Detection of &lt;I&gt;kat&lt;/I&gt;G and &lt;I&gt;inh&lt;/I&gt;A mutations to guide isoniazid and ethionamide use for drug-resistant tuberculosis

Vr, Bollela; Ei, Namburete; Cs, Feliciano; Macheque, David Gabriel; Lh, Harrison; Ja, Caminero Luna

doi:10.5588/ijtld.15.0864

Cited by 98 publications

(75 citation statements)

References 29 publications

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“…However, this finding did not represent a statistically significant difference. [38] This subject remains unanswered by our study and could be an area for further research.…”

Section: Researchmentioning

confidence: 87%

“…[37] Our study did not investigate the relationship between INH resistance-conferring mutations and history of prior use of INH. Bollela et al [38] reported a direct link between prior INH exposure for latent or active TB and predominance of katG mutations. They found that a katG mutation was more frequent among isolates from patients with a history of INH use than in those with no INH exposure (68.8% v. 31.2%).…”

Section: Researchmentioning

confidence: 99%

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Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa

2019

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Background. Multidrug-and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB) threaten local and global control of the disease. The molecular line-probe assay (LPA) provides rapid diagnosis and early management of MDR-TB. The LPA detects mutations of katG and inhA genes associated with isoniazid (INH) resistance in Mycobacterium tuberculosis isolates. The katG and inhA genes are associated with high-and low-level INH resistance, respectively, as well as cross-resistance to ethionamide in the case of inhA gene mutations. Patients with MDR-TB due to an inhA mutation could benefit from the use of high-dose INH -instead of ethionamide -in their MDR-TB regimen. Objectives. To determine the frequencies of katG and inhA mutations that conferred INH resistance among MDR-TB isolates during 2014 -2016 in Free State (FS) Province of South Africa. Methods. We retrospectively reviewed MDR-TB isolates assayed with GenoType MTBDRplus (Hain Lifescience, Germany) (LPA) at the central TB laboratory of Universitas Academic Hospital, Bloemfontein, FS, and calculated the frequencies of katG and inhA mutations. Results. Among 918 MDR-TB isolates, the prevalence of katG, inhA and katG plus inhA mutations was 63.9%, 13.4% and 22.7%, respectively. Approximately 60% (n=536; 58.4%) of the isolates were obtained from male patients. The patients' ages ranged from 1 to 89 (median 37) years. The Xhariep district had the highest incidence of INH resistance-conferring mutations in the province. Conclusions. katG-associated mutations are the predominant INH resistance-conferring mechanism among MDR-TB isolates in the FS. Patients infected with isolates that harbour the katG mutation are unlikely to benefit from high-dose INH therapy in the bedaquiline (BDQ)-containing modified short MDR-TB regimen. They may, however, benefit from the inclusion of ethionamide in the regimen. Dual katG and inhA gene mutations make these patients unlikely to respond to either high-dose INH or ethionamide and should now be considered for either the BDQ-containing long MDR-TB regimen or an individualised treatment regimen, depending on fluoroquinolone susceptibility. Clinicians should familiarise themselves with interpreting various INH resistance-conferring mutation results and their implications for management of MDR-TB treatment.S Afr Med J 2019;109(9):659-664. https://doi.

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“…However, this finding did not represent a statistically significant difference. [38] This subject remains unanswered by our study and could be an area for further research.…”

Section: Researchmentioning

confidence: 87%

Section: Researchmentioning

confidence: 99%

Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa

2019

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“…As with rpo B gene, the frequency of kat G mutations and inh A mutations has been seen to vary geographically; a higher prevalence of kat G mutations in Mozambique have been noted compared with Brazil where mutations in inh A promoters is more commonly associated with isoniazid resistance (Bollela et al . ). This suggests a diversifying spectrum of mutational patterns involved in MDR.…”

Section: Resultsmentioning

confidence: 97%

GenoType MTBDRplus assay for screening and characterization of isoniazid and rifampicin resistance-associated mutations in multidrug-resistant Mycobacterium tuberculosis from India

Sethi

Yadav

Khaneja³

et al. 2017

Lett Appl Microbiol

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To the best of our knowledge this is the largest study evaluating the GenoType-MTBDR line probe assay from India. We have studied the prevalence of mutations encoding rifampicin and isoniazid resistance in different patient groups based on criteria for multidrug resistance (MDR) suspicion. The translational impact of this study is in the design of customized country- or region-wise line probe assay strips. The identification of a few mutations in particular patient groups and the detection of wild type deletion mutants with no observable mutations both point toward the need for such customization enabling us to combat the rising trend of MDR tuberculosis.

