Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in new patients in Peru

Setting:

Primary health care centres in Callao, Peru.

Objectives:

To evaluate the effect of universal access to the microscopic-observation drug susceptibility (MODS) assay on treatment outcomes in new and primary multidrug-resistant tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing (DST).

Design:

Retrospective review of tuberculosis (TB) registers and clinical records before (2007) and after (2009) the introduction of MODS in 2008.

Results:

There were 281 patients in each cohort. Favourable treatment outcomes for 2007 (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to 0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183) in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a significant reduction in time to diagnosis of drug-susceptible (from 118 to 33 days, P < 0.001) and MDR-TB (from 158 to 52 days, P = 0.003) was observed in the 2009 cohort.

Conclusion:

Universal access to MODS increased DST coverage, reduced the time required to obtain DST results and was associated with reduced failure rates. MODS can make an important contribution to TB management and control in Peru.     

耐多药结核病的预防和综合治疗探讨

耐多药结核病(MDR-TB)指的是致病结核菌至少同时耐异烟肼(INH)和利福平(RFP)。据报道全世界约有2/3的结核病人处于发生耐多药结核病的危险之中。WHO估计1/7结核病人在中国,1/4耐多药结核病人在中国。耐多药结核病是当前结核病防治工作中亟待解决的问题,因此,掌握耐多药结核病产生的原因,进一步积累经验和研究新的药物,综合治疗,才能达到治愈的目的,控制结核病尤其是耐多药结核病的流行。本文根据近期相关的研究进展,就耐多药结核病产生的原因,综合治疗与预防向读者作一专题介绍供同道在临床实践中参考。     

贵州省2014―2020年耐多药结核病患者三类治疗延迟现况及其影响因素

  目的  分析贵州省2014―2020年耐多药结核病(multidrug-resistant tuberculosis, MDR-TB)患者三类治疗延迟现况及影响因素。  方法  从“结核病管理信息系统”中收集患者信息；趋势χ2检验分析率随时间变化趋势；χ2检验和多因素logistic回归分析模型用于延迟因素分析。根据患者治疗延迟天数将其分为三类:第I类(延迟>1 d)、第II类(延迟>7 d)和第III类(延迟>14 d)。  结果  2014―2020年贵州省登记的1 309例MDR-TB患者中第I、II和III类治疗延迟率分别为43.6%、30.0%和22.7%。三类延迟率均随时间变化呈总体下降趋势(均有P＜0.001)。但2019年12月―2020年延迟率较以往有所升高，其中2019年12月延迟率最高达47%；2020年总体延迟率较2019年上升。农民、有固定职业、来自毕节市诊疗机构、采用传统药物敏感性试验诊断、既往接受过抗结核病治疗和确诊时住院治疗的患者更容易发生延迟(均有P＜0.05)。  结论  贵州省2014―2020年MDR-TB患者三类治疗延迟率均较高，虽呈逐年下降趋势，但自2019年12月起延迟率较以往有所升高。职业、诊疗机构、诊断方式、抗结核病治疗史和确诊时治疗模式是患者治疗延迟的影响因素，应采取综合措施以降低治疗延迟的发生。     

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.     

2010-2013年如皋市耐多药肺结核患者分析

目的通过对如皋市耐多药肺结核(MDR-TB)患者的来源及转归进行分析,探索适合该地区MDR-TB的发现策略。方法 2010-2013年收集该市所有涂阳结核病患者的痰标本,开展药敏检查,分析不同来源患者中的MDR-TB发现及转归情况。结果 4年间确诊MDR-TB患者36例,结核病患者中MDR-TB检出率为9.3%,其中86.1%的MDR-TB患者来源于MDR-TB高危人群。初治凃阳者MDR-TB检出率为1.7%,MDR-TB高危人群为34.8%,差异有统计学意义(P0.001)。MDR-TB高危人群中,慢性排菌患者MDR-TB检出率为57.1%,复发患者为34.7%,其他复治患者为22.2%,2月或3月末未发现涂片仍阳性者。纳入治疗的MDR-TB患者治疗成功率为67.7%。不同来源的MDR-TB高危人群MDR-TB检出率及治疗成功率差异均无统计学意义(P0.05)。结论该市MDR-TB疫情低于全国水平,MDR-TB高危人群是该市发现耐多药肺结核最主要人群。     

Factors Associated with Multi-Drug Resistant Tuberculosis among TB Patients in Selected Treatment Centers of Amhara Region: A Case-Control Study

