Acquisition of second-line drug resistance and extensive drug resistance during recent transmission of Mycobacterium tuberculosis in rural China.
Multidrug-resistant tuberculosis (MDR-TB) is prevalent in countries with a high TB burden, like China. As little is known about the emergence and spread of second-line drug (SLD) -resistant TB, we investigate the emergence and transmission of SLD-resistant Mycobacterium tuberculosis in rural China. In a multi-centre population-based study, we described the bacterial population structure and the transmission characteristics of SLD-resistant TB using Spoligotyping in combination with genotyping based on 24-locus MIRU-VNTR (mycobacterial interspersed repetitive unit-variable-number tandem repeat) plus four highly variable loci for the Beijing family, in four rural Chinese regions with diverse geographic and socio-demographic characteristics. Transmission networks among genotypically clustered patients were constructed using social network analysis. Of 1332 M. tuberculosis patient isolates recovered, the Beijing family represented 74.8% of all isolates and an association with MDR and simultaneous resistance between first-line drugs and SLDs. The genotyping analysis revealed that 189 isolates shared MIRU-VNTR patterns in 78 clusters with clustering rate and recent transmission rate of 14.2% and 8.3%, respectively. Fifty-three SLD-resistant isolates were observed in 31 clusters, 30 of which contained the strains with different drug susceptibility profiles and genetic mutations. In conjunction with molecular data, socio-network analysis indicated a key role of Central Township in the transmission across a highly interconnected network where SLD resistance accumulation occurred during transmission. SLD-resistant M. tuberculosis has been spreading in rural China with Beijing family being the dominant strains. Primary transmission of SLD-resistant strains in the population highlights the importance of routine drug susceptibility testing and effective anti-tuberculosis regimens for drug-resistant TB.
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China.
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Y
Hu
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Tuberculosis Center, Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
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Mathema
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China.
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Zhao
Tuberculosis Center, Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
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Chen
Department of Chronic Infectious Diseases, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, China.
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Lu
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China.
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Wang
Tuberculosis Center, Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
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Kreiswirth
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China. Electronic address: bxu@shmu.edu.cn.
B
B
Xu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002681:China / Q000453:epidemiology; D004269:DNA, Bacterial / Q000032:analysis; D054908:Extensively Drug-Resistant Tuberculosis / Q000635:transmission*; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018598:Minisatellite Repeats; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D010802:Phylogeny; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology / Q000635:transmission*; D055815:Young Adult
D004269:DNA, Bacterial
Beijing family; Mycobacterium tuberculosis; rural China; second-line drug resistance transmission; transmission network