Recurrence due to relapse or reinfection with Mycobacterium tuberculosis: a whole-genome sequencing approach in a large, population-based cohort with a high HIV infection prevalence and active follow-up

Guerra-Assunção, J. A. et al. (2015) Recurrence due to relapse or reinfection with Mycobacterium tuberculosis: a whole-genome sequencing approach in a large, population-based cohort with a high HIV infection prevalence and active follow-up. Journal of Infectious Diseases, 211(7), pp. 1154-1163. (doi: 10.1093/infdis/jiu574) (PMID:25336729) (PMCID:PMC4354982)

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Abstract

Background. Recurrent tuberculosis is a major health burden and may be due to relapse with the original strain or reinfection with a new strain. Methods. In a population-based study in northern Malawi, patients with tuberculosis diagnosed from 1996 to 2010 were actively followed after the end of treatment. Whole-genome sequencing with approximately 100-fold coverage was performed on all available cultures. Results of IS6110 restriction fragment-length polymorphism analyses were available for cultures performed up to 2008. Results. Based on our data, a difference of ≤10 single-nucleotide polymorphisms (SNPs) was used to define relapse, and a difference of >100 SNPs was used to define reinfection. There was no evidence of mixed infections among those classified as reinfections. Of 1471 patients, 139 had laboratory-confirmed recurrences: 55 had relapse, and 20 had reinfection; for 64 type of recurrence was unclassified. Almost all relapses occurred in the first 2 years. Human immunodeficiency virus infection was associated with reinfection but not relapse. Relapses were associated with isoniazid resistance, treatment before 2007, and lineage-3 strains. We identified several gene variants associated with relapse. Lineage-2 (Beijing) was overrepresented and lineage-1 underrepresented among the reinfecting strains (P = .004). Conclusions. While some of the factors determining recurrence depend on the patient and their treatment, differences in the Mycobacterium tuberculosis genome appear to have a role in both relapse and reinfection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Crampin, Professor Mia
Authors: Guerra-Assunção, J. A., Houben, R. M. G. J., Crampin, A. C., Mzembe, T., Mallard, K., Coll, F., Khan, P., Banda, L., Chiwaya, A., Pereira, R. P. A., McNerney, R., Harris, D., Parkhill, J., Clark, T. G., and Glynn, J. R.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
Journal Name:Journal of Infectious Diseases
Publisher:Oxford University Press
ISSN:0022-1899
ISSN (Online):1537-6613
Published Online:21 October 2014
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Journal of Infectious Diseases 211(7):1154-1163
Publisher Policy:Reproduced under a Creative Commons License

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