Heath Kelly

Australian National University, Canberra, Australian Capital Territory, Australia

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Publications (195)782.78 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: There is increasing evidence demonstrating influenza vaccine effectiveness (VE) in the prevention of influenza in children, including the very young. Data demonstrating the effectiveness against severe disease, including hospitalisation, are limited. We aimed to determine the VE of the southern hemisphere trivalent inactivated influenza vaccine (TIV) in preventing laboratory-confirmed influenza-associated hospitalisation in children. Patients and methods: Laboratory records were used to identify children with confirmed influenza hospitalised (i.e., cases) during a 5 year period (2008, 2010-2013) at the only tertiary paediatric facility in Western Australia. Cases and time, age and ward matched controls were retrospectively reviewed to determine risk factors, vaccination status and outcome. Adjusted odds ratios and VE estimates were derived using conditional logistic regression models. Results: Three hundred and eighty five cases were identified (Influenza A, 64.9%; Influenza B: 35.1%). Influenza-like illness and pneumonia were the most frequent presentation (74.5% and 23.9%, respectively). The median length of stay was 2 days (Interquartile range 1-4 days). Twenty children (5.2%) required admission to the intensive care unit. Vaccine uptake in cases and controls was low (4.9% and 8.5%, respectively). Three hundred and six case-control pairs were included in the VE analysis, of which 19 pairs were informative with discrepant vaccination status. VE (fully vaccinated vs. unvaccinated) was estimated to be 62.3% (95% CI: -6.6%, 86.7%). Conclusion: In this study, the point estimate for the effectiveness of TIV in preventing influenza-associated hospitalisation in children was similar to that reported for emergency or outpatient attended, laboratory-confirmed influenza, yet confidence intervals were wide. Vaccine uptake remains low. Studies, enroling larger numbers of children, ideally with higher vaccine uptake, are needed to provide additional evidence on TIV protection against influenza hospitalisation in children.
    Vaccine 11/2015; DOI:10.1016/j.vaccine.2015.10.122 · 3.62 Impact Factor
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    ABSTRACT: During the 2009 influenza pandemic, uncertainty surrounding the severity of human infections with the influenza A(H1N1)pdm09 virus hindered the calibration of the early public health response. The case fatality risk was widely used to assess severity, but another underexplored and potentially more immediate measure is the hospitalization fatality risk (HFR), defined as the probability of death among H1N1pdm09 cases who required hospitalization for medical reasons. In this review, we searched for relevant studies published in MEDLINE (PubMed) and EMBASE between April 1, 2009, and January 9, 2014. Crude estimates of the HFR ranged from 0% to 52%, with higher estimates from tertiary-care referral hospitals in countries with a lower gross domestic product, but in wealthy countries the estimate was 1%-3% in all settings. Point estimates increased substantially with age and with lower gross domestic product. Early in the next pandemic, estimation of a standardized HFR may provide a picture of the severity of infection, particularly if it is presented in comparison with a similarly standardized HFR for seasonal influenza in the same setting. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    American journal of epidemiology 07/2015; 182(4). DOI:10.1093/aje/kwv054 · 5.23 Impact Factor
  • Paul V Effler · Heath A Kelly ·

    Vaccine 06/2015; 33(42). DOI:10.1016/j.vaccine.2015.05.020 · 3.62 Impact Factor
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    ABSTRACT: The factors that determine the characteristic seasonality of influenza remain enigmatic. Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in Asia. To help reveal the drivers of seasonality we investigated the origins and evolution of influenza viruses sampled during inter-seasonal periods in Australia. To this end we conducted an expansive phylogenetic analysis of 9912, 3804, and 3941 hemagglutinnin (HA) sequences from influenza A/H1N1pdm, A/H3N2, and B, respectively, collected globally during the period 2009-2014. Of the 1475 viruses sampled from Australia, 396 (26.8% of Australian, or 2.2% of global set) were sampled outside the monitored temperate influenza surveillance season (1 May - 31 October). Notably, rather than simply reflecting short-lived importations of virus from global localities with higher influenza prevalence, we documented a variety of more complex inter-seasonal transmission patterns including "stragglers" from the preceding season and "heralds" of the forthcoming season, and which included viruses sampled from clearly temperate regions within Australia. We also provide evidence for the persistence of influenza B virus between epidemic seasons, in which transmission of a viral lineage begins in one season and continues throughout the inter-seasonal period into the following season. Strikingly, a disproportionately high number of inter-seasonal influenza transmission events occurred in tropical and subtropical regions of Australia, providing further evidence that climate plays an important role in shaping patterns of influenza seasonality.
    PLoS Pathogens 06/2015; 11(6):e1004991. DOI:10.1371/journal.ppat.1004991 · 7.56 Impact Factor
  • Ian G Barr · Heath A Kelly ·

