精进臻善 惟实励新:世界卫生组织《2022年全球结核病报告》解读

结核病防控工作亟待创新性的研究与发展，以加快实现终止结核病策略。2022年10月27日，世界卫生组织发布了《2022年全球结核病报告》,对全球结核病领域的研究和创新进展进行更新。笔者就报告中结核病研究领域新诊断技术、新药与新方案，以及新疫苗等研究及创新要点进行解读，并结合我国相关领域的研究进展进行分析，以期为我国结核病防治领域同行掌握结核病研究动态，进一步开展原创性科研和创新提供参考。     

世界卫生组织《2023年全球结核病报告》解读

2023年11月7日,世界卫生组织发布了《2023年全球结核病报告》,该报告围绕全球结核病疫情负担、登记报告、治疗转归、创新进展等内容展示了全球结核病防控工作的基本要点。作者通过对该报告的全球结核病负担、诊疗现状等方面进行解读,为结核病领域工作者全面了解全球结核病疫情现状、防控策略、行动及进展提供参考。     

《2022年全球结核病报告》要点解读

在新型冠状病毒感染大流行背景之下, 2022年10月27日世界卫生组织发布了《2022年全球结核病报告》。过去十余年虽然结核病发病率缓慢下降, 病死率减少约1/3, 但新型冠状病毒感染大流行逆转了这个积极趋势。《2022年全球结核病报告》显示, 2021年全球结核病、耐药结核病和结核病死亡患者数量均增长, 对世界卫生组织终止结核病目标的实现构成了严峻挑战。本文对其要点进行解读, 希望有关部门对结核病的防控引起重视, 对促进结核病的发病率、病死率的缓解和推动终止结核病的目标的实现发挥一定的积极作用。     

全球加速扩展结核病预防性治疗行动计划背景下的中国对策

为加速全球结核病预防性治疗扩展,世界卫生组织于2021年6月发布了全球结核病防治2.0版行动计划,要求各国政府和利益相关者积极行动,加大投资力度,扩大结核病筛查范围和发现力度,积极推进结核病预防性治疗,确保实现2018年联合国高级别会议政治宣言承诺的目标。为此,笔者结合我国结核病防治工作需要,系统梳理了开展结核病预防性...     

2022年WHO全球结核病报告：全球与中国关键数据分析

结核病是仅次于新型冠状病毒感染（COVID-19）的第二大传染性疾病杀手,也是全球第十三大死亡原因。《2022年全球结核病报告》（以下简称2022年报告）显示：2021年,全世界估计新增1060万结核病患者,其中600万人是成年男性,340万人是成年女性,120万人是儿童。HIV感染者占总数的6.7%。新诊断的患有结核病并向各国政府报告的病例数从2020年的580万恢复到2021年的640万,仍有约420万未被诊断或未被报告。结核病发病率上升,死亡病例数有所增加。2021年,由结核病引起的死亡病例数估计是由HIV感染引起的死亡病例数的两倍多。2021年新增45万例利福平耐药结核病（RR-TB）患者,明显高于2020年,然而耐药结核病的治疗覆盖率及治疗成功率依然较低。2022年报告提示COVID-19大流行在全球结核病防治工作中的影响仍在继续。2022年报告呼吁多部门加倍努力,增加对基本结核病服务和研究的资助,减轻和扭转COVID-19大流行对结核病防治服务的负面影响,以实现终结结核病的目标和拯救生命。     

结核病若干问题研究进展

结核病是由结核分枝杆菌引起的一种严重危害人类健康的慢性传染病。据世界卫生组织（world Health Organi—zation，WHO）2010年全球结核病控制报告显示[1]，2009年全球新发结核病患者940万，共有结核病患者1400万，死于结核病者130万。结核病给人类的健康带来了如此巨大的负担，人类一直致力于结核病诊断、治疗、预防等方面的研究。笔者将从以下5个方面来介绍结核病研究的一些进展。     

