Diagnosis and treatment of demodicosis in dogs and cats 犬猫的蠕形螨病的诊断和治疗 Clinical consensus guidelines of the World Association for Veterinary Dermatology 世界兽医协会皮肤病临床治疗指南 翻译：蔡欢 校对：王帆
7 Treatment 7治疗 7.1 General considerations 7.1总则 Demodicosis varies from mild localized to severe generalized disease. Mild localized disease will resolve spontaneously in most cases. How many dogs with more severe disease would also resolve spontaneously without treatment is unclear. Although a study has attempted to evaluate the proportion of dogs with the generalized form of the disease that undergo spontaneous remission, such studies are difficult to conduct and robust data are lacking to answer this question. In addition, in most countries it is considered unethical to withhold treatment of dogs with severe demodicosis and owners of such dogs usually will not consent to observation instead of interventional (and typically efficacious) acaricidal therapy. Nevertheless, there is some evidence that spontaneous remission can occur in a subset of dogs with generalized disease. 蠕形螨病从轻度的局灶性疾病到严重的全身性疾病不等。在大多数情况下，轻度的局部疾病会自愈。尚不清楚有多少只蠕形螨感染更严重患犬不经治疗也能自愈。尽管一项研究试图评估患有全身性蠕形螨病犬自愈的比例，但此类研究难以进行，并且缺乏可靠的数据来回答这个问题。另外，在大多数国家中，不治疗严重感染的犬被认为是不道德的，并且犬的主人通常不会同意用观察来代替使用杀螨治疗（并且通常是有效的）。尽管如此，仍有一些证据表明自愈可发生在一部分患有全身性疾病的犬中。
Anecdotally, intact female dogs with generalized demodicosis in remission after successful treatment may show disease recurrence when in oestrus. Some of the present authors also have seen this. In a female Dobermann pinscher four recurrences each associated with oestrus were seen until the owner agreed to neutering. In a study of American Staffordshire terriers, Staffordshire bull terriers and pugs with demodicosis from Sweden, the rate of recurrence was not increased in the group of intact bitches. 有趣的是，未绝育的雌性全身性蠕形螨病患犬在治疗成功病情得到缓解后，在发情期可能会复发。目前一些作者也已经注意到了这一点。在一只雌性杜宾犬中，发现四次与发情有关的复发，直到宠主同意绝育。在对来自瑞典的美国斯塔福㹴，斯塔福斗牛㹴和巴哥犬的研究中，未绝育母犬的复发率并未增加。
In juvenile dogs, treatment of the demodicosis and possibly the secondary bacterial infection, if present, is typically sufficient without the need for further diagnostic investigation. By contrast, for those cats and dogs with adult-onset disease, the possibility of an underlying, immunosuppressive disease should be investigated. In one dog with adult-onset demodicosis, treatment of the primary disease resulted in resolution of the demodicosis. In another study evaluating dogs with adult-onset demodicosis, four of nine dogs in which the primary disease was diagnosed and treated successfully were cured. By contrast, only three of 25 dogs in which no underlying disease was diagnosed or the concurrent disease could not be treated were cured. However, even extensive investigation for underlying diseases is not always successful in identifying a cause for the demodicosis. In one larger study, 30% of the adult dogs had idiopathic demodicosis. 在幼犬中，通常需要对蠕形螨病和可能的继发细菌感染（如果存在）进行治疗，而无需进一步的诊断观察。相比之下，对于那些患有其他疾病的猫和犬，应该关注其潜在的免疫抑制性疾病的可能性。在一只患有蠕形螨病的成年犬中，对其原发疾病的治疗使其蠕形螨病得到消退。在另一项评估蠕形螨病成年犬的研究中，九只犬在成功诊断和治疗原发疾病后，有四只犬的蠕形螨病被治愈。相比之下，在没有诊断出潜在疾病或无法治疗并发疾病的25只蠕形螨病犬中，只有三只犬的蠕形螨病治愈了。但是，即使对潜在疾病进行大量的研究，也始终无法成功地确定蠕形螨病的病因。在一项较大的研究中，有30％的成年犬患有特发性蠕形螨病。
Regardless of the specific miticidal therapy, treatment success is monitored both clinically and by repeated skin scrapings. Generally, it is recommended to examine dogs and cats with demodicosis monthly. At each recheck, skin scrapings are taken from the same sites as in previous visits. In addition to clinical improvement, the numbers of mites and immature stages should decrease with each visit. If clinical improvement does not occur and mite numbers fail to improve, a change in therapy should be considered. Clients need to be informed that their pets may look better before the mites have been eliminated, thus the need to comply with monthly evaluations until the patient is deemed parasitologically cured. They also need to be educated about the potentially slow improvement in clinical signs over several weeks to months. 不管具体的杀螨疗法如何，都需要通过临床症状和持续刮片来监测治疗效果。通常，建议蠕形螨病患犬患猫每月复诊。每次复查时，都从之前取样的相同部位进行皮肤刮片。除临床症状改善外，每次检查发现的螨虫成虫和未成熟阶段螨虫的数量均应减少。如果临床症状没有改善并且螨虫数量没有减少，则应考虑改变治疗方法。需要告知宠物主人，在消除蠕形螨之前，他们的宠物可能会看起来很好，但需要按时每月复查评估，直到患病动物视为治愈。还需要对他们进行教育，未来几周到几个月的临床症状都可能改善缓慢。
Miticidal therapy should be continued four weeks beyond the second set of negative monthly scrapings to decrease the risk of a disease recurrence. In dogs that responded very slowly to therapy, treatment may be extended even further. In a systematic review of 124 dogs reported to have failed the initial therapy, two thirds responded to a change of therapy. Similarly, of 40 dogs with recurring demodicosis within 12 months after initially responding to therapy, more than two thirds went into remission after another treatment course with the same or an alternative medication. A follow-up of at least 12 months after treatment cessation has been recommended before calling a dog cured, although in some studies the disease recurred after more than 12 months of remission in a few dogs. 在每月的刮片检查中，当第二次出现阴性时，应再继续进行四周的杀螨治疗，以降低疾病复发的风险。对于在治疗中好转非常慢的犬，治疗可能会进一步延长。一项对124只据报道初始治疗失败的犬的系统评估显示，三分之二的犬在改变治疗方式后有好转。同样，在最初治疗有好转后的12个月内，有40只犬蠕形螨病复发，这其中又有超过三分之二的犬在接受相同或替代药物的另一疗程后得到缓解。建议在停止治疗后至少随访12个月，然后称其为治愈犬，但在一些研究中，一些犬的疾病在好转超过12个月后复发。
Consensus Statement 7 Treatment for generalized demodicosis should be monitored clinically and microscopically every month until the second negative skin scraping. Miticidal therapy should be continued four weeks beyond the second set of negative monthly scrapings to decrease the risk of a disease recurrence. 共识声明7：对全身性蠕形螨病的治疗，应每月检测临床症状和显微镜检查，直到第二次皮肤刮片为阴性再停止。在第二次皮肤刮片为阴性后，应继续进行杀螨治疗四周，以降低疾病复发的风险。
In most dogs with demodicosis, secondary bacterial infection will develop with time. In the past, systemic antibiotic therapy was recommended for all dogs in which a secondary bacterial infection could be demonstrated clinically and cytologically. However, in a randomized controlled trial evaluating 58 dogs with generalized demodicosis, half of the dogs were treated with systemic antibiotics in addition to miticidal therapy with daily ivermectin and topical weekly benzoyl peroxide shampoo, the other half received only shampoo and ivermectin. There was no significant difference between groups in the time to cytological resolution of the bacterial pyoderma, the time to negative skin scrapings and to clinical remission. Systemic antibiotics may not be needed because topical therapy with antimicrobial shampoo was as effective in cases with mild to moderate secondary pyoderma. In dogs with severe deep pyoderma, previous antibiotic treatment or dogs with bacterial infections associated with the presence of rod-shaped bacteria on cytological samples then bacterial culture and sensitivity should be recommended as a basis for the selection of appropriate antibiotic therapy. As the prevalence of skin infections with multiresistant bacteria is increasing, antibiotic stewardship with a judicial use of systemic antibiotics is recommended, and topical antibacterial therapy alone should be considered for the majority of dogs with demodicosis. 随着时间推移，大多数蠕形螨病患犬会出现继发性细菌感染。过去，建议对所有可在临床和细胞学上证实有继发细菌感染的犬进行全身性抗生素治疗。但是，在一项评估了58例全身性蠕形螨病犬的随机对照试验中，两组病犬均接受每日伊维菌素杀螨治疗和每周外用过氧化苯甲酰香波，但其中一组的病犬还接受了全身性抗生素治疗。在细菌性脓皮病的细胞学消退时间、皮肤刮片为阴性的时间和临床症状缓解的时间方面，各组之间没有显著差异。因为在轻度至中度继发性脓皮病的情况下，外用抗菌香波进行治疗是有效的，所以可能不需要使用全身性抗生素。在患有严重深部脓皮病的犬中，已使用过抗生素治疗的犬或在细胞学样本上存在杆菌感染的犬，应建议先做细菌培养和药敏试验来选择适当的抗生素治疗。随着多重耐药细菌引起的皮肤病感染率上升，建议通过合理使用全身性抗生素来进行抗生素管理，并且对于大多数患有蠕形螨病的犬，应考虑单独外部抗菌治疗。
Consensus Statement 8 In dogs with demodicosis, systemic antibiotics will typically not be needed and topical antibacterial therapy combined with good miticidal agents will be sufficient unless severe bacterial infection is present. 共识声明8：在蠕形螨病患犬中，通常不需要全身性抗生素治疗，除非存在严重的细菌感染，否则外部抗菌疗法与良好的杀螨剂相结合就足够了。
7.2 Amitraz 7.2双甲脒 Amitraz as a leave-on rinse has been the approved mainstay treatment for canine generalized demodicosis in many countries for decades. It is a diamide, N’ -(2,4-dimethylphenyl)-N-[(2,4-dimethylphenyl)imino]1-8methyl]-N-methylmethanidamide. Amitraz is a monoamine oxidase inhibitor, an alpha 2-adrenergic agonist and inhibits prostaglandin synthesis. In addition to the rinse, amitraz also is available in a 9% tick preventive collar, reported as a sole therapy and in combination with other ectoparasiticides. However, amitraz tick collar efficacy for canine demodicosis is controversial. Pilot studies of the spot-on products (in combination with metaflumizone and with fipronil) reported successful treatment of canine generalized demodicosis. However, pemphigus foliaceus-like drug reactions were reported with both products. The manufacturers of both products have discontinued the production of those spot-ons. 几十年来，双甲脒作为一个免冲洗的浸泡剂，已成为许多国家公认的犬全身性蠕形螨病的主要治疗剂。它是一种二酰胺，N'-（2,4-二甲基苯基）-N-[（2,4-二甲基苯基）亚氨基] 1-8甲基] -N-甲基甲酰胺。双甲脒是一种单胺氧化酶抑制剂，是一种α2-肾上腺素能激动剂，可抑制前列腺素的合成。除浸泡以外，还可以使用含9％双甲脒的蜱虫预防项圈，已有单独治疗和与其他体外驱虫药联用的报道。但是，双甲脒防蜱项圈对犬蠕形螨病的疗效具有争议。初步研究表明，该产品（与氰氟虫腙和非泼罗尼联用）能成功治疗犬全身性蠕形螨病。但是，两种产品均有落叶型天疱疮样药物反应报道。两种产品的制造商都已停止生产这些产品。
