氟嗪酸、对氨基水杨酸异烟肼、利福喷丁三联治疗难治性肺结核疗效观察

目的　探讨氟嗪酸、对氨基水杨酸异烟肼 (力克肺疾 )、利福喷丁三联化疗方案治疗难治性肺结核的临床疗效。方法　将 83例难治性肺结核患者随机分成 2组。治疗组 4 2例患者采用氟嗪酸、力克肺疾、利福喷丁治疗 ,疗程 9个月 ;对照组 4 1例患者采用异烟肼、利福平、乙胺丁醇、吡嗪酰胺治疗 ,疗程亦为 9个月。观察并比较两组患者症状、痰菌、X线结果及药物副作用。结果　疗程结束后 ,治疗组痰菌阴转率和X线示病灶吸收好转率均明显高于对照组 (P <0 .0 0 5 )。结论　氟嗪酸、力克肺疾、利福喷丁三联用药是目前治疗难治性肺结核的较好化疗方案 ,且安全。     

Health service providers' perceptions of barriers to tuberculosis care in Russia

The Russian Federation has witnessed a marked rise in rates of tuberculosis (TB) over the past decade. Public health TB control institutions remain broadly modelled along pre-1990 lines despite substantial programmes of investment and advocacy in implementing the World Health Organization's 'Directly Observed Treatment--short course' (DOTS) strategy. In 2002, we undertook a qualitative study to explore health care providers' perceptions of existing barriers to access to TB services in Samara Oblast in Russia. Six focus group discussions were conducted with physicians and nurses from facilities in urban and rural areas. Data were analyzed using a framework approach for applied policy research. Barriers to access to care were identified in interconnected areas: barriers associated with the health care system, care process barriers, barriers related to wider contextual issues, and barriers associated with patients' personal characteristics and behaviour. In the health care system, insufficient funding was identified as an underlying problem resulting in a decrease in screening coverage, low salaries, staff shortages, irregularities in drug supplies and outdated infrastructure. Suboptimal collaboration with general health services and social services limits opportunities for care and social support to patients. Worsening socioeconomic conditions were seen both as a cause of TB and a major obstacle to access to care. Behavioural characteristics were identified as an important barrier to effective care and treatment, and health staff favoured compulsory treatment for 'noncompliant' patients and involvement of the police in defaulter tracing. TB was profoundly associated with stigma and this resulted in delays in accessing care and barriers to ensuring treatment success.     

Estimating the cost of TB and its social impact on TB patients and their households

Illness often poses a significant financial burden on individuals and their households, and tuberculosis (TB) is no exception. Although TB treatment is free in Nigeria, patients are likely to incur costs due to multiple visits during treatment. The purpose of this study was 1) to examine the health-seeking behaviour of TB patients and the costs borne by TB patients in Nigeria, and 2) to assess the social impact of TB disease on TB patients and their families/households. Of 260 TB patients surveyed, the majority (74.7%) were aged between 20 and 49 years. TB patients expended an average of US$52.02 (N = 8323.58, at the rate of US$1 = N = 160) per person on all visits associated with diagnosis and receipt of diagnostic test results. Overall, households experienced a shortfall of about US$57.30 (N = 9174.72) or 24.9% of income loss due to TB illness. Further analysis revealed that 9.7% of TB patients relied on children of school age or below to finance the costs of TB illness.     

丽水市结核病防治十年规划成本效益分析

目的:分析丽水市结核病防治10年规划的成本效益,评价结核病防治规划实施效果。方法:依据全国结核病防治规划(2001—2010)终期评估实施方案,自评与抽评相结合,分析9县、市、区的评估数据。结果:2001—2009年规划期间共减少约4 364例新发病例,所产生的直接效益约297.31万元,间接效益约6.70亿元,投入的社会成本为1 614.21万元,效益成本比为41.67。结论:丽水市结核病十年规划的实施完全符合疾病控制中的成本-效益原则,对降低丽水市结核病疫情具有重要意义。     

TB-LAMP法检测阳性痰标本再培养增加耐药肺结核发现率

目的 评价结核分枝杆菌环介导等温扩增法(TB-LAMP)在检测肺结核患者痰标本LAMP阳性后再培养及表型药物敏感试验对耐药结核分枝杆菌的检出效果。方法 随机收集2017年5月至2019年2月于遵义医科大学附属医院结核病专科门诊就诊和结核病区住院的疑诊肺结核患者7823例,每例留取4份痰标本,随机分别进行1份痰涂片镜检、2份传统罗氏培养和1份TB-LAMP核酸检测,将TB-LAMP阳性标本进一步行传统罗氏培养及表型药物敏感试验,分析TB-LAMP阳性标本再培养对耐药结核病的诊断价值,提高对耐药结核病的防治意识。采用graphpad prism6.0软件进行分析,χ2检验,P<0.05为差异具有统计学意义。结果 所纳入的可疑肺结核患者7823例,TB-LAMP法、传统罗氏培养和涂片镜检的阳性检出率分别为16.6%、7.8%和4.6%,痰TB-LAMP法阳性检出率与痰涂片抗酸染色、传统L-J培养检查相比,差异具有统计学意义(分别为χ2＝593.57,P＜0 .01;χ2＝283.49,P＜0 .01)。TB-LAMP阳性痰标本再培养阳性率为44%(574/1298),其中52.8%(303/574)与传统结核分枝杆菌培养共同阳性,另外47.2%(271/574)为传统结核分枝杆菌培养阴性,而TB-LAMP阳性标本再培养阳性;228株结核分枝杆菌临床分离株进行结核分枝杆菌药物敏感试验,敏感结核分枝杆菌占75%(171/228),耐药结核分枝杆菌25%(57/228),其中RR-/MDR-TB为12.72%(29/228)。结论 TB-LAMP阳性标本再培养可提高RR-/MDR-TB发现率,为耐药结核病的早诊断、早治疗、减少传播提供了检测思路,值得推广应用。     

结核病诊断技术及其临床应用

对TB作出及时准确的早期诊断对控制TB疫情至关重要。近年来随着生物技术和分子生物学的快速发展,在改善原有诊断技术的基础上也引入了多种新的TB诊断技术。新型培养技术大大缩短了细菌学检查和结核菌药敏试验的时间;分子扩增技术的应用(比如PCR)使得当日诊断成为现实;血清学方法的改善以及噬菌体测定等新技术的引入给TB临床诊断带来了希望。本文对TB的临床诊断、实验室诊断及最新技术进行了综述。     

Decentralised care for the management of child contacts of multidrug-resistant tuberculosis

Setting:

Cape Town, South Africa.

Objective:

To determine the number of multidrug-resistant tuberculosis (MDR-TB) child contacts routinely identified by health services, and whether a model of decentralised care improves access.

Methods:

All MDR-TB source cases registered in Cape Town from April 2010 to March 2011 were included. All child contacts assessed at hospital and outreach clinics were recorded from May 2010 to June 2011. Electronic probabilistic matching was used to match source cases with potential child contacts; the number of children accessing decentralised (Khayelitsha) and hospital-based care was compared.

Results:

Of 1221 MDR-TB source cases identified, 189 (15.5%) were registered in Khayelitsha; 31 (16.4%) had at least one child contact assessed. In contrast, 95 (9.2%) of the 1032 source cases diagnosed in the other Cape Town subdistricts (hospital-based care) had at least one child contact assessed (P = 0.003). Children in Khayelitsha were seen at a median of 71 days (interquartile range [IQR] 37–121 days) after source case diagnosis compared to 90 days (IQR 56–132 days) in other subdistricts (P = 0.15).

Conclusion:

Although decentralised care led to an increased number of child contacts being evaluated, both models led to the assessment of a small number of potential child MDR-TB contacts, with considerable delay in assessment.     

我国学生结核分枝杆菌潜伏感染和预防治疗现状

目的了解上海市浦东新区大中专院校肺结核患者学生密切接触者结核潜隐感染(LTBI)的情况及影响因素。方法2017年1月1日—12月31日采用结核分枝杆菌特异性细胞免疫反应检测(酶联免疫法)(QFT)对479例肺结核患者学生密切接触者的LTBI情况进行检测,同时收集性别、年龄、户籍、接触时间等信息并进行单因素和多因素分析。结果479例学生密切接触者的平均年龄为(20.8±1.4)岁,QFT试验结果阳性47例。同寝室室友以及同楼层寝室且同班级的密切接触学生QFT阳性率(30.0%和12.5%)显著高于一般接触者(7.3%)。多因素分析结果显示,男生密切接触者发生LTBI的风险高于女生(OR=3.72,95%CI：1.06~12.99);累计接触时间≥80 h的学生密切接触者发生LTBI的风险高于累计接触时间＜40 h者(OR=3.33,95%CI：1.12~9.86)。结论LTBI与接触程度和接触时间显著相关,其中同寝室室友以及同楼层寝室且同班级的密切接触学生是LTBI的高风险人群,应当在现有学校结核病防控的基础上增加对密切接触者的早期LTBI筛查,并尽早向LTBI者提供预防性治疗等。     

Screening of new entrants for tuberculosis: responses to port notifications

BACKGROUND: Tuberculosis in England and Wales is associated with recently arrived immigrants. Screening new entrants for tuberculosis has received considerable attention recently. Despite several calls to reorganize screening processes for new entrants because of perceived ineffectiveness, some systems at ports have remained largely unchanged, including notification arrangements. METHODS: A postal questionnaire was sent to Consultants in Communicable Disease Control (CsCDC) who normally receive port health notification forms from London Heathrow Port Health Control Unit relating to new entrants who had either been screened and found to have a normal chest X-ray, not had an chest X-ray due to pregnancy or young age or whose examination was inconclusive (Port 101 and 102 forms). RESULTS: Almost half of the responding CsCDC attempted to follow-up all Port 101 and 102 referrals; of these CsCDC, 46 percent reported that they were actually able to follow-up under 50 percent. CsCDC had developed their own criteria to aid decisions as to which referrals to follow-up. CONCLUSION: The follow-up by CsCDC of new entrants passing through Heathrow Port Health Control Unit who have been screened and found to have a normal chest X-ray, not had an X-ray due to pregnancy or young age, or whose examination was inconclusive varies considerably and there is no consistent national practice. Substantial efforts are being expended on attempting to follow-up new entrants, many of whom may be at low risk of tuberculosis. The effectiveness (and efficiency) of this approach is probably low.     

缺少医疗服务肺结核患者发现比例变化与分析

目的 分析新涂阳肺结核病例中缺少医疗服务的肺结核患者发现的比例变化，评价其发现水平与病例发现的关系。方法 对湖南省实施的国际防痨和肺部疾病联合会合作项目中新涂阳肺结核病例登记月报表进行统计。分析项目地区不同来源发现的新涂阳肺结核病例中缺少医疗服务的肺结核患者的比例与变化趋势，比较项目地区在两轮项目实施中发现的新涂阳肺结核病例中缺少医疗服务的肺结核患者的比例的变化。结果 在第一轮项目中，新涂阳肺结核病例中缺少医疗服务患者的比例为87．9％，随着时间的推移，该比例有增高的趋势。不同来源病例中，医院机构转诊发现的新涂阳肺结核病例中缺少医疗服务患者的比例为88．5％，肺结核可疑症状者就诊发现新涂阳肺结核病例中缺少医疗服务患者的比例为87．5％。不同来源病例发现比例元差别（P〉0．05）。在第二轮项目中，缺少医疗服务患者的比例为56．2％，明显低于第一轮患者的比例（P〈0．05）。结论 新涂阳肺结核病例中缺少医疗服务患者的比例，随着项目的不断扩展和深入，比例明显减少。显示出通过加强肺结核病例的转诊和就诊，肺结核病例登记率增高，病例发现延误减少，缺少医疗服务患者的比例减少。     

结核分枝杆菌耐多药情况分析

目的：评估上海市近年来耐多药结核病（MDR—TB）发生情况。方法：对本市2749株结核分枝杆菌耐药性测定结果进行分析。结果：共查出234株耐多药菌株，其中新发病。组156株（6．8％），复治病人组35株（18．9％），外地病人组43株（15．8％）。234株耐多药菌株中，耐2药133株（56．8％），耐3药66株（28．2％），耐4药35株（15．0％）。耐2药菌株中，以HR耐药为主，占27．8％。耐3药菌株中，以HRS耐药为主，占66．7％。复治病人和外地病人组的耐多药率显著高于新发病人组，P＜0．01。结论：必须加强对复治病人和外地病人的管理和治疗。     

中国汉族人群结核易感基因多态性与耐药结核病相关性研究

目的 了解结核易感基因SLC11A1基因、VDR基因、MBL基因以及IFNG基因多态性在中国汉族人群敏感和耐药结核病患者中的分布,探讨其与耐药结核病发生的相关性.方法 使用焦磷酸测序法、Real-time探针法、SNaPshot法测定229例敏感肺结核(敏感组)和230例耐药肺结核(耐药组)患者的VDR基因、SLC11A1基因、MBL基因、IFNG基因的单核苷酸多态性(SNP).结果 VDR基因多态性位点在敏感组和耐药组间差异均无统计学意义(P＞0.05).SLC11A1基因的INT4位点基因型和等位基因频率在敏感组和耐药组间差异有统计学意义(P值分别为0.031、0.046);INT4位点在隐性遗传模型假定下,敏感组和耐药组间差异具有统计学意义(OR=5.756,95%CI:1.261～26.269,P=0.011),结合该位点各种组合下的OR值间的数量关系,确定该位点的遗传模型符合隐性遗传模型.MBL基因Q/P位点基因型和等位基因频率在敏感组和耐药组间差异有统计学意义(P值分别为0.029、0.033);在隐性遗传模型假定下,MBL基因Q/P位点基因型和等位基因频率在不同组别间差异有统计学意义(OR=9.290,95%CI:1.167～73.949,P=0.011).IFNG基因的多态性位点在敏感组和耐药组之间的分布无统计学意义.结论 SLC11A1基因的INT4位点和MBL基因Q/P位点可能与中国汉族人群耐药结核病的发生具有一定的相关性.

Abstract：

Objective To investigate the distribution of polymorphisms of SLC11A1 gene,VDR gene,MBL gene and IFNG gene with susceptibility to tuberculosis (TB) in Chinese Han population suffering from drug-sensitive TB and drug-resistant TB so as to identify the correlation between gene polymorphisms and the development of drug-resistant TB.Methods Single nucleotide polymorphisms (SNP) of VDR gene,SLC11A1 gene,MBL gene,IFNG gene were typed and analyzed by pyrosequencing,Real-time Probe and SNaPshot among 229 patients with drug-sensitive TB and 230 patients with drug-resistant TB.Results The polymorphic foci of VDR gene from the drug-sensitive TB group and the drug-resistant TB group showed no significant difference (P＞0.05).The genotype of INT4 site and allelic frequency of SLC11A1 gene for drug-sensitive TB group were significantly different from those for drug-resistant TB group(P=0.031,0.046).If recessive inheritance was assumed,the genotypes of INT4 site from the two groups were significantly different (0R=5.756,95% CI:1.261-26.269,P=0.011).Considering the relationship between OR values under various combination,our findings confirmed that the genetic mode of INT4 site was in accordance with recessive inheritance.The genotypes of Q/P site and allelic frequencies of MBL gene from drug-sensitive and drug-resistant groups were significantly different (P=0.029,0.033).The difference still existed under the hypothesis of recessive inheritance (OR=9.290,95% CI:1.167-73.949,P=0.011).The polymorphic foci of IFNG gene from the two groups showed no significant difference.Conclusion INT4 sites on SLC11A1 gene and Q/P site on MBL gene were probably associated with the development of drug-resistant TB in Chinese Han population.Further study on this issue would be helpful in locating the population at high risk of drug-resistant TB and exploring the effective intervention to decrease the incidence of this disease.     

Planning to improve global health: the next decade of tuberculosis control

The Global Plan to Stop TB 2006-2015 is a road map for policy-makers and managers of national programmes. It sets out the key actions needed to achieve the targets of the Millennium Development Goals relating to tuberculosis (TB): to halve the prevalence and deaths by 2015 relative to 1990 levels and to save 14 million lives. Developed by a broad coalition of partners, the plan presents a model approach combining interventions that can feasibly be supplied on the ground. The main areas of activity set out in the plan are: scaling up interventions to control tuberculosis; promoting the research and development of improved diagnostics, drugs and vaccines; and engaging in related activities for advocacy, communications and social mobilization. Scenarios for the planning process were developed; these looked at issues both globally and in seven epidemiological regions. The scenarios made ambitious but realistic assumptions about the pace of scale-up and implementation coverage of the activities. A mathematical model was used to estimate the impact of scaling up current interventions based on data from studies of tuberculosis biology and from experience with tuberculosis control in diverse settings. The estimated costs of the activities set out in the Global Plan were based on implementing interventions and researching and developing drugs, diagnostics and vaccines; these costs were US$ 56 billion over 10 years. When translated into cost per disability adjusted life year averted, these costs compare favourably with those of other public health interventions. This approach to planning for global tuberculosis control is a valuable example of developing plans to improve global health that has relevance for other health issues.     

结核分枝杆菌分子生物学分型技术研究进展

结核病是全球严重威胁人类健康的重大传染病之一,耐药结核,特别是耐多药结核患者逐年增多,致使全球结核病的流行形势非常严峻.分子生物学技术在结核分枝杆菌主要流行菌株的确定、耐药性监测、结核病感染、暴发以及传染源追踪等方面是十分有效的检测手段.     

2003-2007年鹰潭市结核病控制项目效果评价

目的了解鹰潭市结核病预防与控制现状,评价项目实施及达标情况,为今后结核病控制提供参考依据。方法牛挺掂结核病控制项目的基线资料,对结核病发现、治疗和控制效果进行分析。结果可疑帅结核病人就诊率、活动性肿结核病人发现牢、涂阳病人发现率和治愈率分别由项目实施初期的26．6／10万、11．3／10万、7．2／10万和53．8％上升到2005年的256．7／10万、121．2／10万、60．0／10万和89．O％。结论鹰潭市结核病控制项目效果显著,但在病人转诊、追踪和全程督导工作上还有待加强。     

老年肺结核病的误诊原因分析

目的 探讨老年肺结核的误诊原因，提高老年肺结核的诊断水平。方法 采用临床分析方法，对收治误诊的66例老年肺结核病人进行分析。结果 误诊患者年龄分布差异无显著性；农民患者误诊高(71．2％)；因病就诊高(98．5％)，主要是合并症和并发症；延误诊治(54．5％)和医源性误诊(45．5％)并存。平均误诊468．74d，平均住院治疗时间16．58d。未完成强化治疗者55例，占83．33％。结论 提高老年呼吸道病患者尤其是农民患者对结核病的认识，及时到专科医院就诊，重视老年呼吸道疾病的诊断，减少延误诊断。     

2005—2017年新疆14个地州市基于传染病动力学结核病流行状况定量研究

目的对新疆 14个地（州、市）结核病发病数据进行建模分析,定量给出新疆各地（州、市）结核病的流行状况,并对新疆各地（州、市）结核病新发病数进行预测。方法采用动力学模型对新疆14个地（州、市）2005—2014年的结核病数据进行拟合,利用2015—2017年结核病数据进行验证,对验证结果进行评价,得到各地区参数的估计值和基本再生数（R0）,并对各地（州、市）2018—2022年新发结核病数据进行预测。结果2015—2017年结核病数据验证结果显示,实际值均落在预测值曲线95%置信区间内,模型拟合效果良好。南疆喀什地区R0为11.38 (95%CI:11.33～11.50),东疆地区乌鲁木齐市和北疆地区的伊犁哈萨克自治州R0分别为5.46 (95%CI:5.28～5.50)、2.22 (95%CI:2.18～2.28),南疆地区结核病疫情远高于北疆和东疆地区,尤其是喀什地区结核病疫情最严重。2018—2022年预测结果显示,大部分地区结核病新发病数在波动中呈缓慢增长趋势。结论此结核病动力学模型拟合良好,具有可行性,可以用来预测结核病新发病数,同时应采取干预措施,加强对南疆地区的管理,控制结核病的流行。     

