|Investigating the association between the maternal Immunoglobulin-G (IgG) repertoire during pregnancy and the infant’s risk of IgE mediated food allergy.
|Pillar/s: Immunity and Inflammation
Maternal IgG antibodies, potentially carrying epitopes of the maternal gut microbiota, appear to play a key role in foetal innate immune development. This is of interest, as we and others have previously shown that innate immune responses at birth are associated with subsequent allergic outcomes. Exposure to a diverse microbial environment during pregnancy is associated with reduced risk of the infant developing allergic disease. It is plausible to that this may be mediated by the foetal immune programming effect of a more diverse maternal gut microbiome, and in turn, more diverse repertoire of maternal IgG to gut microbiota.
Our aim is to investigate the association between the maternal Immunoglobulin-G (IgG) repertoire during pregnancy and the infant’s risk of IgE mediated food allergy.
|Investigations into the role played by red foxes (Vulpes vulpes) in the epidemiology of Mycobacterium ulcerans infections in Victoria, Australia.
|Pillar/s: Clinical and Public Health; Population Health and biology; Molecular Biology.
The epidemiology of Mycobacterium ulcerans (MU) infections in Victoria is not fully understood, yet cases are increasing and the disease is spreading into new endemic areas. Recent studies have reported and pointed to the possibility of a zoonotic transmission pathway from native mammals, specifically possums, being reservoir hosts (Blasdell et al., 2022).
A recent study performed by our group investigating environmental risk factors for presence of MU in Victoria, identified a high proportion of fox faeces as positive for M. ulcerans DNA, with evidence of viability on further testing (Blasdell et al., 2022). This finding suggests that foxes may have a role in the transmission of MU in Victoria. We hypothesize that foxes predate possums, become infected by MU in the process, and may likely shed viable bacteria in the environment contributing to potential exposure and infection of humans and other animals with MU through broken skin (Blasdell et al., 2022). Foxes also roam large distances, and it is therefore plausible that they have a role in introducing viable MU bacteria into new environments resulting in the development of new endemic areas.
This pilot study aims to investigate the potential role played by red foxes (Vulpes vulpes) in the epidemiology of Mycobacterium ulcerans in Victoria.
The study aims:
|An artificial intelligence fact checking tool for the identification of vaccine misinformation.
|Pillar/s: Clinical and Public Health
The proliferation of health-related misinformation on social media has emerged as a major public health concern as it can have serious consequences for individual health decisions and behaviours (Montagni et al., 2021). However, detecting and combating misinformation has become increasingly challenging due to the sheer volume and diversity of data on social media platforms, as well as the complex patterns of misinformation propagation. Fortunately, advances in AI technology have opened up new avenues for analyzsng and detecting health-related misinformation at scale (Shu et al., 2017).
To explore what AI can offer to address this challenge, this pilot project will track the source, style and spread of verified misinformation to identify vaccine misinformation features from various perspectives, including textual and visual patterns, temporal characteristics, linguistic features, dissemination behaviours, and source credibility. This holistic approach to analysing the key components of health-related misinformation will yield a more nuanced understanding of how misinformation spreads and how it can be effectively detected and countered.
In this pilot, we will use this information to develop an AI driven health misinformation fact-checking tool that combines advanced text classification algorithms with innovative visualization patterns for real-time detection and analysis of vaccine-related misinformation on social media. Our tool will be designed to be robust and accessible to the public, empowering users to access, understand, and evaluate health-related information in a more informed and responsible manner. The tool will be continually refined through use as new data inputs increase discernment of ‘tell-tale’ characteristics of misinformation.
In developing this proof-of-concept tool, this research will have a direct impact on combating the spread of harmful vaccine misinformation and lay the groundwork for future AI application in the curation of health information in social media, increasing consumer ability to discern reliable health related information from that which is not.
|The role of host proteins in influenza virus pathogenesis and immunity-what can we learn from single-cell RNA-sequencing.
|Pillar/s: Molecular biology; Immunity and Inflammation
Influenza virus infection represents an ongoing threat to communities worldwide. Yearly vaccine efficacy varies between 50-70% in healthy adults and requires annual reformulation given accumulation of mutations in virus sequence. Ongoing antiviral effectiveness is also susceptible to virus mutation. Both prevention/intervention strategies rely on targeting of the virus itself. The Stambas lab over the last decade has focused its research on the impact of host protein expression on influenza virus pathogenesis and immunity. We were the first to attribute a direct role for extracellular matrix enzymes in influenza specific immunity (McMahon, M., et al. PLoS Biol 14, e1002580, 2016) and lead this field internationally.
