Dados do Trabalho

Título

Genomic-based surveillance reveals important traits on drug-resistant Mycobacterium tuberculosis in Southern Brazil

Introdução

Drug resistance (DR) is among the main factors for the maintenance of tuberculosis (TB) as one of the deadliest diseases in the world. Genomic surveillance of DR and its transmission patterns are a powerful tool for the TB control.

Objetivo (s)

Characterize the genomic diversity of drug-resistant M. tuberculosis circulating in Southern Brazil.

Material e Métodos

We used a whole-genome sequencing approach, drug susceptibility testing (DST) and clinical-epidemiological investigation in order to undertake a retrospective population-based study on DR-TB in Rio Grande do Sul, the largest state in Southern Brazil. A total of 118 DR Mycobacterium tuberculosis strains sampled statewide from 2015 to 2018 were included.

Resultados e Conclusão

All strains were assigned to Lineage 4 with a high sublineage-level diversity; higher frequency of 4.1.2.1 (Haarlem/RD182), 4.3.4.1 [Latin American and Mediterranean (LAM)] and 4.3.3 (LAM/RD115) sublineages. An important genomic diversity was also seen among first-line drugs resistance-related variants. A substantial amount of distinct mutations that confer resistance to anti-TB drugs, including novel and likely endemic mutations and rpoB disputed mutations occurring in 20% of the strains. The latter are of special importance given its association with lower drug resistance levels and association with unreliable detection using qualitative phenotypic based methods (MGIT). Using a five single nucleotide polymorphism threshold for cluster delineation, we found that 28.8% of the strains was linked to recent transmission; the most of these were multidrug resistant strains. Significant resistance amplification in the region was demonstrated through different resistance profiles and the intracluster emergence of novel mutations.
This study described the diversity of Mycobacterium tuberculosis strains, the basis of DR, and ongoing transmission dynamics across the largest state in Southern Brazil, revealing an uncontrolled transmission scenario coupled with resistance emergence/amplification. The data obtained thereby stresses the urgent need for transmission control state-wide.

Palavras-chave

Keywords: Tuberculosis; Drug resistance; Transmission; Whole-genome sequencing.

Agradecimentos

Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant. No. 17/1265-8 INCT-TB).