High prevalence of phenotypic pyrazinamide resistance and its association with pncA gene mutations in Mycobacterium tuberculosis isolates from Uganda.
PLoS One
; 15(5): e0232543, 2020.
Article
em En
| MEDLINE
| ID: mdl-32413052
ABSTRACT
INTRODUCTION:
Susceptibility testing for pyrazinamide (PZA), a cornerstone anti-TB drug is not commonly done in Uganda because it is expensive and characterized with technical difficulties thus resistance to this drug is less studied. Resistance is commonly associated with mutations in the pncA gene and its promoter region. However, these mutations vary geographically and those conferring phenotypic resistance are unknown in Uganda. This study determined the prevalence of PZA resistance and its association with pncA mutations. MATERIALS ANDMETHODS:
Using a cross-sectional design, archived isolates collected during the Uganda national drug resistance survey between 2008-2011 were sub-cultured. PZA resistance was tested by BACTEC Mycobacterial Growth Indicator Tube (MGIT) 960 system. Sequence reads were downloaded from the NCBI Library and bioinformatics pipelines were used to screen for PZA resistance-conferring mutations.RESULTS:
The prevalence of phenotypic PZA resistance was found to be 21%. The sensitivity and specificity of pncA sequencing were 24% (95% CI, 9.36-45.13%) and 100% (73.54% - 100.0%) respectively. We identified four mutations associated with PZA phenotypic resistance in Uganda; K96R, T142R, R154G and V180F.CONCLUSION:
There is a high prevalence of phenotypic PZA resistance among TB patients in Uganda. The low sensitivity of pncA gene sequencing confirms the already documented discordances suggesting other mechanisms of PZA resistance in Mycobacterium tuberculosis.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pirazinamida
/
Tuberculose Pulmonar
/
Tuberculose Resistente a Múltiplos Medicamentos
/
Amidoidrolases
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Mycobacterium tuberculosis
/
Antituberculosos
Limite:
Humans
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article