Infectious Diseases
We aim to change the trajectory of global childhood and adult health to reduce the impact of infectious diseases and allergies.
Improving the diagnosis, treatment and prevention of infectious diseases in children is at the heart of everything we do. To achieve this, our research comprises both clinical and laboratory-based studies, with a focus on global collaboration to engage the brightest minds in infectious diseases.
Our clinical research includes randomised controlled trials, observational studies and systematic reviews of best practice. Our laboratory research encompasses basic and applied immunological, as well as microbiological studies, to explore the mechanisms by which pathogens interact with the host immune response and cause disease.
Our focus
We have a particular interest in infections that are important to child health worldwide, such as COVID-19, tuberculosis and other respiratory infections, diarrhoeal illnesses and neonatal sepsis.
A key focus of our current work is the investigation of the heterologous - or off-target - effects of Bacille Calmette-Guérin (BCG) vaccination. Our team is investigating the hypothesis that the immunomodulatory effects of BCG influence the development of infant immunity to enhance protection against infections and reduce susceptibility to allergic disease.
In adults, our multinational BRACE trial is the world’s largest study on the off-target effects of the BCG vaccine, with almost 7,000 healthcare workers enrolled in Australia, Brazil, Spain, the Netherlands and the United Kingdom.
Another focus area is the optimisation of antimicrobial used to improve the quality of care for children with infectious diseases and the prevention of harm from antimicrobial therapy, specifically in children.
Professor Nigel Curtis | Murdoch Children's Annual Showcase 2020
Professor Nigel Curtis is a paediatric infectious diseases physician and clinician scientist and leader of the Infectious Diseases Research Group at the Murdoch Children's Research Institute. Nigel is asking whether a 100-year-old vaccine can protect healthcare workers against COVID-19?
BRACE trial in the media
This Australian-led study is the world’s largest trial on the off-target effects of Bacille Calmette-Guérin (BCG) vaccine. More than 6800 healthcare workers are enrolled in Australia, Brazil, Spain, the Netherlands and the United Kingdom.
BRACE trial - Behind the Scenes
Take a peek behind the curtain of the world’s largest trial on the off-target effects of BCG vaccine. Follow sample shipments from across the globe to the MCRI laboratories, see our clinics in action and learn what the data team is up to, as the BRACE trial seeks to determine whether BCG vaccine reduces the incidence of symptomatic and severe COVID-19, as well as other respiratory illnesses and allergic diseases.
BRACE in Brazil
The BRACE trial extended into Brazil when COVID-19 infections were skyrocketing. Hear from our investigators Associate Professor Julio Croda and Professor Margareth Dalcolmo about how the multinational BCG vaccine study is going, and what will happen next.
BRACE video Clinical Trials Day 2021
Hear from Ann Ginsberg, of the Bill & Melinda Gates Foundation, about how the BRACE trial has risen to the challenge of running the largest BCG vaccine study for healthcare workers during the global pandemic.
MIS BAIR - BCG for allergy and infection reduction study
A vaccine that was routinely used in Australia to prevent tuberculosis in the 80s could reduce the rate of allergies and infections in infants and children.
Our projects
BCG vaccination to Reduce the impAct of COVID-19 in hEalthcare workers (The BRACE trial)
Launched in March 2020, this Australian-led study has become the world’s largest trial on the off-target effects of BCG vaccine. Almost 7,000 healthcare workers are enrolled in Australia, Brazil, Spain, the Netherlands and the United Kingdom. Besides preventing severe tuberculosis in children, BCG vaccine has off-target (non-specific or immunomodulatory) effects. This multicentre, randomised controlled clinical trial is working to determine whether BCG vaccine reduces the incidence of symptomatic and severe COVID-19 as well as other respiratory illness and allergic diseases.
The BRACE COVID-19-Specific vaccine sub-study (BCOS) is investigating the impact of BCG vaccine on the response to the Pfizer, AstraZeneca and CoronaVac COVID-19 vaccines, and their impact on SARS-CoV-2 variants.
Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR)
Until the 1980s, BCG vaccine was given to Australian children to prevent tuberculosis (TB). Routine administration was discontinued because of the country’s low prevalence of TB. However, BCG is still administered to over 120 million infants worldwide each year. In high-mortality countries, neonatal BCG vaccination is associated with a halving in mortality in the first year of life. Research also shows the 100-year-old vaccine boosts immunity to protect against respiratory viral infections. The Murdoch Children's Research Institute launched the MIS BAIR trial in 2015. The study team is following the lives of over 1200 Melbourne children from birth to primary school exploring the immune boosting effects of BCG and whether this vaccine can reduce the risk of infectious diseases, as well as food allergy, eczema and asthma in infants and children.
The BabyBAIR study
In this cohort study, we are investigating how BCG vaccination modifies the immune response to subsequent (in vitro) challenge with viral and bacterial pathogens unrelated to TB in healthy children and young adults.
Disease risk and prediction of immunity
Are there biomarkers that predict severity of COVID-19, respiratory infections and allergy? What are the major causes of inter-individual variability in immune responses to pathogens and vaccines? Using samples from the extensive biobank of samples combined with clinical data from our large international trials, we are identifying biomarkers for prediction, and key factors that influence disease risk, vaccine responses, anti-pathogen immunity and immune development.
TB diagnosis: biomarkers for immunodiagnosis and monitoring of treatment
These studies aim to determine sensitivity and specificity of our novel cytokine biomarkers in children and adults in high TB prevalence settings, and their ability to distinguish between latent TB infection and active TB. This validation is a critical step in the development of a new generation of low cost, point-of-care immunodiagnostic assays for TB.
Mycobacterial-specific response to BCG
Besides investigating the non-specific effects of BCG, we are also investigating the mycobacterial-specific response to BCG vaccination. These studies are investigating the immune response to BCG and the influence of vaccine strain, age of administration, as well as maternal vaccination on response to BCG. Optimisation of antimicrobial use studies includes:
- VANC trial: RCT of continuous versus intermittent dosing of vancomycin in neonates
- Optimising vancomycin dosing in young infants using a web app
- BonE and joint infections in children—Simplifying Treatment in children (BEST) trial
- Recycling older antimicrobials (fosfomycin) for multi-drug resistant infections
- Adverse drug reactions in children—assessing causality, severity and avoidability of ADRs
- Multicentre prospective study of the role an immune evaluation in children with IPD
- Role of pharmacogenomics in azole dosing in immunocompromised children
- Salivary drug monitoring for azole antifungals in children
- An electronic medical record-embedded antibiotic allergy delabeling program
- Role of pharmacogenomics in predicting antibiotic allergy
- Cost effectiveness of an immune work up in children with IPD
- DOSE optimisation in Cystic Fibrosis Kids (DOSE CF kids)
- S. aureus Network Adaptive Platform trial (SNAP) PKPD sub-study
Funding
BRACE trial funding
- The Bill & Melinda Gates Foundation (INV-017302)
- The Minderoo Foundation (COV-001)
- Sarah and Lachlan Murdoch
- The Royal Children's Hospital Foundation (2020-1263 BRACE Trial)
- Health Services Union NSW,
- The Peter Sowerby Foundation
- The Ministry of Health Government of South Australia
- The NAB Foundation
- The Calvert-Jones Foundation
- The Modara Pines Charitable Foundation
- The UHG Foundation Pty Ltd
- Epworth Healthcare
- The University of Melbourne Research and Training Program scholarship
- The Clifford Family scholarship
- Australian Government Research Training Program (RTP) Scholarship administered by the University of Melbourne and Murdoch Children’s Research Institute PhD Top-Up Scholarship
- The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health (Health Protection Program Agreement # 4-4GFBE88)
- Individual donors
MIS BAIR funding
- National Health and Medical Research Council
- Mercy Health
- Meyer Foundation
- European Society for Paediatric Infectious Diseases
- Swiss National Science Foundation
- Nossal Institute for Global Health
- Aranday Foundation
Other group funders
- John Burge Trust
- The Myer Foundation
Collaborations
- Radboud University Nijmegen Medical Centre
- University of Oxford
- University College London
- Instituto de Medicina Tropical Alexander von Humboldt Cayetano Heredia University
- Groningen University Nijmegen Medical Centre
- Telethon Kids Institute
- South Australian Health and Medical Research Institute (SAHMRI)
- The Children's Hospital at Westmead
- University hospital in Utrecht (UMCU)
- University of Exeter
- National Centre for Immunisation Research and Surveillance (NCIRS)
- Peter Doherty Institute
- Microbiological Diagnostic Unit Public Health Laboratory
- Victorian Infectious Diseases Reference Laboratory
- Hudson Institute of Medical Research
External collaborations/partnerships
BRACE trial
- Eight regional centres and 35 sites in UK, Spain, Netherland, Brazil and Australia.