The amitraz rinse has been shown to be an effective treatment option in many studies. This evidence for efficacy was confirmed by systematic reviews. Amitraz rinses require adequate skin contact for optimal efficacy. Therefore, it is recommended to clip the hair coat in medium- and long-haired dogs. The hair should be kept short throughout the treatment period. The rinse should be applied with a sponge and the skin soaked thoroughly and allowed to dry without rinsing. Dogs should not get wet between rinses, to avoid washing off the amitraz. Gentle removal of crusts and surface debris with a shampoo is recommended before application of the amitraz rinse. Dogs should be lightly towel dried after shampooing and water rinsing before the application of the amitraz rinse. 在许多研究中，证明了双甲脒浸泡是一种有效的治疗选择。疗效的证据已通过系统评价得到证实。双甲脒浸泡需要与皮肤充分接触才能获得最佳效果。因此，建议中长毛犬剪断被毛。在整个治疗期间，应保持短毛状态。浸泡应使用海绵，彻底浸透皮肤，然后干燥，无需冲洗。犬在使用双甲脒浸泡期间不要淋湿，避免洗掉双甲脒。建议在使用双甲脒浸泡之前，先用香波轻柔地去除结痂和表面皮屑。香波用水冲洗后，应先用干毛巾轻轻擦干患犬，然后再使用双甲脒浸泡。
Rinses should be performed in a well-ventilated area and protective clothing should be worn by the handler, as adverse effects such as respiratory problems have been observed in humans. Care should be taken to avoid inappropriate ingestion or excessive exposure. In addition to respiratory adverse effects, many other adverse effects have been reported in humans associated with amitraz poisoning. A systematic review in humans analyzed 32 studies describing 310 cases of amitraz poisoning. The most commonly reported clinical features of amitraz poisoning were altered sensorium, miosis, hyperglycaemia, bradycardia, vomiting, respiratory failure, hypotension and hypothermia. Diabetic humans should avoid all contact with amitraz. Reported adverse effects of amitraz in dogs included depression, sleepiness, ataxia, pruritus, urticaria, oedema, skin irritations, polyphagia, polydipsia, hypotension, bradycardia, hyperglycaemia, vomiting and diarrhoea. Severe reactions or intoxications in dogs can be antagonized with yohimbine or atipamezole. Additional symptomatic treatment may be added. Smaller breed dogs, in particular toy-breed dogs, such as Pomeranians and Chihuahuas, are at increased risk for toxicity and deaths have been reported. Chihuahuas are specifically excluded on the label. Amitraz should be used with caution in very young, geriatric and/ or debilitated animals. Because amitraz is ana2-adrenergic agonist, sedating agents that also area-adrenergic agonists (e.g. benzodiazepines, xylazine) should be avoided due to possible synergistic toxicity. 应在通风良好的地方进行浸泡，操作人员应穿戴防护服，因为在人类中已观察到诸如呼吸系统问题之类的不利影响。应注意避免不当摄入或过度暴露。除呼吸不良反应外，也有许多与双甲脒中毒有关的人类不良反应报道。一项针对人类的系统综述分析了32项研究，描述了310例双甲脒中毒病例。据报道，最常见的双甲脒中毒的临床症状是影响感觉中枢、瞳孔缩小、高血糖症、心动过缓、呕吐、呼吸衰竭、低血压和体温过低。糖尿病人应完全避免接触双甲脒。据报道，双甲脒对犬的不良反应包括抑郁、嗜睡、共济失调、瘙痒、荨麻疹、水肿、皮肤刺激、多食、多饮、低血压、心动过缓、高血糖、呕吐和腹泻。犬的严重反应或中毒可用育亨宾或阿替米唑拮抗。可以使用其他对症治疗方法。小型犬，特别是玩具犬，例如博美犬和吉娃娃犬，中毒风险增大，也有死亡报道。标签上明确禁用于吉娃娃。在非常年幼、年老和/或虚弱的动物中应谨慎使用双甲脒。由于双甲脒是α2-肾上腺素能激动剂，应避免使用α类肾上腺素能激动剂（例如苯二氮卓类、赛拉嗪），因为它们可能具有协同毒性。
The recommended concentration varies from 0.025% to 0.06% once weekly to every two weeks. Clinical efficacy increases with increasing concentration and shorter treatment intervals. Intensive protocols with daily rinsing of alternating body halves at a concentration of 0.125% or weekly treatment with an amitraz concentration of 1.25% have been reported in dogs not responding to conventional therapies. In the latter report, each time, dogs were treated once with atipamezole (0.1 mg/kg intramuscularly) followed by yohimbine (0.1 mg/kg) orally (p.o.) once daily for three days to minimize systemic adverse effects with each weekly treatment. Treatment of pedal demodicosis with amitraz rinses may be especially problematic in wet environments because it is difficult to maintain sufficient amitraz on the pedal skin in these circumstances. Daily treatment of the paws or using other treatment modalities may be needed. As many as 20% of dogs with generalized demodicosis do not attain negative scraping results or experience a recurrence when treatment with amitraz is discontinued. The success rate of amitraz rinses was reported to be lower in dogs with adult-onset demodicosis. 推荐的浓度从0.025％到0.06％，频率从每周一次到每两周一次。临床疗效随浓度增加和治疗间隔时间缩短而增加。据报道，对常规治疗无效的犬，可每日用浓度为0.125％的双甲脒浸泡半个身体的强化方案，或每周用浓度为1.25%的双甲脒进行治疗。在后一份报告中，每次都用阿替美唑(0.1mg/kg肌注)，口服育亨宾(0.1mg/kg口服)，连续三天，以减少每周一次治疗的全身性不良反应。在潮湿的环境中，用双甲脒洗液治疗蠕形螨性足炎可能有难度，因为在这种情况下很难在足部皮肤上保持足够的双甲脒。可能需要每日治疗爪部或使用其他治疗方式。当停止使用双甲脒治疗时，多达20％的患有全身性蠕形螨病的犬没有获得阴性的刮片结果或复发。据报道，成年蠕形螨病犬的双甲脒洗液成功率较低。
Combining amitraz with other miticidal therapies has been reported previously but is currently rarely used because of the high efficacy of other therapies. There is a report of potentiated neurotoxicity in a dog treated with ivermectin and amitraz. 先前已经报道过将双甲脒与其他杀螨疗法相结合，但是由于其他疗法的高功效，目前很少联合使用。有报道称，用伊维菌素和双甲脒治疗的犬会增强神经毒性。
Consensus Statement 9 Weekly amitraz rinses at 0.025–0.05% are effective for canine demodicosis; long-haired animals should be clipped. 共识声明9：每周0.025-0.05％的双甲脒冲洗对犬蠕形螨病有效。长毛动物应剪毛。
7.3 Ivermectin 7.3伊维菌素 Ivermectin is derived from the fermentation of molecularly synthesized Streptomyces avermitilis. Since its introduction as a broad-spectrum parasiticide in 1981, it has become widely used in veterinary medicine. For almost two decades, ivermectin was the most commonly used macrocyclic lactone in the treatment of canine demodicosis. However, it is only approved in dogs for the prevention of the heartworm Dirofilaria immitis–all other applications are considered extra-label. 伊维菌素来源于分子合成的阿维链霉菌的发酵。 自从1981年作为广谱杀寄生虫剂引入以来，它已在兽医学中广泛使用。 在将近二十年中，伊维菌素是犬蠕形螨病治疗中最常用的大环内酯类药物。但是，它仅在犬中被批准用于预防犬心丝虫病-所有其使应用均被视为标签外。
Preliminary studies using ivermectin for the treatment of demodicosis evaluated various dosages and routes of administration. Initial results indicated that daily oral administration of ivermectin was the most efficacious protocol whilst weekly subcutaneous (s.c.) administration at 0.4 mg/kg or use of a 0.5% ivermectin topical pour on three times weekly yielded poor results.Several studies have examined the use of oral ivermectin at varying dosages with contrasting results. Oral administration at 350 μg/kg and 400 μg/kg daily demonstrated poor efficacy with only 30% and 48% rates of cure, respectively. However, small sample size and concurrent administration of other drugs may have negatively impacted the results of these trials. By contrast, the cure rate was 85% in another study when ivermectin was administered at 300μg/kg p.o. daily; similar results were achieved using 500–600μg/kg. The currently recommended protocols generally employ 300–600μg/kg p.o. once daily until four to eight weeks beyond parasitological cure. 使用伊维菌素治疗蠕形螨病的初步研究评估了各种剂量和给药途径。初步结果表明，每日口服伊维菌素是最有效的方案，而每周皮下（sc）给药0.4 mg / kg或每周3次使用0.5％伊维菌素外部给药的效果不佳。一些研究对比了伊维菌素在不同剂量下的结果。每日以350μg/ kg和400μg/ kg的口服剂量显示疗效差，分别只有30％和48％的治愈率。但是，小的样本量和同时使用了其他药物可能会对这些试验的结果产生负面影响。相比之下，在另一项研究中，当伊维菌素以300μg/ kg 每日口服给药时，治愈率为85％;使用500–600μg / kg时，治愈率相近。目前推荐的方案通常是使用300–600μg / kg口服每日一次，直到蠕形螨治愈后的四到八周。
