伤寒Typhoidfever

1、2022-3-221伤寒伤寒Typhoid fever2022-3-222概述(Introduction)u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.u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,

2、hepatosplenomegaly, rose spots ，leukocytopenia u并发症: 肠出血,肠穿孔 Complications：gastrointestinal haemorrhage or perforation 2022-3-223病原学 EtiologynD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.u普通培养基中可生长，含胆汁培养基更佳u抵抗力强： 喜湿冷(水中:23周 冰冻:数月) 怕干

3、热(60 15分钟或煮沸即可灭活) 化学消毒剂可灭活 2022-3-224Virulence characteristicsu毒素：菌体裂解时释放 cytotoxins , Invasion factorsn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 2022-3-225表面抗原与毒力有关,具有抗吞

4、噬和抗溶菌的作用 Vi抗原抗原抗原性弱，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因为为所以所以本本质质Vi antigen impedes phagocytosis and contributes to the ability of S. typhi to survive normal host-defense mechanisms.2022-3-226流行病学 Epidemiology （一）How is typhoid fever spread?u传染源:患者和带菌者 The carriers and the people who have active t

5、yphoid fever shed S. Typhi in their stools or urine.u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. 2022-3-227u传播途径: 消化道传播 如污染的

6、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.u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)2022-3-228ChickenTurkeyDuckFeed / waterEnvi

7、ronmentBreeder flockEggsRodents and wild birdsProcessingManSources of contaminationnMost common vehicles are beef, turkey, eggs, pork, and chicken2022-3-229流行病学 Epidemiology （二）u世界各地均有本病发生，热带和亚热带为多u常年发病，夏秋为多u儿童和青壮年为多，无性别差异u发病与卫生、经济条件相关2022-3-2210Epidemiology nIn 2000, the global annual incidence of

8、typhoid fever was estimated to be around 21.7 million cases with 216,510 deaths per year. DISTRIBUTION OF TYPHOID u我国发病率4.08-10.45/10万， 每年报告病例5.1-12万例 2022-3-2211发病机制 Pathogenesis (一)u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。 uAfter being swallowed, the S. typhi bacteria are taken in by mononuclea

9、r phagocytes and multiply within these cells. This period of time is the 10 to 14-day incubation period of typhoid fever2022-3-2212发病机制 Pathogenesis (二)u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。nWhen huge numbers of bacteria fill an individual phagocyte, they spill out of the cell and

10、into the bloodstream, where their presence begins to cause symptoms. 2022-3-2213发病机制 Pathogenesis (三)u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。uThe bacteria move from the bloodstream into certain tissues of the body, including the gallbladder and lymph tissue of the intestine. The tissues

11、 response to this invasion causes severe inflammationand large of bacteria were secreted in patients stool.2022-3-2214发病机制 Pathogenesis (四)u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。2022-3-2215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

12、液再次进入血液第一次菌血症第二次菌血症2022-3-2216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.2022-3-2217病理 Pathology（三）u第2周:肿大的淋巴结坏死u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u第4周:溃疡逐渐愈合,不留疤痕2022-3-2218临床表现 Clinical characteristicsn潜伏期723天,一般为1014天nThe Incubation Period: From 7

13、days to over 23days, usual range 10-14 days. 2022-3-2219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2022-3-2220极期 Fastigium (第2,3周): 高热,稽留热为主，持续1014天u消化道症状：纳差,腹胀,便秘(少数有腹泻), 可有右下腹轻压痛；u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u循环系统症状：相

14、对缓脉或重脉。u肝脾肿大，玫瑰疹。2022-3-2221u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。u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.2022-3-2222 What are the signs and symptoms of typhoid fever?na sustained fever as high as 39 to 40 C；nfeeling weak, or loss of app

15、etitendiarrheanconstipationnstomach painnheadachenmalaisennonproductive coughnslow heart rate (bradycardia)nHepatosplenomegalyn rose spots2022-3-2223五种临床类型 Clinical typeu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。u普通型(moderate type)：u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

16、脾大较明显。u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。u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。2022-3-2224n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。n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。2022-3-22

17、25辅助检查 Laboratory test（一）外周血检查(Test of peripheral blood)u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 disappearu白细胞总数、中性粒细胞减少 leukocytopenia2022-3-2226辅助检查 Laboratory test（二）-病原学培养血培养骨髓培养粪便培养尿培养十二指场引流胆汁培养阳性率12周时阳性率最高(8090%).第4周后不易检出.复发时可再度阳性阳性率高于血培养.且阳性持续时间长34周的阳性率较高34周有时可为阳性.很少应用.可作为带菌者的诊疗评价