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“…Las mutaciones en los genes de Mycobacterium tuberculosis katG e inhA, han sido reportados como los responsables del 60 -80% de los aislados resistentes a isoniacida [27][28][29][30] .…”

Section: Discussionunclassified

Determinación de la mutación S315T del gen katG en aislados resistentes a Isoniacida de Mycobacterium tuberculosis mediante PCR-RFLP

Sánchez-Domínguez

Nicola-Salas

Morey-León

2018

Infect

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Cómo citar este artículo: J. Sánchez-Domínguez, et al. Determinación de la mutación S315T del gen katG en aislados resistentes a Isoniacida de Mycobacterium tuberculosis mediante PCR-RFLP. Infectio 2018; 22(4): 178-184 ResumenObjetivo: determinar la mutación S315T del gen katG en aislados de Mycobacterium tuberculosis resistentes a isoniacida mediante la técnica PCR-RFLP. Materiales y métodos: A partir de 68 aislados de Mycobacterium tuberculosis se realizó el análisis de polimorfismo en productos de amplificación de 1054 y 630 pb que contenían la mutación S315T del gen katG mediante PCR-RFLP empleando las enzimas de restricción MspI y SatI. Mediante SPSS se determinó sensibilidad, especificidad, valores predictivo positivo y negativo, coeficientes de probabilidad positivo y negativo. Resultados: El 74,46% de aislados fenotípicamente resistentes y 4,76% fenotípicamente sensibles presentaron la mutación del gen katG S315T. La PCR-RFLP para S315T del gen katG presentó 85,4% de sensibilidad y 95,2% de especificidad con MspI y 85,4% de sensibilidad y 94,4% de especificidad con SatI. Discusión: La PCR-RFLP tiene una alta capacidad resolutiva que depende de la enzima que se emplee como se observó en estudios previos. La presencia de la mutación S315T en pacientes vírgenes al tratamiento sugiere la circulación de aislados resistentes a Isoniacida. Conclusión: La PCR-RFLP resultó una alternativa válida y rápida para el diagnóstico de la resistencia a isoniacida, mediante la detección de la mutación S315T del gen katG en comparación con el método convencional de las proporciones.Palabras Clave: Mutaciones, Polimorfismo, Isoniacida, PCR-RFLP, Mycobacterium tuberculosis, katG. Determination of S315T mutation within the katG gene in isoniazid-resistant Mycobacterium tuberculosis isolate by PCR-RFLP AbstractObjetive: To determine the S315T mutation of the katG gene in Mycobacterium tuberculosis isoniazid-resistant isolates by PCR-RFLP. Materials and Methods: Polymorphism analysis of 1054 and 630 bp products containing the S315T mutation of the katG gene was performed by PCR-RFLP using the MspI and SatI restriction enzymes from 68 Mycobacterium tuberculosis isolates. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratio were determined using SPSS. Results: 74.46% of isoniazid-resistant and 4.76% of isoniazid-sensitive isolates showed the S315T mutation in katG gene. The PCR-RFLP for S315T of the katG gene had 85.4% sensitivity and 95.2% specificity with MspI and 85.4% sensitivity and 94.4% specificity with SatI. Discussion: The PCR-RFLP has a high resolutive capacity that depends on the enzyme that is used as it was observed in previous studies. The presence of the S315T mutation in treatment-naive patients suggests the circulation of isolates resistant to isoniazid. Conclusion: PCR-RFLP is a valid and rapid alternative for the diagnosis of isoniazid resistance, by detection of S315T mutation in the katG gene compared to the conventional method of proportions.

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Detection of <I>kat</I>G and <I>inh</I>A mutations to guide isoniazid and ethionamide use for drug-resistant tuberculosis

Cited by 98 publications

References 29 publications

Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa

Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa

GenoType MTBDRplus assay for screening and characterization of isoniazid and rifampicin resistance-associated mutations in multidrug-resistant Mycobacterium tuberculosis from India

Determinación de la mutación S315T del gen katG en aislados resistentes a Isoniacida de Mycobacterium tuberculosis mediante PCR-RFLP

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