Studying circulating resistances using the Deeplex platform

In order to control TB, one of the threats is the emergence and dissemination of Mycobacterium tuberculosis strains resistant to drugs, especially rifampicin, the anti-TB drug with best bactericidal and sterilizing activity, as well as the new drugs recommended by the WHO for the treatment of rifampicin-resistant TB or multidrug resistant TB (resistant to both rifampicin and isoniazid), i.e. bedaquiline and linezolid. For the correct treatment of patients, prompt detection of resistance to any of the drugs is crucial. It is also important to know the resistances that are circulating in settings with high TB and drug-resistance TB burden. About 500 000 new cases of rifampicin-resistant or multidrug resistant TB are estimated to emerge each year; however, in the latest data (from 2019), only one in three cases were reported to have been treated.

In line of this, we are studying the circulating resistances in Ukraine (in Odessa region) and Moldova with Deeplex, a test based on targeted next generation sequencing (NGS) that detects mutations associated with resistance to first-line drugs (rifampicin, isoniazid, ethambutol, and pyrazinamide) and second-line drugs (fluoroquinolones, bedaquiline, linezolid, clofazimine, amikacin, streptomycin, and ethionamide), directly from sputum samples collected from patients with rifampicin-resistant TB detected by GeneXpert. In addition to mutations associated with drug resistance, with Deeplex we perform strain genotyping at lineage and sublineage levels by the spoligotyping target (CRISPR/Direct Repeat locus) and phylogenetic single nucleotide polymorphisms in drug resistance-associated genomic targets.

Leading partners: IGTP, IFTIP, and SD Center

Collaborating partners: ONU