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.
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