平衡腸道菌群,有助于預防壞死性腸炎.doc

平衡腸道菌群，有助于預防壞死性腸炎Balanced intestinal microflora help prevent necrotic enteritis壞死性腸炎是一種疾病，世界各地的影響雞和火雞。某些因素被稱為易患這種疾病的鳥。保持健康的腸道菌群平衡，似乎是在預防戰(zhàn)略的關鍵因素。受影響的羊群需要加以處理，以減少死亡損失。Tahseen阿齊茲博士，北卡羅來納州羅利，羅林斯動物疫病診斷實驗室，美國和H.約翰巴恩斯博士，獸醫(yī)學院，北卡羅來納州立大學，羅利，北卡羅來納，美國壞死性腸炎(NE)是雞，火雞，其他一些鳥類物種和產(chǎn)氣莢膜梭菌引起的腸道細菌性疾病。本病的特點是由致病細菌產(chǎn)生的毒素破壞腸粘膜。它是全球分布，導致肉雞生產(chǎn)商由于死亡率相當大的財務損失，并在其溫和的亞臨床形式，窮人的經(jīng)濟增長和飼料利用率，。在商業(yè)上提高了肉雞，臨床疾病通常發(fā)生在2至5周的年齡。致病細菌壞死性腸炎是由產(chǎn)氣莢膜梭菌，革蘭氏陽性，桿狀，孢子形成，厭氧細菌造成的。產(chǎn)氣莢膜梭菌是無處不在，發(fā)現(xiàn)在用枯枝落葉，土壤和腸道健康的鳥類。大量的產(chǎn)氣莢膜梭菌污染的飼料和枯枝落葉已令人信服地牽連作為一個傳染源。疾病發(fā)生時產(chǎn)氣莢膜梭菌在腸道消長產(chǎn)生烈性毒素，嚴重損害腸黏膜。從腸道吸收的毒素產(chǎn)生毒血癥(血液中的毒素)，這是鳥的死亡負責。因此，NE是一種“腸毒血癥”。產(chǎn)氣莢膜梭菌分為五個toxinotypes(A，B，D，和E)基于四(，和絲毫的主要毒素)。在大多數(shù)的來自東北案件的菌株鍵入C型阿爾法類型所產(chǎn)生的毒素引起的少數(shù)情況下，A和C，-C型產(chǎn)生的毒素，并可能由生物體產(chǎn)生的其他毒素的損害負責腸，腸毒血癥，死亡的鳥。產(chǎn)氣莢膜梭菌是肉雞消化道正常菌群的一部分。通常情況下，可以發(fā)現(xiàn)在作物，十二指腸，空腸，回腸，健康的鳥類盲腸。產(chǎn)氣莢膜梭菌在腸道內(nèi)的人口受營養(yǎng)，環(huán)境因素和鳥腸道的健康狀況。分子分型(遺傳指紋)已經(jīng)表明，在羊群的健康鳥類的腸道產(chǎn)氣莢膜梭菌菌株有較高的遺傳多樣性，而從鳥類在東北爆發(fā)的菌株只有一個，或不太常用，兩種遺傳類型。發(fā)病是部分不明NE的發(fā)病機制尚不完全清楚。有令人信服的證據(jù)表明，產(chǎn)氣莢膜梭菌菌株的毒力變化，東北有機體(“東北株”)的某些菌株引起。為什么這些是能夠誘導東北仍是未知。一些研究表明，一個單一的毒株，在東北爆發(fā)的排水量在雞腸道產(chǎn)氣莢膜梭菌的遺傳異質性腸道人口。但是，目前尚不清楚這些東北致病株分子特性或致病因素，使他們能夠有效競爭和選擇性增殖腸道產(chǎn)生組織損傷。到目前為止，沒有什么特別的產(chǎn)氣莢膜梭菌的遺傳類型已被確定，導致東北。聚類分析產(chǎn)氣莢膜梭菌的分離與NE的健康雞和雞的腸道，并沒有表明，NE是由產(chǎn)氣莢膜梭菌菌株屬于一個特定的基因型血統(tǒng)造成。毒素，產(chǎn)氣莢膜梭菌toxinotype生產(chǎn)A型，是一種重要的致病因素致病的有機體。它是一種磷脂水解紅細胞，白細胞，血小板(血小板)，內(nèi)皮細胞和肌肉細胞的細胞膜中的磷脂;由于其水解的財產(chǎn)，溶血，細胞毒性，壞死，并可能致命的毒素。