猫跳蚤防治最新进展--（2）目前算是异噁唑啉类的全面总结

王帆

Recent Advancements in the Control of Cat Fleas

猫跳蚤防治最新进展

作者：Michael K. Rust

翻译：王帆

5.Chemical Treatments

5.化学治疗

Several reviews have covered the development and efficacy of various therapies to control cat fleas. In recent years, the research and development focus has been on treating the pet, rapidly killing adult fleas, and preventing the flea life cycle from maintaining itself.

几篇综述涵盖了控制猫跳蚤的各种疗法的发展和功效。近年来，研究和开发的重点是治疗宠物、迅速杀死跳蚤成虫、阻止跳蚤生命周期的自我维持。

5.1Aminoglycosides

5.1氨基糖苷类

Spinosad is an insecticidal compound derived from natural products from the fermentation of the bacterium Saccharopolyspora spinosa. Given orally to dogs, it provides >95% kill of C. f. felis for several months. Spinetoram, an analogue of spinosad, is even more active than spinosad. A laboratory study with dogs indicated that 30–60 mg/kg of spinetoram provided excellent kill of adult fleas for 2–3 months. In a laboratory and field study conducted in Europe, topical application of spinetoram to cats provided 99.1% reductions of C. f. felis at day 60 whereas fipronil + methoprene provided a 92.3% reduction. Topical applications of spinetoram provided 96% reductions through day 37, providing about the same speed of activity against adult fleas as imidacloprid and fipronil + methoprene.

多杀菌素是一种杀虫剂，从中刺糖多胞菌提取的细菌天然发酵产物。犬口服，可以持续数月杀死＞95%的猫栉首蚤。乙基多杀菌素是多杀菌素的类似物，比多杀菌素更活跃。实验结果表明，30-60 mg/kg的乙基多杀菌素对跳蚤成虫的杀灭效果良好，可维持2-3个月。在欧洲进行的一项实验室和临床研究中，猫外用乙基多杀菌素可在第60天减少99.1%的猫栉首蚤，而非泼罗尼+甲氧普烯可减少92.3%。外用乙基多杀菌素可在第37天降低96%，对跳蚤成虫的活性与吡虫啉+非泼罗尼+甲氧普烯相同。

5.2Insect Growth Regulators

5.2昆虫生长调节剂

The use of insect growth regulators (IGRs), such as methoprene and pyriproxyfen to inhibit egg hatching and larval development in the environment, and oral applications of lufenuron to interfere with egg viability, have played important roles in developing our understanding of successful cat flea pest management. Combination treatments with adulticides and IGRs interrupted the flea life cycle and controlled fleas inside residences.Other IGRs, such as chlorfluazuron and dicyclanil (0.78 and 0.3 ppm lethal concentration [LC95] in larval rearing medium), are as active as methoprene and pyriproxyfen against cat fleas, and may be promising candidates. Interestingly, pyriproxyfen synergized the activity of methoprene against larval cat fleas with a combination of pyriproxyfen:methoprene (10:1) being twice as active (LC50 0.20 ppm in larval rearing medium) as either methoprene or pyriproxyfen alone. The synergism permitted lower concentrations of each IGR to be applied and still be effective.

使用昆虫生长调节剂(IGRs)，如甲氧普烯和吡丙醚能抑制环境中的卵孵化和幼虫发育，以及口服氯芬奴隆能干扰卵的生存能力，在我们已知的能成功治理猫跳蚤方法中发挥重要作用。杀虫剂和IGR联用可阻断跳蚤生命周期，控制跳蚤在居住环境内的活动。其他IGR，如氟啶脲和环虫腈(幼虫致死浓度为0.78和0.3 ppm [LC95])抑制猫跳蚤的活性与甲氧普烯和吡丙醚相同，可能有望作为候选。有趣的是，当吡丙醚与甲氧普烯联用时，甲氧普烯(10:1)的活性(LC50 0.20 ppm)是甲氧普烯和吡丙醚单独作用的两倍。这种协同作用允许使用低浓度IGR，且仍然有效。

The combination of imidacloprid and methoprene and imidacloprid and pyriproxyfen were synergistic against larval fleas. Some combinations of fipronil and methoprene or fipronil and pyriproxyfen were synergistic, but in some cases, they were antagonistic. Synergistic combinations allow the concentrations of the adulticide and IGR to be reduced, and still provide the same activity as higher concentrations of the adulticides alone. In a laboratory study, cats topically treated with fipronil + methoprene + pyriproxyfen were allowed to contact carpets. Pieces of carpet were removed and provisioned with flea rearing medium and cat flea eggs. The plugs of treated carpets prevented 86–98% egg development over a 15-week period, effectively interrupting the life cycle.

吡虫啉，甲氧普烯，吡虫啉与吡丙醚联用对跳蚤幼虫具有协同作用。非泼罗尼与甲氧普烯联用或非泼罗尼与吡丙醚联合有协同作用，但在某些情况下，也有拮抗作用。协同作用可降低杀虫剂和IGR的浓度，但仍能提供与较高浓度的单一杀虫剂相同的活性。在一项实验室研究中，用猫外用非泼罗尼+甲氧普烯+吡丙醚来接触地毯。取下地毯块，备上养蚤培养基和猫跳蚤卵。经过处理的地毯在15周内阻止了86-98%的卵发育，有效地中断了生命周期。

In 2013, a spot-on to treat dogs containing fipronil and novaluron was registered. To date there are no published results concerning its efficacy.

