Now showing 1 - 10 of 21
  • Publication
    Journal Article
    Using Genomics to Understand the Epidemiology of Infectious Diseases in the Northern Territory of Australia.
    The Northern Territory (NT) is a geographically remote region of northern and central Australia. Approximately a third of the population are First Nations Australians, many of whom live in remote regions. Due to the physical environment and climate, and scale of social inequity, the rates of many infectious diseases are the highest nationally. Molecular typing and genomic sequencing in research and public health have provided considerable new knowledge on the epidemiology of infectious diseases in the NT. We review the applications of genomic sequencing technology for molecular typing, identification of transmission clusters, phylogenomics, antimicrobial resistance prediction, and pathogen detection. We provide examples where these methodologies have been applied to infectious diseases in the NT and discuss the next steps in public health implementation of this technology.
      4824
  • Publication
    Journal Article
    Genomics-informed responses in the elimination of COVID-19 in Victoria, Australia: an observational, genomic epidemiological study.
    (2021-07-09)
    Lane, Courtney R
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    Sherry, Norelle L
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    Porter, Ashleigh F
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    Duchene, Sebastian
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    Horan, Kristy
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    Andersson, Patiyan
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    Wilmot, Mathilda
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    Turner, Annabelle
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    Dougall, Sally
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    Johnson, Sandra A
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    Sait, Michelle
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    Gonçalves da Silva, Anders
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    Ballard, Susan A
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    Hoang, Tuyet
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    Stinear, Timothy P
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    Caly, Leon
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    Sintchenko, Vitali
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    Graham, Rikki
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    McMahon, Jamie
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    Smith, David
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    Leong, Lex Ex
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    Cooley, Louise
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    Schwessinger, Benjamin
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    Rawlinson, William
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    van Hal, Sebastiaan J
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    Stephens, Nicola
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    Catton, Mike
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    Looker, Clare
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    Crouch, Simon
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    Sutton, Brett
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    Alpren, Charles
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    Williamson, Deborah A
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    Seemann, Torsten
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    Howden, Benjamin P
    BACKGROUND: A cornerstone of Australia's ability to control COVID-19 has been effective border control with an extensive supervised quarantine programme. However, a rapid recrudescence of COVID-19 was observed in the state of Victoria in June, 2020. We aim to describe the genomic findings that located the source of this second wave and show the role of genomic epidemiology in the successful elimination of COVID-19 for a second time in Australia. METHODS: In this observational, genomic epidemiological study, we did genomic sequencing of all laboratory-confirmed cases of COVID-19 diagnosed in Victoria, Australia between Jan 25, 2020, and Jan 31, 2021. We did phylogenetic analyses, genomic cluster discovery, and integrated results with epidemiological data (detailed information on demographics, risk factors, and exposure) collected via interview by the Victorian Government Department of Health. Genomic transmission networks were used to group multiple genomic clusters when epidemiological and genomic data suggested they arose from a single importation event and diversified within Victoria. To identify transmission of emergent lineages between Victoria and other states or territories in Australia, all publicly available SARS-CoV-2 sequences uploaded before Feb 11, 2021, were obtained from the national sequence sharing programme AusTrakka, and epidemiological data were obtained from the submitting laboratories. We did phylodynamic analyses to estimate the growth rate, doubling time, and number of days from the first local infection to the collection of the first sequenced genome for the dominant local cluster, and compared our growth estimates to previously published estimates from a similar growth phase of lineage B.1.1.7 (also known as the Alpha variant) in the UK. FINDINGS: Between Jan 25, 2020, and Jan 31, 2021, there were 20 451 laboratory-confirmed cases of COVID-19 in Victoria, Australia, of which 15 431 were submitted for sequencing, and 11 711 met all quality control metrics and were included in our analysis. We identified 595 genomic clusters, with a median of five cases per cluster (IQR 2-11). Overall, samples from 11 503 (98·2%) of 11 711 cases clustered with another sample in Victoria, either within a genomic cluster or transmission network. Genomic analysis revealed that 10 426 cases, including 10 416 (98·4%) of 10 584 locally acquired cases, diagnosed during the second wave (between June and October, 2020) were derived from a single incursion from hotel quarantine, with the outbreak lineage (transmission network G, lineage D.2) rapidly detected in other Australian states and territories. Phylodynamic analyses indicated that the epidemic growth rate of the outbreak lineage in Victoria during the initial growth phase (samples collected between June 4 and July 9, 2020; 47·4 putative transmission events, per branch, per year [1/years; 95% credible interval 26·0-85·0]), was similar to that of other reported variants, such as B.1.1.7 in the UK (mean approximately 71·5 1/years). Strict interventions were implemented, and the outbreak lineage has not been detected in Australia since Oct 29, 2020. Subsequent cases represented independent international or interstate introductions, with limited local spread. INTERPRETATION: Our study highlights how rapid escalation of clonal outbreaks can occur from a single incursion. However, strict quarantine measures and decisive public health responses to emergent cases are effective, even with high epidemic growth rates. Real-time genomic surveillance can alter the way in which public health agencies view and respond to COVID-19 outbreaks. FUNDING: The Victorian Government, the National Health and Medical Research Council Australia, and the Medical Research Future Fund.
