Disequilibria in the Distribution ofrpoBAlleles in Rifampicin-ResistantM. tuberculosisIsolates from Germany and Sierra Leone

Abstract

The effectiveness of culture-independent resistance predictions by molecular techniques is dependent on the number and the frequency of accessible resistance-associated genomic mutations. We have characterized an rpoB gene region involved in rifampicin resistance in 49 Mycobacterium tuberculosis isolates resistant to rifampicin from Germany and Sierra Leone. The determined frequencies of mutations differed between both countries of origins as well as with respect to previously reported distributions of resistance mutations. It is concluded that at least for some isolates the acquisition of mutations leading to rifampicin resistance in clinical samples of M. tuberculosis is a non-random process which may lead to a geographical and temporal dependence of the sensitivities of molecular typing techniques for rifampicin resistance predictions.

Evaluation and Use of the Laboratory Methods in Diagnosis and Control of Tuberculosis

“…Hybridized PCR product was detected, and the LiPA results were evaluated as described elsewhere (4). In contrast with previous reports (Table 2) (8,13,19,20,22,26,27,30,31), the frequency of occurrence of particular mutations was different in the isolates from East Hungary, with 11 (37.9%) isolates carrying the less common D516V mutation. Nine (31.0%) isolates had an S531L mutation, and two (6.9%) isolates had an H526D mutation.…”

“…In addition, other studies revealed that mutations associated with RMP resistance can also occur in other regions of the rpoB gene, although less frequently (6,7,23). It has also been shown elsewhere that the information provided by these molecular tests can serve as a molecular epidemiological marker since the relative frequency of the alleles associated with resistance can vary geographically (10,20).…”

“…In Hungary, after 20 years of decline, between 1990 and 1995 the incidence of tuberculosis displayed an increase of almost 25% (rising from 31/100.000 to 39/100.000) [20]. To stop the negative trend, in 1994 the National Tuberculosis Program was developed to optimised the efforts in fight against TB in Hungary.…”

Molecular Characterization of Rifampin-Resistant Isolates of Mycobacterium tuberculosis from Hungary by DNA Sequencing and the Line Probe Assay

“…In addition, other studies revealed that mutations associated with RMP resistance can also occur in other regions of the rpoB gene, although less frequently (6,7,23). It has also been shown elsewhere that the information provided by these molecular tests can serve as a molecular epidemiological marker since the relative frequency of the alleles associated with resistance can vary geographically (10,20).Therefore, the aim of the present study was to determine the drug resistance profile of 29 RMP-resistant M. tuberculosis isolates obtained in East Hungary and to detect and identify mutations present in the rpoB gene. Two molecular assays were used.…”

Development of Multiplex Assay for Rapid Characterization ofMycobacterium tuberculosis

“…In a previous study (43), 90% of MDR-TB cases were identified by merely targeting rpoB codon 531, rpoB codon 526, and katG codon 315, three codons that are included in the assay. Specific mutations in these codons are generally the dominant mechanisms of MDR in many regions, but their prevalence, and thus the percentage of MDR identified with these codons, may differ considerably between regions (4,7,22,29,36). This may be partially a consequence of the genetic background of prevalent strains (14,17).…”