title: Characterisation of Mycobacterium tuberculosis isolates lacking IS6110 in Viet Nam.
abstract: METHODS
  The molecular diagnosis of tuberculosis (TB) in Viet Nam is often based on the detection of insertion sequence (IS) 6110 in Mycobacterium tuberculosis. However, 8-11% of M. tuberculosis strains in South-East Asia do not contain this target and this undermines the validity of these molecular tests.
  
  
  OBJECTIVE
  We quantified the frequency of M. tuberculosis strains lacking IS6110 in rural Viet Nam and studied their epidemiological and clinical characteristics.
  
  
  METHODS
  Consecutively diagnosed adult TB patients in rural Southern Viet Nam submitted two sputum samples for culture, IS6110 restriction fragment length polymorphism (RFLP) spoligotyping and 15-loci variable number tandem repeat typing. Polymerase chain reaction (PCR) was performed to confirm the absence of IS6110 elements in strains lacking IS6110 hybridisation in RFLP.
  
  
  RESULTS
  Among 2664 TB patient isolates examined, 109 (4.1%) had no IS6110 element. Compared to other strains, these no-copy strains were less often resistant to anti-tuberculosis drugs, particularly to streptomycin (adjusted OR 0.2, 95%CI 0.1-0.5), and showed significant geographic variation. No associations with TB history or demographic factors were found.
  
  
  CONCLUSIONS
  Strains without the IS6110 target pose a problem in Viet Nam as regards false-negative molecular TB diagnosis in PCR. Compared to other strains circulating in Viet Nam, no-copy strains are more susceptible to anti-tuberculosis drugs.
authors.affiliation: Pham Ngoc Thach Hospital, Ho Chi Minh City, Viet Nam.
authors.forename: M N T
authors.initials: MN
authors.lastname: Huyen
authors.forename: E W
authors.initials: EW
authors.lastname: Tiemersma
authors.forename: K
authors.initials: K
authors.lastname: Kremer
authors.forename: P
authors.initials: P
authors.lastname: de Haas
authors.forename: N T N
authors.initials: NT
authors.lastname: Lan
authors.forename: T N
authors.initials: TN
authors.lastname: Buu
authors.forename: C
authors.initials: C
authors.lastname: Sola
authors.forename: F G J
authors.initials: FG
authors.lastname: Cobelens
authors.forename: D
authors.initials: D
authors.lastname: van Soolingen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054458:Amplified Fragment Length Polymorphism Analysis; D000995:Antitubercular Agents / Q000627:therapeutic use; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000032:analysis*; D024881:Drug Resistance, Bacterial; D005188:False Negative Reactions; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018598:Minisatellite Repeats; D025202:Molecular Diagnostic Techniques; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012423:Rural Health; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology* / Q000635:transmission; D014744:Vietnam / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D004251:DNA Transposable Elements; D004269:DNA, Bacterial