title: Extensive transmission of isoniazid resistant M. tuberculosis and its association with increased multidrug-resistant TB in two rural counties of eastern China: a molecular epidemiological study.
abstract: BACKGROUND
  The aim of this study was to investigate the molecular characteristics of isoniazid resistant Mycobacterium tuberculosis (MTB), as well as its contribution to the dissemination of multi-drug resistant TB (MDR-TB) in rural areas of eastern China.
  
  
  METHODS
  A population-based epidemiological study was conducted in two rural counties of eastern China from 2004 to 2005. In total, 131 isoniazid resistant MTB isolates were molecularly characterized by DNA sequencing and genotyped by IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping.
  
  
  RESULTS
  The katG315Thr mutation was observed in 74 of 131 isoniazid resistant isolates and more likely to be MDR-TB (48.6%) and have mutations in rpoB gene (47.3%). Spoligotyping identified 80.2% of isoniazid resistant MTB isolates as belonging to the Beijing family. Cluster analysis by genotyping based on IS6110 RFLP, showed that 48.1% isoniazid resistant isolates were grouped into 26 clusters and katG315Thr mutants had a significantly higher clustering proportion compared to those with katG wild type (73%.vs.18%; OR, 12.70; 95%CI, 6.357-14.80). Thirty-one of the 53 MDR-TB isolates were observed in 19 clusters. Of these clusters, isoniazid resistance in MDR-TB isolates was all due to the katG315Thr mutation; 18 clusters also contained mono-isoniazid resistant and other isoniazid resistant isolates.
  
  
  CONCLUSIONS
  These results highlighted that isoniazid resistant MTB especially with katG315Thr is likely to be clustered in a community, develop extra resistance to rifampicin and become MDR-TB in Chinese rural settings.
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Sven
authors.initials: S
authors.lastname: Hoffner
authors.forename: Weili
authors.initials: W
authors.lastname: Jiang
authors.forename: Weibing
authors.initials: W
authors.lastname: Wang
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015373:Bacterial Typing Techniques; D002374:Catalase / Q000235:genetics; D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D016172:DNA Fingerprinting; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D012150:Polymorphism, Restriction Fragment Length; D012424:Rural Population; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D007538:Isoniazid