18、已用抗菌素者,做血块培养,可增加阳性机会尤其适用于已用抗菌素治疗,血培养阴性者2022-3-2227 Isolation of S. typhi from blood, stool, or other clinical specimennBlood cultures usually become positive in the first week of illness in 80% of patients who have not taken antibiotics. nBone marrow cultures remain highly (90%) sensitive. nCulture

19、of intestinal secretions can be positive despite a negative bone marrow culture.n If blood, bone marrow, and intestinal secretions are all cultured, the yield of a positive culture is 90%. nStool cultures while negative in 60 to 70% of cases during the first week, can become positive during the thir

20、d to the fourth week of infection in untreated patients.2022-3-2228辅助检查 Laboratory test （三）肥达反应 Widal testuO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。u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。u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。u存在假阳性和假阴性。2022-3-2229u肥达反应对诊断

21、伤寒仅有辅助辅助作用,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. 2022-3-2230辅助检查（四）-分子生物学技术uDNA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.2022-3-2231并发症 complicationsn肠穿孔:最严重,发生率3%4%,

22、见于极期,部位(回肠末段）n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. 2022-3-2232complicationsu中毒性肝炎 hepatitis u中毒性心肌炎 myocarditisu支气管炎或支气管肺炎 pneumoniau急性胆囊炎 cholecystitisu周围神经炎 peripheral neuritis2022-3-2

23、233诊断(Diagnosis)u流行病学资料:u临床表现:u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2022-3-2234DiagnosisnClinical Criteria Insidious onset of sustained fever, headache, malaise, anorexia, relative bradycardia, constipation or diarrhea, and nonproductive cough. nLaboratory Criteria for Surveillance Purposes Isola

24、tion of S. typhi from blood, stool, or other clinical specimen. nSurveillance 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. nNOTE: Isolation of the orga

25、nism is required for confirmation. Serologic evidence alone is not sufficient for diagnosis. 2022-3-2235全国伤寒、副伤寒监测方案全国伤寒、副伤寒监测方案 -病例定义 n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。2022-3-2236n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。2

26、022-3-2237确诊病例n临床诊断病例+以下项目之一者n 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；n 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。2022-3-2238Differential 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 acutemi

27、liarytuberculosis 革兰阴性杆菌感染 Gram negative bacteria infection 恶性组织细胞病 malignant histiocytosis 2022-3-2239治疗（一）：一般治疗u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u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u对症处理： 发热:物理降温为主 便秘:灌肠,开塞露等,禁用泻药禁用泻药 毒血症明显可予地塞米松 24mg/d,13d)2022-3-2240治疗（二）：病原治疗u喹诺酮类药物：首选 孕妇和儿童

28、禁用如：氧氟沙星 0.2 Bid 疗程(体温正常后继续用1014天)u三代头孢类：如：头孢他啶 2.0 Bid(成人) 疗程(1014天) 50mg/kg Bid(儿童) 2022-3-2241氯霉素n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。n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。n耐药菌的出现 2022-3-2242慢性带菌者的治疗u喹诺酮类：例：氧氟沙星 0.3 Bid 疗程6周u磺胺类：例

29、：复方磺胺甲恶唑 2片 Bid 疗程13个月u氨苄西林+丙磺舒 疗程46周 36g/d 11.5g/du内科疗效不佳或合并胆囊炎，胆石症者，可手术切除胆囊2022-3-2243治疗（三）：并发症的治疗u肠穿孔：u肠出血：u中毒性心肌炎：2022-3-2244TreatmentnAntibiotics are the treatment of choice for typhoid fever. Quinolones are extremely effective and lowers fever fairly quickly.n Chloramphenicol (Chloromycetin) i

30、s also the effective medication for S. typhi. The patients symptoms begin to improve slightly after only 24-48 hours of receiving the medication. nCarriers of S. typhi requires treatment with one or even two different medications over a period of four to six weeks. Treatment with oral amoxicillin, T

31、MP-SMZ, ciprofloxacin, or norfloxacin has been shown to be 80% effective in eradicating chronic carriage of susceptible organisms.2022-3-2245n Those with severe gastrointestinal bleeding may require intravenous (IV) feedings until they are able to digest food. nIn 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 treatm