    The Lancet Infectious Diseases 03/2015; 15(6). DOI:10.1016/S1473-3099(15)70084-8 · 22.43 Impact Factor
  • Heath Kelly · Benjamin J Cowling ·

    The Lancet 01/2015; 385(9979). DOI:10.1016/S0140-6736(15)60074-5 · 45.22 Impact Factor
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    ABSTRACT: The influenza virus undergoes frequent antigenic drift, necessitating annual review of the composition of the influenza vaccine. Vaccination is an important strategy for reducing the impact and burden of influenza, and estimating vaccine effectiveness (VE) each year informs surveillance and preventative measures. We aimed to describe the influenza season and to estimate the effectiveness of the influenza vaccine in Victoria, Australia, in 2013.Methods Routine laboratory notifications, general practitioner sentinel surveillance (including a medical deputising service) data, and sentinel hospital admission surveillance data for the influenza season (29 April to 27 October 2013) were collated in Victoria, Australia, to describe influenza-like illness or confirmed influenza during the season. General practitioner sentinel surveillance data were used to estimate VE against medically-attended laboratory confirmed influenza. VE was estimated using the case test negative design as 1 − adjusted odds ratio (odds of vaccination in cases compared with controls) × 100%. Cases tested positive for influenza while non-cases (controls) tested negative. Estimates were adjusted for age group, week of onset, time to swabbing and co-morbidities.ResultsThe 2013 influenza season was characterised by relatively low activity with a late peak. Influenza B circulation preceded that of influenza A(H1)pdm09, with very little influenza A(H3) circulation. Adjusted VE for all influenza was 55% (95%CI: −11, 82), for influenza A(H1)pdm09 was 43% (95%CI: −132, 86), and for influenza B was 56% (95%CI: −51, 87) Imputation of missing data raised the influenza VE point estimate to 64% (95%CI: 13, 85).Conclusions Clinicians can continue to promote a positive approach to influenza vaccination, understanding that inactivated influenza vaccines prevent at least 50% of laboratory-confirmed outcomes in hospitals and the community.
    Vaccine 11/2014; 33(2). DOI:10.1016/j.vaccine.2014.11.019 · 3.62 Impact Factor
  • Heath A Kelly ·

    The Medical journal of Australia 11/2014; 201(10):560-1. DOI:10.5694/mja14.01281 · 4.09 Impact Factor
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    Allen C. Cheng · Heath Kelly ·

    Australian and New Zealand Journal of Public Health 10/2014; 38(5). DOI:10.1111/1753-6405.12303 · 1.98 Impact Factor
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    ABSTRACT: We present preliminary results of influenza vaccine effectiveness (VE) in New Zealand using a case test-negative design for 28 April to 31 August 2014. VE adjusted for age and time of admission among all ages against severe acute respiratory illness hospital presentation due to laboratory-confirmed influenza was 54% (95% CI: 19 to 74) and specifically against A(H1N1)pdm09 was 65% (95% CI:33 to 81). For influenza-confirmed primary care visits, VE was 67% (95% CI: 48 to 79) overall and 73% (95% CI: 50 to 85) against A(H1N1)pdm09.
    Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 08/2014; 19(34). DOI:10.2807/1560-7917.ES2014.19.34.20884 · 5.72 Impact Factor
  • H Kelly · Bj Cowling ·

    Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 07/2014; 19(27). DOI:10.2807/1560-7917.ES2014.19.27.20850 · 5.72 Impact Factor
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    ABSTRACT: Vaccine effectiveness may wane with increasing time since vaccination. This analysis used the Victorian sentinel general practitioner (GP) network to estimate vaccine effectiveness for trivalent inactivated vaccines in the 2012 season. A test-negative design was used where patients presenting to GPs with influenza-like illness who tested positive for influenza were cases and noncases were those who tested negative. Vaccination status was recorded by GPs. Vaccine effectiveness was calculated as (1-odds ratio) × 100%. Estimates were compared early versus late in the season and by time since vaccination. Virus isolates were assessed antigenically by hemagglutination inhibition assay in a selection of positive samples and viruses from healthy adults who experienced a vaccine breakthrough were analyzed genetically. The adjusted vaccine effectiveness estimate for any type of influenza was 45% (95% CI: 8,66) and for influenza A(H3) was 35% (95% CI: -11,62). A non-significant effect of waning effectiveness by time since vaccination was observed for A(H3). For those vaccinated <93 days of presentation vaccine effectiveness was 37% (95% CI: -29,69), while for those vaccinated ≥93 days before presentation it was 18% (95% CI: -83,63). Comparison of early versus late in the season estimates was very sensitive to the cut off week chosen for analysis. Antigenic data suggested that low vaccine effectiveness was not associated with poor vaccine match among the A(H3) viruses. However, genetic analysis suggested nucleotide substitutions in antigenic sites. In 2012, the trivalent influenza vaccine provided moderate protection against influenza and showed limited evidence for waning effectiveness. Antigenic and genetic data can provide additional insight into understanding these estimates. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2014; 86(6). DOI:10.1002/jmv.23847 · 2.35 Impact Factor
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    ABSTRACT: Introduction: Parental attitudes towards vaccination significantly influence vaccine uptake. The A(H1N1)pdm09 influenza pandemic was followed in 2010 by an unprecedented increase in febrile reactions in children receiving trivalent inactivated influenza vaccine manufactured by bioCSL. Uptake of TIV in children <5 years in Western Australia (WA) decreased in 2010 and has remained low. The impact of pandemic A(H1N1)pdm09 and adverse-events on parental attitudes towards vaccination is uncertain. Materials and methods: A parental attitudes survey towards influenza illness and vaccination was conducted as part of the West Australian Influenza Vaccine Effectiveness study. Vaccination status was assessed by parental interview and confirmed by the national register and/or vaccine providers. Parental attitudes from vaccinated and unvaccinated children and attitudes in 2008-2009 and 2010-2012 were compared. Principal Component Analysis was conducted to determine core attitudes that influenced vaccine uptake. Results: Vaccination history and parental attitude surveys were available from 2576 children. Parents of fully vaccinated children less frequently stated that influenza was a mild disease, more frequently stated that influenza vaccine was safe and were less frequently worried about vaccine side effects. Uptake of influenza vaccine decreased significantly from 2010 onwards. From 2010, parents were less concerned about severe influenza, but more concerned about vaccine side effects and safety. Despite this significant shift in attitudes towards influenza vaccine, parental acceptance of vaccines on the national immunisation program did not change. Principal Component Analysis revealed that attitudes around vaccine safety and efficacy were the most important attitudes impacting on vaccine uptake. Conclusions: Parental attitudes to influenza vaccine changed from 2010. Confidence in the WA preschool influenza vaccination program remains low yet appeared unchanged for other vaccines. Restoring public confidence in childhood influenza vaccination is needed before uptake can be improved.
    Vaccine 05/2014; 32(32). DOI:10.1016/j.vaccine.2014.05.055 · 3.62 Impact Factor
  • E G Thomas · J M McCaw · H A Kelly · K A Grant · J McVernon ·
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    ABSTRACT: SUMMARY Influenza surveillance enables systematic collection of data on spatially and demographically heterogeneous epidemics. Different data collection mechanisms record different aspects of the underlying epidemic with varying bias and noise. We aimed to characterize key differences in weekly incidence data from three influenza surveillance systems in Melbourne, Australia, from 2009 to 2012: laboratory-confirmed influenza notified to the Victorian Department of Health, influenza-like illness (ILI) reported through the Victorian General Practice Sentinel Surveillance scheme, and ILI cases presenting to the Melbourne Medical Deputising Service. Using nonlinear regression, we found that after adjusting for the effects of geographical region and age group, characteristics of the epidemic curve (including season length, timing of peak incidence and constant baseline activity) varied across the systems. We conclude that unmeasured factors endogenous to each surveillance system cause differences in the disease patterns recorded. Future research, particularly data synthesis studies, could benefit from accounting for these differences.
    Epidemiology and Infection 04/2014; 143(02):1-13. DOI:10.1017/S0950268814000764 · 2.54 Impact Factor
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    ABSTRACT: Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). A case test-negative design was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalisation with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in South and Central Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season. The propensity and season adjusted vaccine effectiveness (VE) was estimated as 39% (95% CI 16;56). The VE point estimate against influenza A (H1N1) was lower than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 59% (95% CI 26;77) in patients aged 45-64 years but only 8% (-78;53) in those aged 65 years and above. Prospective surveillance for SARI has been successfully established in NZ. This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against influenza positive hospitalisation.
    Vaccine 04/2014; 32(29). DOI:10.1016/j.vaccine.2014.04.013 · 3.62 Impact Factor
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    ABSTRACT: There are few studies evaluating the effectiveness of trivalent influenza vaccination (TIV) in young children, particularly in children <2 years. The Western Australian Influenza Vaccine Effectiveness Study commenced in 2008 to evaluate a program providing TIV to children aged 6 to 59 months. An observational study enrolling children with influenza-like illness presenting to a tertiary pediatric hospital was conducted (2008-2012). Vaccination status was determined by parental questionnaire and confirmed via the national immunization register and/or vaccine providers. Respiratory virus polymerase chain reaction and culture were performed on nasopharyngeal samples. The test-negative design was used to estimate vaccine effectiveness (VE) by using 2 control groups: all influenza test-negative subjects and other-virus-detected (OVD) subjects. Adjusted odds ratios were estimated from models with season, month of disease onset, age, gender, indigenous status, prematurity, and comorbidities as covariates. Subjects enrolled in 2009 were excluded from VE calculations. Of 2001 children enrolled, influenza was identified in 389 (20.4%) children. Another respiratory virus was identified in 1134 (59.6%) children. Overall, 295 of 1903 (15.5%) children were fully vaccinated and 161 of 1903 (8.4%) children were partially vaccinated. Vaccine uptake was significantly lower in 2010-2012 after increased febrile adverse events observed in 2010. Using test-negative controls, VE was 64.7% (95% confidence interval [CI]: 33.7%-81.2%). No difference in VE was observed with OVD controls (65.8%; 95% CI: 32.1%-82.8%). The VE for children <2 years was 85.8% (95% CI: 37.9%-96.7%). This study reveals the effectiveness of TIV in young children over 4 seasons by using test-negative and OVD controls. TIV was effective in children aged <2 years. Despite demonstrated vaccine effectiveness, uptake of TIV remains suboptimal.
    PEDIATRICS 04/2014; 133(5). DOI:10.1542/peds.2013-3707 · 5.47 Impact Factor
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    James E Fielding · Heath A Kelly · Geoffry N Mercer · Kathryn Glass ·
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    ABSTRACT: Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a systematic literature review of the duration of influenza A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness and receipt of antiviral treatment. Studies were identified by searching the PubMed database using the keywords 'H1N1', 'pandemic', 'pandemics', 'shed' and 'shedding'. Any study of humans with an outcome measure of viral shedding was eligible for inclusion in the review. Comparisons by age, degree of severity and antiviral treatment were made with forest plots. The search returned 214 articles of which 22 were eligible for the review. Significant statistical heterogeneity between studies precluded meta-analysis. The mean duration of viral shedding generally increased with severity of clinical presentation, but we found no evidence of longer shedding duration of influenza A(H1N1)pdm09 among children compared with adults. Shorter viral shedding duration was observed when oseltamivir treatment was administered within 48 hours of illness onset. Considerable differences in the design and analysis of viral shedding studies limit their comparison and highlight the need for a standardised approach. These insights have implications not only for pandemic planning, but also for informing responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has become established as the seasonal H1N1 influenza virus.
    Influenza and Other Respiratory Viruses 12/2013; 8(2). DOI:10.1111/irv.12216 · 2.20 Impact Factor
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    ABSTRACT: To assess the magnitude and severity of the 2012 influenza season in Victoria, Australia using surveillance data from five sources. Data from influenza notifications, sentinel general practices, a sentinel hospital network, a sentinel locum service and strain typing databases for 2012 were descriptively analysed. Influenza and influenza-like illness activity was moderate compared to previous years, although a considerable increase in notified laboratory-confirmed influenza was observed. Type A influenza comprised between 83% and 87% of cases from the general practitioners, hospitals and notifiable surveillance data. Influenza A/H3 was dominant in July and August, and most tested isolates were antigenically similar to the A/Perth/16/2009 virus used in the vaccine. There was a smaller peak of influenza type B in September. No tested viruses were resistant to any neuraminidase inhibitor antivirals. Higher proportions of type A/H3, hospitalized cases and those with a comorbid condition indicated for influenza vaccination were aged 65 years or older. Influenza vaccination coverage among influenza-like illness patients was 24% in sentinel general practices and 50% in hospitals. The 2012 influenza season in Victoria was average compared to previous years, with an increased dominance of A/H3 accompanied by increases in older and hospitalized cases. Differences in magnitude and the epidemiological profile of cases detected by the different data sources demonstrate the importance of using a range of surveillance data to assess the relative severity of influenza seasons.
    11/2013; 4(3):42-50. DOI:10.5365/WPSAR.2013.4.2.007
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    ABSTRACT: Health authorities find thresholds useful to gauge the start and severity of influenza seasons. We explored a method for deriving thresholds proposed in an influenza surveillance manual published by the World Health Organization (WHO). For 2002-2011, we analysed two routine influenza-like-illness (ILI) datasets, general practice sentinel surveillance and a locum medical service sentinel surveillance, plus laboratory data and hospital admissions for influenza. For each sentinel dataset, we created two composite variables from the product of weekly ILI data and the relevant laboratory data, indicating the proportion of tested specimens that were positive. For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. From the thresholds, we compared the seasonal onset, end and intensity across all datasets from 2002-2011. Correlation between datasets was assessed using the mean correlation coefficient. The median week of peak activity was week 34 for all datasets, except hospital data (week 35). Means and medians were comparable and the 90% upper CIs were similar to the 95(th) percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. The composite variables improved the agreements between the ILI and other datasets. Datasets were well correlated, with mean correlation coefficients of >0.75 for a range of combinations. Thresholds for influenza surveillance are easily derived from historical surveillance and laboratory data using the approach proposed by WHO. Use of composite variables is helpful for describing influenza season characteristics.
    PLoS ONE 10/2013; 8(10):e77244. DOI:10.1371/journal.pone.0077244 · 3.23 Impact Factor
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    ABSTRACT: Background: There are few studies evaluating the effectiveness of the Southern Hemisphere trivalent influenza vaccination (TIV) in children or TIV effectiveness in children <2 years. The Western Australian Influenza Vaccine Effectiveness study commenced in 2008 to evaluate a state-based program providing TIV to children aged 6-59 months. Methods: An observational study enrolling children presenting to a tertiary paediatric hospital with influenza-like-illness was conducted from 2008-12. Vaccination status was determined by parental questionnaire and confirmed using the national immunisation register and/or vaccine providers. Fully vaccinated was defined as i) two doses of TIV ≥21 days apart and ≥14 days prior to presentation or ii) one dose ≥14 days prior to presentation and two or more doses in a previous year. Nasopharyngeal sampling for respiratory virus PCR and culture was performed. The test-negative design was used to estimate vaccine effectiveness (VE). Fully vaccinated and unvaccinated children were compared using two control groups: influenza test negative subjects (test negative controls) and subjects in whom another virus was detected (other virus detected controls). Adjusted odds ratios were estimated from models with season, week of disease onset, age, sex, Indigeneity, prematurity and comorbidities as covariates. Subjects enrolled in 2009 were excluded from VE calculations. VE was estimated for the influenza season. Results: Of 2408 children enrolled (median: 1.9y), 21.0% required hospital admission. Only 15.3% of children had significant comorbidities. Influenza was identified in 469 children (fluA, 13.7%; fluB: 5.8%). Another respiratory virus was identified in 1493 children (62.0%). Overall, 16.6% children were fully vaccinated and 8.4% partially vaccinated. Using test negative controls, VE for children recruited through the emergency department (2008, 2010-2012) was 63.8% (95%CI: 27.4-81.9%). No significant difference in VE was observed with other virus detected controls (68.2%; 95%CI: 26.5-86.2%). The VE for children < 2 years was 87.7% (95%CI: 39.5-97.5%). Conclusion: This study demonstrates the effectiveness of the Southern Hemisphere TIV in young children over multiple seasons using both test negative controls and other virus detected controls. TIV was effective in children aged <2 years.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013

Publication Stats

3k Citations
782.78 Total Impact Points


  • 2012-2015
    • Australian National University
      • National Centre for Epidemiology & Population Health Research
      Canberra, Australian Capital Territory, Australia
  • 1999-2015
    • Victorian Infectious Diseases Reference Laboratory
      Melbourne, Victoria, Australia
  • 2013
    • PathWest Laboratory Medicine
      Perth City, Western Australia, Australia
  • 2011
    • University of Vic
      Vic, Catalonia, Spain
  • 2002-2011
    • University of Melbourne
      • • Population Mental Health Group
      • • Department of Paediatrics
      Melbourne, Victoria, Australia
  • 2010
    • University of Western Australia
      • School of Computer Science and Software Engineering
      Perth City, Western Australia, Australia
  • 2009
    • University of Queensland 
      • School of Population Health
      Brisbane, Queensland, Australia
  • 2003-2008
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
    • Melbourne Health
      Melbourne, Victoria, Australia
  • 2005
    • Murdoch Childrens Research Institute
      Melbourne, Victoria, Australia