加强结核病实施性研究 促进“终止结核病”目标实现

世界卫生组织在2015年提出了“终止结核病策略”（End-TB）,其目标是2035年在全球终止结核病流行。而提供以患者为中心的综合结核病治疗和预防服务、提供强有力的政策和支持系统,以及加强研究与创新是实现这一最新策略的三大重要支柱。     

结核病实验室诊断技术研发进展

世界卫生组织2009年全球结核病控制报告显示,全球现有1370万结核病患者,每年发病人数为927万,我国发病人数居世界第二位.近十余年来,结核病实验室诊断技术突飞猛进,其中一些技术已经过临床验证并获得一些权威机构的认证,然而,我国多数地区的结核病实验室诊断仍停留在痰涂片镜检、痰结核菌培养及PPD皮试等传统方法.本文介绍近十余年来具有代表性的几项结核病实验室诊断新技术的研发情况.     

耐多药结核病临床研究的回顾与展望

近年来全球结核病发病率呈现居高不下之势,据世界卫生组织（World Health Organization,WHO）2009年全球结核病控制报告显示,全球每年约有800万新发结核病例,约有200万因结核死亡,其中我国每年新发结核病150万例,每年约有13万人死于结核病。     

《结核病免疫治疗专家共识（2022年版）》要点解读

《2022年全球结核病报告》显示,2021年全球结核病、耐药结核病和结核病死亡患者数量均增长,对WHO终止结核病目标的实现构成了严峻挑战。TB/HIV/COVID-19的三重感染重创了全球结核病防治成果,故全球终止结核病策略的如期实现必将是任重道远。全球结核病疫情的新变化,对结核病治疗提出了新的挑战。虽然敏感结核病和耐药结核病患者的化学药物治疗在缩短疗程和提高疗效等方面取得了较大新进展,但是短程全口服新方案仍未在全球推广使用,一线和二线抗结核药物的不良反应较大,结核病的免疫治疗可能为目前化疗困境提供了新的机遇。作者就《结核病免疫治疗专家共识(2022年版)》要点进行解读,希望对提高结核病治疗成功率发挥一定的积极作用。     

实事求是抓住核心 脚踏实地精准防控

随着WHO提出2035年消灭结核病的伟大目标,对结核潜伏感染者进行预防性干预作为重要的创新策略受到了国内外的重视。中国是全球结核病第二高负担国家,结核病防控形势十分严峻。在这种情形下更需要对我国结核病疫情保持清醒的认识,抓住结核病控制的核心和重点。作者从结核潜伏感染的定义、潜伏感染人群发病的时间,以及国外结核病控制的成功经验等方面,进一步说明在结核病高负担国家.近期传播是导致结核病高疫情的主要原因,发现传染源仍然是目前结核病控制的核心;同时,提出重视留取痰液质量和建立区域性实验室是提高我国病原学检测能力、发现传染源、控制结核病传播的重要手段。     

儿童结核病的实验室诊断现状与进展

儿童结核病是全球结核病防控工作的重要组成部分,诊断儿童结核病主要依靠实验室检查结果,但由于儿童结核病本身和标本的特殊性,实验室准确、快速地诊断儿童结核病仍面临挑战。病原学诊断作为儿童结核病诊断的金标准,其敏感度不佳;以超敏结核分枝杆菌和利福平耐药基因检测(Xpert MTB/RIF Ultra)为代表的新型分子生物学检测技术因其较高的敏感度和较短的检测时间有其应用前景;结核菌素皮肤试验(TST)被WHO推荐用于中低收入国家;直接抗原检测技术在少菌、肺外结核标本中敏感度高,在儿童结核病的检测中具有独特价值;其他免疫学新方法对于区分潜伏和活动性结核感染方面具有重要意义;此外,目前已有检测结核分枝杆菌感染后基因表达、蛋白质产生和生物标志物变化的新方法投入研究。留取多份标本或不同标本类型、不同检测方法联合检测有助于提高儿童结核病的检出率。提高结核病在现有方法和非侵入性、易获取标本中的检出率,以及评估新的生物标志物和新技术的适用性是未来儿童结核病实验室诊断研究的方向。     

