title: Whole-genome sequencing to detect recent transmission of Mycobacterium tuberculosis in settings with a high burden of tuberculosis.
abstract: Whole genome sequencing (WGS) of Mycobacterium tuberculosis has been used to trace the transmission of M. tuberculosis, the causative agent of tuberculosis (TB). Previously published studies using WGS were conducted in developed countries with a low TB burden. We sought to evaluate the relative usefulness of traditional VNTR and SNP typing methods, WGS and epidemiological investigations to study the recent transmission of M. tuberculosis in a high TB burden country. We conducted epidemiological investigations of 42 TB patients whose M. tuberculosis isolates were classified into three clusters based on variable-number tandem repeat (VNTR) typing. We applied WGS to 32 (76.2%) of the 42 strains and calculated the pairwise genomic distances between strains within each cluster. Eighteen (56.3%) of the 32 strains had genomic differences ≥100 SNPs with every other strain, suggesting that direct transmission did not likely occurred. Ten strains were grouped into four WGS-based clusters with genomic distances ≤5 SNPs within each cluster, and confirmed epidemiological links were identified in two of these clusters. Our results indicate that WGS provides reliable resolution for tracing the transmission of M. tuberculosis in high TB burden settings. The high resolution of WGS is particularly useful to confirm or exclude the possibility of direct transmission events defined by traditional typing methods.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: taoluo.fdu@gmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yangstoptb@gmail.com.
authors.forename: Chongguang
authors.initials: C
authors.lastname: Yang
authors.affiliation: Tuberculosis (TB) Control Center of Heilongjiang Province, No. 40, Youfang Street, Harbin, Heilongjiang 150030, China. Electronic address: Lily_pengj@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of TB Control, Songjiang District of Shanghai Municipal Center for Disease Control and Prevention, 1050 North Xi Lin Road, Shanghai 201620, China. Electronic address: luluyer-1194@163.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: sunguomei@gmail.com.
authors.forename: Guomei
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention, Shanghai 200336, China. Electronic address: wu790429@sina.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of TB Control, Songjiang District of Shanghai Municipal Center for Disease Control and Prevention, 1050 North Xi Lin Road, Shanghai 201620, China. Electronic address: jxp654321@163.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of TB Control, Songjiang District of Shanghai Municipal Center for Disease Control and Prevention, 1050 North Xi Lin Road, Shanghai 201620, China. Electronic address: hjj987654321@163.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Hong
authors.affiliation: Tuberculosis (TB) Control Center of Heilongjiang Province, No. 40, Youfang Street, Harbin, Heilongjiang 150030, China. Electronic address: hljlfb@163.com.
authors.forename: Fabin
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention, Shanghai 200336, China. Electronic address: meijiansh@yahoo.com.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Mei
authors.affiliation: University of California, Davis, School of Medicine, One Shields Avenue, Davis, CA 95616, USA. Electronic address: kderiemer@ucdavis.edu.
authors.forename: Kathryn
authors.initials: K
authors.lastname: DeRiemer
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: qgao99@yahoo.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015373:Bacterial Typing Techniques / Q000379:methods; D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D016358:Contact Tracing; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D016680:Genome, Bacterial; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial
keywords: Contact tracing; Genotyping; Transmission; Tuberculosis; Whole genome sequencing