It was concluded that serum protein and IgG(T) responses were of limited value as an aid to diagnosis of parasitism because of numerous difficulties of interpretation.     

猪蛔虫性别特异基因在第三、四期幼虫的表达谱研究

为研究猪蛔虫性别特异基因在第三期、第四期幼虫的表达情况，本研究采用表达谱基因芯片技术，从所构建的猪蛔虫雌、雄成虫cDNA消减文库中分别挑取克隆，制备成cDNA微阵列芯片、标记有荧光素Cy5-dUTP和Cy3-dUTP的各组探针（L3＋♀；L3＋♂；L4＋♀；L4＋♂）分别与制备好的芯片进行杂交、扫描，原始信号值经均一化处理后，获取每个点的Ratio值（Ratio=Cy5／Cy3）．根据该值筛选出表达差异最明显的841个克隆，进行测序分析，在获得的707个有效序列中有61个是猪蛔虫新的ESTs、将在第三、四期幼虫以及成虫中显著表达的克隆进行排列组合比较，获得各期特有和各期之间共有的表达克隆一在第三期幼虫中，雌、雄性别特异基因分别有21和9个，编码的主要蛋白有卵黄原前导蛋白、睾丸幼胚蛋白等；在第四期幼虫中特异表达的雌、雄性别基因分别有22和6个，其中免疫抑制卵巢信息蛋白、主要精子纤维蛋白（MFP）等表达明显本项研究结果不仅初步阐明了猪蛔虫性别特异基因在第三、四期幼虫的表达情况，而且亦为筛选控制猪蛔虫病的“关键”基因并阐明其功能奠定了基础。     

Effect of repeated oxfendazole treatments on small strongyle infections in Shetland ponies

Overwintering of horse cyathostomes as inhibited third stage larvae (L3) and the effect of repeated oxfendazole (OFZ) treatment on strongyle infections were studied in an experiment with two groups of three Shetland ponies. Both groups were grazed together from May 28 to November 11, 1986 and subsequently housed. Treatments with 10 mg OFZ kg-1 were given on May 26, July 1 and July 28 and again one week before each group was necropsied in December and April, respectively. Worm populations of both groups were dominated by inhibited early L3. The proportion of fourth stage larvae (L4) was significantly higher in April than in December. The faecal egg counts showed that the OFZ treatment in May was more effective than those in July. This resulted in high pasture larval counts from the end of August onwards. The final treatments revealed a low efficacy against L3 and L4 but not against adult worms.     

Epidemiology and control of equine strongylosis at Newmarket

Seasonal rises in mean faecal egg output were observed in grazing ponies in spring (578 eggs per gram) and in summer (930 epg) on 30 April and 2 September, respectively, in untreated ponies. Pasture infectivity reached a peak of 18,486 third stage larvae (L3)/kg on 17 September, two weeks after peak egg counts, coincidental with abundant September rainfall (103.0 mm). Differentiation of infective larvae from pasture showed the cyathostomes (small strongyles) to be predominant, but Trichostrongylus axei assumed major importance from late August to October. The large strongyles were rarely detected: Strongylus vulgaris was found only once and S edentatus only twice. The most effective parasite prophylaxis was achieved by twice weekly removal of faeces. In this group, concentrations of infective L3 on pasture reached a maximum of 1000 L3/kg, compared to 18,486 L3/kg for a control group and 4850 to 10,210 L3/kg for anthelmintic treatment groups. The removal of faeces increased the grazing area by about 50 per cent, by eliminating the characteristic separation of horse pasture into roughs and lawns. Spring and summer anthelmintic treatments of mature ponies with oxibendazole were effective in reducing the late season rise in pasture infectivity to 4850 L3/kg, but treatment of young ponies (mainly yearlings) with ivermectin every eight weeks or oxibendazole every four weeks resulted in pasture infectivity as high as 10,000 L3/kg. There was evidence of cyathostome resistance to benzimidazole drugs.     

