Published ahead of print on June 9, 2005, doi:10.1164/rccm.200503-449OC Am. J. Respir. Crit. Care Med., Volume 172, Number 5, September 2005, 636-642 A more recent version of this article appeared on September 1, 2005
Submitted on March 22, 2005 Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-resistance PatternsAnnelies van Rie1,1 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, USA, 2 Department of Medical Biochemistry, Stellenbosch University, DST/NRF Centre of Excellence in Biomedical Tuberculosis Research / MRC Centre for Molecular and Cellular Biology, Tygerberg, South Africa, 3 Department of Paediatrics and Child Health, Stellenbosch University, Desond Tutu TB Centre, Tygerberg, South Africa * To whom correspondence should be addressed. E-mail: rw1{at}sun.ac.za.
Rationale: Multiple infections with different strains of Mycobacterium tuberculosis may occur in settings where the infection pressure is high. The relevance of mixed infections for the patient, clinician and control program remains unclear. Objectives: This study aimed to describe reinfection and mixed infection as underlying mechanisms of changing drug-susceptibility patterns in serial sputum cultures. Methods: Serial M. tuberculosis sputum cultures from patients diagnosed with multi-drug-resistant (MDR)-tuberculosis were evaluated by phenotypic drug-susceptibility testing and mutation detection methods. Genotypic analysis was done by IS6110 DNA fingerprinting and a novel strain-specific PCR amplification method. Measurements and Main Results: DNA fingerprinting analysis of serial sputum cultures from 48 MDR-tuberculosis patients attributed 10 cases to reinfection and 1 case to mixed infection. In contrast, strain-specific PCR amplification analysis in 9 of the 11 cases demonstrated mixed infection in 5 cases, reinfection in 3 cases and laboratory contamination in 1 case. Analysis of clinical data suggests that first-line therapy can select for a resistant sub-population, while poor adherence or second-line therapy resulted in the re-emergence of the drug-susceptible sub-populations. Conclusions: We have shown that in some patients with MDR-tuberculosis, mixed infection may be responsible for observations attributed to reinfection by DNA fingerprinting. We conclude that treatment and adherence determines which strain is dominant. We hypothesize that treatment with second-line drugs may lead to re-emergence of the drug susceptible strain in patients with mixed infection. Key words: Mycobacterium tuberculosis, reinfection, mixed infections, drug-resistance.
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
