title: Molecular epidemiology of Mycobacterium tuberculosis complex in Singapore, 2006-2012.
abstract: BACKGROUND
  Tuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics.
  
  
  METHODS
  Non-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias.
  
  
  RESULTS
  A total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates - higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis.
  
  
  CONCLUSIONS
  Our work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally.
authors.affiliation: Singapore Tuberculosis Elimination Programme, Tan Tock Seng Hospital, Singapore, Singapore.
authors.forename: Leo Kang-Yang
authors.initials: LK
authors.lastname: Lim
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Li Hwei
authors.initials: LH
authors.lastname: Sng
authors.affiliation: Centre for Infectious Diseases Epidemiology and Research, Saw Swee Hock School of Public Health, Singapore, Singapore.
authors.forename: Wah
authors.initials: W
authors.lastname: Win
authors.affiliation: Singapore Tuberculosis Elimination Programme, Tan Tock Seng Hospital, Singapore, Singapore.
authors.forename: Cynthia Bin-Eng
authors.initials: CB
authors.lastname: Chee
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, Singapore ; Centre for Infectious Diseases Epidemiology and Research, Saw Swee Hock School of Public Health, Singapore, Singapore.
authors.forename: Li Yang
authors.initials: LY
authors.lastname: Hsu
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Estelle
authors.initials: E
authors.lastname: Mak
authors.affiliation: Centre for Infectious Diseases Epidemiology and Research, Saw Swee Hock School of Public Health, Singapore, Singapore ; Centre for Quantitative Medicine, Graduate Medical School, Singapore, Singapore.
authors.forename: Arul
authors.initials: A
authors.lastname: Earnest
authors.affiliation: Centre for Infectious Diseases Epidemiology and Research, Saw Swee Hock School of Public Health, Singapore, Singapore ; Department of Emergency Medicine, Singapore General Hospital, Singapore, Singapore.
authors.forename: Marcus Eng-Hock
authors.initials: ME
authors.lastname: Ong
authors.affiliation: Ministry of Health, Singapore, Singapore.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Cutter
authors.affiliation: Singapore Tuberculosis Elimination Programme, Tan Tock Seng Hospital, Singapore, Singapore.
authors.forename: Yee Tang
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000502:physiology; D012846:Singapore / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology* / Q000635:transmission; D055815:Young Adult