伤寒Typhoidfever

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,伤寒,Typhoid fever,9/21/2024,1,概述(Introduction),为伤寒沙门杆菌所致的急性传染病,Typhoid is a serious, acute infectious disease , caused by the bacterium,Salmonella,typhi,.,临床特点,:,持续发热,相对缓脉,全身中毒症状和消化道症状,玫瑰疹,肝脾肿大,白细胞减少,Clinical Features,:,sustained fever, marked headache, malaise, anorexia, relative,bradycardia,hepatosplenomegaly, rose spots,，,leukocytopenia,并发症,:,肠出血,肠穿孔,Complications,：,gastrointestinal,haemorrhage,or perforation,9/21/2024,2,病原学 Etiology,D群沙门菌，革兰阴性短杆菌，长13.5m，宽0.50.8m。无芽胞、无荚膜，有鞭毛。,Salmonella typhi,gram negative rod, motile by peritrichous flagella.,普通培养基中可生长，含胆汁培养基更佳,抵抗力强：,喜湿冷(水中:23周 冰冻:数月),怕干热(60 15分钟或煮沸即可灭活),化学消毒剂可灭活,9/21/2024,3,Virulence characteristics,毒素：菌体裂解时释放,cytotoxins, Invasion factors,三种抗原抗体系统：,菌体,O,抗原、鞭毛,H,抗原、 表面,Vi,抗原,somatic O antigen, surface Vi antigen,，,flagellar,H antigen.,菌体,O,抗体、鞭毛,H,抗体、表面,Vi,抗体,somatic O antibody, surface Vi antibody,，,flagellar,H antibody,9/21/2024,4,表面抗原与毒力有关,具有,抗吞噬和抗溶菌的作用,Vi抗原,抗原性弱，刺激机体产生短暂低效价抗体,伴随活菌一起存在,测定Vi抗体有助于检出带菌者,因为,所以,本质,Vi antigen impedes phagocytosis and contributes to the ability of S. typhi to survive normal host-defense mechanisms.,9/21/2024,5,流行病学 Epidemiology （一）,How is typhoid fever spread?,传染源,:,患者和带菌者,The carriers and the people who have active typhoid fever shed S.,Typhi,in their stools or urine.,慢性带菌者,:,排菌期,3,个月以上,(,主要传染源,) Asymptomatic carriers, who have recovered from the symptoms of the disease but continue to carry the bacteria. This carrier state occurs in about 3% of all individuals recovered from typhoid fever.,9/21/2024,6,传播途径,:,消化道传播,如污染的水源,(,重要途径,爆发流行,),污染的食物,(,也可引起流行,),日常生活接触,(,散发病例,),另外,:,苍蝇,蟑螂也可传递病菌,Typhoid is spread via the fecal-oral route and this can be through food or drink that has been contaminated by the,faeces,of a typhoid patient or carrier of the bacteria.,易感人群,:,普遍易感,病后获持久免疫力,(,仅,2%,的人第二次发病,),9/21/2024,7,Sources of contamination,Most common vehicles are beef, turkey, eggs, pork, and chicken,9/21/2024,8,流行病学 Epidemiology （二）,世界各地均有本病发生，热带和亚热带为多,常年发病，夏秋为多,儿童和青壮年为多，无性别差异,发病与卫生、经济条件相关,9/21/2024,9,Epidemiology,In 2000, the global annual incidence of typhoid fever was estimated to be around 21.7 million cases with 216,510 deaths per year.,DISTRIBUTION OF TYPHOID,我国发病率4.08-10.45/10万，,每年报告病例5.1-12万例,9/21/2024,10,发病机制,Pathogenesis,(一),潜伏期,(,第一次菌血症,):,人食入伤寒沙门菌后,细菌在小肠淋巴组织内繁殖，经胸导管入血。,After being swallowed, the,S.,typhi,bacteria are taken in by mononuclear phagocytes and multiply within these cells. This period of time is the 10 to 14-day incubation period of typhoid fever,9/21/2024,11,发病机制,Pathogenesis,(二),初期,(,第二次菌血症,):,细菌随血液入肝脾,胆囊,骨髓等组织器官内并大量繁殖,再次入血并释放内毒素,引起临床症状。