title: Detecting mutation pattern of drug-resistant Mycobacterium tuberculosis isolates in Himachal Pradesh using GenoType(®) MTBDRplus assay.
abstract: BACKGROUND
  Tuberculosis (TB) is a major public health problem in India and a principal cause of death in adults, especially among the economically productive age group. India accounts for one-fifth of the global burden of TB. It is estimated that about 40% of Indian population is infected with TB bacillus. The GenoType® MTBDRplus molecular method allows rapid diagnosis of the clinical samples and detection of the most common mutations in the genes associated with rifampicin (R) and isoniazid (H) resistance.
  
  
  OBJECTIVE
  To study the drug resistance and mutational patterns in multidrug-resistant (MDR) suspects clinical strains using GenoType® MTBDRplus assay.
  
  
  METHODS
  A total of 770 sputum samples of the MDR-TB suspects were included in this study, which were received at Intermediate Reference Laboratory, Government TB Sanatorium, Dharampur, Solan, Himachal Pradesh from the Designated Microscopy Centres of Himachal Pradesh for the culture and susceptibility testing. All the 521 Mycobacterium tuberculosis complex (MTBC) strains were subjected to GenoType® MTBDRplus (HAIN Lifescience) assay to detect molecular resistance pattern to first line anti-tubercular drugs (isoniazid and rifampicin).
  
  
  RESULTS
  Of 770 samples, 556 (72.20%) were from male and 214 (27.80%) were from female. Among the 521 MTBC strains, 19.76% were found to be MDR and mono-resistance to isoniazid and rifampicin was detected in 8.63% and 6.14% strains respectively. About 74.81%, 76.35% and 5.40% strains harboured known mutation in rpoB, katG and inhA genes respectively.
  
  
  CONCLUSIONS
  In rpoB gene, the most common mutation is associated with S531 L region. The GenoType® MTBDRplus assay is a rapid test for the detection of the most common mutations in MDR-TB strains. In our study, unknown rpoB gene mutations were found in 25.18% strains that may further be detected by gene sequencing.
authors.affiliation: Intermediate Reference Laboratory, Government Tuberculosis Sanatorium, Dharampur, Solan, Himachal Pradesh, India.
authors.forename: C
authors.initials: C
authors.lastname: Thakur
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: A K
authors.initials: AK
authors.lastname: Gupta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000382:microbiology*; D055815:Young Adult
chemical_list: D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit