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. 2024 Jan;43(1):73-85.
doi: 10.1007/s10096-023-04693-8. Epub 2023 Nov 9.

A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country

Juliana Maira Watanabe Pinhata  1 , Lucilaine Ferrazoli  2 , Flávia de Freitas Mendes  2 , Maria Gisele Gonçalves  2 , Michelle Christiane da Silva Rabello  3 , Kelen Teixeira Ghisi  2 , Vera Simonsen  2 , Roberta Figueiredo Cavalin  4 , Ana Angélica Bulcão Portela Lindoso  4 , Rosângela Siqueira de Oliveira  2
Affiliations

A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country

Juliana Maira Watanabe Pinhata et al. Eur J Clin Microbiol Infect Dis. 2024 Jan.

Abstract

Purpose: To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil.

Methods: Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB.

Results: Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64 years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes.

Conclusion: We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.

Keywords: Drug resistance; Extensively drug-resistant tuberculosis; Gene sequencing; Isoniazid; Line probe assay; Multidrug-resistant tuberculosis.

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References

    1. World Health Organization (WHO). WHO global TB report 2022 [Internet]. 2022. Available at: https://www.who.int/publications/i/item/9789240061729 . Accessed 10 Dec 2022
    1. Wingfield T, Boccia D, Tovar M, Gavino A, Zevallos K, Montoya R et al (2014) Defining catastrophic costs and comparing their importance for adverse tuberculosis outcome with multi-drug resistance: a prospective cohort study, Peru. PLoS Med [Internet]. 11:e1001675. https://doi.org/10.1371/journal.pmed.1001675 - DOI - PubMed - PMC
    1. Ministério da Saúde. Boletim Epidemiológico da Tuberculose no Brasil – Março de 2023 [Internet]. 2023. Available at : https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins... . Accessed 05 Apr 2023
    1. Ministério da Saúde (2022) Série histórica do número de casos novos e de incidência de tuberculose. Brasil, Regiões e Unidades Federadas de residência por ano diagnóstico (1990 a 2021). Available at: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/t/tuberculose/sit... . Accessed 09 Apr 2023
    1. Soini H, Musser JM (2001) Molecular diagnosis of mycobacteria. Clin Chem 47:809–14. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11325882 . Accessed 08 Nov 2022

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