Experimental Edema Disease of Swine (E. Coli ENTEROTOXEMIA) III. Pathology and Pathogenesis

Experimental colibacillary (Escherichia coli) enterotoxemia as described in this report mimics natural edema disease both clinically and in gross pathology. The histopathology is characterized by accumulations of non-inflammatory edema and by arteriopathy. The smaller arterial and arteriolar changes recorded here are similar to those described in natural edema disease. The vascular changes described in recovered cases of experimental colibacillary enterotoxemia concur with those reported in so-called subacute and chronic edema disease. The arteriolar changes that occur in colibacillary enterotoxemia of swine are comparable to those associated with hypertension.

Thin sections of cerebral cortex from four pigs with acute experimental edema disease were examined by electron microscopy in an attempt to demonstrate brain edema. Sections from one pig taken during the convulsive phase of disease revealed dilatation of perivascular glial processes. However, examination of sections taken from three other pigs during an earlier phase of the neurological disturbance revealed no significant lesions. We were unable to ascertain the role of brain edema in the pathogenesis of the nervous system disturbance in these experiments.

     

Experimental Edema Disease of Swine (E. Coli ENTEROTOXEMIA) I. Detection and Preparation of an Active Principle

Freeze-thaw lysates prepared from strains of Escherichia coli belonging to serogroups O138, O139, and O141 contained a principle (edema disease principle) which induced edema disease in swine. All freeze-thaw lysates contained endotoxic activity that tended to obscure the edema disease syndrome and methods were developed to reduce such activity. Freeze-thaw lysates prepared from E. coli O139 induced the most characteristic edema disease syndrome. Partially purified edema disease principle prepared from O139 freeze-thaw lysates by sequential precipitation with ammonium sulphate and streptomycin sulphate had increased specific activity with markedly reduced endotoxic activity. This material was insoluble at acidic pH but readily soluble at alkaline pH. The effective molecular weight of edema disease principle, based on retention and filtration properties of diaflo membranes, appeared to be greater than 50,000 and less than 100,000. The biological activity of edema disease principle was thermolabile. Sodium deoxycholate treatment of edema disease principle further reduced endotoxic activity. A thermolabile, ammonium sulphate precipitable material was prepared from E. coli O139 that induced a predictable syndrome which resembled edema disease clinically and pathologically following intravenous inoculation in pigs.     

Treatment of Edema Disease of Swine

Antihistamine (Allermin) was used sucessfully in the treatment of naturally occurring edema disease of swine under the field and laboratory conditions. A high recovery rate (88.8%) was obtained in the group of pigs with mild clinical signs. The intravenous route of Allermin administration had definite beneficial value. The release of histamine induced by circulating immune-complexes may be responsible for the clinical signs characteristic of edema disease.

Three pigs that recovered clinically following the Allermin treatment were examined histologically. Fibrinoid persisted in the vascular walls at least 30 days after the initiation of the treatment. The fibrinoid vasculitis, generalized eosinophilia at the tissue level, and favorable response of pigs to antihistamine treatment suggest that edema disease may be caused by allergy.

     

猪水肿病菌株毒素的抽提、鉴定和产毒量比较

对分离自江苏、上海等地的１５株仔猪水肿病菌株进行了毒素抽提，细胞毒性和动物试验鉴定结果表明，其中１４株能产生水肿病毒素（ＳＬＴ－Ⅱｖ），说明水肿病的发生与毒素密切相关。本文比较了这些菌株的产毒量，筛选出４株高产毒素菌株。     

Testing and Identification of Carp Edema Virus Disease in Cultured Koi

An acute infectious diseases occurred in a koi farm in Fangshan district, Beijing, and it resulted in mortalities of more than 50%.The main symptoms of sick koi were gills necrosis, kidney erosion and edema,which were similar to the clinical signs of koi herpes virus disease (KHVD).But PCR tests showed negative results for KHV. For further diagnosis, bacterial cultures, transmission electron microscopy studies, virus isolation and PCR tests were used. Electron microscopic observation revealed pox virus particles having a size of about 200 nm×400 nm in the kidney. 548 and 180 bp fragments were amplified from organs of sick koi by PCR method using specific primers of carp edema virus (CEV). The fragments were sequenced and analysed. The results showed that they were shared 100% nucleotide identity with CEV-H504. All the results indicated that this disease was carp edema virus disease, caused by a kind of pox virus, CEV. This was the first report on the CEV of cultured koi in China.     

