Abdullah Swaid, Stocker Thomas, Kang Hyungsuk, Scott Ian, Hayward Douglas, Jaensch Susan, Ward Michael P, Jones Malcolm K, Kotze Andrew C, Šlapeta Jan
The University of Queensland, School of Veterinary Science, Gatton 4343, QLD, Australia.
Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.
Int J Parasitol. 2025 Mar;55(3-4):173-182. doi: 10.1016/j.ijpara.2024.12.001. Epub 2024 Dec 22.
Canine hookworm (Ancylostoma caninum), a gastrointestinal nematode of domestic dogs, principally infects the small intestine of dogs and has the potential to cause zoonotic disease. In greyhounds and pet dogs in the USA, A. caninum has been shown to be resistant to multiple anthelmintics. We conducted a molecular survey of benzimidazole resistance in A. caninum from dogs at veterinary diagnostic centers in Australia and New Zealand. First, we implemented an internal transcribed spacer (ITS)-2 rDNA deep amplicon metabarcoding sequencing approach to ascertain the species of hookworms infecting dogs in the region. Then, we evaluated the frequency of the canonical F167Y and Q134H isotype-1 β-tubulin mutations, which confer benzimidazole resistance, using the same sequencing approach. The most detected hookworm species in diagnostic samples was A. caninum (90%; 83/92); the related Northern hookworm (Uncinaria stenocephala) was identified in 11% (10/92) of the diagnostic samples. There was a single sample with coinfection by A. caninum and U. stenocephala. Both isotype-1 β-tubulin mutations were present in A. caninum, 49% and 67% for Q134H and F167Y, respectively. Mutation F167Y in the isotype-1 β-tubulin mutation was recorded in U. stenocephala for the first known time. Canonical benzimidazole resistance codons 198 and 200 mutations were absent. Egg hatch assays performed on a subset of the A. caninum samples showed significant correlation between 50% inhibitory concentration (IC) to thiabendazole and F167Y, with an increased IC for samples with > 75% F167Y mutation. We detected 14% of dogs with > 75% F167Y mutation in A. caninum. Given that these samples were collected from dogs across various regions of Australia, the present study suggests that benzimidazole resistance in A. caninum is widespread. Therefore, to mitigate the risk of resistance selection and further spread, adoption of a risk assessment-based approach to limit unnecessary anthelmintic use should be a key consideration for future parasite control.
犬钩虫（犬弓首线虫）是家犬的一种胃肠道线虫，主要感染犬的小肠，并有引发人畜共患病的可能。在美国的灵缇犬和宠物犬中，犬弓首线虫已被证明对多种驱虫药具有抗性。我们对澳大利亚和新西兰兽医诊断中心犬的犬弓首线虫苯并咪唑抗性进行了分子调查。首先，我们采用内部转录间隔区（ITS）-2核糖体DNA深度扩增子元条形码测序方法，以确定该地区感染犬的钩虫种类。然后，我们使用相同的测序方法评估了赋予苯并咪唑抗性的典型F167Y和Q134H同型-1β-微管蛋白突变的频率。诊断样本中检测到最多的钩虫种类是犬弓首线虫（90%；83/92）；在11%（10/92）的诊断样本中鉴定出相关的北方钩虫（狭头钩口线虫）。有一个样本同时感染了犬弓首线虫和狭头钩口线虫。两种同型-1β-微管蛋白突变均存在于犬弓首线虫中，Q134H和F167Y分别为49%和67%。狭头钩口线虫首次被记录到存在同型-1β-微管蛋白突变F167Y。不存在典型的苯并咪唑抗性密码子198和200突变。对一部分犬弓首线虫样本进行的虫卵孵化试验表明，对噻苯达唑的50%抑制浓度（IC）与F167Y之间存在显著相关性，F167Y突变>75%的样本IC增加。我们在犬弓首线虫中检测到14%的犬F167Y突变>75%。鉴于这些样本是从澳大利亚不同地区的犬中采集的，本研究表明犬弓首线虫中的苯并咪唑抗性很普遍。因此，为降低抗性选择和进一步传播的风险，采用基于风险评估的方法来限制不必要的驱虫药使用应是未来寄生虫控制的关键考虑因素。
