International Tuberculosis Research in China

国际结核病研究在中国

• 批准号: 8157068
• 负责人: Clifton Barry
• 金额: $ 89.65万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8157068
• 关键词: China; International; Research; Tuberculosis

The Peoples Republic of China has the second highest incidence of TB in the world, with a 2004 estimated rate of 101 cases/100,000 persons/year. Based on the data of the 4th national TB epidemiological survey in 2000, it is estimated that there were 1.96 million pulmonary TB cases. With an established MDR-TB prevalence of 10.7%. There were an estimated 209,720 cases of pulmonary, bacteriologically confirmed MDR-TB in China in 2000. Of note, about half of all prevalent cases of TB disease in 2000 were extrapulmonary. Much of this MDR disease is located in a few places in China with Henan Provence having the highest number of reported cases. In 2009 NIAID Deputy Director Auchincloss signed a letter of intent with the Henan Provincial Bureau of Health to establish a collaborative research center in Zheng Zhou, capital of Henan province. As a result, the provincial government has committed to construction of a new infectious disease hospital to house the research facility and better accommodate the heavy burden of patients in Henan Province. Construction of that facility has begun and completion is expected within two years. Study team members have made multiple trips for training and multiple outside training activities have been conducted to get the Chinese study team ready for initiation of an observational protocol in their current hospital. The initial protocol was approved by the NIAID IRB in January 2010, but enrollment only commenced after the lab renovation and installation of the NIAID-provided equipment was completed in July 2010. The hospital clinical laboratory has been upgraded to the point that clinical samples can be processed at the appropriate safety level. A prospective, longitudinal Natural History study titled A Natural History Study of Tuberculosis in China: Correlates of a Successful Response in Treatment (10-I-N060) has been initiated to monitor 150 subjects with suspected TB at the Henan Provincial Chest Hospital during their initial response to antituberculous chemotherapy. The subjects are divided into three cohorts suspected to have TB: A) AFB smear positive pulmonary disease, B) smear negative pulmonary disease, and C) extra pulmonary disease (EPTB) in order to reflect the range of TB confirmation and treatment at Henan Provincial Chest Hospital. We will also enrolling 25 controls to determine baseline values for immunologic responses and laboratory values. In this exploratory study, we will be looking at the change in total volume of disease by CT scan at baseline, 2 and 6 months. In addition, we will monitor chemotherapeutic regimens, changes in the host immune response, overall changes in clinical parameters, initial and acquired drug-resistance of the infecting isolates, and changes in bacterial and host markers in subject samples during chemotherapy. In each case, we will look for associations of these parameters with rates of disease resolution correlated with specific structural features determined by CT scanning the site of TB disease (with the exception of TB meningitis and cutaneous TB, for which there is no specific lesion to follow radiographically). This study will allow us to evaluate the use of initial presentation entry criteria in future clinical trials, eventual TB diagnosis confirmation using these entry categorizations, impact of initial regimen selection and subsequent modifications, mycobacterial strain characteristics, extent of disease, types of lesions and host immunologic response to the overall outcome of chemotherapy as well as to potentially identify surrogate markers for improving monitoring of the response to chemotherapy. Currently 20 subjects have been enrolled into the study in 2 months with 9 subjects in cohort A and B respectively and 2 subjects in Cohort C. The 8 follow up visits are being successfully scheduled within the window period by the Chinese staff and all subjects are returning for these visits. The first subject who was enrolled in March has just completed the study for a total enrollment on August 30, 2010 of 20. Study personnel are culturing samples, collecting and freezing plasma, performing gamma interferon stimulation assays, and filling out CRFs on a regular basis. The Open Clinica database designed for the study has been released and is being finalized with data entry expected to begin after the NIAID teams next visit to the site.

中华民国是世界上结核病发病率第二高的国家，2004 年估计发病率为每年每 10 万人 101 例。根据2000年第四次全国结核病流行病学调查数据，估计全国肺结核病例为196万例。 确定的耐多药结核病患病率为 10.7%。 2000年，中国估计有209,720例经过细菌学证实的肺部耐多药结核病病例。值得注意的是，2000年所有流行结核病病例中约有一半是肺外结核病。 这种耐多药疾病大部分集中在中国的少数几个地方，其中河南普罗旺斯报告的病例数最多。 2009年，NIAID副主任Auchincloss与河南省卫生厅签署了在河南省省会郑州建立合作研究中心的意向书。因此，省政府承诺建造一所新的传染病医院来容纳研究设施，并更好地容纳河南省沉重的患者负担。该设施的建设已经开始，预计在两年内完工。研究小组成员多次出差参加培训，并进行了多次外部培训活动，为中国研究小组在目前所在医院启动观察方案做好准备。最初的方案于 2010 年 1 月获得 NIAID IRB 批准，但在 2010 年 7 月完成实验室改造和 NIAID 提供的设备安装后才开始入组。医院临床实验室已升级到可以采集临床样本的程度。在适当的安全级别进行处理。 一项名为《中国结核病自然史研究：治疗成功反应的相关性》(10-I-N060) 的前瞻性、纵向自然史研究已启动，以监测河南省胸科医院 150 名疑似结核病患者的初始治疗过程。对抗结核化疗的反应。将受试者分为三组疑似结核病患者：A) AFB 涂片阳性肺部疾病、B) 涂片阴性肺部疾病和 C) 肺外疾病 (EPTB)，以反映河南省结核病确诊和治疗的范围胸科医院。我们还将招募 25 名对照来确定免疫反应的基线值和实验室值。在这项探索性研究中，我们将通过 CT 扫描观察基线、2 个月和 6 个月时疾病总量的变化。此外，我们将监测化疗方案、宿主免疫反应的变化、临床参数的总体变化、感染分离株的初始和获得性耐药性，以及化疗期间受试者样本中细菌和宿主标志物的变化。在每种情况下，我们都会寻找这些参数与疾病消退率之间的关联，而疾病消退率与通过 CT 扫描结核病部位确定的特定结构特征相关（结核性脑膜炎和皮肤结核除外，因为这两种疾病没有特定的病灶）遵循射线照相）。这项研究将使我们能够评估初始表现进入标准在未来临床试验中的使用、使用这些进入分类的最终结核病诊断确认、初始治疗方案选择和后续修改的影响、分枝杆菌菌株特征、疾病程度、病变类型和宿主对化疗总体结果的免疫反应，以及潜在地识别替代标记以改善对化疗反应的监测。 目前，2个月内已有20名受试者入组，其中A组和B组各9名受试者，C组2名受试者。中方工作人员在窗口期内成功安排了8次随访，所有受试者均已返回对于这些访问。 3月份入组的第一名受试者刚刚完成研究，总入组时间为2010年8月30日，研究人员正在培养样本、采集和冷冻血浆、进行γ干扰素刺激试验、定期填写CRF 。为该研究设计的 Open Clinica 数据库已经发布，并正在最终确定，数据输入预计将在 NIAID 团队下次访问该站点后开始。