平衡肠道菌群,有助于预防坏死性肠炎.doc

平衡肠道菌群，有助于预防坏死性肠炎Balanced intestinal microflora help prevent necrotic enteritis坏死性肠炎是一种疾病，世界各地的影响鸡和火鸡。某些因素被称为易患这种疾病的鸟。保持健康的肠道菌群平衡，似乎是在预防战略的关键因素。受影响的羊群需要加以处理，以减少死亡损失。Tahseen阿齐兹博士，北卡罗来纳州罗利，罗林斯动物疫病诊断实验室，美国和H.约翰巴恩斯博士，兽医学院，北卡罗来纳州立大学，罗利，北卡罗来纳，美国坏死性肠炎(NE)是鸡，火鸡，其他一些鸟类物种和产气荚膜梭菌引起的肠道细菌性疾病。本病的特点是由致病细菌产生的毒素破坏肠粘膜。它是全球分布，导致肉鸡生产商由于死亡率相当大的财务损失，并在其温和的亚临床形式，穷人的经济增长和饲料利用率，。在商业上提高了肉鸡，临床疾病通常发生在2至5周的年龄。致病细菌坏死性肠炎是由产气荚膜梭菌，革兰氏阳性，杆状，孢子形成，厌氧细菌造成的。产气荚膜梭菌是无处不在，发现在用枯枝落叶，土壤和肠道健康的鸟类。大量的产气荚膜梭菌污染的饲料和枯枝落叶已令人信服地牵连作为一个传染源。疾病发生时产气荚膜梭菌在肠道消长产生烈性毒素，严重损害肠黏膜。从肠道吸收的毒素产生毒血症(血液中的毒素)，这是鸟的死亡负责。因此，NE是一种“肠毒血症”。产气荚膜梭菌分为五个toxinotypes(A，B，D，和E)基于四(，和丝毫的主要毒素)。在大多数的来自东北案件的菌株键入C型阿尔法类型所产生的毒素引起的少数情况下，A和C，-C型产生的毒素，并可能由生物体产生的其他毒素的损害负责肠，肠毒血症，死亡的鸟。产气荚膜梭菌是肉鸡消化道正常菌群的一部分。通常情况下，可以发现在作物，十二指肠，空肠，回肠，健康的鸟类盲肠。产气荚膜梭菌在肠道内的人口受营养，环境因素和鸟肠道的健康状况。分子分型(遗传指纹)已经表明，在羊群的健康鸟类的肠道产气荚膜梭菌菌株有较高的遗传多样性，而从鸟类在东北爆发的菌株只有一个，或不太常用，两种遗传类型。发病是部分不明NE的发病机制尚不完全清楚。有令人信服的证据表明，产气荚膜梭菌菌株的毒力变化，东北有机体(“东北株”)的某些菌株引起。为什么这些是能够诱导东北仍是未知。一些研究表明，一个单一的毒株，在东北爆发的排水量在鸡肠道产气荚膜梭菌的遗传异质性肠道人口。但是，目前尚不清楚这些东北致病株分子特性或致病因素，使他们能够有效竞争和选择性增殖肠道产生组织损伤。到目前为止，没有什么特别的产气荚膜梭菌的遗传类型已被确定，导致东北。聚类分析产气荚膜梭菌的分离与NE的健康鸡和鸡的肠道，并没有表明，NE是由产气荚膜梭菌菌株属于一个特定的基因型血统造成。毒素，产气荚膜梭菌toxinotype生产A型，是一种重要的致病因素致病的有机体。它是一种磷脂水解红细胞，白细胞，血小板(血小板)，内皮细胞和肌肉细胞的细胞膜中的磷脂;由于其水解的财产，溶血，细胞毒性，坏死，并可能致命的毒素。是由不同菌株C.在体外产气荚膜梭菌毒素的数量大的变化，但相同的遗传类型的菌株生产相同数量的毒素。然而，三产气荚膜梭菌毒素的量从东北病灶中分离出的是不从产生的毒素从肠道健康的鸟类株的数量显著不同。最近，另一种新型的毒素(NetB的)已被确定在一定的产气荚膜梭菌菌株。最初，这种毒素被认为是产气荚膜梭菌菌株能够造成东北的重大和关键的致病因子，但最近公布的研究表明，NetB的阴性菌株也能够造成鸡实验挑战NE。当然，作为NetB的NE的发病机制中的致病因子的作用需要进一步调查。诱发因素被发现在健康鸡的小肠，通常是在小的数字，产气荚膜梭菌。它colonises肉鸡肠道内孵化后几个小时，并增加生物体的数量逐步初始定植后。事件导致后续生产过快增长，产气荚膜梭菌(乘法)在小肠的毒素和肠粘膜损害，知之甚少。然而，某些因素被称为易患鸟类对NE。据推测，这些因素尚未得到澄清的机制，促进产气荚膜梭菌的过快增长。这些因素包括：1。小肠球虫病。从受损的粘膜渗出的富含蛋白质的渗出物，产气荚膜梭菌的生长提供必要的营养。产气荚膜梭菌的最低增长要求，包括多种氨基酸和多种生长因子和维生素。在现代化，集约化的家禽生产，球虫病可能是在野战条件下的最重要的诱发因素。在我们的经验，东北的情况下，通常伴有不同程度的巨型艾美耳球虫感染。2。高谷物，如黑麦，小麦和大麦的饲料含有高层次消化，易溶于水，非淀粉多糖。这些颗粒被认为是易患肠内容物的粘度增加对NE。3。动物性蛋白质，如鱼粉和骨粉，高量，增加饮食中NE的风险相比，饲料用植物蛋白源制定。增加的风险已被归因于高甘氨酸和蛋氨酸水平的动物蛋白与动物蛋白来源;加强这两个产气荚膜梭菌在体外生长4。动物脂肪(猪油和牛油混合物)增加产气荚膜梭菌的数量在回肠，与豆油相比。5。火鸡，已与东北ascaridiasis，球虫病，出血性肠炎。6。高放养密度，高纤维的枯枝落叶，突然改变饮食的管理因素，包括东北的发病率也增加了。然而，在许多东北爆发，这些因素都可以被牵连诱发肉鸡涌向疾病。甚至被认为是已知的诱发因素时，它仍然是难以重现疾病的实验。可能有其他的诱发因素尚未确定。临床症状和病变通常情况下，东北有一个很短的临床过程。历史通常没有先兆的临床症状，在羊群中发现雀鸟死。一些鸟类死亡前几个小时可能会出现无精打采，昏昏欲睡。鸟类与温和，东北亚临床形式的影响，可能不会死，但显示降低增重和饲料转化率较高，在处理增加谴责由于肝脏病变。在肠道病变通常局限于空肠和回肠。它的变化在外观上，从鸟鸟取决于感染的严重程度，发展阶段，存在或球虫病的情况下，新鲜的尸体。当鸟类有东北，最好检查病变安乐死或新鲜的死鸟。一旦肠道开始分解后死亡，东北病变往往是不太明显。空肠和回肠，可能会出现扩张，有薄，易碎的墙，充满气体或含有杂物掺绿色或略带红色的液体。在温和的情况下，肠粘膜有粒状或有些粗糙的外观。在严重的情况下黏膜是绿色，棕色或红棕色变色，并出现显着增厚，粗糙，或天鹅绒。绿色，红色，棕色，或粉红色的假膜覆盖和松散坚持粘膜的膜碎片可能进入管腔蜕。在罕见的病例，在肝脏和胆囊扩大在墙上的白色斑点(胆囊炎)点(灶性坏死)可能是seen.Microscopically，NE的标志性病变是在受影响的部分黏膜绒毛弥漫性坏死小肠。一般都是绒毛坏死和嗜酸性粒细胞(粉色)坏死碎片与众多的大，杆状细菌沿外缘的碎片，取代。情况严重的fibrinonecrotic膜坚持基本可行黏膜。在球虫病并发，艾美耳属的发育阶段的案件。坏死碎片和固有层内可见。如果有肉眼病变的肝脏或胆囊，肝组织坏死，胆囊壁与众多大，病灶内，杆状细菌显微镜下看到。诊断东北格罗斯和微观病变是NE的特点和诊断。眼观病变的NE可以像艾美耳brunetti引起的，但组织NE可以证实。请记住，NE和球虫病往往同时发生。受影响的小肠段两端结扎，并尽快交付厌氧细菌培养实验室，产气荚膜梭菌的分离，可以尝试。不冻结的标本，产气荚膜梭菌的营养细胞死在冷冻温度。另外，在厌氧的传输介质拭子可用于文化黏膜病变。拭子应尽快交付给诊断实验室。细菌培养的结果，需要在临床病史，肉眼病变，最好微观病变的情况下解释。有效的治疗方法与NE的影响鸡群通常是通过饮水给予抗生素治疗。如果产气荚膜梭菌是敏感的抗生素，羊群应迅速响应处理。应遵循用药的包装上推荐的治疗剂量和时间，以确保治疗效果。青霉素，四环素，林可霉素，红霉素是首选药物治疗东北。如果羊群不响应在24-48小时内治疗，需要考虑以下的可能性：(1)NE的不正确的诊断，(2)产气荚膜梭菌的抗生素产生耐药性，(3)不正确的用药剂量， (4)存在并发疾病，如球虫病。产气荚膜梭菌是敏感的几个饲料抗生素生长促进剂。使用这些抗生素作为饲料添加剂，抑制肠道产气荚膜梭菌的数量和减少NE的发病率。然而，自1997年以来，欧盟已禁止使用的几个增长促进包括ardamycin，阿伏霉素，杆菌肽锌，维吉尼亚霉素，泰乐菌素，螺旋霉素，已与东北增加发生关联抗生素的。产气荚膜梭菌是敏感的离子通道的抗球虫药莫能菌素，盐霉素和甲基盐霉素。纳入这些抗球虫药的饲料，是有效减少肠道产气荚膜梭菌的数量和保护对实验NE。预防策略鸟类的肠道包含相互竞争的几种细菌在肠道环境;东北发生时，产气荚膜梭菌在肠道消长。保持健康的肠道菌群平衡，似乎是在东北预防的关键因素。给予一定的有益细菌(尤其是乳杆菌)鸟类是有效地防止，或至少减少，NE的严重性。所谓的“竞争排斥”产品含有不同的细菌提供商业和值得尝试农场与经常性的NE问题。竞争排斥的产品应给予鸟尽快孵化后。在这些产品中的有益细菌可能会降低产气荚膜梭菌在小鸡的殖民统治。（文章来源：）无论是抗球虫药或疫苗接种，预防球虫病，可能是最重要的措施，应采取防止东北。当球虫疫苗的管理，这是非常重要的后续疫苗生产商的指示，以避免过度暴露鸟艾美耳球虫卵囊。需要特别注意在接种后的头两个星期剂量的疫苗接种，接种疫苗的设备维护和校准，羊群管理支付。我们遇到的NE和球虫病并发的情况下，在2-3周鸡苗，其中球虫疫苗已在孵化管理。 NE的预防涉及的干预策略，考虑到所有的因素，可能增加疾病的风险。Balanced intestinal microflora help prevent necrotic enteritisNecrotic enteritis is a disease affecting chickens and turkeys throughout the world. Certain factors are known to predispose birds to this disease. Keeping a healthy balance of intestinal microflora seems to be a key element in the prevention strategy. Affected flocks need to be treated to minimise death losses.By Dr. Tahseen Aziz, Rollins Animal Disease Diagnostic Laboratory, Raleigh, NC, USA and Dr. H. John Barnes, College of Veterinary Medicine, NC State University, Raleigh, NC, USANecrotic enteritis (NE) is an enteric bacterial disease of chickens, turkeys, and a few other avian species caused by Clostridium perfringens. The disease is characterised by damage to the intestinal mucosa by toxins produced by the causative bacteria. It is worldwide in distribution and causes considerable financial losses to broiler producers due to mortality and, in its milder subclinical form, poor growth and feed utilisation. In commercially raised broiler chickens, clinical disease usually occurs between 2 and 5 weeks of age.The causative bacteriumNecrotic enteritis is caused by C. perfringens, a gram-positive, rod-shaped, spore-forming, anaerobic bacterium. C. perfringens is ubiquitous, found in used litter, soil, and intestinal tracts of healthy birds. Feed and litter contaminated with large numbers of C. perfringens have been convincingly implicated as a source of infection. The disease occurs when C. perfringens overgrows in the intestinal tract and produces potent toxins that severely damage the intestinal mucosa. Toxins absorbed from the intestinal tract produce a toxemia (toxin in blood), which is responsible for death of the bird. Thus, NE is a type of “enterotoxemia”.C. perfringens is divided into five toxinotypes (A, B, C, D, and E) based on four major toxins (alpha, beta, epsilon, and iota). The majority of isolates from NE cases are type A, with a few cases caused by type C. Alpha toxin produced by types A and C, beta toxin produced by type C, and possibly other toxins produced by the organism are responsible for the damage to the intestine, enterotoxemia, and death of the bird.C. perfringens is part of the normal flora of the digestive tract of broilers. Typically, it can be found in the crop, duodenum, jejunum, ileum, and ceca of healthy birds. The population of C. perfringens in the intestine is affected by nutritional and environmental factors and