Robust fit of Bayesian mixed effects regression models with application to colony forming unit count in tuberculosis research

Early bactericidal activity of tuberculosis drugs is conventionally assessed using statistical regression modeling of colony forming unit (CFU) counts over time. Typically, most CFU counts deviate little from the regression curve, but gross outliers due to erroneous sputum sampling are occasionally present and can markedly influence estimates of the rate of change in CFU count, which is the parameter of interest. A recently introduced Bayesian nonlinear mixed effects regression model was adapted to offer a robust approach that accommodates both outliers and potential skewness in the data. At its most general, the proposed regression model fits the skew Student t distribution to residuals and random coefficients. Deviance information criterion statistics and compound Laplace‐Metropolis marginal likelihoods were used to discriminate between alternative Bayesian nonlinear mixed effects regression models. We present a relatively easy method to calculate the marginal likelihoods required to determine compound Laplace‐Metropolis marginal likelihoods, by adapting methods available in currently available statistical software. The robust methodology proposed in this paper was applied to data from 6 clinical trials. The results provide strong evidence that the distribution of CFU count is often heavy tailed and negatively skewed (suggesting the presence of outliers). Therefore, we recommend that robust regression models, such as those proposed here, should be fitted to CFU count.     

老年结核病患者对中国结核病控制的影响

目的 分析在现代结核病控制策略(DOTS策略)下老年结核病患者对中国结核病控制的影响。方法 根据2000年全国结核病流行病学抽样调查中老年结核病的患病特征,对照分析在实施DOTS策略地区和非DOTS策略地区老年结核病患者的发现、治疗和管理现状。结果 ≥65岁年龄组肺结核涂阳患病率为440/10万,是各年龄组平均涂阳患病率的3.6倍;≥65岁老年人涂阳病例数占全人口涂阳病例数的28.6％;在已实施DOTS策略的13个省和未实施DOTS策略的15个省中,老年涂阳病例数分别占各年龄组涂阳病例数的28.8％和28.9％;1992～2000年在实施DOTS策略的13省新涂阳病例登记数中,≥65岁老年结核病患者占11.4％。结论 老年结核病患者涂阳患病率高,不论在实施DOTS策略地区或非DOTS策略地区,所有涂阳病例中老年涂阳病例构成比例大,而新涂阳病例登记比例却最低。老年结核病患病率高、发现率低是结核病控制工作中值得关注的问题。     

2008-2017年西藏自治区肺结核流行特征

目的  了解和分析2008-2017年西藏自治区肺结核流行特征,为西藏地区防控肺结核疫情提供参考依据。方法  采用描述性流行病学研究方法,对2008-2017年西藏自治区肺结核疫情监测数据进行分析。结果  2008-2017年西藏自治区肺结核平均报告发病率为105.70/10万,标化报告发病率为108.10/10万,其肺结核报告发病率EAPC=-1.83%（t=3.119,P=0.014）,表明10年间西藏地区肺结核报告发病率平均以1.83%的速度下降;男女肺结核报告发病数性别比为1.48：1,男性报告发病率高于女性;65~74岁年龄段的老年人群肺结核报告发病率最高,为270.55/10万;肺结核报告发病数最多的职业为农民,其次为牧民和学生;日喀则市及其藏南地区为肺结核疫情高发区域。结论  西藏自治区肺结核报告发病率呈下降趋势,但疫情仍较为严重,应有针对性的对日喀则市及其藏南等疫情高发地区和农牧民、学生等人群采取有效措施,进一步控制和降低西藏地区肺结核疫情。