Efficacy of milbemycin oxime against experimentally induced Ancylostoma caninum and Uncinaria stenocephala infections in dogs.

Twenty-eight helminth-naive Beagles, 16 to 26 weeks old, were inoculated with 200 third-stage larvae each of Ancylostoma caninum and Uncinaria stenocephala 5 times at weekly intervals. Dogs were randomly allocated to 4 groups of 7 on the basis of fecal egg counts, and treatments were randomly assigned. Groups 1 and 3 were given milbemycin oxime at a dosage of 500 micrograms/kg of body weight, PO, on day 0 and on days 0 and 30, respectively; groups 2 and 4 were nontreated controls. Fecal egg counts were evaluated before and after treatments. Feces were collected daily for 7 days after the final treatment for recovery of worms passed, and all dogs were euthanatized 7 days after the final treatment for recovery of worms retained. A 65.7% reduction from the pretreatment value for geometric mean hookworm egg count was found 7 days after the first treatment, and a 97.1% reduction 7 days after the second treatment. Although milbemycin oxime had 96.5% and 99.5% controlled efficacy against A caninum after 1 or 2 treatments, respectively, it lacked efficacy against U stenocephala. The geometric mean number of U stenocephala and the total number of hookworms retained after 1 or 2 treatments were not significantly different from the numbers retained by the corresponding control groups.     

Effects of milbemycin oxime on adult hookworms in dogs with naturally acquired infections

Previous work indicated that adult Ancylostoma caninum can be removed from experimentally infected dogs, using a formulation of milbemycin oxime at dosage of 0.5 mg/kg of body weight. To determine the efficacy of this treatment in dogs naturally infected with adult hookworms, 24 mixed-breed dogs with patent hookworm infections were purchased from an out-of-state vendor, and 6 male and 6 female dogs were assigned to either a control group or a group that would be treated. Dogs were treated 10 days after their arrival and were euthanatized 1 week after treatment. Beginning 3 days before treatment, fecal samples were collected daily from all dogs, and the number of Ancylostoma eggs per gram of dry weight of feces was determined from each sample. By 1 week after treatment, the mean number of eggs being passed by the treated dogs had dropped from 12,700 to 10 eggs/g of dried feces; there was no apparent change in fecal egg counts for dogs of the control group. At necropsy, the mean number of adult A caninum in dogs of the treated and control groups was 1.3 and 56, respectively; in these naturally infected dogs, efficacy of treatment was calculated to be 97.8%. The mean number of adult Trichuris vulpis recovered in dogs of the control and treated groups at necropsy was 24 and 0, respectively, which yielded treatment efficacy of 100%. Although Uncinaria stenocephala and Toxocara canis appeared also to be removed by use of this dosage, too few dogs were in the study to calculate meaningful efficacies.(ABSTRACT TRUNCATED AT 250 WORDS)     

The efficacy of milbemycin oxime against pre-adult Spirocerca lupi in experimentally infected dogs

The aim of this investigation was to determine the efficacy of milbemycin oxime in preventing the oesophageal encapsulation of Spirocerca lupi, following the experimental infection of dogs. Two studies were conducted which involved a total of 21 purpose-bred Beagles. Each dog was infected with approximately 40, third stage infective S. lupi larvae. The larvae were dissected from scarabaeid beetles that had been collected from areas endemic for spirocercosis. In the first study, milbemycin oxime (minimum dose 0.5mg/kg body weight) was administered to seven dogs on day 30 post-infection. Seven other dogs served as untreated controls. In the second study, milbemycin oxime (also at a minimum dose of 0.5mg/kg body weight) was administered to four of seven infected dogs on day 28 post-infection. Treatment was repeated at 14- or 28-day intervals. All of the dogs, from both studies, were euthanized 168 or 169 days after infection. All S. lupi were recovered, and lesions in the thoracic aorta and oesophagus were described and quantified. A single treatment with milbemycin oxime was 79.8% effective in preventing the establishment of S. lupi in the oesophagus. This treatment significantly (p<0.05) reduced both the number of S. lupi within the oesophagus and the size of the oesophageal nodules. The efficacy of anthelmintic treatment was increased to 100% when repeat doses of milbemycin oxime were administered at 14- or 28-day intervals. These repeat treatments completely prevented the establishment of S. lupi within the oesophagus and thereby averted the development of oesophageal nodules. As expected, none of the treatment protocols reduced S. lupi related damage within the aorta because the administration of milbemycin oxime only began after the larvae had completed their first stage of migration.     

