【作者】 张岚；

【导师】 成诗明； 陈伟；

【作者基本信息】 中国疾病预防控制中心 ， 公共卫生， 2008， 硕士

【摘要】 背景结核病是严重危害人类健康的主要传染病之一,在全球范围内广泛存在。中国是全球22个结核病高负担国家之一。目前耐药性已经成为我国未来结核病控制起主要限制性作用的因素和需要重点关注的问题。2000年第四次全国结核病流行病学抽样调查报告(简称流调)资料显示:我国肺结核病人获得性耐药率46.5%,获得性耐多药率17.1%。2003年,世界卫生组织/国际抗结核及肺部疾病联合会(WHO/IUATLD)全球抗结核药物耐药监测结果证实,获得性耐药率中值为23.3%(0-82.1%),结核病耐多药率(MDR-TB)中值为7.7%(0-58.3%),已治疗的病人与未治疗病人相比较,耐药率高4倍,而MDR-TB高10倍。复治涂阳肺结核病人的耐药性关系到治疗的成败,了解研究地区耐药性的特征及其影响因素,提出有针对性地控制耐药性发生的措施和建议,有助于减低耐药性产生,提高肺结核病人的治愈率和治疗成功率。目的1、了解甘肃省三个地区复治涂阳肺结核病人的耐药情况,分析耐药水平和耐药特征;2、了解甘肃省三个地区复治涂阳肺结核病人的耐药性影响因素及其治愈率的影响因素;3、有针对性地提出改善甘肃省耐药性发生的政策性措施和建议,有助于提高全省肺结核患者的治愈率和肺结核病人治疗成功率。方法以非概率目的抽样方法,将甘肃省在爱德基金会与世界宣明会项目期间进行药物敏感性试验的项目地区,甘南、临夏、定西三市(州)作为研究现场,将2004年9月至2005年8月登记管理的所有复治涂阳病例以县为单位累计,共166例复治涂阳肺结核病例纳入,作为研究对象。1、采取连续性调查方法,对研究对象进行定量研究。2、定量研究通过问卷调查及监测资料相结合来实现。数据使用SPSS13.0软件进行统计分析,采用x~2检验和logistic回归多因素分析。结果1、复治涂阳肺结核病人的耐药水平和耐药特征三地区复治涂阳肺结核监测病例总耐药率为50.0%,耐多药率为24.1%,高于全国2000年第四次流调结果继发耐药率(46.5%)和MDR率(17.1%)水平。在本次监测的166株结核分枝杆菌株中,耐单药率为13.9%(23/166),四种主要抗结核药物以两种一线药物单耐药为主,两种一线抗结核药物INH和REP的耐药率分别为32.5%、35.2%,高于全国流调数据(31.0%,29.5%)。四种监测的药物中以REP耐药率最高,四种抗结核药物耐药率之间比较有显著性差异。不同年龄、性别、民族的复治涂阳肺结核的耐药率无显著差异。不同地区的耐药率与耐多药率存在统计学差异,农村耐药率高于城镇。复治涂阳不同登记分类中,以临夏登记分类的其他复治耐药率最高为34.0%,不同类型复治涂阳肺结核患者耐药率之间变化存在统计学差异。本次研究提示:患者的文化程度普遍偏低,初中及以下所占76.5%,受文化程度所限,对结核病认知差,易造成治疗不规律和治疗失败,产生耐药性。初治时没有接受过健康教育的患者其耐药率明显高于接受了结核病相关知识的患者,不规则治疗或中断治疗其耐药率高于其他规律治疗者。初治治疗管理的方式不同其耐药率差别有显著性意义。2、复治涂阳肺结核病人耐药的影响因素本文研究结果显示:单因素分析居住地不同、文化程度、不同登记分类、初治诊断机构、是否接受宣传教育、累计用药时间、有无合并症、督导者、督导管理方式、既往不规则治疗和中断治疗等对耐药率变化的差异有显著意义。进一步对p＜0.05的变量进行多因素Logistic分析,患者的受教育程度、患者居住地区、有无合并症、患者在化疗过程中所接受的督导方式是甘肃三地区耐药的主要影响因素。3、复治涂阳耐药肺结核病人治疗转归情况及影响因素本次调查显示,甘肃三地区复治涂阳耐药肺结核患者的化疗效果(治愈率)与三地区人口学特征有关,在单因素分析中,患者的年龄、不同民族、文化程度、职业和不同居住地与患者的治愈率有关。耐药数量、不同复治类型、初治时2月末阴转、是否中断与中断次数等为影响疗效的因素。多因素分析:患者年龄与耐药数量为影响疗效的主要因素。结论甘肃三地区总耐药率与耐多药率均高于全国流调水平。但各地区之间耐药率水平不一,临夏地区耐药率高于其他两地区,耐药药物的顺位不尽相同。提示三地区应加强耐药病人的诊断治疗,同时加强肺结核病人的督导管理工作,减少耐药病人的产生。农村耐药率和耐多药率显著高于城镇。说明我省三地区农村的结核病防治工作比较薄弱,也表明对抗结核药物管理的混乱以及各级医院和诊所的医生用药不规范。复治涂阳不同登记分类中,初治失败病人的耐药率和耐多药率均高于其他类型,这可能与初治失败病例的初始耐药有关,应加强初治耐药监测,对初治失败病例是否探讨给予个体化化疗方案。在本次研究中,我们发现综合性医院在总病人中所占比例50%以上,是造成复治病人及其耐药产生的首要因素。由于患者未在结防专业机构就诊或其他的原因,造成患者未能得到合理的化疗和管理,甚至已经产生耐药,这与非结防机构对结核病人归口管理落实不够,截留不规律医治有关。初治时没有接受过健康教育的患者其耐药率明显高于接受了结核病相关知识的患者,提示加强宣传教育,提高患者自我意识,减少中断、可以使患者完成规律化疗疗程,降低耐药甚至耐多药率,减少传染源。患者的受教育程度、患者居住地区、有无合并症、患者在化疗过程中所接受的督导方式是甘肃三地区耐药的主要影响因素。女性治愈率低于男性,这可能与传统风俗习惯有关,女性特别是农村女性对自己的身体状况不顾及,而往往会不规律或不满疗程结束治疗;老年患者由于对药物的耐受能力有限,同时部分老年患者是多次治疗的慢性患者,而在登记治疗时没有将病史陈述,提示今后应关注弱势群体的耐药性监测与防治。耐多药的治疗效果比耐单药更差。因此,加强对治疗病人的督导管理,减少复治耐药病人的产生非常重要。结核病的耐药问题已经成为我省三个地区结核病防治的难点,耐药是影响复治疗效的重要因素,高耐药和耐多药不可避免地伴随着复治的低治疗成功率。对于预防耐药及耐多药结核病的产生,应及时根据痰结核菌药物敏感性试验的结果,以便制定合理的化疗方案,同时严格执行WHO所推行的直接督导下的短程化疗(DOT)方案,在强化规范治疗的基础上减少复治耐药传染源的产生。更多还原

【Abstract】 BackgroundTuberculosis is one of the main infectious diseases that are harmful to the health of people all over the world.China is one of the 22 high-burden countries and ranked the second in the list in terms of the number of tuberculosis(TB) patients.China started DOTS since 1990s to control tuberculosis and gained a significant achievement.However,drug-resistance is one of the most problems that it limits and effects our tuberculosis control strategy from now on.According to the results of the fourth national epidemiological sampling survey on TB conducted in 2000,China was one of the highest TB epidemic countries in the world characterized by the secondary resistance rate was 46.5%,and 27.8%for the total drug-resistance.The multi-drug resistance(MDR) rate was 17.1%,and the total rate 10.7%for the secondary resistance.The drug-resistance was the