2013年，一种犬用非泼罗尼+双苯氟脲的滴剂被注册。到目前为止，还没有关于其功效的公布结果。

5.3Isoxazolines

5.3异噁唑啉类

An exciting new class of insecticides, the isoxazolines, was registered in 2014 and emerged on the ectoparasiticide market in 2015. Isoxazolines are potent inhibitors of γ-aminobutyric acid (GABA)-gated channels and affect l-glutamate-gated chloride channels to a lesser extent. They are second-generation non-competitive antagonists of GABA receptors. Isoxazolines circumvent resistance by attacking new binding regions on the chloride channels. No cross-resistance exists with other non-competitive antagonists, such as fipronil or the macrocyclic lactones such as abamectin and emamectin benzoate. Enough differences between insect and mammalian receptors occur to make them selective to insects, and Acari, and excellent candidates as ectoparasiticides. The toxic effects may also extend to Crustacea, as lotilaner was shown to be a powerful antagonist GABA chloride channel of sea lice. Laboratory studies and field trials of new isoxazoline compounds, and combination products published prior to 2017 have been reviewed by Rust. To date afoxolaner, fluralaner, lotilaner, and sarolaner are commercialized.

2014年，一种令人兴奋的新型杀虫剂——异噁唑啉注册，并于2015年出现在体外驱虫药市场。异噁唑啉是γ-氨基丁酸(GABA)门控通道的有效抑制剂，对L-谷氨酸门控氯通道影响较小。它们是GABA受体的第二代非竞争性拮抗剂。异噁唑啉通过攻击氯离子通道上新的结合区域来规避抗性。与其他非竞争性拮抗剂不存在交叉耐药性，如非泼罗尼或大环内酯类，如阿维菌素和埃玛菌素。昆虫和哺乳动物的受体之间存在着很大差异，这使得它们对昆虫和蜱螨亚纲有选择性，且在体外驱虫药中是最佳选择。毒性作用也可能影响到甲壳类动物，因为洛蒂拉纳被证明是一种强有效的海虱氯通道拮抗剂。Rust对2017年之前发表的新异噁唑啉化合物和组合产品的实验室研究和现场试验进行了回顾。目前已有商品化阿福拉纳、氟雷拉纳、洛蒂拉纳和沙罗拉纳。

In addition to killing adult cat fleas, the isoxazolines also kill mites, ticks, lice, triatomine bugs, mosquitoes, biting flies, and sea lice. Some endoparasites also appear to be affected. This remarkable breadth of activity against Insecta, Arachnida, and Crustacea will revolutionize the control of endo and ectoparasites on cats and dogs. In a study in Sicily and southern Italy, a topical treatment of fipronil + permethrin and an oral dose of afoxolaner + milbemycin oxime was provided to each dog. In addition to killing fleas and ticks, the combination treatment provided a broad spectrum of protection against Anaplasma spp., Borrelia spp., Ehrlichia spp., and dog heartworm.

除能杀死猫跳蚤成虫外，异噁唑啉还能杀死螨虫、蜱虫、虱子、锥蝽臭虫、蚊子、咬蝇和海虱。对一些体内寄生虫似乎也有作用。这种大范围针对昆虫纲、蛛形纲和甲壳纲的明显效果，将彻底改变对犬猫体内和体外寄生虫的控制管理。在西西里岛和意大利南部的一项研究中，对每只犬进行了外用非泼罗尼+苄氯菊酯且口服阿福拉纳+米尔贝肟。除了杀死跳蚤和蜱虫外，这种联合治疗还避免感染无形体、螺旋体、埃里希体和犬心丝虫。

The Project Lake Survey of veterinarians and dog owners regarding their experiences with isoxazoline products indicated that 48.2% of the 2751 respondents had used them. Of the 1768 positive respondents, 66.6% indicated that the dogs had responded with adverse events to the treatment ranging from hair loss to death. As the authors indicate, there are a number of limitations in evaluating voluntary survey data. Palmieri et al. write, “However, FDA (Food and Drug Administration) and EMA (European Medicine Agency) AE (adverse event) reports and Project Lake Survey evidence consistently demonstrate in three separate, distinct data sets that the neurotoxicity is not arthropod-specific, and that post-marketing serious AE are much higher than in the IND (Investigational New Drug) submission studies.” Clearly, additional investigations and surveys are warranted.

针对兽医和宠主使用异噁唑啉产品的经验进行的LAKE项目调查显示，在2751名回访者中，48.2%曾使用过异噁唑啉产品。在1768名回访结果较好的受访者中，66.6%的犬对治疗有不良反应，从脱毛到死亡不等。正如作者指出的，在评估自愿调查数据时存在许多局限性。Palmieri等人写道，“然而，FDA(食品和药物管理局)和EMA(欧洲药品管理局)的AE(不良事件)报告和Lake项目调查证据一致表明，在三个独立、不同的数据集中，神经毒性不是节肢动物特有的，上市后严重的AE比IND(临床试验新药)提交研究要高得多。”显然，需要进行更多的研究调查和回访调查。

5.3.1Afoxolaner

5.3.1阿福拉纳

Afoxolaner first appeared on the market in 2014 as an oral chewable dose for dogs. A chronology of the development of afoxolaner for dogs is provided by Letendre et al.. In addition, afoxolaner also was topically active against fleas and ticks. In a laboratory study with cats, a single oral dose of afoxolaner provided 100% kill of adult fleas within 48 h and 99.5 and 95% reductions for 42 and 63 days, respectively. In a laboratory study, the number of fleas on dogs orally dosed with afoxolaner was reduced by 100% for at least 22 days. An oral dose of afoxolaner + milbemycin oxime to naturally infested dogs provided ≥96.1% reductions of fleas at day 30. In a field trial with 37 naturally infested dogs in Tampa FL, USA, dogs were provided an oral dose of afoxolaner. Within 7 days, there was a 93% reduction in the number of fleas counted on the dogs and a 99.9% reduction at 30 days. There was a 100% reduction in the number of adult fleas emerging within the residences at 60 days.