Persistent efficacy of moxidectin canine sustained-release injectable against experimental infections of Ancylostoma caninum and Uncinaria stenocephala in dogs

The efficacy of moxidectin canine sustained-release injectable administered at fixed intervals before administration of an oral hookworm challenge was evaluated in 40 laboratory dogs. Groups of eight dogs were treated with the moxidectin sustained-release formulation by SC injection approximately 3, 4, 5, or 6 months before being given oral inoculations with 300 Ancylostoma caninum larvae on Day 0 and 400 Uncinaria stenocephala larvae one day later. Dogs were euthanized 21 days after parasite inoculations. Fecal samples and the intestinal contents collected at necropsy from each dog were examined for hookworms. Fecal egg count reductions based on geometric means relative to controls were 99.2% (3 months) to 81.2% (6 months). The reduction in A. caninum worm recoveries at 3, 4, 5, and 6 months based on geometric means were 94.7%, 90.3%, 82.0%, and 60.2%, respectively. The mean reductions in U. stenocephala worm counts at these intervals were 94.6%, 85.3%, 71.6%, and 48.2%,respectively.     

Effect of milbemycin oxime against Ancylostoma caninum in dogs with naturally acquired infection

Twenty-six mixed-breed (14 males, 12 females) dogs were used in a double-blind study to evaluate the effect of milbemycin oxime against naturally acquired infection with Ancylostoma caninum. Dogs were ranked and paired, on the basis of number of hookworm eggs/g of feces, and treatment was randomly assigned. Each dog was given either the study drug or placebo (1 tablet/11.4 kg [0.5 mg/kg] of body weight). Eggs per gram of feces enumeration was done on days 3 and 7 after treatment, and dogs were euthanatized on day 7. On day 3, 5 of the 13 dogs in the milbemycin-treated group had hookworm eggs in the feces (results of the McMaster test). In these dogs, mean number of eggs per gram of feces had decreased markedly (from 5,289 to 452) and, by day 7, was 114. At necropsy, 16 A caninum adults were recovered from 2 of the milbemycin-treated dogs. On day 3, 12 of the 13 dogs in the placebo-treated group had hookworm eggs in the feces. Mean number of eggs per gram of feces in these dogs decreased slightly (from 5,243 to 2,646), but did not decrease further by day 7. A mean number of 54.4 A caninum adults was recovered from 12 of the 13 placebo-treated dogs at necropsy. Milbemycin oxime had 97.8% efficacy against A caninum. Results also indicated that milbemycin oxime may be effective against Trichuris vulpis, but not against Dipylidium caninum.     

Anthelmintic activities of ivermectin against immature and adult Dictyocaulus viviparus

Eighteen calves about 3 months old were inoculated with 3,000 Dictyocaulus viviparus infective larvae. Three groups of 6 calves each were formed. Thirteen days after inoculations, 3 of the 6 group 1 control calves were given vehicle subcutaneously (SC) and the group 2 calves were given ivermectin at the dose rate of 200 micrograms/kg, SC. Thirty-five days after inoculation, the remaining 3 calves in group 1 were given vehicle SC and the group 3 calves were given ivermectin at the dose rate of 200 micrograms/kg, SC. Necropsies were performed 42 days after inoculations. A total of 474 D viviparus was recovered from the group 1 control calves, whereas none was recovered from the calves treated when the nematodes were in the 4th stage of development (group 2) or adult stage (group 3).     

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.     

Dose-titration studies of ivermectin against experimental Ancylostoma caninum and Uncinaria stenocephala infections

Dose-titration trials of ivermectin were conducted on pups with dual experimental infections of 4th-stage larvae or adult Ancylostoma caninum and Uncinaria stenocephala. Ivermectin was administered orally or subcutaneously at dosages of 0.006, 0.012, or 0.024 mg/kg of body weight. Maximal or near maximal (greater than or equal to 96% to 100%) anthelmintic effect was observed for both stages of development for each hookworm species by either route of administration at a dosage of 0.024 mg/kg. Responses for all of the aforementioned categories were linearly related to increasing log dosage of ivermectin, with common slopes (regression coefficients). Regression analysis also provided estimates of the minimal dosages required to produce maximal reduction in worm burden for each stage, species, and route of administration. The estimated ivermectin dosages for maximal efficacy ranged from a low of 0.014 mg/kg for adult A caninum by oral treatment to 0.044 mg/kg for 4th-stage larvae of U stenocephala by oral treatment.     

