Resumo

MVELASE, Nomonde R. et al. Consequences of rpoB mutations missed by the GenoType MTBDRplus assay in a programmatic setting in South Africa. Afr. J. Lab. Med. [online]. 2023, vol.12, n.1, pp.1-8. ISSN 2225-2010.  http://dx.doi.org/10.4102/ajlm.v12i1.1975.

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

Palavras-chave : tuberculosis; rifampicin resistance; rpoB mutations; MTBDRplus; discordance.

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