Despite its frequent successful use in the treatment of demodicosis, it is unlikely that ivermectin will ever become labelled for this purpose due to its potential toxicity. Dogs treated with ivermectin should be closely monitored for potential neurotoxicity, especially ivermectin-sensitive breeds such as collie breeds, Australian shepherd dogs, Shetland and old English sheepdogs or dogs treated with high doses of ivermectin. Clinical signs of toxicosis may include mydriasis, lethargy, vomiting, ataxia, tremors and temporary blindness, which may rapidly progress to seizures, stupor, coma, respiratory failure and death. Mydriasis is typically the first clinical sign of ivermectin toxicity and the last to resolve. There is no specific antidote for ivermectin toxicosis. Depending on their severity, the clinical signs typically resolve within days to weeks following cessation of the drug along with supportive care. In the case of an acute oral overdose, repeated doses of activated charcoal may be administered in an effort to disrupt enterohepatic recirculation. Intravenous lipid emulsion therapy has been shown to be effective in the treatment of adverse reactions to all lipophilic drugs including ivermectin. Its effect is thought to be due to the lipid sink mechanism whereby the drug is drawn out of the tissues and sequestered into a lipid phase within the intravascular space, thereby decreasing CNS tissue concentrations. Physostigmine, a parasympathomimetic alkaloid and reversible cholinesterase inhibitor, has been shown to cause short-term improvement in neurological signs but is not recommended for prolonged use due to its significant cholinergic effects and only temporary action. Flumazenil, a gamma-aminobutyric acid (GABA)-antagonist, has been shown to reverse the effects of ivermectin in experimental models in rodents. However, its clinical efficacy in dogs has yet to be demonstrated. 尽管伊维菌素在蠕形螨病的治疗中屡获成功，但由于其潜在的毒性，因此不可能将伊维菌素批准为该病治疗。应密切监测用伊维菌素治疗的犬的潜在神经毒性，尤其是对伊维菌素敏感的品种，例如牧羊犬，澳大利亚牧羊犬，设得兰牧羊犬和古代牧羊犬或用高剂量伊维菌素治疗的犬。中毒的临床症状可能包括瞳孔扩大、嗜睡、呕吐、共济失调、震颤和暂时性失明，这些症状可能会迅速发展为癫痫发作、木僵、昏迷、呼吸衰竭和死亡。瞳孔扩大通常是伊维菌素毒性要解决的第一个临床症状，也可能是最后一个。没有针对伊维菌素中毒的特异性解毒剂。根据其严重程度，临床症状通常在停药后数天至数周内以及支持治疗后消失。在急性口服用药过量的情况下，可重复口服活性炭，以破坏肠肝循环。静脉注射脂肪乳治疗已被证明可有效治疗包括伊维菌素在内的所有亲脂性药物的不良反应。认为其作用归因于脂质吸收机制，即将药物从组织中抽出并隔离在血管内的脂质相中，从而降低了中枢神经系统组织浓度。毒扁豆碱是一种拟副交感神经碱和可逆胆碱酯酶抑制剂，已被证明可使伊维菌素引起的神经系统症状得到短期改善，但不建议长时间使用，因为它具有显著的胆碱能作用，且仅具有暂时性作用。氟马西尼是一种γ-氨基丁酸（GABA）拮抗剂，已被证明可以逆转伊维菌素在啮齿动物实验模型中的作用。但是，其在犬中的临床功效尚未得到证实。
Ivermectin toxicity can occur as a result of acute overdose, elevated serum concentration following long-term administration or associated with genetic susceptibility which is seen most commonly in herding breeds such as collie breeds, Australian shepherd dogs, Shetland and old English sheepdogs and their crosses but also has been recognized to occur in other breeds. Not uncommonly, this results in a severe and sometimes fatal idiosyncratic neurotoxicosis. Ivermectin-sensitivity occurs in individuals that carry a frame shift deletion mutation of the ABCB1 gene (formerly multi-drug resistance gene, mdr1), which is responsible for producing P-glycoprotein (P-gp), an ATP-dependent transmembrane transporter protein which plays an important role in the blood–brain barrier. The deletion mutation causes P-gp synthesis to terminate prematurely resulting in severely truncated, nonfunctional P-gp molecules. Consequently, transport of certain drugs out of the central nervous system (CNS) is impaired, leading to accumulation of drug within the CNS to toxic levels. Ivermectin is among the substrates for P-gp and therefore, individuals that are homozygous for this autosomal recessive gene demonstrate the ivermectin-sensitive phenotype. Dogs can be tested for the ABCB1-1êgenotype before beginning ivermectin therapy through a number of laboratories. However, dogs without this defect also may show signs of toxicity. 伊维菌素的毒性可能是由于急性用药过量，长期用药后血清浓度升高或与遗传易感性有关引起的，这种易感性在牧羊犬、澳大利亚牧羊犬、设得兰群岛和古老的英国牧羊犬及其杂交中最常见，但也被认为存在于其他品种中。并不少见，这会导致严重的，有时甚至致命的特发性神经中毒。伊维菌素敏感性在携带ABCB1基因（以前为多药耐药基因，mdr1）的移码缺失突变的个体中发生，该基因负责产生P糖蛋白（P-gp），这是一种在血脑屏障中发挥重要作用的三磷酸腺苷依赖性跨膜转运蛋白。缺失突变导致P糖蛋白合成过早终止，从而导致产生截短的无功能P糖蛋白分子。因此，某些药物在中枢神经系统（CNS）的运输受到损害，导致CNS内药物的积累达到毒性水平。伊维菌素是P糖蛋白的底物之一，因此，对该常染色体隐性基因纯合体表现出对伊维菌素敏感的表型。在开始进行伊维菌素治疗之前，一些实验室可以对犬进行ABCB1-1ê基因型测试。但是，没有这种缺陷的犬也可能显示出毒性迹象。
In ivermectin-sensitive individuals, toxicity may be apparent 4–12 h after oral administration. Slow titration up to the therapeutic dose over several days is recommended when instituting ivermectin therapy in all breeds of dogs to enable close monitoring for adverse reactions and early identification of ivermectin-sensitive individuals. A starting dose of 0.05 mg/kg on Day 1 is recommended, then 0.1 mg/kg on Day 2 followed by incremental doses of 0.1 mg/kg/day until the final dose is achieved. Treatment should cease and an alternate therapy be considered if neurological signs develop during this titration period. 在对伊维菌素敏感的个体中，口服后4–12小时可能出现明显的毒性。在所有犬种中均采用伊维菌素治疗时，建议在几天内缓慢增至治疗剂量，以便密切监测不良反应并尽早确定对伊维菌素敏感的个体。建议在第1天起始剂量为0.05 mg / kg，然后在第2天起始剂量为0.1 mg / kg，然后以0.1 mg / kg /天的增量剂量给药，直至达到最终剂量。如果在增量过程中出现神经系统症状，应停止治疗并考虑另一种治疗方法。
Owing to ivermectin’s long half-life (80±30 h), serum concentrations rise over weeks until after perhaps six weeks a steady-state is reached. Subchronic ivermectin toxicity also has been reported following longterm therapy as serum drug concentrations accumulate to toxic levels. In a study of 28 dogs that developed subchronic toxicity while being treated for demodicosis with ivermectin or other macrocyclic lactones, only one dog was heterozygous and all others were homozygous for the normal ABCB1 gene. Interestingly, 10 dogs in this study were concurrently receiving one or more drugs that also are substrates of P-gp such as ketoconazole, ciclosporin or glucocorticoids. The concurrent use of ivermectin with other P-gp substrates should be avoided whenever possible. In addition, use of spinosad-containing products should be avoided as mild to moderate ivermectin toxicosis has been reported when these drugs are used concurrently. Spinosad has been shown to be a potent inhibitor of canine P-gp which accounts for its impact on ivermectin pharmacokinetics. In Europe and in the USA, under the Animal Medicinal Drug Use Clarification Act (AMDUCA), off-label therapies should only be used in instances where a drug licensed for the purpose of treating demodicosis has either failed or is contra-indicated. 由于伊维菌素的长半衰期（80±30小时），血清浓度会持续数周上升，直到大概六周后才达到稳态。长期治疗后还报道了亚慢性伊维菌素的毒性，因为血清药物浓度会累积到毒性水平。在一项对28只用伊维菌素或其他大环内酯治疗蠕形螨病时，出现亚慢性毒性的犬进行的研究中，只有一只犬是杂合子，所有其他犬都是正常ABCB1基因的纯合子。有趣的是，该研究中的10只犬同时接受一种或多种也是P糖蛋白底物的药物治疗，例如酮康唑、环孢素或糖皮质激素。应尽可能避免将伊维菌素与其他P糖蛋白底物同时使用。此外，应避免使用含多杀菌素的产品，因为据报道，当同时使用这些药物时，会出现轻度至中度伊维菌素中毒。多杀菌素已被证明是一种强有力的犬P糖蛋白抑制剂，这解释了它对伊维菌素药代动力学的影响。在欧洲和美国，根据《动物药物使用说明法》（AMDUCA），标签外疗法应仅在许可用于治疗蠕形螨病的药物失效或禁用的情况下使用。
7.4 Milbemycin oxime 7.4米尔贝肟 Milbemycin oxime is the fermentation product of Streptomyces hygroscopus aureolacrimosus. It is approved in many countries as an endoparasiticide. In some countries, oral milbemycin oxime is licensed for the treatment of canine demodicosis at a dose of 0.5–2 mg/kg daily. In studies from the USA and Australia, a clearly higher success rate was seen with the higher dose of 1–2 mg/kg compared to 0.5–1 mg/kg p.o. However, these studies were conducted in referral practices with potentially more chronic and severely affected cases. By contrast, a Swedish study showed a good response with the low dose protocol, possibly because most dogs in that study were diagnosed early in the disease and had not previously been treated with other miticides. Alternatively, a different genetic background of the dogs or different sensitivity of the mites to milbemycin oxime may have influenced the results. The success rate of milbemycin oxime was shown to be much lower in dogs with adult-onset demodicosis. 米尔贝肟是吸水链霉菌的发酵产物。它在许多国家被批准为体内驱虫药。在某些国家/地区，米尔贝肟已获许可以每日0.5–2 mg / kg的剂量口服治疗犬蠕形螨病。在美国和澳大利亚进行的研究中，较高口服剂量的米尔贝肟1-2 mg / kg比0.5-1 mg / kg的治愈成功率明显更高。但是，这些研究是在转诊医院进行的，可能涉及更多的慢性病和重病患者。相比之下，瑞典的一项研究显示低剂量方案反应良好，可能是因为该研究中的大多数犬在疾病早期就被诊断出，并且先前未接受过其他杀螨剂的治疗。另外，犬的不同遗传背景或蠕形螨对米尔贝肟的敏感性也可能影响结果。在成年发病犬蠕形螨病中，米尔贝肟的治疗成功率被证明要低得多。
There seems to be a high safety margin with milbemycin oxime. It has been administered to rough collies at a dose of 2.5 mg/kg daily for 10 days with no adverse effects observed. However, dogs homozygous for the ABCB1-1ê(MDR-1) mutation developed ataxia with milbemycin oxime at a dose of only 1.5 mg/kg daily, although they tolerated the drug at 0.6 mg/kg/day. In herding breeds, it is thus prudent to evaluate the ABCB1-1ê(MDR-1) genotype and to use lower doses or increase the dose gradually in dogs homozygous for the ABCB1-1ê(MDR-1) mutation similar to what has been recommended for oral ivermectin. 米尔贝肟的安全性似乎很高。每日以2.5 mg / kg的剂量将其施用给粗毛牧羊犬，持续10天，未观察到不良反应。然而，对于ABCB1-1ê(MDR-1)基因纯合的犬，虽然它们耐受米尔贝肟的剂量为0.6 mg / kg / 天，但在每日剂量仅为1.5 mg / kg的情况下，它们发生了共济失调。因此，在牧羊类品种中，谨慎的做法是评估ABCB1-1ê(MDR-1)基因型，并在ABCB1-1ê(MDR-1)基因纯合的犬中使用较低剂量或逐渐增加剂量，类似于口服伊维菌素时的推荐用药方法。
