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1、结 核 病 Tuberculosis(TB),In 1882 Koch demonstrated that Mycobacterium tuberculosis is the causative agent of TB in human.TB can involve any and every organs,but primary pulmonary tuberculosis is most common form of TB.More and more active cases of TB is reported because HIV infection and drug-resistan
2、t TB.WHO declared the global emergency of TB in 1993,unfortunately,the incidence of TB in China is high.,1.Generality,结核病的历史,尽管是一种古老的疾病，仍是重要的公众健康的问题；在发展中国家结核病仍在蔓延：-贫困，-快速的城市化进程，-人类免疫缺限病毒感染伴有免疫功能低下，-新的药物耐药。,历史-三个发现,Koch，1882,BCG研制成功，1908，,SM的发现-1944，1950年-PSA、INH、RFP相继问世,可喜三个里程碑已是已是比较遥远的历史,结核感染后发展趋势,
3、12 M,年龄小和或免疫低下儿童原发感染后不久就展成活动性结核病,2.Etiology This agent is a member of the family Mycobacteriaceae,the chief characteristic of which is acid fastness.Dried tubercle bacilli kept in the dark may survive and remain virulent for many months,but they can be killed by exposure to direct sunlight at 120min
4、.,Mycobacteria grow slowly,isolation from clinical specimens on solid synthetic media usually takes 3-6weeks,and durg senceptibility testing requires an additional 4 weeks.Mycobacteria can be detected in 1-3 weeks in selective liquid medium using radiolabeled nutrients(BACTEC system),and durg sencep
5、tibility can be determined in an additional 3-5 days.,3.Epidemiology,TB infection occurs after the inhalation of infective droplet nuclei containing M.TB.TB case rates began to rise in USA in 1985.Environmental factors such as socioeconomic status,overcrowding,poor nutrition,inadequate health care p
6、lay the major role in incidence.Genetics may play a small role,Transmision,Transmision of M.TB is person to person.Transmision rarely occurs by direct contact with infected discharge or contaminated fomite.Chance of transmision increases when patient has acid-fast smear of sputum,extensive upper lob
7、e infiltrate or cavity,severe and forceful cough.,Most children are infected with M.tuberculosis in their home by someone close to them in US.Childhood TB also occur in elementary school and high school,nursery school,day care center,and so on.There is a slight predominance of TB among females in ch
8、ildhoodTB is most common in children 5 years of age,4发病机制,结核菌,胞内菌,细胞免疫,杀灭细菌,局部病灶,播散,体液免疫,抗体,变态反应,PPD阳性,5诊断,1力求早期诊断，以改善严重型小儿结核的预后2小儿的特殊性，病原学确诊困难3小儿结核的诊断多以临床诊断为主，强调综合分析综合判断,结核病,临床诊断,病原诊断,病史,结核中毒症状,接种和接触史,PPD皮试,ESR,结核抗体,X线胸片,纤支镜检查,淋巴结活检,染色或培养找结核菌,找结核菌抗原,？,美国结核病控制指南建议计分方法,临床特征 计分(分)咳嗽4周 1肺炎治疗3周无改善 1发热2周
9、或不能用其他原因解释 1麻疹后2个月尚未恢复 23岁以下近3个月体质量不增 13岁以上小儿体质量不增或下降 2营养不良治疗无效 1严重营养不良住院治疗无效 2与抗酸染色阳性者共同居住 2母亲或生活密切接触者抗酸染色阳性 4接种过卡介苗(BCG)-1,02分，可能性很小；34分，可疑：TST、胸部X片；5分或以上，可能性很大，临床治疗,Tuberculin skin test:PPD test,Host-related factors:very youth age;malnutrition;immunosuppression by disease or drugs;viral infection