2014年，阿福拉纳首次作为犬口服咀嚼剂上市。Letendre等人提供了犬用阿福拉纳的发展年表。此外，外用阿福拉纳对跳蚤和蜱虫也有活性。在一项针对猫的实验室研究中，单次口服阿福拉纳可在48小时内100%杀灭跳蚤成虫，42天和63天内分别减少99.5天和95%。在一项实验室研究中，口服阿福拉纳的犬身上的跳蚤数量至少在22天内减少了100%。口服阿福拉纳+米尔贝肟治疗自然感染的犬，在第30天可减少≥96.1%的跳蚤。在美国佛罗里达州坦帕市对37只自然感染的犬进行的一项临床试验中，为犬提供口服剂量的阿福拉纳。在7天内，犬跳蚤数量下降93%，30天下降99.9%。在60天内，居住环境出现的跳蚤成虫数量减少了100%。

In a laboratory study, there was 100% kill of the tick Haemaphysalis elliptica on dogs treated with afoxolaner, and it protected them from contracting Babesia rossi. In a laboratory study with dogs, fipronil + permethrin spot-on provided faster knockdown and greater repellency of ticks that did an oral application of afoxolaner. Both treatments provided >90% anti-attachment of Rhipicephalus sanguineus for at least 14 days. An oral dose of afoxolaner + milbemycin oxime provided ≥94.4% reductions of ticks on naturally infested dogs at day 30.

在一项实验室研究中，用阿福拉纳治疗的犬，100%杀死了椭圆形血蜱，并且避免感染巴贝斯虫。在一项对犬进行的实验室研究中，与口服阿福拉纳相比，非泼罗尼+苄氯菊酯滴剂对蜱虫的驱避作用起效更快更有效。两种治疗方法抑制红扇头蜱的粘附作用均＞90%，至少持续14天。自然感染患犬口服阿福拉纳+米尔贝肟可在第30天减少≥94.4%的蜱虫。

5.3.2Fluralaner

5.3.2氟雷拉纳

In a simulated home environment, where natural environmental infestations could reinfest pets, a single topical application of fluralaner provided nearly 100% reductions of fleas on cats and dogs for 12 weeks. In a laboratory study with cats infested with a field isolate of C. f. felis not controlled by fipronil, a spot-on application of fluralaner + moxidectin provided nearly 100% control for the entire 93-day study, whereas a topical application of fipronil + methoprene provided from 65.6 to 30.6% reductions over the same period. In a laboratory study with short haired cats, a single topical application of fluralaner or three topical applications monthly of selamectin + sarolaner provided >94.6% kill of adult cat fleas for 90 days.

在一个模拟家庭环境中，自然环境感染了跳蚤，可以再次感染宠物，单一外用氟雷拉纳可以在12周内几乎100%降低猫和犬身上的跳蚤。在一项实验室研究中，在室外感染猫栉首蚤的患猫，使用了氟雷拉纳+莫昔克丁滴剂，在研究的93天时间内，能几乎达到100%控制管理,而外用非泼罗尼+甲氧普烯在同期提供的清除率65.6到30.6%。在短毛猫的实验室研究中，单次外用氟雷拉纳或每月一次，使用了三次外用赛拉菌素+沙罗拉纳可在90天内提供＞94.6%的猫跳蚤成虫杀死率。

Topical fluralaner applied to naturally infested cats from 18 different veterinary clinics across 11 USA states provided 99.0% reduction of C. f. felis at week 12. Topical applications of fipronil + methoprene provided a 75.4% reduction. In a similar study with dogs, topically applied fluralaner and fipronil + methoprene provided 99.9 and 93.0% reductions of cat fleas at week 12. A single topical application of fluralaner to naturally infested cats provided 100% reductions of C. f. felis for up to 84 days.

对来自美国11个州的18个不同兽医诊所的自然感染的猫进行外用氟雷拉纳治疗，在第12周时对猫栉首蚤清除率达到99.0%。外用非泼罗尼+甲氧普烯清除率达到75.4%。在犬的一项类似研究中，外用氟雷拉纳和非泼罗尼+甲氧普烯可在第12周对猫跳蚤清除率分别达到99.9和93.0%。对自然感染的猫单次外用氟雷拉纳对猫栉首蚤清除率达到100%，持续长达84天。

In a large study with 707 cats from 332 households in Germany and Spain, a single spot-on application of fluralaner + moxidectin on cats provided 97 and 98% reductions in ticks and fleas, respectively, throughout the 12-week study. A topical fipronil applied for three consecutive months provided 74.5% reductions at 12 weeks.

