Genetic Diversity and Drug Susceptibility of Mycobacterium tuberculosis Isolates in a Remote Mountain Area of China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We determined the genetic diversity of Mycobacterium tuberculosis (MTB) in a remote mountainous area of southwest China and evaluated the resolving ability of single nucleotide polymorphism (SNP) genotyping combined with variable number tandem repeat (VNTR) genotyping for Beijing family strains in association with drug resistance status.</p><p><b>METHODS</b>Three hundred thirty-one MTB strains were isolated from patients living in mountainous regions of southwest China, and 8-loci SNP, VNTR-15 genotyping assays, and drug susceptibility testing of 9 drugs were performed.</p><p><b>RESULTS</b>A total of 183 [55.29% (183/331)] strains were classified into the Beijing family. Of the 183 strains, 111 (60.66%) were defined as modern Beijing strains. The most predominant modern Beijing sub-lineage and ancient Beijing sub-lineage were Bmyc10 [39.34% (72/183)] and Bmyc25 [20.77% (38/183)], respectively. Of the isolates, 19.64% (65/331) were resistant to at least 1 of the 9 anti-TB drugs and 17 [4.98% (17/331)] MTB isolates were multi-drug resistant tuberculosis (MDR-TB). Two hundred sixty-one isolates showed a clustering rate of 14.18% (37/261) and a discriminatory index of 0.9990. The Beijing lineage exhibited a significantly higher prevalence of MDR-TB, as well as resistance to isoniazid (INH), rifampin (RIF), and para-aminosalicylic acid (PAS) when analyzed independently (P = 0.005, P = 0.017, P = 0.014, and P = 0.006 respectively). The Beijing lineage was not associated with genetic clustering or resistance to any drug. In addition, genetic clustering was not associated with drug resistance.</p><p><b>CONCLUSION</b>MTB strains demonstrate high genetic diversity in remote mountainous areas of southwest China. Beijing strains, especially modern Beijing strains, are predominant in remote mountainous area of China. The combination of 8-loci SNPs and VNTR-15 genotyping is a useful tool to study the molecular epidemiology of MTB strains in this area.</p>

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the prevalence of primary drug-resistant tuberculosis (TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis (MDR-TB).</p><p><b>METHODS</b>A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains.</p><p><b>RESULTS</b>Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75 (80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65 (69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine (31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531L rpoB mutation.</p><p><b>CONCLUSION</b>This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.</p>

Relationship between Beijing genotypes of Mycobacterium tuberculosis and drug-resistant phenotypes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the distribution of the Beijing genotypes of Mycobacterium tuberculosis (M. tuberculosis) and the relationships between Beijing genotype strains and drug-resistant phenotypes in China.</p><p><b>METHODS</b>Clinical isolates were collected during a 9-month research period from April to December in 2008 in six geographic regions of China. One isolate that had been biochemically confirmed to be a member of the M. tuberculosis complex was collected from each patient. The demographic data of the patients (eg. sex, age, and history of tuberculosis) as well as the drug resistance patterns and sources of the clinical isolates were collected. Drug susceptibility testing was performed using proportion method. Beijing genotypes of M. tuberculosis were identified by spacer oligonucleotide typing or insertion of IS6110 in the genomic dnaA-dnaN locus.</p><p><b>RESULTS</b>Among the 410 M. tuberculosis clinical isolates, 67.1% (275/410) isolates were Beijing genotypes of M. tuberculosis. Significantly larger proportions of tuberculosis patients were infected with Beijing genotypes in the northeastern regions of China than that of in the central-western regions (chi2 = 20.50, P = 0.000). No significant associations were found either between Beijing genotype strains and patients' age, sex, or treatment history. Multidrug-resistant isolates and rifampin-resistant isolates were more common among Beijing genotype strains than among non-Beijing strains (P = 0.002, P = 0.005).</p><p><b>CONCLUSIONS</b>About two third of the clinical isolates of M. tuberculosis in China are Beijing genotypes. Beijing genotype strains are not correlated with patients' age, sex, treatment history. People living in the northeastern regions of China are more susceptible to Beijing genotypes than those living in the central-western of China. Beijing genotype strains tend to be rifampin-resistant or multidrug-resistant.</p>