7.5 Moxidectin 7.5莫昔克丁 Moxidectin, a macrocyclic lactone derived from the fermentation of Streptomyces spp., has demonstrated comparable efficacy to that of other macrocyclic lactones in the treatment of canine generalized demodicosis. Daily administration at 300–400µg/kg p.o. yielded cure rates of 72–85% and 500µg/kg administered every 72h showed similar results. When oral administration (500 µg/kg) was compared to the subcutaneous route (500–1,000µg/kg), each administered every 72 h, rates of cure were 75% and 86%, respectively. Adverse effects were reported in 10–37% of dogs in these studies, but were mostly mild and included emesis, salivation, anorexia, lethargy, dyspnoea and facial oedema. Because these occurred more frequently with subcutaneous administration, the oral route is preferable. The efficacy of moxidectin appears to be similar to that of ivermectin; although neurological signs such as mydriasis, tremor, ataxia and seizures have been reported with overdoses, moxidectin seems to be better tolerated by ivermectin-sensitive individuals than is ivermectin. Nevertheless, a gradual dose increase over several days similar to what is recommended for ivermectin seems prudent to identify the few dogs intolerant to the drug, before adverse effects become severe and potentially fatal. 莫昔克丁是一种源自链霉菌属发酵的大环内酯类药物，在犬全身性蠕形螨病的治疗中已显示出与其他大环内酯类药物相当的功效。每日300-400µg/kg口服治愈率达72–85％，这与每72h使用500µg / kg起到的效果相似。将口服（500 µg / kg）与皮下注射（500–1,000µg / kg）进行比较时，每72小时给药一次，治愈率分别为75％和86％。在这些研究中，据报告有10-37％的犬有不良反应，但主要是轻度的，包括呕吐、流涎、厌食、嗜睡、呼吸困难和面部水肿。因为这些在皮下给药中更频繁地发生，所以首选口服给药。莫昔克丁的功效似乎与伊维菌素相似。尽管据报道，莫昔克丁使用过量会出现诸如瞳孔散大、震颤、共济失调和癫痫等神经症状，但对伊维菌素敏感的犬相比伊维菌素，对莫昔克丁的耐受性更好。尽管如此，在不良反应变得严重甚至可能致命之前需谨慎使用，用药期内逐渐增加剂量类似于口服伊维菌素时的推荐用药方法，以识别出一些对药物不耐受的犬。
Topical application appears to be better tolerated than either of the aforementioned routes. A 2.5% preparation of moxidectin combined with 10% imidacloprid was welltolerated even in ivermectin-sensitive breeds that were given three monthly applications of up to five times the recommended dose. When applied every two weeks, efficacy was greater in dogs with juvenile- versus adultonset disease, similar to studies using other treatment protocols. In a study comparing varying application rates of the moxidectin/imidacloprid spot-on, a significant dose-dependent effect was observed resulting in enhanced efficacy with more frequent application than once monthly. No adverse events occurred in the moxidectin/imidacloprid-treated dogs. By contrast, in the same study, three dogs became intoxicated while receiving daily ivermectin at 500 µg/kg p.o. Although ivermectin was more efficacious than moxidectin/imidacloprid in this study, weekly application of the latter yielded good clinical results and represents a safe therapeutic option. Follow-up data also revealed good long-term effects with no relapse of disease within one year of parasitological cure. Based on the demonstrated dose-dependent efficacy, this product has been registered for weekly use in dogs with demodicosis in many countries and should be considered in mild to moderate cases. 外用似乎比上述任何一种途径都具有更好的耐受性。2.5％莫昔克丁与10％吡虫啉混合制剂，即使在对伊维菌素敏感的品种中使用，每月三次，最高剂量为推荐剂量的五倍也具有良好的耐受性。当每两周使用一次时，相比于使用其他治疗方案的研究，对幼年期和成年期患犬疗效更高。在一项比较莫昔克丁/吡虫啉不同使用率的研究中，观察到显着的剂量依赖性效应，与每月一次相比，更频繁地使用可提高疗效。在莫昔克丁/吡虫啉治疗的犬中未发生不良事件。相比之下，在同一项研究中，每日接受500 µg / kg伊维菌素口服的犬中有3只犬出现中毒。尽管在本研究中伊维菌素比莫昔克丁/吡虫啉更有效，但每周使用过程中后者产生了更好的临床效果，是一种安全的治疗选择。随访数据还显示了后者良好的长期效果，在蠕形螨治愈后的一年内没有复发。基于已证明的剂量依赖性功效，该产品在许多国家/地区已注册为每周一次用于患有蠕形螨病的犬的治疗，在轻至中度蠕形螨感染的情况下应考虑使用。
Further research is required to evaluate the impact of the topical moxidectin/imidacloprid preparation in the prevention of relapse of demodicosis following parasitological cure. One pilot study evaluated the response to once monthly treatment in twelve dogs with relapsing juvenileand adult-onset generalized demodicosis following parasitological cure. All but one dog remained in remission during the 12 month trial. Because this spot-on is commonly prescribed for young dogs as a monthly agent for the treatment and prevention of other parasitic diseases, its influence on the progression of localized demodicosis to the more generalized form should be evaluated. However, the high rate of spontaneous resolution of localized disease complicates interpretation of such studies. 需要进一步的研究来评估外用莫昔克丁/吡虫啉制剂在预防蠕形螨病后预防蠕形螨病复发方面的作用。一项前瞻性研究评估了蠕形螨治愈后，十二只复发性幼龄和成年发作的全身性蠕形螨犬对每月一次的治疗的反应。在12个月的试验中，除一只犬以外的所有犬均保持好转状态。因为这种滴剂通常作为幼犬每月一次的驱虫药用于治疗和预防其他寄生虫病，所以应评估其对局灶性蠕形螨病发展为全身性疾病的影响。但是，局部疾病自愈的高比率使此类研究的阐明方法变得复杂。
7.6 Doramectin 7.6多拉菌素 Doramectin is a longer-acting macrocyclic lactone that has been reported as a successful treatment for canine demodicosis. In the first study, 23 dogs were injected once weekly with 600 μg/kg s.c. for 5– 23 weeks. Ten of the dogs were cured, seven relapsed after 1–24 months (two of which responded to repeat doramectin treatment) and six were lost to followup. None of the animals in this study were reported to show any adverse effects with therapy. In a second study, doramectin was given orally to 29 dogs with generalized demodicosis with good efficacy. Ataxia as an adverse effect of doramectin therapy for demodicosis was seen in one golden retriever. Another study involved 400 client-owned dogs treated with weekly doramectin injections (0.6 mg/kg s.c.), 232 of which successfully completed the protocol. Two hundred and twenty of these dogs (94.8%) achieved clinical remission with two consecutive negative skin scrapes collected two weeks apart. The time taken to achieve this remission ranged from four to 20 weeks (mean duration 7.1 weeks). Three dogs (1.3%) relapsed within a month of treatment cessation but all were successfully treated with a second round of injections. Ten (4.3%) were failures, with no detectable difference in mite numbers seen on follow-up skin scrapings (mean treatment duration 6.4 weeks). The treatment was well-tolerated and only two adverse reactions were seen, one was a local irritation reaction at the injection site and the other ataxia, both developing during therapy and resolved when therapy was withdrawn. Of 17 adult animals (older than four years), 47% had an underlying concurrent disease diagnosed. The efficacy was lower in this group and only 66.7% achieved remission in 6– 8 weeks (mean duration 7.1 weeks). 多拉菌素是一种长效大环内酯类药物，据报道可成功治疗犬蠕形螨病。在第一个研究中，每周给23只犬皮下注射600μg/ kg。持续5-23周。十只犬治愈了，七只犬在1-24个月后复发（其中两只对多拉菌素的重复治疗有反应），六只失去了联系。据报道，该研究中的任何动物均未显示出任何治疗不良反应。在第二项研究中，将多拉菌素给29例全身性蠕形螨病犬口服，疗效良好。多拉菌素治疗蠕形螨病的副作用，是在一只金毛猎犬身上发现了共济失调。在一只金毛寻回犬中发现共济失调是多拉菌素疗法对蠕形螨病的不利影响。另一项研究涉及400只接受每周多拉菌素皮下注射（0.6 mg / kg）治疗的宠物犬，其中232只成功完成了治疗方案。这些犬中的220只（94.8％）临床症状得到了缓解，连续两次出现阴性皮肤刮片相隔两个星期。得到缓解的时间为4至20周（平均持续时间7.1周）。在停止治疗的一个月内有三只犬（1.3％）复发，但所有犬均经过第二轮皮下注射后成功治疗。十只（4.3％）为失败者，在后续皮肤刮片（平均治疗时间6.4周）后发现螨虫数量无可检测的差异。该治疗耐受性良好，仅观察到两种不良反应，一种是在注射部位的局部刺激反应，另一种是共济失调，二者均在治疗过程中发生并在停止治疗后得以缓解。在17只成年犬（大于4岁）中，有47％的犬发现了潜在的并发疾病。该组的疗效较低，在6-8周（平均持续时间7.1周）中仅有66.7％的患犬得到了缓解。
In a further study, sixteen dogs were treated with 600μg/kg doramectin s.c. once weekly and 13 dogs received 600 μg/kg doramectin p.o. twice weekly. The mean time to achieve negative skin scrapings was 13 and 12 weeks, respectively (P=0.955). Adult-onset demodicosis affected five of 16 and two of 13 dogs, respectively (P=0.662). The success rate for treatment was 13 of 16(81%) of dogs receiving subcutaneous injections once weekly and 12 of 13 (92%) dogs receiving oral dosaging twice weekly. (P=0.691). Adverse effects were not observed in any dog. Oral administration of doramectin twice weekly does not achieve a more rapid resolution of canine generalized demodicosis than administration by subcutaneous injection once weekly, but treatment success was the same with both protocols. Finally one report described using doramectin in a 2-week-old litter of nine pug dogs which were presented with pustular lesions covering several areas of the body. All puppies were safely and effectively treated with 0.6 mg/kg/week doramectin with clinical lesions resolved within four weeks and mite negative by eight weeks. Overall this appears to be a well-tolerated and useful therapy for the treatment of canine generalized demodicosis. 在进一步的研究中，16只犬用600μg/ kg多拉菌素皮下注射治疗，每周一次，有13只犬接受多拉菌素600μg/ kg口服，每周两次。出现阴性皮肤刮片的平均时间分别为13周和12周（P = 0.955）。16只犬中的5只和13只犬中的2只（P = 0.662）患有成年发病犬蠕形螨病。治疗的成功率分别为81％（每周皮下注射一次的16只犬中的13只）和92％（每周两次口服给药的13只犬中的12只）。（P＝0.691）。在任何犬中均未观察到不良反应。每周两次口服多拉菌素并不能比每周一次皮下注射更快地解决犬全身性蠕形螨病，但是两种方案的治疗成功率均相同。最后，一份报告描述了在一窝2周大的9只哈巴哥犬中，这些犬均出现了覆盖身体几个区域的脓疱性病变，使用多拉菌素。用0.6毫克/千克/周的多拉菌素对所有幼犬进行安全有效的治疗，临床病变在4周内消失，蠕形螨在8周内消失。总体而言，这似乎是对犬全身性蠕形螨病耐受良好且有用的疗法。
Consensus Statement 10 Oral ivermectin at 0.3–0.6 mg/kg daily, moxidectin at 0.3–0.5 mg/kg daily, milbemycin oxime at 1.0–2.0 mg/kg daily and doramectin injected subcutaneously every week at 0.6 mg/kg are effective therapies for canine demodicosis, but an initial gradual dose increase is recommended for systemic moxidectin and ivermectin to identify dogs sensitive to toxicosis induced by those macrocyclic lactones. Topical moxidectin/imidacloprid should be considered for mild-moderate cases of canine demodicosis. 共识声明10：口服伊维菌素每日0.3–0.6 mg / kg，莫昔克丁每日0.3–0.5 mg / kg，米尔贝肟每日1.0–2.0 mg / kg和多拉菌素每周皮下注射0.6 mg / kg是犬蠕形螨病的有效疗法，但是对于口服莫昔克丁和伊维菌素，初始剂量建议逐步增加，以分辨那些会因大环内酯类药物中毒的犬。轻度中度蠕形螨病犬应考虑外用莫昔克丁/吡虫啉。