在一项对来自德国和西班牙332个家庭的707只猫进行的大型研究中，在整个12周的研究中，对猫使用一次氟雷拉纳+莫昔克丁滴剂，对蜱虫和跳蚤清除率分别达到97和98%。连续3个月外用非泼罗尼在12周的清除率达到74.5%。

5.3.3Lotilaner

5.3.3洛蒂拉纳

An oral dose of lotilaner given to dogs provided 100% kill of adult fleas within 24 h. There was a 98.5% reduction in the number of eggs laid at 24 h and no eggs were laid any period afterwards. When the dogs were challenged with adult fleas, there was a 100% kill for 30 days. An oral dose of lotilaner to cats with an existing C. f. felis infestation provided 100% kill within 24 h. In a second study, 97.4% of the fleas were killed within 8 h. When cats were challenged with adult cat fleas, lotilaner provided 98.6% kill for at least 35 days.

给犬口服洛蒂拉纳，24 h内100%杀灭跳蚤成虫，24 h产卵量减少98.5%，此后无卵产。当用跳蚤成虫来感染犬时，可实现100%的杀死率，并维持30天。在第二项研究中，97.4%的跳蚤在8小时内被杀。当猫感染猫跳蚤时，洛蒂拉纳杀灭率为98.6%，持续时间至少为35天。

Several studies have been conducted to determine the speed at which fleas are killed by lotilaner. In a laboratory study with dogs with existing infestations of C. f. felis, lotilaner provided 64 and 99.6% reductions in the number of fleas counted at 2 and 8 h, respectively. An oral dose of lotilaner to dogs provided 89.9% kill of existing cat flea infestations at 4 h and 100% kill at 12 h. When treated, dogs were challenged with adult fleas for up to 35 days, there was >97% kill at 4 h.

已经进行了几项研究，以确定洛蒂拉纳杀死跳蚤的速度。在一项实验室研究中，感染猫栉首蚤患犬，洛蒂拉纳在2小时和8小时分别减少了64%和99.6%的跳蚤。给犬口服洛蒂拉纳，4h时对猫跳蚤的杀灭率为89.9%，12h时杀灭率为100%。犬洛蒂拉纳治疗后，持续35天进行跳蚤成虫感染试验，4小时内杀灭率＞97%。

Client-owned dogs from 10 veterinary clinics in the USA were dosed with lotilaner or afoxolaner. Lotilaner reduced the number of fleas by 99.3, 99.9, and 100% at 30, 60, and 90 days, respectively. Afoxolaner provided 98.3, 99.8, and 99.8% reductions at 30, 60, and 90 days, respectively. On day 90, all the dogs dosed with lotilaner were flea free and 93% of dogs were flea free when treated with afoxolaner.

来自美国10家兽医诊所的家养犬使用了洛蒂拉纳或阿福拉纳。在30、60和90天时，洛蒂拉纳可使跳蚤数量分别下降99.3、99.9和100%。在30、60和90天，阿福拉纳分别降低了98.3、99.8和99.8%。第90天，洛蒂拉纳组均无蚤，阿福拉纳组无蚤率为93%。

In a laboratory study, an oral dose of lotilaner to dogs provide 100% kill of Ixodes ricinus within 8 h. Treatment provided protection for 35 days. Similarly, in laboratory studies with four common species of ticks, an oral dose of lotilaner provided greater than 98% efficacy against Dermacentor variabilis, R. sanguineus, Amblyomma americanum, and Ixodes scapularis for at least 4 weeks. Similarly, a single oral dose of lotilaner to dogs provided >98% efficacy against I. ricinus, R. sanguineus, and Dermacentor reticulatus for at least 35 days. In a laboratory study, a single oral dose of lotilaner provided >97% reduction in the number of Haemaphysalis longicornis attached to dogs at 48 h.

在一项实验室研究中，给犬口服洛蒂拉纳可在8小时内100%杀灭蓖子硬蜱。治疗可提供35天的保护。同样，在对四种常见蜱的实验室研究中，口服洛蒂拉纳对变异革蜱、红扇头蜱、美洲花蜱和肩突硬蜱持续作用达4周，有效性超过98%。同样地，犬单次口服洛蒂拉纳对蓖子硬蜱、红扇头蜱和网纹革蜱有效率＞98%，且至少持续35天。在一项实验室研究中，单次口服洛蒂拉纳可在48小时内使附着在犬身上的长角血蜱数量减少97%。

5.3.4Sarolaner

5.3.4沙罗拉纳

The development of sarolaner and supporting studies are discussed by Woods and McTier. Sarolaner was about 10 times more toxic to C. f. felis than afoxolaner or fluralaner in membrane feeding studies. Oral doses of sarolaner provided 100% reduction in the number of fleas retrieved from dogs for up to 35 days. The activity of sarolaner was not negatively affected by the dieldrin resistant mutation at CfRDL-S285 channel. In a laboratory study with dogs, topical applications of sarolaner to dogs provided 100 and 87% kill of fleas at day 1 and 28, respectively, after a six-hour challenge. The treatment with fipronil + methoprene + pyriproxyfen provided 88.8 and 83% reductions of fleas at days 1 and 28, respectively.

Woods和McTier讨论了沙罗拉纳的发展和相关研究。在“膜喂养”研究中，沙罗拉纳对猫栉首蚤的毒性大约是阿福拉纳或氟雷拉纳的10倍。口服沙罗拉纳可在长达35天内100%减少犬身上的跳蚤数量。沙罗拉纳活性不受CfRDL-S285通道狄氏剂耐药突变的负面影响。在一项犬的实验室研究中，犬外用沙罗拉纳6h再暴露，在第1天和第28天分别有100%和87%的杀蚤效果。非泼罗尼+甲氧普烯+吡丙醚治疗后，第1天和第28天的跳蚤数分别减少了88.8%和83%。

In a field study in USA, 479 dogs in 293 households were given oral doses of sarolaner or spinosad monthly for 3 consecutive months. At day 90, sarolaner and spinosad provided 99.9 and 99.8% reduction in the number of fleas on dogs, respectively. In a field study conducted in west Central Florida, 26 dogs were orally dosed with sarolaner or a spinosad chewable. Both treatments provided >99% reduction of fleas for at least 60 days. The number of fleas trapped in the structures was reduced by 100% in sarolaner and 99.8% in the spinosad treated dogs.

在美国的一项临床研究中，293个家庭的479只犬连续3个月每月口服沙罗拉纳或多杀菌素。在第90天，沙罗拉纳和多杀菌素对犬身上跳蚤清除率分别有99.9%和99.8%。在佛罗里达中心西部进行的一项临床研究中，26只犬口服了沙罗拉纳或多杀菌素咀嚼片。两种方法均可使跳蚤减少＞99%，持续至少60天。研究中，使用沙罗拉纳的犬跳蚤数量减少了100%，使用多杀菌素的犬中减少了99.8%。

The combination of selamectin + sarolaner topically applied to cats in Europe provided a 99.4% reduction in flea counts at day 90. A comparative treatment of imidacloprid + moxidectin provided a 96.3% reduction in the number of cat fleas. In another study, topical application of selamectin + sarolaner provided a 99.8% reduction of C. f. felis at day 90. Clinical signs of flea allergy dermatitis (FAD) were reduced in 86.7 to 100% of the cats. A topical treatment of imidacloprid + moxidectin provided 95.5% reductions in the number of fleas counted at day 90 and 66.7 to 100% reduction in clinical signs of FAD. In a field study in Japan, 67 cats were topically treated with selamectin + sarolaner or fipronil + methoprene. The selamectin + sarolaner provided 99.5 and 99.9% reduction in numbers of fleas on the cats at days 14 and 30, respectively. Fipronil + methoprene provided 97.6 and 98.6% at days 14 and 30, respectively. In Australia, 104 cats were enrolled in clinical studies. A topical application of selamectin + sarolaner for 3 consecutive months provided 98, 100, and 100% control of cat fleas at days 30, 60, and 90, respectively.

在欧洲，猫外用赛拉菌素+沙罗拉纳在第90天跳蚤数减少99.4%。吡虫啉+莫昔克丁治疗后，猫跳蚤数下降96.3%。在另一项研究中，外用赛拉菌素+沙罗拉纳可在第90天使猫栉首蚤减少99.8%。猫跳蚤过敏性皮炎(FAD)临床症状减少86.7-100%。外用吡虫啉+莫昔克丁治疗后，第90天跳蚤数减少了95.5%，临床症状减少了66.7-100%。在日本的一项临床研究中，67只猫外用赛拉菌素+沙罗拉纳或非泼罗尼+甲氧普烯。赛拉菌素+沙罗拉纳可使猫跳蚤数在第14天和第30天分别减少99.5和99.9%。非泼罗尼+甲氧普烯在第14天和第30天分别为97.6和98.6%。在澳大利亚，有104只猫参加了临床研究。连续3个月外用赛拉菌素+沙罗拉纳，第30、60和90天对猫跳蚤有效率分别为98、100和100%。

In a laboratory study with dogs, an oral dose of sarolaner provided 86.2 and 96.5% reductions in Ixodes holocyclus at 8 and 12 h, respectively whereas an oral dose of afoxolaner provided 21.3 and 85.0% reductions at 8 and 12 h, respectively. When treated dogs were challenged at day 35, sarolaner and afoxolaner provided 65.2 and 21.0% efficacy at 12 h, respectively. Oral doses of sarolaner, moxidectin, and pyrantel to laboratory dogs provided 99.7% reductions in C. f. felis for at least 35 days with no eggs being laid during the 35 days. The treatment began killing fleas within 4 h and all the fleas were dead at 8 h. When moxidectin and pyrantel were applied to dogs, they had no effect on fleas.

在一项犬的实验室研究中，口服沙罗拉纳在8和12小时分别使全环硬蜱减少86.2和96.5%，而口服阿福拉纳在8和12小时分别减少21.3和85.0%。当治疗犬在第35天感染时，沙罗拉纳和阿福拉纳在12小时的有效性分别为65.2和21.0%。给实验犬口服沙罗拉纳、莫昔克丁和噻吩嘧啶，至少35天，可使猫栉首蚤减少99.7%，且35天内没有产卵。犬使用莫昔克丁和噻吩嘧啶对跳蚤无明显杀灭作用。

A clinical field trial of 150 dogs dosed with sarolaner + moxidectin + pyrantel provided a 99.0% reduction in cat flea counts at day 30 and a 99.7% reduction at day 60. Clinical signs of FAD declined from 45.7 to 6.9%. Similarly, in a field study with dogs in Europe and the USA, an oral dose of sarolaner + moxidectin + pyrantel provided ≥97.9% reductions in flea counts at day 30. In a large multi-location study in the USA, oral doses of sarolaner + moxidectin + pyrantel provided 99.0 and 99.7% at days 30 and 60, respectively.

