Abstract
BackgroundMultidrug resistance is a critical factor in tuberculosis control. To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in Mycobacterium tuberculosis isolates from a national reference center.Methods and FindingsNinety-nine multidrug resistant isolates from 12 Brazilian states were studied. Drug-resistance patterns were determined and the rpoB and katG genes were screened for mutations. Genotypic diversity was investigated by IS6110-RFLP and Luminex 47 spoligotyping. Mutations in rpoB and katG were seen in 91% and 93% of the isolates, respectively. Codon 315 katG mutations occurred in 82.8% of the isolates with a predominance of the Ser315Thr substitution. Twenty-five isolates were clustered in 11 groups with identical IS6110-RFLP patterns while 74 showed unique patterns with no association between mutation frequencies or susceptibility profiles. The most prevalent spoligotyping lineages were LAM (47%), T (17%) and Haarlen (12%). The Haarlen lineage showed a higher frequency of codon 516 rpoB mutations while codon 531 mutations prevailed in the other isolates.ConclusionsOur data suggest that there were no major multidrug resistant M. tuberculosis strains transmitted among patients referred to the reference center, indicating an independent acquisition of resistance. In addition, drug resistance associated mutation profiles were well established among the main spoligotyping lineages found in these Brazilian multidrug resistant isolates, providing useful data for patient management and treatment.
Highlights
Tuberculosis (TB) is an infectious disease caused by bacteria of the Mycobacterium tuberculosis complex
Our data suggest that there were no major multidrug resistant M. tuberculosis strains transmitted among patients referred to the reference center, indicating an independent acquisition of resistance
Drug resistance associated mutation profiles were well established among the main spoligotyping lineages found in these Brazilian multidrug resistant isolates, providing useful data for patient management and treatment
Summary
Tuberculosis (TB) is an infectious disease caused by bacteria of the Mycobacterium tuberculosis complex. Multidrug resistant (MDR) M. tuberculosis strains are highly pathogenic and show great dissemination capacity. The global average of MDR-TB estimated for newly reported TB cases in 2012 was 3.6%, being slightly higher in high MDR-TB burden countries with 4.2% [1]. According to the World Health Organization (WHO), in 2012 there were an estimated 8.6 million new TB cases in the world representing a burden of 1.3 million deaths (including 320,000 deaths among HIV-positive patients). TB, is a highly relevant public health issue in Brazil, being the third cause of death from infectious diseases. To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in Mycobacterium tuberculosis isolates from a national reference center
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