Transmission Of Tuberculosis And Drug Resistant Tuberculosis

Tuberculosis is an old transmitted disease that is still threatening human health. In the middle of nineteen centry, with the apperence of BCG vaccine and anti-tuberculosis drugs, people thought it would be under control. But from the nineteen nineties, with the pandemic of human immunodeficiency virus (HIV), the emergence of drug-resistance tuberculosis, and co-infection with other diseases like diabeates, tuberculosis came back and become one of the most important public health problems again. According to the annual report from World Health Organization (WHO), there were about 9,400,000 new tuberculosis cases and 1,700,000 casualties in 2009 worldwide.Drug resistant tuberculosis, especially multidrug resistant (MDR) and extensive drug resistant (XDR) tuberculosis are the new challenges of tuberculosis control. In the "Report of the Baseline Survey of Drug Resistant Tuberculosis in China" (conducted in 2007-2008) published by the Ministry of Health of PR China, in all sputum positive tuberculosis patients, the drug resistant rate is 37.79%, drug resistant rate among new cases is 35.16%, and drug resistant rate among treated cases is as high as 55.17%(95%CI 50.01%-60.21%), which means there will be 560,000 drug resistant tuberculosis cases annually, among them,459,000 are new cases, and 101,000 are retreated cases.China has about 15% of the global burden of tuberculosis. However, WHO estimates that one third of the world's MDR tuberculosis cases are in China. DOTs (Directly Observed Treatment Short Course) strategy had been performed in China since 1990s and covered the whole country now. The discovery rate of new sputum smear positive patients is more than 70%; cure rate is higher than 85%. But drug resistant tuberculosis patient number didn't decease. There are also reports from other countries and regions that DOTs strategy cannot decrease tuberculosis incidence rate. There is no catholicon for all countries and nations to stop tuberculosis immediately, because each country or region has its own situation. Thus each country should find their own characteric of tuberculosis transmission to develop their own way to control the disease. For this porpose, we conducted the study, sought to determine the characteristics, prevalence, and relative frequency of ongoing transmission of MDR and XDR tuberculosis in Shanghai, one of the largest cities in Asia. For the 4,379 culture positive tuberculosis cases diagnosed during March 2004 through November 2007 with drug susceptibility test results available,247 (5.6%) were infected with a MDR strain of M. tuberculosis and 11 (6.3%) of the 175 MDR patients whose isolate was tested for susceptibility to second-line drugs, were XDR. More than half of the patients with MDR and XDR were newly diagnosed and had no prior history of tuberculosis treatment. Nearly 55% of the MDR-TB patients and 45.5% of the XDR-TB patients had been successfully treated. Ongoing transmission of MDR and XDR strains is a serious problem in Shanghai.From the second line drug susceptibility test performed in the MDR-TB isolates, we found that there are acturally 24.8% new patients and 40.7% retreated patients resistant to fluoroquinolone. Also this kind of antobiotic had been widely used to treat other bacteria infections. To determine the prevalence level of fluoroquinolone resistance among TB patients, we performed a case-control study among 605 clinical TB patients in Shanghai, China. Mutations in the quinolone resistance determining region (QRDR) of gyrA were found in 81.5% of fluoroquinolone resistant M. tuberculosis isolates in Shanghai and it was used as the molecular marker of the fluoroquinolone resistance phenotype in this study. GyrA mutation was found in 1.9% clinical isolates that were pan-susceptible to first-line drugs, and 21.5% of MDR isolates. Among all fluoroquinolone resistant patients,49.2% of them are new patients. Transmission of drug resistant tuberculosis is an important problem in Shanghai.Transmission of drug resistant tuberculosis is serious in Shanghai, then what about the drug susceptibilible tuberculosis? Using molecular epidemiology method, we performed a population-based prospective study in selected districts and counties in three provinces from December 2006 through December 2008 to detect transmission of tuberculosis and to identify the risk factors for transmission of M. tuberculosis in China.We isolated and successfully cultured M.tuberculosis from 896 patients, some petients refused the questionaire, so there are 794 patients inrolled in this study, among them,24.7% were from Shandong province,34.9% from Sichuan province and 40.4% from Shanghai. Each patient has one sample included in the analysis.From genotyping, we found 19 clusters with 43(13.4%,43/321) isolates in Shanghai,12 clusters with 30 (10.8%,30/296) isolates in Sichuan, and28 clusters with 78(39.8%,78/196) isolates in Shandong. The cluster rate in Shandong is 25.5%, significantly different from the rate in Shanghai (OR3.23,95% CI:2.17%-4.80%, p<0.00005) or Sichuan(OR5.44,95% CI:3.31%-9.05%, p<0.00005).We found epidemiological links between pathets in 6 clusters.To detemine the risk factors of tuberculosis transmission, we compared the clusterd patients and non-clustered patients, found that work as a farmer, low family monthly income and sputum smear positive are the independent risk factors of tuberculosis.All these studies indicate that transmission of tuberculosis, including drug resistant tuberculosis is an important problem in China. There should be increased emphasis on finding sites of transmission and implementing environmental controls. Sputum smear positive patients are more likely to cause transmission; the early detection, appropriate treatment and case management of sputum smear positive patients are also important.