title: Multidrug-resistant and heteroresistant Mycobacterium tuberculosis and associated gene mutations in Ethiopia.
abstract: BACKGROUND
  The prevalence of multidrug-resistant tuberculosis (TB) among new and retreatment cases in 2011 in Ethiopia was 2.7% and 17.9%, respectively. However, data on heteroresistance and gene mutation profiles of Mycobacterium tuberculosis were not documented.
  
  
  METHODS
  A cross-sectional study was conducted on 413 TB-positive clinical specimens submitted between 2012 and 2014 to Bahir Dar Regional Laboratory Center for confirmation of multidrug resistance. Resistance determining genes were analyzed using a line probe assay.
  
  
  RESULTS
  Of 413M. tuberculosis isolates, 150 (36.3%) were multidrug-resistant, 19 (4.6%) were resistant only to rifampicin, and 26 (6.3%) were resistant to isoniazid. Of 169 rifampicin-resistant and 176 isoniazid-resistant isolates, only eight (4.7%) showed rifampicin heteroresistance and only two (1.13%) showed isoniazid heteroresistance. Failing of the rpoB WT8 gene with corresponding hybridization of rpoB MUT3 (S531L substitution) accounted for 85 (50.3%) rifampicin-resistant mutations. Among 176 isoniazid-resistant isolates, 155 (88.1%) strains had the Ser315Thr1 substitution.
  
  
  CONCLUSIONS
  The prevalence of multidrug-resistant M. tuberculosis was high in the study area. Ser531Leu and Ser315Thr1 substitutions were the highest gene mutations for rifampicin and isoniazid, respectively.
authors.affiliation: Department of Medical Microbiology, Immunology and Parasitology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia. Electronic address: nigusdaniel@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mekonnen
authors.affiliation: Department of Regional Mycobacteriology Laboratory, Bahir Dar Regional Health Research Laboratory Center, Bahir Dar, Ethiopia.
authors.forename: Aschalew
authors.initials: A
authors.lastname: Admassu
authors.affiliation: Department of Medical Microbiology, Immunology and Parasitology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.
authors.forename: Wondemagegn
authors.initials: W
authors.lastname: Mulu
authors.affiliation: National Center of Tropical Medicine, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Amor
authors.affiliation: National Center of Tropical Medicine, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Benito
authors.affiliation: Department of Regional Mycobacteriology Laboratory, Bahir Dar Regional Health Research Laboratory Center, Bahir Dar, Ethiopia.
authors.forename: Woynshet
authors.initials: W
authors.lastname: Gelaye
authors.affiliation: Department of Medical Microbiology, Immunology and Parasitology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.
authors.forename: Fantahun
authors.initials: F
authors.lastname: Biadglegne
authors.affiliation: Department of Medical Microbiology, Immunology and Parasitology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.
authors.forename: Bayeh
authors.initials: B
authors.lastname: Abera
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015995:Prevalence; D012293:Rifampin / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin
keywords: Ethiopia; Gene mutations; Heteroresistance; Multidrug-resistant tuberculosis