Genomic epidemiological analysis identifies high relapse among individuals with recurring tuberculosis and provides evidence of household recent TB transmission in Ghana.

Abstract Objective We investigated the cause of recurring tuberculosis (rcTB) among pulmonary TB participants recruited from a prospective population-based study conducted between July 2012 and December 2015. Methods Mycobacterium tuberculosis complex isolates obtained from rcTB cases were characterized by standard mycobacterial genotyping tools in addition to whole genome sequencing, followed by phylogenetic analysis to assess strain relatedness. Results A greater proportion (58.3%, 21/36) of individuals with rcTB episodes had TB recurrence within 12 months post treatment. Only 19.4% (7/36) of participants with rcTB harbored a strain with isoniazid (INH) resistance at baseline of which 29% (2/7) were additionally resistant to rifampicin. However, 27.8% (10/36) harbored an INH resistant strain upon recurring of which 40% (4/10) were MDR-TB strains. Recurrent TB was attributed to relapse (same strain) in 75.0% (27/36) of participants with 25.0% (9/36) attributed to re-infection. Conclusion Our findings indicate that unresolved previous infection due to inadequate treatment may be the major cause of rcTB.