This project will therefore focus on two host proteins, A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs 7 (ADAMTS7) and Cytokine inducible SH2-containing protein (CISH) and their role in pathogenesis and immunity (ADAMTS7 forms part of the extracellular matrix and CISH regulates immunity through control of cell-to-cell proteins known as cytokines). Preliminary studies in our mouse models have shown that the absence of these host proteins in knockout mice influences outcomes of disease, and as such, these host proteins may represent key drug targets for translation into the clinic through development of novel therapeutics. We intend to use single cell RNA sequencing (scRNA-seq) to explore and understand host gene expression following influenza virus infection at multiple timepoints (innate and adaptive immunity) after infection in our knockout models and compare these gene expression profiles to wild-type (WT) controls to better understand the impact and role of ADAMTS7 and CISH proteins in pathogenesis and immunity.
|Investigating risk factors and outcomes of long COVID using health service utilisation data following acute COVID-19 in Victoria.
|Pillar/s: Clinical and Public Health; Population Health and biology
COVID-19 continues to cause a high burden of disease worldwide and has resulted in large numbers of admissions to hospital and death1. The extent of the burden is further impacted by additional complexities beyond the acute infection including but not limited to the development of persistent, fluctuating or new symptoms three or more months following acute COVID-19 infection1, 2, 3. The persistence and development of new symptoms associated with COVID-19 after three months post-acute COVID-19has been described by the World Health Organisation as Post COVID-19 condition or Long COVID3.
An estimated 10-15% of COVID-19 cases experience persistent post-acute symptoms or Long COVID4. This translates to over 300,000 cases in Victoria out of the three million cases notified from the start of the pandemic5. Long COVID is a multi-organ syndrome which includes a broad diversity of presentations, resulting in patients needing to access a wide range of services6. Estimates predict that at least half of Long COVID sufferers will continue to experience symptoms for more than 1 year, and will therefore need to use these multiple health services for a prolonged period2.
There is limited knowledge on how the persistent, fluctuating or new symptoms experienced by people with Long COVID will impact service use, resource allocation and health service delivery. Risk and protective factors for development of Long COVID are also unknown.
From health-service utilisation data of cases diagnosed between January 2020 and June 2022, a Long COVID cohort will be identified out of individuals who utilised health services three months following a COVID-19 diagnosis. A COVID-19 recovered cohort will also be characterised from non-health service users to be used as a comparison group.
From the health service utilisation data, we aim to:
|Artificial Intelligence-based drug resistance screening of malaria parasites using ‘Read Until’.
|Pillar/s: Population Health and biology
There have been several platforms used to explore molecular markers of drug resistance in malaria parasites including long read Whole Genome Sequencing (WGS) using Nanopore sequencing, short read WGS using Illumina sequencing and targeted (amplicon-based) sequencing.
WGS is hindered by contamination with large amounts of human genomic material and targeted sequencing requires laboratory expertise to design the experiments, developing specific primers to amplify target genes. New methods that overcome these issues at low cost are urgently needed. A new targeted sequencing method developed in 2016 called ‘Read Until’ which allows the Nanopore device to be programmed to selectively sequence target genes from whole genome libraries. This approach will reduce library prep time and expertise needed in the laboratory since whole genomic DNA preparations from human blood samples could be used together with simple-to-use library preparation kits. Consequently, both time and effort will be reduced in return for increased data output (coverage) for desired target regions of the genome.
