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

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.