health status of the gut of the bird . Molecular typing (genetic fingerprinting) has shown that isolates of C. Perfringens from the intestines of healthy birds in a flock have high genetic diversity, whereas isolates from birds in a NE outbreak are only one, or less commonly, two genetic types.Pathogenesis is partly unclearThe pathogenesis of NE is not fully understood. There is convincing evidence that C. perfringens strains vary in virulence and that NE is caused by certain strains of the organism (“NE strains”). Why these are capable of inducing NE remains unknown. Several studies have shown that in a NE outbreak, a single virulent strain displaces the genetically heterogeneous enteric population of C. perfringens in the intestinal tract of the chicken. However, it is not clear what molecular properties or virulence factors these NE-causing strains have that enable them to effectively compete and selectively proliferate in the gut to produce tissue damage. So far, no particular genetic type of C. perfringens has been identified that causes NE. Cluster analysis of C. perfringens isolates from intestinal tracts of healthy chickens and chickens with NE did not show that NE is caused by C. Perfringens strains that belong to a specific genotypic lineage.Alpha toxin, produced by C. perfringens toxinotype type A, is an important virulence factor in the pathogenicity of the organism. It is a phospholipase that hydrolyses phospholipids in membranes of red blood cells, white blood cells, platelets (thrombocytes), endothelial cells, and muscle cells; because of its hydrolytic property, the toxin is hemolytic, cytotoxic, necrotising, and potentially lethal. Large variations in the amount of alpha toxin are produced by different isolates of C. perfringens in vitro, but isolates of the same genetic type produce the same amount of alpha toxin.However, the amount of alpha toxin produced by C. perfringens isolated from NE lesions is not significantly different from the amount of the toxin produced by isolates from the intestine of healthy birds. Recently, another novel toxin (NetB) has been identified in certain strains of C. perfringens. Initially, this toxin was thought to be the major and critical virulence factor in C. perfringens strains capable of causing NE, but recently published research indicates that NetB-negative strains are also capable of causing NE in experimentally challenged chickens. Certainly, the role of NetB as a virulence factor in the pathogenesis of NE needs further investigation.Predisposing factorsC. perfringens is found in the small intestine of healthy chickens, usually in small numbers. It colonises the intestines of broiler chickens within a few hours after hatching and the numbers of the organism increase gradually after initial colonisation. Events leading to excessive growth (multiplication) of C. perfringens in the small intestine, with subsequent production of toxin and damage to the intestinal mucosa, are poorly understood.However, certain factors are known to predispose birds to NE. It is presumed that these factors promote excessive growth of