Title: Consequences of rpoB mutations missed by the GenoType MTBDRplus assay in a programmatic setting in South Africa
Authors: Mvelase NR, Cele LP, Singh R, Naidoo Y, Giandhari J, Wilkinson E, de Oliveira T, Swe-Han KS, Mlisana KP.
Journal: Afr J Lab Med.,12(1):1975. doi: 10.4102/ajlm.v12i1.1975: (2023)
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.
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Citation: Mvelase NR, Cele LP, Singh R, Naidoo Y, Giandhari J, Wilkinson E, de Oliveira T, Swe-Han KS, Mlisana KP. Consequences of rpoB mutations missed by the GenoType MTBDRplus assay in a programmatic setting in South Africa Afr J Lab Med.,12(1):1975. doi: 10.4102/ajlm.v12i1.1975: (2023).