title: Drug resistance-related mutations in multidrug-resistant Mycobacterium tuberculosis isolates from diverse geographical regions.
abstract: BACKGROUND
  Drug resistance in Mycobacterium tuberculosis is associated with chromosomal mutations in selected genes. These mutations can be screened for an early warning system for drug-resistant tuberculosis. The prevalence of individual mutations differs geographically, which must be considered in developing globally applicable screening tests.
  
  
  METHODS
  In order to analyse the geographical distribution and frequency of mutations conferring resistance to rifampicin, isoniazid and fluoroquinolones, the researchers investigated the presence of mutations in the rpoB gene, the katG gene, the mabA-inhA promoter region and the gyrA gene in clinical isolates of multidrug-resistant tuberculosis (MDR-TB) from Belarus, China, Iran/Iraq, Honduras, Romania and Uganda. For each study site, the researchers described the distribution of specific mutations in 20 clinical MDR-isolates.
  
  
  RESULTS
  The distribution of resistance-related mutations varied significantly between the study sites. Settings with a high incidence of MDR-TB, such as Belarus, showed a narrower spectrum of mutations related to rifampicin and isoniazid resistance and also a higher prevalence of fluoroquinolone resistance than study sites with a lower MDR-TB prevalence.
  
  
  CONCLUSIONS
  This study confirms that there are significant geographical differences in the distribution of resistance-related mutations and suggests that an increased understanding of such differences in the specific distribution of resistance conferring mutations is crucial for development of new, generally applicable, molecular tools for rapid diagnosis of drug-resistant TB. The fact that a narrower distribution of mutations in high MDR-TB prevalence settings was seen suggests that much of the problems in these settings can be a result of an ongoing transmission of certain MDR-TB strains.
authors.affiliation: Escuela de Microbiologia, Universidad Nacional Autonoma de Honduras, Tegucigalpa, Honduras; Division of Global Health (IHCAR), Karolinska Institutet, Stockholm, Sweden; Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Senia
authors.initials: S
authors.lastname: Rosales-Klintz
authors.affiliation: Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Jureen
authors.affiliation: Republican Scientific and Practical Center for Pulmonology and Phthisiology, Minsk, Belarus.
authors.forename: Aksana
authors.initials: A
authors.lastname: Zalutskayae
authors.affiliation: Republican Scientific and Practical Center for Pulmonology and Phthisiology, Minsk, Belarus.
authors.forename: Alena
authors.initials: A
authors.lastname: Skrahina
authors.affiliation: School of Public Health, Fudan University, Shanghai, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
authors.affiliation: School of Public Health, Fudan University, Shanghai, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Escuela de Microbiologia, Universidad Nacional Autonoma de Honduras, Tegucigalpa, Honduras.
authors.forename: Lelany
authors.initials: L
authors.lastname: Pineda-Garcia
authors.affiliation: Azadi Teaching Hospital, College of Medicine, University of Dohuk, Dohuk, Iraq; National Research Institute of TB and Lung Disease, Tehran, Iran.
authors.forename: Muayad Aghali
authors.initials: MA
authors.lastname: Merza
authors.affiliation: Hospital of Pneumophtisiology, Brasov, Romania.
authors.forename: Ionela
authors.initials: I
authors.lastname: Muntean
authors.affiliation: Department of Medical Microbiology, School of Medical Sciences, Makerere University, Kampala, Uganda.
authors.forename: Freddie
authors.initials: F
authors.lastname: Bwanga
authors.affiliation: Department of Medical Microbiology, School of Medical Sciences, Makerere University, Kampala, Uganda.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. Electronic address: sven.hoffner@smi.se.
authors.forename: Sven E
authors.initials: SE
authors.lastname: Hoffner
keywords: MDR-TB; gyrA gene; katG gene; mabA-inhA operon; rpoB gene