,When huge numbers of bacteria fill an individual phagocyte, they spill out of the cell and into the bloodstream, where their presence begins to cause symptoms.,9/21/2024,12,发病机制,Pathogenesis,(三),极期,:,细菌随血播散全身,部分经肠粘膜再次入侵肠道淋巴组织,产生严重的炎症反应,;,大量细菌经肠道随粪便排出。,The bacteria move from the bloodstream into certain tissues of the body, including the gallbladder and lymph tissue of the intestine. The tissues response to this invasion causes severe,inflammationand,large of bacteria were secreted in patients stool.,9/21/2024,13,发病机制,Pathogenesis,(四),恢复期,:,随着免疫反应,(,细胞免疫,),的作用,细胞内伤寒杆菌被消灭,病变逐渐愈合,患者康复,.,仅少数患者,(2%5%),因胆囊长期保留细菌并排菌而成为慢性带菌者。,9/21/2024,14,胆囊-肠道-粪排菌,皮肤-血栓出血-玫瑰疹,肾-尿,肝脾-肿大,骨髓,伤寒和副伤寒的致病过程,伤寒和甲型副伤寒杆菌,小肠上部粘膜,肠系膜淋巴结,固有层淋巴结,进入血液,再次进入血液,第一次菌血症,第二次菌血症,9/21/2024,15,病理 Pathology（一）,全身单核-吞噬细胞系统的增生性反应,回肠下段淋巴组织最明显。,The reticuloendothelial system multiply.,9/21/2024,16,病理 Pathology（三）,第,2,周,:,肿大的淋巴结坏死,第,3,周,:,坏死组织脱落,溃疡形成，波及血,管可致肠出血,侵入肌层和浆膜层,可致肠穿孔,第,4,周,:,溃疡逐渐愈合,不留疤痕,9/21/2024,17,临床表现 Clinical characteristics,潜伏期723天,一般为1014天,The Incubation Period,:,From 7 days to over 23days, usual range 10-14 days.,9/21/2024,18,临床分期 Clinical classification,初期 Early period (第一周):,发热:阶梯形上升,可高达39 40, 发热前可有畏寒,少有寒颤和大汗,伴全,身不适,纳差,乏力,咽痛,咳嗽,9/21/2024,19,极期 Fastigium (第2,3周):,高热,稽留热为主，持续1014天,消化道症状：纳差,腹胀,便秘,(,少数有腹泻,),可有右下腹轻压痛；,神经系统症状：淡漠表情,反应迟钝,听力下降,精神恍惚，重者有中毒性脑病,:,谵妄,昏迷,病,理反射,循环系统症状：相对缓脉或重脉。,肝脾肿大，玫瑰疹,。,9/21/2024,20,缓解期,period of decline(,第,3,4,周,):,体温逐渐下降,食欲好转,腹胀逐渐消失,脾脏缩小，但本期仍可出现各种并发症。,恢复期,Convalescent period(,第,5,周,):,体温,食欲复常,。,通常在,1,个月左右完全康复,.,有并发症,原有慢性病,体弱者病程较长,.,9/21/2024,21,What are the signs and symptoms of typhoid fever?,a sustained fever as high as 39 to 40 C；,feeling weak, or loss of appetite,diarrhea,constipation,stomach pain,headache,malaise,nonproductive cough,slow heart rate (bradycardia),Hepatosplenomegaly,rose spots,9/21/2024,22,五种临床类型 Clinical type,轻型,(mild type ):,发热,38,全身毒血症状轻,病程,短,(13,周,),常见于早期已用有效抗生素治疗者,和年幼儿童,。,普通型,(moderate type),：,迁延型,(persistent type):,因机体免疫力低，病程迁,延,，,可达,5,周以上甚至数月,肝脾大较明显,。,逍遥型,(ambulatory type):,毒血症状轻；但部分患者,可因肠出血或肠穿孔为首发症状,。,暴发型,(,fulmimant,type):,可有高热,休克,中毒性脑病,中毒性肝炎,中毒性心肌炎,DIC,等,。,9/21/2024,23,复发(relapse):,退热后,13周再现临床症状，血培养,阳性,多见于免疫力低者，因潜伏于,吞噬细胞中的细菌大量繁殖入血所,致,症状较初发轻，病程短，并发症少。,再燃(recrudescence) :病后23周,体温未复常,时，又再,上升，持续57天后回到正常。血培养,阳性，可能与菌血症未完全控制有关，,症状加重，常见于抗菌治疗不彻底者。