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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: A retrospective observational study
The Lancet Respiratory Medicine, Volume 1, No. 10, Year 2013
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Description
Background: Recurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing-which is more accurate than conventional typing used to date-to assess the frequency of recurrence and to gain insight into the biological basis of re-infection. Methods: We assessed patients from the REMoxTB trial-a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence. Findings: We assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0-6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease. Interpretation: Whole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials. Funding: Wellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership. © 2013 Bryant et al. Open Access article distributed under the terms of CC BY.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3861685/bin/mmc1.pdf
Authors & Co-Authors
Bryant, Josephine
United Kingdom, Hinxton
Wellcome Sanger Institute
Harris, Simon R.
United Kingdom, Hinxton
Wellcome Sanger Institute
Parkhill, Julian
United Kingdom, Hinxton
Wellcome Sanger Institute
Dawson, Rodney
South Africa, Cape Town
University of Cape Town
Diacon, Andreas Henri
South Africa, Stellenbosch
Stellenbosch University
Van Helden, Paul D.
South Africa, Stellenbosch
Stellenbosch University
Pym, Alexander S.
South Africa, Durban
Africa Health Research Institute
Mahayiddin, Aziah Ahmad
Malaysia, Kuala Lumpur
Institute of Respiratory Medicine
Chuchottaworn, Charoen
Thailand, Bangkok
Chest Disease Institute
Sanne, Ian
South Africa, Johannesburg
Helen Joseph Hospital
Louw, Cheryl Emily
South Africa, Brits
Madibeng Centre for Research
Boeree, Martin Johan
Netherlands, Nijmegen
Radboud University Medical Center
Höelscher, Michael
Germany, Munich
Klinikum Der Universität München
Germany, Munich
German Center for Infection Research Dzif
McHugh, Timothy Daniel
United Kingdom, London
University College London
Bateson, Anna L.C.
United Kingdom, London
University College London
Hunt, Robert D.
United Kingdom, London
University College London
Mwaigwisya, Solomon
United Kingdom, London
University College London
Wright, Laura
United Kingdom, London
University College London
Gillespie, Stephen H.
United Kingdom, St Andrews
School of Medicine
Bentley, Stephen D.
Germany, Munich
German Center for Infection Research Dzif
Statistics
Citations: 184
Authors: 20
Affiliations: 13
Identifiers
Doi:
10.1016/S2213-2600(13)70231-5
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Study Design
Randomised Control Trial
Cohort Study
Study Locations
South Africa