Tuberculosis in Asia

1. Philippines: The development, expansion and maintenance of pilot area activities: Cristina B. Giango (Technical Division, Cebu Provincial Health Office, the Philippines) In 1994, the Department of Health developed the new NTP policies based on WHO recommendations and started a pilot project in Cebu Province in collaboration with the Japan International Cooperation Agency. To test its feasibility and effectiveness, the new NTP policies were pre-tested in one city and one Rural Health Unit. The test showed a high rate of three sputum collection (90%), high positive rate (10%), and high cure rate (80%). Before the new guidelines were introduced, the new policy was briefed, a baseline survey of the facility was conducted, equipment was provided, and intensive training was given. Recording/Reporting forms and procedures were also developed to ensure accurate reporting. Supervision, an important activity to ensure effective performance, was institutionalized. Laboratory services were strengthened, and a quality-control system was introduced in 1995 to ensure the quality of the laboratory services. With the implementation of DOTS strategy, barangay health workers were trained as treatment partners. In partnership with the private sector, the TB Diagnostic Committee was organized to deliberate and assess sputum negative but X-ray positive cases. The implementation of the new NTP guidelines in Cebe Province has reached a satisfactory level, the cure rate and positive rate have increased, and laboratory services have improved. Because of its successful implementation, the new NTP guidelines are now being used nationwide. 2. Nepal: The DOTS Strategy in the area with hard geographic situation: Dirgh Singh Bam (National Tuberculosis Center, Nepal) Three groups of factors characterize the population of Nepal: 1) Socio-cultural factors, e.g. migration, poverty, language; 2) Environmental factors, e.g. geography and climate; and 3) Political factors, prisoners and refugee populations. These factors pose particular problems for implementing DOTS in various ways. Socio-cultural and environmental factors are particularly important in Nepal, and several measures have been developed to overcome these difficulties. One is active community participation through the DOTS committee. The committee consists of a group of motivated people, including social workers, political leaders, health services providers, journalists, teachers, students, representatives of local organizations, medical schools and colleges, industries, private practitioners, and TB patients. One DOTS committee is formed in every treatment center. A key role of the DOTS committee is to identify local problems and their solutions. It increases public awareness about TB and DOTS; supports people with TB in the community by providing treatment observers and tracing late patients; and encourages cooperation among health institutions, health workers, NGOs, and political leaders. The case finding rate is now 69%, and nearly 95% of diagnosed TB cases are being treated under DOTS. The treatment success rate of new smear-positive cases is nearly 90%. Thus, DOTS increases the case finding and treatment success. 