A population-based genomic epidemiological study of the source of tuberculosis infections in an emerging city: Shenzhen, China

Abstract

Background Tuberculosis (TB) in emerging cities is often a disease of recent immigrants, and understanding this epidemiology is crucial for designing effective control and prevention strategies. Methods We conducted a retrospective population-based genomic epidemiological study of culture-positive pulmonary TB patients diagnosed between June 2014 and November 2017 in the Bao'an District of Shenzhen, a Chinese city with dramatic recent growth. After whole genome sequencing, transmission clusters were defined as strains differing by no more than 12 SNPs. Findings Of 1696 culture-positive TB patients, 93•8% (1591/1696) were migrants, with 51•6% (821/1591) employed in housekeeping or unemployed. Of the 1460 migrants with known residence time, 47•7% (697/1460) developed TB within two years after arriving in Bao'an. Only 12•2% (207/1696) of Bao'an isolates were in genomic clusters, indicating that recent transmission was not the primary cause of TB in Bao'an. The isolates’ median terminal branch length was 56 SNPs, more than could have accumulated since the arrival of the migrants in Bao'an. The migrants’ isolates had genotypic distributions similar to those in their home provinces. One strain isolated in Bao'an belonged to a clade circulating in the patient's home province, providing further evidence that the strains were brought to Bao'an with the migrants. Interpretation TB in the Bao'an District is principally caused by reactivation of infections acquired by migrants in their home provinces. Nearly half developed TB within two years after arriving in Bao'an, suggesting a need for increased TB screening of migrants, especially housekeeping workers and the unemployed. Funding Sanming Project of Medicine in Shenzhen; National Science and Technology Major Project of China; Natural Science Foundation of China.

Transmission of multidrug-resistant tuberculosis in Beijing, China: An epidemiological and genomic analysis

“…Internal migrants are thought to play an important role in TB transmission (24)(25)(26). For example, TB in the Baoan District of Shenzhen principally stems from the reactivation of infections acquired by migrants in their home provinces (27). However, our results showed that the clustering rate among local residents was higher than among internal migrants, suggesting that the former played a major role in MDR-TB transmission, especially in the central urban area of Beijing.…”

High proportion of tuberculosis transmission among social contacts in rural China: a 12-year prospective population-based genomic epidemiological study

“…Strains were classified into different lineages according to Liu et al [ 12 ]. Strains belonging to lineage 2 (L2), also termed the Beijing family, were divided into L2.3, representing “modern” Beijing and other sub-lineages considered “ancient” Beijing [ 13 ].…”

“…Drug-resistance profiles were predicted for 14 anti-TB drugs based on the mutations reported to be associated with resistance [ 14 ], using Whole-genome sequencing (WGS) data as described previously [ 13 ]. Pan-susceptible TB was defined as strains without mutations associated with resistance to the four first-line drugs (isoniazid, rifampicin, ethambutol and pyrazinamide).…”

High proportion of tuberculosis transmission among social contacts in rural China: a 12-year prospective population-based genomic epidemiological study

“…Drug-resistance profiles were predicted for 14 anti-TB drugs based on the mutations reported to be associated with resistance, 14 using Whole-genome sequencing (WGS) data as described previously. 15 Pan-susceptible TB was defined as susceptibility to the four first-line drugs (isoniazid, rifampicin, ethambutol and pyrazinamide). Multidrug-resistant TB (MDR-TB) was defined as resistance to at least isoniazid and rifampicin.…”