是由不同菌株C.在體外產(chǎn)氣莢膜梭菌毒素的數(shù)量大的變化，但相同的遺傳類型的菌株生產(chǎn)相同數(shù)量的毒素。然而，三產(chǎn)氣莢膜梭菌毒素的量從東北病灶中分離出的是不從產(chǎn)生的毒素從腸道健康的鳥類株的數(shù)量顯著不同。最近，另一種新型的毒素(NetB的)已被確定在一定的產(chǎn)氣莢膜梭菌菌株。最初，這種毒素被認為是產(chǎn)氣莢膜梭菌菌株能夠造成東北的重大和關鍵的致病因子，但最近公布的研究表明，NetB的陰性菌株也能夠造成雞實驗挑戰(zhàn)NE。當然，作為NetB的NE的發(fā)病機制中的致病因子的作用需要進一步調(diào)查。誘發(fā)因素被發(fā)現(xiàn)在健康雞的小腸，通常是在小的數(shù)字，產(chǎn)氣莢膜梭菌。它colonises肉雞腸道內(nèi)孵化后幾個小時，并增加生物體的數(shù)量逐步初始定植后。事件導致后續(xù)生產(chǎn)過快增長，產(chǎn)氣莢膜梭菌(乘法)在小腸的毒素和腸粘膜損害，知之甚少。然而，某些因素被稱為易患鳥類對NE。據(jù)推測，這些因素尚未得到澄清的機制，促進產(chǎn)氣莢膜梭菌的過快增長。這些因素包括：1。小腸球蟲病。從受損的粘膜滲出的富含蛋白質的滲出物，產(chǎn)氣莢膜梭菌的生長提供必要的營養(yǎng)。產(chǎn)氣莢膜梭菌的最低增長要求，包括多種氨基酸和多種生長因子和維生素。在現(xiàn)代化，集約化的家禽生產(chǎn)，球蟲病可能是在野戰(zhàn)條件下的最重要的誘發(fā)因素。在我們的經(jīng)驗，東北的情況下，通常伴有不同程度的巨型艾美耳球蟲感染。2。高谷物，如黑麥，小麥和大麥的飼料含有高層次消化，易溶于水，非淀粉多糖。這些顆粒被認為是易患腸內(nèi)容物的粘度增加對NE。3。動物性蛋白質，如魚粉和骨粉，高量，增加飲食中NE的風險相比，飼料用植物蛋白源制定。增加的風險已被歸因于高甘氨酸和蛋氨酸水平的動物蛋白與動物蛋白來源;加強這兩個產(chǎn)氣莢膜梭菌在體外生長4。動物脂肪(豬油和牛油混合物)增加產(chǎn)氣莢膜梭菌的數(shù)量在回腸，與豆油相比。5?；痣u，已與東北ascaridiasis，球蟲病，出血性腸炎。6。高放養(yǎng)密度，高纖維的枯枝落葉，突然改變飲食的管理因素，包括東北的發(fā)病率也增加了。然而，在許多東北爆發(fā)，這些因素都可以被牽連誘發(fā)肉雞涌向疾病。甚至被認為是已知的誘發(fā)因素時，它仍然是難以重現(xiàn)疾病的實驗?？赡苡衅渌恼T發(fā)因素尚未確定。臨床癥狀和病變通常情況下，東北有一個很短的臨床過程。歷史通常沒有先兆的臨床癥狀，在羊群中發(fā)現(xiàn)雀鳥死。一些鳥類死亡前幾個小時可能會出現(xiàn)無精打采，昏昏欲睡。鳥類與溫和，東北亞臨床形式的影響，可能不會死，但顯示降低增重和飼料轉化率較高，在處理增加譴責由于肝臟病變。在腸道病變通常局限于空腸和回腸。它的變化在外觀上，從鳥鳥取決于感染的嚴重程度，發(fā)展階段，存在或球蟲病的情況下，新鮮的尸體。當鳥類有東北，最好檢查病變安樂死或新鮮的死鳥。一旦腸道開始分解后死亡，東北病變往往是不太明顯。空腸和回腸，可能會出現(xiàn)擴張，有薄，易碎的墻，充滿氣體或含有雜物摻綠色或略帶紅色的液體。在溫和的情況下，腸粘膜有粒狀或有些粗糙的外觀。在嚴重的情況下黏膜是綠色，棕色或紅棕色變色，并出現(xiàn)顯著增厚，粗糙，或天鵝絨。綠色，紅色，棕色，或粉紅色的假膜覆蓋和松散堅持粘膜的膜碎片可能進入管腔蛻。