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
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.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Addressing Diseases in Africa
- Tuberculosis: The Struggle Continues
- Genetic Susceptibility to Tuberculosis
- Protein Expression in Mycobacterium tuberculosis Differs with Growth Stage and Strain Type
- Molecular Detection of Early Appearance of Drug Resistance during Mycobacterium tuberculosis Infection
- Prevalence of Anti-mycolic Acid Antibodies in Patients with Pulmonary Tuberculosis Co-infected with HIV
- Reduction of the Rate of False-Positive Cultures of Mycobacterium tuberculosis in a Laboratory with a High Culture Positivity Rate
- Enhanced Immune Response in Mycobacterium bovis Bacille Calmette Guerin (BCG)-Infected IL-10-Deficient Mice
- The ELISPOT Assay: An Easily Transferable Method for Measuring Cellular Responses and Identifying T Cell Epitopes
- Coreceptor Usage and Biological Phenotypes of HIV-1 Isolates
- Overcoming Multidrug Resistance in Taxane Chemotherapy
- 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
- Synergism between Urinary Prothrombin Fragment 1 and Urine: A Comparison of Inhibitory Activities in Stone-Prone and Stone-Free Population Groups
- Immunoglobulin G and Subclass Responses to Plasmodium falciparum Antigens: A Study in Highly Exposed Cameroonians
- Infrequent Somatic Deletion of the 5' Region of the COL1A2 Gene in Oesophageal Squamous Cell Cancer Patients
- The Quantitative Analysis of Zearalenone and Its Derivatives in Plasma of Patients with Breast and Cervical Cancer
- Genetic Polymorphism of Cytochrome P450 1A1 (CYP1A1) and Glutathione Transferases (M1, T1 and P1) among Africans
- Meetings and Awards
Articles in the same Issue
- Addressing Diseases in Africa
- Tuberculosis: The Struggle Continues
- Genetic Susceptibility to Tuberculosis
- Protein Expression in Mycobacterium tuberculosis Differs with Growth Stage and Strain Type
- Molecular Detection of Early Appearance of Drug Resistance during Mycobacterium tuberculosis Infection
- Prevalence of Anti-mycolic Acid Antibodies in Patients with Pulmonary Tuberculosis Co-infected with HIV
- Reduction of the Rate of False-Positive Cultures of Mycobacterium tuberculosis in a Laboratory with a High Culture Positivity Rate
- Enhanced Immune Response in Mycobacterium bovis Bacille Calmette Guerin (BCG)-Infected IL-10-Deficient Mice
- The ELISPOT Assay: An Easily Transferable Method for Measuring Cellular Responses and Identifying T Cell Epitopes
- Coreceptor Usage and Biological Phenotypes of HIV-1 Isolates
- Overcoming Multidrug Resistance in Taxane Chemotherapy
- 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
- Synergism between Urinary Prothrombin Fragment 1 and Urine: A Comparison of Inhibitory Activities in Stone-Prone and Stone-Free Population Groups
- Immunoglobulin G and Subclass Responses to Plasmodium falciparum Antigens: A Study in Highly Exposed Cameroonians
- Infrequent Somatic Deletion of the 5' Region of the COL1A2 Gene in Oesophageal Squamous Cell Cancer Patients
- The Quantitative Analysis of Zearalenone and Its Derivatives in Plasma of Patients with Breast and Cervical Cancer
- Genetic Polymorphism of Cytochrome P450 1A1 (CYP1A1) and Glutathione Transferases (M1, T1 and P1) among Africans
- Meetings and Awards