Molecular detection of early appearance of drug resistance during Mycobacterium tuberculosis infection

Thomas C. Victor, Hyeyoung Lee, Sang Nae Cho, Annemarie M. Jordaan, Gian van der Spuy, Paul D. van Helden, Robin Warren

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

During the early development of drug resistance in Mycobacterium tuberculosis (M. tuberculosis) infection only a small proportion of resistant bacteria are present within a milieu of sensitive bacteria. This complicates the use of molecular methods to predict the presence of a resistant phenotype and has been largely ignored in many of the newly developed molecular methods. In this study, mixtures of DNA from M. tuberculosis strains with known wild-type and mutant sequences were used to evaluate the sensitivity of three different molecular methods for detection of drug resistance. The dot-blot and amplification refractory mutation system (ARMS) methods showed sensitivities that approach those of routine phenotypic methods and are able to detect the presence of mutant sequences at a ratio of 1 in 50 (corresponding to 2% mutant sequences). This is 10-fold more sensitive than the commercial kit. The ARMS method was also used to investigate the use of molecular methods to identify mixed infections, and both drug-resistant and susceptible strain populations were identified in a single clinical isolate. These findings highlight the applicability of molecular methods to the rapid detection of drug resistance in tuberculosis patients, particularly in those who are non-compliant and in contacts of known drug-resistant tuberculosis patients, and assistance in limiting the spread of drug-resistant strains.

Original languageEnglish
Pages (from-to)876-881
Number of pages6
JournalClinical Chemistry and Laboratory Medicine
Volume40
Issue number9
DOIs
Publication statusPublished - 2002 Jan 1

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Biochemistry, medical

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