Consequences of rpoB mutations missed by the GenoType MTBDRplus assay in a programmatic setting in South Africa

African Journal of Laboratory Medicine

 
 
Field Value
 
Title Consequences of rpoB mutations missed by the GenoType MTBDRplus assay in a programmatic setting in South Africa
 
Creator Mvelase, Nomonde R. Cele, Lindiwe P. Singh, Ravesh Naidoo, Yeshnee Giandhari, Jennifer Wilkinson, Eduan de Oliveira, Tulio Swe Swe-Han, Khine Mlisana, Koleka P.
 
Subject Medical Microbiology tuberculosis; rifampicin resistance; rpoB mutations; MTBDRplus; discordance
Description Background: Rifampicin resistance missed by commercial rapid molecular assays but detected by phenotypic assays may lead to discordant susceptibility results and affect patient management.Objective: This study was conducted to evaluate the causes of rifampicin resistance missed by the GenoType MTBDRplus and its impact on the programmatic management of tuberculosis in KwaZulu-Natal, South Africa.Methods: We analysed routine tuberculosis programme data from January 2014 to December 2014 on isolates showing rifampicin susceptibility on the GenoType MTBDRplus assay but resistance on the phenotypic agar proportion method. Whole-genome sequencing was performed on a subset of these isolates.Results: Out of 505 patients with isoniazid mono-resistant tuberculosis on the MTBDRplus, 145 (28.7%) isolates showed both isoniazid and rifampicin resistance on the phenotypic assay. The mean time from MTBDRplus results to initiation of drug-resistant tuberculosis therapy was 93.7 days. 65.7% of the patients had received previous tuberculosis treatment. The most common mutations detected in the 36 sequenced isolates were I491F (16; 44.4%) and L452P (12; 33.3%). Among the 36 isolates, resistance to other anti-tuberculosis drugs was 69.4% for pyrazinamide, 83.3% for ethambutol, 69.4% for streptomycin, and 50% for ethionamide.Conclusion: Missed rifampicin resistance was mostly due to the I491F mutation located outside the MTBDRplus detection area and the L452P mutation, which was not included in the initial version 2 of the MTBDRplus. This led to substantial delays in the initiation of appropriate therapy. The previous tuberculosis treatment history and the high level of resistance to other anti-tuberculosis drugs suggest an accumulation of resistance. 
 
Publisher AOSIS
 
Contributor University of KwaZulu-Natal, National Health Laboratory Service
Date 2023-02-06
 
Type info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion — Laboratory analysis
Format text/html application/epub+zip text/xml application/pdf
Identifier 10.4102/ajlm.v12i1.1975
 
Source African Journal of Laboratory Medicine; Vol 12, No 1 (2023); 8 pages 2225-2010 2225-2002
 
Language eng
 
Relation
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https://ajlmonline.org/index.php/ajlm/article/view/1975/2562 https://ajlmonline.org/index.php/ajlm/article/view/1975/2563 https://ajlmonline.org/index.php/ajlm/article/view/1975/2564 https://ajlmonline.org/index.php/ajlm/article/view/1975/2565
 
Coverage South Africa Africa African
Rights Copyright (c) 2023 Nomonde R. Mvelase, Lindiwe P. Cele, Ravesh Singh, Yeshnee Naidoo, Jennifer Giandhari, Eduan Wilkinson, Tulio de Oliveira, Khine Swe Swe-Han, Koleka P. Mlisana https://creativecommons.org/licenses/by/4.0
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