title: Comparison of the socio-demographic and clinical features of pulmonary TB patients infected with sub-lineages within the W-Beijing and non-Beijing Mycobacterium tuberculosis.
abstract: BACKGROUND
  Highly lethal outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are increasing. Mycobacterium tuberculosis variant Beijing family and its members is regarded as a successful clone of M. tuberculosis that is associated with drug resistance in China. Understanding the genetic characteristics and molecular mechanism of drug resistant tuberculosis within Beijing family may help to clarify its origin and evolutionary history and the driving forces behind its emergence and current dissemination.
  
  
  METHODS
  Totally of 1222 Mycobacterium tuberculosis isolates were recovered from patients in six counties of two provinces in eastern China within 2010/2012. Strain lineage and its major subgroups were studied respectively by using Spoligotyping and MIRU-VNTR. The 1st-line drug susceptibility was analyzed by proportional method and 2nd-line drug susceptibility was determined by the HAINs MTBDRsl test. The genetic characterization of drug resistance was analyzed by sequencing the previously reported genes and loci associated with drug resistance together with the multiple genotyping including MIRU-VNTR, Spoligotyping and LSP genotyping.
  
  
  RESULTS
  Of the 1222 Mtb isolates, 298 (24.4%) were resistant to 1st-line drug and 73 (5.9%) were simultaneously resistant to INH and RIF namely MDR-TB. Respectively 23.8% of 1st-line drug resistant TB and 12.0% of the drug susceptible TB contained the mutation associated with 2nd-line drugs by HAINs test. The Spoligotyping of 1222 Mtb isolates revealed the 967 (79.1%) of the isolates belonged to the W-Beijing family. Within W-Beijing family, 78.8% MDR-TB were observed in the isolates with simultaneous deletion of RD105 and RD207, with sub-lineage 181 accounting for 75% of MDR-TB. Analysis of 24 MIRU-VNTR loci revealed that 88.2% (15/17) of MDR and extensively drug resistant (XDR) clustered isolates were sub-lineage 181.
  
  
  CONCLUSIONS
  Sublineage 181 might have the capacity to spread throughout the general community in rural China. This is the first report on the extensive association of sub-lineage 181 with MDR TB and possibly pre-XDR TB and XDR TB. It is important to monitor sublineage 181 to verify its heightened transmission and understand its importance in the global MDR-TB and XDR-TB epidemics.
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China. Electronic address: yhu@fudan.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA. Electronic address: barun.mathema@gmail.com.
authors.forename: Barun
authors.initials: B
authors.lastname: Mathema
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China. Electronic address: 14211020080@fudan.edu.cn.
authors.forename: Xubin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China. Electronic address: 14211020004@fudan.edu.cn.
authors.forename: Dange
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China. Electronic address: wljiang@fudan.edu.cn.
authors.forename: Weili
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China.
authors.forename: Weibing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China. Electronic address: bxu@shmu.edu.cn.
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use; D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D010641:Phenotype; D012959:Socioeconomic Factors; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology* / Q000635:transmission; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology* / Q000635:transmission
chemical_list: D000995:Antitubercular Agents
keywords: Beijing family; Multidrug resistance; Sublineage; Tuberculosis