10、;live-virus vaccines;overwhelming TB can depress skin test reaction.Most common reasons of false-negative are poor technique and misreading results.False-positive can be caused by cross-sensitization to antigens of NTM,结核菌素试验结果判断,PPD皮试,阳性,接种过卡介苗,感染过结核,活动性结核依据之一,新近感染结核,阴性,未感染过结核,变态反应前期,假阴性反应,技术误差,How
11、 to evaluate result of skin test,Appropriate size of induration a positive skin test varies with related epidemiologic and risk factors Children with no risk factors for TB,skin test reactions are usually false positive.Children with high risk factors for TB,a reactive area 10mm is considered positi
12、ve,PPD阳性,自然感染,接种反应,反应强，10mm阳性反应时间长，7天阳性持续时间长硬结质地较硬、边界清楚,反应弱，10mm阳性反应时间短，3天阳性持续时间短硬结质地较软、边界不清,全血特异性IFN-检测：与PPD试验有同样的诊断意义,T SPOTTB 测 定 法：也 称 为 酶 联 免 疫 斑 点 技 术(ELISPOT)，是一种体外检测单个核细胞水平特异性抗体（干扰素）分泌功能的免疫学新技术。结核分枝杆菌具有特异的抗原，包括早期分泌抗原靶6(ESAT-6)和培养滤液蛋白(CFP-10)。,Liebeschuetz S Lancet，2004364：2196-2203,全血特异性IFN-
13、检测：比PPD特异性、敏感性高,结核杆菌特异抗原刺激致敏T细胞释放的IFN-；与传统TST中使用PPD相比特异性较高，这些抗原不存在卡介苗疫苗株和大部分环境里的分枝杆菌上；有免疫系统受损或是免疫功能不全不受影响，比TST试验的敏感性好。,阳性预测值为49.6%(CI,40.6%-58.6%),阴性预测值85.9%(CI,78.5%-93.3%),结论：较高的T-SPOT.TB阴性预测值提示阴性结果有助于排除活动性结核病的诊断，较低的T-SPOT.TB阳性预测值限制其在诊断活动性结核病的应用。,TsT和ELISPOT对293例结核患儿检测结果,TsT和ELISPOT对293例结核患儿检测结果,免
14、疫系统受损或是免疫功能不全不受影响,6治疗,（1).治疗原则：早期，联合，适量，规则，分段，全程,(2)抗痨药物,1INH、RFP：全杀药，酸、碱环境中均有效2SM、PZA：半杀药，前者在碱性中效佳；后者在酸性中较好3EMB、ETH：为抑菌剂4其他药物：喹诺酮类，环丝氨酸及其他抗痨药物的衍生物,(3)化疗方案,1标准疗法：INHRFP：疗程为912月2短程疗法：是结核病控制的一次革命性变革。具体方案：2HRZ4HR；2SHRZ4HR；2EHRZ4HR,(4)预防性化疗,适应征：1密切接触者；23岁，未接种卡介苗而PPD阳性；3PPD最近由阴性转阳性；4PPD阳性结核中毒症状；5PPD阳性者患麻
15、疹或百日咳；6PPD阳性者需使用免疫抑制剂方法：INH 疗程69月。,(5)潜伏结核感染的治疗,定义：由结核菌感染引起的结核菌素试验阳性，X线胸片或临床无活动性结核证据者。INH：69月，适用于一般结核感染患者,(6)抗痨药物的毒副作用,1药物的过敏反应2药物的毒性作用3INH：肝损，周围神经炎4RFP：肝损，过敏反应5PZA：肝损6SM：肾、耳毒性7EMB：视神经的损害,5的病人难以完成化疗,7.Prevention,Case finding and treatmentBCG vaccinationINH treatment for prevention TB,BCG vaccine has
16、 been used since 1921.However,the data concerning its use are variable and inconsistent.The protective efficacy of the first dose of BCG vaccine against miliary tuberculosis or tuberculous meningitis is remarkably important.Nevertheless,results regarding pulmonary tuberculosis have been inconsistent
17、,either showing no efficacy or a protective efficacy rate around 80%.,原发性肺结核,primary pulmonary tuberculosis,一概述,原发性肺结核(primary pulmonary tuberculosis)，是原发性结核病中最常见者，主要包括原发综合征和支气管淋巴结核。前者由肺原发病灶、局部淋巴结病变和两者相连的淋巴管炎组成。,小儿原发性肺结核的特点：,1、组织及器官对结核菌高度敏感2、淋巴系统广泛累及3、全身播散的倾向4、以钙化为主的愈合方式,二病理转归,原发结核,吸收好转,恶化,进展,钙化,硬结,
18、血行播散,空洞,干酪肺炎,胸膜炎,肺不张、肺气肿,免疫功能低下患儿常伴有种种恶化进展:1、结核性胸膜炎及叶间胸膜炎2、肺原发病灶周围炎或淋巴结周围炎3、原发空洞形成4、支气管结核5、干酪性肺炎6、急性粟粒性结核及结核性脑膜炎,三临床表现,1结核中毒症状2疱疹性结膜炎、皮肤结节性红 斑和多发性一过性关节炎3、胸内肿大淋巴结的压迫症状4、体查发现周围淋巴可有肿大5、部分患者可无明显的临床症状,四、诊断,1、病史临床表现2、PPD皮试3、X胸片胸部CT检查4、纤维支气管镜检查5、实验室检查,气道受压的症状 的鉴别,哮喘；肉样瘤变、恶性纵隔肿瘤（淋巴瘤、成纤维细胞瘤）；慢性真菌感染（组织胞浆病）；支原体感染。,纵隔淋巴结增大表现,可有喉返神经麻痹；淋巴管堵塞（乳糜胸）；心包炎；气管食管瘘、可累及胸壁和胸骨；受累结节和气管治愈后，纤维化可能导致永久性支气管狭窄或支气管扩张。,
