Relapse or reinfection with tuberculosis: a whole genome sequencing approach in a large population-based cohort with high HIV prevalence and active follow-up.


Guerra-Assunção, JA; Houben, RM; Crampin, AC; Mzembe, T; Mallard, K; Coll, F; Khan, P; Banda, L; Chiwaya, A; Pereira, RP; McNerney, R; Harris, D; Parkhill, J; Clark, TG; Glynn, JR; (2015) Relapse or reinfection with tuberculosis: a whole genome sequencing approach in a large population-based cohort with high HIV prevalence and active follow-up. The Journal of infectious diseases, 211 (7). pp. 1154-63. ISSN 0022-1899 DOI: 10.1093/infdis/jiu574

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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.<br/> 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.<br/> 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).<br/> 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.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: MEIRU
PubMed ID: 25336729
Web of Science ID: 354697500017
URI: http://researchonline.lshtm.ac.uk/id/eprint/2006430

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