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Diabetes is associated with genotypically drug-resistant tuberculosis


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 2019; 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. We examined if diabetes was associated with genotypic drug resistance against individual drugs or with MDR-TB for the two countries separately and combined, with multilevel multivariable logistic regression, taking into account the country of origin and adjusting for age, gender, HIV-infection, previous TB treatment, and M. tuberculosis lineage.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Ruesen has nothing to disclose.

Conflict of interest: Dr. Chaidir has nothing to disclose.

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

Conflict of interest: Dr. van Ingen has nothing to disclose.

Conflict of interest: Dr. Critchley has nothing to disclose.

Conflict of interest: Dr. Hill has nothing to disclose.

Conflict of interest: Dr. Ruslami has nothing to disclose.

Conflict of interest: Dr. Santoso has nothing to disclose.

Conflict of interest: Dr. Huynen has nothing to disclose.

Conflict of interest: Dr. Dockrell has nothing to disclose.

Conflict of interest: Dr. Moore has nothing to disclose.

Conflict of interest: Dr. Alisjahbana has nothing to disclose.

Conflict of interest: Dr. van Crevel has nothing to disclose.

  • Received July 30, 2019.
  • Accepted November 16, 2019.
  • Copyright ©ERS 2019

sumber : https://erj.ersjournals.com/content/early/2019/11/19/13993003.01891-2019

 
 

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