This project aims to validate Read Until as an artificial intelligence (AI)-based method to conduct drug resistance profiling of malaria parasites using genomic DNA from whole blood.
|Implementation of point-of-care C-reactive protein testing for diagnostic antimicrobial stewardship in respiratory tract infections in primary care: a pilot feasibility study.
|Pillar/s: Clinical and Public Health
This project is built on our track record of investigations on how to foster implementation of antimicrobial stewardship (AMS) programs in Australian primary care. Our formative research program (2017-2021) has led us to design a novel general practitioner-pharmacist antimicrobial stewardship (GPPAS) implementation model to optimise antimicrobial use in primary care in Australia. With support from IMPACT seed grant 2023, the GPPAS model is on track for pilot evaluation in rural and regional Victoria.
The proposed project is a part of the GPPAS pilot program to assess feasibility of implementing point-of-care C-reactive protein (CRP) testing program to support GPs and community pharmacists’ management of respiratory infections (RTIs). Point-of-care CRP testing program will be implemented in two GP-pharmacy collocated settings from rural and regional Victoria. The project aims to understand the clinical and operational feasibility, and cost-effectiveness in optimising antimicrobial use in RTIs. The pilot feasibility data will help refine the GPPAS program and develop cluster randomized controlled trials to seek future external grants.
|Molecular Tests for Personalised Antimalarial Treatments at the Point-of-care in Low- and Middle-Income Countries.
|Pillar/s: Clinical and Public Health; Population Health and biology
Inaccurate diagnosis and/or presumptive treatment of malaria infections have contributed to poor treatment outcomes that have resulted in the emergence and spread of antimalarial resistance (AMR). Knowing the parasite species (e.g., Plasmodium falciparum or vivax) and its AMR marker profile (based on nucleotide polymorphisms in the parasite genome) for a malaria infection, will strengthen evidence-led antimalarial treatments that will be most effective to clear resistant parasites in an infection, i.e., “Personalised treatment”.
The parasite genomic data need to inform personalised antimalarial treatment is beyond the capabilities of microscopy and RDTs but possible with PCR and/or sequencing, which are often inaccessible in low- and middle-income countries (LMICs). Furthermore, the requirement for skilled labour, complicated DNA extractions and expensive laboratory equipment to operate make PCR less attractive for routine diagnosis and/or inaccessible to Community Health Centres in rural and remote areas of Africa and the Asia-Pacific.
This study aims to develop molecular tests/assays, based on the loop mediated isothermal amplification (LAMP) platform, for the detection of AMR parasites.
LAMP has comparable diagnostic performance as PCR but without the complexities of PCR. This study will develop – 1) LAMP assays to detect and differentiate Plasmodium falciparum and vivax infections, and 2) LAMP assays to detect falciparum parasites with key AMR markers associated with resistance to chloroquine, sulphadoxine-pyrimethamine and the artemisinin combination therapies (ACTs). Ultimately, these assays will be integrated into portable isothermal instruments for point-of-care diagnosis of malaria and AMR testing in LMICs.
|B-Connected: expanding access to hepatitis B care in the Barwon South-West Region of Victoria.
|Pillar/s: Clinical and Public Health
In Australia, very few people living with hepatitis B receive monitoring and only half of the people requiring treatment are on treatment – the remainder are at risk of cancer and cirrhosis. In 2016, the World Health Organization (WHO) announced a global strategy to eliminate hepatitis B and hepatitis C as public health threats by 2030. In line with this, the Australian government has released a national strategy to eliminate hepatitis B and hepatitis C.
Australia is not on track to reach the national hepatitis B elimination targets. Treatment uptake is higher in cities than regional areas. One of the major barriers to accessing care in the Barwon South West region (BSW) is the limited number of healthcare services providing care. Currently treating physicians in the area are limited to the specialists in Geelong, Warrnambool and Ballarat and two general practitioners (GPs), both located in Geelong.
The aim of this study is to gather evidence to support community-based hepatitis B care pathways in BSW.
This research project will map the distribution of people at risk of hepatitis B, hepatitis B notifications and current hepatitis B healthcare providers in the region to identify areas where there is a need for greater access to care. The research team will then conduct interviews with community-based healthcare providers in those areas to gain insight into their current practice and what models of care they think will be appropriate for their practice and their patient’s needs. This project will inform hepatitis B service delivery in BSW, and act as a hepatitis B elimination template for other rural and regional areas of Australia.
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