title: Genotypic assessment of drug-resistant tuberculosis in Baghdad and other Iraqi provinces using low-cost and low-density DNA microarrays.
abstract: We report on a molecular investigation carried out to ascertain the prevalence of drug-resistant tuberculosis (TB) and the specific gene mutations responsible for resistance to rifampicin (RIF) and/or isoniazid (INH) in Iraq. In total, 110 clinical isolates from category II TB cases from Baghdad (58%) and several Iraqi provinces (42%) were analysed using colorimetric, low-cost and low-density (LCD) microarrays (MYCO-Direct and MYCO-Resist LCD array kits) to identify the point mutations responsible for resistance in Mycobacterium tuberculosis isolates. We found 76 patients (69.1%) had resistant strains, of which 40 (36%) were multidrug-resistant (MDR)-TB. Where mono-resistance was identified, it was found to be predominantly to RIF (83%). The most common mutations were rpoB S531L (50%), inhA C15T (25%) and katG S315T (15%). The most common MDR-TB genotypes were rpoB S531L with inhA C15T (60%) and rpoB S531L with katG S315T (20%). Where phenotypic analysis of clinical isolates was also performed, genotypic data were found to show excellent correlation with phenotypic results. Correlation was found between the MYCO-Resist LCD array and GenoType MTBDRplus for detection of resistance to RIF. Our study shows MDR-TB in 36% of category II TB cases in Baghdad and surrounding Iraqi provinces, which reflects the World Health Organization findings based on phenotypic studies. Diagnosis of TB and MDR-TB using culture-based tests is a significant impediment to global TB control. The LCD arrays investigated herein are easy to use, sensitive and specific molecular tools for TB resistance profiling in resource-limited laboratory settings.
authors.affiliation: Biotechnology Department, College of Science, Baghdad University, Baghdad, Iraq.|Division of Infection and Pathway Medicine, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Dalal Saleh
authors.initials: DS
authors.lastname: Al-Rubaye
authors.affiliation: Division of Infection and Pathway Medicine, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Grace
authors.initials: G
authors.lastname: Henihan
authors.affiliation: Department of Medical Microbiology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
authors.forename: Ameraa K Abas
authors.initials: AKA
authors.lastname: Al-Abasly
authors.affiliation: Scottish Mycobacteria Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
authors.forename: Amie-Louise
authors.initials: AL
authors.lastname: Seagar
authors.affiliation: Department of Medical Microbiology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
authors.forename: Azhar Ab F
authors.initials: AAF
authors.lastname: Al-Attraqchi
authors.affiliation: Division of Infection and Pathway Medicine, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Holger
authors.initials: H
authors.lastname: Schulze
authors.affiliation: Tuberculosis and Chest Diseases Unit, Preventive Medicine and Environmental Directorate, Ministry of Health, Baghdad, Iraq.
authors.forename: Dhafer Salman
authors.initials: DS
authors.lastname: Hashim
authors.affiliation: Tuberculosis and Chest Diseases Unit, Preventive Medicine and Environmental Directorate, Ministry of Health, Baghdad, Iraq.
authors.forename: Jinan Khalid
authors.initials: JK
authors.lastname: Kamil
authors.affiliation: Scottish Mycobacteria Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Laurenson
authors.affiliation: Division of Infection and Pathway Medicine, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Till T
authors.initials: TT
authors.lastname: Bachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002648:Child; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D020411:Oligonucleotide Array Sequence Analysis / Q000191:economics / Q000379:methods*; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D002374:Catalase