world problem in 2003,that the WHO/IUATLD drug resistance surveillance project had proved by half of the 109 countries and regions.The median of the drug-resistance rate was 23.3%(0-82.1%) and 7.7%(0-58.3%) for MDR-TB among the secondary resistance cases.Compared the retreated cases,the 4 times resistance rate with those never re-treatments,and 10 times for the MDR-TB.The resistance of the re-treatment patients is concerned the results of the full intermittent chemotherapy of the TB cases.To investigate and analyze the factors of TB drug-resistance in the three cities in Gansu,and provide the available advice for the improvement successful rate of TB cases.ObjectiveTo survey the sustain of drug-resistant and to analyze its levels and characters of the registered and management re-treatment smear positive patients among three citiesTo survey the factors influencing of drug-resistance and the cure rate for the re-treatment smear positive patients among three cities.To carry out the available and suitable methos or stratigies and to improve the cure rate of the re-treatment smear positive patients among three cities.MethodsGannan,Dingxi,Linxia three prefectures which implement the AD and the world XMH project were selected at the first stratify by no percentment aim random sampling method.And to investigate and analyze the sustain of treatment of the re-treatment smear positive patients among three cities,while analyzing drug-resistant levels and characters of the registered and management re-treatment smear positive patients among three cities of the whole year from 2004.9 to 2005.8.Totally 166 re-treatment smear positive pulmonary tuberculosis patients were eligible.1.To analyze retrospectively totally re-treatment smear positive pulmonary tuberculosis patients and use the quantities methods.2.To implement the study and combine the surveillance data and survey sample.SPSS 13.0 was used to analyze data.Chi-square test and multi-variance unconditional logistic regression were used to analyze the factors influencing of the re-treatment smear positive pulmonary tuberculosis patients among the three prefectures..ResultsThe TB drug-resistance and MDR-TB rates of the three prefectures in gansu are 50%and 24.1%,respectively.Those are higher than the national survey levels.among of the whole sputum TB samples,the single resistance rate is 13.9%.The mostly cases of initial resistance resisted to one drug,and those of acquired resistance resisted to multi 4 drugs.There was significant difference among the three prefectures drug-resistance rates.REP is the highest drug resistance rates of the four anti-tb drugs.The drug-resistance rates of INH and REP are 35.5%and 32.5%respectively and higher than the national TB level(31.0%,29.5%).There is no significant deference among the age,sex.nation of the three prefectures.the drug-resistance in the countryside is significant higher than that of the city and town.the others re-treatment smear positive drug-resistance rate in Linxia is the highest of the monitored prefectures(34.0%).The result of this study show that this may associate with factors,such as economic status,education level,accessibility to health care.There are 21.1%of the all patients detected by the TB professial dispensary,However,the initial smear positive TB cases were detected by the general hospital and town private initial,and occupied 51.8%,6.6%,28.9% respectively.The new smear positive TB patients who have not been taught the TB healthy