养殖锦鲤鲤鱼浮肿病的检测与鉴定

北京房山某锦鲤养殖场锦鲤发生大量死亡,患病锦鲤呈烂鳃、肾脏糜烂、身体浮肿;症状类似锦鲤疱疹病毒（koi herpes virus,KHV）感染,但经PCR检测排除了KHV感染。为进一步确定病原,对发病鱼进行了临床症状观察、病毒分离、细菌分离培养、病鱼组织超薄切片电镜观察和PCR扩增等检测。通过病鱼组织超薄切片电镜观察,在肾脏内可见200 nm×400 nm的痘病毒样颗粒。抽提病毒核酸后,用已知的鲤鱼浮肿病毒（carp edema virus,CEV）的保守序列设计2对引物进行PCR扩增,扩增出548和180 bp片段,测序结果和GenBank公布的CEV H504株序列完全一致。根据发病鱼临床症状和实验室检测结果,最终确定该病为CEV引起的鲤鱼浮肿病。这是在中国首次发现的鲤鱼浮肿病。     

消肿二苓对实验性猪水肿病的药效

为探讨中西复方制剂消肿二苓对实验性猪水肿病疗效特进行本研究.结果表明,该制剂对实验兔具有明显的利尿作用,与兔正常尿量相比,差异极显著(P＜0.01),用试管二倍稀释法测定其对猪大肠杆菌的最低抑菌浓度(MIC)为0.125 mg/L,明显优于环丙沙星(P＜0.01).该制剂对实验性猪水肿病的疗效显著,其治愈率为100%,高于环丙沙星药物对照组,与感染对照组相比,差异极显著(P＜0.01).     

An experimental model for subclinical edema disease (Escherichia coli enterotoxemia) manifest as vascular necrosis in pigs.

An experimental model for subclinical edema disease was developed in weanling pigs. In multiple experiments, 3-week-old pigs were weaned, then inoculated intragastrically with 10(10) colony-forming units of an SLT-IIv-positive strain of Escherichia coli originally isolated from a pig with edema disease (principals). Control pigs were inoculated with a nonpathogenic E coli strain. Of 39 principals, 8 developed clinical edema disease within 14 days after inoculation. However, 20 of 21 principals that did not develop clinical signs of edema disease, but were submitted for necropsy examination at 14 days after inoculation, had characteristic vascular lesions of edema disease. Vascular lesions, found principally in ileum and brain, consisted of segmental necrosis of myocytes in the tunica media of small arteries and arterioles. None of the pigs inoculated with a nonpathogenic strain of E coli developed edema disease or vascular lesions. None of the principals necropsied at 2 days after inoculation had vascular lesions. Development of vascular lesions by 14 days after inoculation was used as the end point for detecting subclinical edema disease in the model.     

沙拉沙星对实验性猪链球菌病及猪水肿病的药效学

将兽医专用氟喹诺酮类药物沙拉沙星以不同治疗方案分别对实验性猪链球菌病和猪水肿病进行药效学研究。在每天总剂量相同的情况下 ,每天 1次与每天 2次给药取得了较好而相似的疗效 (P>0 .0 5 ) :对猪链球菌病 ,每天总剂量为 10 m g/ kg时 ,肌注给药的治愈率分别为 10 0 %和 90 %,但在迅速改善临床症状方面 ,每天 1次给药优于每天 2次(P<0 .0 5 ) ;对猪水肿病 ,每天总剂量为 5 mg/ kg时 ,肌注给药的治愈率均为 10 0 %。结果表明 ,在总剂量相同时 ,以大剂量、长间隔与以较小剂量、短间隔治疗实验性猪链球菌病与猪水肿病 ,均取得相当的疗效。     

Chick Edema Disease Syndrome in Young Turkey Poults

Two feeding bioassays were conducted to study the mortality pattern, incidence of edema and ascites formation and plasma composition of turkey poults fed diets containing varying levels of toxic fat (fat contaminated with polychlorinated dibenzo-p-dioxins) and/or salt. No significant changes in plasma concentrations of electrolyte and total protein and packed cell volume were observed in slaughtered poults fed diets containing toxic fat compared with poults fed a normal diet. However, a positive dose-response relationship between levels of dietary toxic fat (0,2 and 5%) and incidence of mortality with edema, ascites and hydropericardium was observed in poults fed diets containing 1% salt. The toxic effects of polychlorinated dibenzo-p-dioxins were accentuated by increasing the level of salt (0.5, 1 and 3%) in the diet. Mortality started at nine days of age and increased on days 10 and 11. The present experiments demonstrated that gross pathological changes similar to those reported for “chick edema disease” caused by feeding polychlorinated dibenzo-p-dioxins, could also be produced in young turkey poults. The etiology of the toxic effects of these organic compounds in edema formation is discussed.     

