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.

Research paper by José Afonso JA Guerra-Assunção, Rein M G J RM Houben, Amelia C AC Crampin, Themba T Mzembe, Kim K Mallard, Francesc F Coll, Palwasha P Khan, Louis L Banda, Arthur A Chiwaya, Rui P A RP Pereira, Ruth R McNerney, David D Harris, Julian J Parkhill, Taane G TG Clark, Judith R JR Glynn

Indexed on: 23 Oct '14Published on: 23 Oct '14Published in: The Journal of infectious diseases


Recurrent tuberculosis is a major health burden and may be due to relapse with the original strain or reinfection with a new strain.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.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).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.

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