A potential early clinical phenotype of necrotizing meningoencephalitis in genetically at‐risk pug dogs

BackgroundNecrotizing meningoencephalitis (NME) in the pug dogs is a fatal neuroinflammatory disease associated with rapid progression and poor response to conventional immunosuppressive therapy. Diagnosis is typically made after severe neurological abnormalities have manifested.Hypothesis/ObjectivePug dogs at genetic risk for NME might manifest neurological abnormalities before developing pathognomonic clinical signs of NME.AnimalsThirty‐six pug dogs less than 4 years of age asymptomatic for NME.MethodsProspective observational cohort study with germline genome‐wide genotyping. Neurological examinations were performed 4 weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination.ResultsThe overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8/24 (33%) genetically at‐risk dogs and 0/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8/8, reduced menace response in 5/8, and lateralizing postural reaction deficits in 5/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype (P = .03).Conclusions and Clinical ImportanceOur findings suggest the presence of a novel early clinical phenotype of NME in apparently asymptomatic genetically at‐risk pugs which might be used to plan early diagnostic and therapeutic clinical trials.     

致动物脑膜炎粪肠球菌人工感染小鼠脑部模型的建立

为了构建粪肠球菌人工感染小鼠脑部损伤模型,以清洁级昆明小鼠为实验动物,将实验室保存的致羔羊脑膜炎粪肠球菌进行复苏,用寇氏法测定小鼠半数致死量(LD50),并以LD50剂量、1/2 LD50的剂量、2/3 LD50剂量感染小鼠,观察临床症状,选择2、4、8、12、24、36、48、60、72、84 h共10个时间点,无菌取其脑部、内脏组织进行细菌的分离鉴定,并观察病理组织学变化。结果显示,粪肠球菌的LD50为7.59×10^8CFU;感染小鼠后,其致死率1/2 LD50剂量组为3.7%,小于2/3 LD50剂量组的13.0%;1/2 LD50剂量组脑组织开始出现病理变化是在感染后12 h,晚于2/3 LD50剂量组(6 h),病理变化与后者相比较轻。结果表明,选择以2/3 LD50剂量为小鼠感染模型的最佳剂量。该动物模型的建立为进一步研究粪肠球菌感染小鼠导致脑炎奠定了基础。     

致脑膜炎多杀性巴氏杆菌的分离鉴定及全基因组重测序

旨在了解致脑膜炎多杀性巴氏杆菌的生物学特性及其引起脑部感染的生物学基础。本研究从有神经症状的病死猪脑组织中分离鉴定1株多杀性巴氏杆菌SD001,对其开展血清杀菌试验、胞内存活试验、小鼠感染试验,并利用纳米孔测序技术对其进行全基因组测序。SD001相对于猪其他器官中分离的多杀性巴氏杆菌而言表现出更强的抗血清杀菌的能力,其在小鼠巨噬细胞内存活的能力也较强。小鼠感染试验显示,相同剂量的细菌经血液感染后,SD001在小鼠血液和脑组织中的载菌量显著高于猪肺炎型多杀性巴氏杆菌(P ≤ 0.01),并且SD001造成了小鼠脑组织发生炎症等病理损伤,提示SD001可能造成血流感染并引起小鼠脑膜炎。纳米孔测序显示,SD001的全基因组大小约为2.45 Mb,平均GC含量为40.25%,编码2 281个蛋白以及77个RNA;SD001基因组中含有2条CRISPR结构、5个基因岛、7条前噬菌体序列;毒力基因预测结果显示,SD001含有233个毒力基因;基因分型结果显示,SD001为荚膜：LPS：MLST基因型A:L6:ST10。SD001感染可以引起脑膜炎,其较强的抗血清杀菌能力以及能形成血流感染的能力可能是SD001引起脑部感染的重要原因,在兽医临床关于中枢神经系统感染的诊断中应该纳入多杀性巴氏杆菌感染的可能性。     