致猪水肿病大肠埃希菌多重PCR检测方法的建立及应用

本研究旨在建立一种快速鉴定致猪水肿病大肠埃希菌的多重PCR检测方法.分别针对大肠埃希菌16S rDNA、志贺毒素Stx2e A亚基和菌毛F18ab A亚基保守序列设计合成3对特异性引物,优化多重PCR反应条件,并进行特异性和敏感性检测.结果显示,阳性对照菌株扩增产物大小分别为1 062、733和313 bp.特异性和灵敏性检测结果表明,与肠炎沙门菌、多杀性巴氏杆菌、胸膜肺炎放线杆菌、副猪嗜血杆菌、支气管败血波氏杆菌和猪链球菌等猪常见致病菌均无交叉反应;菌体直接扩增法最低检出量为1 875 CFU.利用建立的多重PCR检测方法对分离收集的128株大肠埃希菌进行鉴定,得到36株致猪水肿病大肠埃希菌,其中30株既有菌毛F18ab又产志贺毒素Stx2e,另外6株仅产志贺毒素Stx2e.结果表明,本试验所建立的多重PCR检测方法对致猪水肿病大肠埃希菌的快速诊断和流行病学调查具有一定的应用价值.     

海安县猪水肿病的流行病学与病原特性研究

对江苏省海安县2003年5月～2004年5月各乡镇猪水肿病的发病和死亡情况进行了流行病学调查，发现猪水肿病在海安地区呈零星散发性发生，发病率为0.31％～1．84％，死亡率为0．07％—0．56％，病死率为16．0％～35．0％。水肿病主要侵害仔猪，育成猪也偶有发生，一般以气温比较高的季节多发。同时从疑似猪水肿病的病料中分离到12株大肠杆菌，经O血清型鉴定，5株为0139，2株为O45，O55、O93，O9、O101、O119各1株。经多重PCR检测毒素基因(STa，STb、LT、SLT-2e)和大肠杆菌粘附素单抗(F4、F5、F6、F41、F18)检测茵毛，共6个分离株带有SLT-2e基因，其中O139分离株5株，055分离株1株，其余6株均带STb基因。12个分离株中，单独表达F18菌毛的4株(O1392株，O45、O119各1株)，F5 F411株(O93)，F41 F181株(O139)，F5 F41 F182株(均为O139)。经药敏试验，多数分离株对壮观霉素和新霉素高度敏感。     

齐齐哈尔市猪水肿病病原的分离鉴定及药敏试验

对齐齐哈尔市10个市县猪场送检的30份疑似仔猪水肿病病料进行了实验室检测.经过分离培养、形态学检查、生化鉴定、致病性试验,分离到致病性大肠埃希菌27株.应用微量平板凝集试验,对分离的致病菌进行血清型鉴定.结果表明,以O138、O139、O9血清型最多,共22株,占分离致病菌的81%.药敏试验结果显示,同一猪场不同血清型组的药物敏感性无显著差异,不同猪场相同血清型组和不同猪场不同血清型组的药物敏感性除丁胺卡那外,各组间均不相同.     

猪水肿病大肠杆菌分离、鉴定及药敏试验

本实验从疑似猪水肿病的病例分离到5株大肠杆菌,O抗原鉴定结果表明所有菌株均为O139血清型;应用F18ab菌毛单克隆抗体对这5株大肠杆菌能否表达F18ab菌毛进行了鉴定,结果表明其中2个菌株能表达F18ab菌毛;利用聚合酶链式反应(PCR)对志贺氏菌样毒素Ⅱ型变异体(SLT-Ⅱe)操纵子基因保守区进行了扩增,结果发现在能表达F18ab菌毛2个菌株中可扩增一段特异性序列。以上数据表明这2株大肠杆菌为致仔猪水肿病大肠杆菌。药敏试验表明这两株菌株均对氟哌酸、妥布霉素、庆大霉素、利福平等抗生素高度敏感。     

仔猪水肿病病原菌的分离鉴定

从江苏淮安某猪场具有典型水肿病临床症状和剖检变化的发病猪组织分离的菌株中挑选5株大肠杆菌,分别命名为JS0001、JS0002、JS0003、JS0004和JS0005。通过培养特性、菌体形态、染色特性、生化鉴定及血清学试验等一系列方法对其进行系统鉴定,并对这5株细菌进行抗药性、溶血性、Vero细胞毒性和小白鼠致病性等试验。试验结果表明,JS0001、JS0002、JS0004和JS0005表现β型溶血,腹腔接种小白鼠,JS0001、JS0002、JS0003、JS0004对其具有较高致病性;5株细菌药敏特性基本一致：对痢特灵（FR）、头孢噻肟（CTX）、阿米卡星（AN）敏感,对头孢曲松（CRO）敏感性最高,而对阿莫西林(AMX)、多西环素(DO)等药物具有耐药性。JS0002、JS0004能够分泌Vero细胞毒素,确定为产类志贺毒素大肠杆菌（SLTEC）。血清学试验结果表明,JS0002、JS0004的血清型为O₁₃₉,JS0001、JS0003为O₁₄₁。     

An Attempt to Experimentally Produce Edema Disease in Swine by Oral Administration of Escherichia Coli Serotype 0139:K82:H1

Diarrhea, reduced appetite, and nervousness were observed following oral exposure of six pigs to freeze-thaw extract and living culture of E. coli strain 0139:K82:H1.

