Molecular Detection Of Mutations Associated With First And Second-Line Drug Resistance In Extensively Drug Resistance Tuberculosis And The Mechanism Inducing Drug Resistance In China

Since 1990s Global tuberculosis epidemic peaked up, and the appearance of drug resistance tuberculosis was one of the important reasons.First have seen the worldwide appearance of multidrug-resistant (MDR) tuberculosis, then followed by extensively drug-resistant (XDR) tuberculosis. Drug resistance severely threatens tuberculosis control, since it raises the possibility of a return to an era in which drugs are no longer effective. The number of countries reporting at least one case of XDR-TB had risen to 58 by January, 2010, although this change is probably a result of increased efforts to identify XDR tuberculosis rather than an increase in prevalence or distribution of the disease.According to the 2007-2008 Chinse national tuberculosis resistance baseline survey reports, nealy 56 million new cases were found per year, 120,000 cases were MDR-TB, and XDR-TB about 10,000 cases per year. The treatment for XDR-TB has not been confirmly established This disease needs at least 4 to 5 drugs to treatment at least 18-24 months. Some studies had found XDR-TB having 5.45 times of mortality risk than MDR tuberculosis.Diagnosis of drug-resistant tuberculosis relies onPPD,clinical features,X-ray and drug susceptibility tests of M tuberculosis strains,which needed 4-8 weeks.Delays in diagnosis lead to clinical deterioration, death, and further transmission.Rapid tests with higher sensitivity and specificity were needed for TB control.To get a better understanding of XDR-TB, we characterized 115 XDR-TB isolates and serial isolates recovered from 7 patients with XDR-TB,by use sequencing of rpoB, katG, mabA-inhA-promoter, pncA, embB, rpsL, rrs, and gyrA.sequencing of rpoB, katG, mabA-inhA-promoter, pncA, embB, rpsL, rrs,and and gyrA. And used 16 loci of VNTR for 7patients.Mutations predominant among XDR-TB were S315T (katG) (83.48%of isolates), S531L, D513G(rpoB) (45.42%,22.60%of isolates), D94G/N/A/H (gyrA) (47.8%ofisolates), K43R(rpsL) (68.42%of isolates),and A1401G (rrs) (43.20%of isolates),M3061/N/L(embB)(58.33%of isolates) and 72.17%of isolates had pncA mutation. S315T (katG), S531 L(rpoB).D94G/N/A/H (gyrA) and M3061 (embB) appeared more frequently in high resistance islates than Iow resistance isolates.For the 7 XDR-TB evolution patients,we found 3 of them were infected by homology isoltes with the same VNTR results.4 of them were infected by heterogeneity isolates with different VNTR results.6 of them were infected by drug resistant isolates.And 3 of them had mixed infection.4 patients had acquired and amplified resistance. Exogenous infection of drug resistant tuberculosis was a important infactor inducing XDR-TB.More endeavour should be done to prevent drug resistant tuberculosis transmission.