,9/21/2024,24,辅助检查 Laboratory,test（一）,外周血检查(Test of peripheral blood),嗜酸性粒细胞减少或消失，随病情好转而恢复，复发时再减少或消失,eosinophil,reduce or disappear,白细胞总数,、,中性粒细胞减少,leukocytopenia,9/21/2024,25,辅助检查 Laboratory,test,（二）-病原学培养,9/21/2024,26,Isolation of,S. typhi,from blood, stool, or,other clinical specimen,Blood cultures usually become positive in the first week of illness in 80% of patients who have not taken antibiotics.,Bone marrow cultures remain highly (90%) sensitive.,Culture of intestinal secretions can be positive despite a negative bone marrow culture.,If blood, bone marrow, and intestinal secretions,are all cultured, the yield of a positive culture is 90%.,Stool cultures while negative in 60 to 70% of cases during the first week, can become positive during the third to the fourth week of infection in untreated patients.,9/21/2024,27,辅助检查 Laboratory,test （三）,肥达反应 Widal test,O,抗体升高,H,抗体不高,可能为发病早期,; H,抗体升高,O,抗体不高,可能是曾患过伤寒或接种过疫苗,或非特异性回忆反应。,阳性率,:,病后,1,周开始阳性,34,周阳性率最高,(,70%),维持数月，约,10%30%,患者该反应始终阴性。,阳性标准,:,未经免疫者,O,抗体,1:80,H,1:160,为阳性；或每,57,天复查一次，抗体滴度逐渐上升,意义大。,存在假阳性和假阴性。,9/21/2024,28,肥达反应对诊断伤寒仅有,辅助,作用,不是确诊的唯一依据。,Widal,test given high rates of false-,positivity,and false-negativity, is not sufficient for diagnosis.,9/21/2024,29,辅助检查（四）-分子生物学技术,DNA,探针、,PCR,方法检测伤寒沙门氏菌，敏感性提高，但尚未在临床应用。,Polymerase chain reaction and DNA probe assays are being developed.,9/21/2024,30,并发症,complications,肠穿孔:最严重,发生率3%4%,见于极期,部位(回肠末段）,肠出血:最常见,发生率2%8%,见于24周, 饮食不当及腹泻为诱因。,The most common complication is a gastrointestinal haemorrhage or perforation resulting from intestinal ulceration.,9/21/2024,31,complications,中毒性肝炎,hepatitis,中毒性心肌炎,myocarditis,支气管炎或支气管肺炎,pneumonia,急性胆囊炎,cholecystitis,周围神经炎,peripheral neuritis,9/21/2024,32,诊断,(Diagnosis),流行病学资料,:,临床表现,:,实验室检查,:,白细胞减少，,嗜酸性粒细胞减少或消失,确诊,:,病原学伤寒杆菌培养阳性,9/21/2024,33,Diagnosis,Clinical Criteria,Insidious onset of sustained fever, headache, malaise, anorexia, relative bradycardia, constipation or diarrhea, and nonproductive cough.,Laboratory Criteria for Surveillance Purposes,Isolation of,S. typhi,from blood, stool, or other clinical specimen.,Surveillance Case Definitions,Confirmed:,A clinically compatible case that is laboratory confirmer.,Probable:,A clinically compatible case that is epidemiologically,linked to a confirmed case in an outbreak.,NOTE:,Isolation of the organism is required for confirmation. Serologic evidence alone is not sufficient for diagnosis.,9/21/2024,34,全国伤寒、副伤寒监测方案,-病例定义,疑似病例,在伤寒、副伤寒流行地区，不明原因持续发热或反复发热3天或以上，体温38，伴头痛、乏力、腹部不适等症状，但实验室检验结果尚未明确的病例。,9/21/2024,35,临床诊断病例,不明原因持续发热或反复发热5天或以上，体温39，头痛、全身乏力、表情淡漠、相对缓脉、伴消化道症状或皮肤充血或多系统受累表现，白细胞总数低或正常。,9/21/2024,36,确诊病例,临床诊断病例+以下项目之一者,从血、骨髓、粪便、尿等任一种标本分离到伤寒或副伤寒沙门菌；,血清特异性抗体阳性：肥达氏反应“O”抗体凝集效价1：80，伤寒或副伤寒鞭毛抗体凝集效价1：160，恢复期血清效价4倍以上增高。,9/21/2024,37,Differential diagnosis,流行性斑疹伤寒,epidemic typhus,地方性斑疹伤寒 endemic typhus,钩体病 leptospirosis,病毒感染 viral infection,疟疾 malaria,急性布氏杆菌病 acute brucellosis,急性血行播散型结核病 acutemiliarytuberculosis,革兰阴性杆菌感染 Gram negative bacteria infection,恶性组织细胞病,malignant histiocytosis,9/21/2024,38,治疗（一）：一般治疗,隔离与休息：病人体温正常,15,天或隔,5,天大便培养一次，,连续,2,次阴性解除隔离，密切接触者观察,23,天,饮食与护理：进易消化少纤维营养丰富饮食,须循序渐进,否则可诱发肠出血,肠穿孔,对症处理：,发热,:,物理降温为主,便秘,:,灌肠,开塞露等,禁用泻药,毒血症明显可予地塞米松,24mg/d,13d),9/21/2024,39,治疗（二）：病原治疗,喹诺酮类药物：首选,孕妇和儿童禁用,如：氧氟沙星,0.2 Bid,疗程,(,体温正常后继续用,1014,天,),三代头孢类：,如：头孢他啶,2.0 Bid(,成人,),疗程,(1014,天,),50mg/kg Bid(,儿童,),9/21/2024,40,氯霉素,成人剂量每日12g，小儿每日2550mg/kg，分4次口服，重症患者可增加剂量。