title: Genotype heterogeneity of Mycobacterium tuberculosis within geospatial hotspots suggests foci of imported infection in Sydney, Australia.
abstract: In recent years the State of New South Wales (NSW), Australia, has maintained a low tuberculosis incidence rate with little evidence of local transmission. Nearly 90% of notified tuberculosis cases occurred in people born in tuberculosis-endemic countries. We analyzed geographic, epidemiological and genotypic data of all culture-confirmed tuberculosis cases to identify the bacterial and demographic determinants of tuberculosis hotspot areas in NSW. Standard 24-loci mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-24) typing was performed on all isolates recovered between 2009 and 2013. In total 1692/1841 (91.9%) cases with confirmed Mycobacterium tuberculosis infection had complete MIRU-24 and demographic data and were included in the study. Despite some year-to-year variability, spatio-temporal analysis identified four tuberculosis hotspots. The incidence rate and the relative risk of tuberculosis in these hotspots were 2- to 10-fold and 4- to 8-fold higher than the state average, respectively. MIRU-24 profiles of M. tuberculosis isolates associated with these hotspots revealed high levels of heterogeneity. This suggests that these spatio-temporal hotspots, within this low incidence setting, can represent areas of predominantly imported infection rather than clusters of cases due to local transmission. These findings provide important epidemiological insight and demonstrate the value of combining tuberculosis genotyping and spatiotemporal data to guide better-targeted public health interventions.
authors.affiliation: Sydney Medical School and the 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: NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research - Pathology West, Sydney, Australia; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, Sydney, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Jelfs
authors.affiliation: Sydney Medical School and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia; School of Public Health, The University of Sydney, Sydney, Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Hill-Cawthorne
authors.affiliation: Sydney Medical School and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Marais
authors.affiliation: Sydney Medical School and the 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. Electronic address: vitali.sintchenko@sydney.edu.au.
authors.forename: Vitali
authors.initials: V
authors.lastname: Sintchenko
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D002648:Child; D004269:DNA, Bacterial; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D062306:Geography, Medical; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics*; D062206:Spatial Analysis; D062211:Spatio-Temporal Analysis; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology*; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial
keywords: Genotyping; Geospatial hotspot; Molecular epidemiology; Mycobacterium tuberculosis