犬利什曼病(CanL),由婴儿利什曼原虫引起的,是一种在欧洲越来越重要的复杂疾病。临床表现起因于通过多种宿主-寄生虫相互作用的宿主免疫应答的下调。虽然有几个因素可能会影响CanL进展,这是第一个已知的研究评估其不同临床阶段的危险因素在一个大的转诊医院人群(n=35.669)从一个流行地区,超过20年。还进行了针对选择特征的全基因组扫描以探索对婴儿乳球菌感染的临床易感性的基因组成分。CanL的患病率为3.2%(I期16.7%;II期43.6%;III期32.1%;IV期7.6%)。犬种(杂种),体重(<10公斤),生活条件(室内),定期驱虫治疗,接种利什曼原虫疫苗可显着降低传播风险和发展为严重临床形式的风险。相反,合并症的检测与高级临床形式有关,尤其是慢性肾病,瘤形成,隐睾,感染性气管支气管炎和尿酸尿石症,尽管这些不影响临床结局。还检测到严重临床阶段的风险增加与病史(肾脏或皮肤相关表现)和体格检查(眼部发现)之间的显着关联。强调其在CanL转诊病例中的诊断价值。发现16个品种明显更容易发生利什曼病的严重阶段(例如大丹犬,罗威纳,英国斯普林格猎犬,拳击手,美国斯塔福德郡梗,金毛猎犬),而20个品种表现出临床抗性表型,因此,更有可能对婴儿乳杆菌产生有效的免疫反应(例如Pointer,Samoyed,西班牙Mast犬,西班牙灰狗,英语二传手,西伯利亚哈士奇)。这些品种的基因组分析检索到12个选择区域,63个候选基因,并精确定位了多个生物学途径,如未折叠蛋白反应的IRE1分支,这可能在婴儿乳球菌感染的临床易感性中起关键作用。
Canine leishmaniosis (CanL), caused by Leishmania infantum, is a complex disease of growing importance in Europe. Clinical manifestations result from the down-modulation of the host immune response through multiple host-parasite interactions. Although several factors might influence CanL progression, this is the first known study evaluating risk factors for its different clinical stages in a large referral hospital population (n = 35.669) from an endemic area, over a 20 year period. Genome-wide scans for selection signatures were also conducted to explore the genomic component of clinical susceptibility to L. infantum infection. The prevalence of CanL was 3.2% (16.7% stage I; 43.6% stage II; 32.1% stage III; 7.6% stage IV). Dog breed (crossbreed), bodyweight (<10 kg), living conditions (indoors), regular deworming treatment, and being vaccinated against Leishmania significantly decreased the transmission risk and the risk for developing severe clinical forms. Conversely, the detection of comorbidities was associated with advanced clinical forms, particularly chronic kidney disease, neoplasia, cryptorchidism, infectious tracheobronchitis and urate urolithiasis, although those did not impact the clinical outcome. Significant associations between an increased risk of severe clinical stages and findings in the anamnesis (renal or skin-related manifestations) and physical examination (ocular findings) were also detected, highlighting their diagnostic value in referred cases of CanL. Sixteen breeds were found to be significantly more susceptible to developing severe stages of leishmaniosis (e.g. Great Dane, Rottweiler, English Springer Spaniel, Boxer, American Staffordshire Terrier, Golden Retriever), while 20 breeds displayed a clinical resistantance phenotype and, thus, are more likely to mount an efficient immune response against L. infantum (e.g. Pointer, Samoyed, Spanish Mastiff, Spanish Greyhound, English Setter, Siberian Husky). Genomic analyses of these breeds retrieved 12 regions under selection, 63 candidate genes and pinpointed multiple biological pathways such as the IRE1 branch of the unfolded protein response, which could play a critical role in clinical susceptibility to L. infantum infection.