Rifampicin resistance conferring mutations among Mycobacterium tuberculosis strains in Rwanda

Cuella-Martin, I, Semuto Ngabonziza, JC, Torrea, G, Meehan, C ORCID: https://orcid.org/0000-0003-0724-8343, Mulders, W, Ushizimpumu, B, De Weerdt, L, Keysers, J, De Rijk, WB, Decroo, T, De Jong, BC and Rigouts, L, 2023. Rifampicin resistance conferring mutations among Mycobacterium tuberculosis strains in Rwanda. International Journal of Mycobacteriology, 12 (3), pp. 274-281. ISSN 2212-5531

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Abstract

Background: The World Health Organization-endorsed phenotypic and genotypic drug-susceptibility testing (gDST/pDST) assays for the detection of rifampicin-resistant (RR) tuberculosis (TB), may miss some clinically relevant rpoB mutants, including borderline mutations and mutations outside the gDST-targeted hotspot region. Sequencing of the full rpoB gene is considered the reference standard for rifampicin DST but is rarely available in RR-TB endemic settings and when done indirectly on cultured isolates may not represent the full spectrum of mutations. Hence, in most such settings, the diversity and trends of rpoB mutations remain largely unknown.

Methods: This retrospective study included rpoB sequence data from a longitudinal collection of RR-TB isolates in Rwanda across 30 years (1991–2021).

Results: Of 540 successfully sequenced isolates initially reported as RR-TB, 419 (77.6%) had a confirmed RR conferring mutation. The Ser450 Leu mutation was predominant throughout the study period. The Val170Phe mutation, not covered by rapid gDST assays, was observed in only four patients, three of whom were diagnosed by pDST. Along with the transition from pDST to rapid gDST, borderline RR-associated mutations, particularly Asp435Tyr, were detected more frequently. Borderline mutants were not associated with HIV status but presented lower odds of having rpoA-C compensatory mutations than other resistance-conferring mutations.

Conclusion: Our analysis showed changes in the diversity of RR-TB conferring mutations throughout the study period that coincided with the switch of diagnostic tools to rapid gDST. The study highlights the importance of rapid molecular diagnostics reducing phenotypic bias in the detection of borderline rpoB mutations while vigilance for non-rifampicin resistance determinant region mutations is justified in any setting.

Item Type:	Journal article
Publication Title:	International Journal of Mycobacteriology
Creators:	Cuella-Martin, I., Semuto Ngabonziza, J.C., Torrea, G., Meehan, C., Mulders, W., Ushizimpumu, B., De Weerdt, L., Keysers, J., De Rijk, W.B., Decroo, T., De Jong, B.C. and Rigouts, L.
Publisher:	Medknow Publications
Date:	2023
Volume:	12
Number:	3
ISSN:	2212-5531
Identifiers:	Number Type 10.4103/ijmy.ijmy_103_23 DOI 1822071 Other
Rights:	© 2023 International Journal of Mycobacteriology. This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	18 Oct 2023 08:56
Last Modified:	18 Oct 2023 08:56
URI:	https://irep.ntu.ac.uk/id/eprint/50003

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