耐多药结核病的分子机制研究进展

耐药结核病尤其耐多药结核病的发生和流行是当前结核病疫情回升的主要原因之一,成为结核病控制的重要障碍.本文从耐多药结核病的发展现状出发,归纳了各种耐单药结核病、耐多药结核病已有的分子机制研究,从耐多药结核病发病治疗现状、分子生物学、耐多药检测技术角度指出了目前国内外耐多药结核病已有的分子机制研究成果,在此基础上对耐多药结核病发病的分子机制规律的研究前景予以了展望.     

耐多药结核病的分子机制研究进展

耐药结核病尤其耐多药结核病的发生和流行是当前结核病疫情回升的主要原因之一,成为结核病控制的重要障碍.本文从耐多药结核病的发展现状出发,归纳了各种耐单药结核病、耐多药结核病已有的分子机制研究,从耐多药结核病发病治疗现状、分子生物学、耐多药检测技术角度指出了目前国内外耐多药结核病已有的分子机制研究成果,在此基础上对耐多药结核病发病的分子机制规律的研究前景予以了展望.     

耐多药结核病的分子机制研究进展

耐药结核病尤其耐多药结核病的发生和流行是当前结核病疫情回升的主要原因之一,成为结核病控制的重要障碍.本文从耐多药结核病的发展现状出发,归纳了各种耐单药结核病、耐多药结核病已有的分子机制研究,从耐多药结核病发病治疗现状、分子生物学、耐多药检测技术角度指出了目前国内外耐多药结核病已有的分子机制研究成果,在此基础上对耐多药结核病发病的分子机制规律的研究前景予以了展望.     

耐多药结核病诊断方法研究进展

耐多药结核病的防治对于结核病的防控具有重要意义,已成为结核病防治的难点和热点问题。早期对结核病患者进行耐多药检测能够提高耐多药结核病患者的治疗成功率。耐多药结核病的诊断方法包括传统的培养方法及新型分子生物学诊断方法。作者对耐多药结核病的诊断方法进行综述,以期为耐多药结核病防治提供科学依据。     

广西壮族自治区贵港市涂阳肺结核患者耐药现状调查

当前我国耐多药肺结核危害日益凸显,不久的将来可能出现以耐药为主的结核病流行态势,对我国结核病控制造成严重威胁。为了解本地区耐药肺结核病的流行现状、流行规律及影响因素,给政府合理制定本地区耐药肺结核防控策略提供科学依据,对贵港市所辖城区和桂平市涂阳肺结核患者进行了耐药性现状调查。     

山东地区登记肺结核患者一线抗结核药物耐药特征分析

正结核病是危害人类健康的慢性传染疾病,给人类的呼吸道造成威胁。复治肺结核虽然在肺结核病中所占的比例较低,但如果不积极的治疗,有可能成为肺结核病的主要来源。复治肺结核患者的耐药情况和流行病学特征在肺结核的防控和治疗上具有重要的意义。耐药结核病,特别是耐多药及泛耐药的流行与传播,给结核病的防控带来巨大压力。为了解山东地区肺结核患者结核分枝杆菌耐药的趋势,本研究对山东地区登记肺结核患者一线抗结核药物耐药特征进行分析。     

耐多药结核病诊治进展

介绍 随着耐药结核菌耐药范围不断扩大,广泛耐药结核病逐渐成为全球健康问题。耐多药结核病治疗难度大、费用高,在许多地区甚至无法治愈[1]。随着HIV流行导致院内耐多药结核病例数量激增,耐多药结核病的流行及二线抗结核药物广泛应用和使用不当,是目前耐多药结核病产生的关键因素。     

881例疑似耐多药肺结核患者的耐药性分析

分析北京市结核病防治机构(简称“结防机构”)和结核病定点医院疑似耐多药肺结核患者的耐药状况,为耐多药肺结核的临床诊断、治疗和防控工作提供参考。     

左氧氟沙星辅助治疗127例耐多药肺结核临床疗效研究

<正>耐多药肺结核(MDR-TB)是指体外分离的结核菌至少同时耐受传统一线抗痨药物异烟肼和利福平的结核病。伴随全球结核病耐多药上升,我国耐多药结核病流行亦日益严峻,目前已成为全球27个耐多药结核高负担国家之一,每年新增患者12万例[1]。据报道,9.4%MDR-TB为广泛耐多药[2]。因此,积极寻求新的高效抗结核药物成为广大医务科研工作者日益关注的课题。本研究应用左氧氟沙星辅助治疗127例耐多     

