Abstract
Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.
Highlights
Tuberculosis (TB) is the leading cause of death among infectious diseases, given that 10 million people became ill in 2017
The management of multidrug-resistant TB (MDR-TB) is characterised by delayed diagnosis, uncertainty of the extent of bacillary drug resistance, imprecise standardised drug regimens and dosages, very long duration of therapy and high frequency of adverse events associated with a high morbidity and mortality [2]
MDR-TB is characterised as a resistance to isoniazid (INH) and RIF, and XDR-TB is defined as a resistance to all first-line drugs plus at least one fluoroquinolones and second-line injectable [1]
Summary
Tuberculosis (TB) is the leading cause of death among infectious diseases, given that 10 million people became ill in 2017. An estimated 1.6 million people died because of the disease (including 300 000 among people with HIV). Drug-resistant TB (DR-TB) is a continuing threat with 558 000 new cases with resistance to rifampicin (RIF), the most effective first-line drug, of which 82% had multidrug-resistant TB (MDR-TB), and only 160 684 DR-TB were detected. In a meta-analysis of 74 studies, including 17 494 DR-TB participants [3], the pooled treatment success rate was 26% in extensively drug-resistant TB (XDR-TB) patients and 60% in MDR-TB patients. MDR-TB is characterised as a resistance to isoniazid (INH) and RIF, and XDR-TB is defined as a resistance to all first-line drugs plus at least one fluoroquinolones and second-line injectable (kanamycin, amikacin or capreomycin) [1]
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