犬口服国产米尔贝肟片的相对生物利用度研究

本研究旨在建立犬血浆中米尔贝肟的LC-MS/MS检测方法,评价国产米尔贝肟片在犬体内的相对生物利用度。对12条比格犬采用开放、随机、交叉、单剂量给药,口服国产米尔贝肟片、进口米尔贝肟片。LC-MS/MS测定犬血浆中米尔贝肟的浓度,3p97药动学计算软件处理血浆药物-时间数据。该方法低浓度(5ng/mL)回收率高于85%,最低定量限为5ng/mL;健康犬口服进口和国产米尔贝肟片的药物动力学最佳数学模型均为一级吸收一室模型。本研究中建立的HPLC-MS/MS检测方法可用于口服给药后犬血浆中米尔贝肟含量的测定;口服国产米尔贝肟片与进口米尔贝肟片的相对生物利用度为99.07%。     

Anthelmintic activity of ivermectin against immature gastrointestinal nematodes of sheep

Twenty-four lambs of mixed breeding with mixed experimental infections of Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus axei, and T colubriformis were allotted to 4 groups. One group (control) was given the vehicle propylene glycol, and the others were given 100, 200, or 300 micrograms of ivermectin/kg of body weight by mouth. Twelve days after treatment, the sheep were necropsied. The compound was greater than 99% effective against immature stages of 4 nematode species at all dosages, except at the 100 micrograms/kg dosage, where efficacy was 96% against H contortus.     

Unambiguous identification of Ancylostoma caninum and Uncinaria stenocephala in Australian and New Zealand dogs from faecal samples

Hookworms (Ancylostomatidae) are well-known parasites in dogs due to their health impacts and zoonotic potential. While faecal analysis is the traditional method for detection, improvements in husbandry and deworming have decreased their prevalence in urban owned dogs. Drug resistance in Ancylostoma caninum is becoming a discussion point in small animal practices across the region. This study aimed to identify hookworm species present in Australian and New Zealand dogs using molecular techniques. The ITS-2 and isotype-1 β-tubulin assays were used to identify and quantify hookworm species. Results showed absence of coinfection in Australian samples from Greater Sydney region belonging either to A. caninum or Uncinaria stenocephala, while New Zealand samples were a mixture of A. caninum and U. stenocephala. The amplified isotype-1 β-tubulin sequences exhibited susceptibility to benzimidazole drugs. Rare mutations were identified in A. caninum and U. stenocephala sequences, representing a small percentage of reads. This study highlights the importance of molecular techniques in accurately identifying and quantifying hookworm species in dog populations.     

Therapeutic and prophylactic efficacy of milbemycin oxime (Interceptor) against Thelazia callipaeda in naturally exposed dogs

Two trials were conducted to evaluate the therapeutic and prophylactic activity of milbemycin oxime (Interceptor, Novartis Animal Health) against the eye-worm Thelazia callipaeda (Spirurida, Thelaziidae) infection. In Trial 1, the therapeutic efficacy of milbemycin oxime was evaluated in 55 naturally infected dogs treated with min. 0.5mg/kg milbemycin oxime. The dogs were clinically examined for the presence of eyeworms before and again 7 days after treatment. Dogs still positive were given a second treatment and re-checked again a week later. Forty-eight of the 55 dogs tested negative 1 week after treatment (87.3% reduction of infection rate). Following the second treatment 6 of these 7 dogs tested negative 1 week later resulting, after two treatments, in a reduction of infection rate of 98.2%. In Trial 2, the prophylactic efficacy of milbemycin oxime was evaluated in 60 uninfected dogs. Thirty dogs were treated with milbemycin oxime monthly from June to November with the recommended dose rate for the prevention of heartworm disease (> or =0.5mg/kg), 30 dogs served as untreated controls. At the end of the trail 1 dog in the treated group and 10 dogs in the control group became infected during the trial. The incidence of infection differed significantly between treated and control dogs (p=0.0056). The efficacy of the prophylactic use of a monthly treatment with milbemycin oxime showed 90% efficacy in reducing T. callipaeda infection rate.     

