科目：传染病学                        任课教师姓名：全俊
授课对象： 临床医学生                 专业：五年制
授课内容：伤寒与副伤寒 (typhoid fever and paratyphoid fever)
授课时数：3学时                        授课方式：课堂讲授 (中、英文双语教学) 

教学工具：多媒体

目的要求：掌握伤寒的病原学、传染源、传播途径、病理特点、典型的临床表现及诊断、治疗要点。了解副伤寒在临床表现上与伤寒有何异同。
教学重点：
①伤寒、副伤寒的病原、传染源、传播途径；
②伤寒的病理特点及基本病理改变；
③伤寒的病程分期，极期典型的临床表现，常见并发症；
④伤寒不同病期病原学检查标本的合理采集；肥达反应的意义判定；
⑤伤寒治疗的首选药物及其疗程。
教学难点：
①伤寒的临床病理联系
②复发、再燃的定义；
③肥达反应的意义判定。
授课设计：
①同步播放多媒体课件；
②授课过程中采用提问的方式复习以往所学的知识，如常见出疹性疾病的出疹顺序、皮疹特点、常见发热性疾病的热型等；
③首先介绍沙门菌属的分群，使学生对伤寒、副伤寒的病原菌有个总体的认识；
④前后呼应，讲解临床表现时结合基础内容，如为什么肠穿孔好发于回盲部？为什么在病程的2～3周多发？为什么在胆囊容易形成慢性带菌？
⑤重点详细讲授伤寒，而副伤寒则主要与伤寒对照，概括介绍其在临床表现上的异同点；
⑥讲课中随时介绍相关专业英语单词，并作英文小结。
一．概述（General review） （10分钟）
Typhoid fever is an acute illness. It is caused by infection of Salmonalla typhi, which belongs to family salmonallae. This disease is transmitted by fecal-oral route. Most often, acquisition of organisms occurs by ingestion of food or water contaminated with human excreta.
The basic pathological change of typhoid fever is the hyperplasia of mononuclear-phagocyte system., which is characterized by hyperplasia, ulceration and necrosis of ileocecal lymphoid tissue. The first typical manifestation of this disease is fever, which is often initially of the remittent type, rising in a stepwise fashion during the first week of illness, after which it becomes sustained. In addition to fever, patients may have neuropsychiatric manifestations, relative bradycardia, rose spots, hepatosplenomegaly, leukopenia and eosinopenia. Most symptoms resive by the forth week of infection without antimicrobial therapy. But some serious complications, such as intestinal perforation and hemorrhage, may occur during the third to the forth week of the illness.
二、病原学（Etiology） （15分钟）
1. Introduce the definition and some important serogroups of salmonellae.
2.This bacillus is gram-negative and non-spore-forming . It is motile by peritrichous
flagella, and consists of three antigens, namely somatic O, surface Vi and flagella H antigens.
3.The viability of Salmonalla typhi .
三、流行病学（Epidemiology） （5分钟）
1. Source of Infection：patients and carrier
Routes of transmission: faecal to orally
2. Susceptible population: rifeness
3. Epidemiologic feature
四、发病机制（pathogenesis） （15分钟）
伤寒沙门菌→胃（大部分被胃酸灭活）→小肠上段（呈碱性，含胆汁和营养物，有利于细菌生长繁殖）→小肠粘膜上皮细胞及巨噬细胞（粘膜下层）内繁殖—（经淋巴管）→小肠壁集合、孤立淋巴结及肠系膜淋巴结内繁殖—（经门静脉、胸导管入血）→第一次菌血症（无症状，抵抗力强者可不发病）→肝、脾、骨髓、淋巴结等单核-吞噬系统细胞内及胆囊内→第二次菌血症→出现症状：

