Infectious Diseases
We aim to change the trajectory of global child 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 practices. 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 respiratory infections (e.g., tuberculosis and COVID-19) 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 vaccination influence the development of infant immunity to enhance protection against infections and reduce susceptibility to allergic disease.
In infants, our MIS BAIR trial is investigating the beneficial off-target effects of neonatal BCG vaccination in protecting against infection, eczema, allergy and asthma.
In adults, our multinational BRACE trial of the off-target effects of BCG vaccination randomised in 6,828 healthcare workers in Australia, Brazil, Spain, the Netherlands and the United Kingdom.
Another research area is identifying determinants of immunity and susceptibility to infections using a multi-omics approach.
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 Murdoch Children's Research Institute. Nigel is investigating whether a 100-year-old vaccine can protect healthcare workers against COVID-19.
BRACE trial in the media
This Australian-led study is amongst the world’s largest trial on the off-target effects of Bacille Calmette-Guérin (BCG) vaccine. More than 6,800 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 definitive trial on the off-target effects of BCG vaccine. Follow sample shipments from across the globe to the Murdoch Children's 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 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.
BCG vaccination to Reduce the impAct of COVID-19 in hEalthcare workers (The BRACE trial)
Launched in March 2020, this Australian-led study is among the world’s largest trial on the off-target effects of the BCG vaccine in healthcare workers. A total of 6,828 participants enrolled in Australia, Brazil, Spain, the Netherlands and the United Kingdom. Besides preventing severe tuberculosis in children, the BCG vaccine has off-target (non-specific or immunomodulatory) effects. This multicentre, randomised controlled clinical trial is working to determine whether the BCG vaccine reduces the incidence of symptomatic and severe COVID-19 as well as other respiratory illness and allergic diseases. The trial’s primary outcomes were published in April 2023. Analysis is ongoing for the 12-month secondary and exploratory outcomes, as well as extensive immunological studies.
The BRACE COVID-19-Specific vaccine sub-study (BCOS) is investigating the impact of the 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, the 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.
Murdoch Children's Research Institute launched the MIS BAIR trial in 2015. The study team is following the lives of over 1,200 Melbourne children from birth to primary school to explore 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) challenges 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 the 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.
Funding
BRACE trial funding
- Bill & Melinda Gates Foundation
- Minderoo Foundation
- The Royal Children's Hospital Foundation
- Sarah and Lachlan Murdoch
- Health Services Union NSW
- Peter Sowerby Foundation
- SA Health
- The Insurance Advisernet Foundation
- NAB Foundation
- The Calvert-Jones Foundation
- Modara Pines Charitable Foundation
- UHG Foundation Pty Ltd
- Epworth HealthCare
- Swiss National Science Foundation
- 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
- Individual donors
MIS BAIR funding
- National Health and Medical Research Council
- Mercy Health
- The Myer Foundation
- Aranday Foundation
- European Society for Paediatric Infectious Diseases
- Swiss National Science Foundation
- Nossal Institute for Global Health
Other group funders
Collaborations
External collaborations/partnerships
BRACE trial
- 36 sites in the UK, Spain, Netherlands, Brazil and Australia
- 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
- Universidade Federal de Mato Grosso do Sul (UFMS)
- Fundação Oswaldo Cruz (Oswaldo Cruz Foundation; FIOCRUZ)
- Fundação de Medicina Tropical Dr Heitor Vieira Dourado (FMT-HVD)
- National Centre for Immunisation Research and Surveillance (NCIRS)
International
- Radboud University Medical Centre (UMC) (Netherlands)
- University of Oxford (UK)
- University of São Paulo (Brazil)
- Cayetano Heredia University (Peru)
- Kenya Medical Research Institute (KEMRI)
- University of Fribourg (Switzerland)
- University of Geneva (Switzerland)
- Harvard University (USA)
- Stanford University (USA)
National
Featured publications
Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers.
Pittet LF, Messina NL, Orsini F, Moore CL, Abruzzo V, Barry S, Bonnici R, Bonten M, Campbell J, Croda J, Dalcolmo M, Gardiner K, Gell G, Germano S, Gomes-Silva A, Goodall C, Gwee A, Jamieson T, Jardim B, Kollmann TR, Lacerda MVG, Lee KJ, Lucas M, Lynn DJ, Manning L, Marshall HS, McDonald E, Munns CF, Nicholson S, O'Connell A, de Oliveira RD, Perlen S, Perrett KP, Prat-Aymerich C, Richmond PC, Rodriguez-Baño J, Dos Santos G, da Silva PV, Teo JW, Villanueva P, Warris A, Wood NJ, Davidson A, Curtis N; BRACE Trial Consortium Group. N Engl J Med. 2023 Apr 27;388(17):1582-1596. doi: 10.1056/NEJMoa2212616. PMID: 37099341.
Off-target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19.
Messina, N.L., Germano, S., McElroy, R., Rudraraju, R., Bonnici, R., Pittet, L.F., Neeland, M.R., Nicholson, S., Subbarao, K., Curtis, N. Clin Transl Immunol. 2022, 11:e1387. doi.org/10.1002/cti2.1387
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.
Neonatal BCG vaccination is associated with a long-term DNA methylation signature in circulating monocytes.
Bannister S, Kim B, Domínguez-Andrés J, Kilic G, Ansell BRE, Neeland MR, Moorlag SJCFM, Matzaraki V, Vlahos A, Shepherd R, Germano S, Bahlo M, Messina NL, Saffery R, Netea MG, Curtis N, Novakovic B. Sci Adv. 2022 Aug 5;8(31):eabn4002. doi: 10.1126/sciadv.abn4002. Epub 2022 Aug 5. PMID: 35930640; PMCID: PMC9355358.
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