3. Cambodia: HIV/TB and the health sector reform: Tan Eang Mao (National Center for Tuberculosis and Leprosy Control, Cambodia) Cambodia is one of the 23 high burden countries of tuberculosis in the world. Moreover, HIV/AIDS has been spreading rapidly since 1990s, which is worsening the tuberculosis epidemics. To cope with the burden, Cambodia has started implementation of DOTS in 1994 and has expanded it to most of public hospitals across the country by 1998. NTP of Cambodia is now enjoying high cure rate of more than 90%. However, due to the constraints such as weak infrastructure and the poverty, it is proved that many of TB sufferers do not have access to the TB services, resulting in still low case detection rate. It is for this reason that the NTP has decided to expand DOTS to health center and community level based on the new health system. Its pilot program that has been carried out in collaboration with JICA and WHO since 1999 has achieved promising results with high detection and cure rates. All of the over 900 health centers across the country will be involved in DOTS strategy by 2005. In the fight against TB/HIV, National Center for TB Control is providing free TB screening for PLWH (people living with HIV/AIDS), and it is developing a comprehensive plan of TB/HIV care including home delivery DOT services. 4. China: The World Bank Project and the Prevalence Survey in China: Hong Jin DuanMu (National Tuberculosis Control Center, China) Since 1992, China has utilized a World Bank loan to implement TB control projects among 560 million people in 13 provinces. Free diagnosis and treatment services have been provided to all patients, and a fully supervised standard short-course chemotherapy was applied to all diagnosed tuberculosis patients. In 1999, more than 190,000 smear-positive cases, ten times the number in 1992, were detected, and the registration rate of new cases reached 30 per 100,000 population. From 1992 to 1999, a total of 1.40 million smear-positive TB patients were discovered. The cure rate of smear-positive TB patients has been improved to an overall cure rate of 93.6%. The cure rates for the new cases and re-treatment patients were 95.1% and 89.6%, respectively. The fourth nationwide random survey for the epidemiology of tuberculosis was conducted in 2000. The prevalence of active tuberculosis was 367/100,000, the prevalence of infectious tuberculosis was 160/100,000, and the prevalence of smear-positive tuberculosis was 122/100,000. The tuberculosis mortality was 9.8/100,000. 5. Vietnam: The road to reaching the Global Target: Le Ba Tung (Pham Ngoc Thach Tuberculosis and Lung Disease Center, Vietnam) TB control activities started in 1957 and were reorganized in 1986 with the technical assistance of IUATLD, KNCV and material assistance of Medical Committee Netherlands Vietnam (MCNV). The New National TB Control Program follows the main directives of WHO and IUATLD's procedures of case-finding, chemotherapy and management. Passive case-findings are based on sputum smear. Chemotherapy with priority for smear positive cases is 3SHZ/6S2H2 for new cases and 3HRE/6H2R2E2 for retreated cases, which is undertaken with directly observed therapy (DOT strategy) mainly at commune health posts. Since 1989, DOTS strategy with 2SHRZ/6HE for new cases and 2SHRZE/1HRZE/5H3R3E3 for retreated cases has gradually been introduced in districts and communes of every province. In 1995, the government established the National and Provincial TB Control Steering Committees and has provided incentives for detected smear positive cases and cured smear positive cases. The government has also started strengthening the program of managerial and supervisory capacity for TB staff and has promoted the cooperation of all associated organizations of TB control. The WHO global surveillance and monitoring project reports that in 2000 Vietnam reached the global target, i.e., 99.8% population covered by DOTS with 80% of expected new smear positive cases being detected and a high cure rate ranging from 85.3% in 1989 to 90.3% in 1999. A distinguishing aspect of TB control in Vietnam is the effective international partnerships combined with high political commitment of the government nationally and provincially as well as active participation of all organizations in the community.     

