Transmission is a Noticeable Cause of Resistance Among Treated Tuberculosis Patients in Shanghai, China.

It is generally believed that drug resistance among treated tuberculosis (TB) patients is as a result of acquired drug resistance due to inappropriate treatment. Previous studies have shown that primary drug resistance caused by transmission also plays a role among treated cases. Differentiating the two types of drug resistance will help in developing appropriate strategies for control of drug resistant tuberculosis. In this study, we tested the hypothesis that drug resistance among treated TB patients is mainly caused by primary resistance rather than acquired resistance. Defining resistance profiles by molecular drug susceptibility test, we used Unit Variable Number Tandem Repeats (VNTR) to genotype and Whole Genome Sequencing (WGS) to confirm the accordance of the first and last Mycobacterium tuberculosis isolates from treated pulmonary TB patients in Shanghai from 2009-2015. Among 81 patients with increasing drug resistance, out of 390 patients enrolled, paired isolates from 59.3% (48/81) had different VNTR patterns indicating primary drug resistance. Our results have demonstrated that primary resistance due to exogenous reinfection is the major cause of drug resistance among treated TB patients in Shanghai; thus, strategies aimed at preventing and interrupting transmission are urgently needed to effectively reduce the epidemic of drug resistant tuberculosis.

Prevalence and transmission of pyrazinamide resistant Mycobacterium tuberculosis in China.

Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, however, there are relatively few available data on PZA resistant (PZA-R) rate in China. From June 2009 to June 2012, we selected 493 isolates from five field settings in China to investigate PZA-R by pncA gene sequencing. The result showed that PZA-R rate was 1.0% (2/196) among pan-susceptible isolates, 3.1% (4/130) among isoniazid (INH) mono-resistant isolates, 14.0% (6/43) among rifampin (RIF) mono-resistant isolates and 43.5% (54/124) among multidrug resistant (MDR) isolates. MDR tuberculosis (TB), RIF mono-resistance, and retreatment were found to be risk factors for PZA-R. Newly diagnosed PZA-R TB patients and clustered isolates with identical pncA mutations indicate that transmission of PZA-R isolates plays an important role in emergence of PZA-R TB. The results suggest that, it is necessary to conduct PZA susceptibility test among MDR isolates and modify the treatment regimens accordingly.