C. perfringens through mechanisms that are yet to be clarified. These factors include:1. Small intestinal coccidiosis. Protein-rich exudate leaking from the damaged mucosa may provide necessary nutrients for the growth of C. perfringens. The minimum growth requirement of C. perfringens includes several amino acids and many growth factors and vitamins. In modern, intensive poultry production, coccidiosis is probably the most important predisposing factor under field conditions. In our experience, NE cases are commonly associated with varying degrees of Eimeria maxima infection.2. Diets high in cereal grains such as rye, wheat, and barley contain high levels of indigestible, water soluble, non-starch polysaccharides. These grains are believed to predispose to NE by increasing the viscosity of the intestinal contents.3. High amounts of animal protein, such as fish meal and bone meal, in the diet increase the risk of NE compared to feed formulated with plant sources of protein. The increased risk associated with animal sources of protein has been attributed to high glycine and methionine levels in animal protein; both of which enhance C. perfringens growth in vitro4. Animal fat (mixture of lard and tallow) increases the numbers of C. perfringens in the ileum, compared with soy oil.5. In turkeys, NE has been associated with ascaridiasis, coccidiosis, and hemorrhagic enteritis.6. Management factors that include high stocking density, high fibre litter, and sudden changes in diet also increase the incidence of NE.However, in many NE outbreaks none of these factors can be implicated as predisposing the broiler flock to the disease. Even when known predisposing factors are considered, it is still difficult to reproduce the disease experimentally. There are probably other predisposing factors that are yet to be identified.Clinical signs and lesionsTypically NE has a short clinical course. The history usually states that birds in the flock are found dead without premonitory clinical signs. Some birds may appear listless and lethargic for a few hours before death. Birds affected with the mildest, subclinical form of NE, may not die but show reduced weight gains and higher feed conversion ratios, with increased condemnations at the processing due to liver lesions.The lesion in the intestinal tract is usually confined to the jejunum and ileum. It varies in appearance from bird to bird depending on the severity of infection, stage of development, presence or absence of coccidiosis, and freshness of the carcass. When birds have NE it is best to examine euthanised or fresh dead birds for lesions. Once the intestine starts to decompose after death, NE lesions tend to be less obvious. The jejunum and ileum may appear dilated, have a thin, friable wall, and be filled with gas or contain green or red-tinged fluid admixed with debris. In mild cases the intestinal mucosa has a granular or somewhat roughened appearance.In severe cases the mucosa is discoloured green, brown, or redbrown, and it appears markedly thickened, roughened, or velvety. A green, red, brown, or pink pseudomembrane