7.7 Isoxazolines 7.7异噁唑啉类 Recently, a new group of parasiticides also effective against canine demodicosis has been introduced to veterinary medicine. These ectoparasiticides are isoxazolines and include fluralaner, sarolaner, afoxolaner and lotilaner. These molecules have been shown to target a binding site that inhibits insect and acarine ligand-gated chloride channels, in particular those gated by the neurotransmitter GABA, thereby blocking pre-and postsynaptic transfer of chloride ions across cell membranes. Prolonged isoxazoline-induced hyperexcitation results in uncontrolled activity of the CNS and death of insects and acarines. The selective toxicity of isoxazolines between insects, acarines and mammals may be inferred by the differential sensitivity of the insects’ and acarines’ GABA receptors versus mammalian GABA receptors. 最近，已经将一类对犬蠕形螨病也有效的新的杀虫剂引入了兽药。这些杀外寄生虫剂是异恶唑啉类，包括氟雷拉纳、沙罗拉纳、阿福拉纳和洛替拉纳。这些分子已证明可以靶向一个结合位点，该结合位点抑制昆虫和螨类配体门控的氯离子通道，特别是由神经递质γ-氨基丁酸门控的氯离子通道，从而阻断氯离子穿过细胞膜的突触前和突触后转移。异噁唑啉诱导的长时间过兴奋导致中枢神经系统活动失控，从而造成昆虫和螨虫死亡。异噁唑啉在昆虫、螨虫和哺乳动物之间的选择性毒性，可以通过其对昆虫和螨虫的γ-氨基丁酸受体相对于哺乳动物γ-氨基丁酸受体的不同敏感性来推断。
7.7.1Fluralaner 7.7.1氟雷拉纳 Fluralaner(4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-benzamide) is a rapidly absorbed isoxazoline,that reaches maximum concentrations within 24 h and is quantifiable in plasma for up to 112 days after a single oral administration. Absorption is increased when fluralaner is given with food; it is predominantly excreted unchanged in the faeces by hepatic elimination. It is administered orally every three months. The long interval between treatments may increase owner compliance and thus successful treatment outcome. Fluralaner can be used without additional risk for collie breeds and other sensitive herding breeds that have the MDR1 mutation. Following intravenous administration fluralaner exhibits a relatively high apparent volume of distribution, a low plasma clearance, a long terminal half-life of 12–15 days, and a long mean residence time of 15– 20 days, thereby demonstrating a long persistence of fluralaner in both dogs and cats. 氟雷拉纳（4- [5-（3,5-二氯苯基）-4,5-二氢-5-（三氟甲基）-3-异恶唑基] -2-甲基-N- [2-氧代-2-[（2,2 （2-三氟乙基）氨基]乙基]-苯甲酰胺）是一种快速吸收的异恶唑啉类，在24小时内达到最大浓度，单次口服后达112天仍然可在血浆中测量到。氟雷拉纳与食物同服时，吸收会增加；主要是通过肝脏代谢在粪便中无分解排泄出来。每三个月口服一次。治疗间隔时间长可能会增加患者对药物的依从性，从而提高治疗效果。使用氟雷拉纳不会对牧羊犬品种和其他具有MDR1基因缺陷的牧羊犬品种产生额外风险。静脉内给药后，氟雷拉纳表现出相对较高的表观分布量，较低的血浆清除率，较长的终末半衰期12–15天以及较长的平均停留时间15–20天，从而证明氟雷拉纳在犬和猫体内的持久性很高。
Fluralaner every three months was compared to a spot-on containing imidacloprid/moxidectin administered once monthly. A reduction of 99.8% and 98%, respectively, in mite numbers was achieved after 28 days. Scrapings were negative in all dogs treated with fluralaner after 56 days. However, the dogs used in this study came from South Africa were probably not comparable to privately owned dogs in Europe or North America. In a larger clinical study, 163 dogs of various breeds with generalized demodicosis (63% with juvenile- and 37% with adult-onset of the disease) were treated with fluralaner once at a single dose of 25 mg/ kg. The majority of dogs (87%, all of the dogs with juvenile onset and most with adult-onset demodicosis) had negative skin scrapings after one month and all dogs were negative on scraping after two months. Adverse effects were not seen. A further study that included 67 dogs also demonstrated that fluralaner when given at the recommended dose for flea and tick prevention was effective for the treatment of canine generalized demodicosis. In 46 individuals with adultonset demodicosis 63%, 85% and 100% cure rates were observed after two, three and four months, respectively. In 21 dogs diagnosed with juvenile-onset demodicosis in this same study, 81% and 100% cure rates were observed after two and three months, respectively. 将每三个月使用一次的氟雷拉纳与含有莫昔克丁/吡虫啉每月一次给药的外用滴剂进行比较。28天后，螨虫数量分别减少了99.8％和98％。56天后所有用氟雷拉纳治疗的犬的刮片均为阴性。但是，这项研究中使用的犬来自南非，可能与欧洲或北美的宠物犬不具有可比性。在一项更大的临床研究中，163只患有全身性蠕形螨病的不同品种的犬(63%为幼年型，37%为成年型)接受了氟雷拉纳剂量为25mg/kg的单次治疗。大多数犬(87%，所有幼年发病的犬和大多数成年发病的蠕形螨病犬)在一个月后出现阴性皮肤刮片，并且所有的犬在两个月后刮片时都是阴性的。一项包括67只犬的进一步研究还表明，以建议的剂量预防跳蚤和蜱虫时给予氟雷拉纳可有效治疗犬全身性蠕形螨病。在两个月，三个月和四个月内，在46只成年性蠕形螨病犬中，治愈率分别为63％，85％和100％。在同一项研究中，在21例被诊断为幼年性蠕形螨病的犬中，经过两个月和三个月的观察，治愈率分别达到81％和100％。
Adverse reactions in fluralaner-treated dogs in studies evaluating flea and tick control were uncommon to rare. During a 12-week period, only four of 223 fluralaner-treated dogs (2.0%) had an adverse event, this was in all cases transient gastrointestinal-related signs including vomiting and anorexia. In toxicity studies, administration of fluralaner at the highest recommended treatment dose (56 mg/kg p.o.) at eight-week intervals caused no clinical signs, the safety margin in healthy dogs 8 weeks or older and weighing ³2 kg was more than five times the labelled dose. Of 224 dogs participating in a 182 day field study, 7.1%, 6.7% and 4.9% showed emesis, decreased appetite and diarrhoea, respectively. Lethargy, polydipsia and flatulence were seen in 5.4%, 1.8% and 1.3% of the dogs, respectively. 在评估跳蚤和蜱虫控制的研究中，经氟雷拉纳治疗的犬出现不良反应很少见。在12周的时间内，在223例接受氟雷拉纳治疗的犬中，只有4例发生不良反应，在所有情况下都是与胃肠道相关的短暂症状，包括呕吐和厌食症。在毒性研究中，给予氟雷拉纳的最高推荐剂量（56 mg / kg po），每隔八周一次，没有引起临床症状，健康的8周龄或8周龄犬且体重≥2 kg的犬的安全系数是推荐剂量的五倍以上。在参加182天实地研究的224条犬中，分别有7.1％，6.7％和4.9％出现呕吐，食欲下降和腹泻。分别有5.4％，1.8％和1.3％的犬出现嗜睡，多饮和肠胃气胀。
Fluralaner can be used without additional risk for collies and other sensitive herding breeds that have the MDR1 mutation. No adverse events were observed subsequent to fluralaner treatment of ABCB1-1ê(—/—)Collies at three times the highest expected clinical dose. Fluralaner seems to be an effective, safe and convenient treatment option for all breeds of dogs with generalized demodicosis. However, due to anecdotal very rare neurological adverse effects, it is recommended in the package insert to use fluralaner with caution in dogs with pre-existing epilepsy. 使用氟雷拉纳不会对牧羊犬和其他具有MDR1基因缺陷的牧羊犬种产生额外风险。在以最高预期临床剂量的三倍对ABCB1-1（-/-）牧羊犬进行氟雷拉纳治疗后，未观察到不良反应。氟雷拉纳似乎是所有患有全身性蠕形螨病的犬种的一种有效，安全和便捷的治疗选择。然而，由于传闻中非常罕见的神经系统副作用，因此在包装说明书中建议在患有癫痫病的犬中谨慎使用氟雷拉纳。
7.7.2Afoxolaner 7.7.2阿福拉纳 Afoxolaner[1-Naphthalenecarboxamide,4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)] is one of the members of the isoxazoline family. In a variety of studies, afoxolaner was demonstrated to be a highly effective and safe form of flea and tick control. 阿福拉纳[1-萘甲酰胺，4-（5-（3-氯-5-（三氟甲基）苯基）-4,5-二氢-5-（三氟甲基）-3-异恶唑基）-N-（2-氧-2-（（2,2,2-三氟乙基）氨基）乙基）]是异恶唑啉家族的成员之一。在各种研究中，已证明阿福拉纳是一种高效且安全的控制跳蚤和蜱虫的方式。
Afoxolaner is a palatable beef-flavoured product that can be given with or without food. After oral administration to dogs, it is rapidly absorbed into the systemic circulation, where the drug becomes active. Afoxolaner is highly protein bound (>99%) and the unbound fraction distributes moderately into tissues. It is slowly eliminated from the body via biliary excretion of free afoxolaner and via hepatic metabolism and subsequent biliary and renal clearance of afoxolaner metabolites. This slow clearance gives afoxolaner a long half-life in dogs and sustained ectoparasitic activity. In an oral bioavailability study, afoxolaner was rapidly absorbed (Tmax=2–4 h), achieved a maximum plasma concentration (Cmax)of 1,655±332 ng/mL, demonstrated a bioavailability of 73.9% and exhibited a terminal plasma half-life of 15 days. Company-generated study data showed no differences in pharmacokinetics in fed or fasted dogs supporting that it can be given without food. 阿福拉纳是一种牛肉风味产品，可以与食物一起食用，也可以不与食物一起食用。犬口服给药后，它会迅速吸收到全身循环系统中，在那里药物开始起效。阿福拉纳与蛋白质的结合程度高（> 99％），未结合的部分适度分布到组织中。游离的阿福拉纳通过肝脏代谢，随后阿福拉纳的代谢物由胆汁和肾脏清除作用，从体内缓慢清除。这种缓慢的清除使阿福拉纳在犬中具有较长的半衰期，并具有持续驱虫活性。在一项口服药的生物利用度研究中，阿福拉纳被快速吸收（Tmax = 2-4小时），达到最大血浆浓度（Cmax）为1,655±332 ng / mL，证明其生物利用度为73.9％，并且血浆终末半衰期为15天。公司产生的研究数据表明，犬是否喂食或禁食在药代动力学方面没有差异，这证明阿福拉纳无需与食物同服。
Adverse reactions in flea and tick studies are rare. In a 90-day US field study of 415 dogs, vomiting was seen in 17 (4.1%), dry flaky skin in 13 (3.1%), diarrhoea without blood in 13 (3.1%) and lethargy in seven (1.7%). Only five dogs showed anorexia during the study and two of those dogs experienced anorexia with the first dose but not subsequent doses. Three dogs in that field study had a history of seizures. One dog experienced a seizure on the same day after receiving first and second dosing and a third seizure one week after the third dosing but completed the study. One other dog with a history of seizures had one seizure 19 days after the third dose. The third dog with a history of seizures had no seizures during the study trial. The safety profile of afoxolaner was further evaluated in two studies in 8-week-old beagle dogs. In the first study, 32 beagle dogs were randomly assigned to receive 1×, 3× or 5× the maximum exposure dose (6.3 mg/kg). Treatments were administered at three dose intervals of one month (days 0, 28 and 56) followed by three fortnightly dose intervals (days 84, 98 and 112). Physical examinations, and blood collections for clinical pathological analysis and afoxolaner plasma concentrations, were performed throughout the study. No afoxolaner-related changes were observed in growth, physical variables, clinical pathological variables or tissues examined histologically. No clinically or statistically significant health abnormalities related to the administration of afoxolaner were observed. Vomiting and diarrhoea were observed sporadically across all groups including the controls. In the second study, afoxolaner was combined with milbemycin and the same protocol was repeated as performed in the first study. No treatment-related changes were observed in any of the examinations described above. Vomiting and diarrhoea were observed sporadically across all groups including the control group. 168 In the USA, afoxolaner is approved to be given to 8-week-old puppies. The safety of afoxolaner in breeding, pregnant and lactating dogs has not been evaluated. 在跳蚤和蜱虫的研究中不良反应很少见。在美国对415只犬进行的为期90天的现场研究中，有17只（4.1％）呕吐，13只出现片状皮肤干燥（3.1％），无血腹泻13只（3.1％）和嗜睡7只（1.7％）。在研究过程中，只有五只犬表现出厌食症，其中两只犬在第一次给药时出现厌食症，但在随后的给药中没有出现。在研究期间仅五只犬表现出厌食，并且其中两只犬在第一剂但随后没有再出现厌食。在该现场研究中，三只犬有癫痫病史。一只犬在接受第一和第二次给药后于同一天癫痫发作，而在第三次给药一周后发生第三次癫痫，但完成了研究。在第三次给药之后19天，另一只具有癫痫病史的犬发生了一次癫痫。在研究试验期间，第三只有癫痫病史的犬没有癫痫发作。在8周龄的比格犬中进行的两项研究中进一步评估了阿福拉纳的安全性。在第一个研究中，随机分配32只小比格犬接受最大暴露剂量（6.3 mg / kg）的1倍、3倍或5倍用药。先以一月一次的三个剂量间隔（第0、28和56天）进行治疗，然后再进行三个两周一次的剂量间隔（第84、98和112天）进行治疗。在整个研究过程中，进行了体格检查和血液采集，以进行临床病理分析和阿福拉纳血浆浓度测定。在发育、体况、临床病理变量或组织学检查中未观察到与阿福拉纳相关的变化。没有观察到与服用阿福拉纳有关的临床或统计学上显着的体况异常。在包括对照组在内的所有组中偶尔观察到呕吐和腹泻。在第二项研究中，将阿福拉纳与米尔贝肟联合使用，并重复和第一项研究相同的方案。在上述任何检查中均未观察到与用药相关的变化。在包括对照组的所有组中偶发地观察到呕吐和腹泻。在美国，已批准将阿福拉纳用于8周大的幼犬。还没有评估过阿福拉纳在繁殖犬，妊娠犬和哺乳犬中的安全性。
Afoxolaner is registered for treatment of canine demodicosis in Europe and has been shown to be highly effective for treatment of demodicosis in case reports and one controlled study.The controlled published report looked at eight dogs diagnosed with generalized demodicosis and compared the efficacy with a topical combination of imidacloprid/moxidectin. Afoxolaner was administered at the recommended dose (³2.5 mg/kg) on days 0, 14, 28 and 56, and the topical combination of imidacloprid/moxidectin was given at the same intervals at the recommended concentration. Clinical examinations and deep skin scrapings were performed every month to evaluate the effect on mite numbers and the resolution of clinical signs. The percentage reductions of mite counts were 99.2%, 99.9% and 100% on days 28, 56 and 84, respectively, in the afoxolaner-treated group, compared to 89.8%, 85.2% and 86.6% on days 28, 56 and 84 in the imidacloprid/moxidectin-group. Mite reductions were significantly higher on days 28, 56 and 84 in the afoxolaner-treated group compared to the imidacloprid/moxidectin treated group. 阿福拉纳已在欧洲注册用于治疗犬蠕形螨病，并在病例报告和一项对照研究中显示出对犬蠕形螨病的治疗非常有效。对照发表的报告对八只被诊断患有全身性蠕形螨病的犬进行了研究，并将其与含吡虫啉/莫昔克丁的驱虫滴剂的疗效进行了比较。在第0、14、28和56天以推荐剂量（2.5mg / kg）使用阿福拉纳，并以相同的间隔以推荐的浓度给予吡虫啉/莫昔克丁的驱虫滴剂。每月进行临床检查和皮肤深刮，以评估对螨虫数量的影响和临床症状的缓解情况。接受阿福拉纳治疗组在第28、56和84天螨虫计数减少的百分比分别为99.2％，99.9％和100％，而吡虫啉/莫昔克丁驱虫滴剂治疗组在28、56和84天，螨虫计数减少的百分比分别为89.8％，85.2％和86.6％。与吡虫啉/莫昔克丁滴剂治疗组相比，在用阿福拉纳治疗组的第28、56和84天螨虫的减少量明显更高。
In a large series of clinical case evaluations at a referral dermatology practice, 102 cases of generalized demodicosis were treated with excellent results. Of the 102 cases, 68 were dogs with adult-onset demodicosis. The product was administered at 2.5 mg/kg p.o., initially used every two weeks in the first 10 dogs. With the high degree of efficacy seen in those dogs, the dosage was reduced to monthly in the remaining cases. Ninety percent of the cases were negative after two months of treatment, the remaining dogs after three months. The only dog needing administration every two weeks was on immunosuppressive therapy for pemphigus foliaceus that became mite-positive when the interval was increased to four weeks, but remained mite-negative when afoxolaner was administered every two weeks. In a further study, 50 dogs with generalized demodicosis were treated with afoxolaner alone (Nexgardâ) or combined with milbemycin (Nexgard Spectraâ) with 2.5–2.7 mg/kg once monthly and the number of mites on skin scrapings was reduced by 87.6%, 96.5% and 98.1% on days 28, 56 and 84, respectively, and 36 of 50 dogs had negative skin scrapings after three months. A more recent study looked at afoxolaner combined with milbemycin (Nexgard Spectra ) at the dosage of 2.5–6.3 mg/kg p.o. every four weeks in dogs with juvenile-onset (n=4) and adult-onset (n=11) generalized demodicosis with a variety of clinical lesions. The rate of decrease in mite counts was 91.2%, 99.8% and 99.9% on days 28, 56 and 84, respectively. Based on these data, afoxolaner seems to be an effective, safe and convenient treatment option for dogs with generalized demodicosis. 在转诊皮肤病学临床中进行的一系列临床病例评估中，治疗102例全身性蠕形螨病取得了优异的效果。在102例病例中，有68例是成年发病蠕形螨病患犬。该产品以口服2.5 mg / kg的剂量给药，最初每两周在头10只犬中使用。由于在那些犬中看到了很高的功效，在其余病例中，剂量减少到了每月一次。90％的病例治疗两个月后刮片阴性，其余犬三个月后消失。唯一一只是在对落叶型天疱疮进行免疫抑制治疗的犬需要每两周给药一次，当给药间隔时间增加到四周一次时，检查发现了螨虫，但当每两周给药一次时未发现螨虫，复查也为阴性。在一项进一步的研究中，单独使用阿福拉纳或与米尔贝肟联合使用按2.5-2.7 mg / kg剂量每月使用治疗50例全身性蠕形螨病的犬，在第28、56和84天刮片检查发现螨虫的数量减少了87.6％，96.5％和98.1％，并且50只犬中有36只在三个月后做皮肤刮片为阴性。最近的一项研究观察了在幼年 (n=4)和成年 (n=11)并伴有各种临床症状的全身性蠕形螨病犬中，每四周一次使用2.5-6.3mg/kg的剂量口服含阿福拉纳与米尔贝肟的产品。在第28、56和84天，螨虫数量的减少率分别为91.2％，99.8％和99.9％。基于这些数据，对于患有全身性蠕形螨病的犬，阿福拉纳似乎是一种有效，安全且方便的治疗选择。
7.7.3 Sarolaner 7.7.3沙罗拉纳 Sarolaner[1-(5-((5S)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3’-H-spiro(azetidine-3,1’-(2) benzofuran)-1-yl)-2-(methylsulfonyl) ethanone] was discovered through a targeted synthesis and screening programme, and was selected for development on the basis of structural uniqueness, potency, mammalian safety and pharmacokinetic suitability. This isoxazoline can be used safely for puppies from eight weeks of age. In an initialin vivo study in dogs, sarolaner demonstrated robust efficacy (³99.8%) for 35 days against both fleas and adult ticks. Sarolaner chewable tablets are generally well-tolerated with rare treatment-related adverse reactions. The majority of observed adverse events are typical of those commonly seen in the general dog population. In a 90 day study, vomiting was observed in 10 of 315 dogs (3.5%) and lethargy in eight dogs (2.5%). Sarolaner is currently authorized as chewable tablet with indications for the treatment of fleas, ticks, demodicosis and ear mites in dogs. In one study, 16 dogs with generalized demodicosis were treated either with monthly oral sarolaner or with a weekly spot-on containing imidacloprid and moxidectin. The sarolaner-treated dogs and the dogs treated with the spot-on had a reduction of over 99% and 96% in mite numbers after one month and negative scrapings after one month and after 11 weeks, respectively. In addition, theDemodex-infested dogs showed a marked improvement in their clinical signs. There were no treatment-related adverse events observed. A subsequent noninferiority study compared the same two products in 81 client-owned dogs. Parasitological cure in dogs treated with sarolaner was achieved in 93% after three months and 100% after five months, confirming the efficacy of sarolaner against canine generalized demodicosis. 沙罗拉纳 [1-(5’-((5S)-5-(3，5-二氯-4-氟苯基)-5-(三氟甲基)-4，5-二氢异噁唑-3-基)-3’-H-螺(氮杂环丁烷-3，1’-(2)苯并呋喃)-1-基)-2-(甲基磺酰基)乙酮]是通过有针对性的合成和筛选方案发现的，并基于结构独特性、效果、哺乳动物安全性和药物动力学适宜性而被选择开发。这种异恶唑啉类药物可以安全地用于8周以上的幼犬。在对犬的体内初步研究中，沙罗拉纳表现出了对跳蚤和蜱虫成虫强大的功效（99.8％）长达35天。沙罗拉纳咀嚼片通常具有良好的耐受性，治疗的相关不良反应很罕见。观察到的大多数不良反应是在普通犬群中都常见的典型不良反应。在一项为期90天的研究中，观察到315只犬中有10只（3.5％）呕吐，八只犬（2.5％）嗜睡。沙罗拉纳目前被批准为咀嚼片，可用于治疗跳蚤、蜱、蠕形螨和耳螨。在一项研究中，对16例全身性蠕形螨病犬进行了每月一次口服沙罗拉纳或每周一次的含吡虫啉和莫昔克丁的滴剂治疗。在一个月之后，用沙罗拉纳治疗的犬和用滴剂治疗的犬的螨虫数量分别减少了99%和96%，皮肤刮片结果分别在在一个月后和11周之后为阴性。此外，受蠕形螨感染的犬的临床症状也有明显改善。没有观察到与治疗有关的不良反应。随后的一项研究在81只宠物犬中比较了相同的两种产品。三个月后用沙罗拉纳治疗的犬的蠕形螨治愈率达到93％，五个月后达到100％，这证实了沙罗拉纳对犬全身蠕形螨病的功效。
