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Genotype heterogeneity of Mycobacterium tuberculosis within geospatial hotspots suggests foci of imported infection in Sydney,Australia
Institution:1. Sydney Medical School and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia;2. NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research – Pathology West, Sydney, Australia;3. Centre for Infectious Diseases and Microbiology – Public Health, Westmead Hospital, Sydney, Australia;4. School of Public Health, The University of Sydney, Sydney, Australia;1. Division of HIV, Infectious Diseases and Global Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA;2. Berkeley School of Public Health, University of California, Berkeley, CA, USA;3. Makerere University and University of California, San Francisco, Research Collaboration, Kampala, Uganda;4. Kenya Medical Research Institute, Nairobi, Kenya;5. School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda;6. Infectious Diseases Research Collaboration, Kampala, Uganda;1. DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, and South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa;2. Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa;3. Department of Global Health Equity, Brigham and Women''s Hospital, Boston, MA, USA;4. KNCV Tuberculosis Foundation, The Hague, Netherlands;5. Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, Netherlands;6. University College London, London, UK;7. Interactive Research & Development, Karachi, Pakistan;8. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA;9. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;1. Centre de réadaptation en dépendance de Montréal – Institut Universitaire, Canada;2. Hôpital Charles LeMoyne Research Centre Longueuil (QC), Canada;3. Institut national de la recherche scientifique, Centre Urbanisation Culture Société, Montréal, Québec, Canada;4. Department of Mathematics and Statistics, University of Canterbury, New Zealand;5. Department of Community Health Sciences, Université de Sherbrooke, Qc, Canada;1. Ifakara Health Institute, Dar es Salaam, Tanzania;2. Swiss Tropical and Public Health Institute, Basel, Switzerland;3. University of Basel, Basel, Switzerland;4. Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa;5. Department of Electrical Engineering, Faculty of Engineering and the Built Environment, University of Cape Town, Cape Town, South Africa;6. National Tuberculosis and Leprosy Program, Dar es Salaam, Tanzania;7. Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
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.
Keywords:Molecular epidemiology  Genotyping  Geospatial hotspot
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