BackgroundMulti-drug Resistant Tuberculosis (MDR-TB) is found to be a major public health problem both in developed and developing countries. Ethiopia is one of the 30 high MDR-TB burden countries in the world. Although several studies were done to identify the determinants of MDR-TB, the reported findings are heterogeneous across the world.MethodsUnmatched case-control study was conducted at Debre Markose Referral Hospital, Debre Birhan Referral Hospital, and Boru Media District Hospital in Amhara Region, Northern Ethiopia, from March 01/2019- April 30/2019. Cases were all tuberculosis patients with culture or line probe assay confirmed mycobacterium tuberculosis resistant to at least both Isoniazid and Rifampicin and registered on second-line TB treatment. Controls were all patients with Bacteriological (molecular) proven drug-susceptible TB strains and whose recent smears result were turned to negative and registered as cured from January 01/2014 – December 31/2018. A pre-tested checklist was used to collect the data.ResultOf the total reviewed documents (393), 98 cases and 295 controls were involved in this study. And, 54(55.1%) among cases and 162(54.9%) among controls were males. sixty nine(70.4%) among cases and 163(55.3) among controls were within the age group of 26–45 years. In the multivariable logistic regression analysis, age between 26–45 years old (AOR=3.35; 95% CI: 1.15, 9.77), previous history of TB treatment (AOR= 14.2; 95%CI: 7.8, 25.3) and being HIV positive (AOR=4.4; 95% CI: 1.8, 10.4) were significantly associated with MDR-TB.ConclusionAge between 26–45 years old, previously treated cases and TB/HIV co-infection were identified as the determinants of MDR-TB. Special attention should be given to age between 26–45 years old, previous history of TB treatment and TB/HIV co-infection to prevent and control MDR-TB in the local context.     

湖北省全球基金耐多药结核病项目阶段性实施结果分析

目的分析湖北省全球基金耐多药结核病（MDR-TB）项目（以下简称＂项目＂）阶段性实施结果,总结＂项目＂实施过程中的耐多药肺结核诊断、治疗和管理策略的成功经验与不足,提出改进措施,为湖北省下一步耐多药结核病控制工作提供科学依据。方法收集＂项目＂执行期间5个项目单位的月报表和季度报表,进行回顾性研究,使用SPSS 17.0软件对数据进行统计分析,率的比较采用χ2检验,P〈0.05为差异有统计学意义。结果 2006年10月～2012年2月,共筛查培养耐多药肺结核可疑者5 176例,培养阳性率为87.06%。对培养阳性患者痰样本进行药敏试验4 233例,实验室确诊MDR-TB共873例,MDR-TB检出率为22.88%,不同登记分类的可疑者MDR-TB检出率差异有统计学意义（χ2=302.98,P〈0.05）。确诊的873例MDR-TB中纳入治疗521例（纳入治疗率为73.07%）,等待治疗160例,未纳入治疗192例。192例未纳入治疗患者中不能组成有效方案、治疗前死亡和拒治分别占30.73%、24.48%和23.44%。治疗满6月患者数315例,6月末痰涂片阴转率为72.70%,痰培养阴转率为67.62%。结论通过＂项目＂的实施,以地（市）为中心开展耐多药结核病治疗管理的模式、标准化治疗方案为主的治疗策略是可行的。耐多药结核病诊断治疗管理水平等方面有待进一步加强。     

Countrywide audit of multidrug-resistant tuberculosis and treatment outcomes in Mongolia

Setting:

Eighteen treatment units for multidrug-resistant tuberculosis (MDR-TB) in Mongolia.

Objective:

To determine the total number of MDR-TB cases detected, their resistance patterns, the proportion and characteristics of cases starting treatment, the delay between diagnosis and treatment initiation, and the relation between treatment outcomes and drug resistance.

Design:

Retrospective cohort study using routine programme data.

Results:

Of 268 MDR-TB cases detected, 168 (63%) were resistant to HRES, 59 (22%) to HRS, 34 (13%) to HR and 7 (3%) to HRE. Of the 268 MDR-TB patients, 139 (52%) started treatment: 69 (50%) were secondary and/or university students, 35 (25%) were unemployed, 24 (17%) were currently employed and 14 (8%) retired, disabled or status was unrecorded. The median time from MDR-TB diagnosis to treatment initiation was 137 days (IQR 43–218). The treatment success rate was 69%; 9% failed treatment, which may indicate extensively drug-resistant TB (XDR-TB) or pre-XDR-TB.

Conclusion:

Close to seven in 10 patients in Mongolia had a successful treatment outcome, which is encouraging. Specific problems included the high proportion of students, about half of all diagnosed patients accessed treatment and there was an unacceptable delay of 4 months to treatment. These issues need to be addressed.     