Other international
- Radboud UMC (Netherlands)
- University of São Paulo (Brazil)
- University of Oxford (UK)
- Hospital Universitario Virgen del Rocío (Spain)
- Cayetano Heredia University (Peru)
- University of Freiberg (Switzerland)
- Harvard University (USA)
- University of Southern Denmark (Denmark)
- University of Otago (NZ)
- University of Montreal (Canada)
- University College London (UK)
National
- Peter Doherty Institute
- Centenary Institute
- Telethon
- Monash University
- University of Queensland
- University of Sydney
- The University of Melbourne, Health Economics Unit
- ANZPID network
- SNAP trial network
- BEAT CF network
Featured publications
- How Common Is Long COVID in Children and Adolescents?
Zimmermann P, Pittet L, Curtis N. Pediatr Infect Dis J. Sept 2021 doi: 10.1097/INF.0000000000003328. - Neonatal Bacille Calmette-Guérin Vaccination and Infections in the First Year of Life: The MIS BAIR Randomized Controlled Trial.
Messina NL, Pittet LF, Gardiner K, Freyne B, Francis KL, Zufferey C, Abruzzo V, Morrison C, Allen KJ, Flanagan KL, Ponsonby AL, Robins-Browne R, Shann F, South M, Vuillermin P, Donath S, Casalaz D, Curtis N.
J Infect Dis. 2021 Oct 13;224(7):1115-1127. doi: 10.1093/infdis/jiab306. PMID: 34146093. - Mycobacterium tuberculosis-specific cytokine biomarkers for the diagnosis of childhood TB in a TB-endemic setting.
Sudbury EL, Otero L, Tebruegge M, Messina NL, Seas C, Montes M, Rìos J, Germano S, Gardiner K, Clifford V, Gotuzzo E, Curtis N.
J Clin Tuberc Other Mycobact Dis. 2019 Apr 25;16:100102. doi: 10.1016/j.jctube.2019.100102. PMID: 31720428; PMCID: PMC6830137. - Continuous Versus Intermittent Vancomycin Infusions in Infants: A Randomized Controlled Trial.
Gwee A, Cranswick N, McMullan B, Perkins E, Bolisetty S, Gardiner K, Daley A, Ward M, Chiletti R, Donath S, Hunt R, Curtis N.
Pediatrics. 2019 Feb;143(2):e20182179. doi: 10.1542/peds.2018-2179. PMID: 30700564. - Neonatal BCG Vaccination Influences Cytokine Responses to Toll-like Receptor Ligands and Heterologous Antigens.
Freyne B, Donath S, Germano S, Gardiner K, Casalaz D, Robins-Browne RM, Amenyogbe N, Messina NL, Netea MG, Flanagan KL, Kollmann T, Curtis N.
J Infect Dis. 2018 May 5;217(11):1798-1808. doi: 10.1093/infdis/jiy069. PMID: 29415180.