Abstract：
Previous reports of macrocyclic lactone (ML) resistance in Dirofilaria immitis, the parasitic nematode which causes heartworm disease, have mainly been from the southern Mississippi Delta region. Southeast Missouri (SEMO), forming the northern boundary of this region, has not previously been well studied. The area is an ideal propagation region for heartworm infection and possibly for the spread of ML resistance. To assess whether D. immitis isolates infecting domestic canines in SEMO exhibit evidence of resistance to MLs, domestic canines, presented to veterinary facilities testing positive for heartworms through antigen and microfilariae (MF) examination, were utilized in the study. Using a descriptive epidemiological cross-sectional study, from March 2021 through February 2022, blood sample collection from 96 canines living in SEMO testing positive for heartworms were analyzed. MiSeq technology was utilized to sequence specific genetic markers associated with susceptibility/resistance for MLs in D. immitis isolates. Genomic data revealed most D. immitis isolates had genotypic profiles consistent with resistance to MLs. Of the 96 samples tested, 91 (94.8%) had a resistant genotype, 4 (4.2%) had a mixed genotype, and 1 sample (1%) genotyped as susceptible. While detailed and reliable medical histories were not available for most canines, detailed medical history from 2 canines indicated evidence of phenotypic resistance that was consistent with their genotypes. However, in vivo preventive tests are needed to confirm a high frequency of phenotypic ML resistance in D. immitis from this region. Increasing resistance patterns to MLs indicate the approach to heartworm prevention/treatment protocol should be reconsidered. New measures may be required to stop heartworm disease.
摘要：
以前报道过的大环内酯（ML）抗性在狄丝菌中，导致心丝虫病的寄生线虫，主要来自密西西比河三角洲南部地区。密苏里州东南部（SEMO），形成了这个地区的北部边界，以前没有得到很好的研究。该区域是心丝虫感染的理想传播区域，也可能是ML抗性传播的理想传播区域。为了评估在SEMO中感染家犬的D.immitis分离株是否表现出对MLs的抗性，家犬，通过抗原和微丝虫（MF）检查，将其提交给兽医机构，在研究中使用。使用描述性流行病学横断面研究，从2021年3月至2022年2月,我们分析了在SEMO检测为阳性的心丝虫中生活的96只犬的血液样本.使用MiSeq技术对与D.immitis分离物中的MLs的易感性/抗性相关的特异性遗传标记进行测序。基因组数据显示，大多数D.immitis分离株的基因型分布与对MLs的抗性一致。在测试的96个样本中，91（94.8％）具有抗性基因型，4（4.2％）具有混合基因型，1个样本(1%)基因分型为易感。虽然大多数犬科动物没有详细可靠的病史，来自2只犬的详细病史表明表型抗性的证据与它们的基因型一致.然而,需要进行体内预防性试验,以确认来自该地区的D.immitis的表型ML耐药频率很高.增加对MLs的抵抗模式表明，应重新考虑心虫预防/治疗方案的方法。可能需要采取新的措施来阻止心丝虫病。
