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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 and Robin Warren
Published/Copyright: June 1, 2005
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Volume 40 Issue 9

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.

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Published Online: 2005-06-01
Published in Print: 2002-09-24

Copyright © 2002 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

  1. Addressing Diseases in Africa
  2. Tuberculosis: The Struggle Continues
  3. Genetic Susceptibility to Tuberculosis
  4. Protein Expression in Mycobacterium tuberculosis Differs with Growth Stage and Strain Type
  5. Molecular Detection of Early Appearance of Drug Resistance during Mycobacterium tuberculosis Infection
  6. Prevalence of Anti-mycolic Acid Antibodies in Patients with Pulmonary Tuberculosis Co-infected with HIV
  7. Reduction of the Rate of False-Positive Cultures of Mycobacterium tuberculosis in a Laboratory with a High Culture Positivity Rate
  8. Enhanced Immune Response in Mycobacterium bovis Bacille Calmette Guerin (BCG)-Infected IL-10-Deficient Mice
  9. The ELISPOT Assay: An Easily Transferable Method for Measuring Cellular Responses and Identifying T Cell Epitopes
  10. Coreceptor Usage and Biological Phenotypes of HIV-1 Isolates
  11. Overcoming Multidrug Resistance in Taxane Chemotherapy
  12. Accurate Microsatellite Typing and Inter-study Comparison: Pitfalls and Solutions Using Interferon-γ (IFNG) and Natural Resistance-associated Mocrophage Protein 2 (NRAMP2) Genes as Examples
  13. Synergism between Urinary Prothrombin Fragment 1 and Urine: A Comparison of Inhibitory Activities in Stone-Prone and Stone-Free Population Groups
  14. Immunoglobulin G and Subclass Responses to Plasmodium falciparum Antigens: A Study in Highly Exposed Cameroonians
  15. Infrequent Somatic Deletion of the 5' Region of the COL1A2 Gene in Oesophageal Squamous Cell Cancer Patients
  16. The Quantitative Analysis of Zearalenone and Its Derivatives in Plasma of Patients with Breast and Cervical Cancer
  17. Genetic Polymorphism of Cytochrome P450 1A1 (CYP1A1) and Glutathione Transferases (M1, T1 and P1) among Africans
  18. Meetings and Awards
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