High time to use rapid tests to detect multidrug resistance in sputum smear-negative tuberculosis in Belarus

Setting: Belarus (Eastern Europe) is facing an epidemic of multidrug-resistant tuberculosis (MDR-TB). In 2012, rapid molecular diagnostics were prioritised for sputum smear-positive pulmonary tuberculosis (PTB) patients to diagnose MDR-TB, while pulmonary sputum smear-negative pulmonary TB (SN-PTB) patients were investigated using conventional methods, often delaying the diagnosis of MDR-TB by 2–4 months.Objective: To determine the proportion of MDR-TB among SN-PTB patients registered in 2012 and associated clinical and demographic factors.Design: Retrospective cohort study using countrywide data from the national electronic TB register.Results: Of the 5377 TB cases registered, 2960 (55%) were SN-PTB. Of the latter, 1639 (55%) were culture-positive, of whom 768 (47%) had MDR-TB: 33% (363/1084) were new and 73% (405/555) previously treated patients. Previous history of treatment, age, region, urban residence, human immunodeficiency virus (HIV) status and being a pensioner were independently associated with MDR-TB.Conclusion: About half of culture-positive SN-PTB patients have MDR-TB and this rises to over 7/10 for retreatment cases. A national policy decision to extend rapid molecular diagnostics universally to all PTB patients, including SN-PTB, seems justified. Steps need to be taken to ensure implementation of this urgent priority, given the patient and public health implications of delayed diagnosis.     

12省项目地区1157例耐多药肺结核患者治疗情况分析

目的 分析中国全球基金耐多药肺结核项目患者治疗情况,为制定适合我国国情的耐多药肺结核患者治疗策略提供参考依据.方法 通过项目月报表、季报表和专题收集耐多药肺结核患者治疗及痰菌阴转数据,分析患者纳入治疗情况、标准化治疗方案使用情况和6月末痰菌阴转情况.结果 1 157例确诊耐多药肺结核患者,仅700例(60.5％)患者纳入抗结核药物化学治疗;收集治疗方案的473例患者中,433例(91.5％)患者使用标准化治疗方案;259例完成6个月治疗的患者中,6月末痰涂片和痰培养阴转率分别为79.4％和78.6％.结论 确诊耐多药肺结核患者纳入治疗比例偏低,大部分患者能够接受二线抗结核药物组成的标准化治疗方案,并取得较好的初步治疗效果.     

Screening retreatment tuberculosis patients for drug resistance in mid-west Nepal: how well are we doing?

Setting: Multidrug-resistant tuberculosis (MDR-TB, defined as resistance to isoniazid and rifampicin) is poorly detected in Nepal; one reason may be poor functioning of culture and drug susceptibility testing (CDST) services for retreatment tuberculosis (TB) patients.Objectives: To determine, among retreatment TB patients in mid-west Nepal, 1) the number of patients registered for treatment between July 2011 and July 2012; 2) the number submitting sputum specimens for CDST to the Central Reference Laboratory (CRL), Kathmandu, along with the results; and 3) the length of time for submission and receipt of specimens.Design: Retrospective cohort study involving the review of treatment and laboratory registers from the Nepalgunj TB Referral Centre and the CRL.Results: Of 431 retreatment patients, 66 (15%) submitted sputum samples, of which 63 reached the CRL. Of these, 39 (62%) were culture-positive; 13 (33%) patients had MDR-TB. The CDST results of 19 patients were received back at the TB Referral Centre. The median turnaround time from sending specimens to receipt of results at the TB Referral Centre was 119 days.Conclusion: Less than 10% of retreatment TB patients in mid-West Nepal had CDST results recorded, leading to the underdiagnosis of MDR-TB in the region. Urgent solutions are needed to rectify this problem.     

2015-2017年度韶关市结核病就诊患者耐多药情况分析

  目的  探析位于粤北山区的韶关市2015-2017年度耐多药肺结核患者（multi drug resistant pulmonary tuberculosis,MDR-TB）的筛查情况。  方法  回顾性分析562例可疑MDR-TB患者及新患者的临床资料,所有患者均接受了传统药敏试验,统计异烟肼（isonicotinyl hydrazide,INH）、利福平（rifampicin,RFP）、乙胺丁醇（Ethambutol,EMB）、链霉素（streptomycin,SM）、氧氟沙星（ofloxacin,Ofx）、卡那霉素（kanamycin,Km）耐药情况及MDR-TB筛查结果。  结果  传统药敏试验结果中,SM的耐药率最高,达19.22%（108/562）,KM的耐药率最低,为4.45%（25/562）。562例患者的传统确诊结果显示,MDR-TB检出率为6.94%（39/562）。MDR-TB检出率在性别、年龄、文化程度、地区之间均无统计学意义（均有P>0.05）;不同患者类型的MDR-TB检出率之间有统计学意义（P < 0.001）。  结论  肺结核患者耐药率顺位依次为链霉素、异烟肼、利福平、乙胺丁醇、氧氟沙星和卡那霉素。复治组患者的单耐药率、耐多药率均高于初治组。应以复治患者为重点,扩大筛查范围,及时治愈初治患者。     

