| Tuberculosis (TB) reemergence and spread are of worldwide concern, which is largely due to substantial levels of migration of people, increasing circulation of drug-resistant TB, HIV/AIDS epidemic and neglect of national tuberculosis program. Widespread of drug-resistant tuberculosis is considered an important factor of resurgence of TB in China. During the last decade, TB in China has remained a high drug-resistance rate, which renders China one of the hotspots of MDR-TB according to WHO/IUATLD drug-resistance surveillance project. Rural area is home to about eighty percent of TB patients in China at present time, extensive investigation on drug-resistant tuberculosis is urgent at these sites.We determined the susceptibility of four first-line anti-tuberculosis drugs for initial isolates from both new and previously treated TB cases from 2 counties in north Jiangsu province by standardized proportion method. The profile of resistance to all the four drugs were analysed. We conducted an extensive survey on determinants of drug-resistant tuberculosis in rural area using a questionnaire designed on the basis of the previous qualitative study. To further understand the molecular mechanism of drug resistance, a PCR-SSCP assay was used to detect mutations in rpoB gene confering resistance to RIF, and a PCR-RFLP assay to detect a particular substitution in codon 315 (katG S315T), which is associated with INH resistance. Also, we tried to use VNTR typing to characterize M.TB isolates from the study sites, analysed the factors for VNTR clustering. The results are as follows.1. The qualitative study showed that the failure of treatment of tuberculosis is associated with man-made factors in the course of diagnosis and treatment of tuberculosis. Delay in health seeking, poor compliance to treatment is a problem in the county without DOTS program. Aged TB patients generally have longer delay time in health seeking and poor compliance to treatment regimens because of age, disability and bad economic status. Limited health education and propagand about TB led to misdiagnosis, delay in diagnosis, abuse of antibiotics, irregular treatment and a prolonged period of treatment. All of these are possible factors of drug-resistance. 2. Drug susceptibility testing (DST) showed that, among the 152 patients with DST results, 32.9% were resistant to at least one of the first-line anti-tuberculosis drugs. Initial and acquired drug resistance rate were 28.6% and 48.5%, respectively. Resistance to STR and INH (31 cases) is the most common resistance pattern. Resistance rate to INH, STR, RIF and EMB is 26.3%, 24.3%, 18.4% and 10.5%, successively. 17.1% were resistant to both INH and RIF (MDR). Of the 28 RIF resistant isolates 26 (92.9%) were resistant to INH,supporting the idea of using RIF resistance as a surrogate marker for MDR-TB. These study sites should be a hotspot of MDR-TB according to WHO/IUATLD.3. Determinants of drug-resistance in rural north Jiangsu province included, previous treatment for TB, residence in the county without DOTS program, indifference to their health condition and delay in health seeking for more than 1 month. Male patients have a higher resistance rate, and both the youngest and eldest patients have lower rates of resistance. Patients suffering from chronic disease also have lower drug resistance rate. Tuberculosis control program have positive impact on preventing drug-resistance. In the context of a well-functioning DOTS program, drug-resistant TB still has a profoundly adverse impact on treatment outcome. Drug resistance rate and MDR rate are both high in new TB cases, indicating some possible transmission of drug-resistant strains even in the county with DOTS program.4. The overall prevalence of muations in rpoB gene of RIF-resistant strains from the two counties is 71.4%. No mutations were detected in the RIF-susceptible strains. Rifampin resistance arises due to mutations in rpoB gene encoding the DNA-dependent RNA polymerase. 47.5% of the INH-resistant strains have katG S315T substit...
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