Botulism

　　Clostridium botulinum was first isolated by van Ermengen in a food poisoning incident in Belgium in 1897. The bacterial body is 2-4 μm long and 0.5-2 μm wide, with 4-8 flagella, capable of movement, without a capsule, and grows in anaerobic environments, easily forming spores. Young bacterial bodies are Gram-positive, while the old bacterial bodies that form spores are negative. This bacterium is widely present in nature, existing in soil, vegetables, fruits, grains, and can also be found in animal feces. The spores are highly heat-resistant, retaining activity after boiling for 6 hours, and can only be killed by autoclaving at 120℃ for 20 minutes or by dry heat at 180℃ for 5-15 minutes. It is not sensitive to commonly used disinfectants, and it takes 5% phenol or 20% formaldehyde solution for 24 hours, or 10% hydrochloric acid solution for 1 hour to kill it. The botulinum toxin is an exotoxin secreted by Clostridium botulinum, which is essentially a polypeptide. According to the antigenicity of the exotoxin, it is currently divided into eight types: A, B, C(Ca, Cb), D, E, F, and G. The types A, B, and E are the main causes of human illness, with type F and G occasionally reported. Type C and D mainly cause diseases in wild water birds, cattle, horses, ducks, chickens, and minks. Among the known chemical and biological toxins, the botulinum toxin is extremely toxic, with a lethal dose for humans of about 2 μg, and is a neurotoxin. Type A has the strongest affinity for nerve tissue, followed by type E, and type B is weaker. The toxin is resistant to gastric acid but sensitive to heat, and can be destroyed by 80℃ for 30 minutes or 100℃ for 10 minutes. Under conditions of dryness, sealing, darkness, and normal temperature, the toxin can be preserved for many years. Therefore, the toxin in canned food contaminated by Clostridium botulinum can retain its toxicity for a relatively long time. The toxin and the toxoids treated with formaldehyde have antigenicity, and vaccination of animals can produce antitoxin serum, which can neutralize the same-type toxin.

　　人摄入被肉毒梭菌外毒素污染的食物，不能被胃酸和消化酶破坏。由于肉毒梭菌毒素在菌体内是以无毒性前体存在，受自身产生的激活酶作用变成有活性毒素，肠道胰蛋白酶有激活作用。肉毒梭菌外毒素在胃和小肠内被蛋白溶解酶分解成小分子后，吸收进入血液循环，到达运动神经突触和胆碱能神经末梢。其作用可分为两个阶段。第一阶段，毒素与神经末梢表面部分可逆性结合，可被相应的抗毒素中和。第二阶段，毒素处于乙酰胆碱释放部位，邻近的受体发生不可逆结合，从而抑制神经传导递质-乙酰胆碱的释放，使肌肉不能收缩，导致眼肌、咽肌以及全身骨骼肌处于持续瘫痪状态。肉毒中毒病理变化呈非特异性，病理改变不一定能反映出中毒程度。因为中毒越重，死亡越快，组织病变反而较轻。尸检偶见脑神经核、脊髓前角退行变，脑膜充血、水肿，肝、脾、肾及其他器官可见充血和小血栓形成。婴儿肉毒中毒的发病年龄均小于6个月，其发病原理与上述不同。主要是婴儿食用的食品中测不出毒素，但患儿粪便可查到肉毒梭菌及其毒素。故提示可能由于食入肉毒梭菌芽孢或繁殖体，虽不含外毒素，但菌体在肠道繁殖产生外毒素，经肠黏膜吸收后出现症状。

　　肉毒素目前常用于医学美容，由于其具有很强的神经麻痹作用，可以造成神经支配的肌肉瘫痪，故面部局部使用有很好的去皱作用(实质上是已发生了面部的局部肌肉无法活动)，但如使用不当进入血液循环将可能危及患者生命。重症患者抢救不及时多数死亡，病死率30％-60％，死亡原因多为延髓麻痹所致呼吸衰竭，心功能不全及误吸肺炎所致继发性感染。

　　肉毒中毒的潜伏期12～36h，最短为2～6h，长者可达8～10天，中毒剂量愈大则潜伏期愈短，病情亦愈重。
　　起病突然，病初可有头痛、头昏、眩晕、乏力、恶心、呕吐（E型菌恶心呕吐重，A型菌及B型菌较轻）；稍后，眼内外肌瘫痪，出现眼部症状，如视力模糊、复视、眼睑下垂、瞳孔散大、对光反射消失、口腔及咽部潮红，伴有咽痛，如咽肌瘫痪，则致呼吸困难，肌力低下主要见于颈部及肢体近端，由于颈肌无力，头向前倾或倾向一侧，腱反射可呈对称性减弱。
　　植物神经末梢先兴奋后抑制，故泪腺、汗腺及涎腺等先分泌增多而后减少，血压先正常而后升高，脉搏先慢后快，常有顽固性便泌、腹胀、尿潴留，病程中神志清楚，感觉正常，不发热，轻者5～9日内逐渐恢复，但全身乏力及眼肌瘫痪持续较久。

　　肉毒中毒的预防包括以下方面：

　　1、严格执行食品管理法，对罐头食品、火腿、腌腊食品的制作和保存应进行卫生检查，对腌鱼、咸肉、腊肠必须蒸透、煮透、炒透才能进食，禁止食用发酵或腐败的食物。罐头食品顶部膨出现象或有变质者均应禁止出售。

　　2. If botulism occurs among co-eaters, uninfected individuals can be considered for the administration of 1000-2000U of polyvalent serum as a preventive measure, and observation should be conducted. Those who must frequently consume canned food in their daily life can be given botulinum toxin vaccines, 1ml per dose, subcutaneous injection, once a week, for a total of three injections.