knowledge,have significant higher drug-resistance rate than that of the others.The results of this study shew that the risk factors of MDR-TB rate were living conditions,the education,the model of supervision and the complication,the difference has very significant.To analogize the factors using the multi- Logistic statistics,the living condition,the education,the other disease with TB,and the methods of supervision.It is relate to the population characters of the study units of three prefectures in Gansu including age,sex,education,status and living-conditions.Univariate analysis showed that the following 3 variables were correlated to t he efficacy of re-treatment:drug resistance,different retreated types,and the negative rate of the 2 month treatment.In multivariate analysis,it was confirmed that drug resistance,and the patients age were significantly associated with retreated outcomes.ConclusionThe drug-resistance rate and MDR-TB are both higher than the average level. but the drug-resistance level of three prefectures and the anti-drug resistance rage grade is not same.the drug-resistance rate of Linxia prefecture is significant higher than the other districts.To improve the treatment of drug-resistance cases,and improve the management and supervision of the TB patients,reduce the drug-resistance cases.The drug-resistance in the country is significant higher than that of the city and town,it is shown that we are weak of TB control and prevention in the three prefectures.And the doctors of the universal hospitals and private clinic have not available use the TB drugs.In this study,it is shown that the status of the re-treatment smear positive TB patients is very complicate,the reasons which effect the drug-resistant are more, and which had closely relationship or limited each other.General hospital occupy 50%of all patients the proportion,it is the main factor to lead to re-treatment and drug-resistant.because the TB patients initial treat units were not the TB professional institute but the general or private hospitals,it led that they had not the suitable treatment and management mode beside to irregularly treated and to lead to drug-resistant.The new smear positive TB patients who have not been taught the TB healthy knowledge,have significant higher drug-resistance rate than that of the others.it shows to improve and enhance the health promotion of TB,and to improve the patients awareness of themselves to decline the outgeneral treatment and drug-resistance.There are some main risk factors such as knowledge,the living condition the other disease and the supervision during the initial treatment.It is possible for the traditional custom the female cure rate of TB is lower than the male.the old have high drug-resistance rate.The effect of treatment of the MDR-TB less than that of the single, therefore,enhance management of TB patients during the treatment.and to reduce the drug -resistance of re-treatment of smear positive cases.It not only reduce the TB patients economic burden but also decline the drug-resistance.The TB drug-resistant has been the difficult problem,and the drug-resistant is the main reason,high drug-resistant or MDR-TB reduce the successful rate of treatment.To timely be drug-resistant surveillance and to carry out the available and suitable chemotherapy regimens,withwhile implementing direct observe treatment short-course by the WHO,to reduce the infectious disease of re-treatment smear positive TB patients.更多还原