在150只犬的临床试验中，沙罗拉纳+莫昔克丁+噻吩嘧啶在第30天和第60天的猫跳蚤数分别降低了99.0%和99.7%。FAD临床症状由45.7%下降至6.9%。同样，在欧洲和美国对犬进行的一项临床研究中，口服沙罗拉纳+莫昔克丁+噻吩嘧啶可使第30天的跳蚤数减少97.9%。在美国的一项大型多地点研究中，口服沙罗拉纳+莫昔克丁+噻吩嘧啶在第30天和第60天分别有效率为99.0%和99.7%。

In laboratory studies on dogs, an oral dose of sarolaner + moxidectin + pyrantel provided 98.9% kill of existing infestations of the five most common ticks in the USA. At day 28, >88% kill was achieved 48 h after exposing the ticks to the treated dogs. In a laboratory test, an oral dose of sarolaner + moxidectin + pyrantel provided 100% efficacy of existing infestations of African yellow dog ticks, H. elliptica, on dogs and weekly re-infestations for 35 days. Similarly, sarolaner + moxidectin + pyrantel provided 100% efficacy for 21 days against H. longicornis and ≥97.4% efficacy for 35 days. In another study, sarolaner + moxidectin + pyrantel provided 99.4% kill of black legged tick I. scapularis at 24 h and provided a 94.2% reduction of ticks for at least 28 days.

在对犬进行的实验室研究中，口服沙罗拉纳+莫昔克丁+噻吩嘧啶可杀灭美国五种最常见的蜱虫，杀灭率为98.9%。第28天，治疗犬感染蜱虫48 h后，杀灭率＞88%。在实验室试验（每周一次再感染持续35天）中，口服沙罗拉纳+莫昔克丁+噻吩嘧啶对感染非洲黄蜱（椭圆血蜱）患犬有效率100%。同样，沙罗拉纳+莫昔克丁+噻吩嘧啶对长角血蜱的杀灭率为100%持续21天，有效率≥97.4%持续35天。在另一项研究中，沙罗拉纳+莫西丁素+噻吩嘧啶在24 h时对黑腿蜱（肩突硬蜱）的杀灭率为99.4%，杀灭率为94.2%，持续28天。

In a field study in Japan, 67 cats were topically treated with selamectin + sarolaner or fipronil + methoprene. Selamectin + sarolaner provided 97.5 and 97.7% reductions of the number of the tick H. longicornis at days 14 and 30, respectively. Fipronil + methoprene provided 91.5 and 93.4% reduction in ticks at days 14 and 30. In a field study with naturally infested dogs, and an oral dose of sarolaner + moxidectin + pyrantel provided ≥94.8% reduction of ticks at 30 days. An oral dose of afoxolaner +milbemycin oxime provided ≥94.4% reduction in the number of ticks at day 30. The ticks included in the test were I. ricinus, Ixodes hexagonus, R. sanguineus, and D. reticulatus.

在日本的一项临床研究中，67只猫外用了赛拉菌素+沙罗拉纳或非泼罗尼+甲氧普烯。赛拉菌素+沙罗拉纳可使长角血蜱数量在第14天和第30天分别减少97.5和97.7%。非泼罗尼+甲氧普烯在第14天和第30天分别降低了91.5和93.4%。在一项对自然感染的犬进行的临床研究中，口服沙罗拉纳+莫昔克丁+噻吩嘧啶 三十天内蜱虫减少了94.8%。口服阿福拉纳+米尔贝肟30天内蜱虫减少94.4%。试验蜱虫包括蓖麻硬蜱、六角硬蜱、红扇头蜱和网状蜱。

5.3.5Additional Uses

5.3.5其他应用

The label directions and control claims for each of the isoxazoline insecticides registered vary. In addition to controlling fleas and ticks, isoxazolines in combination with endoparasiticides (i.e., macrocyclic lactones) allow the broader spectrum to intestinal nematodes and heartworm.

每一种已登记的异噁唑啉杀虫剂的标签说明和管理声明各不相同。除了控制跳蚤和蜱虫外，异噁唑啉与体内杀虫剂(即大环内酯类)联合使用，对肠道线虫和心线虫的范围更广。

In a recent review, the use of isoxazolines to control Demodex mites in dogs was concluded to be effective, with few adverse side effects. Oral doses of afoxolaner or afoxolaner + milbemycin oxime to dogs provided 98.1% reduction in the number of Demodex mites at day 84. At day 84, 62.5% of the dogs were considered mite free. Skin lesions and pruritus were significantly reduced in the treated dogs. In another study, a single oral dose of afoxolaner + milbemycin oxime to dogs provided >95% reduction in the number of Demodex mites by day 28. The most significant decreases in mites and lesions occurred during the first 7 days. In a study of healthy dogs with populations of Demodex mites, cutaneous populations of Demodex over the 90-day period were not affected by a treatment of fluralaner or afoxolaner. It was suggested that isoxazoline treatments may not completely eliminate Demodex mites, but only return them to a more natural population level.

