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Carolien Ruesen, Lidya Chaidir, Cesar Ugarte-Gil, Jakko van Ingen, Julia A. Critchley, Philip C. Hill, Rovina Ruslami, Prayudi Santoso, Martijn A. Huynen, Hazel M. Dockrell, David A.J. Moore, Bachti Alisjahbana, Reinout van Crevel

European Respiratory Journal 2020 55: 1901891; DOI: 10.1183/13993003.01891-2019

Extract

Diabetes is associated with failure of tuberculosis (TB) treatment, but it is unclear whether this is related to genotypic drug resistance of the infecting mycobacteria. We used whole genome sequencing (WGS) to examine 1365 known drug resistance mutations in 896 Mycobacterium tuberculosis isolates from TB patients that were screened for diabetes using HbA1c testing as part of the TANDEM project [1]. Ethical approval was received from the London School of Hygiene and Tropical Medicine and institutional review boards in Indonesia and Peru. In Peru we selected all available M. tuberculosis isolates from TANDEM patients (44 with and 445 without diabetes), and in Indonesia we selected all available isolates from diabetic patients (n=115) plus a subset of isolates from non-diabetic patients (n=292) from the same clinics, during the same time period, frequency-matched by age. We used TB Profiler version 0.3.8 [2] to determine M. tuberculosis lineage and drug resistance. A phylogeny was constructed using PhyML version 3.0 [3], and the minimum pairwise distance for isolates was calculated separately for patients with and without diabetes, stratified by country.

In a study in Peru and Indonesia, diabetes was associated with an increased risk of tuberculosis caused by Mycobacterium tuberculosis strains with resistance mutations, particularly against rifampicin, and this was not explained by previous TB treatment http://bit.ly/2QCvUEM

Acknowledgements

We thank the Oxford Genomics Centre at the Welcome Centre for Human Genetics (funded by Welcome Trust grant reference 203141/Z/16/Z) for the generation and initial processing of the whole genome sequencing data.

Footnotes

• Support statement: This work was supported by the TANDEM project, which was funded by the European Union's Seventh Framework Programme (FP7/2007–2013) under grant agreement number 305279. Whole genome sequencing: CRyPTIC consortium, funded by a Welcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z) and the Bill and Melinda Gates Foundation Trust (OPP1133541).

• Conflict of interest: C. Ruesen has nothing to disclose.

• Conflict of interest: L. Chaidir has nothing to disclose.

• Conflict of interest: C. Ugarte-Gil has nothing to disclose.

• Conflict of interest: J. van Ingen has nothing to disclose.

• Conflict of interest: J.A. Critchley has nothing to disclose.

• Conflict of interest: P.C. Hill has nothing to disclose.

• Conflict of interest: R. Ruslami has nothing to disclose.

• Conflict of interest: P. Santoso has nothing to disclose.

• Conflict of interest: M.A. Huynen has nothing to disclose.

• Conflict of interest: H.M. Dockrell has nothing to disclose.

• Conflict of interest: D.A.J. Moore has nothing to disclose.

• Conflict of interest: B. Alisjahbana has nothing to disclose.

• Conflict of interest: R. van Crevel has nothing to disclose.

• Received July 30, 2019.
• Accepted November 16, 2019.

• Copyright ©ERS 202