　　During war, the enemy may disseminate botulinum toxin aerosol or botulinum toxin crystals to contaminate water sources. If necessary, immunization should be carried out for relevant personnel.

　　To confirm botulism, the following examinations need to be performed:

　　1. Pathogenetic examination

　　After heating the suspected food, vomit, or feces for 20 minutes, inoculate the blood agar for anaerobic bacterial culture to detect the pathogenic bacteria. For wound-type botulism, the toxin can be found in the serum or isolated from the wound and cultured under anaerobic conditions, which can make a definite diagnosis.

　　2. Toxin test

　　1. Animal experiment: Feed the extracted fluid of the test specimen to animals or inject it into the abdominal cavity of guinea pigs or mice, with a control group set up. Treat the specimen with a heat treatment of 80℃ for 30 minutes or add mixed botulinum antitoxin to the specimen. If the animals in the test group experience paralysis and death while the control group does not, the diagnosis of the disease can be established.

　　2. Neutralization test: Inject 0.5ml of each type of antitoxin serum into the abdominal cavity of a mouse, followed by the injection of 0.5ml of the specimen, with a control group set up to judge the toxin and typing.

　　2. Chick eye inoculation test: Inject 0.1-0.3ml of the toxin-containing extract below the corner of the eye of domestic poultry, depending on the size of the fowl. The eyelids close, or paralysis and difficulty breathing occur, and death occurs within tens of minutes to several hours. This can be used as a rapid diagnosis.

　　3. Electromyogram examination

　　There are characteristics such as muscle fiber tremors, decreased single stimulus response, increased electrical potential with repeated stimulation, short-duration, low-amplitude multi-phase movements, and increased electrical potential, which are helpful for the diagnosis of the disease.

　　After botulism, the following dietary methods can be adopted to maintain a light and nutritious diet, and to avoid eating unrefreshed or spoiled food.

　　Salt detoxification(folk remedy)

　　Indications: Food poisoning.

　　Recipe: 60 grams of salt.

　　Usage: Roast salt until it turns yellow, dissolve it in boiling water for oral administration to induce vomiting; or use 1 tablespoon of salt, fry it and then decoct the soup for drinking. Alternatively, drink a large amount of 0.5% saltwater, then stimulate the throat with fingers or feathers to promote vomiting.

　　The treatment of botulism is divided into the following three categories:

　　1. General treatment

　　1. Eliminate toxins in the gastrointestinal tract: Since botulinum toxin is easily destroyed in alkaline solutions and its toxicity is weakened in the presence of oxidizing agents, when botulism is diagnosed or suspected, 5% sodium bicarbonate or 1:4000 potassium permanganate solution can be used for gastric lavage to remove ingested toxins. For those without intestinal paralysis, laxatives and enemas can be used to expel unabsorbed toxins in the intestines, but magnesium citrate and magnesium sulfate should not be used. Because magnesium can enhance the neuromuscular blocking effect of botulinum toxin.

　　2. Symptomatic treatment: Strengthen nursing care, closely observe the changes in the condition, for those with secretions in the respiratory tract that cannot be excreted spontaneously, regular sputum aspiration should be performed, and tracheotomy should be chosen if necessary. Once respiratory failure occurs, artificial respiration should be used as soon as possible to assist breathing, and tracheal intubation can be performed for mild cases. For severe intestinal obstruction patients, nasogastric decompression should be applied. For those with urinary retention, continuous catheterization should be performed. For those with difficulty swallowing, nasogastric feeding or intravenous infusion should be used, and appropriate antibacterial drugs should be administered when secondary infections such as pneumonia occur. For patients with traumatic botulism, thorough debridement must be performed, and antiserum should be administered.

　　3. Fluid and nutrition supplementation: For those with difficulty swallowing, nasogastric feeding or intravenous infusion of daily necessary fluids, electrolytes and other nutrients should be administered.

　　2. Antitoxin treatment

　　Refined botulinum antitoxin serum can neutralize toxins in body fluids. It is generally recommended to use it early and in sufficient quantity. Before the toxin type is identified, multivalent antitoxin (A, B, E mixed trivalent antitoxin) 50,000 to 100,000 U should be administered intramuscularly or intravenously once, and repeated administration after 6 hours. In severe cases, it is not advisable to reduce the dose or discontinue the drug prematurely. When the toxin type is clear, the same type of antitoxin serum should be used for injection. Before the injection of antitoxin serum, a skin sensitivity test should be performed. If it is positive, it is necessary to start with a small dose and gradually increase the desensitization injection until the condition is relieved. The treatment of botulism in infants, due to the rare toxins in the child's blood, it is generally not recommended to use antitoxins, and mainly symptomatic treatment is adopted. Recently, some people have advocated the use of high-dose penicillin, which can reduce the production and absorption of botulinum toxin A in the intestines.

　　3. Other treatments

　　Pyridine can stimulate the sprouting of neurons, can shorten the course of the disease; Guanidine hydrochloride has the effect of promoting the release of acetylcholine by peripheral nerves, so it is considered to have an improvement effect on paralysis and respiratory function, the dose is 15-50mg/(kg·d), which can be administered nasally, but it is ineffective for patients with severe respiratory failure. Adverse reactions include gastrointestinal reactions, numbness, muscle spasms, irregular heartbeat, etc. Antibiotics are only suitable for patients with concurrent infections.