在最近的一篇综述中，使用异噁唑啉来控制犬的蠕形螨是有效的，副作用很少。口服阿福拉纳或阿福拉纳+米尔贝肟可在第84天使犬的蠕形螨数量减少98.1%。第84天，62.5%的犬无螨虫。治疗后的犬的皮肤病变和瘙痒明显减少。在另一项研究中，单次口服阿福拉纳+米尔贝肟可使犬在第28天的蠕形螨数量减少＞95%。在使用前7天螨虫和皮肤病变明显减少。在一项对健康犬蠕形螨数的研究中，90天里皮肤蠕形螨数量没有受到氟雷拉纳或阿福拉纳治疗的影响。提示异噁唑啉治疗可能不能完全消除蠕形螨，而只能使其恢复到更自然的数量水平。

An oral dose of afoxolaner to dogs provided 99.4% reduction of ear mites Otodectes cynotis at day 28. Topical applications of fluralaner to cats provided 100% control of the ear mite by day 7 and provided protection for at least 84 days. A single application of selamectin + sarolaner provided 94.4% reduction of O. cynotis within 30 days compared with a 72% reduction when treated with imidacloprid + moxidectin. An oral dose of afoxolaner to cats naturally infested with ear mites provided 100% efficacy for at least 35 days.

口服阿福拉纳可在第28天减少99.4%的耳螨。猫外用氟雷拉纳在第7天可100%控制耳螨，并提供至少84天的保护。单次使用赛拉菌素+沙罗拉纳在30天内可使耳螨降低94.4%，而使用吡虫啉+ 莫昔克丁可降低72%。自然感染耳螨患猫口服一次阿福拉纳有效率100%，持续35天。

Oral doses of afoxolaner or afoxolaner + milbemycin oxime provided >98% reduction in the number of Sarcoptes mites from skin scrapings from dogs for 2 months. An oral dose of afoxolaner or fluralaner to dogs provided 100% kill of the bug Triatoma infestans (a principal vector of Chagas disease) for 51 days. Less blood was consumed by bugs feeding on dogs treated with afoxolaner than fluralaner for some unknown reason.

犬口服阿福拉纳或阿福拉纳+米尔贝肟2个月可使皮肤刮片疥螨数量减少＞98%，持续2个月。给犬口服阿福拉纳或氟雷拉纳100%杀灭锥蝽臭虫(锥虫病的主要媒介)，持续51天。由于某些未知的原因，用阿福拉纳治疗的犬，虫子吸血量比氟雷拉纳治疗的犬少。

Yellow-fever mosquitoes, Aedes aegypti, were allowed to feed on dogs dosed with afoxolaner. Mosquitoes readily fed on the dogs indicating that the treatment was not repellent. At 24 h after feeding, 98 and 75.3% of the female mosquitoes were killed when exposed to dogs on day 2 and 29 after the dogs were dosed, respectively.

黄热病蚊子、埃及伊蚊，会叮咬服用阿福拉纳的犬。蚊子还是会叮咬犬，这表明这种治疗并不具驱避作用。叮咬给药后的犬24h后，第2天和第29天，雌蚊杀灭率98%和75.3%。

The use of systemic insecticides to control phlebotomine fly vectors has been reviewed by Gomez and Picado. The flies are responsible for transmission of zoonotic visceral leishmaniasis. An oral dose of fluralaner to dogs provided 60–80% mortality of phlebotomine flies for 30 days, but moxidectin, spinosad, and afoxolaner did not increase mortality of the flies. In a laboratory study, dogs dosed with afoxolaner provided 100, 95.9 and 75.5% mortality of Phlebotomus perniciosus within 48 h after feeding. Flies fed on both treated and untreated dogs and the afoxolaner was not repellent.

Gomez和Picado综述了使用全身性杀虫剂控制白蛉虫媒的情况。白蛉是人畜共患病内脏型利什曼病的传播途径。给犬口服氟雷拉纳30天后，白蛉死亡率为60-80%，而莫昔克丁、多杀菌素和阿福拉纳并没有增加白蛉的死亡率。在一项实验室研究中，犬口服阿福拉纳48小时后，恶毒白蛉死亡率分别为100%、95.9%和75.5%。白蛉会叮咬治疗过和未治疗过的犬，阿福拉纳没有驱避作用。

An indirect effect of treating pets with isoxazolines is the prevention of dog tapeworm transmission by infected adult fleas. An oral dose of afoxolaner + milbemycin oxime provided indirect protection to dogs from ingesting adult cat fleas infected with cysticercoid larvae of Dipylidium caninum. Topical or oral fluralaner treatments prevented dogs from acquiring dog tapeworm.

用异噁唑啉治疗宠物的一个间接效果是防止受感染的跳蚤成虫传播犬绦虫。口服阿福拉纳+米尔贝肟可间接保护犬食入感染了犬复孔绦虫囊尾蚴幼虫的猫跳蚤成虫。外用或口服氟雷拉纳治疗可防止犬感染犬绦虫。

An oral dose of sarolaner + moxidectin + pyrantel or afoxolaner + milbemycin oxime to dogs naturally infected with ascarid nematodes and hookworms provided >99% reduction of fecal egg counts. A topical dose of selamectin + sarolaner prevented the development of feline heartworm Dirofilaria immitis in cats.

自然感染蛔虫线虫和钩虫的犬，口服沙罗拉纳+莫昔克丁+噻吩嘧啶或阿福拉纳+米尔贝肟可使粪便虫卵减少＞99%。猫外用赛拉菌素+沙罗拉纳可防止心丝虫感染。

Dogs naturally infested with canine screwworm myiasis were treated with five different insecticides or drugs. Nitenpyram killed all fly larvae within 6 h, and spinosad + milbemycin oxime killed them within 7 h. Within 24 h, all fly larvae were killed with afoxolaner + milbemycin oxime. There was a synergism between spinosad and milbemycin oxime.