江西省全球基金肺结核项目地区耐多药可疑者 筛查情况分析

摘要:目的　分析江西省全球基金耐多药肺结核项目地区耐多药肺结核患者筛查情况,为江西省下一步在全省开展耐多药肺结核防治发现工作提供借鉴。方法　收集、分析项目地市2012年1月1日-2013年9月30日间,耐多药肺结核可疑者相关报表资料。结果　对耐多药肺结核可疑者757例开展痰培养,培养阳性627例（占90.5%）;开展药敏试验的610例可疑者中,确诊耐多药肺结核患者和广泛耐药肺结核患者分别为90例和3例,初治失败、复治失败和其他患者中确诊耐多药及广泛耐药肺结核率分别为61.57%、71.5%和66.7%,结论　以5类高危人群和反复多年治疗不愈患者作为主要筛查对象,更符合成本效益的防治原则。     

Multidrug-resistant tuberculosis in central Asia

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major threat to TB control, particularly in the former Soviet Union. To determine levels of drug resistance within a directly observed treatment strategy (DOTS) program supported by Médecins Sans Frontières in two regions in Uzbekistan and Turkmenistan, Central Asia, we conducted a cross-sectional survey of smear-positive TB patients in selected districts of Karakalpakstan (Uzbekistan) and Dashoguz (Turkmenistan). High levels of MDR-TB were found in both regions. In Karakalpakstan, 14 (13%) of 106 new patients were infected with MDR-TB; 43 (40%) of 107 previously treated patients were similarly infected. The proportions for Dashoguz were 4% (4/105 patients) and 18% (18/98 patients), respectively. Overall, 27% of patients with positive smear results whose infections were treated through the DOTS program in Karakalpakstan and 11% of similar patients in Dashoguz were infected with multidrug-resistant strains of TB on admission. These results show the need for concerted action by the international community to contain transmission and reduce the effects of MDR-TB.     

福建省耐多药结核分枝杆菌耐药相关基因突变特征

目的初步分析福建耐多药结核病(multi-resistant tuberculosis,MDR-TB)临床分离结核分枝杆菌利福平和异烟肼的耐药相关基因突变情况。方法自福建福州肺科医院收集耐多药结核分枝杆菌临床分离菌株,采用PCR测序技术测定利福平和异烟肼耐药相关基因,包括rpoB、katG、inhA和mabA-inhA,并与标准菌株基因序列比对,分析基因突变特点。结果共对67株MDR-TB菌株进行了分析,91.04%的菌株在rpoB81 bp RRDR区发生突变,其中,88.06%(59/67)的MDR-TB菌株在rpoB531、526和516位发生突变;79.10%的菌株在katG、inhA或mabA-inhA上发生突变,59.70%(40/67)的菌株在katG315或者mabA-inhA(-15)位发生突变,没有检测到同时在inhA结构基因和基因调节区发生突变的菌株。结论 PCR-DNA测序分析技术可以用于检测MDR-TB临床分离菌株对RFP和INH的药物敏感性。     