Consensus Statement 11 A number of studies have evaluated the efficacy of isoxazolines for canine demodicosis in pet dogs. The published data are very encouraging and make this drug class an excellent treatment option for dogs with demodicosis. 共识声明11：大量研究评估了异恶唑啉类对犬蠕形螨病的功效。公开的数据非常令人鼓舞，并使该类药物成为蠕形螨病患犬的绝佳治疗选择。
7.7.4 Lotilaner 7.7.4洛替拉纳 Lotilaner (CredelioTM, Elanco) is the newest isoxazoline molecule and was evaluated against Demodex spp. in 10 naturally infested dogs with generalized demodicosis. Dogs were treated with 20 mg/kg p.o. on days 0, 28 and 56. The pre-treatment mite counts based on skin scrapings performed at five different sites were reduced by >99.9% (P<0.0001) up to 56 days after the first and second monthly doses. No live mites were detected in any dog after Day 56 and including Day 84 post-treatment, indicating that this drug may also be effective against canine demodicosis. 洛替拉纳是最新的异恶唑啉类药物，并针对其对蠕形螨的治疗效果进行了评估。在十只患有全身性蠕形螨病的出没于自然的犬中。分别在第0、28和56天口服给予20 mg / kg剂量的洛替拉纳。在进行了第二次每月一次的剂量给药后的第56天，基于在五个不同位置进行的皮肤刮片相比于治疗前的刮片，螨虫计数减少了> 99.9％（P <0.0001）。在治疗后第56天（包括治疗后第84天），在任何犬中均未检测到活螨，这表明该药可能也能有效对抗犬蠕形螨病。
7.8 Other drugs 7.8其他药物 Various other drugs have been used to treat generalized demodicosis. As described above, an immune aberration seems to contribute to the development of generalized demodicosis. Thus, it seems logical that immunomodulatory agents may be beneficial for dogs with demodicosis and a number of those agents were evaluated in several studies. 各种其他药物已用于治疗全身性蠕形螨病。如上所述，免疫异常似乎有助于全身性蠕形螨病的发展。因此，似乎合理的是免疫调节剂对患蠕形螨病的犬可能是有益的，并且在一些研究中对这些药剂进行了评估。
A mycobacterial cell wall component, muramyl dipeptide, was injected at 0.2 mg/kg s.c. weekly in dogs with generalized demodicosis either as monotherapy or in combination with amitraz at two different concentrations (0.025% and 0.05% twice weekly) and compared to therapy with amitraz alone at 0.025% twice weekly. Remission was achieved in all dogs. The study numbers were very small (two dogs per treatment group) and there was no follow-up period, thus it is difficult to ascertain if the muramyl dipeptide was of any benefit. Muramyl dipeptide also was shown in a separate study to increase the lymphocyte response to mitogens in eight dogs with demodicosis, without reaching the comparative values of healthy dogs. Adverse effects were not mentioned. 将分枝杆菌细胞壁成分—胞壁酰二肽以0.2 mg/kg 每周皮下注射给患有全身性蠕形螨病的犬，作为单一疗法或以两种不同浓度(0.025%和0.05%每周两次)与双甲脒单独治疗(0.025%每周两次)相比较。所有的犬都得到了缓解。研究数据非常少（每个治疗组两只犬），没有随访期，因此很难确定胞壁酰二肽是否有益处。在另一项8只蠕形螨病患犬研究中还显示了胞壁酰二肽可增加淋巴细胞对有丝分裂原的反应，但未达到与健康犬的比较价值。没有提到有不良反应。
Levamisole at a dose from 3 to 10 mg/kg given at different intervals was used in two studies, which showed a positive effect on lymphocyte proliferation assays, but did not improve efficacy based on clinical or parasitological resolution of demodicosis. 两项研究分别使用了3至10 mg / kg剂量的左旋咪唑，显示出对淋巴细胞增殖测定的积极作用，但根据蠕形螨病的临床或寄生虫学解决方案并未提高疗效。
In another study, 16 dogs with generalized demodicosis were treated either with amitraz rinses at 0.0375% every five days alone or in combination with 2 mL of inactivated Parapox virus suis s.c. on days 0, 2 and 9. The dogs receiving combination therapy achieved remission within 85 days compared to 104 days in the control group (P<0.05), although a power analysis was not presented. To the best of the authors’ knowledge, this is the first randomized trial showing a beneficial effect of an immunostimulant as treatment for canine demodicosis. 在另一项研究中，16只患有全身性蠕形螨病的犬在第0、2和9天分别接受了0.0375%双甲脒溶液单独治疗或与2 mL灭活的猪副痘病毒剂皮下注射联合使用。接受联合疗法的犬在85天内得到了缓解，而对照组为104天（P <0.05），但没有呈现一个强有力的分析。据作者所知，这是展现出免疫刺激剂对犬蠕形螨病的治疗具有有益作用的第一项随机试验。
Thirty-six dogs with generalized demodicosis were treated with 1,000 mg of vitamin E daily, weekly amitraz rinses at 0.05% or a combination of both therapies. All dogs went into remission, the dogs on combination therapy had the shortest time until remission (7.1 weeks versus 7.3 weeks with amitraz only and 8.5 weeks with vitamin E only) but a statistical evaluation was not performed. Compared to a control group, affected dogs had lower serum vitamin E concentrations. However, it was not known if inadequate dietary intake of vitamin E at the beginning of the study or the disease caused this difference. When the mean serum vitamin E concentration was compared among dogs with pyoderma, generalized demodicosis and normal dogs, no significant differences were found between groups. 36只患有全身性蠕形螨病的犬每日接受1000毫克维生素E治疗，每周接受0.05%双甲脒冲洗或两种药物的组合疗法。所有的犬都进入缓解期，接受联合治疗的犬达到缓解期的时间最短7.1周，（仅使用双甲脒的7.3周，仅使用维生素E的8.5周），但未进行统计学评估。与对照组比较，患病犬的血清维生素E浓度较低。但是，尚不清楚在研究开始时饮食中维生素E摄入不足或是疾病是否引起了这种差异。当比较脓皮病患犬、全身蠕形螨病犬和正常犬的平均血清维生素E浓度时，各组之间无显着差异。
Lufenuron is a chitin synthesis inhibitor. As chitin is found in the shells and exoskeletons of all life stages of Demodex spp. it was proposed that this compound might interrupt the life cycle of the Demodex mite. However, lufenuron at mean doses of up to 15.8 mg/kg three times weekly for 2–3 months did not lead to improvement of canine demodicosis. 氯酚奴隆是几丁质合成抑制剂。甲壳素存在于蠕形螨的所有生命阶段的壳和外骨骼中。有人提出，这种化合物可能会中断蠕形螨的生命周期。然而，使用平均剂量高达15.8 mg/kg的氯酚奴隆每周三次，持续2-3个月，并未使犬蠕形螨病得到改善。
Three dogs with generalized demodicosis were sprayed weekly with a deltamethrin spray at 0.005%. After three weekly applications, there was no difference in clinical signs or numbers of mites on skin scrapings. Deltamethrin at 12.5% was used in another report and compared with an indigenous preparation containing extracts of Mallotus phillipensis, Oleum pinus, Oleum terebinth and Sulphur sublimatum. Topicals were applied twice daily until skin scrapings were negative, which took seven days in the group treated with the indigenous preparation and 11 days for deltamethrin. Dogs had to be restrained for 1 h after the topical application to prevent excessive licking. Skin scrapings were still negative in all dogs one month after cessation of therapy. 每周用0.005％的溴氰菊酯喷雾剂喷洒三只患有全身性蠕形螨病的犬。每周一次使用三周后，在临床症状或使用皮肤刮片检查螨虫数量上没有发现改善。在另一份报告中使用了12.5%的溴氰菊酯，并与一种含有木通、松籽油、松节油和硫黄提取物的本土制剂进行了比较。每日外用两次直到皮肤刮片呈阴性后停止，在用本土制剂治疗的组中，这需要7天，溴氰菊酯需要11天。外用药后，犬必须被约束1小时，以防止过度舔。停止治疗一个月后，所有犬只的皮肤刮片仍为阴性。
Homeopathic preparations containing Sulphur 200, Heparsulphuris 200 or Psorinum 200 were given orally at five drops daily for five weeks to three groups of six puppies experimentally infected with Demodex canis. The post-treatment mean demodicosis indices were lower in the groups treated with Sulphur 200 and Psorinum 200 compared with the group treated with Heparsulphuris 200 and a control group, but neither complete clinical nor microscopic resolution could be achieved. A herbal preparation containing extracts of Cedrus deodara, Azadirecta indica andEmbelia ribeswas sprayed on lesions of 14 juvenile dogs with apparent generalized demodicosis. Dogs were re-evaluated after 24 h and if skin scrapings were still positive for D. canis, dogs were retreated once. Subsequent weekly skin scrapings for six weeks were negative in all dogs. 对实验感染犬蠕形螨的3组6只幼犬，每日口服5滴含有硫磺200、Heparsulphuris 200或Psorinum 200的顺势疗法制剂，给药时间为5周。与用Heparsulphuris 200的和对照组相比，用硫磺200和Psorinum 200治疗组的治疗后平均蠕形螨指数较低，但均无法完全达到临床或显微镜下的治愈。一种草药制剂，含有雪松、印度楝树和茶藨子的提取物，喷洒在14只患有明显全身性蠕形螨病的幼犬的病变部位。24小时后对犬进行重新评估，如果皮肤刮片仍然表现犬蠕形螨阳性，则对犬再进行一次治疗。随后六周的每周一次皮肤刮片检查，所有的犬都是阴性的。
Closantel ({N 9–5-chloro-4-(4-chlorophenyl cyanomethyl)-2-methylphenyl}-2-hydroxyl 3,5 diiodobenzamide) is an anthelminthic of the salicylanilide family and was used to treat nine juvenile dogs with generalized demodicosis at a dose of 5 mg/kg s.c. for the first injection and 2.5 mg/kg s.c. for subsequent weekly injections. All dogs improved, but only six dogs went into remission based on assessment of skin scrapings, after six injections. A follow-up period was not specified. 氯氰碘柳胺（{N 9–5-氯-4-（4-氯苯基氰基甲基）-2-甲基苯基} -2-羟基3,5二碘代苯甲酰胺）是水杨酰苯胺类的驱虫药，用于治疗9例全身性蠕形螨病的幼犬第一次皮下注射剂量为5 mg / kg 和随后每周皮下注射2.5 mg / kg。所有的犬都有改善，但根据对皮肤刮的片评估，有六只犬在六次注射后才进入缓解期。没有规定固定的随访时间。
Overall, for almost all of those drugs there is insufficient evidence to be recommended as treatment of canine generalized demodicosis, either due to low numbers of patients in the studies, unclear methods, insufficient efficacy or prominent adverse effects. There is some evidence for efficacy of inactivated Parapox virus suis subcutaneously as a concurrent treatment to amitraz. 总体而言，由于研究中患病动物样本数少，试验方法不清晰，疗效不足或不良反应明显，几乎所有这些药物都没有足够的证据表明可以推荐用于犬全身性蠕形螨病的治疗。有证据表明，灭活的猪副痘病毒皮下注射同时使用双甲脒治疗是有效的。
7.9 Treatment of feline demodicosis 7.9猫蠕形螨病的治疗 A number of drugs have been used to treat feline demodicosis, including organophosphate baths, rotenone, lime sulfur dips, amitraz rinses, ivermectin orally and by injection, selamectin, milbemycin oxime and a moxidectin/imidacloprid spot-on. 许多药物已用于治疗猫的蠕形螨病，包括有机磷酸盐浴、鱼藤酮、石硫合剂浸泡、双甲脒洗液、伊维菌素口服和注射、赛拉菌素、米尔贝肟和莫昔克丁/吡虫啉滴剂。
