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塞拉菌素加萨罗那尔局部制剂预防猫伊氏锥虫大环内酯类耐药株发展的疗效。

The efficacy of a topical formulation of selamectin plus sarolaner in preventing the development of a macrocyclic lactone-resistant strain of Dirofilaria immitis in cats.

机构信息

Zoetis, Veterinary Medicine Research and Development, 333 Portage Street Kalamazoo, MI 49007, USA.

Zoetis, Veterinary Medicine Research and Development, 333 Portage Street Kalamazoo, MI 49007, USA.

出版信息

Vet Parasitol. 2020 Jun;282:109122. doi: 10.1016/j.vetpar.2020.109122. Epub 2020 May 11.

DOI:10.1016/j.vetpar.2020.109122
PMID:32460111
Abstract

Revolution®/Stronghold® Plus, a topical endectocide incorporating 6 mg/kg selamectin plus 1 mg/kg sarolaner, is approved for use in cats to prevent heartworm disease. The efficacy of selamectin has not previously been evaluated against any macrocyclic lactone (ML)-resistant heartworm strains in cats for prevention of heartworm disease. In this study, an experimental combination formulation of selamectin (6 mg/kg) plus sarolaner (2 mg/kg) was assessed for preventing the development of a ML-resistant strain of Dirofilaria immitis in cats. Forty purpose-bred domestic shorted-haired cats (20 males; 20 females) from 7-9 months of age and negative for heartworm antigen prior to study inclusion were used. On Day -30, cats were inoculated with 100 D. immitis L (ZoeMO strain) subcutaneously in the inguinal area. Cats were randomly allocated to one of the following four treatments with associated dosing regimens: T01 (vehicle-treated control on Days 0, 28, and 56), T02 (single dose of selamectin plus sarolaner combination on Day 0 only), T03 (selamectin plus sarolaner combination on Days 0, 28, and 56) or T04 (single dose of selamectin on Day 0 only). All treatments were administered topically in an isopropyl alcohol-based formulation. Selamectin was administered at 6 mg/kg in both standalone and combination formulations. Sarolaner was administered at 2 mg/kg. Cats were necropsied on Day ∼145 (∼175 days post infection) and adult worms were counted. Nine of ten cats in the control group (T01) were infected with adult worms (range, 1-23; geometric mean, 3.5). In contrast, all cats in T03 had zero heartworms. Only two cats in T02 (0-3; 0.2) and a single cat in the T04 (0-1; 0.1) had heartworms. Compared to T01 (control cats), all treated cats had significantly (p < 0.0001) reduced worm burdens, with treatment efficacies of 100% (T03), 93.5% (T02) and 98% (T04). A topical combination of selamectin (6 mg/kg) plus sarolaner (2 mg/kg) was 100% efficacious in preventing the development of an ML-resistant strain of D. immitis (ZoeMO) in cats when administered as three consecutive monthly treatments. A single dose was highly (93.5%) but incompletely effective.

摘要

Revolution®/Stronghold® Plus 是一种局部用的驱虫药,包含 6 毫克/千克的塞拉菌素和 1 毫克/千克的萨罗拉纳,获批用于预防猫的心脏蠕虫病。塞拉菌素的疗效以前并未针对猫的任何大环内酯类(ML)耐药性心脏蠕虫菌株进行过评估,以预防心脏蠕虫病。在这项研究中,评估了一种塞拉菌素(6 毫克/千克)加萨罗拉纳(2 毫克/千克)的实验组合配方,以预防猫的 ML 耐药性犬恶丝虫感染。40 只专门饲养的家养短毛猫(20 只雄性;20 只雌性),年龄在 7-9 个月,在研究开始前均为心脏蠕虫抗原阴性。在第-30 天,将 100 条犬恶丝虫 L(ZoeMO 株)皮下接种到腹股沟区域。猫被随机分配到以下四种治疗组之一,并进行相关剂量方案治疗:T01(第 0、28 和 56 天给予安慰剂)、T02(第 0 天给予塞拉菌素加萨罗拉纳组合的单剂量)、T03(第 0、28 和 56 天给予塞拉菌素加萨罗拉纳组合)或 T04(第 0 天给予塞拉菌素的单剂量)。所有治疗均以异丙醇为基础的制剂进行局部给药。塞拉菌素在单独使用和组合制剂中的剂量均为 6 毫克/千克。萨罗拉纳的剂量为 2 毫克/千克。猫在大约 145 天(感染后大约 175 天)进行尸检,计数成虫。对照组(T01)中的 10 只猫中有 9 只(范围为 1-23;几何平均值为 3.5)感染了成虫。相比之下,T03 组中的所有猫均未发现心虫。T02 组中只有 2 只猫(0-3;0.2)和 T04 组中的 1 只猫(0-1;0.1)有心虫。与 T01(对照组猫)相比,所有接受治疗的猫的蠕虫负担均显著(p<0.0001)降低,治疗效果分别为 100%(T03)、93.5%(T02)和 98%(T04)。当作为连续三个月的三次治疗时,塞拉菌素(6 毫克/千克)加萨罗拉纳(2 毫克/千克)的局部联合使用对预防猫的 ML 耐药性犬恶丝虫(ZoeMO)的发生具有 100%的疗效。单次剂量的疗效非常高(93.5%)但不完全。

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