title: Whole Genome Sequencing Demonstrates Limited Transmission within Identified Mycobacterium tuberculosis Clusters in New South Wales, Australia.
abstract: Australia has a low tuberculosis incidence rate with most cases occurring among recent immigrants. Given suboptimal cluster resolution achieved with 24-locus mycobacterium interspersed repetitive unit (MIRU-24) genotyping, the added value of whole genome sequencing was explored. MIRU-24 profiles of all Mycobacterium tuberculosis culture-confirmed tuberculosis cases diagnosed between 2009 and 2013 in New South Wales (NSW), Australia, were examined and clusters identified. The relatedness of cases within the largest MIRU-24 clusters was assessed using whole genome sequencing and phylogenetic analyses. Of 1841 culture-confirmed TB cases, 91.9% (1692/1841) had complete demographic and genotyping data. East-African Indian (474; 28.0%) and Beijing (470; 27.8%) lineage strains predominated. The overall rate of MIRU-24 clustering was 20.1% (340/1692) and was highest among Beijing lineage strains (35.7%; 168/470). One Beijing and three East-African Indian (EAI) clonal complexes were responsible for the majority of observed clusters. Whole genome sequencing of the 4 largest clusters (30 isolates) demonstrated diverse single nucleotide polymorphisms (SNPs) within identified clusters. All sequenced EAI strains and 70% of Beijing lineage strains clustered by MIRU-24 typing demonstrated distinct SNP profiles. The superior resolution provided by whole genome sequencing demonstrated limited M. tuberculosis transmission within NSW, even within identified MIRU-24 clusters. Routine whole genome sequencing could provide valuable public health guidance in low burden settings.
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia.|Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Sydney, Australia.
authors.forename: Ulziijargal
authors.initials: U
authors.lastname: Gurjav
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia.|Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Outhred
authors.affiliation: Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Sydney, Australia.|NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research-Pathology West, Sydney, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Jelfs
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia.|Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Sydney, Australia.
authors.forename: Nadine
authors.initials: N
authors.lastname: McCallum
authors.affiliation: Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Sydney, Australia.
authors.forename: Qinning
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia.|School of Public Health and Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Hill-Cawthorne
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia.|Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Marais
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia.|Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Sydney, Australia.
authors.forename: Vitali
authors.initials: V
authors.lastname: Sintchenko
mesh_terms: D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D016680:Genome, Bacterial; D060005:Genotyping Techniques; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D009517:New South Wales / Q000453:epidemiology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology* / Q000382:microbiology*; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial