Whole genome sequencing provides additional insights into recurrent tuberculosis classified as endogenous reactivation by IS6110 DNA fingerprinting.

Anzaan Dippenaar, Margaretha De Vos, Florian M Marx, Sabir A Adroub, Paul D van Helden, Arnab Pain, Samantha L Sampson, Robin M Warren

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13 Scopus citations


Recurrent tuberculosis (TB) after successful TB treatment occurs due to endogenous reactivation (relapse) or exogenous reinfection. We revisited the conclusions of relapse in a high TB incidence setting that were drawn on the basis of IS6110 restriction fragment length polymorphism (RFLP) analysis in a large retrospective cohort study in suburban Cape Town, South Africa. Using whole genome sequencing (WGS), we undertook pair-wise genome comparison of Mycobacterium tuberculosis strains cultured from diagnostic sputum samples collected at the index and recurrent TB episode for 25 recurrent TB cases who had been classified as relapse based on identical DNA fingerprint patterns in the earlier study. We found that paired strain genome sequences were identical or showed minimal variant differences in 22 of 25 recurrent TB cases, consistent with relapse. One showed 20 variant differences, suggestive of exogenous reinfection. Two of the 25 had mixed infections, each with the index episode strain detected as the dominant strain at recurrence in one of these patients, the minority strain harboured drug-resistance conferring mutations (rpoB, katG). In conclusion, our study highlights the additional value of WGS for investigating recurrent TB in settings with high infection pressure and closely related circulating strains, where the extent of re- and mixed infection may be underestimated.

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): BAS/1/1020-01-01
Acknowledgements: This work was supported by the South African National Research Foundation (NRF) Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council (SAMRC) Centre for TB Research, and King Abdullah University of Science and Technology (KAUST award number BAS/1/1020-01-01). The authors acknowledge the Tuberculosis Omics Research (TORCH) Consortium headed by Prof Annelis van Rie for financial support. SLS is funded by the South African Research Chairs Initiative of the Department of Science and Technology and NRF of South Africa, award number UID 86539. Any opinion, finding and conclusion or recommendation expressed in this material is that of the authors and the NRF does not accept any liability in this regard. The authors declare no competing financial interests. Whole genome sequence data have been deposited at the European Nucleotide Archive under accession number PRJEB32341.


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