Consequences of rpoB mutations missed by the GenoType MTBDR plus 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

doi:10.4102/ajlm.v12i1.1975

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

Afr J Lab Med. 2023 Feb 6;12(1):1975. doi: 10.4102/ajlm.v12i1.1975. eCollection 2023.

Authors

Nomonde R Mvelase^{1

2}, Lindiwe P Cele³, Ravesh Singh^{1

2}, Yeshnee Naidoo^{4

5}, Jennifer Giandhari⁴, Eduan Wilkinson^{4

5}, Tulio de Oliveira^{4

5

6}, Khine Swe Swe-Han^{1

2}, Koleka P Mlisana^{1

2

6}

Affiliations

¹ Department of Medical Microbiology, KwaZulu-Natal Academic Complex, National Health Laboratory Service, Durban, South Africa.
² School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
³ Department of Public Health, Epidemiology and Biostatistics Unit, Sefako Makgatho Health Sciences University, Pretoria, South Africa.
⁴ KwaZulu-Natal Research Innovation and Sequencing Platform, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
⁵ Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa.
⁶ Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, 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: MTBDRplus; discordance; rifampicin resistance; rpoB mutations; tuberculosis.