Original Research

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

Nomonde R. Mvelase, Lindiwe P. Cele, Ravesh Singh, Yeshnee Naidoo, Jennifer Giandhari, Eduan Wilkinson, Tulio de Oliveira, Khine Swe Swe-Han, Koleka P. Mlisana
African Journal of Laboratory Medicine | Vol 12, No 1 | a1975 | DOI: https://doi.org/10.4102/ajlm.v12i1.1975 | © 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 | This work is licensed under CC Attribution 4.0
Submitted: 06 June 2022 | Published: 06 February 2023

About the author(s)

Nomonde R. Mvelase, Department of Medical Microbiology, KwaZulu-Natal Academic Complex, National Health Laboratory Service, Durban, South Africa; and, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Lindiwe P. Cele, Department of Public Health, Epidemiology and Biostatistics Unit, Sefako Makgatho Health Sciences University, Pretoria, South Africa
Ravesh Singh, Department of Medical Microbiology, KwaZulu-Natal Academic Complex, National Health Laboratory Service, Durban, South Africa; and, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Yeshnee Naidoo, KwaZulu-Natal Research Innovation and Sequencing Platform, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; and, Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa
Jennifer Giandhari, KwaZulu-Natal Research Innovation and Sequencing Platform, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
Eduan Wilkinson, KwaZulu-Natal Research Innovation and Sequencing Platform, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; and, Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa
Tulio de Oliveira, KwaZulu-Natal Research Innovation and Sequencing Platform, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; and, Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa; and, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa
Khine Swe Swe-Han, Department of Medical Microbiology, KwaZulu-Natal Academic Complex, National Health Laboratory Service, Durban, South Africa; and, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Koleka P. Mlisana, Department of Medical Microbiology, KwaZulu-Natal Academic Complex, National Health Laboratory Service, Durban, South Africa School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; and, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, South Africa

Abstract

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.

 


Keywords

tuberculosis; rifampicin resistance; rpoB mutations; MTBDRplus; discordance

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