Análise das mutações relacionadas à resistência aos fármacos de 1ª e 2ª linhas do tratamento da tuberculose pulmonar

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), classified as a neglected disease. Epidemiological research points to high mortality and incidence rates of TB on a global scale. Mutations in the Mtb genome, in genes such as rpoB, katG, inhA, oxyR-ahpC, gyrA, pncA, embB, rpsL, gidB, rrS, ethA, and Rv1258c, are responsible for decreasing susceptibility to specific drugs used in treatment. This drug resistance is considered a significant public health problem associated with the disease, as it results in several consequences, such as increased morbidity and mortality, treatment difficulties, and disease control challenges. In this context, the present research evaluated the mutation profile associated with antituberculosis drug resistance in pulmonary TB patients treated at a referral hospital in Fortaleza, Ceará. Sampling was done by convenience, and 100% of the clinical isolates (33/33) of pulmonary TB included in this study were resistant to at least one drug. Of the total samples, 24 had complete clinical data. Of these, 95.8% (23/24) had a phenotypic resistance profile to isoniazid and 83.3% (20/24) to rifampicin. Various sociodemographic data, comorbidities, lifestyle habits, and clinical characteristics were evaluated and compared with the resistance profile, with no significant results identified. Of the 33 isolates, 32 presented genetic mutations via allele-specific multiplex polymerase chain reaction (PCR-MAS), corresponding to a rate of 97% (32/33). These mutations indicated resistance to the following drugs: rifampicin, isoniazid, streptomycin, ethambutol, and fluoroquinolones. Only 24.2% of isolates (8/33) had intact DNA for Whole Genome Sequencing (WGS), and all belonged to lineage 4 of the Mtb complex. Regarding sublineage, about 50% (4/8) belonged to the 4.3.4.1 subgroup. Among the eight samples evaluated by WGS, a resistance rate of 62.5% (5/8) was identified, and these mutations suggested resistance to rifampicin, isoniazid, streptomycin, and ethionamide. Among the isolates studied, we detected a high prevalence of resistance to the main drugs used in TB treatment, rifampicin and isoniazid. The study highlights the relevance of genomic surveillance of Mtb to understand and combat antibiotic resistance, as well as to develop effective measures for the control, prevention, and treatment of tuberculosis.