may cover and loosely adhere to the mucosa; pieces of the membrane may slough into the lumen. In rare cases, spots (multifocal necrosis) in the liver and an enlarged gall bladder with white spots in the wall (cholecystitis) may be seen.Microscopically, the hallmark lesion of NE is diffuse necrosis of the mucosal villi in the affected segment of the small intestine. Usually all of the villi are necrotic and replaced by eosinophilic (pink) necrotic debris, with numerous large, rod-shaped bacteria along the outer margin of the debris. In severe cases a fibrinonecrotic membrane adheres to the underlying viable mucosa. In cases of concurrent coccidiosis, developmental stages of Eimeria spp. are seen within the necrotic debris and lamina propria. If there are gross lesions in the liver or gall bladder, necrosis of hepatic tissue and the wall of the gall bladder with numerous large, intralesional, rod-shaped bacteria is seen microscopically.Diagnosing NEGross and microscopic lesions are characteristic and diagnostic of NE. Grossly, lesions of NE can resemble those caused by Eimeria brunetti; however NE can be confirmed histologically. Remember that NE and coccidiosis often occur concurrently. Isolation of C. perfringens may be attempted by ligating an affected segment of intestine at both ends and delivering it as soon as possible to a laboratory for anaerobic bacterial culture. Do not freeze the specimen, as the vegetative cells of C. perfringens die at freezing temperature. Alternatively, a swab in an anaerobic transport medium may be used to culture the mucosal lesions. The swab should be delivered to the diagnostic lab as soon as possible. The results of bacterial culture need to be interpreted in the context of clinical history, gross lesions, and preferably microscopic lesions.Effective treatmentFlocks affected with NE are usually treated with antibiotics administered via drinking water. If C. perfringens is sensitive to the antibiotic, the flock should rapidly respond to treatment. The dose and duration of treatment recommended on the package of the medication should be followed to ensure efficacy of the treatment. Penicillin, tetracycline, lincomycin, and erythromycin are drugs of choice for treating NE.If the flock does not respond to treatment within 24-48 hours, the following possibilities need to be considered: (1) incorrect diagnosis of NE, (2) resistance of C. perfringens to the antibiotic, (3) incorrect dose of medication, and (4) presence of concurrent disease, such as coccidiosis. C. perfringens is sensitive to several in-feed antibiotic growth promoters. Use of these antibiotics as feed additives suppresses the numbers of C. perfringens in the intestinal tract and reduces the incidence of NE.However, since 1997 the European Union has banned the use of several growth promoting antibiotics including avoparcin, ardamycin, bacitracin, virginiamycin, tylosin, and spiramycin, which has been associated with increased occurrence of the NE. C. perfringens is sensitive to the ionophorous coccidiostats monensin, salinomycin, and narasin. Incorporating these coccid