      1591
  • Publication
    Journal Article
    Whole-Genome Sequencing to Differentiate Relapse From Reinfection in Community-Onset Bacteremic Acinetobacter baumannii Pneumonia.
    (2019-06-01) ; ; ;
    Piera KA
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    Sarovich DS
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    Davis JS
    Community-onset bacteremic Acinetobacter baumannii pneumonia recurred in 3 of 30 (10%) patients followed prospectively, all with ongoing hazardous alcohol intake, 3-56 months after initial pneumonia. Paired isolates underwent whole-genome sequencing. Phylogenetic analysis showed that recurrence strains were all distinct from preceding strains, indicating reinfection in susceptible individuals rather than relapse.
      715
  • Publication
    Journal Article
    Tuberculosis in Australia's tropical north: a population-based genomic epidemiological study.
    (2021-07-31) ;
    Horan K
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    Farmer B
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    Globan M
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    Stephenson E
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    Popple T
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    ;
    Kaestli M
    ;
    Seemann T
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    Vandelannoote K
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    Lowbridge C
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    Stinear TP
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    Williamson DA
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    ;
    BACKGROUND: The Northern Territory (NT) has the highest tuberculosis (TB) rate of all Australian jurisdictions. We combined TB public health surveillance data with genomic sequencing of Mycobacterium tuberculosis isolates in the tropical 'Top End' of the NT to investigate trends in TB incidence and transmission. METHODS: This retrospective observational study included all 741 culture-confirmed cases of TB in the Top End over three decades from 1989-2020. All 497 available M. tuberculosis isolates were sequenced. We used contact tracing data to define a threshold pairwise SNP distance for hierarchical single linkage clustering, and examined putative transmission clusters in the context of epidemiologic information. FINDINGS: There were 359 (48%) cases born overseas, 329 (44%) cases among Australian First Nations peoples, and 52 (7%) cases were Australian-born and non-Indigenous. The annual incidence in First Nations peoples from 1989-2019 fell from average 50.4 to 11.0 per 100,000 (P<0·001). First Nations cases were more likely to die from TB (41/329, 12·5%) than overseas-born cases (11/359, 3·1%; P<0·001). Using a threshold of ≤12 SNPs, 28 clusters of between 2-64 individuals were identified, totalling 250 cases; 214 (86%) were First Nations cases and 189 (76%) were from a remote region. The time between cases and past epidemiologically- and genomically-linked contacts ranged from 4·5 months to 24 years. INTERPRETATION: Our findings support prioritisation of timely case detection, contact tracing augmented by genomic sequencing, and latent TB treatment to break transmission chains in Top End remote hotspot regions.
      1221
  • Publication
    Journal Article
    What is the Role of Lateral Flow Immunoassay for the Diagnosis of Melioidosis?
    (2022-03-21) ;
    Woerle C
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    Mayo M
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    ;
    BACKGROUND: Culture of Burkholderia pseudomallei remains the gold standard for diagnosis of melioidosis but is not possible in many resource-limited settings where melioidosis is endemic. Direct identification of B. pseudomallei antigen in clinical samples has been developed using a lateral flow immunoassay (LFA) targeting B. pseudomallei capsular polysaccharide. METHODS: We summarized the findings from the 8 studies to date of the Active Melioidosis Detect (AMD) LFA and compared these with our results from 232 patients with culture-confirmed melioidosis. We have also optimized the methodology for testing different clinical samples. RESULTS: Sensitivity and specificity for different samples were broadly similar in our study to those published from Thailand, India, Laos, and Malaysia. One hundred thirty of 232 (56%) of our melioidosis patients were positive on 1 or more AMD tests: 27% for serum (rising to 39% in those with bacteremic melioidosis and 68% in those with septic shock), 63% for urine (72% in bacteremic melioidosis and 90% in septic shock), 85% in sputum that was culture positive, and 83% in pus that was culture positive. Heating sputum and pus samples increased sensitivity. Faint false-positive urine bands seen on earlier AMD versions were not seen when retested using the most recent version, AMD-Plus. CONCLUSIONS: While the sensitivity of melioidosis LFA is low overall for blood samples, there is potential for use as a rapid diagnostic: testing serum and urine from those with severe sepsis who may have melioidosis and testing sputum and pus samples from clinically relevant scenarios. Prospective studies of patients with sepsis and other clinical presentations resembling melioidosis are required to ascertain if the specificity of AMD-PLUS is adequate to enable diagnosis of melioidosis with a high positive predictive value.