中药治疗耐多药结核病的研究进展

耐多药结核病是由耐多药结核分枝杆菌原发感染或抗结核药物用药不当产生继发耐药所致,已成为世界卫生组织2035年终止结核病流行策略的一大阻碍,目前治愈率不理想。因此,迫切需要开发新的抗结核药物或治疗方法。中医药在减轻结核病症状、联合西药治疗耐多药结核病,以及提高患者针对结核分枝杆菌的免疫水平方面已有很多研究。作者对中药抗结核治疗的体外及人体试验研究进展进行综述,以期为临床医生提供更多的有关中西医结合治疗结核病的思路和策略。     

Multidrug-resistant and extensively drug-resistant tuberculosis: implications for the HIV epidemic and antiretroviral therapy rollout in South Africa

Drug-resistant tuberculosis (TB) is emerging as a major clinical and public health challenge in areas of sub-Saharan Africa where there is a high prevalence of human immunodeficiency virus (HIV) infection. TB drug-resistance surveillance in this region has been limited by laboratory capacity and the public health infrastructure; however, with the maturation of the HIV epidemic, the burden of drug-resistant TB is increasing rapidly. The recent discovery of large numbers of cases of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB in South Africa likely represents an unrecognized and evolving epidemic rather than sporadic, localized outbreaks. The combination of a large population of HIV-infected susceptible hosts with poor TB treatment success rates, a lack of airborne infection control, limited drug-resistance testing, and an overburdened MDR-TB treatment program provides ideal conditions for an MDR-TB and XDR-TB epidemic of unparalleled magnitude. In the present article, we review the history of drug-resistant TB in South Africa, describe its interaction with the HIV epidemic and the resultant consequences, and suggest measures necessary for controlling MDR-TB and XDR-TB in this context. A successful response to the emergence of MDR-TB and XDR-TB will necessitate increased resources for and collaboration between TB and HIV programs.     

Impact of the growing HIV-1 epidemic on multidrug-resistant tuberculosis control in Latvia.

Latvia, a country with levels of multidrug-resistant (MDR) TB among the highest in the world, experienced a 58-fold increase in HIV seroprevalence among all persons tested in the country from 1996 through 2001. In addition, HIV seroprevalence among TB cases increased from 0.4% to 1.4%, and among MDR-TB cases from 0% to 5.6% from 1998 through 2001, potentially compromising gains made to date in controlling the country's MDR-TB epidemic. The following will be critical to the future of MDR-TB control in Latvia: containing HIV transmission in the country, particularly among injection drug users who comprised 72% of all HIV cases reported in the country by the end of 2001, as well as 81% of all MDR-TB cases co-infected with HIV; expanding capabilities to more rapidly detect and successfully treat patients with MDR-TB; developing mutual TB control strategies between the National TB and AIDS programs; and continuing to improve institutional infection control measures, particularly in hospitals and prisons where an increasing number of persons infected with HIV come into contact with persons with active MDR-TB.     

Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing

South Africa has high rates of tuberculosis (TB), including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Expanding access to culture and drug susceptibility testing (DST) for TB diagnosis may help control this epidemic, but the potential impact of existing and novel TB diagnostics is uncertain. By fitting to World Health Organization epidemiological estimates, we developed a compartmental difference-equation model of the TB/HIV epidemic among South African adults. Performing culture and DST in 37% of new cases and 85% of previously treated cases was projected to save 47,955 lives (17.2% reduction in TB mortality, 95% simulation interval (S.I.) 8.9-24.4%), avert 7,721 MDR-TB cases (14.1% reduction, 95% S.I. 5.3-23.8%), and prevent 46.6% of MDR-TB deaths (95% S.I. 32.6-56.0%) in South Africa over 10 years. Used alone, expanded culture and DST did not reduce XDR-TB incidence, but they enhanced the impact of transmission-reduction strategies, such as respiratory isolation. In South Africa, expanding TB culture and DST could substantially reduce TB, and particularly MDR-TB, mortality. Control of XDR-TB will require additional interventions, the impact of which may be enhanced by improved TB diagnosis.     

Inadequacy of the current WHO re-treatment regimen in a central Siberian prison: treatment failure and MDR-TB.

Multidrug-resistant tuberculosis (MDR-TB) threatens the progress of global control efforts. Prisons represent a high risk setting for development and transmission of MDR-TB. In a Siberian TB referral prison (Kemerovo region), the treatment failure rate is 35% (June 1996-March 1997), despite implementation of a strict DOTS program and use of the World Health Organization Category 2 re-treatment regimen for all new cases. Among 164 patients (December 1997-March 1998), initial resistance to isoniazid and rifampin is 22.6%. Such a rate is a warning call to reconsider prison control strategies, and importantly, to address the treatment regimens necessary to combat an institutional epidemic of MDR-TB.     