用五种不同的杀虫剂或药物治疗自然感染的犬蝇蛆病。烯啶虫胺在6 h内杀死所有苍蝇幼虫，多杀菌素+米尔贝肟在7 h内杀死所有苍蝇幼虫，阿福拉纳+米尔贝肟在24 h内杀死所有苍蝇幼虫。多杀菌素与米尔贝肟有协同作用。

The rapid prevention of adult flea feeding has been shown to be important in reducing the effects of FAD. Fluralaner and afoxolaner both provided dramatic improvement of FAD in dogs. Similarly, a topical application of fluralaner decreased all the FAD signs on cats beginning at day 7 and continuing until day 84. An oral dose of fluralaner resolved 90% of 20 cases of FAD at day 84 and 94% of 16 cases at day 168. FAD symptoms were dramatically reduced in dogs treated with sarolaner or spinosad at day 90. Oral applications of sarolaner or spinosad provided 62–67% reduction in FAD as measured by the Canine Atopic Dermatitis Extent and Severity Index-4 scale. Spinetoram was better at reducing FAD compared with the fipronil + methoprene treatment. The topical application of fluralaner provided significant reduction in clinical signs of FAD in cats. Oral doses of sarolaner + moxidectin + pyrantel or afoxolaner + milbemycin oxime dramatically reduced the symptoms of FAD in naturally infested dogs within 30 days. In a multiple location study in the USA, an oral dose of sarolaner + moxidectin + pyrantel or afoxolaner dramatically reduced the clinical signs of FAD with dogs.

快速防止跳蚤成虫叮咬已被证明对减少FAD有重要作用。氟雷拉纳和阿福拉纳均能显著改善犬的FAD。同样，外用氟雷拉纳可从第7天开始直至第84天，降低猫的所有FAD症状。口服氟雷拉纳20例FAD在第84天缓解率90%，16例FAD在第168天缓解率94%。用沙罗拉纳或多杀菌素治疗的犬的FAD症状在90天里明显减轻。根据犬特应性皮炎严重程度指数-4量表测定，口服沙罗拉纳或多杀菌素可使FAD降低62-67%。乙基多杀菌素在降低FAD方面优于非泼罗尼+甲氧普烯治疗。猫外用氟雷拉纳FAD的临床症状明显减轻。口服沙罗拉纳+莫昔克丁+噻吩嘧啶或阿福拉纳+米尔贝肟可在30天内显著减轻自然感染犬的FAD症状。在美国的一项多地点研究中，口服沙罗拉纳+莫昔克丁+噻吩嘧啶或阿福拉纳可明显减轻犬FAD临床症状。

5.4Formulations

5.4剂型

The use of pet collars has been popular for decades even though there was little published evidence that they controlled flea populations on pets. However, collars containing 10% imidacloprid + 4.5% flumethrin provide effective control of fleas for up to 8 months. In vitro lab studies have shown that the combination of imidacloprid and flumethrin synergizes their toxicity against fleas and ticks. Collars containing imidacloprid + flumethrin provided a 100% reduction in flea numbers on dogs at days 120 and 210, whereas deltamethrin collars provided only 76.7 and 66.7% reduction at days 120 and 210, respectively. The use of an imidacloprid + flumethrin collar on cats on the Isles of Lipari and Vulcano reduced flea infestations by 79.4, 100, and 93.6% at 210, 270, and 360 days, respectively.

几十年来，宠物项圈的使用一直很流行，尽管很少有公开发表的证据表明它们能控制宠物身上的跳蚤数量。而含10%吡虫啉+4.5%氟氯苯菊酯的项圈可有效防治跳蚤长达8个月。体外实验室研究表明，吡虫啉+氟氯苯菊酯联用对跳蚤和蜱虫的毒性具有协同作用。吡虫啉+氟氯苯菊酯项圈在120天和210天时均能使犬跳蚤数量减少100%，而溴氰菊酯项圈在120天和210天时仅能分别减少76.7%和66.7%。在利帕里群岛和瓦卡诺群岛，猫使用吡虫啉+氟氯苯菊酯项圈在210天、270天和360天时，跳蚤感染分别减少了79.4%、100%和93.6%。

In addition to controlling fleas and ticks, collars containing either imidacloprid + flumethrin or deltamethrin, provided 88.3 and 61.8% efficacy in preventing the transmission of Leishmania infantum by phlebotomine sand flies. In a study with cats, the imidacloprid + flumethrin collar prevented 75% of feline Leishmania infection. In another study, imidacloprid + flumethrin collars provided a preventive effect of 71.5% in the transmission of Bartonella in cats. The collar provides an effective measure to reduce the risks of both diseases.

除控制跳蚤和蜱虫外，含吡虫啉+氟氯菊酯或溴氰菊酯的项圈对预防白蛉型沙蝇传播利什曼原虫的有效性分别为88.3%和61.8%。在一项针对猫的研究中，吡虫啉+氟氯苯菊酯项圈预防了75%的猫利什曼原虫感染。在另一项研究中，吡虫啉+氟氯苯菊酯项圈对巴尔通体在猫体内传播的预防效果为71.5%。项圈是降低这两种疾病风险的有效措施。

曾医生

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