Otitis media‐interna and secondary meningitis associated with Corynebacterium pseudotuberculosis infection in a horse

A one‐year‐old Thoroughbred colt was evaluated because of facial nerve paralysis, ataxia and fever. Neurological evaluation found the colt to be obtunded and grade 3/5 ataxic in all 4 limbs. Right‐sided facial nerve paralysis was present and a large, deep corneal ulcer noted in the right eye. Signs of vestibular disease were also present, including circling towards the right and horizontal nystagmus. A complete blood count showed mild leucocytosis, neutrophilia and hyperfibrinogenaemia. A computed tomography (CT) examination of the skull was performed under general anaesthesia and a diagnosis of right sided otitis media‐interna was made. Culture of fluid taken from the middle ear and cerebrospinal fluid collected from the atlanto‐occipital site yielded pure growth of Corynebacterium pseudotuberculosis. Initial therapy consisted of antimicrobial treatment with cefotaxime and anti‐inflammatory treatment with flunixin meglumine. Six days after initiating treatment, the colt developed Clostridium difficile associated colitis. The colitis resolved with supportive care and the colt was discharged from the hospital receiving chloramphenicol. Eight months later, the colt continued to be mildly ataxic (grade 1/5), with a slight head tilt and facial nerve paralysis. To the authors' knowledge, this is the first reported case of otitis media‐interna due to C. pseudotuberculosis in the horse.     

猪链球菌2型引起脑膜炎致病机制的研究进展

猪链球菌2型感染给世界养猪业造成巨大损失的同时也给公共卫生安全造成了威胁。至今对于猪链球菌2型的致病机制还不是很清楚，作者对国内外猪链球菌2型感染后引起机体脑膜炎的致病机制作一综述。     

Neural angiostrongylosis in three captive rufous bettongs (Aepyprymnus rufescens)

Neurological disease attributed to migration of the rat lungworm ( Angiostrongylus cantonensis ), is described in three captive rufous bettongs ( Aepyprymnus rufescens ). Clinical signs, including ascending paralysis and multifocal neurological deficits, were similar to those seen in other species. Histologically, the severity of meningoencephalomyelitis ranged from mild to moderate. In one animal cerebrospinal fluid contained a high percentage of eosinophils but peripheral blood cell counts were within normal limits. Treatment with dexamethasone, diazepam and vitamin E was unsuccessful. The prognosis for bettongs with this disease is poor. The susceptibility of this species to this disease has implications for enclosure design.     

A syndrome of facial paralysis of dairy calves in the Franklin district of New Zealand

AIM: To determine the aetiology of a syndrome characterised by facial paralysis in calves (facial paralysis syndrome; FPS); describe the epidemiology of the syndrome on an affected case farm; and define the intra-farm prevalence of affected calves, and inter-farm prevalence of affected dairy farms, in the Franklin district of New Zealand.

CASE HISTORY AND CLINICAL FINDINGS: An investigation was carried out on a town-supply dairy farm experiencing an outbreak of FPS in calves during the autumn of 2007, following a previous outbreak during the spring of 2006; 21 calves were affected in both outbreaks. Post-mortem examinations of three affected calves revealed no infectious aetiological agent in neurological tissues despite tests for viruses, bacteria and Mycoplasma species. Tests on hepatic tissues for vanadium toxicity were inconclusive.

SURVEY OF DAIRY FARMS: Results from a postal survey of 177/325 (54%) farms established the yearly prevalence of affected farms, based on farmer diagnosis, was 11%, and there was a median two (range 1–25) affected calves on those farms. There was no evidence of spatial clustering of affected farms after accounting for the underlying farm density, or of an increase in the number of affected farms between 2003 and 2007.

CLINICAL RELEVANCE: Facial paralysis syndrome is an unusual condition that has not been reported in other districts of New Zealand or in other countries. It is probable that this syndrome will continue to occur at a low to moderate prevalence, and have a significant impact on a small number of farms.