耐多药结核病患者细胞免疫功能的初步研究

目的 动态观察耐多药结核病患者机体细胞免疫状态,为临床诊治用药提供支持,为以后耐多药结核病的免疫治疗打下初步基础。 方法 用绝对浓度法进行药敏试验,筛选出耐多药结核(Multi-drug resistant tuberculosis,MDR-TB)患者50例,药物敏感性结核(drug-susceptible tuberculosis,S-TB)患者50例,另于体检者中选取健康对照(healthycontrol,HC)20例,流式细胞分析淋巴细胞亚群(CD4⁺、CD3⁺、CD8⁺分子等),酶联免疫吸附法 (enzyme-linked immunosorbent assay,ELISA)检测血清细胞因子(IFN-γ、IL-2、IL-4 和IL-10等),比较耐多药结核病患者血清学与全敏结核病患者血清、正常人血清之间的差异。 结果 各组间CD3⁺分子百分比差异无统计学意义,健康组与各结核组CD4⁺、CD8⁺、CD4⁺/CD8⁺ 百分比差异有统计学意义,耐多药结核组与结核敏感组CD4⁺、CD8⁺、CD4⁺/CD8⁺ 百分比差异有统计学意义。健康组与各结核组IFN-γ、IL-2、IL-4 和IL-10的浓度差异均有统计学意义,耐多药结核组与结核敏感组IL-2、IL-4 和IL-10的浓度差异有统计学意义。耐多药结核组CD4⁺、CD4⁺/CD8⁺比值、IL-2显著低于结核敏感组,CD8⁺、IL-4 和IL-10显著高于结核敏感组(P<0.05)。 结论 结核病患者细胞免疫功能均下降,表现为CD4⁺淋巴细胞百分比降低, CD8⁺淋巴细胞百分比升高, CD4⁺/CD8⁺比值降低甚至倒置,增强抗结核免疫反应的细胞因子IFN-γ、IL-2浓度降低而抑制此反应的细胞因子IL-4和IL-10浓度升高。耐多药结核病患者较敏感结核病患者的细胞免疫功能进一步下降,表现为上述变化更加显著,使病情表现更加复杂及增加了治疗难度。     

肺结核患者结核杆菌耐药情况及耐多药结核病的危险因素

目的 明确肺结核患者的耐药情况，探索耐多药结核病（MDR-TB）的危险因素，为MDR-TB的防治提供依据。方法 收集肺结核患者468例，分为初治患者365例和复治患者103例。采用比例法检测结核分枝杆菌对抗结核药物的敏感性。应用单因素及多因素logistic回归分析MDR-TB发生的危险因素。结果 468例患者的总耐药率、耐多药率和广泛耐药率分别为25.85%、11.97%、3.21%。复治患者总耐药率（49.51%）、耐多药率（34.95%）和广泛耐药率（10.68%）高于初治患者（分别为19.18%、5.48%、1.10%），差异均有统计学意义（P<0.05）。6种抗结核药中，总体耐药顺位由高至低依次为：异烟肼（INH） > 利福平（RFP） > 氧氟沙星（OFX） > 乙胺丁醇（EMB） > 链霉素（SM） > 卡那霉素（KM）。单因素及多因素logistic回归分析显示，居住农村（OR=2.316，95% CI：1.604~5.118）、复治（OR=6.150，95% CI：4.728~13.824）、有结核空洞（OR=3.219，95% CI：2.405~8.627）、治疗过程中断（OR=5.826，95% CI：4.610~12.507）及首次治疗未联合用药（OR=2.508，95% CI：1.813~5.646）是MDR-TB的危险因素。结论 肺结核患者耐药率较高，影响MDR-TB发生的危险因素较多，需积极采取干预措施，控制MDR-TB的发生。     

Characteristics and outcome of multidrug-resistant tuberculosis in a low-incidence area

Objectives

To characterize multidrug-resistant tuberculosis (MDR-TB) patients treated in a low endemic area in France and to determine risk factors for resistance. We also analyzed the efficacy and tolerability of tuberculosis (TB) treatment.

2012-2017年辽宁省耐多药结核病患者特征分析

目的对耐多药肺结核患者的检出情况及分布特征进行分析,了解辽宁省耐多药结核病的流行规律。方法利用《结核病管理信息系统》,通过收集2012-2017年辽宁省耐多药结核病患者筛查信息进行分析,对患者的筛查、MDR-TB检出、性别构成、年龄结构、职业分布等进行探讨。结果进行药敏试验并报告结果的可疑者筛查数为12001例,确诊MDR-TB患者2094例,检出率为17.45%。复治失败患者的检出率最高,新患者的检出率最低,差异有统计学意义(X^2=1233.84,P<0.05)。其中男性患者1601例(占76.46%),女性患者493例(占23.54%),差异无统计学意义(P=2.64,P>0.05)。35~64岁组MDR-TB患者检出率最高,65岁以上组检出率最低,差异有统计学意义(X^2=114.47,P<0.05).2012-2017年MDR-TB患者检出2017年最高,2015年最低,差异有统计学意义(X^2=20.91,P<0.05)。除其他职业外,医务人员MDR-TB检出率最高为22.73%,其次是家政、家务及待业。结论应全面实行耐多药结核病的筛査工作,加强医院感染控制工作,重点关注学校结核病疫情控制及重点人群,减少耐多药结核病的产生。     

Multidrug-resistant Mycobacterium tuberculosis in HIV-infected persons, Peru

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima, Peru, and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%) of 965 patients who were HIV-negative or of unknown HIV status (p<0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB.