research

susceptibility to paediatric infection (SPIn)

summary

Infections are a normal part of growing up. Some children are more susceptible to infection and some develop more severe infection than others. Our research investigates why these differences occur. The findings will help develop new ways to prevent and treat infection. We are particularly interested in infection and cardiovascular health, including the role of infection in the development of atherosclerosis (hardening of the arteries). We are involved in international studies of Kawasaki disease, a poorly understood condition that may damage the coronary arteries of children. Kawasaki disease affects about 200 children per year in Australia and thousands worldwide, making it the most common cause of acquired childhood heart disease.

group leader(s)

David Burgner  Dr David Burgner
  Susceptibility to Paediatric Infection (SPIn)   
  Murdoch Childrens Research Institute
  Royal Children's Hospital
  Flemington Road
  Parkville Victoria 3052
 

  T +61 3 9936 6530
  E david.burgner@mcri.edu.au

   group leader biography

current research projects

Project 1: Genetic determinants of Kawasaki disease - The International Kawasaki Disease Genetic Consortium

Our group plays a leading role in this international collaboration, which involves researchers from 12 countries investigating genetic determinants of Kawasaki disease susceptibility and outcomes. We have published the two major genome-wide association studies of Kawasaki disease (PLoS Genetics 2009 and Nature Genetics 2011) and are currently undertaking a number of state-of-the-art genomic studies, particularly through collaboration with the Genome Institute of Singapore. We are also leading a number of epidemiological, cardiovascular and immunological studies of Kawasaki disease, including the most comprehensive investigation of Australian Kawasaki disease epidemiology to date.

Project 2:   The relationship between childhood infection and inflammation, and cardiovascular risk

This series of collaborative studies with the Telethon Institute of Child Health Research (WA) and The Menzies School of Health Research (NT), The Young Finns Study (Turku, Finland) is investigating the relationship between childhood infection, markers of atherosclerosis and cardiovascular risk in adulthood. Most studies involve large data linkage analyses, often using total population data. Studies to investigate underlying biological mechanisms are planned.

Project 3: The determinants of the development of atherosclerosis in early life - The Barwon Infant Study

Atherosclerosis commences early in life, and continues for decades before causing disease. We are investigating the early development of atherosclerosis from birth onwards in a large and unique Victorian birth cohort study of 1250 infants - The Barwon Infant Study. We are particularly interested in the role of maternal factors, fetal growth and early life infections.

Project 4: Perinatal determinants of atherosclerosis and cardiovascular health.

We are collaborating with Monash University and the Royal Women's Hospital, Melbourne on studies looking at the impact of (i) maternal diabetes (ii) neonatal infection in premature infants and (iii) perinatal inflammation on the development of atherosclerosis, which also includes a murine model of intrauterine inflammation in atherosclerosis-prone mice.

Project 4: Why are preterm infants so susceptible to infection?

This NHMRC-supported collaborative research is based in Western Australia, with some research activity at MCRI. We have described functional in vitro differences in innate immune responses in preterm infants (compared to full-term infants and adults) and the modulating effects of perinatal inflammation on post-natal immune function. We are currently undertaking a prospective study to identify the post-natal immunological phenotype that identifies preterm infants who subsequently develop bacterial infection

team members

  • Kate Mccloskey - PhD Student (UoM Paeds)

publications

  • Breunis WB., Davila S., Shimizu C., Oharaseki T., Takahashi K., van Houdt M., Khor CC., Wright VJ., Levin M., Burns JC., Burgner D., Hibberd ML., Kuijpers TW., On behalf of the International Kawasaki Disease Genetics Consortium. Disruption of vascular homeostasis in Kawasaki Disease patients: Involvement of vascular endothelial growth factor and angiopoietins. Arthritis & Rheumatism (2011) PubMed
  • Burgner D., Carter K., Webster R., Kuijpers TW. Kawasaki disease, childhood allergy and the hygiene hypothesis. PEDIATRIC ALLERGY AND IMMUNOLOGY 22 (7) : 751 - 751(2011) PubMed
  • Connell TG., Zar HJ., Nicol MP. Advances in the Diagnosis of Pulmonary Tuberculosis in HIV-Infected and HIV-Uninfected Children. JOURNAL OF INFECTIOUS DISEASES 204 (2011)
  • Crighton G., Haeusler G., Pati N., Connell TG. PNEUMOCYSTIS JIROVECI PNEUMONIA IN AN INFANT WITH SEVERE FOLATE DEFICIENCY. PEDIATRIC INFECTIOUS DISEASE JOURNAL 30 (8) : 721 - 723(2011) PubMed
  • Currie AJ., Curtis S., Strunk T., Riley K., Liyanage K., Prescott S., Doherty D., Simmer K., Richmond P., Burgner D. Preterm Infants Have Deficient Monocyte and Lymphocyte Cytokine Responses to Group B Streptococcus. INFECTION AND IMMUNITY 79 (4) : 1588 - 1596(2011) PubMed
  • Gill PJ., Burgner D., Harnden A. Persistent fever and rash in a young child. BRITISH MEDICAL JOURNAL (2011) PubMed
  • Khandaker G., Marshall H., Peadon E., Zurynski Y., Burgner D., Buttery J., Gold M., Nissen M., Elliott EJ., Burgess M., Booy R. Congenital and neonatal varicella: impact of the national varicella vaccination programme in Australia. ARCHIVES OF DISEASE IN CHILDHOOD 96 (5) : 453 - 456(2011) PubMed
  • Khor CC., Davila S., Breunis WB., Lee YC., Shimizu C., Wright VJ., Yeung RSM., Tan DEK., Sim KS., Wang JJ., Wong TY., Pang JX., Mitchell P., Cimaz R., Dahdah N., Cheung YF., Huang GY., Yang WL., Park IS., Lee JK., Wu JY., Levin M., Burns JC., Burgner D., Kuijpers TW., Hibberd ML., Lau YL., Zhang J., Ma XJ., Liu F., Wu L., Yoo JJ., Hong SJ., Kim KJ., Kim JJ., Park YM., Hong YM., Sohn S., Jang GY., Ha KS., Nam HK., Byeon JH., Yun SW., Han MK., Lee KY., Hwang JY., Rhim JW., Song MS., Lee HD., Kim DS., Lee JM., Chang JS., Tsai FJ., Liang CD., Chen MR., Chi H., Chiu NC., Huang FY., Chang LY., Huang LM., Kuo HC., Huang KP., Lee ML., Hwang B., Huang YC., Lee PC., Odam M., Christiansen FT., Witt C., Goldwater P., Curtis N., Palasanthiran P., Ziegler J., Nissen M., Nourse C., Kuipers IM., Ottenkamp JJ., Geissler J., Biezeveld M., Tacke C., Filippini L., Brogan P., Klein N., Shah V., Dillon M., Booy R., Shingadia D., Bose A., Mukasa T., Tulloh R., Michie C., Newburger JW., Baker AL., Rowley AH., Shulman ST., Mason W., Takahashi M., Melish ME., Tremoulet AH., Viswanathan A., Rochtchina E., Attia J., Scott R., Holliday E., Harrap S. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. NATURE GENETICS 43 (12) : 1241 (2011)
  • Khor CC., Davila S., Shimizu C., Sheng S., Matsubara T., Suzuki Y., Newburger JW., Baker A., Burgner D., Breunis W., Kuijpers T., Wright VJ., Levin M., Hibberd ML., Burns JC. Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease. JOURNAL OF MEDICAL GENETICS 48 (7) : 467 - 472(2011) PubMed
  • Rye MS., Bhutta MF., Cheeseman MT., Burgner D., Blackwell JM., Brown SDM., Jamieson SE. Unraveling the genetics of otitis media: from mouse to human and back again. MAMMALIAN GENOME 22 (40575) : 66 - 82(2011) PubMed
  • Rye MS., Wiertsema SP., Scaman ESH., Oommen J., Sun W., Francis RW., Ang W., Pennell CE., Burgner D., Richmond P., Vijayasekaran S., Coates HL., Brown SD., Blackwell JM., Jamieson SE. FBXO11, a regulator of the TGF beta pathway, is associated with severe otitis media in Western Australian children. GENES AND IMMUNITY 12 (5) : 352 - 359(2011) PubMed
  • Strunk T., Doherty D., Jacques Mbiostat A., Simmer K., Richmond P., Kohan R., Charles A., Burgner D. Histologic chorioamnionitis is associated with reduced risk of late-onset sepsis in preterm infants. PEDIATRICS 129 (1) : 134 - 141(2011) PubMed
  • Webster RJ., Carter KW., Warrington NM., Loh AM., Zaloumis S., Kuijpers TW., Palmer LJ., Burgner DP. Hospitalisation with infection, asthma and allergy in Kawasaki disease patients and their families: genealogical analysis using linked population data. PLOS ONE (2011) PubMed

competitive funding

NHMRC
NHFA

collaborations & affiliations

Telethon Institute of Child Health Research
Sydney Medical School
The Genome Institute of Singapore
The Young Finns Study, Turku, Finland
Harvard Medical School
Academic Medical Centre, Amsterdam