      2159
  • Publication
    Journal Article
    Extended detection and isolation of Murray Valley encephalitis virus in whole blood and urine.
    (2019-11-19)
    Caly L
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    Davidson N
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    Ghimire R
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    Rajaratnam B
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    Marrow J
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    ; ;
    Druce J
      1493
  • Publication
    Journal Article
    The use of whole genome sequencing for tuberculosis public health activities in Australia: a joint statement of the National Tuberculosis Advisory Committee and Communicable Diseases Genomics Network.
    (2023-02-28)
    Donnan EJ
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    Marais BJ
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    Coulter C
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    Waring J
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    Bastian I
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    Williamson DA
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    Sherry NL
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    Bond K
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    Sintchenko V
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    Horan K
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    Cooley L
    ;
    Denholm JT
      3871
  • Publication
    Journal Article
    Genomic epidemiology links Burkholderia pseudomallei from individual human cases to B. pseudomallei from targeted environmental sampling in Northern Australia.
    (2022-01-26)
    Webb JR
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    Mayo M
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    Rachlin A
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    Woerle C
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    Rigas V
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    Harrington G
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    Kaestli M
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    Each case of melioidosis results from a single event when a human is infected by the environmental bacterium Burkholderia pseudomallei. Darwin in tropical northern Australia has the highest incidences of melioidosis globally and the Darwin Prospective Melioidosis Study (DPMS) commenced in 1989, documenting all culture confirmed melioidosis cases. From 2000-2019 we sampled DPMS patient's environments for B. pseudomallei when a specific location was considered to have been where infection occurred. With the aim to use genomic epidemiology to understand B. pseudomallei transmission and infecting scenarios. Environmental sampling was performed at 98 DPMS patient sites, where we collected 975 environmental samples (742 soil; 233 water). Genotyping matched the clinical and epidemiologically linked environmental B. pseudomallei for 19 patients (19%), with the environmental isolates cultured from soil (n=11) or water (n=8) sources. B. pseudomallei isolates from patients and their local environments that matched on genotyping were whole genome sequenced (WGS). Of the 19 patients with a clinical-environmental genotype match, 17 pairs clustered on a Darwin core genome single-nucleotide polymorphism (SNP) phylogeny, later confirmed by single ST phylogenies and pairwise comparative genomics. When related back to patient clinical scenarios, the matched clinical and environmental B. pseudomallei pairs informed likely modes of infection: percutaneous inoculation, inhalation, and ingestion. Targeted environmental sampling for B. pseudomallei can inform infecting scenarios for melioidosis and dangerous occupational and recreational activities and identify hot spots of B. pseudomallei presence. However, WGS and careful genomics are required to avoid overcalling the relatedness between clinical and environmental isolates of B. pseudomallei.
      2481
  • Publication
    Journal Article
    Burkholderia pseudomallei and melioidosis.
    (2023-10-04) ;
    Limmathurotsakul D
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    Dunachie SJ
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    Wiersinga WJ
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    Burkholderia pseudomallei, the causative agent of melioidosis, is found in soil and water of tropical and subtropical regions globally. Modelled estimates of the global burden predict that melioidosis remains vastly under-reported, and a call has been made for it to be recognized as a neglected tropical disease by the World Health Organization. Severe weather events and environmental disturbance are associated with increased case numbers, and it is anticipated that, in some regions, cases will increase in association with climate change. Genomic epidemiological investigations have confirmed B. pseudomallei endemicity in newly recognized regions, including the southern United States. Melioidosis follows environmental exposure to B. pseudomallei and is associated with comorbidities that affect the immune response, such as diabetes, and with socioeconomic disadvantage. Several vaccine candidates are ready for phase I clinical trials. In this Review, we explore the global burden, epidemiology and pathophysiology of B. pseudomallei as well as current diagnostics, treatment recommendations and preventive measures, highlighting research needs and priorities.
      512