米尔贝肟片对犬血液学指标的影响

为了评价米尔贝肟片对犬的安全性,将24只本地健康杂种犬,随机分为4组,分别按0.5、1.5、2.5、5.0 mg/kg体重剂量(相当于临床推荐剂量的1、3、5、10倍)食喂米尔贝肟片,每组6只,连续给药3 d.在用药前及用药后1、3、7、14 d测定其体温、体重、血常规及肝肾功能指标.结果表明,与给药前相比,4种剂量的米尔贝肟片对犬血常规及肝肾功能指标无显著影响,且动物体温、体重及临床表现均正常.说明米尔贝肟片对犬可安全用药.     

米尔贝肟对自然感染疥螨病犬的治疗效果

为了评价米尔贝肟对临床自然感染疥螨犬的治疗效果,选用自然感染疥螨犬65例,随机选择5条服用伊维菌素,另外60条随机分为3组,分别服用高剂量(2g/kg体重)、中剂量(1g/kg体重)、低剂量(0.5g/kg体重)的米尔贝肟。给药后2、14、28、42d和56d,刮取皮屑,检查螨虫和虫卵,同时观察临床症状。试验结束时米尔贝肟高剂量组、伊维菌素组的无螨虫犬的比例和螨虫的下降率均为100%,临床症状如红疹、结痂、过度角化等现象均消失,所有动物毛发都开始大范围重生;米尔贝肟中、低剂量组结果稍差。米尔贝肟按2g/kg体重剂量,每周1次,连续用药3周,给药对自然感染疥螨病犬有很好的治疗效果。     

Efficacy of milbemycin oxime against naturally acquired or experimentally induced Ancylostoma spp and Trichuris vulpis infections in dogs.

The efficacy of milbemycin oxime was evaluated at dosages of 0.25, 0.50, and 0.75 mg/kg of body weight in dogs naturally infected with mature Ancylostoma spp, at a dosage of 0.50 mg/kg in dogs with experimentally induced immature and mature A caninum, and at dosages of 0.55 to 0.86 mg/kg in dogs naturally infected with mature Trichuris vulpis. Milbemycin oxime was 95 and 99% effective against mature Ancylostoma spp at dosages of 0.50 and 0.75 mg/kg, respectively, but only 49% effective at a dosage of 0.25 mg/kg. Efficacy was 49% against pulmonary L3-L4 stages of A caninum (36 hours after inoculation), greater than 80% against L4 (120 hours after inoculation) and early L5 stages (216 hours after inoculation), and greater than 90% against experimentally induced mature stages (360 hours after inoculation). Milbemycin oxime was also 97% effective in the removal of mature Tr vulpis from naturally infected dogs. Adverse reactions were not observed following treatment in any of the dogs.     

Anthelmintic activity of paraherquamide in dogs

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and Penicillium charlesii, was tested against the common gastrointestinal nematodes of dogs at a single oral dosage of 0.5, 1.0, or 2.0 mg kg⁻¹. Efficacy was poor (less than 85%) against Ancylostoma caninum, Uncinaria stenocephala, Toxascaris leonina, Trichuris vulpis, and Strongyloides stercoralis at the low- and mid-dosage levels. At the high dosage level, good efficacy (91%) was observed only against S. stercoralis. Adverse reactions were observed in all dogs at every dosage level and included depression, ataxia, and protrusion of the nictitating membrane.     

Efficacy of moxidectin 6-month injectable and milbemycin oxime/lufenuron tablets against naturally acquired trichuris vulpis infections in dogs

Efficacy of moxidectin injection (ProHeart 6 Sustained Release Injectable for Dogs, Fort Dodge Animal Health) against naturally acquired infections of Trichuris vulpis was compared with that of milbemycin oxime/lufenuron tablets (Sentinel Flavor Tabs, Novartis Animal Health). Eighteen dogs infected with T. vulpis were ranked by egg counts and randomly allocated to treatment with moxidectin (170 micro g/kg), milbemycin (500 micro g/kg)/lufenuron (10 mg/kg), or to an untreated control group (six dogs per treatment). Dogs were euthanized for worm counting 7 days after treatment. Efficacy of milbemycin/lufenuron against T. vulpis was 99.6 %, compared with 67.5 % for moxidectin. The commercial formulation of milbemycin oxime/lufenuron provided excellent control of whipworm infection, whereas moxidectin demonstrated variable efficacy against this parasite.