Tuberculosis in St. Petersburg and the Baltic Sea region

Tuberculosis (TB) remains a global public health concern and challenges the national structures for infection control and health care, as well as international institutions, to develop and implement new strategies to control and combat this disease. In our report, we investigated the TB epidemiological situation in St. Petersburg and the countries around the Baltic Sea using national epidemiological statistics and epidemiological reports of international organizations, such as the WHO and Euro-TB. After the disintegration of the Soviet Union, a steep increase in tuberculosis was seen in the Russian Federation, St. Petersburg and the Baltic States, after which it stabilized at levels significantly higher compared to the Nordic countries. Moreover, the epidemiological situation in St. Petersburg and the Baltic States was aggravated by the emergence and spread of TB/HIV coinfection, as well as that of drug-resistant M. tuberculosis, which imposed further difficulties in gaining control of TB. During the studied period, the TB burden in neither St. Petersburg nor Baltic States has had a significant impact on the epidemiology in the low TB burden neighbouring countries around the Baltic Sea.     

Tuberculosis: trends and the twenty-first century

The global burden of tuberculosis is enormous, even if estimates are somewhat uncertain. The forces counteracting control measures, namely demographic factors, drug resistance, HIV, migration, poverty and marginalization, are enormous as well. With accelerated reforms in tuberculosis programs important progress can be made towards the control of tuberculosis early in the 21st century. This is confirmed by studying reports from countries where control measures have been implemented and sustained. Well-functioning programs can make good use of technological progress, such as improved tools for diagnosis and treatment, when these become available at an affordable cost. It is important now to use the opportunity of increased resources in order to reform tuberculosis programs. The biggest impact on global tuberculosis control in the 21st century can be made in Asia. Success in this part of the world depends on political commitment. Elsewhere, the main forces counteracting control measures are HIV in Africa and multidrug resistance in parts of Europe and the former Soviet Union. Here solutions are still on the drawing board. The long time-frame for tuberculosis control when using the currently recommended strategy, the uncertain impact of "improved" tools on this time-frame and the constant threat that political commitment will not be sustained are reasons why field workers look towards new technology in hope of progress in vaccine research. Here, the prospects are uncertain and the forecasted time-frame is long. Skeptics even doubt that an effective vaccine can be developed. However, when predicting progress it is important to realize that it is for the most part unpredictable.     

Epidemiology of Tuberculosis in Mexico, 1981-1998. Inconsistencies between reports of the WHO and the Ministry of health

OBJECTIVE: To describe the tuberculosis morbidity and mortality trends in Mexico, by comparing the data reported by the Ministry of Health (MH) and the World Health Organization (WHO) between 1981 and 1998. MATERIAL AND METHODS: The number of cases notified in the past few years, their rates, and the trends of the disease in Mexico were analyzed. The incidence of smear-positive pulmonary tuberculosis was estimated for 1997 and 1998 with the annual tuberculosis infection risk (ATIR), to estimate the percentage of bacilliferous cases in 1997-1998. RESULTS: WHO reported more tuberculosis cases for Mexico than the MH. However, this difference has decreased throughout the years. The notification of smear-positive cases remained stable during 1993-1998. The estimated percentages of detection were 66% for 1997 and 26% for 1998 (based on ATIR of 0.5%). Tuberculosis mortality decreased gradually (6.7% per year) between 1990 and 1998, whereas the number of new cases increased, suggesting the persistence of disease transmission in the population. CONCLUSIONS: Inconsistencies between case notifications from national data and WHO were considerable, but decreased progressively during the study period. According to ATIR estimations, a considerable number of infectious tuberculosis cases are not detected. The English version of this paper is available at: http://www.insp.mx/salud/index.html.     

抗结核药品固定剂量复合制剂的临床使用专家共识

全球现代结核病控制策略提出,对肺结核患者持续不间断地供应抗结核药品,对初治肺结核患者实行标准化短程化疗方案治疗和全程管理,其目的是为提高肺结核患者规范治疗率和治愈率。为了进一步提高肺结核患者治疗的依从性,减少患者每次口服药品片数,简化医生开药处方,防止由于治疗用药处方不合理、服药剂量不恰当所致的耐药结核病的发生,1994年WHO和国际防痨与肺部疾病联合会(IUATLD)推荐对肺结核患者使用抗结核药品固定剂量复合制剂(FDC)。我国相继在不同省(自治区、直辖市)开展了多项FDC在国家结核病防治规划中应用的实施性研究,结果表明FDC对肺结核治疗的可行性和有效性,为FDC纳入到国家结核病防治规划提供了重要科学依据。本共识经全国有关结核病防治、临床和基础研究等领域的专家反复讨论,对FDC使用的意义、药效学和药代动力学、我国FDC的多项应用研究结果、我国FDC的制剂类型和规格,以及FDC的临床使用建议等,形成了《抗结核药品固定剂量复合制剂的临床使用专家共识》,为制订全国抗结核药品使用策略和肺结核患者的治疗用药提供参考。     

Tuberculosis treatment outcomes in Europe: a systematic review.

