Case study and question,A 31-year-old woman with face pain came to the hospital. She was unable to open her mouth because of facial muscle spasms and had been unable to eat for 4 days because of severe pain in her jaw. The doctor found the patient trismus牙关紧闭 and risus sardonicus苦笑面容. Her husband complained that 1 week before, she had incurred a puncture刺伤 wound to her toe while walking in her garden.,1.How should this diagnosis be confirmed？ 2. What is the procedure for treating this patient？ 3.Should management wait until the lab results are available？ 4.What is the long term prognosis预后for this patient？,She had cleaned the wound and removed a mall pieces of wood from it, but she had not sought medical attention,Category,Clostridium Species,diseases including gas gangrene气性坏疽, tetanus破伤风and botulism肉毒杆菌中毒. pseudomembranous colitis假膜的结肠炎(PC) and food poisoning. Main pathogensis factors are exotoxins. perfringens, tetani, botulinum, difficile,Biochemical Characteristics,Gram(+); long and slender菌体细长;,peritrichous flagella周鞭毛, no capsule无荚膜,terminal located round spore(drum-stick apperance使细菌呈鼓槌状)芽胞正圆，位于菌体顶端its diameter greater than vegetative cell.,Morphology,BIOCHEMICAL CHARACTERISTICS,Culture:obligate anaerobic; swarming occures on blood agar, faint hemolysis血平板上，有微弱溶血. does not ferment any carbohydrate and proteins.,BIOCHEMICAL CHARACTERISTICS,Resistance: tolerate boiling for 60 min.alive several ten years in soil. Classification and Antigenic Types: C tetani is the only species. There are no serotypes,General introduction,C tetani is found worldwide. Ubiquitous in soil, it is occasionally found in intestinal flora of humans and animals C.tetani is the cause of tetanus,or lockjaw. When spores are introduced into wounds by contaminated soil or foreign objects such as nails or glass splinters,Pathogenic condition 致病条件,Wound need form anaerobic microenvironment伤口需形成厌氧微环境 Wound narrow and deep（刺伤puncture ），soil stain泥土污染 extensive wound大面积创伤、 suffer burns烧伤，much necrotic tissue坏死组织多，local deficiency blood局部组织缺血 Aerobe and facultative anaerobemixed infection; polyinfection有需氧菌或兼性厌氧菌混合感染的伤口Only local multiply,non-nvasive ,main exotoxin effect 无侵袭力，仅在局部繁殖，其致病作用完全有赖于病菌所产生的外毒素,Clostridium Tetani,Pathogenesis of tetanus caused by C tetani,Pathogenicity,No invasiveness; toxemia毒血症 produces two exotoxins: tetanolysin破伤风溶血毒素, and tetanospasmin破伤风痉挛毒素(a kind of neurotoxin, toxicity strong毒性极强,对人致死量1g) The actions of tetanospasmin,retrograde transport 逆向运转to (CNS) Delitescence潜伏期：a few days to several weeks The two animal species most susceptible to this toxemia are horses and humans.,tetanospasmin破伤风痉挛毒素,结构 菌体：一条多肽 释出菌体：轻链（A链）-S-S-重链（B链） B链：神经节苷脂结合的单位,可提纯制疫苗 A链：活性亚单位毒性作用,Clostridium tetani -Tetanospasmin,disseminates播散systemically binds to ganglioside神经甘脂 receptors inhibitory neurones in CNS glycine 甘氨酸 Neurotransmitter神经递质 stops nerve impulse to muscles spastic paralysis痉挛性麻痹 severe muscle contractions and spasms can be fatal,Mechanisms of tetanospasmin,spastic paralysis (rigid paralysis),破伤风痉挛毒素作用机制,膜的转位 通过重链N端的介导产生膜的转位使轻链进入胞质溶胶 胞质溶胶中作用靶的改变 A链发挥毒性作用，使储存抑制性神经介质小泡膜蛋白发生改变，阻止抑制性神经介质-氨基丁酸的释放，使肌肉活动的兴奋与抑制失调，造成麻痹性痉挛,破伤风痉挛毒素作用机制,与神经系统的结合 B链识别运动神经元外胞浆膜上的受体并结合，促使毒素进入细胞内小泡中 内在化作用 小泡从外周神经末稍沿神经轴突逆行向上，到达运动神经元细胞体，进入传入神经末稍，最终进入中枢神经系统,典型的症状,苦笑面容,muscles(trismus or lockjaw牙关紧闭, risus sardonicus苦笑,in neonates; infection typically originates from umbilical切断脐带stump残端;very poor prognosis in infants预后不良,the body extremely rigid, and opisthotonos角弓反张(a spasm in which the head and heels足跟 are bent backward and the body bowed forward),cramping痉挛 and twitching抽搐 of muscles,the neck and jaw muscles (trismus).,Clinical Manifestations,no fever but sweats profusely 多汗 pain, especially in the area of the wound Complications include fractures骨折, bowel impaction肠嵌塞, intramuscular hematoma血肿, muscle ruptures肌肉撕裂, and pulmonary, renal, and cardiac problems,Immunity免疫性,Humoral immunity(antitoxin抗毒素) The disease does not produce immunity in the patient.病后不会获得牢固免疫力 Active immunity人工免疫follows vaccination with tetanus toxoid类毒素 破伤风免疫属外毒素免疫，主要是发挥中和作用（毒素与中枢神经组织结合非常牢固，一旦结合即非抗毒素所能中和）,Epidemiology,In some developing countries, tetanus is still one of the ten leading causes of death, and neonatal tetanus accounts for approximately one-half of the cases worldwide. In the US, intravenous drug abusers have become another population with an increasing incidence of clinical tetanus In untreated tetanus, the fatality rate is 90% for the newborn and 40% for adults.,Diagnosis,Diagnosis is primarily by the clinical symptoms (above). The wound may not be obvious. It is important for the clinician to be aware that toxigenic strains of C tetani can grow actively in the wound of an immunized person. Numerous syndromes, including rabies and meningitis, have symptoms similar to those of tetanus and must be considered in the differential diagnosis.,infantDPT (diptheria, pertussis, tetanus)三联疫苗tetanus toxoid 破伤风类毒素antigenicno exotoxic activity 免疫程序：3、4、5月 3次 2、7岁加强 2次特殊情况 1次,