Recurrence due to Relapse or Reinfection With Mycobacterium tuberculosis: A Whole Genome Sequencing Approach in a Large, Population Based Cohort With a …

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 …