The epidemic of multidrug resistant tuberculosis in China in historical and phylogenetic perspectives

ObjectivesFor the past decade, the epidemic of multidrug resistance tuberculosis (MDR-TB) stays high in China. We investigated the possible driving forces behind the epidemics from phylogenetic and historical perspectives.Methods420 representative strains were selected from the first national drug resistance survey based on their genotypes, drug susceptibility patterns and geographic information. We reconstructed the phylogeny by whole genome sequencing and compared it to the global phylogeny including MDR outbreaks reported in other settings. We estimated the historical trajectory of population dynamics by Bayesian Skygrid plot for all strains and MDR-TB alone. Integrating geographic information and mutations in drug resistance related genes, we investigated the spatial scale of transmission, recent selection of drug resistant mutant, and mechanism for fitness restoration.ResultsThree new subgroups within Beijing clade are described for the first time, but none of the MDR-TB outbreak strains reported in other high MDR-TB burden settings is identified. The overall epidemics experienced two successive phases of expansion at different rates between 1660s and 1950s, followed by a sharp decline till today. Four fifths of the clustered MDR-TB strains suggest transmission of DR strains and nearly half suggest recent selection of (additional) mutations in rpoB. Among all identified transmission events, about one fifth occurred between far distant locations. Possible intergenic and intragenic compensatory mutations both presented in our dataset at comparable frequencies.ConclusionsMDR-TB epidemic in China is not yet driven by the spread of a few highly successful clonal expansions but by repeated emergence of smaller and currently less successful clusters. However, internal migration and undertreatment could escalate MDR-TB epidemic. To prevent generating of drug resistance and restoration of fitness as well as to stop transmission of MDR-TB at early stage, national TB control program needs to strengthen management of floating populations and promote universal drug susceptibility testing in China.     

116例耐多药肺结核治疗转归情况影响因素分析

目的 探讨现阶段广州市耐多药肺结核患者化疗效果及相关影响因素。方法 采用logistic回归分析法对2003年1月至2007年12月在广州市胸科医院和广州市结核病防治所接受二线抗结核药物个体化治疗的116例耐多药肺结核患者化疗效果的诸多影响因素进行回顾性分析。结果 116例耐多药肺结核患者中男性75例,占64.7%;女性41例,占35.3%。年龄在20～84岁之间,平均年龄（44.26±17.57）岁。116例耐多药肺结核患者治愈率55.2%（64/116）;失败率25.0%（29/116）;因结核病死亡8例,因其他疾病死亡5例,死亡率11.2%（13/116）。多因素logistic回归模型分析结果显示：未规则治疗（OR=13.745;95%CI:3.147~60.034）、化疗方案不合理（OR=9.897;95%CI:2.528~38.747）、肺部空洞性病灶（OR=10.295;95%CI:2.002~52.949）是现阶段广州市耐多药肺结核患者治疗失败和病死的危险因素。结论 根据药敏结果和肺部空洞情况制定合理的治疗方案,强化对耐多药肺结核患者治疗督导管理,可以降低耐多药肺结核患者治疗失败率和病死率,控制耐多药肺结核的流行。     

Drug-resistant tuberculosis and HIV in Ukraine: a threatening convergence of two epidemics?

OBJECTIVE: To investigate anti-tuberculosis (TB) drug resistance rates in Donetsk Oblast, Ukraine, and to explore the association between the epidemics of human immunodeficiency virus (HIV) and multidrug-resistant TB (MDR-TB). METHODS: All consecutive newly diagnosed and previously treated patients with sputum smear-positive TB presenting to all TB units in Donetsk Oblast over 12 months were invited to take part in the study. A total of 1293 and 203 patients with TB were tested for HIV and MDR-TB in the civilian and penitentiary sectors, respectively. RESULTS: Of those enrolled for the study, 307 were HIV-positive, 379 had MDR-TB, and 97 had MDR-TB and HIV co-infection. MDR-TB rates in the civilian sector were respectively 15.5% (95%CI 13.1-17.8) and 41.5% (95%CI 36.4-46.5) in newly diagnosed and previously treated TB patients. Among prisoners, MDR-TB rates were 21.8% (95%CI 12.4-31.2) in new cases and 52.8% (95%CI 43.9-61.7) in previously treated TB cases. HIV status was significantly associated with MDR-TB (OR 1.7, 95%CI 1.3-2.3). CONCLUSIONS: High MDR-TB rates and a positive association between MDR-TB and HIV epidemics were found in Donetsk Oblast. Urgent measures to improve HIV prevention, control of drug-resistant TB and collaboration between HIV and TB control activities need to be implemented without further delay.     