The two treatments most frequently reported as successful are lime sulfur dips and amitraz rinses. Lime sulfur dips were used at 2% every 5–7 days and were successful in 22 of 24 cats. Adverse effects were not seen. Amitraz rinses were typically used at a concentration of 0.0125% to 0.025% up to 0.1% weekly and 12 of 14 cats responded to treatment. However, both treatments are not always well-tolerated by the affected cats. In a case series, eight of 13 cats in one household showed pruritic skin disease and skin scrapings were positive for D. gatoi in two of those cats. Weekly administration of a spot-on containing moxidectin/imidacloprid for 10 weeks was well-tolerated and pruritus resolved in all cats following treatment. Thus, at least for D. gatoi, this spot-on may be a more convenient efficacious therapy. 最常报告的两种成功的治疗方法是石硫合剂浸泡和双甲脒冲洗。每5-7天使用2％的石硫合剂浸泡，在24只猫中有22只成功。未见不良反应。通常使用双甲脒洗液，其浓度为每周0.0125％至0.025％（最高0.1％），并且14只猫中有12只对治疗有反应。但是，这两种治疗方法并不总是对患猫有很好的耐受性。在一个案例系列中，一个家庭的13只猫中有8只表现出瘙痒性皮肤病，并且其中的两只猫的皮肤刮片表现出戈托伊蠕形螨阳性。每周一次给予含有莫昔克丁/吡虫啉的滴剂连续10周，所有的猫对其耐受性良好，治疗后瘙痒症状也均得到缓解。因此，至少对于感染戈托伊蠕形螨而言，这种驱虫滴剂可能是更方便的有效疗法。
Oral fluralaner has been used in a cat with demodicosis, leading to rapid resolution of clinical signs and negative skin scrapings. 口服氟雷拉纳已用于蠕形螨病患猫中，可快速缓解临床症状和出现皮肤刮片阴性。
Consensus Statement 12 Demodicosis in cats may be treated with weekly lime sulfur dips at a concentration of 2% or amitraz baths at a concentration of 0.0125%. An easier alternative may be weekly administration of a spot-on containing moxidectin/imidacloprid. 共识声明12：猫的蠕形螨病可以每周用浓度为2％的石硫合剂浸泡或浓度为0.0125％的双甲脒浴液治疗。较容易的替代方法是每周一次外用含莫昔克丁/吡虫啉的滴剂。
8 Prognosis and future outlook 8预后及未来展望 With the advent and widespread use of isoxazoline therapy for flea and tick control, the future incidence of canine demodicosis could be impacted. How prominent this effect will be remains to be seen in the coming years. Anecdotally, treatment of 15 breeding bitches with 25 mg/kg fluralaner 10 days prior to the scheduled mating and three months later with a second dose, resulted in a marked reduction in the numbers of puppies breaking out with demodicosis compared to the previous consistent production of litters developing the disease. In this trial, all bitches were treated with 25 mg/kg fluralaner 10 days before the scheduled mating and three months later with a second dose. All 15 bitches included in the study gave birth to litters of healthy puppies and 14 of those 15 litters did not develop demodicosis in the first 12 months, and two puppies of one litter developed localized demodicosis only. The obtained result indicates a high efficiency of fluralaner not only as a treatment, but also as a preventative strategy in cases of breed-predisposed, generalized, juvenile onset canine demodicosis. Although these results are impressive, isoxazoline therapy should not replace the need for withholding affected and carrier dogs from breeding programmes. 随着异恶唑啉疗法控制跳蚤和蜱虫的广泛应用，将来可能会影响犬的蠕形螨病的发病率。在未来几年中，这种效果将如何表现尚待观察。有趣的是，15只配种母犬在计划交配前10天服用25毫克/千克的氟雷拉纳，3个月后第二次服用氟雷拉纳，与之前生产的患蠕形螨病幼犬的数量相比，用药后感染蠕形螨病的幼犬数量显著减少。在该试验中，所有母犬均在计划交配前10天用25 mg / kg 氟雷拉纳处理，三个月后再次使用。研究中包括的所有15只母犬都产下了健康的幼犬，其中14只母犬在头12个月内没有发生蠕形螨病，产下的一窝幼犬中的两只只发生了局灶性蠕形螨病。所获得的结果表明氟雷拉纳不仅作为一种治疗方法是高效的，而且作为一种预防策略也适用于易感犬种的全身性幼年犬蠕形螨病。尽管这些结果令人印象深刻，但异恶唑啉疗法不应取代从繁殖计划中剔除受感染和携带蠕形螨犬的规定。
There also is concern about the possible impact of isoxazoline therapy on normal canine cutaneous Demodex populations. Demodex mites are considered part of the microbiota of most mammals, including dogs. Under normal circumstances, they appear to live as commensals, feeding on their host’s sebum and are only opportunistically pathogenic. Similar to bacterial flora found on the skin, in humans follicular mites have been shown to contain immune-reactive lipase, which can produce free fatty acids from sebum triglycerides. Therefore, the mites could play a role in the defence of the skin against pathogenic bacteria, particularly against Staphylococcus aureus and Streptococcus pyogenes. 人们还担心异恶唑啉疗法可能对正常犬科皮肤蠕形螨种群产生影响。蠕形螨被认为是大多数哺乳动物（包括犬）的微生物群的一部分。在正常情况下，它们看起来像是共生微生物，以宿主的皮脂为食，并且只是机会性致病。与皮肤上发现的细菌菌群相似，人类毛囊螨中已显示出含有免疫反应性脂肪酶，该酶可从皮脂甘油三酯中产生游离脂肪酸。因此，螨虫可以在皮肤防御病原菌，特别是在抵抗金黄色葡萄球菌和化脓性链球菌方面发挥作用。
The investigation of the normal cutaneous Demodex populations has been, until recently, elusive due to the low number of individual mites present on healthy dogs. The development of PCR techniques targeting Demodex-DNA in skin samples has allowed advancement of the study of Demodex populations. A previous study using a real-time PCR (RT-PCR) for D. canis detected Demodex-DNA in approximately 18% of healthy dogs after sampling hairs from two to five body sites. Direct proportionality between the number of positive dogs and the number of sampled sites and hairs was demonstrated clearly, as positive results increased to 100% when the number of sampled sites increased to 20. Another study investigated whether healthy dogs treated with the isoxazolines afoxolaner and fluralaner at the labelled dose for flea and tick prevention would maintain a normal population of Demodex mites as part of their cutaneous microbiota. The study demonstrated that after 30 and 90 days of treatment, healthy dogs still had Demodex mites similar to the population of healthy dogs not receiving these treatments. However, PCR also will detect antigen from dead mites, the duration of the study was only three months and, to the best of the authors’ knowledge, the maximum time to eliminate dead mites from the follicle is not known although the interfollicular epidermal turnover is faster than three months. These data may suggest that dogs receiving isoxazoline treatment maintain Demodex populations as part of their cutaneous microbiota, despite the apparent ability of these medications to resolve clinical demodicosis. To date, no studies have been performed to detect Demodex-DNA post-treatment in dogs with demodicosis. Isoxazolines may not affect Demodex mites in normal dogs to the same degree or may have no effect at all on normal mite populations in unaffected dogs. More studies of longer duration are needed to characterize the response of the Demodex populations in dogs with clinical disease to isoxazolines and in comparison to other treatments for demodicosis. 对正常皮肤蠕形螨种群的调查直到最近还很难进行，因为健康犬上螨虫的数量很少。针对皮肤样品中的蠕形螨DNA的PCR技术的发展使蠕形螨种群的研究得以发展。先前的一项研究使用实时PCR (RT-PCR)对犬蠕形螨进行检测，大约18%的健康犬在从两到五个身体部位采集毛发后检测到蠕形螨。阳性犬的数量与取样部位和毛发的数量之间的直接比例关系被清楚地证明，当取样部位的数量增加到20个时，阳性结果增加到100%。另一项研究调查了以预防跳蚤和蜱虫的推荐剂量服用异恶唑啉类阿福拉纳和氟雷拉纳的健康犬，用药后蠕形螨数量将保持其作为皮肤微生物群一部分的正常种群数量。该研究表明，经过30天和90天的治疗，健康犬的蠕形螨数量仍与未接受这些药物治疗的健康犬相似。然而，PCR也将用于检测来自死螨的抗原，研究的持续时间只有三个月，就作者所知，从毛囊中消除死螨的最大时间是未知的，尽管毛囊间表皮更新时间快于三个月。这些数据可能表明接受异恶唑啉治疗的犬将保持蠕形螨种群做为皮肤微生物群的一部分，但这些药物具有解决临床蠕形螨病的明显能力。迄今为止，还没有进行研究来检测蠕形螨病犬治疗后的蠕形螨-DNA的研究。异恶唑啉可能不会对正常犬的蠕形螨产生与患病犬相同程度的影响，或者对未患病犬的正常蠕形螨种群完全没有影响。需要更多的持续时间更长的研究以确定患有临床疾病的犬中蠕形螨种群对异恶唑啉的反应以及与其他蠕形螨病治疗方法进行比较。
Currently the isoxazoline derivatives have shown impressive results in controlling demodicosis and are likely to be the mainstay therapy for many years to come. The development of resistance is less likely to occur due to their selective inhibition of insect and acarid GABACls and GluCls. This novel binding site is key to the innovative activity profile, which bypasses the critical cross-resistance observed in other noncompetitive antagonists and will likely slow development of resistance to this class of molecules. A combination product combining afoxolaner and milbemycin oxime has been released in Europe for flea, tick, nematode infestation and heartworm prevention. No studies have been reported to date regarding demodicosis treatment with this product. However, the combined molecules of afoxolaner and milbemycin oxime could have additive effects, as both have efficacy for Demodex mites as sole molecules. In view of these developments, further derivatives and combinations are likely to be approved and more treatment options will likely become available in the future. 目前，异恶唑啉衍生物在控制蠕形螨病方面已显示出令人印象深刻的结果，并可能在未来许多年内成为主流疗法。由于选择性抑制昆虫和螨虫的γ-氨基丁酸和γ-氨基葡糖，因此不太可能产生抗性。这个新颖的结合位点是创新活性谱的关键，它绕开了在其他非竞争性拮抗剂中观察到的关键交叉耐药性，可能会减慢对此类分子的耐药性。在欧洲已经发布了一种结合了阿福拉纳和米尔贝肟的组合产品，用于预防跳蚤、蜱虫、线虫感染和预防心丝虫病。迄今为止，还没有关于该产品治疗蠕形螨病的研究报道。但是，阿福拉纳和米尔贝肟的组合产品可能具有累加作用，因为它们单独使用都对蠕形螨病具有功效。鉴于这些发展，将来可能会批准进一步的衍生物和组合，并且将来可能会有更多的治疗选择。
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发表于 2022-6-29 09:05:06
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