待体温降至正常并稳定23日后减为半量，再继续给药1014日。,少数患者可发生粒细胞减少，严重者可发生再生障碍性贫血，伴有G6PD缺陷的患者，用药后可发生溶血。个别患者可出现中毒性精神病，但停药后可恢复。,耐药菌的出现,9/21/2024,41,慢性带菌者的治疗,喹诺酮类：,例：氧氟沙星,0.3 Bid,疗程,6,周,磺胺类：,例：复方磺胺甲恶唑,2,片,Bid,疗程,13,个月,氨苄西林,+,丙磺舒 疗程,46,周,36g/d 11.5g/d,内科疗效不佳或合并胆囊炎，胆石症者，可手术切除胆囊,9/21/2024,42,治疗（三）：并发症的治疗,肠穿孔：,肠出血：,中毒性心肌炎：,9/21/2024,43,Treatment,Antibiotics are the treatment of choice for typhoid fever. Quinolones are extremely effective and lowers fever fairly quickly.,Chloramphenicol (Chloromycetin) is also the effective medication for,S. typhi,. The patients symptoms begin to improve slightly after only 24-48 hours of receiving the medication.,Carriers of,S. typhi,requires treatment with one or even two different medications over a period of four to six weeks. Treatment with oral amoxicillin, TMP-SMZ, ciprofloxacin, or norfloxacin has been shown to be 80% effective in eradicating chronic carriage of susceptible organisms.,9/21/2024,44,Those with severe gastrointestinal bleeding may require intravenous (IV) feedings until they are able to digest food.,In the case of a carrier with gallstones, surgery may need to be performed to remove the gallbladder. This measure is necessary because typhoid bacteria are often housed in the gallbladder, where they may survive in spite of antibiotic treatment.,9/21/2024,45,预后,与病轻轻重、治疗及患者免疫状况有关。,在抗菌药物问世以前，病死率约为20%，大都死于严重的毒血症、营养不良、肺炎、肠出血及肠穿孔。现病死率明显下降（0.5%1%）。,老年人,婴幼儿,营养不良,明显贫血者预后差,病后获持久免疫力。,3%的患者成为慢性带菌者。,9/21/2024,46,Prognosis,Untreated, typhoid fever runs a course of anywhere from four to eight weeks, but can take many months for full recovery.,The prognosis for recovery is good for most patients. In the era before effective antibiotics were discovered, about 20% of all typhoid fever patients died of the infection. Now, however, fewer than 1% of patients who receive prompt antibiotic treatment will die.,The mortality rate is highest in the very young and very old, and in patients suffering from malnutrition.,3% become permanent carriers.,9/21/2024,47,预防,控制传染源 患者 接触者 慢性带菌者,切断传播途径 水源,饮食卫生管理， 消灭蚊蝇,保护易感人群,口服 减毒活菌苗,Ty21A 50%96%,注射 多糖菌苗,(,外膜抗原,Vi),试验阶段,9/21/2024,48,PREVENTION AND CONTROL,To eliminate salmonellae that cause enteric fever since the bacteria survive only in human hosts and are spread by contaminated food and water.,To monitor their food and water intake carefully.,To consider vaccination,.,9/21/2024,49,