MDR-TB--its characteristics and control in Asia-Pacific rim symposium in USJCMSP 10th international conference on emerging infectious diseases in the Pacific rim

The strategy of directly observed treatment, short course (DOTS) is achieving substantial progress in coverage and quality improvements worldwide. However, the problem of multi-drug-resistant tuberculosis (MDR-TB) has emerged as a new challenge to TB control in both developing and industrialized countries. The effort of various countries of the Pacific Rim to fight this problem, one of the negative progenies from the 20th century, was a major theme of the conference. Asia, WHO's Southwest Asia and Western Pacific Regions, combined, account globally for almost 60% of the newly occurring MDR-TB cases. However, the problem has likely been overlooked, as it was masked by taking averages for countries or wider regions. In this way, we may have lost sight of "hot zones" with extremely high prevalence of MDR-TB in smaller areas or in population segments. The problem was basically a result of the low-quality treatment program, but recently it may be amplified in some areas by the HIV epidemic that is another new challenge to TB strategies. So far, developing countries have not been taking active measures to manage this problem. However, some countries, such as the Philippines and Peru, have undertaken aggressive efforts, supported technically and financially by the new international mechanisms, such as the Stop TB Partnership and the Global Fund to fight AIDS, TB and Malaria. These efforts would be more effective if there were further technical innovation in diagnosis and treatment, supported by a strong political commitment.     

耐多药结核病患者外周血中多药耐药相关跨膜转运蛋白的表达

目的 评价耐多药结核病(MDR-TB)患者外周血中单核细胞P糖蛋白和多药耐药相关蛋白(MRP)表达水平的变化.方法选择2004年9月至2007年12月在武汉市结核病防治所住院治疗的MDR-TB患者89例为耐多药组,其中男52例,女37例;年龄17~62岁,平均(45±6)岁;平均病史3.5年;均符合MDR-TB的诊断标准.同期在武汉市结核病防治所住院的初治结核病患者55例为结核病组,其中男34例,女21例;年龄18~60岁,平均(48±8)岁;平均病史1.2年;痰涂片均为阳性.对照组为武汉市结核病防治所无肺结核史的工作人员31例,其中男19例,女12例;年龄25~62岁,平均(44±5)岁.抽取外周血,采用实时定量PCR法,分别检测单核细胞P糖蛋白和MRP的mRNA水平.多组间比较采用单因素方差分析,组间两两比较采用SNK-q检验.结果 耐多药组P糖蛋白mRNA表达的吸光度值(1.34±0.32)与结核病组(1.12±0.23)和对照组(1.05±0.16)比较,差异无统计学意义(F=0.536,P>0.05).耐多药组MRP的mRNA表达(3.45±0.43)明显高于结核病组(1.23±0.34)和对照组(1.04±0.12),3组比较,差异有统计学意义(F=24.241,P<0.05),耐多药组分别与其他2组比较,差异均有统计学意义(P<0.01).结论 MRP高表达与MDR-TB患者的多耐药存在一定的相关性.

Abstract：

Objective To evaluate the expression of P-glycoprotein (P-pg) and multidrug resistance-associated protein (MRP) mRNA levels in peripheral blood mononuclear cells from multidrug resistant tuberculosis (MDR-TB) patients. Methods The subjects of this study included 3 groups: a non-TB control group, a TB control group and a MDR-TB group. The 31 subjects in the non-TB control group were staff from Wuhan Tuberculosis Prevention and Treatment Institute. The 55 cases in the TB control group were in-patients during September 2004 to December 2007 who were diagnosed as having pulmonary tuberculosis. The 89 cases in the MDR-TB group were in-patients during the same period, but who were diagnosed as having MDR-TB. Peripheral mononuclear cells were isolated and mRNA levels of P-pg and MRP were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK q was used for comparison between 2 groups.Results There was no significant difference in the relative P-pg mRNA levels among the MDR-TB group (1.34±0.32), the non-TB control group (1.05±0.16) and the TB control group (1.12±0.23), F=0.536, P>0.05. The relative MRP mRNA level (3.45±0.43) was the highest in the MDR-TB group (3.45±0.43), as compared to the TB control group (1.23±0.34) and the non-TB control group (1.04±0.12), F=24.241, P<0.05. Conclusion Higher expression of MRP in peripheral mononuclear cells might be related to multidrug resistance in MDR-TB patients.