在罕見的病例，在肝臟和膽囊擴大在墻上的白色斑點(膽囊炎)點(灶性壞死)可能是seen.Microscopically，NE的標志性病變是在受影響的部分黏膜絨毛彌漫性壞死小腸。一般都是絨毛壞死和嗜酸性粒細胞(粉色)壞死碎片與眾多的大，桿狀細菌沿外緣的碎片，取代。情況嚴重的fibrinonecrotic膜堅持基本可行黏膜。在球蟲病并發(fā)，艾美耳屬的發(fā)育階段的案件。壞死碎片和固有層內(nèi)可見。如果有肉眼病變的肝臟或膽囊，肝組織壞死，膽囊壁與眾多大，病灶內(nèi)，桿狀細菌顯微鏡下看到。診斷東北格羅斯和微觀病變是NE的特點和診斷。眼觀病變的NE可以像艾美耳brunetti引起的，但組織NE可以證實。請記住，NE和球蟲病往往同時發(fā)生。受影響的小腸段兩端結扎，并盡快交付厭氧細菌培養(yǎng)實驗室，產(chǎn)氣莢膜梭菌的分離，可以嘗試。不凍結的標本，產(chǎn)氣莢膜梭菌的營養(yǎng)細胞死在冷凍溫度。另外，在厭氧的傳輸介質拭子可用于文化黏膜病變。拭子應盡快交付給診斷實驗室。細菌培養(yǎng)的結果，需要在臨床病史，肉眼病變，最好微觀病變的情況下解釋。有效的治療方法與NE的影響雞群通常是通過飲水給予抗生素治療。如果產(chǎn)氣莢膜梭菌是敏感的抗生素，羊群應迅速響應處理。應遵循用藥的包裝上推薦的治療劑量和時間，以確保治療效果。青霉素，四環(huán)素，林可霉素，紅霉素是首選藥物治療東北。如果羊群不響應在24-48小時內(nèi)治療，需要考慮以下的可能性：(1)NE的不正確的診斷，(2)產(chǎn)氣莢膜梭菌的抗生素產(chǎn)生耐藥性，(3)不正確的用藥劑量， (4)存在并發(fā)疾病，如球蟲病。產(chǎn)氣莢膜梭菌是敏感的幾個飼料抗生素生長促進劑。使用這些抗生素作為飼料添加劑，抑制腸道產(chǎn)氣莢膜梭菌的數(shù)量和減少NE的發(fā)病率。然而，自1997年以來，歐盟已禁止使用的幾個增長促進包括ardamycin，阿伏霉素，桿菌肽鋅，維吉尼亞霉素，泰樂菌素，螺旋霉素，已與東北增加發(fā)生關聯(lián)抗生素的。產(chǎn)氣莢膜梭菌是敏感的離子通道的抗球蟲藥莫能菌素，鹽霉素和甲基鹽霉素。納入這些抗球蟲藥的飼料，是有效減少腸道產(chǎn)氣莢膜梭菌的數(shù)量和保護對實驗NE。預防策略鳥類的腸道包含相互競爭的幾種細菌在腸道環(huán)境;東北發(fā)生時，產(chǎn)氣莢膜梭菌在腸道消長。保持健康的腸道菌群平衡，似乎是在東北預防的關鍵因素。給予一定的有益細菌(尤其是乳桿菌)鳥類是有效地防止，或至少減少，NE的嚴重性。所謂的“競爭排斥”產(chǎn)品含有不同的細菌提供商業(yè)和值得嘗試農(nóng)場與經(jīng)常性的NE問題。競爭排斥的產(chǎn)品應給予鳥盡快孵化后。在這些產(chǎn)品中的有益細菌可能會降低產(chǎn)氣莢膜梭菌在小雞的殖民統(tǒng)治。（文章來源：）無論是抗球蟲藥或疫苗接種，預防球蟲病，可能是最重要的措施，應采取防止東北。當球蟲疫苗的管理，這是非常重要的后續(xù)疫苗生產(chǎn)商的指示，以避免過度暴露鳥艾美耳球蟲卵囊。需要特別注意在接種后的頭兩個星期劑量的疫苗接種，接種疫苗的設備維護和校準，羊群管理支付。我們遇到的NE和球蟲病并發(fā)的情況下，在2-3周雞苗，其中球蟲疫苗已在孵化管理。 NE的預防涉及的干預策略，考慮到所有的因素，可能增加疾病的風險。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