The Hidden Epidemic of Isoniazid-Resistant Tuberculosis in South Africa.
Ann Am Thorac Soc
; 21(10): 1391-1397, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-38935769
ABSTRACT
Rationale Isoniazid-resistant tuberculosis (Hr-TB) is often overlooked in diagnostic algorithms because of reliance on first-line molecular assays testing only for rifampicin resistance. Objectives:
To determine the prevalence, outcomes, and molecular mechanisms associated with rifampin-susceptible, isoniazid-resistant TB (Hr-TB) in the Eastern Cape, South Africa.Methods:
Between April 2016 and October 2017, sputum samples were collected from patients with rifampin-susceptible TB at baseline and at Weeks 7 and 23 of drug-susceptible TB treatment. We performed isoniazid phenotypic and genotypic drug susceptibility testing, including FluoroTypeMTBDR, Sanger sequencing, targeted next-generation sequencing, and whole-genome sequencing.Results:
We analyzed baseline isolates from 766 patients with rifampin-susceptible TB. Of 89 patients (11.7%) who were found to have Hr-TB, 39 (44%) had canonical katG or inhA promoter mutations; 35 (39%) had noncanonical katG mutations (including 5 with underlying large deletions); 4 (5%) had mutations in other candidate genes associated with isoniazid resistance. For 11 (12.4%), no cause of resistance was found.Conclusions:
Among patients with rifampin-susceptible TB who were diagnosed using first-line molecular TB assays, there is a high prevalence of Hr-TB. Phenotypic drug susceptibility testing remains the gold standard. To improve the performance of genetic-based phenotyping tests, all isoniazid resistance-associated regions should be included, and such tests should have the ability to identify underlying mutations.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Testes de Sensibilidade Microbiana
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Tuberculose Resistente a Múltiplos Medicamentos
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Isoniazida
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Mycobacterium tuberculosis
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Antituberculosos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article