The most significance gross change was the appearance of subserosal edema of the mesentry, especially of the mesocolon.

Histological findings included perivascular edema of the brain and reticulum cells as well as lymphocytic aggregates in the renal cortex simulating early neoplasia. Edema of the submucosa of gallbladder, the duodenum, the spiral colon and the fundic stomach as well as the lymph nodes was also observed.

The syndrome which was produced resembled, in many aspects, edema disease although some complicating factors were ob-

     

Attempts to Produce Experimental Edema Disease in Swine by Parenterally Injecting Escherichia Coli Serotype 0139:K82:H1

Twenty-two pigs were inoculated parenterally with various E. coli 0139:K82:H1 preparations. Clinical signs of disease in pigs injected with freeze-thaw extract consisted of early listlessness, diarrhea and, later, hyperirritability of varying intensity in some animals.

Hemorrhagic gastroenteritis involving the duodenum, spiral colon and the fundic portion of the stomach, and ulceration of the fundic stomach were observed at post-mortem examination of pigs inoculated parenterallly with living culture or freeze-thaw extract. No significant lesions were observed in pigs inoculated with ultrasonic or hypotonic acid-saline extract.

In pigs injected with living culture or freeze-thaw extract, the histological alterations consisted of moderate perivascular edema of the brain, marked hepatic parenchymal cell degeneration, hepatic subserosal edema and “toxic” lymph nodes, when compared to the control group.

     

Edema disease.

Edema disease is a common cause of illness and death loss in pigs during the first 2 weeks after weaning. The disease is an enterotoxemia caused by strains of E. coli that colonize the small intestine and produce Stx2e. Bacterial colonization is mediated by F18ab fimbriae. Susceptibility to disease is determined by presence of receptors for these fimbriae on small intestinal epithelial cells and is inherited as a dominant trait. Clinical signs and lesions are largely the result of Stx2e, which causes necrosis of endothelial and smooth muscle cells in small arteries and arterioles. Vascular damage in the brain stem with resultant infarction and malacia is the main cause of death in affected pigs. Studies conducted by veterinary researchers in the 1950s and 1960s identified the cause of the disease and provided future scientists with hypotheses to test regarding the pathogenesis. In the last two decades, studies using molecular-based techniques have allowed for the definitive identification of bacterial virulence factors that mediate intestinal colonization and vascular damage, that is, F18ab fimbriae and Stx2e. Identification of these virulence factors has provided a basis for current and future development of effective preventative measures, for example, vaccines.     

Postanesthetic Pulmonary Edema In an Arab Stallion

A six-year-old arabian stallion was admitted to The Ohio State University Veterinary Hospital for evaluation and repair of a comminuted fracture of the second phalanx. The horse developed impaired arterial oxygenation during surgey and pulmonary edema post-operatively. We postulate that impaired arterial oxygenation resulted from atelectasis of the dependent lung during annesthesia, and the pulmonary edema occurred following re-expansion of the atelectatic of the initiating cause of the edema, removal of excess lung water from the alveoli, and restoration of normal arterial oxygenation. The horse was fully recovered within 12 hours of initiation of clinical signs of respiratory compromise. The horse was fully recovered within 12 hours of initiation of clinical signs of respiratory compromise. This report describes re-expansion pulmonary edema due to reperfusion injury in a horse, treatment of the condition, and a possible explanation of the pathogenesis of this pulmonary pathology.     

致仔猪水肿病大肠杆菌的分离、鉴定及生物学特性

从不同省份发生水肿病的仔猪的脏器中分离到7株细菌，通过菌体形态、菌落形态、革兰氏染色特性、生化特性、血清型等一系列的鉴定，确认为大肠埃希氏菌。动物致病性试验表明，该菌对小鼠有较强的致病性，可引起小鼠死亡。肉汤培养物无菌滤液能致死小鼠且剖检见相关脏器水肿，引起Vero细胞死亡。对主要毒力基因SLT-lle及F18进行扩增，SLT-lle全部阳性，5株F18为阳性。对LT1及ST1扩增则全为阴性。药敏试验证明，各菌株的耐药谱不同。各菌株攻毒于断奶仔猪，均能复制水肿病。