五、病理解剖（pathology） （5分钟）
The basic pathological change of typhoid fever is the hyperplasia of mononuclear-phagocyte system
六、临床表现（clinical manifestations） （35分钟）
1. 潜伏期the incubation period The incubation phase: 10-14 days (7～23days)
2. 初期the prodromal period The temperature rise to 39～40℃ slowly as step ladder during the first week of illness, accompanied by malaise, fatigue, dizziness, myalgia, cough, anorexia and sore throat.
3. 极期
①pyrexia The classical temperature chart varies greatly in typhoid fever, and is present only in the untreated and uncomplicated case.
Classically it shows a step ladder rise in the first week, a plateau during the second week, it will last for 10～14 days, and a gradual fall during the 3rd to 4th weeks.
Febrile types: sustained fever and remittent fever or irregular fever
②gastrointestinal system symptoms The patient shows anorexia, abdominal malaise, abdominal distention and constipation commonly, diarrhea occasionally. Slight lower abdominal tenderness. The patient is found Hepatosplenomegaly and tenderness in palpation at the 1st weekend. The patient will come forth LFT abnormality if he is complicated by toxic hepatitis.
③relative bradycardia The pulse rate is relatively slow comparing to the temperature, and it seldom exceeds 100 per minute. But it is not apparent in children or adult accompanied by toxic cardiomyotitis.
④rose spots It occurs during 7～13 days of illness, lasts for 3～4 days, then disappears. The amount<10, rose-colored, slightly raised and fade on pressure.
mainly on the abdomen and chest.
⑤central nervous system: meningism, deafness, mental dullness
Some patients may be dull, no expression. Slight deafness is common during the first week, and may become more marked in later stage of the illness(typhoid face appearance).
The mental state may vary from normal mentality to muttering delirium, even confusion, but rarely violence(5%～10%). It is relative to the severity of illness.
4. 缓解期remission period The temperature decrease to normal gradually, and all symptoms and signs get better in the 4th week of the illness，but the patient is apt to come out some complications, such as intestinal bleeding and intestinal perforation.
5. 恢复期convalescent period Most symptoms resolve by the fourth week of illness without antimicrobial therapy, and approximately 90% patients survive.
6. 伤寒的临床分型：轻型、普通型、迁延型、逍遥型、爆发型
儿童伤寒与老年伤寒的特点typhoid fever in young and old people
年龄越小越不典型。起病急，发热以弛张热多见，胃肠道症状明显，肝脾肿大突出，玫瑰疹少见，并发支气管炎和支气管肺炎较多，WBC正常或增高。年长儿童病情一般较轻，病程较短，并发症少，病死率低。
老年伤寒:体温多不高，临床表现不典型，神经系统与心血管系统中毒症状重，易并发支气管炎和心功能不全，病程迁延，恢复慢，病死率高。
8.复发与再燃：relapse and recrudescence
复发：少数伤寒患者退热后1-3周临床症状再现,血培养再度阳性，称为复发。
原因：免疫力低，抗生素治疗不彻底，潜伏在病灶中巨噬细胞中的伤寒杆菌繁殖再次入血。病情轻，病程短，并发症少。
再燃：部分伤寒患者(10%-15%)在病后2-3周体温开始下降但尚未恢复正常时，体温又再上升，持续5-7天后才回到正常，称为再燃。再燃时症状加重，可能与菌血症仍未完全控制有关。
七、实验室检查（lab examination） （10分钟）
1. blood routine: leukopenia and eosinopenia
2. culture of Salmonalla typhi :the culture of blood and bone marrow
3. widal test:definition,clinical evaluation
定义：应用伤寒沙门菌O与H抗原，副伤寒甲、乙、丙的鞭毛抗原(A、B、C)，通过凝集反应检测患者血清中的相应抗体，对伤寒与副伤寒有辅助诊断的价值。一般发病后1周左右出现抗体，第2周阳性率达50%，3-4周达高峰（70%），效价亦较高并可维持数月；约有10％～30％患者肥达反应始终为阴性。

注意事项： O≥1:80,H≥1:160有辅助诊断的意义或动态观察，滴度4倍增高；O升高H不高：伤寒早期；H升高O不高：伤寒已治愈：O产生快，消失快；预防接种：H产生迟，持续时间长;回忆反应：其他发热性疾病所致；早期用抗生素：O、H不高。D群（伤寒）与A、B群（副伤寒甲、乙）有部分共同O抗原，可产生交叉反应, 所以O抗体升高只代表沙门菌属感染；10%—30%始终阴性：见于感染轻，抗体产生不足者；早期用抗生素；一般情况差的老年人和免疫力低下者。血吸虫病、溃疡性结肠炎、风湿病、败血症、结核病等可以出现假阳性，因为这些病人免疫紊乱。
◆肥达反应对诊断伤寒有帮助，但不能作为确诊依据。
八、诊断（diagnosis） （10分钟）
1.clinical diagnosis以下情况可考虑伤寒：
⑴持续发热1周以上、体温阶梯上升呈稽留热、相对缓脉、伤寒面容、玫瑰疹、肝脾肿大、白细胞不升高。
⑵持续发热1周以上，白细胞不升高并有嗜酸性粒细胞减少甚至消失的病人。
2.lab diagnosis:bacterial culture,widal test
3.differential diagnosis
九、治疗（treatment） （15分钟）
㈠ general treatment and nursing
1.激素：毒血症明显时可在足量有效抗生素前提下少量使用激素，DXM2～4mg，氢化可的松50～100mg或强的松5mg/日×3天。
2.高热：适当物理降温，不滥用退热药，防虚脱。
3.便秘：可用石蜡油、开塞露或N.S低压灌肠，禁用高压灌肠和泻剂。
4.腹泻：应低糖低脂饮食，可给予黄连素，不宜使用鸦片类制剂。
5.腹胀：应少食牛奶豆奶及糖类，可用松节油热敷或肛管排气，禁用新斯的明类药物。
㈡ antibacterial therapy
①FAQS 用药3～5天退热，热退后继用10～14天。用法，优缺点。孕妇和儿童不宜。
②cephalothin
③chloranfenicol 1.5～2g/日，热退后减半，再用10～14天，总疗程2～3周。
1. the treatment of major complications:
十、预防(prevention) （3分钟）
1. Control the source of infection ：treat patients and carrier
2. Interrupt the routes of transmission:三管一灭，注意卫生
3. Protect susceptible people: TAB immunization
思考题(questions)： （2分钟）
1.何谓Widal test ？如何评价其临床意义？
2.不同时期如何选择培养标本？
3.何谓复发、再燃及第一次菌血症？
4.试述伤寒发病机理、病理与临床表现的关系？