Insights on the complexity of a dormant Mycobacterium tuberculosis cluster once transmission is resumed

Genotyping tools allow identifying active and epidemiologically intricate Mycobacterium tuberculosis transmission clusters to understand their complexity, namely, mixed infections and coexistence of clonal variants. We carried out a thorough analysis of the epidemiological and bacteriological complexity of a cluster in Almería, Spain. The cluster had initially been associated with Moroccan migrants and no secondary cases were identified for four years, reappearing in Spanish-born individuals. In one of the cases, two Mycobacterium tuberculosis clonal variants were identified. We re-analysed the cluster, supported on characterizing multiple cultured isolates and respiratory specimens, whole genome sequencing and epidemiological interviews of the involved cases. Our findings show that a cluster initially considered to have restarted activity due to a new transmission hot spot and with only a single case harbouring a small degree of clonal complexity is, in fact, a cluster currently growing due to coincidental reactivations of past exposures, with clonal complexity transmitted all along the cluster, including a case in whom clonal complexity was amplified, likely due to a prolonged diagnostic delay.