In order to facilitate the control of tuberculosis (TB), the World Health Organization (WHO) has defined a standardised short-course chemotherapy and a strategy, directly observed therapy. In 2000, WHO surveillance of TB treatments in Europe recorded a successful outcome rate of 77%. The aim of this report is to estimate treatment outcomes in European countries based on published studies and to identify their determinants. A systematic review was conducted of published reports of TB treatment outcomes in Europe. Meta-analysis, meta-regression and subgrouping were used to pool treatment outcomes and analyse associations with mean age, sex, immigration status and multidrug resistance. Of the 197 articles identified in the search, 26 were eligible for the review; 74.4% of outcomes were successful, 12.3% were unsuccessful and 6.8% of patients died. Heterogeneity was high for all outcomes. National estimates were possible for six countries. Multidrug resistance was inversely associated with successful outcome, which were fewer in populations with >9% multidrug-resistant TB, and in patients aged <44 yrs. Successful tuberculosis treatment outcomes were below the 85% threshold suggested by the World Health Organization. There was an inverse association with levels of multidrug-resistant tuberculosis. The unexplained heterogeneity between the studies for unsuccessful outcomes seems to be due to differing interpretations given to World Health Organization definitions.     

Expert consensus of clinical application of fixed-dose combination formulations

全球现代结核病控制策略提出,对肺结核患者持续不间断地供应抗结核药品,对初治肺结核患者实行标准化短程化疗方案治疗和全程管理,其目的是为提高肺结核患者规范治疗率和治愈率。为了进一步提高肺结核患者治疗的依从性,减少患者每次口服药品片数,简化医生开药处方,防止由于治疗用药处方不合理、服药剂量不恰当所致的耐药结核病的发生,1994年WHO和国际防痨与肺部疾病联合会(IUATLD)推荐对肺结核患者使用抗结核药品固定剂量复合制剂(FDC)。我国相继在不同省(自治区、直辖市)开展了多项FDC在国家结核病防治规划中应用的实施性研究,结果表明FDC对肺结核治疗的可行性和有效性,为FDC纳入到国家结核病防治规划提供了重要科学依据。本共识经全国有关结核病防治、临床和基础研究等领域的专家反复讨论,对FDC使用的意义、药效学和药代动力学、我国FDC的多项应用研究结果、我国FDC的制剂类型和规格,以及FDC的临床使用建议等,形成了《抗结核药品固定剂量复合制剂的临床使用专家共识》,为制订全国抗结核药品使用策略和肺结核患者的治疗用药提供参考。     

Tuberculosis

Tuberculosis results in an estimated 1·7 million deaths each year and the worldwide number of new cases (more than 9 million) is higher than at any other time in history. 22 low-income and middle-income countries account for more than 80% of the active cases in the world. Due to the devastating effect of HIV on susceptibility to tuberculosis, sub-Saharan Africa has been disproportionately affected and accounts for four of every five cases of HIV-associated tuberculosis. In many regions highly endemic for tuberculosis, diagnosis continues to rely on century-old sputum microscopy; there is no vaccine with adequate effectiveness and tuberculosis treatment regimens are protracted and have a risk of toxic effects. Increasing rates of drug-resistant tuberculosis in eastern Europe, Asia, and sub-Saharan Africa now threaten to undermine the gains made by worldwide tuberculosis control programmes. Moreover, our fundamental understanding of the pathogenesis of this disease is inadequate. However, increased investment has allowed basic science and translational and applied research to produce new data, leading to promising progress in the development of improved tuberculosis diagnostics, biomarkers of disease activity, drugs, and vaccines. The growing scientific momentum must be accompanied by much greater investment and political commitment to meet this huge persisting challenge to public health. Our Seminar presents current perspectives on the scale of the epidemic, the pathogen and the host response, present and emerging methods for disease control (including diagnostics, drugs, biomarkers, and vaccines), and the ongoing challenge of tuberculosis control in adults in the 21st century.