Comparison of two control systems for cyathostome infections in the horse and further aspects of the epidemiology of these infections

The small strongylid infections of two groups of three yearling female Shetland ponies and one yearling Shetland tracer pony were studied. One group was set stocked from April to November and was treated monthly with 5 mg kg-1 albendazole from two days before turnout until July. The other group grazed similar pasture until July, was treated with 5 mg kg-1 albendazole and subsequently removed to pasture grazed by sheep from April to July. The tracer ponies were added to both groups in September. The efficacy of both methods was not completely satisfactory probably because of low efficacy of anthelmintic treatment. There were no significant differences between the cyathostome burdens of the two groups. A high proportion of the cyathostome populations of all ponies consisted of inhibited early third stage larvae (L3). The finding of low numbers of immature fifth-stage worms in the tracer ponies indicated that the considerable adult burdens in the permanent ponies originated from infection picked up before the tracer ponies were added. In the group which was removed to sheep pasture after treatment in July it was likely that the majority of the adult worm burden had been ingested as infective larvae before treatment.     

Effect of early season ivermectin and pyrantel treatments on strongylid infections in young Shetland ponies in The Netherlands

Two groups of three ponies were used to study the effect of three ivermectin or pyrantel treatments given at intervals of 5 weeks at the beginning of the grazing season. Although each pyrantel treatment resulted in a greater than 95% reduction in faecal egg counts during the first 3 weeks, high pasture larval counts were seen from the beginning of August onwards and substantial cyathostomine burdens were found at necropsy in December. The ivermectin treatments resulted in an even more pronounced reduction in faecal egg output, and the pasture larval counts and cyathostomine burdens at necropsy were considerably lower than in the pyrantel group. The proportion of inhibited early L3 of the cyathostomines was lower in the ivermectin than in the pyrantel group. Faecal egg output of the large strongyles was completely suppressed in the ivermectin group. Nevertheless, Strongylus vulgaris larvae were found in the arteries of all three ponies, possibly as a result of overwintering of infective larvae on pasture. In the pyrantel group, the egg output of Strongylus edentatus and, to a much lesser extent, Strongylus vulgaris, was not completely suppressed.     

Control of gastro-intestinal parasitism in sheep with ivermectin delivered via an intraruminal controlled-release capsule

The efficacy of ivermectin delivered by an intraruminal controlled-release capsule against gastro-intestinal nematodes of sheep was evaluated under controlled conditions. In seven Australian studies involving 170 Merino or Merino x Border Leicester sheep, intraruminal capsules developed for 20-40 kg or 40-80 kg sheep, and delivering 0.8 or 1.6 mg of ivermectin/day respectively for 100 days (minimum dose 20 microg/kg/day), were evaluated. Studies were designed to test the therapeutic efficacy against naturally acquired and induced infections treated at the adult and fourth larval stage, and the prophylactic efficacy against naturally acquired and induced infections with third stage infective larvae. The predominant pathogenic nematodes of sheep were represented. Two studies included known benzimidazole- and levamisole-resistant nematode strains. Sheep were necropsied for total nematode counts 21-8.5 days after treatment. The efficacy of the ivermectin controlled-release capsule was generally >99% against all nematode species tested, including those confirmed to be benzimidazole- and levamisole-resistant. High therapeutic activity was demonstrated against existing adult and fourth larval stage nematode infections at the time of treatment, and high prophylactic efficacy was shown against incoming third stage larvae of all species and strains tested.     

Inhibited development of cyathostominae in the horse in the early third stage

Inhibited early third stage larvae of Cyathostominae were found in the digested mucosa of the large intestine of 12 yearling, female Shetland ponies, which were used in two grazing experiments. The ponies were killed in late autumn. In some ponies the inhibited larvae were very abundant and in most animals the majority of the Cyathostominae populations consisted of these early third stage larvae, suggesting that the phenomenon has an epidemiological significance.     

Evidence of multiple anthelmintic resistance in a strain of Teladorsagia circumcincta (Ostertagia circumcincta) isolated from goats in Scotland

The efficacy of ivermectin, fenbendazole and levamisole was determined in lambs individually infected with 5000 third stage larvae of Teladorsagia (Ostertagia) species isolated from a herd of goats with a history of benzimidazole resistance and where the efficacy of ivermectin had also suffered an apparent decline. Efficacies, calculated using geometric means, for groups where treatments were directed against adult worms were 90.3 per cent (ivermectin), 43.4 per cent (fenbendazole) and 100 per cent (levamisole). The efficacy of ivermectin against immature stages was 83.2 per cent. Ivermectin was highly effective (99.9 per cent) against a known susceptible ovine strain of Teladorsagia.     

Efficacy of an ivermectin and pyrantel pamoate combination against adult hookworm, Ancylostoma braziliense, in dogs

A chewable tablet incorporating ivermectin and pyrantel was tested in 12 Beagle dogs for efficacy against the adult hookworm, Ancylostoma braziliense. The dogs were administered infective larvae of A braziliense orally. Twenty-one days after infection the dogs were weighed and allocated randomly to receive either an oral treatment with ivermectin and pyrantel in a beef-based chewable tablet or no treatment. The chewable tablet was a commercially available product, which was made to deliver ivermectin at 6 μg/kg and pyrantel at 5.0 mg/kg to each dog. Seven days after treatment the dogs were euthanased, necropsied, and examined for adult hookworms. At necropsy, no adult A braziliense was observed in any of the 6 treated dogs and all 6 dogs that had been left untreated were infected with adult A braziliense (range, 48 to 161). It was concluded that this combination product is 100% efficacious against adult A braziliense.     

Antibody responses of ponies to initial and challenge infections of Strongylus vulgaris

An indirect fluorescent antibody assay (IFA) was developed using Strongylus vulgaris third stage larvae (L3) as antigens. Observations using the IFA indicate that a species-specific antibody response to S. vulgaris L3 develops in S. vulgaris-infected ponies and that some surface L3 antigens are shared by adult worms. Sequential antibody levels against S. vulgaris were measured in strongyle-naive and in immune ponies following initial and challenge infections using the IFA and an indirect hemagglutination assay (IHA). Antibody levels measured by IFA increased faster following initial infections than did levels measured by IHA. Antibody levels appear to increase following challenge infections of immune ponies when measured with the IFA, but not with the IHA. Significant differences in antibody titers were not seen between ponies which developed colic following challenge infections and those that did not develop colic. Antibodies were not detectable in ponies unexposed to larval migrations, but which received surgical implantation of S. vulgaris adults into the cecum.     

Sequential mesenteric arteriography in pony foals during repeated inoculations of Strongylus vulgaris and treatments with ivermectin

Semiselective mesenteric arteriography was performed at regular intervals (inoculation weeks [IW] 0, 11, 18, and 24) in 9 of 10 pony foals raised to be free of parasites. Fifty infective larvae (L3) of Strongylus vulgaris were administered weekly for 4 weeks, then every 2 weeks through the 20th week. Three ponies were given ivermectin (oral paste, 0.2 mg/kg of body weight) treatment at IW 8, 16 and 24. Four ponies were inoculated, but did not receive ivermectin, and a third group of 2 ponies acted as uninoculated controls. Control ponies did not have gross or arteriographic lesions, whereas the inoculated untreated ponies had gross and progressive arteriographic lesions typical of verminous arteritis. Arteriographic lesions in the ivermectin-treated inoculated ponies were not as severe those in the untreated inoculated group, and there was either a partial resolution or a lack of progression of arteriographic lesions in all treated ponies. One untreated inoculated pony did not have progressive arterial lesions as did the 3 others in the group, and may develop resistance to the parasite.     

Efficacy of ivermectin against Dictyocaulus arnfieldi in ponies

The efficacy of orally administered ivermectin against induced Dictyocaulus arnfieldi infection was evaluated in a controlled study comprising 12 yearling ponies. Treatment with ivermectin paste, at a dose rate of 200 micrograms/kg bodyweight orally once, was 100 per cent effective against both adult and immature or inhibited stages of the horse lungworm. Similar control of second and third instars of Gastrophilus intestinalis was observed and no nematode eggs were present in faeces from seven to 15 days after treatment when the study was terminated.     

Efficacy of thiabendazole, mebendazole, levamisole and ivermectin against gullet worm, Gongylonema pulchrum: in vitro and in vivo studies

In vitro and in vivo studies were conducted to evaluate the effects of thiabendazole, mebendazole, levamisole and ivermectin against Gongylonema pulchrum. For in vitro assays, third-stage larvae (L3) incubated with the drugs were administered orally to mice and the ability of larvae to invade the gastric mucosa of the animals was examined. After incubation, only those larvae treated with high concentrations of levamisole (1 and 10 microg/ml) were tightly coiled with intestines exhibiting morphological abnormalities. Good dose-response data for the drugs tested was observed at the time of worm recovery from mice, with no worms recovered at the two highest concentrations of levamisole. In vivo efficacy of the drugs against adult worms was evaluated in six groups of three rabbits, each of which was infected with 30 L3 of G. pulchrum and treated with thiabendazole at 100 mg/kg for 3 days, mebendazole at 70 mg/kg for 3 days, levamisole as a single dose of 8 mg/kg, and subcutaneously injected ivermectin as a single dose of 0.2 mg/kg or vehicles of the drugs (control) at 4 months post-infection. Necropsy 14 days after treatment revealed that levamisole, mebendazole and ivermectin reduced worm burdens by 63.2%, 22.8% and 25.8%, respectively, with no reductions in worms observed with thiabendazole. The surviving worms were principally found in the esophagus with the remainder distributed among the buccal mucosa, the tongue, and/or pharyngeal mucosa in all groups. A number of morphologically abnormal eggs were observed within the uterus and ovijector in female worms recovered from the thiabendazole-treated group. These findings suggest that levamisole exhibits in vivo efficacy against G. pulchrum infection and that the larval invasion tests using mice could be used to screen for anthelmintic susceptibility of nematodes.     

Efficacy of ivermectin delivered via a controlled-release capsule against small lungworms (Protostrongylidae) in sheep

To evaluate the efficacy of an ivermectin controlled-release capsule (CRC), which delivers 1.6 mg ivermectin per day intraruminally for 100 days to sheep weighing 40-80 kg (IVOMEC Maximizer CR Capsule for adult sheep, Merial), against small lungworms two studies with 48 naturally infected adult female Merino Landrace sheep were conducted. The sheep were allocated by restricted randomization based on bodyweight to untreated controls or received an ivermectin CRC. Eight sheep per group were necropsied 35, 70 or 105 days post-treatment. Lungworms were recovered by dissection or peptic digestion of the lungs. Baermann/Wetzel technique was used for faecal lungworm larval counts at weekly intervals. The efficacy of treatment was 100% against Dictyocaulus filaria and Protostrongylus rufescens (P < 0.05) at each necropsy day. The efficacy against Protostrongylus brevispiculum, Cystocaulus ocreatus and Neostrongylus linearis increased from 35 to 105 days after administration of the CRC and was found to be 100% (P < 0.01), 96.6% (P < 0.01) or 99% (P < 0.01), respectively, at 105 days post-treatment. The reductions of Muellerius capillaris counts varied and were 96.2% (P < 0.05) at 70 days post-treatment and 44.6% (P > 0.1) at 105 days post-treatment. Faecal lungworm larvae disappeared nearly completely from at least 3 weeks after the ivermectin CRC administration for all protostrongylid species including M. capillaris so that pasture infectivity will be subsequently significantly reduced.     

Efficacy of levamisole against Ostertagia ostertagi in Louisiana cattle during maturation of inhibited larvae (September) and during minimal inhibition (December/January).

Levamisole (LEV) was tested in four experiments to compare efficacy values against Ostertagia ostertagi when larval maturation was occurring (September), following inhibition and also when populations were expected to be largely adult (winter). A primary objective was to determine the importance of developing fourth-stage larvae (DL4) and inhibited, early fourth-stage larvae (EL4) in replacing adult worms lost through treatment and the effect of this on reduced efficacy against adult worms. Young crossbred beef calves ranging in weight from 150 to 230 kg were used in the first (September 1981), second (September 1983) and third experiments (January 1987). Jersey calves of 110 kg average weight were used in the fourth experiment (December 1988). Calves were randomized to groups according to weight and group sizes ranged from three to five calves. All parasite infections were naturally acquired, but a mixture of nematode third-stage larvae (L3) (22,500 per calf), including 20% Ostertagia ostertagi, was inoculated into Jersey calves of Experiment 4 following a 2 week exposure to natural infection. All LEV treatments were by subcutaneous injection at dosages of 6 and 8 mg kg-1. Treatment with ivermectin was used only in Experiment 3 as an efficacy reference. All calves were killed at 8-10 days after treatment. The efficacy of LEV against all developmental stages of Ostertagia ostertagi was consistently low in all experiments and a dose-dependent response was not evident. Large numbers of all Ostertagia ostertagi developmental stages were present in non-treated calves in both September experiments. Percent reduction of adults, DL4 and EL4 at the 6 mg kg-1 and 8 mg kg-1 dosages, respectively, were adults, 51.7 and 23.6 (1981), 8.7 and 51.3 (1983); DL4 40.3 and 13.2 (1981), 37.9 and 33.1 (1983); EL4, 19.6 and 0 (1981), 59.6 and 42.9 (1983). Smaller numbers of Ostertagia ostertagi were present in winter experiments and adult worms greatly outnumbered larval stages. Percent reductions of adults, DL4 and EL4, respectively, were (1987) LEV 6 mg kg-1, 40.2, 0 and 0; ivermectin 200 micrograms kg-1, 98.7, 97.7 and 100.0; (1988) LEV 6 mg kg-1, 62.4, 100.0 and 100.0; LEV 8 mg kg-1, 49.1 65.0 and 74.1. Too few larval stages were present in the latter experiment for valid efficacy values.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ivermectin and milbemycin oxime in experimental adult heartworm (Dirofilaria immitis) infection of dogs

Background: The US Food and Drug Administration reports an increase in the frequency of reports of lack of effectiveness claims for heartworm (HW) prevention products. Hypothesis: At their labeled doses, single doses of commercially available HW prevention products are not completely effective against all field isolates of HW. Animals: Forty‐two HW‐free dogs experimentally inoculated with a recent HW field isolate. Methods: Placebo‐controlled, blinded laboratory clinical trial. Dogs randomly allocated to 1 of 3 treatment groups with 14 dogs per group. Groups were untreated control or PO dosed with milbemycin oxime (MBO) or ivermectin (IVM). Dogs were inoculated with 50 HW third stage larvae 30 days before dosing and necropsy was performed on Day 123 after treatment to enumerate adult HW. Results: Thirteen of 14 control dogs had adult HW detected at necropsy with a geometric mean worm count of 22.3. One HW was found in 1 dog in each of the MBO and IVM treatment groups. Conclusions and Clinical Importance: Two currently approved macrocyclic lactone HW preventives used at their labeled dose rates were <100% effective against a recent HW field isolate, supporting the hypothesis that the effectiveness of a single dose of these preventives can vary. This is important in guiding clients on expectations of product effectiveness.     

Seasonally inhibited development of cyathostomine nematodes in Shetland ponies in The Netherlands

Two groups of three yearling Shetland ponies were used in 1988 to study the epidemiological significance of inhibited development of the Cyathostomine nematodes. In Group 1, acquisition of infections was prevented throughout the grazing season whereas in Group 2 strongylid infections were acquired from the beginning of July until the end of September. Worm counts showed that the Cyathostomine nematode populations of Group 1 ponies mainly consisted of adult worms and those of Group 2 ponies of inhibited early third stage larvae (L3). These results indicate that a large proportion of Cyathostomine larvae which establish between the beginning of July and the end of September inhibit their development. The results also suggest that the pool of inhibited larvae which has overwintered in young ponies will be depleted in autumn.