Transmission dynamics and phylogeography of Mycobacterium tuberculosis in China based on whole-genome phylogenetic analysis.

OBJECTIVES: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. METHODS: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. RESULTS: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. CONCLUSIONS: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.

Epidemiological Trends of Drug-Resistant Tuberculosis in China From 2007 to 2014: A Retrospective Study.

The emergence and spread of drug-resistant tuberculosis (DR-TB) has become the major concern in global TB control nowadays due to its limited therapy options and high mortality. A comprehensive evaluation for the epidemiological trends of DR-TB in mainland China, of which TB incidences remain high, is essential but lacking. This study aimed to describe the trends of DR-TB overtime, especially multidrug-resistant TB (MDR-TB); and to identify unique characteristics of MDR-TB cases compared with drug-susceptible TB cases in Mainland China. We retrospectively analyzed surveillance data collected from 36 TB prevention and control institutions in Shandong Province, China over an 8-year period. Unique characteristics of MDR-TB were identified; Chi-square test for trends and linear regression were used to assess the changes in proportions of different resistance patterns overtime. The overall MDR rate was 6.2% in our sample population. There were no statistically significant changes in the percentage of drug-susceptible, isoniazid (INH) resistance, ethambutol (EMB) resistance, streptomycin (SM) resistance, and MDR TB during our study period except that the overall rifampin (RFP) resistance and rifampin monoresistance (RMR) increased at a yearly rate of 0.2% and 0.1%, respectively. Among those with known treatment histories, a higher MDR rate of 8.7% was observed, in which 53.9% were primary MDR-TB patients, and this rate was increasing at a yearly rate of 4.1% over our study period. MDR-TB patients were more likely to be female (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.05-1.34), aged 25 to 44 years (OR, 1.67; 95%CI, 1.45-1.93), retreated (OR, 11.95; 95%CI, 9.68-14.76), having prior TB contact (OR, 1.89; 95%CI, 1.19-2.78) and having cavity (OR, 1.57; 95%CI 1.36-1.81), or bilateral disease (OR, 1.45; 95%CI 1.19-1.76) on chest radiology. Persistent high levels of MDR-TB, increasing rates of primary MDR-TB and RMR characterize DR-TB cases in mainland China; community-acquired drug resistance may be one of the most modifiable factors in future TB control strategies.

The Relationship between Extensively Drug-Resistant Tuberculosis and Multidrug-Resistant Gram-Negative Bacilli.

OBJECTIVE: The relationship between extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant Gram-negative bacilli (MDR-GNB) is unclear. Identification of the relationship between XDR-TB and MDR-GNB would have important implications for patient care. METHODS: We conducted a retrospective study reviewing the records of patients admitted with a confirmed pulmonary TB from 2011 to 2014. To identify the relationship between XDR-TB and MDR-GNB, univariable comparison and multivariable logistic regression were performed. RESULTS: Among 2962 pulmonary TB patients, 45(1.5%) patients had a diagnosis of XDR-TB. A total of 165 MDR-GNB strains were detected in 143 (4.8%) pulmonary TB patients. XDR-TB patients had a significantly higher occurrence of MDR-GNB than non-XDR-TB patients (24.4% vs. 4.5%; P<0.001). Age (OR 1.02, 95% CI 1.01-1.03), hypoalbuminemia (OR 1.48, 95% CI 1.18-1.85), chronic renal failure (OR 6.67, 95% CI 1.42-31.47), chronic hepatic insufficiency (OR 1.99, 95% CI 1.15-3.43), presence of XDR-TB (OR 6.56, 95% CI 1.61-26.69), and duration of TB diagnostic delay (OR 1.01, 95% CI 1.00-1.02) were the independent risk factors for MDR-GNB infection. CONCLUSIONS: Patients with XDR-TB have a significantly higher risk of being affected by MDR-GNB pathogen. The underlying mechanism association warrant further studies.

Multidrug-Resistant Tuberculosis in Patients with Chronic Obstructive Pulmonary Disease in China.

BACKGROUND: Relatively little is known about the specific relationship and impact from chronic obstructive pulmonary disease (COPD) on multidrug-resistant tuberculsosis (MDR-TB). METHODS: We conducted a retrospective study included patients aged ≥40 years with a confirmed pulmonary TB at three tertiary hospitals (Shandong, China) between January 2011 and October 2014. Univariable and multivariable analyses were performed to identify the relationship of MDR-TB and COPD. RESULTS: A total of 2164 patients aged ≥ 40 years with available results of drug susceptibility test (DST) and medical records were screened for this study: 268 patients with discharge diagnosis of COPD and 1896 patients without COPD. Overall, 14.2% of patients with COPD and 8.5% patients without COPD were MDR-TB. The rate of MDR-TB were significantly higher in patients with COPD (P<0.05). Migrant (odds ratios (OR) 1.32, 95% confidence interval (CI) 1.02-1.72), previous anti-TB treatment (OR 4.58, 95% CI 1.69-12.42), cavity (OR 2.33, 95% CI 1.14-4.75), and GOLD stage (OR 1.86, 95% CI 1.01-2.93) were the independent predictors for MDR-TB among patients with COPD. CONCLUSIONS: MDR-TB occurs more frequently in patients with underlying COPD, especially those with being migrant, previous anti-TB therapy, cavity and severe airway obstruction.