Implications for TB control among migrants in large cities in China: a prospective population-based genomic epidemiology study in Shenzhen

Internal migrants are a challenge for TB control in large Chinese cities and understanding this epidemiology is crucial for designing effective control and prevention strategies. We conducted a prospective genomic epidemiological study of culture-positive TB patients diagnosed between June 1, 2018 and May 31, 2021 in the Longhua District of Shenzhen. Treatment status was obtained from local and national TB registries and all isolates were sequenced. Genomic clusters were defined as strains differing by <= 12 SNPs. Risk factors for clustering were identified with multivariable analysis and then Bayesian models and TransPhylo were used to infer the timing of transmission within clusters. Of the 2277 culture-positive patients, 70.1% (1596/2277) were migrants: 72.1% (1043/1446) of the migrants patients developed TB within two years of arriving in Longhua; 38.8% within 6 months of arriving; and 12.3% (104/843) had TB symptoms when they arrived. Only 15.4% of Longhua strains were in genomic clusters. More than one third (33.6%) of patients were not treated in Shenzhen but were involved in nearly one third of the recent transmission events. Clustering was associated with migrants not treated in Shenzhen, males, and teachers/trainers. TB in Longhua is prinicipally due to reactivation of infections in migrants, but a proportion may have had clinical or incipient TB upon arrival in the district. Patients diagnosed but not treated in Longhua were involved in recent local TB transmission. Controlling TB in Shenzhen will require strategies to comprehensively diagnose and treat active TB in the internal migrant population.